The Johns Hopkins Medical Journal 9 (1898): Difference between revisions

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COIsTTIEIsrTS.
==Contents==


* Development of the Human Intestine and its Position in the Adult. By Franklin P. Mall, 197
* On the Histoaenesis of the Striated Muscle Fibre, and the Growth of the Human Sartorius Muscle. By John Bruce MacCallum 208
* Further Observations on the Chemical Nature of the Active Principle of the Suprarenal Capsule. By John J. Abrl, M.D. 215
* The Lobule of the Spleen. By Franklin P. Mall,  218
* The Development of the Bile-Capillaries as Revealed by Golgi's Method. By William F. Hendrickson, 220
* A Study of the Musculature of the Entire Extra-Hepatic Biliary System, including that of the Duodenal Portion of the Common Bile-duct and of the Sphincter. By William F. HENDRICKiSON, 221
* Development of the Internal Mammary and Deep Epigastric Arteries in Man. By Franklin P. Mall,  232
* Two Instances in which the Musculus Sternalis Existed. — One Associated with other Anomalies. By Henry A. Christian, 235
* On the Pathological Changes in the Spinal Cord in a Case of Pott's Disease. By Sylvan Rosenheim, 240
* The Treatment of Otomycosis by the InsufHation of Boracic Acid and Oxide of Zinc. By Samuel Theobald, M. D., - 251
* Books Received, 252




Development of the Human Intestine and its Position in the Adult. By Franklin P. Mall, 197


On the Histoaenesis of the Striated Muscle Fibre, and the Growth of the Human Sartorius Muscle. By John Bkuce MacCallum, - - - - - - 208
===DEVELOPMENT OF THE HUMAN INTESTINE AND ITS POSITION IN THE ADULT===


Further Observations on the Chemical Nature of the Active Principle of the Suprarenal Capsule. By John J. Abrl, M. D., ------ - - 215
{{Ref-Mall1898a}}


The Lobule of the Spleen. By Franklin P. Mall, - - - - 218
The Development of the Bile-Capillaries as Revealed by Golgi's
Method. By William F. Hendrickson, ------ 220
A Study of the Musculature of the Entire Extra-Hepatic
Biliary System, including that of the Duodenal Portion of the Common Bile-duct and of the Sphincter. By William
F. HENDRICKiSON, __--_--- 221
Development of the Internal Mammary and Deep Epigastric
Arteries in Man. By Franklin P. Mall, ------ 232
Two Instances in which the Musculus Sternalis Existed. — One
Associated with other Anomalies. By Henry A. Christian, 235 On the Pathological Changes in the Spinal Cord in a Case of
Pott's Disease. By Sylvan Rosenheim, ------- 240
The Treatment of Otomycosis by the InsufHation of Boracic
Acid and Oxide of Zinc. By Samuel Theobald, M. D., - 251 Books Received, ----------------- 252
DEVELOPMENT OF THE HUMAN INTESTINE AND ITS POSITION IN THE ADULT.


By Franklin P. Mall, Professor of Anatomy, Johns Hopkins University.
By Franklin P. Mall, Professor of Anatomy, Johns Hopkins University.
Line 23,876: Line 23,855:




ON THE HISTOGENESIS OF THE STRIATED MUSCLE FIBRE, AND THE GROWTH OF THE HUMAN
===ON THE HISTOGENESIS OF THE STRIATED MUSCLE FIBRE, AND THE GROWTH OF THE HUMAN SARTORIUS MUSCLE===


SARTORIUS MUSCLE.
{{Ref-MacCallum1898}}


By John Bruce MacCallum.
By John Bruce MacCallum.
Line 24,707: Line 24,686:
I wish to express my thanks to my assistant. Dr. Walter Jones, for the valuable assistance rendered in making the analyses recorded in this paper.
I wish to express my thanks to my assistant. Dr. Walter Jones, for the valuable assistance rendered in making the analyses recorded in this paper.


===THE LOBULE OF THE SPLEEN===


 
{{Ref-Mall1898b}}
THE LOBULE OF THE SPLEEN.


By Franklin P. Mall. (From the Anatomical Laboratory, Johns Hopkins University.)
By Franklin P. Mall. (From the Anatomical Laboratory, Johns Hopkins University.)
Line 24,772: Line 24,751:




JOHNS HOPKINS HOSPITAL BULLETIN.
===THE DEVELOPMENT OF THE BILE-CAPILLARIES AS REVEALED BY GOLGI'S METHOD===
 
 
 
[Nos. 90-91.
 
 
 
THE DEVELOPMENT OF THE BILE-CAPILLARIES AS REVEALED BY GOLGI'S METHOD.


By William F. Hendrickson. {From the Anatomical Laboratory of the Johns Hopkina University.)
By William F. Hendrickson. {From the Anatomical Laboratory of the Johns Hopkina University.)
Line 25,916: Line 25,887:
X, Those fibres of the sphincter which become detached latersjly and run down the intestine.
X, Those fibres of the sphincter which become detached latersjly and run down the intestine.


===DEVELOPMENT OF THE INTERNAL MAMMARY AND DEEP EPIGASTRIC ARTERIES IN MAN===


 
{{Ref-Mall1898c}}
DEVELOPMENT OF THE INTERNAL MAMMARY AND DEEP EPIGASTRIC ARTERIES IN MAN.


By Franklin P. Mall.
By Franklin P. Mall.
Line 26,077: Line 26,048:




TWO INSTANCES IN WHICH THE MUSCULUS STERNALIS EXISTED.
===TWO INSTANCES IN WHICH THE MUSCULUS STERNALIS EXISTED. WITH OTHER ANOMALIES===
 
WITH OTHER ANOMALIES.


Henry A. Christian.
Henry A. Christian.
Line 26,711: Line 26,680:




ON THE PATHOLOGICAL CHANGES IN THE SPINAL CORD IN A CASE OF POTT'S DISEASE.
===ON THE PATHOLOGICAL CHANGES IN THE SPINAL CORD IN A CASE OF POTT'S DISEASE===


By Sylvan Rosenheim. {From the Anatomical Laboratory of the Johns Hopkins University.)
By Sylvan Rosenheim. {From the Anatomical Laboratory of the Johns Hopkins University.)
Line 27,327: Line 27,296:




I'J--.
(?. — Neuroglia, greatly increased in amount.


O.' Nuclei of neuroglia cells.


M. — Masses of globular material imbedded in the neuroglia, staining a pinkish color.


il.— Empty hole.


v.rizin
H/ — Hole containing a disintegrating nerve fibre.


H." — Holes containing masses of more or less globular appearance, staining a pinkish color. They are probably modified compound granular corpuscles.


H.'" — Holes containing material taking on a yellowish and pinkish coloration. Probably broken down nerve fibres.


C. — Compound granular corpuscle.


Fig. XIV. From various parts of the region of compression. Leitz objective x'j (oil immersion), eye piece 3.


1 and 2. Corpora amylacea — Van Gieson's stains.


F. <]•
3 and 4. Eighth cervical segment. Two large irregular holes, containing cells, the nuclei of which stain a deep red color. The protoplasm contains vacuoles, and in parts looks as if it were made up of small globules. These are probably modified compound granular corpuscles Upson's carmine.


5. Second thoracic segment. Hole containing one of the cor




pora amylacea, which are very numerous at this level. It stains a pink color. Marchi's fluid and Upson's carmine.


6. Same section as 5. Shows several degenerating fibres. In one the axone stains a faint pink color ; in another the axone is barely outlined. Numerous black globules of myelin are seen. The rest of the myelin has a faint yellowish color.


7. A nerve fibre is shown here, with a vacuolar area around the axis-cylinder.


8. Marchi specimen counter-stained in Upson's carmine. Hole containing a degenerating nerve fibre. Tlie axone stains a fairly good pink color. The myelin sheath is represented partly by black granules, partly by a yellowish staining mass.


9. Haematoxylin and eosin. Hole containing three compound granular corpuscles. The nuclei stain black and are granular.


10. Eighth cervical segment. Van Gieson's stain. Swollen ganglion-cell. The protoplasm stains a homogeneous pink color. The nucleus is almost colorless ; the nucleolus stains a deep pink color.


11. Weigert-Pal specimen counter-stained in Upson's carmine. Large hole containing several large black masses, surrounded by ball-like masses, which are outlined by darkly staining rings.






£._ri».;
===THE TREATMENT OF OTOMYCOSIS BY THE INSUFFLATION OF BORACIC ACID AND OXIDE OF ZINC===






Tiiii Johns Hopkins Hospital Billetis Nos. 90-91.
By Samuel Theobald, M. D., Clinical Professor of Ophthalmology and Otology, Johns HojMns University.






Seventeen years ago, in an article published in the American Journal of Otology,! I called attention to the value of a powder containing equal parts of boracic acid and oxide of zinc in the treatment of otomycosis aspergillina. In this article objection was urged to the use of alcohol, the agent most commonly employed for the destruction of aural fungi, on the ground that it not infrequently causes considerable pain when instilled into the auditory canal and tends to aggravate the inflammation of the canal walls and tympanic membrane usually present in otomycosis. A distinct gain, it was pointed out, would be made if a renredy could be found which would effectually destroy the parasite and at the same time exert a beneficial influence upon the inflammation excited by its presence; and such a remedy, it was claimed, had been found in the boracic acid and oxide of zinc powder.


F.ch
Experiments were described which showed the specific action of boracic acid in destroying aspergillus and other fungi, and the drying effect of the oxide of zinc was held to render more effectual the germicidal action of the acid. At the same time, there was abundant evidence to show that the combination of the two, used as suggested (by insufflation), was one of the most efficacious remedies that we possess in overcoming diffuse inflammation of the external ear.


Although in the interval that has elapsed since the publication of this paper, I have used this remedy in all the cases of otomycosis that I have met with, and have never known it fail to destroy effectually the parasite — a single application often accomplishing this result, and more than two applications being seldom needed — I should not feel warranted in bringing the subject again to the attention of otologists but




i' ^ 1


Read before the American Otological Society, July 18, If
fVol. Ill, No. 2, p. 119.






I






'*
for the fact that the majority of them, to judge by the textbooks, still seem to adhere to the practice, which, I think, should long since have become obsolete, of treating these cases by alcohol instillations.*


C omnia
That alcohol is a suitable agent to pour into a diffusely inflamed and painful auditory canal will hardly be maintained by any one; while its relative inefficiency in destroying aspergillus seems to be shown by the statement of Politzer, that the instillations should be kept up for "a year" to prevent a return of the growth,! and that of Hovell, who says they should be repeated " two or three times a day " until the parasite is gotten rid of, and continued at intervals of a week for " several mouths " in order to guard against a relapse.J As opposed to this, we have the one, two or, at most, three applications of the zinc and boracic acid powder, at intervals of 2-1 or 48 hours, immediately and effectually eradicating the parasite, and at the same time, almost invariably, greatly benefiting the attendant inflammation.


The addition of bichloride of mercury or boracic acid to alcohol, as has been recommended, probably increases its parasiticidal effect, but certainly does not lessen its irritant action. Boracic acid and iodoform, mentioned among other agents by Gleason, ought to be efficacious, but, for the sake of our patients and their friends, iodoform should not be used if a less objectionable remedy will accomplish the same purpose. Chinoline salicylate and boracic acid, 1 part to 8 or 1 to 16, recommended by C. H. Burnett,§ is highly extolled by Eobert Barclay.ll I cannot speak of the value of this remedy from






•Compare Politzer, Dencb, McBride, Hovell, Gleason. f Diseases of the Ear, p. 187. t Diseases of the Ear and Naso-pharynx, p. 195. § Medical & Surg. Reporter, Phila., Vol. LXI, p. 539. 1 Burnett's System of Diseases of the Ear, Nose and Throat.




4


252


F. rs. 7.




JOHNS HOPKINS HOSPITAL BULLETIN.




-W-^


[Nos. 90-91.


"g"




personal experience, but I am prepared to believe that it must yield favorable results from the large proportion of boracic acid which it contains.


The boracic acid and oxide of zinc powder is open to the single objection that it is a somewhat insoluble comjioiind, but this is not a serious objection, especially if it be blown into the ear, as it should be, only in sufficient quantity to cover lightly the walls of the meatus aud the tympanic membrane. The parasite destroyed and the inflammation subdued, the removal of that portion of the powder which may have adhered to the membrane and canal walls may be safely left to nature, which, through the outgrowth of the epidermis, will accomplish this completely within the course of a few weeks.


-•**"
A brief description of a single typical case, recently under observation, will suffice to illustrate the action of this remedy and the manner of its employment.


Mr. X, of Baltimore, consulted me in the latter part of May last, because of an uncomfortable " full feeling," attended by slight pain, in the left ear. The history of the case indicated that there had been a slight dermatitis in each auditory canal for a considerable time. The symptoms complained of in the left ear were found to be due to the presence of aspergillus nigricans, which had excited a well-marked diffuse inflammation of the deeper portion of the canal walls and the tympanic membrane.


Fi(i. X.
By the aid of the syringe, probe and forceps the aspergillus was removed as completely as possible aud the meatus was freed of a considerable quantity of exfoliated epithelium. The ear was then dried and the boracic acid and zinc powder blown in lightly. On the following day, although the unpleasant symptoms were entirely relieved, the treatment was repeated as a matter of precaution. This completed the cure, which a lapse of three weeks has shown to be radical.






===BOOKS RECEIVED===






Atlas and Abstract of the Diseases of the Larynx. By Dr. L. Griinwald, of Munich. Authorized Translation from the German. Edited by Charles P. Grayson, M. D. 1898. 12mo. With 107 Colored Figures on 44 Plates. 103 pages. W. B. Saunders, Philadelphia.


On Cardiac Failure and its Treatment, with Especial Reference to the Use of Baths and Exercises. By Alexander Morison, M. D., F. E. C. P 1897. 8vo, 256 pages. The Rebman Publishing Co., London.


F. ds
Hay Fever and its Successful Treatment. By W. C. Hollopeter, A. M.,M. D. 1898. 12mo, 137 pages. P. Blakiston's Son & Co., Philailelphia.




A Report on Vaccination and its Results, Based on the Evidence Taken by the Royal Commission during the Tears 1889-1897. Vol. I. The Text of the Commission Report. 1898. 8vo, 493 pages. New Sydenham Society, London.


,/?"v^< '
A Text-Book upon the Pathogenic Bacteria. For students of medicine, and physicians. By Joseph McFarland, M. D. Second edition, revised and enlarged. 1898. 8vo, 497 pp. W. B. Saunders, Phila.


An American Text-Book of the Diseases of Children. By American teachers. Edited by Louis Starr, M. D., assisted by T. S. Westcott, M. D. Second edition, revised. 1898. 4to, 1244 pp. W. B. Saunders, Philadelphia.


The Diseases of the Stomach. By William W. Van Valzah, A. M., M. D., and J. Douglas Nisbet, A. B., M. D. 1898. 8vo, 674 pp. W. B. Saunders, Philadelphia.


('(1)11 in It F. rs. I,




Twelfth Annual Report of the State Board of Health of the State of Ohio, for the year ending October SI, IS07. 8vo, 308 pp. 1898. The Laning Printing Co., Norwalk, Ohio.


F. rs. ]
Preliminary Report of an Investigation of Rivers and Deep Oround Waters of Ohio, as Sources of Public Water Supplies. By the State Board of Health. 1897-98. 8vo, 259 pp. J. B. Savage Press, Cleveland.


Second Catalogue of the Library of the Peabody Institute of the City of Baltimore, including the additions made since 1882. Part III, E-G. 1898. 4to, 2006 pp. Baltimore.


An American Text-Book of Gynecology, Medical and Surgical, for practitioners and students. By H. T. Byford, M. D., etal. Edited by J. M. Baldy, M. D. Second edition, revised. 1898. 4to, 718pp. W. B. Saunders, Philadelphia.


ir '
A Text-Book of Materia Medica, Therapeutics and Pharmacology. By G. F. Butler, Ph. G., M. D. Second edition, revised. 1898. 8vo, 860 pp. W. B. Saunders, Philadelphia.


King's College Hospital Reports; being the annual report of King's College and the medical department of King's College. Edited by N. Tirard, M. D., F. R. C. P., et al. Vol. IV. {Oct. 1st, 1896-Sept. .30th, 1897). 1898. 8vo, 358 pp. Adlard and Son, London.


The Office Treatment of Hemorrhoids, Fistula, etc., without operation. By Charles B. Kelsey, A. M., M. D. 1898. 12mo, 68 pp. E. R. Pelton, New York.


-F.ct>.l.
Twentieth Century Practice. An International encyclopedia of modern medical science by leading authorities of Europe and America. Ed. by Thos. L. Stedman, M. D. Vol. XV. Infectious Diseases. 1898. 8vo, 658 pp. Wm. Wood & Co., New York.


The Principles and Practice of Medicine. By William Osier, M. D. Third Edition. 1898. 8vo, 1181 pp. D. Appleton & Co., New York.


The Mineral Waters and Health Resorts of Europe. Treatment of chronic diseases by spas and climates with hints as to the simultaneous employment of various physical and dietetic methods. Being a revised and enlarged edition of "The spas and mineral waters of Europe." By H. Weber, M. D., F. R. C. P., and F. P. Weber, M. D., F. R. 0. P. 1898. 8vo, 524 pp. Smith, Elder & Co., London.


A Clinical Text-Book of Medical Diagnosis for Physicians and Students. By Oswald Vierordt, M. D. Authorized translation with additions by F. H. Stuart, A. M., M. D. Fourth American edition, from the fifth German, revised and enlarged. 1898. 8vo, 603 pp. W. B. Saunders, Philadelphia.


Schwlflf anit ItoHenhvlm.
WALTER S. DAVIS, M. D.






September-October, 1898.]
At a meeting held at 4.30 o'clock Wednesday afternoon, on the twenty-eighth of September, in the office of the superintendent of Johns Hopkins Hospital, presided over by Dr. H. M. Hurd, the following resolutions were adopted :


Whereas, we have lost our beloved comrade and fellow-worker, W.\LTER S. Davis ;


Be it Resolved, That we, the Medical Faculty of the Johns Hopkins University and the stafif of the Johns Hopkins Hospital do express to his family our most heartfelt sympathy in their great bereavement.


JOHNS HOPKINS HOSPITAL BULLETIN.
His enthusiasm in the profession was unbounded and always a stimulus to his co-workers ; but we shall remember him particularly for his sterling character, his ever cheerful disposition, and his fidelity as a friend, aud,


Be it further Resolved, That a copy of these resolutions be conveyed to his family and published in the Bulletin of the Johns Hopkins Hospital. THOMAS S. CULLEN,


JAMES F. MITCHELL, GUY L. HUNNER.


251
Committee.






(?. — Neuroglia, greatly increased in amount.
The Johns Hopkins Hospital Bulletins are issued monthly. They are printed by THE FRIEDENWALD CO., Baltimore. Single copies may be procured from Messrs. CITSITINO & CO. and the BALTIMORE NEWS COMPANY. Baltimore. Subscriptions, §1.00 a year, may b» addressed to the publishers, THE JOHNS HOPKINS PRESS, BALTIMORE; single copies will be sent by mail for fifUen cenU each.


O.' Nuclei of neuroglia cells.


M. — Masses of globular material imbedded in the neuroglia, staining a pinkish color.


il.— Empty hole.
BULLETIN


H/ — Hole containing a disintegrating nerve fibre.


H." — Holes containing masses of more or less globular appearance, staining a pinkish color. They are probably modified compound granular corpuscles.


H.'" — Holes containing material taking on a yellowish and pinkish coloration. Probably broken down nerve fibres.
OF


C. — Compound granular corpuscle.


Fig. XIV. From various parts of the region of compression. Leitz objective x'j (oil immersion), eye piece 3.


1 and 2. Corpora amylacea — Van Gieson's stains.


3 and 4. Eighth cervical segment. Two large irregular holes, containing cells, the nuclei of which stain a deep red color. The protoplasm contains vacuoles, and in parts looks as if it were made up of small globules. These are probably modified compound granular corpuscles Upson's carmine.
THE JOHNS HOPKINS HOSPITAL.


5. Second thoracic segment. Hole containing one of the cor




pora amylacea, which are very numerous at this level. It stains a pink color. Marchi's fluid and Upson's carmine.
Vol. IX.- No. 92.]


6. Same section as 5. Shows several degenerating fibres. In one the axone stains a faint pink color ; in another the axone is barely outlined. Numerous black globules of myelin are seen. The rest of the myelin has a faint yellowish color.


7. A nerve fibre is shown here, with a vacuolar area around the axis-cylinder.


8. Marchi specimen counter-stained in Upson's carmine. Hole containing a degenerating nerve fibre. Tlie axone stains a fairly good pink color. The myelin sheath is represented partly by black granules, partly by a yellowish staining mass.
BALTIMORE, NOVEMBER, 1898.


9. Haematoxylin and eosin. Hole containing three compound granular corpuscles. The nuclei stain black and are granular.


10. Eighth cervical segment. Van Gieson's stain. Swollen ganglion-cell. The protoplasm stains a homogeneous pink color. The nucleus is almost colorless ; the nucleolus stains a deep pink color.


11. Weigert-Pal specimen counter-stained in Upson's carmine. Large hole containing several large black masses, surrounded by ball-like masses, which are outlined by darkly staining rings.






THE TREATMENT OF OTOMYCOSIS BY THE INSUFFLATION OF BORACIC ACID AND OXIDE OF ZINC*


GOIsTTEIsTTS.




By Samuel Theobald, M. D., Clinical Professor of Ophthalmology and Otology, Johns HojMns University.


The Diajnosis of the Condition of each Kidney by Inoculation of the Separated Sediments into Guinea-pigs in Suspected Renal Tuberculosis. By Edward Reynolds, M. D., - - - 253


Laparotomy for Intestinal Perforation in Typhoid Fever. By Harvey W. Gushing, M. D., 257


Seventeen years ago, in an article published in the American Journal of Otology,! I called attention to the value of a powder containing equal parts of boracic acid and oxide of zinc in the treatment of otomycosis aspergillina. In this article objection was urged to the use of alcohol, the agent most commonly employed for the destruction of aural fungi, on the ground that it not infrequently causes considerable pain when instilled into the auditory canal and tends to aggravate the inflammation of the canal walls and tympanic membrane usually present in otomycosis. A distinct gain, it was pointed out, would be made if a renredy could be found which would effectually destroy the parasite and at the same time exert a beneficial influence upon the inflammation excited by its presence; and such a remedy, it was claimed, had been found in the boracic acid and oxide of zinc powder.
Spontaneous Hsemorrhagic Septicsemia in a Guinei-pig, caused by a Bacillus. By George H. VVbaver, M. D., - - - - -270


Experiments were described which showed the specific action of boracic acid in destroying aspergillus and other fungi, and the drying effect of the oxide of zinc was held to render more effectual the germicidal action of the acid. At the same time, there was abundant evidence to show that the combination of the two, used as suggested (by insufflation), was one of the most efficacious remedies that we possess in overcoming diffuse inflammation of the external ear.
Antitoxic Relation between Bee Poison and Honey (?). By G. H. Stover, M.D., ------- 271


Although in the interval that has elapsed since the publication of this paper, I have used this remedy in all the cases of otomycosis that I have met with, and have never known it fail to destroy effectually the parasite — a single application often accomplishing this result, and more than two applications being seldom needed — I should not feel warranted in bringing the subject again to the attention of otologists but




Proceedings of Societies :


Read before the American Otological Society, July 18, If
The Hospital Medical Society,
fVol. Ill, No. 2, p. 119.


Broadbent's Sign [Dr. Camac] ; — Aortic Aneurysm [Dr. Brown] ; — Discussion of Mr. MacCallum's Paper on Pathology of Heart Muscle [Dr. Flkxner] ; — Epidemic Cerebrospinal Meningitis — Exhibition of Specimens [Dr. Livingood].


Notes on New Books,


I




274


for the fact that the majority of them, to judge by the textbooks, still seem to adhere to the practice, which, I think, should long since have become obsolete, of treating these cases by alcohol instillations.*


That alcohol is a suitable agent to pour into a diffusely inflamed and painful auditory canal will hardly be maintained by any one; while its relative inefficiency in destroying aspergillus seems to be shown by the statement of Politzer, that the instillations should be kept up for "a year" to prevent a return of the growth,! and that of Hovell, who says they should be repeated " two or three times a day " until the parasite is gotten rid of, and continued at intervals of a week for " several mouths " in order to guard against a relapse.J As opposed to this, we have the one, two or, at most, three applications of the zinc and boracic acid powder, at intervals of 2-1 or 48 hours, immediately and effectually eradicating the parasite, and at the same time, almost invariably, greatly benefiting the attendant inflammation.


The addition of bichloride of mercury or boracic acid to alcohol, as has been recommended, probably increases its parasiticidal effect, but certainly does not lessen its irritant action. Boracic acid and iodoform, mentioned among other agents by Gleason, ought to be efficacious, but, for the sake of our patients and their friends, iodoform should not be used if a less objectionable remedy will accomplish the same purpose. Chinoline salicylate and boracic acid, 1 part to 8 or 1 to 16, recommended by C. H. Burnett,§ is highly extolled by Eobert Barclay.ll I cannot speak of the value of this remedy from
Books Received, ----------------- 275






•Compare Politzer, Dencb, McBride, Hovell, Gleason. f Diseases of the Ear, p. 187. t Diseases of the Ear and Naso-pharynx, p. 195. § Medical & Surg. Reporter, Phila., Vol. LXI, p. 539. 1 Burnett's System of Diseases of the Ear, Nose and Throat.
THE DIAGNOSIS OF THE CONDITION OF EACH KIDNEY BY INOCULATION OF THE SEPARATED SEDIMENTS INTO GUINEA-PIGS IN SUSPECTED RENAL TUBERCULOSIS.


By Edward Reynolds, M.D., Boston, Mass.




252


The direct inspection of tlie air-distended bladder which we owe to Kelly, with its sequelae of easy exploration of the ureters, has already led to great advances towards an accurate knowledge of the urinary diseases of women, and at the present moment, when so much is opening up before us, any new step towards exactness of diagnosis seems worth reporting.


Little is yet known of the natural history of renal tuberculosis; indeed, it is for comparatively few years that we have known that tuberculosis can be primary in the kidney, and the great mass of the profession has not yet realized that this disease is often localized for many years in one kidney before invading the rest of the urinary tract; but in the last three years we have been accumulating a considerable amount of clinical evidence in support of these views, namely, that though renal tuberculosis does in the end kill when untreated, it is often nevertheless so strictly localized in one kidney that the patient may be restored to perfect health after this is removed by nephrectomy. Among the many cases of this nature which we now have may be cited a remarkable one by Vineburg* and three by Kelly. f I am myself able to add three unpublished cases, two of my own and one very remarkable


JOHNS HOPKINS HOSPITAL BULLETIN.




•Medical Record, Feb. 6th, 1898.


[Nos. 90-91.
f Johns Hopkins Hospital Bulletin, Feb.-Mar., 1896.






personal experience, but I am prepared to believe that it must yield favorable results from the large proportion of boracic acid which it contains.
case which I saw in consultation after a nephrectomy by another surgeon. Those who have ever seen how these patients are transformed in nutrition and general health, by the removal of the offending kidney, will be slow to listen to arguments against the ojjeration for cases in which the disease is unilateral, but it is of course justifiable only in such cases, and our success must therefore rest on our power of diagnosing the disease while it is limited to one kidney, and thus confining the operation to cases which are capable of cure by nephrectomy. For this purpose we must not only be able to establish the diagnosis of renal tuberculosis, in advance of the constitutional breakdown of the patient, but must also be able to satisfy ourselves with some positiveness of the health of the other kidney; and striking testimony to the advances which have been made in this subject during the last few years is to be obtained by inspection of the most recent text-books on medical diagnosis. Thus one, which shall be nameless, in the course of three pages devoted to renal tuberculosis, gives under diagnosis only these three clues: the presence in the sediment of the urine of little, yellow, cheesy masses of degenerated tuberculous material ; the presence of pus and other signs of chronic pyelitis from no assignable cause other than tubercle, and, lastly, the presence of tuberculosis in other organs. Even the latest edition of Osier, in which the section on this subject


The boracic acid and oxide of zinc powder is open to the single objection that it is a somewhat insoluble comjioiind, but this is not a serious objection, especially if it be blown into the ear, as it should be, only in sufficient quantity to cover lightly the walls of the meatus aud the tympanic membrane. The parasite destroyed and the inflammation subdued, the removal of that portion of the powder which may have adhered to the membrane and canal walls may be safely left to nature, which, through the outgrowth of the epidermis, will accomplish this completely within the course of a few weeks.


A brief description of a single typical case, recently under observation, will suffice to illustrate the action of this remedy and the manner of its employment.


Mr. X, of Baltimore, consulted me in the latter part of May last, because of an uncomfortable " full feeling," attended by slight pain, in the left ear. The history of the case indicated that there had been a slight dermatitis in each auditory canal for a considerable time. The symptoms complained of in the left ear were found to be due to the presence of aspergillus nigricans, which had excited a well-marked diffuse inflammation of the deeper portion of the canal walls and the tympanic membrane.
254


By the aid of the syringe, probe and forceps the aspergillus was removed as completely as possible aud the meatus was freed of a considerable quantity of exfoliated epithelium. The ear was then dried and the boracic acid and zinc powder blown in lightly. On the following day, although the unpleasant symptoms were entirely relieved, the treatment was repeated as a matter of precaution. This completed the cure, which a lapse of three weeks has shown to be radical.




JOHNS HOPKINS HOSPITAL BULLETIN.


BOOKS RECEIVED.




[No. 92.


Atlas and Abstract of the Diseases of the Larynx. By Dr. L. Griinwald, of Munich. Authorized Translation from the German. Edited by Charles P. Grayson, M. D. 1898. 12mo. With 107 Colored Figures on 44 Plates. 103 pages. W. B. Saunders, Philadelphia.


On Cardiac Failure and its Treatment, with Especial Reference to the Use of Baths and Exercises. By Alexander Morison, M. D., F. E. C. P 1897. 8vo, 256 pages. The Rebman Publishing Co., London.


Hay Fever and its Successful Treatment. By W. C. Hollopeter, A. M.,M. D. 1898. 12mo, 137 pages. P. Blakiston's Son & Co., Philailelphia.
has been considerably rewritten and evidently brought up to date, may be summarized as saying that there is but little chance of making a diagnosis unless we are put upon the track by finding tuberculosis in other organs, though this acute writer does mention the special methods of examination employed by gynecologists and the hope for the future which they afford.


A Report on Vaccination and its Results, Based on the Evidence Taken by the Royal Commission during the Tears 1889-1897. Vol. I. The Text of the Commission Report. 1898. 8vo, 493 pages. New Sydenham Society, London.
It is apparent that these medical descriptions refer to what we from a surgical standpoint should call advanced disease. Our surgical specialty has already led us to the possibility of establishing the diagnosis at a very much earlier stage than this.


A Text-Book upon the Pathogenic Bacteria. For students of medicine, and physicians. By Joseph McFarland, M. D. Second edition, revised and enlarged. 1898. 8vo, 497 pp. W. B. Saunders, Phila.
Though such a diagnosis can be made only by physical examination, a suspicion of tubercular or other renal disease will often be excited by the symptomatology, and this must therefore be briefly reviewed. The early symptoms of the disease will vary greatly both in character and in intensity in different cases, and from time to time in the same case, but will consist typically of pain and tenderness over the abdomen on the affected side, frequency of urination, and sometimes hematuria. These symptoms are, however, equally characteristic of simple pyelitis, renal calculus and new growth in the pelvis of the kidney. There are, indeed, no differences of kind in the symptomatology of these diseases in their early stages, though there are differences in the degree in which the several symptoms are likely to be present.


An American Text-Book of the Diseases of Children. By American teachers. Edited by Louis Starr, M. D., assisted by T. S. Westcott, M. D. Second edition, revised. 1898. 4to, 1244 pp. W. B. Saunders, Philadelphia.
All these diseases are characterized by dull pains over the kidney and along the course of the ureter on the affected side. The pain is often bearing-down in character, and therefore a uterine origin is usually assigned to it; is usually increased by standing ; and is always more or less associated with frequency of micturition, occurring at night as well as in the day-time. Ill all of them the call to micturate is a very urgent one; the pain on micturition is usually leferred to the meatus ; and all are liable to more or less tenesmus at the end of micturition. In all the pain may be increased by jarring or jolting (as in driving over rough roads).


The Diseases of the Stomach. By William W. Van Valzah, A. M., M. D., and J. Douglas Nisbet, A. B., M. D. 1898. 8vo, 674 pp. W. B. Saunders, Philadelphia.
This whole group of symptoms is, however, in reality symptomatic of the amount of inflammation present, and therefore varies with this subsidiary feature of the case. They are often though not always more marked in renal stone than in tlie other diseases.


All the diseases enumerated may be accompanied by hematuria, but this is rare in simple pyelitis ; it is more likely to be profuse in tuberculosis or a new growth than in stone.


In all, the patients are almost equally liable to attacks of mild renal colic, due usually to inflammatory obstruction in the ureter. They differ from the pains excited by the passage of a calculus in being less severe and not followed by the appearance of the stone. These attacks are perhaps less common in new growths than in the other diseases under consideration. Not infrequently, at intervals in the course of these chronic renal diseases (and especially in tuberculosis and simple pyelitis), the inflammatory symptoms will be found to be most marked on the sound side. This is probably because each exacerbation of the disease in the affected side leads to an increased elimination of toxic materials from the functionally more active kidney; and this excites a transitory and some


Twelfth Annual Report of the State Board of Health of the State of Ohio, for the year ending October SI, IS07. 8vo, 308 pp. 1898. The Laning Printing Co., Norwalk, Ohio.


Preliminary Report of an Investigation of Rivers and Deep Oround Waters of Ohio, as Sources of Public Water Supplies. By the State Board of Health. 1897-98. 8vo, 259 pp. J. B. Savage Press, Cleveland.
what acute inflammation in the mucous membrane of the urinary apparatus on the sound side.


Second Catalogue of the Library of the Peabody Institute of the City of Baltimore, including the additions made since 1882. Part III, E-G. 1898. 4to, 2006 pp. Baltimore.
This transposition of symptoms I have seen so frequently (I may say almost constantly) that I am sure it must always be guarded against. The side on which the patient tells us that the symptoms were first noticed is usually the diseased side.


An American Text-Book of Gynecology, Medical and Surgical, for practitioners and students. By H. T. Byford, M. D., etal. Edited by J. M. Baldy, M. D. Second edition, revised. 1898. 4to, 718pp. W. B. Saunders, Philadelphia.
The inquiry into the history should be followed by palpation, both abdominal and bimanual. In all these lesions we find, on palpation, a tenderness which may extend from top to bottom of the urinary tract on the affected, and even on both sides, but which is usually most marked at one or more of three points: namely, over the kidney; at the spot where the ureter crosses the brim of the pelvis, in which ease it is often limited to a spot the size of the finger-tip, midway between the umbilicus and the anterior superior spine of the ilium (McBurney's point or its fellow); and, finally, over the vesical end of the ureter at the side of the cervix, which examination may even detect an enlargement or induration of the ureter. These tender points are again symptomatic of the amount of inflammation present, and therefore usually vary with the amount of pain.


A Text-Book of Materia Medica, Therapeutics and Pharmacology. By G. F. Butler, Ph. G., M. D. Second edition, revised. 1898. 8vo, 860 pp. W. B. Saunders, Philadelphia.
A study of the history and the results of the gynecological examination usually enables us, then, to suspect, and sometimes permits us to postulate, a diagnosis of some renal disease of a surgical nature, but it does not enable us to say what, nor always on which side it is. The special examination now steps in and the real diagnosis begins here.


King's College Hospital Reports; being the annual report of King's College and the medical department of King's College. Edited by N. Tirard, M. D., F. R. C. P., et al. Vol. IV. {Oct. 1st, 1896-Sept. .30th, 1897). 1898. 8vo, 358 pp. Adlard and Son, London.
If a visual examination of the bladder shows that the vesical mucous membrane is substantially normal except in the interureteral region, and that a strongly localized inflammation is present there, the source of that inflammation is probably to be found in the passage of a vicious urine from one or the other ureter. If one ureteral orifice is abnormal in appearance, this probably marks the diseased side. The next and most important step is the catheterization of the ureters and a microscopical and chemical examination of the urine secreted by each kidney. But here the results must be interpreted with the greatest care, as recent advances have made it certain that most of our past opinions on the results of urinalysis must be revised in the light of the new knowledge. This is especially true of renal tuberculosis; the large amounts of degenerated pus and bits of necrotic material which are commonly described as characteristic of the disease being, in fact, found only in locally advanced cases, while the urinary signs of early tuberculosis are usually limited to the detection of pus and the bacilli by the microscope.


The Office Treatment of Hemorrhoids, Fistula, etc., without operation. By Charles B. Kelsey, A. M., M. D. 1898. 12mo, 68 pp. E. R. Pelton, New York.
In the more advanced of the class of cases which are still quite operable we are indeed almost sure to find more or less degenerated pus, but the amount of it varies greatly from time to time, and is not infrequently insignificant. The detection of tubercle bacilli in the sediment of the urine is of some positive value (it is absolute if its confusion with the smegma bacillus is sufficiently carefully excluded; and it should therefore be absolute in the sediment of the urine obtained by ureteral catheterization). Its absence is of no diagnostic value whatever; e.g. I have had a highly trained expert uuike repeated negative reports on the urine from a


Twentieth Century Practice. An International encyclopedia of modern medical science by leading authorities of Europe and America. Ed. by Thos. L. Stedman, M. D. Vol. XV. Infectious Diseases. 1898. 8vo, 658 pp. Wm. Wood & Co., New York.


The Principles and Practice of Medicine. By William Osier, M. D. Third Edition. 1898. 8vo, 1181 pp. D. Appleton & Co., New York.


The Mineral Waters and Health Resorts of Europe. Treatment of chronic diseases by spas and climates with hints as to the simultaneous employment of various physical and dietetic methods. Being a revised and enlarged edition of "The spas and mineral waters of Europe." By H. Weber, M. D., F. R. C. P., and F. P. Weber, M. D., F. R. 0. P. 1898. 8vo, 524 pp. Smith, Elder & Co., London.
November, 1898.'


A Clinical Text-Book of Medical Diagnosis for Physicians and Students. By Oswald Vierordt, M. D. Authorized translation with additions by F. H. Stuart, A. M., M. D. Fourth American edition, from the fifth German, revised and enlarged. 1898. 8vo, 603 pp. W. B. Saunders, Philadelphia.


WALTER S. DAVIS, M. D.


JOHNS HOPKINS HOSPITAL BULLETIN.




At a meeting held at 4.30 o'clock Wednesday afternoon, on the twenty-eighth of September, in the office of the superintendent of Johns Hopkins Hospital, presided over by Dr. H. M. Hurd, the following resolutions were adopted :


Whereas, we have lost our beloved comrade and fellow-worker, W.\LTER S. Davis ;
255


Be it Resolved, That we, the Medical Faculty of the Johns Hopkins University and the stafif of the Johns Hopkins Hospital do express to his family our most heartfelt sympathy in their great bereavement.


His enthusiasm in the profession was unbounded and always a stimulus to his co-workers ; but we shall remember him particularly for his sterling character, his ever cheerful disposition, and his fidelity as a friend, aud,


Be it further Resolved, That a copy of these resolutions be conveyed to his family and published in the Bulletin of the Johns Hopkins Hospital. THOMAS S. CULLEN,
bladder in which tubercular ulcerations were actually visible aud in which a subsequent report was jaositive.


JAMES F. MITCHELL, GUY L. HUNNER.
It is probable that the discharge of the bacilli with the urine is not uniform, and no man can exjiect to search a sediment so thoroughly as to detect the bacillus with certainty if only a few are present; but it is held that if a fresh sediment is injected into the peritoneum of a guinea-pig, the presence of only one or two bacilli will be enough to cause infection in this very sensitive animal. The generally accepted opinion that this is the most delicate test for tuberculosis known, and the great surgical importance of using the most delicate test possible for the determination of the condition of each kidney separately in suspected renal tuberculosis, has then been my reason for injecting the sediments obtained from the kidneys by ureteral catheterization into separate guinea-pigs in each of three cases of suspected renal tuerculosis.


Committee.
If this test is to be of real surgical value two points must be determined with regard to it: 1. Will it give us positive evidence in the early stages of the disease? 2. How absolute is the negative evidence obtained by the negative results from the other kidney in the same case? But neither of these questions can be answered by anything but an extended experience.


One case was positive as regards one kidney only, both the others were wholly negative, though each woman showed evidence of surgical disease in one of her kidneys. I have put off the publication of this report for several mouths in the hope of reporting the ultimate results in the equally important negative cases, but as both patients are still deferring operation* I am publishing the one positive result in the hope of inducing others to try this very delicate test, and also because the individual case is of itself of much interest from the slight development of the disease in the kidney which was removed, and from the very satisfactory improvement in the patient's condition since operation, which certainly so far supports the negative result obtained from the examination of her remaining kidney.


On March 31, 1898, I saw, with Dr. Percy C. Proctor, of Gloucester, Mass., Mrs. P., thirty-one years old, ten years married, multipara, of tuberculous family history, but with good personal history until the beginning of the present illness.


The Johns Hopkins Hospital Bulletins are issued monthly. They are printed by THE FRIEDENWALD CO., Baltimore. Single copies may be procured from Messrs. CITSITINO & CO. and the BALTIMORE NEWS COMPANY. Baltimore. Subscriptions, §1.00 a year, may b» addressed to the publishers, THE JOHNS HOPKINS PRESS, BALTIMORE; single copies will be sent by mail for fifUen cenU each.
Eight years ago, after suffering for some months from backache and bearing-down pain, she suddenly began to pass bloody urine, which gradually returned to the normal after a duration of some weeks. Though partially relieved of her backache after the attack, she has been a semi-invalid ever since. Four years later, in October of 1894, she had a second, similar attack, and on the 17th of February, 1898, a third attack, the haematuria beginning with equally little warning. The pain has always been relieved during the attacks, but has always returned after their cessation, and has never been affected by the act of urination. During these attacks she has passed urine about every half hour daring the day, but only






BULLETIN
While the paper was in press both negative cases came to
operation, and both proved to have non-tubercular disease. Both will be published in detail later.






OF
once or not at all during the night. In the intervals between the attacks she has had no frequency or other abnormalities of urination, (. e. the symptomatology was indistinctive.


On palpation no tenderness could be detected. On examination under ether her genital organs were essentially normal, and a careful visual inspection of the bladder showed no abnormality whatsoever, except that a stream of thin blood trickled steadily downward from the right ureteral orifice, while from the left spouted intermittently a normal looking urine.


The ureters were catheterized and the specimens were submitted to Dr. J. B. Ogdeu, Assistant in Chemistry in the Harvard Medical School, whose reports of the examination of the urine and of the inoculations which he made at my request are here appended:


"On March 22, 1898, two specimens of urine from the right and left ureters — case Mrs. P. — were submitted to me by Dr. Edw. Reynokls, for examination.


THE JOHNS HOPKINS HOSPITAL.
Urine from Right Ureter. — Amount received 10 cc; color, bloody ; reaction, alkaline ; specific gravity could not be taken as quantity of uriue was not sufficient ; urea, 1.01 percent.; albumin, between i and i of 1 per cent. The sediment, which was abundant, con-' sisted chiefly of normal blood. After the blood had been destroyed by means of distilled water, which had been acidulated with acetic acid numerous leucocytes, a few small round and caudate cells (probably ureteral) and rarely a brown granular cast were found. No crystalline elements detected.


Urine from Left Ureter. — Amount received 3cc.; color, pale, slightly turbid ; reaction, acid ; specific gravity could not be taken; urea, 0.95 per cent.; albumin, a trace. The sediment contained frequent normal and abnormal blood globules ami few leucocytes, many medium and small round cells, and numerous small caudate cells as from the ureter. An occasional granular and brown granular cast, and uric acid crystal.


The clinical examination of these specimens did not reveal much toward deciding as to the most probable cause of the clinical symptoms. The uric acid crystals suggested a possible cause of the trouble, but as it was several hours after the urines had been collected before a microscopical examination could be made, they were probably secondary (formed and deposited after the collection of the urine).


Vol. IX.- No. 92.]
The considerable quantity of normal blood in the urine from the right ureter was apparently of traumatic origin, and was the probable cause of the alkalinity of the urine. The presence of numerous leucocytes in the sediment led to the question: Are there more leucocytes than can be accounted for by the amount of blood present? This I was unable to fully decide, although they appeared to be present in somewhat larger numbers than would be expected in that quantity of blood.


The tubular disturbance shown by the presence of casts, although slight, appeared to be more marked in the left kidney than in the right.


Since the question of a tuberculosis of the urinary tract had been raised as a possible cause of the symptoms in this case, it was considered advisable to make as thorough and complete an examination of the urine for tubercle bacilli as was possible, and at the same time, if a tuberculosis existed, to determine wbether one or both kidneys were diseased. Accordingly the sediments of both specimens were washed twice, by decantation, with distilled water, in order to free them fiom albumin and other soluble urinary constituents, a centrifuge being used to settle tbe sediments after each addition of water. Each sediment was then divided into two portions ; one portion was injected into a guinea-pig, and the other was reserved for microscopical examination for tubercle bacilli.


BALTIMORE, NOVEMBER, 1898.




256






JOHNS HOPKINS HOSPITAL BULLETIN.




GOIsTTEIsTTS.


[No. 92.




The Diajnosis of the Condition of each Kidney by Inoculation of the Separated Sediments into Guinea-pigs in Suspected Renal Tuberculosis. By Edward Reynolds, M. D., - - - 253


Laparotomy for Intestinal Perforation in Typhoid Fever. By Harvey W. Gushing, M. D., 257
The injections into the guinea-pigs were made as follows : The barrel and needleof asmall Koch syringe were thoroughly sterilized by dry heat; the abdominal wall of a guinea-pig was thoroughly cleansed and then i cc. of the sediment of the urine from the right ureter was injected into the abdominal cavity. The barrel and needle of the syringe were cleansed and again sterilized. The abdominal wall of another guinea-pig was cleansed, after which ice. of the sediment of the urine from the left ureter was injected into the abdominal cavity.


Spontaneous Hsemorrhagic Septicsemia in a Guinei-pig, caused by a Bacillus. By George H. VVbaver, M. D., - - - - -270
The pigs, following the injections, showed only slight disturbance, from which they recovered in a few days, and were apparently quite well for the eight weeks they were under observation. An examination of the- pigs between the fifth and sixth weeks showed that the one which had been inoculated with the sediment of the urine from the rigtit kidney had, in both groins, enlarged glands, wliich were hard and quite nodular. The one injected with the sediment of the urine from the left kidney showed no enlarged glands and was apparently in a healthy condition. Both animals were then placed under the care of Dr. W. F. Whitney.


Antitoxic Relation between Bee Poison and Honey (?). By G. H. Stover, M.D., ------- 271
On the same day that the inoculations were made the portion of sediment which had been reservo'l for microscopiral examination was centrifugalized, and the sediment placed on cover-glasses was carefully dried, stained and examined. No tubercle bacilli could be found in the limited number of preparations at hand. The - amount of sediment furnished by these small specimens was originally comparatively slight, and since some of the sediment had been used for the inoculation experiments, too little remained for as thorough a. microscopical examination as is often necessary for the detection of tubercle bacilli in the urine."


The patient was kept absolutely in bed on a non-stimulating diet, but the hsematuria continued until the latter part of April, when the bleeding ceased and the pain in the backreturned. As I thought it advisable to give her some weeks in which to regain condition, the pigs were left undisturbed till some weeks later, when I received the following letters from Dr. W. F. Whitney, curator of the Warren Anatomical Museum and Pathologist to the Massachusetts General Hospital. .


"May 2G, 189-;. The guinea-pig inoculated with the urine from the right kidney of Mrs. P. was killed to day, and showed cheesy abscesses in the glands of both groins, in the pus from which a few scattered tubercle bacilli were found. There were also characteristic miliary cheesy nodules in the spleen, as well as a few scattered areas in the liver. Tlie condition is perfectly characteristic of inoculated tuberculosis."


Proceedings of Societies :
June 13, 1898. The guinea-pig inoculated with the urine from the left kidney of Mrs. P. on March 22, 1898, was killed June 9, 1898, and found to be perfectly normal."


The Hospital Medical Society,
As I always think it a pity to disturb the ureter of the sound side by catheterization immediately before an operation, in renal cases, I made no further ureteral examination, but the urine secreted in 24 hours was now collected and submitted to Dr. Ogden, whose report upon it follows :


Broadbent's Sign [Dr. Camac] ; — Aortic Aneurysm [Dr. Brown] ; — Discussion of Mr. MacCallum's Paper on Pathology of Heart Muscle [Dr. Flkxner] ; — Epidemic Cerebrospinal Meningitis — Exhibition of Specimens [Dr. Livingood].
"On June lOth an examination of the twenty-four hour urine showed the following :— Twenty-four hour quantity, 1150 cc; color, pale, turbid; reaction, acid; sp. gr., 1013; urea, 1.13 per cent, or 12.99 grammes in 24 hours; albumin, a slight trace ; bile and sugar absent. The sediment consisted chiefly of pus which was free and in clumps. Considerable squamous and scaly epithelium and a few blood globules; a few small round cells. An occasional hyaline and granular cast with renal cells and little blood adherent.


Notes on New Books,




The greater part of the pus seemed to come from the same source as the squamous and scaly epithelium, in other words, probably from the vagina. I could not be certain that some of the pus did not come from the bladder or from the diseased kidney. There was still evidence of a tubular disturbance (shown by the casts) which had more the appearance of a mild renal congestion than any primary disease of the kidneys.


274
The sediment of this twenty-four hour urine was thoroughly examined for tubercle bacilli, but with a negative result."


June 24th I removed the right kidney by lumbar nephrectomy. The kidney was brought to the surface with great ease and rapidity and was so wholly normal in appearance that nothing but the absolute certainty which I thought myself to possess of its diseased condition would have induced me to remove it. The ureter was thoroughly normal in appearance, was cut some two inches below the kidney, closed in by catgut sutures, and dropped into the wound. On splitting the kidney after its removal the tubercular disease was at once evident, in the shape of numerous miliary tubercles on the mucous membrane of the pelvis.


The very beaittiful painting which is here reproduced was made for me by Miss Florence Byrnes, artist to the Harvard Medical School.


Books Received, ----------------- 275
Dr. Whitney kindly examined the kidney, and his report and the letter which he sent me are inserted below:
 
"The kidney was of normal size. The capsule stripped off easily, showing the surface marked by numerous small, superficial cicatricial depressions. The cortical part was slightly narrow and pale. In the papillary region were a few scattered minute opaque dots, and the pelvis was quite thickly covered with them, and markedly injected. Microscopic examination : The epithelium of the cortical tubules was low and irregular, and the cicatricial depressions were marked by a round-cell infiltration and disappearance of the tubules at that point. The opaque dots were composed of small round and epithelioid cells with an occasional giant cell. The centres were cheesy degenerated. The diagnosis is a miliary tuberculosis of the pelvis and kidney."


Makblehead, Mass., August 13, 1898. Dear Dr. Reynolds: — I enclose the report of the kidney which you desired. The case is certainly favorable, as the local lesions are comparatively slight, and it is interesting that, with so little ulceration and loss of substance, a positive result should have been obtained from the inoculation with the urine.


Yours sincerely,


THE DIAGNOSIS OF THE CONDITION OF EACH KIDNEY BY INOCULATION OF THE SEPARATED SEDIMENTS INTO GUINEA-PIGS IN SUSPECTED RENAL TUBERCULOSIS.
W. F. Whitney.


By Edward Reynolds, M.D., Boston, Mass.
The patient's convaleseucefrom the operation was rapid and satisfactory. She passed from thirty to forty ounces of urine uninterruptedly and never had a bad symptom. 1 have not seen her since, but a letter from Dr. Proctor, dated October 10, 1898, informs me that she is now passing forty ounces of normal urine with no evidence of renal irritation in the sediment. She has gained in flesh and color and is greatly improved in general condition.


The negative results of two examinations of the sediment for tuberculosis, made by an expert at widely separate times, and the positive result of the inoculation of a guinea-pig by one of these same sediments, with the confirmation of this positive result by inspection of the kidney in question, and the improvement of the patient's health after the operation, form certainly a picture of considerable clinical interest, more




The direct inspection of tlie air-distended bladder which we owe to Kelly, with its sequelae of easy exploration of the ureters, has already led to great advances towards an accurate knowledge of the urinary diseases of women, and at the present moment, when so much is opening up before us, any new step towards exactness of diagnosis seems worth reporting.


Little is yet known of the natural history of renal tuberculosis; indeed, it is for comparatively few years that we have known that tuberculosis can be primary in the kidney, and the great mass of the profession has not yet realized that this disease is often localized for many years in one kidney before invading the rest of the urinary tract; but in the last three years we have been accumulating a considerable amount of clinical evidence in support of these views, namely, that though renal tuberculosis does in the end kill when untreated, it is often nevertheless so strictly localized in one kidney that the patient may be restored to perfect health after this is removed by nephrectomy. Among the many cases of this nature which we now have may be cited a remarkable one by Vineburg* and three by Kelly. f I am myself able to add three unpublished cases, two of my own and one very remarkable
THE JOHNS HOPKINS HOSPITAL BULLETIN.






•Medical Record, Feb. 6th, 1898.
NOVEMBER, 1898.


f Johns Hopkins Hospital Bulletin, Feb.-Mar., 1896.






case which I saw in consultation after a nephrectomy by another surgeon. Those who have ever seen how these patients are transformed in nutrition and general health, by the removal of the offending kidney, will be slow to listen to arguments against the ojjeration for cases in which the disease is unilateral, but it is of course justifiable only in such cases, and our success must therefore rest on our power of diagnosing the disease while it is limited to one kidney, and thus confining the operation to cases which are capable of cure by nephrectomy. For this purpose we must not only be able to establish the diagnosis of renal tuberculosis, in advance of the constitutional breakdown of the patient, but must also be able to satisfy ourselves with some positiveness of the health of the other kidney; and striking testimony to the advances which have been made in this subject during the last few years is to be obtained by inspection of the most recent text-books on medical diagnosis. Thus one, which shall be nameless, in the course of three pages devoted to renal tuberculosis, gives under diagnosis only these three clues: the presence in the sediment of the urine of little, yellow, cheesy masses of degenerated tuberculous material ; the presence of pus and other signs of chronic pyelitis from no assignable cause other than tubercle, and, lastly, the presence of tuberculosis in other organs. Even the latest edition of Osier, in which the section on this subject
Miliary Tuberculosis of Kidney.






254
November, 1898.]




Line 27,706: Line 27,713:




[No. 92.
257






has been considerably rewritten and evidently brought up to date, may be summarized as saying that there is but little chance of making a diagnosis unless we are put upon the track by finding tuberculosis in other organs, though this acute writer does mention the special methods of examination employed by gynecologists and the hope for the future which they afford.
especially, as this is, so far as I am aware, the first case in which this test has been used for the esamiiiatioa of each kiduey separately.


It is apparent that these medical descriptions refer to what we from a surgical standpoint should call advanced disease. Our surgical specialty has already led us to the possibility of establishing the diagnosis at a very much earlier stage than this.
As so little is known of frequency of unilateral and primary renal tuberculosis I had hoped that an examination of the records of a large number of autopsies, performed upon subjects who died from other diseases than tuberculosis, might yield something of interest, and accordingly requested Dr. John T. Bottoinley to examine the pathological records of the Boston City Hospital for some years past. He looked over 3300 reports which were consecutive except for the omission of deaths from tubercular disease in other organs of the body, but found only two cases of primary renal tuberculosis, both unilateral, one of which died from fracture of the spine, the other of uremia.


Though such a diagnosis can be made only by physical examination, a suspicion of tubercular or other renal disease will often be excited by the symptomatology, and this must therefore be briefly reviewed. The early symptoms of the disease will vary greatly both in character and in intensity in different cases, and from time to time in the same case, but will consist typically of pain and tenderness over the abdomen on the affected side, frequency of urination, and sometimes hematuria. These symptoms are, however, equally characteristic of simple pyelitis, renal calculus and new growth in the pelvis of the kidney. There are, indeed, no differences of kind in the symptomatology of these diseases in their early stages, though there are differences in the degree in which the several symptoms are likely to be present.
His abstracts of the cases are as follows:


All these diseases are characterized by dull pains over the kidney and along the course of the ureter on the affected side. The pain is often bearing-down in character, and therefore a uterine origin is usually assigned to it; is usually increased by standing ; and is always more or less associated with frequency of micturition, occurring at night as well as in the day-time. Ill all of them the call to micturate is a very urgent one; the pain on micturition is usually leferred to the meatus ; and all are liable to more or less tenesmus at the end of micturition. In all the pain may be increased by jarring or jolting (as in driving over rough roads).
Case I. Surg. Eec. C, Vol. 23, Page 248. Male, 48 years. No venereal diseases, case of scalp wound, alcoholism, and fractured spine.


This whole group of symptoms is, however, in reality symptomatic of the amount of inflammation present, and therefore varies with this subsidiary feature of the case. They are often though not always more marked in renal stone than in tlie other diseases.
Autopsy Eec, Vol. 16, Page 56. Autopsy showed that right


All the diseases enumerated may be accompanied by hematuria, but this is rare in simple pyelitis ; it is more likely to be profuse in tuberculosis or a new growth than in stone.


In all, the patients are almost equally liable to attacks of mild renal colic, due usually to inflammatory obstruction in the ureter. They differ from the pains excited by the passage of a calculus in being less severe and not followed by the appearance of the stone. These attacks are perhaps less common in new growths than in the other diseases under consideration. Not infrequently, at intervals in the course of these chronic renal diseases (and especially in tuberculosis and simple pyelitis), the inflammatory symptoms will be found to be most marked on the sound side. This is probably because each exacerbation of the disease in the affected side leads to an increased elimination of toxic materials from the functionally more active kidney; and this excites a transitory and some


kidney was about normal size ; upper third replaced by several sacs, each corresponding to a pyramid and its accompanying cortex ; each sac had a thin, firm capsule which was filled with opaque, white, cheesy or putty-like material, a little gritty to the touch. In one of the lower pyramids was a similar sac ; no evidence of any inflammation ; microscopic examination negative ; pelvis and ureter normal. Bladder and ai>pendage8 were normal except a few small calcified nodules in prostate.


what acute inflammation in the mucous membrane of the urinary apparatus on the sound side.
Anatomical diagnosis. Stenosis of aortic valve. Chronic passive congestion of spleen and kidneys. Chronic tuberculosis of right kidney. Fracture of spine.


This transposition of symptoms I have seen so frequently (I may say almost constantly) that I am sure it must always be guarded against. The side on which the patient tells us that the symptoms were first noticed is usually the diseased side.
Case II. Med. Rec, Vol. 175, Page 249. Female, 45 years, married. Always well till three months before ; all symptoms pointed to disease of the kidney.


The inquiry into the history should be followed by palpation, both abdominal and bimanual. In all these lesions we find, on palpation, a tenderness which may extend from top to bottom of the urinary tract on the affected, and even on both sides, but which is usually most marked at one or more of three points: namely, over the kidney; at the spot where the ureter crosses the brim of the pelvis, in which ease it is often limited to a spot the size of the finger-tip, midway between the umbilicus and the anterior superior spine of the ilium (McBurney's point or its fellow); and, finally, over the vesical end of the ureter at the side of the cervix, which examination may even detect an enlargement or induration of the ureter. These tender points are again symptomatic of the amount of inflammation present, and therefore usually vary with the amount of pain.
Autopsy Rec, Vol. 3, Page 125. Autopsy. No truly normal tissue remained of left kidney. The entire wall was composed of abscesses of varying sizes, containing a thick almost cheesy pus. Peri-nephritic fat adherent to the wall, also to diaphragm ; nothing important in other organs.


A study of the history and the results of the gynecological examination usually enables us, then, to suspect, and sometimes permits us to postulate, a diagnosis of some renal disease of a surgical nature, but it does not enable us to say what, nor always on which side it is. The special examination now steps in and the real diagnosis begins here.
[The second case could probably have been saved by nephrectomy had the diagnosis been made a few months before. She, however, entered the hospital in the year 1880 and in a dying condition.]


If a visual examination of the bladder shows that the vesical mucous membrane is substantially normal except in the interureteral region, and that a strongly localized inflammation is present there, the source of that inflammation is probably to be found in the passage of a vicious urine from one or the other ureter. If one ureteral orifice is abnormal in appearance, this probably marks the diseased side. The next and most important step is the catheterization of the ureters and a microscopical and chemical examination of the urine secreted by each kidney. But here the results must be interpreted with the greatest care, as recent advances have made it certain that most of our past opinions on the results of urinalysis must be revised in the light of the new knowledge. This is especially true of renal tuberculosis; the large amounts of degenerated pus and bits of necrotic material which are commonly described as characteristic of the disease being, in fact, found only in locally advanced cases, while the urinary signs of early tuberculosis are usually limited to the detection of pus and the bacilli by the microscope.


In the more advanced of the class of cases which are still quite operable we are indeed almost sure to find more or less degenerated pus, but the amount of it varies greatly from time to time, and is not infrequently insignificant. The detection of tubercle bacilli in the sediment of the urine is of some positive value (it is absolute if its confusion with the smegma bacillus is sufficiently carefully excluded; and it should therefore be absolute in the sediment of the urine obtained by ureteral catheterization). Its absence is of no diagnostic value whatever; e.g. I have had a highly trained expert uuike repeated negative reports on the urine from a


LAPAROTOMY FOR INTESTINAL PERFORATION IN TYPHOID FEVER.


A RFPORT OF FOUR CASES, WITH A DISCUSSION OF THE DIAGNOSTIC SIGNS OF PERFORATION. By Harvey W. Gushing, M. D., Resident Surgeon, The Johns Hojjhins Ebspifal


November, 1898.'




The present communication is based upon four recent cases of laparotomy foi- perforating typhoid ulcer, in one of which the abdominal ca\ ity was opened on three successive occasions with recovery.


JOHNS HOPKINS HOSPITAL BULLETIN.
The fact that surgical intervention offers practically the only hope in tlieso cases seems to be studiously overlooked, if we are to judge by the paucity of occasions in which laparotomy has been performed for this condition.


On a recent visit to the military hospital at Fort McPhersou, the writer was told that of thirty autopsies held upon fatal cases of typhoid which had occurred there, perforation was found to have been the cause of death in six instances, one being of the appendicular variety. This would attribute to perforation aloi.e 30 per cent, of the fatalities, a percentage which corresponds with that of Hare of Brisbane, and is almost twice that of Murchison (11.38 per cent.), and three times the figures given by ]ir. Fitz (6.58 per cent, in 4680 cases). In none of these cases had operative intervention been advised, nor do I know of a single instance of operation for the relief of typhoid perforation on any of the possible 2000 cases which have died from typhoid in the field hospitals and elsewhere during the late war.


H the recent statistics of Gesselewitsch and Wanach (Centralblatt f iir die ( rreuzgcbieten der Medizin und Chirurgie, Bd. I, No. 6, p. 382, IS'.IS) are to be relied upon, namely, that lO per cent, of the entire number of fatalities in typhoid are due to perforative peritonitis, we may credit 200 of these deaths to this cause alone. According to the statistics from Fort McPherson and those of Hare, 400, or double the number, would be accounted for in this way.


255




In a recent communication Dr. Nicholas Seun writes: "Strange as it may seem, having seen hundreds of cases of typhoid fever during the war, I was called upon only once to operate for perforation. In that instance the patient was moribund, and I refused to operate. I have reason to believe that this complication was frequently overlooked."


bladder in which tubercular ulcerations were actually visible aud in which a subsequent report was jaositive.
We have four widely different but quite characteristic histories to report:


It is probable that the discharge of the bacilli with the urine is not uniform, and no man can exjiect to search a sediment so thoroughly as to detect the bacillus with certainty if only a few are present; but it is held that if a fresh sediment is injected into the peritoneum of a guinea-pig, the presence of only one or two bacilli will be enough to cause infection in this very sensitive animal. The generally accepted opinion that this is the most delicate test for tuberculosis known, and the great surgical importance of using the most delicate test possible for the determination of the condition of each kidney separately in suspected renal tuberculosis, has then been my reason for injecting the sediments obtained from the kidneys by ureteral catheterization into separate guinea-pigs in each of three cases of suspected renal tuerculosis.
In Case I an early diagnosis and immediate operation, before peritonitis set in, led to recovery.


If this test is to be of real surgical value two points must be determined with regard to it: 1. Will it give us positive evidence in the early stages of the disease? 2. How absolute is the negative evidence obtained by the negative results from the other kidney in the same case? But neither of these questions can be answered by anything but an extended experience.
In Case II general purulent peritonitis with three perforations was present, and it should be considered that the relief of the general peritonitis, and not typhoid perforation which had taken place many hours before, was the objective point of operation.


One case was positive as regards one kidney only, both the others were wholly negative, though each woman showed evidence of surgical disease in one of her kidneys. I have put off the publication of this report for several mouths in the hope of reporting the ultimate results in the equally important negative cases, but as both patients are still deferring operation* I am publishing the one positive result in the hope of inducing others to try this very delicate test, and also because the individual case is of itself of much interest from the slight development of the disease in the kidney which was removed, and from the very satisfactory improvement in the patient's condition since operation, which certainly so far supports the negative result obtained from the examination of her remaining kidney.
In Case III what may be considered as pre-perforative symptoms of peritonitis were present and were neglected. Perforation subsequently occurred with, unfortunately, a virulent streptococcus infection, which proved fatal despite early laparotomy.


On March 31, 1898, I saw, with Dr. Percy C. Proctor, of Gloucester, Mass., Mrs. P., thirty-one years old, ten years married, multipara, of tuberculous family history, but with good personal history until the beginning of the present illness.
Case IV illustrates one of the strange attacks which closely simulate perforation. No lesion was found at the operation, and the exploration had no appreciable effect upon the subsequent course of the fever.


Eight years ago, after suffering for some months from backache and bearing-down pain, she suddenly began to pass bloody urine, which gradually returned to the normal after a duration of some weeks. Though partially relieved of her backache after the attack, she has been a semi-invalid ever since. Four years later, in October of 1894, she had a second, similar attack, and on the 17th of February, 1898, a third attack, the haematuria beginning with equally little warning. The pain has always been relieved during the attacks, but has always returned after their cessation, and has never been affected by the act of urination. During these attacks she has passed urine about every half hour daring the day, but only
Case I. Surgical No. 8009. Typhoid perforation at end of second week. Laparotomy. Suture of perforation. Drainage. Fcecal fistula after 3 days from second perforation. Spontaneous closure of fistula. Seven days later symptoms of perforation. Laparotomy, No perforation found. Obstruction over




258


While the paper was in press both negative cases came to
operation, and both proved to have non-tubercular disease. Both will be published in detail later.




JOHNS HOPKINS HOSPITAL BULLETIN.


once or not at all during the night. In the intervals between the attacks she has had no frequency or other abnormalities of urination, (. e. the symptomatology was indistinctive.


On palpation no tenderness could be detected. On examination under ether her genital organs were essentially normal, and a careful visual inspection of the bladder showed no abnormality whatsoever, except that a stream of thin blood trickled steadily downward from the right ureteral orifice, while from the left spouted intermittently a normal looking urine.


The ureters were catheterized and the specimens were submitted to Dr. J. B. Ogdeu, Assistant in Chemistry in the Harvard Medical School, whose reports of the examination of the urine and of the inoculations which he made at my request are here appended:
[No. 92.


"On March 22, 1898, two specimens of urine from the right and left ureters — case Mrs. P. — were submitted to me by Dr. Edw. Reynokls, for examination.


Urine from Right Ureter. — Amount received 10 cc; color, bloody ; reaction, alkaline ; specific gravity could not be taken as quantity of uriue was not sufficient ; urea, 1.01 percent.; albumin, between i and i of 1 per cent. The sediment, which was abundant, con-' sisted chiefly of normal blood. After the blood had been destroyed by means of distilled water, which had been acidulated with acetic acid numerous leucocytes, a few small round and caudate cells (probably ureteral) and rarely a brown granular cast were found. No crystalline elements detected.


Urine from Left Ureter. — Amount received 3cc.; color, pale, slightly turbid ; reaction, acid ; specific gravity could not be taken; urea, 0.95 per cent.; albumin, a trace. The sediment contained frequent normal and abnormal blood globules ami few leucocytes, many medium and small round cells, and numerous small caudate cells as from the ureter. An occasional granular and brown granular cast, and uric acid crystal.
looked. Two days later laparotomy for acute mtestinal ohstruction with closure of second perforation. Recovery.


The clinical examination of these specimens did not reveal much toward deciding as to the most probable cause of the clinical symptoms. The uric acid crystals suggested a possible cause of the trouble, but as it was several hours after the urines had been collected before a microscopical examination could be made, they were probably secondary (formed and deposited after the collection of the urine).
Herbert H., aged 9, was brought into the medical wards of the Hospital on the 8th of August with the history of having been ill since the first of the month with "pain in his head and stomach." His mother and one brother were also in the hospital, and one brother had just died of "typhoid" at home. On entrance, the temperature was 104.2°, the pulse rapid, the spleen enlarged and the general appearance typhoidal. There was some tenderness noted in the lower right quadrant of the abdomen. There was no Widal reaction obtainable at this time, nor had there been in the case of his brother and mother, who had had a very mild type of fever. The patient was put on the usual bath treatment. August 9th, leucocytes 8400.


The considerable quantity of normal blood in the urine from the right ureter was apparently of traumatic origin, and was the probable cause of the alkalinity of the urine. The presence of numerous leucocytes in the sediment led to the question: Are there more leucocytes than can be accounted for by the amount of blood present? This I was unable to fully decide, although they appeared to be present in somewhat larger numbers than would be expected in that quantity of blood.
Dr. Thayer's note on August 11th says: "Abdomen is a little full. Patient does not flinch on pressure."


The tubular disturbance shown by the presence of casts, although slight, appeared to be more marked in the left kidney than in the right.
There is no further note of unusual interest. The boy was dull, and seemed to be having a rather severe attack. He complained much of pain in his abdomen on being given his tubs.


Since the question of a tuberculosis of the urinary tract had been raised as a possible cause of the symptoms in this case, it was considered advisable to make as thorough and complete an examination of the urine for tubercle bacilli as was possible, and at the same time, if a tuberculosis existed, to determine wbether one or both kidneys were diseased. Accordingly the sediments of both specimens were washed twice, by decantation, with distilled water, in order to free them fiom albumin and other soluble urinary constituents, a centrifuge being used to settle tbe sediments after each addition of water. Each sediment was then divided into two portions ; one portion was injected into a guinea-pig, and the other was reserved for microscopical examination for tubercle bacilli.
On the morning of August 13th (five days after admission) the patient was found to be complaining of abdominal pain. He had vomited twice and his pulse rate had increased. The leucocytes were 9600.


He was seen, in consultation with Dr. Thayer, at 1 P. M. At this time his respirations were 34 ; his pulse 165, rather thready and of poor quality ; temperature 105°. He was crying out and complaining of general colicky abdominal pain. He was very restless ; his expression pinched ; his color quite cyanotic, with lips blue and extremities blue and cold. The abdomen was quite soft and there was no muscle spasm. There was considerable general tenderness, which seemed more marked on the right side. Pressure per rectum in the recto-vesical cul-de-sac seemed to cause especial pain, but no more marked on one side than the other. There was some apparent increase of dulness in the flanks, but no shifting dulness. There was no obliteration of liver dulness. The leucocytes were 16,000. The patient was immediately transferred to the operating-room.


Before the administration of anaesthesia the temperature was 105° (there had been no fall up to this time) and the pulse 170.


256
Operation /.—August 13th, 1898, 1.30 P. M., four hours after first symptoms, under primary chloroform ansestliesia.


Median laparotomy. Partial evisceration. Clostire of perforation. Toilet of peritoneum with salt solution irrigation. Drainage.


An incision was made in the median line below the umbilicus. On opening the peritoneal cavity a considerable amount (perhaps 200 cc.) of sero-purulent fluid escaped, coming chiefly from the pelvis. Cultures were taken from this fluid and it was also immediately examined in cover-slip preparations. It contained a great number of polymorphonuclear leucocytes, but no micro-organisms could be found. The serosa of the intestine was everywhere greatly congested, but evidently the greatest reaction was in the right iliac fossa, where the loops of the ileum were especially injected and covered with a slight fibrinous deposit. The general cavity to the left was walled off with gauze and the loops of the ileum drawn from the wound. The last foot of the small intestine showed several greatly thinned areas corresponding to Peyer's patches. In the centre of one of these areas, the surroundings of which were quite bluish in color, was a small perforation about two millimetres in diameter, from which fluid fasces were flowing. It was about 25 cm. from the caecum and situated in the free


JOHNS HOPKINS HOSPITAL BULLETIN.




surface of the bowel. A few centimetres beyond this were two more patches, which seemed very thin and practically covered by little more than serosa. A few fine, filmy adhesions held the omentum to this part of the bowel.


[No. 92.
The perforation was closed by a circular suture of fine silk taken about the edge of the thinned area, which was fortunately small, measuring about one centimetre in diameter. A similar inversion of the two thin neighboring patches would have been attempted, but the patient's condition at this time demanded immediate attention and the idea was abandoned. His pulse was almost imperceptible and his respirations were very shallow. Hypodermic injections of strychnia were given and an infusion of a litre of salt solution in the pectoral region. The exposed coils of intestine were irrigated and the abdominal cavity was flushed out with salt solution. A strip of bismuth gauze was left in for drainage, leading down to the site of the suture, and another to the two thinned Peyer's patches. The omentum was pulled down over the gauze. The abdominal wound was then partly closed. The operation lasted but twenty minutes from the beginning of ansesthesia till the final closure.


The cultures taken from the fluid found free in the peritoneal cavity remained sterile. No cultures were taken from the material flowing from the perforation.


The patient rallied well from the operation, and in eight hours the pulse had fallen to 112, and the temperature to normal. There was no vomiting, and he slept most of the time for the next twenty-four hours, taking liquid nourishment (albumen water) well, during his waking intervals. Three hundred cubic centimetres of salt solution were given per rectum every four hours for thirst. On the following day the temperature again became elevated ; the day after the leucocytosis disappeared, and for the following ten days the clinical picture was that of an ordinary typhoid in the third week. A faecal fistula developed on the second day, discharging typical peasoup faeces. It was impossible to tell, at that time, whether this discharge came from the broken down suture or from one of the neighboring thinned Peyer's patches, to which the drain led. (It was subsequently proved to come from the latter.)


The injections into the guinea-pigs were made as follows : The barrel and needleof asmall Koch syringe were thoroughly sterilized by dry heat; the abdominal wall of a guinea-pig was thoroughly cleansed and then i cc. of the sediment of the urine from the right ureter was injected into the abdominal cavity. The barrel and needle of the syringe were cleansed and again sterilized. The abdominal wall of another guinea-pig was cleansed, after which ice. of the sediment of the urine from the left ureter was injected into the abdominal cavity.
The boy complained a good deal of abdominal pain at times, and of pain on micturition, but there was no abdominal rigidity or other symptoms of peritoneal inflammation. He was given regular ice sponges, after which he would sleep for long intervals. The fscal fistula ceased to discharge after a few days. There was considerable diarrhcea at this time (cf. Clinical chart).


The pigs, following the injections, showed only slight disturbance, from which they recovered in a few days, and were apparently quite well for the eight weeks they were under observation. An examination of the- pigs between the fifth and sixth weeks showed that the one which had been inoculated with the sediment of the urine from the rigtit kidney had, in both groins, enlarged glands, wliich were hard and quite nodular. The one injected with the sediment of the urine from the left kidney showed no enlarged glands and was apparently in a healthy condition. Both animals were then placed under the care of Dr. W. F. Whitney.
August ISlh. (6 days after opei-afion I.) A positive AVidal reaction was obtained by Dr. Schenck for the first time (in ten minutes in a dilution of 1 to 40). Cultures from the rectum, taken through a high rectal tube, showed only the bacillus coli communis. The patient had a pinched look and was very peevish. The pulse was weak and dicrotic. A crop of rose spots was present on the abdomen.


On the same day that the inoculations were made the portion of sediment which had been reservo'l for microscopiral examination was centrifugalized, and the sediment placed on cover-glasses was carefully dried, stained and examined. No tubercle bacilli could be found in the limited number of preparations at hand. The - amount of sediment furnished by these small specimens was originally comparatively slight, and since some of the sediment had been used for the inoculation experiments, too little remained for as thorough a. microscopical examination as is often necessary for the detection of tubercle bacilli in the urine."
August 25th. {\^ days after operation I.) On the evening of this date, after a very good day, the patient became suddenly much worse and vomited several times. At 9 P. M., when seen in consultation with Dr. Thayer, he was quite


The patient was kept absolutely in bed on a non-stimulating diet, but the hsematuria continued until the latter part of April, when the bleeding ceased and the pain in the backreturned. As I thought it advisable to give her some weeks in which to regain condition, the pigs were left undisturbed till some weeks later, when I received the following letters from Dr. W. F. Whitney, curator of the Warren Anatomical Museum and Pathologist to the Massachusetts General Hospital. .


"May 2G, 189-;. The guinea-pig inoculated with the urine from the right kidney of Mrs. P. was killed to day, and showed cheesy abscesses in the glands of both groins, in the pus from which a few scattered tubercle bacilli were found. There were also characteristic miliary cheesy nodules in the spleen, as well as a few scattered areas in the liver. Tlie condition is perfectly characteristic of inoculated tuberculosis."


June 13, 1898. The guinea-pig inoculated with the urine from the left kidney of Mrs. P. on March 22, 1898, was killed June 9, 1898, and found to be perfectly normal."
NOVBMBEB, 1898.]


As I always think it a pity to disturb the ureter of the sound side by catheterization immediately before an operation, in renal cases, I made no further ureteral examination, but the urine secreted in 24 hours was now collected and submitted to Dr. Ogden, whose report upon it follows :


"On June lOth an examination of the twenty-four hour urine showed the following :— Twenty-four hour quantity, 1150 cc; color, pale, turbid; reaction, acid; sp. gr., 1013; urea, 1.13 per cent, or 12.99 grammes in 24 hours; albumin, a slight trace ; bile and sugar absent. The sediment consisted chiefly of pus which was free and in clumps. Considerable squamous and scaly epithelium and a few blood globules; a few small round cells. An occasional hyaline and granular cast with renal cells and little blood adherent.


JOHNS HOPKINS HOSPITAL BULLETIN.




The greater part of the pus seemed to come from the same source as the squamous and scaly epithelium, in other words, probably from the vagina. I could not be certain that some of the pus did not come from the bladder or from the diseased kidney. There was still evidence of a tubular disturbance (shown by the casts) which had more the appearance of a mild renal congestion than any primary disease of the kidneys.


The sediment of this twenty-four hour urine was thoroughly examined for tubercle bacilli, but with a negative result."
259


June 24th I removed the right kidney by lumbar nephrectomy. The kidney was brought to the surface with great ease and rapidity and was so wholly normal in appearance that nothing but the absolute certainty which I thought myself to possess of its diseased condition would have induced me to remove it. The ureter was thoroughly normal in appearance, was cut some two inches below the kidney, closed in by catgut sutures, and dropped into the wound. On splitting the kidney after its removal the tubercular disease was at once evident, in the shape of numerous miliary tubercles on the mucous membrane of the pelvis.


The very beaittiful painting which is here reproduced was made for me by Miss Florence Byrnes, artist to the Harvard Medical School.


Dr. Whitney kindly examined the kidney, and his report and the letter which he sent me are inserted below:
collapsed and very restless. His abdomen was slightly distended. He was hiccoughing and complaining of abdominal pain. He looked pinched and the extremities were cold and sweating. His leucocytes were only 4000.


"The kidney was of normal size. The capsule stripped off easily, showing the surface marked by numerous small, superficial cicatricial depressions. The cortical part was slightly narrow and pale. In the papillary region were a few scattered minute opaque dots, and the pelvis was quite thickly covered with them, and markedly injected. Microscopic examination : The epithelium of the cortical tubules was low and irregular, and the cicatricial depressions were marked by a round-cell infiltration and disappearance of the tubules at that point. The opaque dots were composed of small round and epithelioid cells with an occasional giant cell. The centres were cheesy degenerated. The diagnosis is a miliary tuberculosis of the pelvis and kidney."
A definite diagnosis of perforation was made and steps taken for immediate operation. An hour later the temperature had fallen four degrees to 98.6°, and the leucocytes had increased to 13,000.


Makblehead, Mass., August 13, 1898. Dear Dr. Reynolds: — I enclose the report of the kidney which you desired. The case is certainly favorable, as the local lesions are comparatively slight, and it is interesting that, with so little ulceration and loss of substance, a positive result should have been obtained from the inoculation with the urine.
Operation II, August 25, 1898, 10.30 P. M.; two hours aftei first symptoms ; under chloroform anaesthesia. Median laparotomy. No cause for symptoms demonstrable. Closure tvifh drainage.


Yours sincerely,
The abdomen was opened beside the first incision, avoiding the site of the fistula. There was no free fluid. The bowels were not injected except to a slight degree in a few places, corresponding to some of Peyer's patches. No evidence whatever of a perforation could be found. There were no adhesions except about the loop of ileum which led to the old sinus and which was surrounded by quite firm omental adhesions. These were not broken up. There was no particular distension of one coil more than another. (There was nothing to suggest the thought of obstruction, and I must confess it did not occur to me. I supposed that I had overlooked a perforation somewhere, but the patient's condition precluded further search.) The wound was closed, with a small drain leading to the omental adhesions.


W. F. Whitney.
The operation lasted thirty-five minutes from the beginning of ausesthetizatiou. Cultures taken from the site of the adhesions remained sterile.


The patient's convaleseucefrom the operation was rapid and satisfactory. She passed from thirty to forty ounces of urine uninterruptedly and never had a bad symptom. 1 have not seen her since, but a letter from Dr. Proctor, dated October 10, 1898, informs me that she is now passing forty ounces of normal urine with no evidence of renal irritation in the sediment. She has gained in flesh and color and is greatly improved in general condition.
The patient's condition did not seem to be materially affected by the operation. The collapse, with cold sweating extremities, the sudden onset of abdominal symptoms, with hiccough, vomiting and pain, the drop of temperature without signs of hfemorrliage and the rapid rise in the leucocytes made operative intervention imperative.


The negative results of two examinations of the sediment for tuberculosis, made by an expert at widely separate times, and the positive result of the inoculation of a guinea-pig by one of these same sediments, with the confirmation of this positive result by inspection of the kidney in question, and the improvement of the patient's health after the operation, form certainly a picture of considerable clinical interest, more
During the following twenty-four hours the condition became progressively worse. All attempts at feeding were followed by immediate vomiting, and euemata were but partially retained. The patient had voided no urine for 18 hours. The lips were parched ; the tongue dry and coated. By the early morning of August 37th (30 hours after operation II) the distension had become more pronounced, and on close inspection, with a candle placed beside the exposed abdomen, a slight visible peristalsis was to be made out, which first demonstrated that obstruction, and not peritonitis, (despite the leucocytosis at this time of 20,000) was responsible for the symptoms, and it was learned that the irrigations, preceding the enemata, since the time of collapse, had not been stained with faecal matter as had previously been the rule.


The child's condition, however, seemed to forbid operative intervention. He was vomiting without effort, restless and in collapse more pronounced than at any time previous. The radial pulse could not be counted. He was given small doses of morphia and strychnia and hot compresses over his abdomen, which quieted him considerably, and four hours later an operation was determined upon.




THE JOHNS HOPKINS HOSPITAL BULLETIN.


Operation III, August 37th, 8.30 A. M. (34 hours after operation II), under chloroform ansesthesia.


Median laparotomy. Acute intestinal obstruction due to adhesions about a second perforation. Obstruction relieved. Perforation sutured. Closure with drainage.


NOVEMBER, 1898.
The recent wound was re-opened. There was no sign whatever of peritonitis. The small intestine, which was greatly distended, was turned out of the abdomen together with that loop of ileum and its surrounding omentum, which had become adherent to the anterior parietes, as a consequence of the drainage at the first operation. In this omental mass was an acute kink of the bowel, about ten centimetres proximal from the old suture, the distal part of the bowel and the colon beyond being completely collapsed. The original suture was intact. At the exact situation of the kink, and covered by the omentum which caused the obstruction, was a second perforation, apparently corresponding to the thin Peyer's patch seen at the first operation.


On freeing the obstructing omentum, gas and faeces in great amount escaped from this perforation, greatly diminishing the distension. The perforation was about 1 cm. in diameter, with rounded edges, showing everted mucous membrane, so that evidently the whole floor of the ulcer had given way. It was closed easily by a single purse-string suture of fine silk. The bowels after irrigation with salt solution were replaced. A small drain of bismuth gauze was inserted down to the wad of omentum, from which cultures had previously been taken. (In these cultures Dr. Clopton found an abundant growth of the bacillus coli communis, of proteus vulgaris, bacillus lactis aerogenes and an organism culturally closely akin to the bacillus typhosus.) The abdominal wound was partially closed.


The operation lasted twenty-five minutes from the beginning of auajsthetization. The patient's pulse could not be counted. He was given 500 cc. of salt solution in each pectoral region and also per rectum.


Throughout the day the child's condition remained most serious. Distension was pronounced with active, visible and painful peristaltic cramps. He was given small doses of morphia, and large hot bichloride fomentations, for which he seemed very grateful, were at short intervals placed over the whole abdomen. He vomited only twice after returning to the ward, and soon began to retain his nourishment. Twelve hours after the operation, flatus first began to pass from the lower bowel. On the following day, though considerable meteorism remained, the bowels moved three times, and considerable diarrhoea persisted for the four or five succeeding days. As the clinical chart shows, the patient, though greatly emaciated and very feeble, returned to his typical typhoidal condition which ran its course in the next ten days.


Miliary Tuberculosis of Kidney.
Convalescence was very tedious. The child had a series of superficial indolent staphylococcus albus abscesses over the back and shoulders which had to be opened, and a protracted bloody mucous diarrhoea set in which kept him thin and weak. The abdominal incision broke down after the third opei'ation, and was slow in healing. He has, however, made a complete recovery.






November, 1898.]
260




Line 27,867: Line 27,876:




257
[No. 92.






especially, as this is, so far as I am aware, the first case in which this test has been used for the esamiiiatioa of each kiduey separately.
In Case I, therefore, we have what is most unusual, a child with early perforation. The symptoms at onset were typical, and the condition was readily diagnosed. The early vomiting was a great help, while the prostration, abdominal pain, tenderness and the leucocytosis made the picture complete before the onset of peritonitis.


As so little is known of frequency of unilateral and primary renal tuberculosis I had hoped that an examination of the records of a large number of autopsies, performed upon subjects who died from other diseases than tuberculosis, might yield something of interest, and accordingly requested Dr. John T. Bottoinley to examine the pathological records of the Boston City Hospital for some years past. He looked over 3300 reports which were consecutive except for the omission of deaths from tubercular disease in other organs of the body, but found only two cases of primary renal tuberculosis, both unilateral, one of which died from fracture of the spine, the other of uremia.
The history of preceding abdominal pain for some days before the actual occurrence of perforation is interesting and, in the light of the subsequent cases, important, in that it most probably was associated with a slight local peritonitis due to the near approach of an ulcer to the general peritoneal surface. From what will be said later it seems possible that clinical symptoms arising from this condition are not uncommon and that they may be utilized in foretelling a perforation, or at all events in putting the attendant on his guard so that the patient may be kept more than ordinarily quiet and tubs omitted, especially if they are disagreeable and resisted.


His abstracts of the cases are as follows:
Among other points of unusual interest is the fact that so prompt intervention was rendered possible, owing to the discernment of Dr. MacCallum, who had charge of the ward, and that the perforation was closed before there was any evidence of peritoneal infection, the cultures from the free fluid remaining sterile.


Case I. Surg. Eec. C, Vol. 23, Page 248. Male, 48 years. No venereal diseases, case of scalp wound, alcoholism, and fractured spine.
The subsequent perforation of a neighboring ulcer showed that it would have been desirable at the first operation to have turned in by a suture those patches which seemed thin, and threatened perforation, as was done by Sifton* in his case with recovery, and also by W. Hill.f In view of the fact, however, that there were several of these areas, and that it did not seem justifiable to further prolong the operation, a strip of gauze was placed leading to the two worst looking patches. Whether the trauma of the gauze was itself responsible for the subsequent perforation, or, whether by forming adhesions, it saved the general cavity from the escape of intestinal contents through a perforation, which would have occurred in any case, must remain undetermined.


Autopsy Eec, Vol. 16, Page 56. Autopsy showed that right
The leucocytosis which at the first operation afforded an apparently certain indication was completely misleading at the second. Here, although in two separate counts the leucocytes were 20,000 there was found no inflammatory reaction to account for the increase. I do not know whether obstruction is usually associated with leucocytosis or notj






kidney was about normal size ; upper third replaced by several sacs, each corresponding to a pyramid and its accompanying cortex ; each sac had a thin, firm capsule which was filled with opaque, white, cheesy or putty-like material, a little gritty to the touch. In one of the lower pyramids was a similar sac ; no evidence of any inflammation ; microscopic examination negative ; pelvis and ureter normal. Bladder and ai>pendage8 were normal except a few small calcified nodules in prostate.
Sifton, H. A.: Chicago Clinical Review, Vol. IV, p. 368, 1894-5.
t Reported by Keen: Surgical Complications and Sequela of Typhoid Fever, 1898, p. 238, Case 40.


Anatomical diagnosis. Stenosis of aortic valve. Chronic passive congestion of spleen and kidneys. Chronic tuberculosis of right kidney. Fracture of spine.
t In a condition of obstruction at the hepatic flexure, following a recent operation for acute appendicitis the patient had a leucocytosis of 44,000 without peritonitis, whereas during the acute stage of his appendicitis tlie leucocytes had been only 23,000. A differential diagnosis between peritonitis and obstruction is most difHcult. Bogart's case was similar to this one, an obstruction simulating general peritonitis. Damner Harrison (Brit. Med. Jour., Oct. 20, 1894, p. 8C5) operated on a typhoid case for perforation, and found an obstruction. Barbe {Etude clinique sur certaines formes des perforations de I'intestin grcle : Importance du diagnostic precoce. These de Paris, 1895) calls attention to similar cases. No record of the number of leucocytes is given by these writers. The high degree of leucocytosis, such as was present in the writer's two


Case II. Med. Rec, Vol. 175, Page 249. Female, 45 years, married. Always well till three months before ; all symptoms pointed to disease of the kidney.


Autopsy Rec, Vol. 3, Page 125. Autopsy. No truly normal tissue remained of left kidney. The entire wall was composed of abscesses of varying sizes, containing a thick almost cheesy pus. Peri-nephritic fat adherent to the wall, also to diaphragm ; nothing important in other organs.


[The second case could probably have been saved by nephrectomy had the diagnosis been made a few months before. She, however, entered the hospital in the year 1880 and in a dying condition.]
It is also noteworthy that the perforation was not associated with an early drop in temperature, contrary to the supposed rule, whereas one of the first symptoms of the obstruction was a fall of four degrees. The importance of immediate intervention was evidenced at the first operation. Practically the same symptoms appeared twelve days later without perforation. As was found subsequently these symptoms were due to an acute obstruction, and at the second operation, which was performed immediately after the onset of symptoms, the real condition was overlooked because at this early period distension of the proximal bowel which would naturally have suggested obstruction had not yet taken place. The question of justifiability of such an immediate intervention on the first symptoms of perforation will be considered later, as well as the difficulty of distinguishing between acute obstruction and perforation in their early stages.


It was learned from this case that a median incision was a bad one as the lesions occur in the right iliac fossa almost as naturally as do appendicular ones. It is also apparent that the mere performance of laparotomy in the course of typhoid fever, provided it is made before the occurrence of septic extravasation, is in itself attended with little more risk than a similar procedure in febrile states, the only apparent drawback to it being the necessary omission of any bath treatment during the subsequent progress of the fever.


I have found in the literature only one instance in which more than one laparotomy has been performed in an attempt to combat intestinal perforation and its sequels. In Bogart's* interesting case a perforation in the ileum, which was closed by the tip of the appendix, occurred in a third attack of fever. Death resulted three days later from obstruction at the hepatic flexure of the colon, an operation for the relief of which was abandoned. Of this case Keen| says : '• I can scarcely think that we would ever be justified in re-opening the abdomen in such a case. Possibly a very exceptional case might justify such a procedure, but a typhoid patient rarely escapes with his life even after one operation and could not be expected to survive a second. The same remark would apply to any new perforation which might occur. Such cases must unfortunately be left to their fate ; but if the surgeon has been careful to search for and suture any impending perforation he has done much to prevent such a disaster."


LAPAROTOMY FOR INTESTINAL PERFORATION IN TYPHOID FEVER.
Dr. Keen's last remark holds true, but it is hard to agree with the statement that a patient should be left to his fate, no matter how desperate the condition, provided surgical intervention offers any chance of relief, forlorn though it may be. The great vitality of some of these patients is illustrated as well by this case as by the remarkable one of Dr. Finney's in which after two relapses, an otitis media, a pleurisy, and phlebitis subsequent to the operation, there was eventually a complete recover}'.


A RFPORT OF FOUR CASES, WITH A DISCUSSION OF THE DIAGNOSTIC SIGNS OF PERFORATION. By Harvey W. Gushing, M. D., Resident Surgeon, The Johns Hojjhins Ebspifal




cases, may possibly be of some diagnostic value in differentiating between these conditions, though in a manner entirely opposed to the usual interpretation.


The present communication is based upon four recent cases of laparotomy foi- perforating typhoid ulcer, in one of which the abdominal ca\ ity was opened on three successive occasions with recovery.
Bogart, J. Bion : Laparotomy for Perforating Typhoid Ulcer of
the Ileum, etc. Annals of Surgery, Vol. 1, 1896, p. 596.


The fact that surgical intervention offers practically the only hope in tlieso cases seems to be studiously overlooked, if we are to judge by the paucity of occasions in which laparotomy has been performed for this condition.
f Keen, W. W.: Surgical Complications and Sequelae of Typhoid Fever, p. 232, 1898.


On a recent visit to the military hospital at Fort McPhersou, the writer was told that of thirty autopsies held upon fatal cases of typhoid which had occurred there, perforation was found to have been the cause of death in six instances, one being of the appendicular variety. This would attribute to perforation aloi.e 30 per cent, of the fatalities, a percentage which corresponds with that of Hare of Brisbane, and is almost twice that of Murchison (11.38 per cent.), and three times the figures given by ]ir. Fitz (6.58 per cent, in 4680 cases). In none of these cases had operative intervention been advised, nor do I know of a single instance of operation for the relief of typhoid perforation on any of the possible 2000 cases which have died from typhoid in the field hospitals and elsewhere during the late war.


H the recent statistics of Gesselewitsch and Wanach (Centralblatt f iir die ( rreuzgcbieten der Medizin und Chirurgie, Bd. I, No. 6, p. 382, IS'.IS) are to be relied upon, namely, that lO per cent, of the entire number of fatalities in typhoid are due to perforative peritonitis, we may credit 200 of these deaths to this cause alone. According to the statistics from Fort McPherson and those of Hare, 400, or double the number, would be accounted for in this way.


November, 1898.]




In a recent communication Dr. Nicholas Seun writes: "Strange as it may seem, having seen hundreds of cases of typhoid fever during the war, I was called upon only once to operate for perforation. In that instance the patient was moribund, and I refused to operate. I have reason to believe that this complication was frequently overlooked."


We have four widely different but quite characteristic histories to report:
JOHNS HOPKINS HOSPITAL BULLETIN.


In Case I an early diagnosis and immediate operation, before peritonitis set in, led to recovery.


In Case II general purulent peritonitis with three perforations was present, and it should be considered that the relief of the general peritonitis, and not typhoid perforation which had taken place many hours before, was the objective point of operation.


In Case III what may be considered as pre-perforative symptoms of peritonitis were present and were neglected. Perforation subsequently occurred with, unfortunately, a virulent streptococcus infection, which proved fatal despite early laparotomy.
261


Case IV illustrates one of the strange attacks which closely simulate perforation. No lesion was found at the operation, and the exploration had no appreciable effect upon the subsequent course of the fever.


Case I. Surgical No. 8009. Typhoid perforation at end of second week. Laparotomy. Suture of perforation. Drainage. Fcecal fistula after 3 days from second perforation. Spontaneous closure of fistula. Seven days later symptoms of perforation. Laparotomy, No perforation found. Obstruction over


Case II. General Ko. 33,970. — Typhoid perforafmi in the fifth iveelc. Laparotomy under cocaine ancesthesia. General peritonitis. Suture of three 2^erf orations in ileum. Deatli four hours after operation.


258
September 3, 1898. William N., aged 18, was brought to the medical wards of the hospital with the history of a febrile attack of three weeks' duration. The patient's mother and sister died at home during his stay in the hospital of " malignant typhoid."


The patient was dull and stupid, and presented a typical typhoidal appearance. The medical note on the abdomen at entrance is as follows: "Abdomen. Peculiarly mottled, especially in inguinal regions, a bluish discoloration, taches bleuiUres. Walls somewhat tense ; grooves obliterated ; everywhere tympanitic. Slighttenderness across upper abdomen in umbilical and epigastric regions. Spleen enlarged, edge readily palpable. Liver. Relative dulness at upper border of 6th rib; absolute in 6th space and extending to costal margin ; towards left extending 3 cm. below xyphoid ; edge palpable."


Sept. 5th. The abdomen was noted by Dr. McCrae as being natural.


JOHNS HOPKINS HOSPITAL BULLETIN.
Sept. 10th. The patient has well-marked diarrhoea with colicky pains.


Sept. 11th. Widal reaction positive in dilution of 1 to 100.


Sept. 12th. Dr. McCrae. "Patient has been complaining of abdominal pain. Abdomen is slightly distended, tense. Rose spots present. Liver dulness present. No abdominal tenderness on palpation. Leucocytes 7500 at 10 A. M." 4 P. M. Patient vomited twice in early afternoon after nourishment. Leucocytes 8400 at 8 P. M.


[No. 92.
Sept. 13th. "Patient has been very ill for 48 hours. Eyes are sunken. He has somewhat the look of collapse. Abdomen is somewhat full with respiratory movements present. The walls are very tense and tender on palpation. Liver dulness absent in mammary line, present in mid-axillary line."


The patient vomited after nourishment at 10 and 12 o'clock last night.


The leucocj'tes on this date were as follows :


looked. Two days later laparotomy for acute mtestinal ohstruction with closure of second perforation. Recovery.
Leucocytes at 9 A. M. 6000


Herbert H., aged 9, was brought into the medical wards of the Hospital on the 8th of August with the history of having been ill since the first of the month with "pain in his head and stomach." His mother and one brother were also in the hospital, and one brother had just died of "typhoid" at home. On entrance, the temperature was 104.2°, the pulse rapid, the spleen enlarged and the general appearance typhoidal. There was some tenderness noted in the lower right quadrant of the abdomen. There was no Widal reaction obtainable at this time, nor had there been in the case of his brother and mother, who had had a very mild type of fever. The patient was put on the usual bath treatment. August 9th, leucocytes 8400.
" " 10 " 7200


Dr. Thayer's note on August 11th says: "Abdomen is a little full. Patient does not flinch on pressure."
" 11 " 8800


There is no further note of unusual interest. The boy was dull, and seemed to be having a rather severe attack. He complained much of pain in his abdomen on being given his tubs.
"12.15 P.M. 6400


On the morning of August 13th (five days after admission) the patient was found to be complaining of abdominal pain. He had vomited twice and his pulse rate had increased. The leucocytes were 9600.
" "1.30 " 6000 operation performed.


He was seen, in consultation with Dr. Thayer, at 1 P. M. At this time his respirations were 34 ; his pulse 165, rather thready and of poor quality ; temperature 105°. He was crying out and complaining of general colicky abdominal pain. He was very restless ; his expression pinched ; his color quite cyanotic, with lips blue and extremities blue and cold. The abdomen was quite soft and there was no muscle spasm. There was considerable general tenderness, which seemed more marked on the right side. Pressure per rectum in the recto-vesical cul-de-sac seemed to cause especial pain, but no more marked on one side than the other. There was some apparent increase of dulness in the flanks, but no shifting dulness. There was no obliteration of liver dulness. The leucocytes were 16,000. The patient was immediately transferred to the operating-room.
" " 2 00 " 70C0


Before the administration of anaesthesia the temperature was 105° (there had been no fall up to this time) and the pulse 170.
At 1 P. M. a note by Dr. Thayer is as follows : Patient lying on back. Tongue beefy, eyes sunken and wide open. Respirations shortand shallow. Patienthasaperitoniticfacies. Green vomitus in sputum cup. Pulse small, 152. Abdomen tense, full and tympanitic. AVith patient on his back there is no hepatic flatness in the mammary line and none till one almost reaches the axillary line. There is dulnebs in either flank which disappears when the patient lies on the opposite side. Frequent vomiting during the examination. There is a well-marked friction throughout the right axilla which is heard all the way down to the costal margin. With patient lying on his left side there is no hepatic flatness anywhere.


Operation /.—August 13th, 1898, 1.30 P. M., four hours after first symptoms, under primary chloroform ansestliesia.
The patient was immediately taken to the operating-room.


Median laparotomy. Partial evisceration. Clostire of perforation. Toilet of peritoneum with salt solution irrigation. Drainage.
Operation at 1.30 P. M. under cocaine anaesthesia. Closure of three perforations in ileum. Irrigation and drainage for general septic peritonitis.


An incision was made in the median line below the umbilicus. On opening the peritoneal cavity a considerable amount (perhaps 200 cc.) of sero-purulent fluid escaped, coming chiefly from the pelvis. Cultures were taken from this fluid and it was also immediately examined in cover-slip preparations. It contained a great number of polymorphonuclear leucocytes, but no micro-organisms could be found. The serosa of the intestine was everywhere greatly congested, but evidently the greatest reaction was in the right iliac fossa, where the loops of the ileum were especially injected and covered with a slight fibrinous deposit. The general cavity to the left was walled off with gauze and the loops of the ileum drawn from the wound. The last foot of the small intestine showed several greatly thinned areas corresponding to Peyer's patches. In the centre of one of these areas, the surroundings of which were quite bluish in color, was a small perforation about two millimetres in diameter, from which fluid fasces were flowing. It was about 25 cm. from the caecum and situated in the free
A linear infiltration of the skin with Schleich's solution was made in the right linea semilunaris. On opening the abdominal cavity there was an e.xplosion of gas followed by the escape of a large amount of stinking material looking like pea-soup stools. The bowels were of a dark bluish color, dis




tended, covered by a thick plastic lymph and everywhere bathed in the foecal extravasation.


surface of the bowel. A few centimetres beyond this were two more patches, which seemed very thin and practically covered by little more than serosa. A few fine, filmy adhesions held the omentum to this part of the bowel.
The CEecum was located, and the first loop of ileum when drawn out showed three large ragged holes about IJ cm. in diameter and with fine bridges across them made by threads of submucosa.* They were closed with Halsted mattress sutures. The appendix and colon were free from perforations. The patient was given a few whiffs of chloroform ; the bowels were turned out, and the abdominal cavity cleaned as thoroughly as possible and irrigated with salt solution. Drainage was left in to the bottom of the pelvis and to the site of the suture.


The perforation was closed by a circular suture of fine silk taken about the edge of the thinned area, which was fortunately small, measuring about one centimetre in diameter. A similar inversion of the two thin neighboring patches would have been attempted, but the patient's condition at this time demanded immediate attention and the idea was abandoned. His pulse was almost imperceptible and his respirations were very shallow. Hypodermic injections of strychnia were given and an infusion of a litre of salt solution in the pectoral region. The exposed coils of intestine were irrigated and the abdominal cavity was flushed out with salt solution. A strip of bismuth gauze was left in for drainage, leading down to the site of the suture, and another to the two thinned Peyer's patches. The omentum was pulled down over the gauze. The abdominal wound was then partly closed. The operation lasted but twenty minutes from the beginning of ansesthesia till the final closure.
The operation lasted 20 minutes.


The cultures taken from the fluid found free in the peritoneal cavity remained sterile. No cultures were taken from the material flowing from the perforation.
Needless to say his condition was desperate with a pulse of 160 and respiration 60.


The patient rallied well from the operation, and in eight hours the pulse had fallen to 112, and the temperature to normal. There was no vomiting, and he slept most of the time for the next twenty-four hours, taking liquid nourishment (albumen water) well, during his waking intervals. Three hundred cubic centimetres of salt solution were given per rectum every four hours for thirst. On the following day the temperature again became elevated ; the day after the leucocytosis disappeared, and for the following ten days the clinical picture was that of an ordinary typhoid in the third week. A faecal fistula developed on the second day, discharging typical peasoup faeces. It was impossible to tell, at that time, whether this discharge came from the broken down suture or from one of the neighboring thinned Peyer's patches, to which the drain led. (It was subsequently proved to come from the latter.)
The patient rallied somewhat after the operation under stimulants and salt infusion, but remained in a state of euthanasia, often seen in severe septic infections, and died four hours later. Unfortunately no post-mortem examination could be made.


The boy complained a good deal of abdominal pain at times, and of pain on micturition, but there was no abdominal rigidity or other symptoms of peritoneal inflammation. He was given regular ice sponges, after which he would sleep for long intervals. The fscal fistula ceased to discharge after a few days. There was considerable diarrhcea at this time (cf. Clinical chart).
The cover-slip preparations taken from the general cavity at operation showed a great diversity of organisms, some cocci, but mostly bacilli of various shapes and sizes, and a great number of pus cells. No streptococci were seen. Nothing was grown out on culture but the bacillus coli communis.


August ISlh. (6 days after opei-afion I.) A positive AVidal reaction was obtained by Dr. Schenck for the first time (in ten minutes in a dilution of 1 to 40). Cultures from the rectum, taken through a high rectal tube, showed only the bacillus coli communis. The patient had a pinched look and was very peevish. The pulse was weak and dicrotic. A crop of rose spots was present on the abdomen.
This case well illustrates the practical hopelessness of operation when perforation, at its onset, has been overlooked, and the operation delayed until the stereotyped symptoms of extensive extravasation, such as obliteration of liver dulness and evidences of shifting free fluid, have appeared. It is such cases as this which render the operative statistics for perforation so uniformly bad. Abbe'sf case, however, makes recovery seem never impossible after operation.


August 25th. {\^ days after operation I.) On the evening of this date, after a very good day, the patient became suddenly much worse and vomited several times. At 9 P. M., when seen in consultation with Dr. Thayer, he was quite
The complete absence of abdominal tenderness and of leucocytosis unfortunately was misleading, but the preceding diarrhoea, abdominal pain and vomiting under ordinary circumstances would have led to early exploration had it not been for the fact that so many of the house cases this fall have complained of adominal pain and tenderness associated with diarrhoea. This point will be referred to later.


The importance of making cover-slip preparations as well as immediate plate cultures from the abdominal contents in cases of peritonitis is well shown by the fact that the bacillus coli communis overgrew all other organisms in what the cover-slips had shown to be a polyinfection. Careful investigations, such as those of FlexuerJ, show what a variety of organisms may be present. Undoubtedly the colon bacillus being more in evidence is frequently held resj)onsible for peritoneal infection due to more virulent but culturally less vigorous organisms. In one of Flexner's cases (Case IV) there was obtained from the peritoneal cavity the bacillus typhi abdominalis, bacillus coli communis, proteus vulgaris,




NOVBMBEB, 1898.]


•Such as are shown in Keen, op. cit., Plate V, Fig. I.


t Abbe, Robert : Perforating Typhoid Ulcer. Peritonitis. Operation. Recovery. Medical Record, Vol. XLVII, p. 1, January 5, 1895.


JOHNS HOPKINS HOSPITAL BULLETIN.
JFlexner, Simon : Certain Forms of Infection in Typhoid Fever. Johns Hopkins Hopital Reports, \'ol. V, 1895.






259
k






collapsed and very restless. His abdomen was slightly distended. He was hiccoughing and complaining of abdominal pain. He looked pinched and the extremities were cold and sweating. His leucocytes were only 4000.
262


A definite diagnosis of perforation was made and steps taken for immediate operation. An hour later the temperature had fallen four degrees to 98.6°, and the leucocytes had increased to 13,000.


Operation II, August 25, 1898, 10.30 P. M.; two hours aftei first symptoms ; under chloroform anaesthesia. Median laparotomy. No cause for symptoms demonstrable. Closure tvifh drainage.


The abdomen was opened beside the first incision, avoiding the site of the fistula. There was no free fluid. The bowels were not injected except to a slight degree in a few places, corresponding to some of Peyer's patches. No evidence whatever of a perforation could be found. There were no adhesions except about the loop of ileum which led to the old sinus and which was surrounded by quite firm omental adhesions. These were not broken up. There was no particular distension of one coil more than another. (There was nothing to suggest the thought of obstruction, and I must confess it did not occur to me. I supposed that I had overlooked a perforation somewhere, but the patient's condition precluded further search.) The wound was closed, with a small drain leading to the omental adhesions.
JOHNS HOPKINS HOSPITAL BULLETIN.


The operation lasted thirty-five minutes from the beginning of ausesthetizatiou. Cultures taken from the site of the adhesions remained sterile.


The patient's condition did not seem to be materially affected by the operation. The collapse, with cold sweating extremities, the sudden onset of abdominal symptoms, with hiccough, vomiting and pain, the drop of temperature without signs of hfemorrliage and the rapid rise in the leucocytes made operative intervention imperative.


During the following twenty-four hours the condition became progressively worse. All attempts at feeding were followed by immediate vomiting, and euemata were but partially retained. The patient had voided no urine for 18 hours. The lips were parched ; the tongue dry and coated. By the early morning of August 37th (30 hours after operation II) the distension had become more pronounced, and on close inspection, with a candle placed beside the exposed abdomen, a slight visible peristalsis was to be made out, which first demonstrated that obstruction, and not peritonitis, (despite the leucocytosis at this time of 20,000) was responsible for the symptoms, and it was learned that the irrigations, preceding the enemata, since the time of collapse, had not been stained with faecal matter as had previously been the rule.
[No. 92.


The child's condition, however, seemed to forbid operative intervention. He was vomiting without effort, restless and in collapse more pronounced than at any time previous. The radial pulse could not be counted. He was given small doses of morphia and strychnia and hot compresses over his abdomen, which quieted him considerably, and four hours later an operation was determined upon.




staphylococcus aureus and the streptococcus pyogenes. I know of no other case in which the bacillus typhosus has been obtained in culture from a general peritonitis following perforation. The organism in our Case I, though akin to it, was not positively identified. Korte* isolated the bacillus from a general peritonitis which originated however from a ruptured suppurating mesenteric gland. Klein also is said to have obtained it, but from a localized peritonitis.


Operation III, August 37th, 8.30 A. M. (34 hours after operation II), under chloroform ansesthesia.
Case III. Surgical No. 8131. — Typhoid perforation at end of fourth week after prolonged abdominal symptoms. General streptococcus per itotiitis. Laparotomy. Suture of perforation. Death after eight hours.


Median laparotomy. Acute intestinal obstruction due to adhesions about a second perforation. Obstruction relieved. Perforation sutured. Closure with drainage.
Sept. 5, 1898, Peter B., colored, aged 31, was admitted to the medical wards complaining of having had " pain in his head and stomach and general weaknpsB" since August 23rd. He had had some diarrhoea and abdominal pain during this time, but had not taken to his bed.


The recent wound was re-opened. There was no sign whatever of peritonitis. The small intestine, which was greatly distended, was turned out of the abdomen together with that loop of ileum and its surrounding omentum, which had become adherent to the anterior parietes, as a consequence of the drainage at the first operation. In this omental mass was an acute kink of the bowel, about ten centimetres proximal from the old suture, the distal part of the bowel and the colon beyond being completely collapsed. The original suture was intact. At the exact situation of the kink, and covered by the omentum which caused the obstruction, was a second perforation, apparently corresponding to the thin Peyer's patch seen at the first operation.
The note on the abdomen at entrance is as follows : "Abdomen looks natural ; no distension ; costal and iliac grooves are well marked ; respiratory movements are present. Some tenderness on palpation, especially in right inguinal and iliac region. Liver dulness begins at the sixth rib and extends to costal margin. Spleen is just palpable." Blood count. Red corpuscles 4,820,000. White corpuscles 5,600.


On freeing the obstructing omentum, gas and faeces in great amount escaped from this perforation, greatly diminishing the distension. The perforation was about 1 cm. in diameter, with rounded edges, showing everted mucous membrane, so that evidently the whole floor of the ulcer had given way. It was closed easily by a single purse-string suture of fine silk. The bowels after irrigation with salt solution were replaced. A small drain of bismuth gauze was inserted down to the wad of omentum, from which cultures had previously been taken. (In these cultures Dr. Clopton found an abundant growth of the bacillus coli communis, of proteus vulgaris, bacillus lactis aerogenes and an organism culturally closely akin to the bacillus typhosus.) The abdominal wound was partially closed.
The Widal reaction was positive in dilution of 1 to 100. The patient was very ill and delirious at times, and on the night after admission jumped ten feet out of the ward window without, however, injuring himself. A slight leucocytosis was found a few days after admission which, coupled with his abdominal pain, occasioned suspicion, and he was watched very closely.


The operation lasted twenty-five minutes from the beginning of auajsthetization. The patient's pulse could not be counted. He was given 500 cc. of salt solution in each pectoral region and also per rectum.
On several occasions the writer saw him in consultation with Dr. McCrae, but the complete absence of objective abdominal symptoms and the fact that there were several patients in the wards with similar subjective symptoms made us hesitate about operative intervention. For ten days he pursued a usual typhoid course, though the leucocytosis at one time reaching 15,200 persisted (cf. Clinical chart) and abdominal pain was constantly complained of. There was no diarrhoea. He was given the usual bath treatment.


Throughout the day the child's condition remained most serious. Distension was pronounced with active, visible and painful peristaltic cramps. He was given small doses of morphia, and large hot bichloride fomentations, for which he seemed very grateful, were at short intervals placed over the whole abdomen. He vomited only twice after returning to the ward, and soon began to retain his nourishment. Twelve hours after the operation, flatus first began to pass from the lower bowel. On the following day, though considerable meteorism remained, the bowels moved three times, and considerable diarrhoea persisted for the four or five succeeding days. As the clinical chart shows, the patient, though greatly emaciated and very feeble, returned to his typical typhoidal condition which ran its course in the next ten days.
Dr.McCrae's note the morning of the 17th inst. states : "General condition good. There is no delirium. Tongue is still coated. Patient frequently lies with knees drawn up. He states that he has very slight abdominal pain this morning. Abdomen is flat, soft on gentle palpation. Patient complains of severe pain when pressure is applied. Muscles at times are rigid, at others soft.


Convalescence was very tedious. The child had a series of superficial indolent staphylococcus albus abscesses over the back and shoulders which had to be opened, and a protracted bloody mucous diarrhoea set in which kept him thin and weak. The abdominal incision broke down after the third opei'ation, and was slow in healing. He has, however, made a complete recovery.
I am inclined to believe that his perforation took place the following night coincident with the drop in temperature (cf. Clinical chart). His pulse at midnight was recorded at 120 and his respirations at 36. By a strange misfortune during rounds the next day at noon he seemed very much better. His pulse was 76 and respirations 22, possibly as a result of the recent tub, and there seemed to be no change in his abdominal condition.


He was quite delirious during the day. There was no nausea or vomiting His leucocytosis had disappeared. At midnight of this day Dr. McCrae found him in considerable pain, lying on his back with his knees drawn up. He was dull and answered questions slowly and unintelligently. Respirations 44. Pulse 120. There was some vomitus on the floor beside the patient's bed. This was the first vomiting that had been noted.


Respiratory movements were absent from the abdomen. There


260




Korte, W.: Erfahrungen fiber die chirurgische Behandlung der
allgemeinen, eitrigen Bauchfellentziindung. Verhandlungen der deutsch. Gesellschaft fur Chirurgie, 21ter Congress, p. 164, 1892.


JOHNS HOPKINS HOSPITAL BULLETIN.




was no fulness but general tenderness on palpation, especially in the right iliac fossa. There was distinct dulness, which was movable, in the right flank. The liver dulness began at the 7th interspace and extended to the costal margin. His leucocytes were 4300.


[No. 92.
September 19th. Operation at 1 A. M. Ether anmsthesia. Laparotomy. General peritonitis. Suture of perforation in ileum. Irrigation. Gauze drainage.


The incision was made through the right rectus sheath, and the muscle drawn toward the median line. On opening the abdominal cavity bubbles of gas and sero-purulent fluid escaped. Cover-slips from this fluid were immediately examined and found to be full of streptococci with an abundance of other pleomorphic organisms.


The ileum was quite distended. For about two feet from the Cfficum, as it was withdrawn, it appeared injected and pretty extensively covered with a delicate, fibrino-plastic lymph which could be readily peeled off in sheets. This pellicle was in many places glistening and quite transparent. There were no adhesions. About 10 cm. above the caecum in the centre of a dark bluish area measuring about li cm. in diameter was a small perforation which was partially occluded by a pouting nubbin of red mucous membrane and from which there seemed to be escaping very little of the intestinal contents at this time. The perforation and thin patch were turned in with Halsted sutures. There was not a great amount of extravasation or free fluid present, certainly not enough to have given shifting dulness.


In Case I, therefore, we have what is most unusual, a child with early perforation. The symptoms at onset were typical, and the condition was readily diagnosed. The early vomiting was a great help, while the prostration, abdominal pain, tenderness and the leucocytosis made the picture complete before the onset of peritonitis.
The eventrated bowel was irrigated and the fibrin wiped off with wet salt sponges. The general cavity was wiped dry with salt sponges. Drainage was inserted to the bottom of the pelvis and to the site of suture and a neighboring thin Peyer's patch.


The history of preceding abdominal pain for some days before the actual occurrence of perforation is interesting and, in the light of the subsequent cases, important, in that it most probably was associated with a slight local peritonitis due to the near approach of an ulcer to the general peritoneal surface. From what will be said later it seems possible that clinical symptoms arising from this condition are not uncommon and that they may be utilized in foretelling a perforation, or at all events in putting the attendant on his guard so that the patient may be kept more than ordinarily quiet and tubs omitted, especially if they are disagreeable and resisted.
The patient stood the operation, which lasted 30 minutes, fairly well. There was no vomiting during or after the anesthesia.


Among other points of unusual interest is the fact that so prompt intervention was rendered possible, owing to the discernment of Dr. MacCallum, who had charge of the ward, and that the perforation was closed before there was any evidence of peritoneal infection, the cultures from the free fluid remaining sterile.
Death supervened 8 hours after the operation. The temperature remained high. There was no vomiting and nourishment was taken frequently. Nutritive and stimulant enemata were given and retained. The clinical picture was one of acute general toxaemia, such as streptococcus infection sometimes produces.


The subsequent perforation of a neighboring ulcer showed that it would have been desirable at the first operation to have turned in by a suture those patches which seemed thin, and threatened perforation, as was done by Sifton* in his case with recovery, and also by W. Hill.f In view of the fact, however, that there were several of these areas, and that it did not seem justifiable to further prolong the operation, a strip of gauze was placed leading to the two worst looking patches. Whether the trauma of the gauze was itself responsible for the subsequent perforation, or, whether by forming adhesions, it saved the general cavity from the escape of intestinal contents through a perforation, which would have occurred in any case, must remain undetermined.
From the peritoneal fluid at operation Dr. Clopton obtained in cultures an abundant growth of the streptococcus pyogenes, the bacillus coli communis, the bac. lactis aerogeues and a yeast fungus.


The leucocytosis which at the first operation afforded an apparently certain indication was completely misleading at the second. Here, although in two separate counts the leucocytes were 20,000 there was found no inflammatory reaction to account for the increase. I do not know whether obstruction is usually associated with leucocytosis or notj
Autopsy. Eleven hours after death. Dr. Nichols.


Anatomical diagnosis. Typhoid fever. Perforation. General fibriuo-purulent peritonitis. Operation. Healing ulcers in ileum, caecum and appendix. Slight ileo-colitis. Suppurating peritoneal gland. Acute splenic tumor. Cloudy swelling of kidneys, etc., etc.


The protocol need not be given here in full. The lesions in the organs were typical of typhoid infection. The peritoneal surfaces were quite generally involved in an inflammatory process with thin adhesions and without the production of much fibrin or pus. The free fluid had a sero-purulent character. There was a second threatening perforation a short


Sifton, H. A.: Chicago Clinical Review, Vol. IV, p. 368, 1894-5.
t Reported by Keen: Surgical Complications and Sequela of Typhoid Fever, 1898, p. 238, Case 40.


t In a condition of obstruction at the hepatic flexure, following a recent operation for acute appendicitis the patient had a leucocytosis of 44,000 without peritonitis, whereas during the acute stage of his appendicitis tlie leucocytes had been only 23,000. A differential diagnosis between peritonitis and obstruction is most difHcult. Bogart's case was similar to this one, an obstruction simulating general peritonitis. Damner Harrison (Brit. Med. Jour., Oct. 20, 1894, p. 8C5) operated on a typhoid case for perforation, and found an obstruction. Barbe {Etude clinique sur certaines formes des perforations de I'intestin grcle : Importance du diagnostic precoce. These de Paris, 1895) calls attention to similar cases. No record of the number of leucocytes is given by these writers. The high degree of leucocytosis, such as was present in the writer's two


"ExWv"'S «\"'^




It is also noteworthy that the perforation was not associated with an early drop in temperature, contrary to the supposed rule, whereas one of the first symptoms of the obstruction was a fall of four degrees. The importance of immediate intervention was evidenced at the first operation. Practically the same symptoms appeared twelve days later without perforation. As was found subsequently these symptoms were due to an acute obstruction, and at the second operation, which was performed immediately after the onset of symptoms, the real condition was overlooked because at this early period distension of the proximal bowel which would naturally have suggested obstruction had not yet taken place. The question of justifiability of such an immediate intervention on the first symptoms of perforation will be considered later, as well as the difficulty of distinguishing between acute obstruction and perforation in their early stages.


It was learned from this case that a median incision was a bad one as the lesions occur in the right iliac fossa almost as naturally as do appendicular ones. It is also apparent that the mere performance of laparotomy in the course of typhoid fever, provided it is made before the occurrence of septic extravasation, is in itself attended with little more risk than a similar procedure in febrile states, the only apparent drawback to it being the necessary omission of any bath treatment during the subsequent progress of the fever.
I
 
I have found in the literature only one instance in which more than one laparotomy has been performed in an attempt to combat intestinal perforation and its sequels. In Bogart's* interesting case a perforation in the ileum, which was closed by the tip of the appendix, occurred in a third attack of fever. Death resulted three days later from obstruction at the hepatic flexure of the colon, an operation for the relief of which was abandoned. Of this case Keen| says : '• I can scarcely think that we would ever be justified in re-opening the abdomen in such a case. Possibly a very exceptional case might justify such a procedure, but a typhoid patient rarely escapes with his life even after one operation and could not be expected to survive a second. The same remark would apply to any new perforation which might occur. Such cases must unfortunately be left to their fate ; but if the surgeon has been careful to search for and suture any impending perforation he has done much to prevent such a disaster."


Dr. Keen's last remark holds true, but it is hard to agree with the statement that a patient should be left to his fate, no matter how desperate the condition, provided surgical intervention offers any chance of relief, forlorn though it may be. The great vitality of some of these patients is illustrated as well by this case as by the remarkable one of Dr. Finney's in which after two relapses, an otitis media, a pleurisy, and phlebitis subsequent to the operation, there was eventually a complete recover}'.






cases, may possibly be of some diagnostic value in differentiating between these conditions, though in a manner entirely opposed to the usual interpretation.
PUOTOGUAl'II OF THE ILKIM I'l' C'aM; 111.
 
Bogart, J. Bion : Laparotomy for Perforating Typhoid Ulcer of
the Ileum, etc. Annals of Surgery, Vol. 1, 1896, p. 596.
 
f Keen, W. W.: Surgical Complications and Sequelae of Typhoid Fever, p. 232, 1898.




Line 28,080: Line 28,087:




261
263






Case II. General Ko. 33,970. — Typhoid perforafmi in the fifth iveelc. Laparotomy under cocaine ancesthesia. General peritonitis. Suture of three 2^erf orations in ileum. Deatli four hours after operation.
distance above the ileo-csecal valve. The mesenteric glands were all swollen, soft, and one showed an area of suppuration the size of a pea. There were two or three small round healing ulcers in the csecum and appendix. The following description is taken directly from the protocol :


September 3, 1898. William N., aged 18, was brought to the medical wards of the hospital with the history of a febrile attack of three weeks' duration. The patient's mother and sister died at home during his stay in the hospital of " malignant typhoid."
The Ileum presents a remarkable appearance. The very edge of the ileo-cEecal valve has preserved its mucous membrane. Above this the mucous membrane has been completely destroyed over a large surface by single, confluent, often suspicious looking ulcers. One has reached the size of 7 cm. in length by 4 cm. in breadth. (This is well shown in the photograph.) The central part of this has a small clot adherent to it, and corresponds to a hajniorrhagic area on the serosa, looking like an imminent perforation situated 4 cm. above the ileo-cajcal valve. These ulcers have the same general characteristics, their edges are raised, seem opaque, congested and partly hismorrhagic. Their base is clean and apparently extends down to the transverse musculature. It is of bright red color, and transverse striae can be plainly seen. About the edges and often running in small strands across the base is a pink, delicate, new growth of epithelium. The general direction of these ulcers is longitudinal. This extensively ulcerated area does not extend much further than 11 cm. from the valve. Fourteen centimetres above the valve is a similar ulcer, puckered and inverted by the silk sutures where the perforation had occurred. This ulcer was not larger than a five-cent piece.


The patient was dull and stupid, and presented a typical typhoidal appearance. The medical note on the abdomen at entrance is as follows: "Abdomen. Peculiarly mottled, especially in inguinal regions, a bluish discoloration, taches bleuiUres. Walls somewhat tense ; grooves obliterated ; everywhere tympanitic. Slighttenderness across upper abdomen in umbilical and epigastric regions. Spleen enlarged, edge readily palpable. Liver. Relative dulness at upper border of 6th rib; absolute in 6th space and extending to costal margin ; towards left extending 3 cm. below xyphoid ; edge palpable."
There are about five small, similar ulcers at various distances apart above this. The whole mucous surface is somewhat congested and there, are .small sub-mucous ecchymoses. Peyer's patches and the solitary follicles are not swollen to any appreciable extent.


Sept. 5th. The abdomen was noted by Dr. McCrae as being natural.
Bacteriological Report — Dr. Harris. — Cultures from the abdominal cavity gave the streptococcus pyogenes. From the spleen and gall-bladder was obtained an actively motile bacillus, which decolorized by Gram, and in cultural characteristics corresponded to the bacillus typhosus. From the liver, kidney and peritoneal gland an organism was obtained which was identified as the bacillus coli communis. Also from the pelvic exudate, lung and peritoneal gland was obtained a bacillus corresponding to the bacillus lactis aerogenes.


Sept. 10th. The patient has well-marked diarrhoea with colicky pains.
This case would appear to be of special importance in that it exemplifies the existence of a definite recognizable condition spoken of above as the pre-perforative stage of ulceration. It seems not unnatural to suppose that, owing to the extreme degree of ulceration of the ileum or possibly of the appendix, some inflammation of the serosa, limited by adhesions, may have taken place. This would account for the abdominal pain, tenderness and leucocytosis of several days duration and the disappearance of the latter after perforation had actually occurred. Doubtless it would have been better to have operated early, and have sutured or drained from any suspicious patch.


Sept. 11th. Widal reaction positive in dilution of 1 to 100.
These preliminary abdominal symptoms undoubtedly somewhat disguised those of perforation with extravasation when it subsequently actually occurred, and the abdomen unfortu


Sept. 12th. Dr. McCrae. "Patient has been complaining of abdominal pain. Abdomen is slightly distended, tense. Rose spots present. Liver dulness present. No abdominal tenderness on palpation. Leucocytes 7500 at 10 A. M." 4 P. M. Patient vomited twice in early afternoon after nourishment. Leucocytes 8400 at 8 P. M.


Sept. 13th. "Patient has been very ill for 48 hours. Eyes are sunken. He has somewhat the look of collapse. Abdomen is somewhat full with respiratory movements present. The walls are very tense and tender on palpation. Liver dulness absent in mammary line, present in mid-axillary line."
nately was not opened until after evidences of general peritonitis had begun to appear.


The patient vomited after nourishment at 10 and 12 o'clock last night.
How often a streptococcus peritonitis has been the cause of death in the fatal operative cases cannot be told, and it is a matter of regret that bacteriological reports showing the variety of peritonitis present in these cases are not more often noted. Keen* says : " There is but a single instance, so far as I know, of a bacteriological examination of the contents of the peritoneum in typhoid perforation." Undoubtedly peritonitides of this nature are very fatal, and the abundance of long streptococcus chains, found in cover-slip preparations during the operation, gave immediately a bad prognosis to what seemed otherwise a favorable case.


The leucocj'tes on this date were as follows :
The extent of peritonitis macroscopically was one such as is not infrequently recovered from in those more fortunate cases in which streptococci are not the paramount infective agent. As Durham f has emphasized, " the more virulent the infection the less marked are the local signs of peritonitis."


Leucocytes at 9 A. M. 6000
A streptococcus infection in typhoid is undoubtedly a very severe complication and Vincent J believes that it carries with it an extremely grave prognosis. Doubtless, considering its frequency in autopsy records of perforation, it has been present in many of the fatal cases which have succumbed after operation. Eeports by Flexner,§ Fraenkelll and others show how frequently streptococci are obtained from the peritoneal exudate at post-mortem examinations after typhoid perforations. Tavel and LanzT[ in their extensive report on peritonitis, recognize the frequency and importance of streptococcus infections, but they seem to have encountered no cases of typhoid perforation at the surgical clinic in Bern, nor has Korte** in his recent paper added any to his two previously published cases.


" " 10 " 7200
It is strange with the degree of ulceration found and the abundance of streptococci present, that there was no diarrhoea in this case. The steady drop in the leucocytes, after the perforation and with the onset of general peritonitis, is a most interesting feature and recalls the condition in Case II, where with the purulent peritonitis no leucocytosis was presen t, though it will be observed that no count was made in the latter case at the time of probable perforation or just before it. It is quite well recognized that in appendicitis the leucocytosis, which may be high (30,000 to 30,000) before, drops after perforation, and


" 11 " 8800


"12.15 P.M. 6400


" "1.30 " 6000 operation performed.
•Op. cit.,p. 220.


" " 2 00 " 70C0
f Durham : On the Clinical Bearing of Some Experiments on Peritoneal Infections. Med. Chir. Trans., London, Vol. LXXX, p. 191, 1897.


At 1 P. M. a note by Dr. Thayer is as follows : Patient lying on back. Tongue beefy, eyes sunken and wide open. Respirations shortand shallow. Patienthasaperitoniticfacies. Green vomitus in sputum cup. Pulse small, 152. Abdomen tense, full and tympanitic. AVith patient on his back there is no hepatic flatness in the mammary line and none till one almost reaches the axillary line. There is dulnebs in either flank which disappears when the patient lies on the opposite side. Frequent vomiting during the examination. There is a well-marked friction throughout the right axilla which is heard all the way down to the costal margin. With patient lying on his left side there is no hepatic flatness anywhere.
^Vincent, M. H.: Etude sur les resultats de 1' association du streptocoque et du bacille typhique. Annales de 1' Institute Pasteur, Vol. VII, p. 141, 1893.


The patient was immediately taken to the operating-room.
^ Flexner, Simon : Certain Forms of Infection in Typhoid Fever, .lohns Hopkins Hospital Reports, Vol. V, 1895.


Operation at 1.30 P. M. under cocaine anaesthesia. Closure of three perforations in ileum. Irrigation and drainage for general septic peritonitis.
II Fraenkel, Euj!. : Zur Aetiologie der Peritonitis. Miinchener med. Wochenschrift, Bd. XXXVII, s. 23, 1890.


A linear infiltration of the skin with Schleich's solution was made in the right linea semilunaris. On opening the abdominal cavity there was an e.xplosion of gas followed by the escape of a large amount of stinking material looking like pea-soup stools. The bowels were of a dark bluish color, dis
H Tavel, E. und Otto Lanz : Ueber die Aetiologie der Peritonitis. Mitteilungen aus Kliniken und medicinischen Instituten der Schweiz, 1898.


Korte, W.: Weiterer Bericbt iiber die chirurgische Behandlung
der diffusen eiterigen Bauchfellentzundung. Mitteilungen aus den Grenzgebieten der Medizin und der Chirurgie, Bd. II, 1897, p. 145.


tended, covered by a thick plastic lymph and everywhere bathed in the foecal extravasation.


The CEecum was located, and the first loop of ileum when drawn out showed three large ragged holes about IJ cm. in diameter and with fine bridges across them made by threads of submucosa.* They were closed with Halsted mattress sutures. The appendix and colon were free from perforations. The patient was given a few whiffs of chloroform ; the bowels were turned out, and the abdominal cavity cleaned as thoroughly as possible and irrigated with salt solution. Drainage was left in to the bottom of the pelvis and to the site of the suture.


The operation lasted 20 minutes.
264


Needless to say his condition was desperate with a pulse of 160 and respiration 60.


The patient rallied somewhat after the operation under stimulants and salt infusion, but remained in a state of euthanasia, often seen in severe septic infections, and died four hours later. Unfortunately no post-mortem examination could be made.


The cover-slip preparations taken from the general cavity at operation showed a great diversity of organisms, some cocci, but mostly bacilli of various shapes and sizes, and a great number of pus cells. No streptococci were seen. Nothing was grown out on culture but the bacillus coli communis.
JOHNS HOPKINS HOSPITAL BULLETIN.


This case well illustrates the practical hopelessness of operation when perforation, at its onset, has been overlooked, and the operation delayed until the stereotyped symptoms of extensive extravasation, such as obliteration of liver dulness and evidences of shifting free fluid, have appeared. It is such cases as this which render the operative statistics for perforation so uniformly bad. Abbe'sf case, however, makes recovery seem never impossible after operation.


The complete absence of abdominal tenderness and of leucocytosis unfortunately was misleading, but the preceding diarrhoea, abdominal pain and vomiting under ordinary circumstances would have led to early exploration had it not been for the fact that so many of the house cases this fall have complained of adominal pain and tenderness associated with diarrhoea. This point will be referred to later.


The importance of making cover-slip preparations as well as immediate plate cultures from the abdominal contents in cases of peritonitis is well shown by the fact that the bacillus coli communis overgrew all other organisms in what the cover-slips had shown to be a polyinfection. Careful investigations, such as those of FlexuerJ, show what a variety of organisms may be present. Undoubtedly the colon bacillus being more in evidence is frequently held resj)onsible for peritoneal infection due to more virulent but culturally less vigorous organisms. In one of Flexner's cases (Case IV) there was obtained from the peritoneal cavity the bacillus typhi abdominalis, bacillus coli communis, proteus vulgaris,
[No. 92.






•Such as are shown in Keen, op. cit., Plate V, Fig. I.
with the onset of general peritonitis often disappears completely.


t Abbe, Robert : Perforating Typhoid Ulcer. Peritonitis. Operation. Recovery. Medical Record, Vol. XLVII, p. 1, January 5, 1895.
I am inclined to believe that in these suspicious cases the tubs should be discontinued. The late appearance of vomiting and its single occurrence shows the unreliability of this symptom for the diagnosis of perforation.


JFlexner, Simon : Certain Forms of Infection in Typhoid Fever. Johns Hopkins Hopital Reports, \'ol. V, 1895.
Case IV. Surgical No. 8154. — Typhoid fever in foiirlli week during relapse. Supposed perforation. Exploratory lajxirotomy negative. Recovery.


Maggie P., aged 15, was admitted to the medical wards, August 8, 1898, in the first week of typhoid fever. The fever pursued a typical course (cf. Clinical chart) without abdominal symptoms, with no leucocytosis and with a positive Widal reaction. A moderately severe phlebitis of the left leg appeared unassociated with leucocytosis on the 33rd day. There was considerable swelling of the leg, and tenderness over the femoral vessels. The temperature reached 10i°, but in a few days dropped to normal, and remained down twelve days. The patient was up in a wheel-chair, and without symptoms.


On September 22nd (the 52nd day after onset) a relapse of the fever came on abruptly, the temperature rising suddenly to 103° and on the following day to 105°. There was some nausea and vomiting, without abdominal tenderness or pain, but associated with a leucocytosis of 16,000. This condition persisted for the succeeding 48 hours, and therightiliacfossa was noted as being slightly resistant. Some tenderness was noticed in the right calf.


k
On September 24th, the child began to complain of abdominal pain. She was seen in the evening in consultation with Dr. McCrae, but there were no objective abdominal symptoms at that time. The condition was much as on the preceding day. There was some tenderness in both calves on pressure.


September 25th, 1.30 A.M., the child awolfe crying out with a sudden sharp pain in the abdomen " unlike anything she had previously had." Some nausea and slight vomiting followed. Leucocytosis 11,000. Two hours later, 3.30 A. M., the patient was again seen by the writer. She was complaining of colicky pain in the abdomen. Her thighs were kept flexed. There was some slight distension present. The liver dulness did not reach the costal margin by a finger's breadth. The walls were somewhat tense, and with moderately deep pressure in the right iliac region muscle spasm was elicited and the patient would cry out with pain. The chief rigidity, however, was above the level of the umbilicus. Her leucocytes had dropped to 8200. She vomited about 20 cc. of nourishment given her just before.


Operation September 25th, 6 A. M., four and one-half hours after the first appearance of symptoms.


262
Exploratory laparotomy. Negative findings. Closure loithout drainage.


An incision was made in the right iliac region. There was no free fluid in the general cavity ; no injection of the peritoneum. The appeudi.x, ileum and ascending colon appeared normal and without adhesions. The Peyer's patches in the ileum were swollen and hard, being felt like buttons through the bowel. The gall-bladder was not distended or inflamed. The pelvic viscera were negative. No thrombi could be palpated in the internal iliac veins. There were no suppurating glands felt in the mesentery. The abdominal wound was closed. The operation lasted only fifteen minutes.


The patient showed no ill effects from the operation. There was no subsequent nausea or vomiting; her leucocytosis dis


JOHNS HOPKINS HOSPITAL BULLETIN.


appeared, and she passed through an uneventful relapse of fever (cf. Clinical chart).


In the light of our previous experience with Cases II and III and with such symptoms as sudden acute abdominal pain, nausea and vomiting with increasing distension, some rigidity and tenderness and leucocytosis (especially a falling leucocytosis), the writer did not dare take the responsibility of withholding operative intervention even though there was some doubt as to the diagnosis. The possibility of an extension of the phlebitis to the internal iliac veins, thus causing some abdominal pain and tenderness, was thought of, but with the preceding phlebitis of September 23nd there had been no leucocytosis, pain or vomiting. The fact that the chief rigidity was above the level of the umbilicus suggested a gall-bladder complication, which in itself would have demanded exploration. The general appearance of the child was not that of collapse following perforation. There was no marked change in pulse, temperature or respiration with the above-mentioned symptoms. Nevertheless, I believed much less responsibility to be associated with an exploratory laparotomy than with running the risk of neglecting a i)erforation until signs of peritonitis should occur.


[No. 92.
The precise cause of the patient's symitoms remains undecided. She was a very nervous child, ai:d there had been some children with acute abdominal affections in the ward during her previous period of convalescence.


Similar cases have been reported. Herrington andBowlby* report an operation on a young girl convalescing from typhoid who had even more marked symptoms of perforation with collapse than those related above. There is no mention of a leucocyte count. A laparotomy revealed no peritoneal lesion. Convalescence was uninterrupted.


General Considerations on Operation for Typhoid Perforation. — In recent years several tables have appeared in which are included all of the supposed authentic cases of operation for this particular complication in typhoid, notably those of Finney, Keen and Monad and Vanverts.


staphylococcus aureus and the streptococcus pyogenes. I know of no other case in which the bacillus typhosus has been obtained in culture from a general peritonitis following perforation. The organism in our Case I, though akin to it, was not positively identified. Korte* isolated the bacillus from a general peritonitis which originated however from a ruptured suppurating mesenteric gland. Klein also is said to have obtained it, but from a localized peritonitis.
Statistics, however, always misleading, are especially so when they concern a question involving so many considerations as are included under the one head of " Results of Operation for Typhoid Perforation."


Case III. Surgical No. 8131. — Typhoid perforation at end of fourth week after prolonged abdominal symptoms. General streptococcus per itotiitis. Laparotomy. Suture of perforation. Death after eight hours.
In the first place two distinct varieties of perforation may be recognized in which the operative prognosis is widely different. In one, the appendicular form, the process takes place in a quiet corner of the abdomen usually remaining localized, owing to the formation of adhesions, for perhaps a long time. In these cases some pre-existing chronic appendicular trouble may predispose toward perforation in the same way as does an ulcer of typhoidal origin in this situation. The condition, then, is practically one of acute perforative appendicitis occurring in the course of typhoid, and has the same prognosis and surgical features as similar conditions unassociated with


Sept. 5, 1898, Peter B., colored, aged 31, was admitted to the medical wards complaining of having had " pain in his head and stomach and general weaknpsB" since August 23rd. He had had some diarrhoea and abdominal pain during this time, but had not taken to his bed.


The note on the abdomen at entrance is as follows : "Abdomen looks natural ; no distension ; costal and iliac grooves are well marked ; respiratory movements are present. Some tenderness on palpation, especially in right inguinal and iliac region. Liver dulness begins at the sixth rib and extends to costal margin. Spleen is just palpable." Blood count. Red corpuscles 4,820,000. White corpuscles 5,600.


The Widal reaction was positive in dilution of 1 to 100. The patient was very ill and delirious at times, and on the night after admission jumped ten feet out of the ward window without, however, injuring himself. A slight leucocytosis was found a few days after admission which, coupled with his abdominal pain, occasioned suspicion, and he was watched very closely.
Herrington, W. C, and Bowlby, A. A. : Typhoid Fever Convalescence; Symptoms of Perforation, Laparotomy ; no Lesion found;
Recovery. Med. Chir. Transactions, London, Vol. LXXX, 1897, p. 127.


On several occasions the writer saw him in consultation with Dr. McCrae, but the complete absence of objective abdominal symptoms and the fact that there were several patients in the wards with similar subjective symptoms made us hesitate about operative intervention. For ten days he pursued a usual typhoid course, though the leucocytosis at one time reaching 15,200 persisted (cf. Clinical chart) and abdominal pain was constantly complained of. There was no diarrhoea. He was given the usual bath treatment.


Dr.McCrae's note the morning of the 17th inst. states : "General condition good. There is no delirium. Tongue is still coated. Patient frequently lies with knees drawn up. He states that he has very slight abdominal pain this morning. Abdomen is flat, soft on gentle palpation. Patient complains of severe pain when pressure is applied. Muscles at times are rigid, at others soft.


I am inclined to believe that his perforation took place the following night coincident with the drop in temperature (cf. Clinical chart). His pulse at midnight was recorded at 120 and his respirations at 36. By a strange misfortune during rounds the next day at noon he seemed very much better. His pulse was 76 and respirations 22, possibly as a result of the recent tub, and there seemed to be no change in his abdominal condition.
November, 1898.]


He was quite delirious during the day. There was no nausea or vomiting His leucocytosis had disappeared. At midnight of this day Dr. McCrae found him in considerable pain, lying on his back with his knees drawn up. He was dull and answered questions slowly and unintelligently. Respirations 44. Pulse 120. There was some vomitus on the floor beside the patient's bed. This was the first vomiting that had been noted.


Respiratory movements were absent from the abdomen. There


JOHNS HOPKINS HOSPITAL BULLETIN.




Korte, W.: Erfahrungen fiber die chirurgische Behandlung der
allgemeinen, eitrigen Bauchfellentziindung. Verhandlungen der deutsch. Gesellschaft fur Chirurgie, 21ter Congress, p. 164, 1892.


265




was no fulness but general tenderness on palpation, especially in the right iliac fossa. There was distinct dulness, which was movable, in the right flank. The liver dulness began at the 7th interspace and extended to the costal margin. His leucocytes were 4300.


September 19th. Operation at 1 A. M. Ether anmsthesia. Laparotomy. General peritonitis. Suture of perforation in ileum. Irrigation. Gauze drainage.
typhoid which give a certain percentage of recovery in uuoperated cases.


The incision was made through the right rectus sheath, and the muscle drawn toward the median line. On opening the abdominal cavity bubbles of gas and sero-purulent fluid escaped. Cover-slips from this fluid were immediately examined and found to be full of streptococci with an abundance of other pleomorphic organisms.
In the other variety the perforation almost always occurs in the freely moving bowel, usually in the lower foot of the ileum.


The ileum was quite distended. For about two feet from the Cfficum, as it was withdrawn, it appeared injected and pretty extensively covered with a delicate, fibrino-plastic lymph which could be readily peeled off in sheets. This pellicle was in many places glistening and quite transparent. There were no adhesions. About 10 cm. above the caecum in the centre of a dark bluish area measuring about li cm. in diameter was a small perforation which was partially occluded by a pouting nubbin of red mucous membrane and from which there seemed to be escaping very little of the intestinal contents at this time. The perforation and thin patch were turned in with Halsted sutures. There was not a great amount of extravasation or free fluid present, certainly not enough to have given shifting dulness.
I believe that Dr. Fitz* first clea'-ly distinguished between these two varieties of perforation in typhoid, emphasizing the fact that many cases would be called appendicitis which, when occurring during typhoid fever, are classed as perforations. Undoubtedly the appendicular cases are much more common thau has been ordinarily supposed. Fitz finds, however, only 3 per cent, in 167 cases. Of the 20 cases of perforation in the pathological records of the Johns Hopkins Hospital there have been 3 appendicular perforations which, grouped with a single case out of the nine of which I am personally cognizant, makes 9.6 per cent, which have occurred in the appendix.


The eventrated bowel was irrigated and the fibrin wiped off with wet salt sponges. The general cavity was wiped dry with salt sponges. Drainage was inserted to the bottom of the pelvis and to the site of suture and a neighboring thin Peyer's patch.
To further quote from Dr. Fitz's paper : " The probability of its occurrence (perforative appendicitis) furnishes the best solution to the prognosis of intestinal perforation in the latter disease (typhoid fever). Most cases of recovery from symptoms of perforation of the bowel iu typhoid fever are those in which an attack of appendicitis is most closely simulated, while the fatal cases of perforation of the bowel in typhoid fever are, in the great majority of instances, those in which other parts of the bowel than the appendix are the seat of of perforation."


The patient stood the operation, which lasted 30 minutes, fairly well. There was no vomiting during or after the anesthesia.
It is of course important to recognize the fact that either of these conditions may be present, but a differential diagnosis can hardly be made, and were such possible, operative interference is as surely indicated as in any acute apj)endicitis. The prognosis in the appendicular varieties, for the reasons given above, is naturally more favorable, but in all cases the earlier surgical intervention is sought the better for the patient. This applies especially to the variety in which the perforation is in the free bowel. Here, also, adhesions presumably form as the nicer approaches the serosa, but inasmuch as they are attached to a movable part of the bowel they cannot be relied upon to hold, and extravasation usually soon takes place. It is with perforation of the ileum that we are chiefly concerned, and in looking for information upon this subject we are hampered because we find commingled iu the statistician's tables, two very different and widely separate conditions, one, the results of operation for typhoid perforation, the other, the results of operation for general peritonitis following typhoid perforation.


Death supervened 8 hours after the operation. The temperature remained high. There was no vomiting and nourishment was taken frequently. Nutritive and stimulant enemata were given and retained. The clinical picture was one of acute general toxaemia, such as streptococcus infection sometimes produces.
The mortality following operation for general septic peritonitis, due to extravasation of intestinal contents, is necessarily high. Could these cases be excluded from the tables we should find that operative interference in typhoid perforation is associated with a moderately low mortality.


From the peritoneal fluid at operation Dr. Clopton obtained in cultures an abundant growth of the streptococcus pyogenes, the bacillus coli communis, the bac. lactis aerogeues and a yeast fungus.
A consideration of our cases, and of some heretofore reported, emphasizes the necessity of early operation upon the first symptoms of perforation, or possibly upon recognizable pre-perforative symptoms, without waiting for the usual signs of peritonitis. It is far better to operate early, needlessly if it so


Autopsy. Eleven hours after death. Dr. Nichols.


Anatomical diagnosis. Typhoid fever. Perforation. General fibriuo-purulent peritonitis. Operation. Healing ulcers in ileum, caecum and appendix. Slight ileo-colitis. Suppurating peritoneal gland. Acute splenic tumor. Cloudy swelling of kidneys, etc., etc.


The protocol need not be given here in full. The lesions in the organs were typical of typhoid infection. The peritoneal surfaces were quite generally involved in an inflammatory process with thin adhesions and without the production of much fibrin or pus. The free fluid had a sero-purulent character. There was a second threatening perforation a short
• Fitz, R. H. : latestinal Perforation in Typhoid Fever : Its Progress and Treatment. Trans, of the Assoc, of Am. Phys., Vol. VI, p. 20n, 1891.






"ExWv"'S «\"'^
eventuate, rather than to wait until symptoms of peritonitis appear and actually demonstrate a perforation by its dread and practically inoperable sequel of general septic infection of the peritoneal cavity.


Any abdominal symptoms occurring in the course of the fever are as urgent indications for a surgical consultation as is the appearance of pain and tenderness in the right iliac fossa under all occasions, and only when this is fully realized will the mortality of these cases approach the low percentage reached in operations for acute perforative appendicitis or perforating gunshot wounds of the abdomen. Delay in these two latter conditions is no longer thought of, and equally prompt intervention ou the first abdominal symptoms in the course of typhoid, without waiting for actual evidence of peritonitis, will similarly reduce its high death-rate. It is hard to understand Dr. Keen's advocating delay until symptoms of shock have passed away and his preference of the second twelve hours for operating, when one appreciates that extravasation, perhaps of virulent organisms, is with all probability continually taking place while we are waiting.


There are of course certain cases, of which Dr. Osier* makes mention, in which perforation gives rise to no signs whatever as the patients are desperately ill and the local features are masked by the severity of the toxtemia. The diagnosis is usually made at such times on the autopsy table. Hospital cases, however, are usually carefully watched and some symptoms almost invariably should give warning of the complication, if not before, certainly at the time of perforation.


I
The figures, however, as they are given, including cases of all descriptions, even those condemned before they reach the operating room, present a comparatively low mortality.


Westf all's statistics (1898) given by Keenf are the most recent, and show 19.36 per cent, of recoveries in 83 collected cases. Those of FinueyJ (1897) include forty-five fairly authentic cases, with eleven recoveries, making his statistics somewhat better with 26.22 per cent, of recoveries. Monad and Vanverts§ consider the mortality to be much greater, namely 88 per cent., contrasted with a supposed 95 per cent, of deaths in unoperated perforations. With this small margin, however, they strongly recommend operation.


It is probable that the last figures morenearly represent the truth, as there are presumably many cases lost from tardy operations, which are never reported, and in the more favorable statistics given above there are doubtless some cases included which are of questionable typhoid origin.


Only in recent years has it become possible by bacteriological examination and by the serum reaction to conclusively demonstrate the nature of certain fevers. The writer recently operated on a perforated appendix associated with a general fibrino-purulent peritonitis due to a colon infection in a patient who subsequently had for three weeks a typical typhoid


PUOTOGUAl'II OF THE ILKIM I'l' C'aM; 111.




Osier : Practice of Medicine, 3d edition, 1898, p. 26.
•f Surgical ComplicationsandSequelsof Typhoid Fever, 1893, p. 234.


November, 1898.]
I Finney, J. M.T.: The Surgical Treatment of PerforatingTyphoid Ulcer. The Annals of Surgery, March, 1897.


gMonad, Ch. et J. Vanverts : Du traitement chirurgical des p^ritonites par perforation dans la lievre typhoide. Revue de Chirurgie. T. XVII, 1897, p 169.




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distance above the ileo-csecal valve. The mesenteric glands were all swollen, soft, and one showed an area of suppuration the size of a pea. There were two or three small round healing ulcers in the csecum and appendix. The following description is taken directly from the protocol :


The Ileum presents a remarkable appearance. The very edge of the ileo-cEecal valve has preserved its mucous membrane. Above this the mucous membrane has been completely destroyed over a large surface by single, confluent, often suspicious looking ulcers. One has reached the size of 7 cm. in length by 4 cm. in breadth. (This is well shown in the photograph.) The central part of this has a small clot adherent to it, and corresponds to a hajniorrhagic area on the serosa, looking like an imminent perforation situated 4 cm. above the ileo-cajcal valve. These ulcers have the same general characteristics, their edges are raised, seem opaque, congested and partly hismorrhagic. Their base is clean and apparently extends down to the transverse musculature. It is of bright red color, and transverse striae can be plainly seen. About the edges and often running in small strands across the base is a pink, delicate, new growth of epithelium. The general direction of these ulcers is longitudinal. This extensively ulcerated area does not extend much further than 11 cm. from the valve. Fourteen centimetres above the valve is a similar ulcer, puckered and inverted by the silk sutures where the perforation had occurred. This ulcer was not larger than a five-cent piece.
[No. 92.


There are about five small, similar ulcers at various distances apart above this. The whole mucous surface is somewhat congested and there, are .small sub-mucous ecchymoses. Peyer's patches and the solitary follicles are not swollen to any appreciable extent.


Bacteriological Report — Dr. Harris. — Cultures from the abdominal cavity gave the streptococcus pyogenes. From the spleen and gall-bladder was obtained an actively motile bacillus, which decolorized by Gram, and in cultural characteristics corresponded to the bacillus typhosus. From the liver, kidney and peritoneal gland an organism was obtained which was identified as the bacillus coli communis. Also from the pelvic exudate, lung and peritoneal gland was obtained a bacillus corresponding to the bacillus lactis aerogenes.


This case would appear to be of special importance in that it exemplifies the existence of a definite recognizable condition spoken of above as the pre-perforative stage of ulceration. It seems not unnatural to suppose that, owing to the extreme degree of ulceration of the ileum or possibly of the appendix, some inflammation of the serosa, limited by adhesions, may have taken place. This would account for the abdominal pain, tenderness and leucocytosis of several days duration and the disappearance of the latter after perforation had actually occurred. Doubtless it would have been better to have operated early, and have sutured or drained from any suspicious patch.
chart and a general typhoidal appearance without leucocytosis, and with no abdominal symptoms. This would undoubtably in former years have been considered an ajipendicular typhoid perforation. Only after persistent negative results with the Widal reaction could we believe the case to be nou-typhoidal.*


These preliminary abdominal symptoms undoubtedly somewhat disguised those of perforation with extravasation when it subsequently actually occurred, and the abdomen unfortu
Another case, which would certainly have been considered a perforation in an ambulatory typhoid had not careful microscopical and bactei'iological study been made of the tissues, is as follows :


The patient, Fred. H., aged 26, having been discharged from the work-house the day previously, entered the hospital January 25, 1897, after 12 hours of acute abdominal distress. He had all the symptoms of general peritonitis, and at operation a single perforation was found in the ileum the size of a five-cent piece and about ten inches above the ileo-csecal valve. He died 6 hours later, and the necropsy revealed an acute splenic tumor, parenchymatous degeneration of the liver and kidneys, but no other intestinal lesions characteristic of typhoid. There were no focal necroses in the liver, and the bacillus typhosus was nowhere obtained in cultures.


nately was not opened until after evidences of general peritonitis had begun to appear.
This case of perforation of the ileum, evidently not typhoid, presents such similarity to the notable one of Miculicz, which is usually admitted to have been of typhoid origin, that I cannot but believe the latter also was due to a perforation not resulting from typhoid fever, though its exact nature must remain uncertain. Doubtless many others of the tabulated perforation cases would likewise be discarded as " not typhoid " could they be scrutinized in the light of more recent and positive methods of diagnosis.


How often a streptococcus peritonitis has been the cause of death in the fatal operative cases cannot be told, and it is a matter of regret that bacteriological reports showing the variety of peritonitis present in these cases are not more often noted. Keen* says : " There is but a single instance, so far as I know, of a bacteriological examination of the contents of the peritoneum in typhoid perforation." Undoubtedly peritonitides of this nature are very fatal, and the abundance of long streptococcus chains, found in cover-slip preparations during the operation, gave immediately a bad prognosis to what seemed otherwise a favorable case.
Diagnosis. — The question of early diagnosis of typhoid perforation is unfortunately but little touched upon in the recent monographs upon the subject, which give little more than a stereotyped picture of pain, collapse, vomiting and abdominal tenderness, a symptom complex which is enough of course in ordinary cases to assure one of the condition. We have seen illustrated by the above cases, however, that this picture is but rarely complete, and the difficulties in the way of the recognition of perforation are frequently so great that it may be overlooked entirely. Two of them also show that other conditions may give the characteristics typical of perforation when this complication has not occurred.


The extent of peritonitis macroscopically was one such as is not infrequently recovered from in those more fortunate cases in which streptococci are not the paramount infective agent. As Durham f has emphasized, " the more virulent the infection the less marked are the local signs of peritonitis."
The complete symptomatology is usually given as follows. During the course of the fever, usually in the third week of a severe attack, most often in male adults there appears, with sudden onset, abdominal pain usually in the right side, associated with more or less tenderness and rigidity. Vomiting follows with more or less irregularity. The onset may be associated with a chill and pyrexia, or with cold extremities, collapse and a drop in temperature often of several degrees. The pulse becomes small and wiry. Leucocytosis is supposed to make its appearance, and soon more or less abdominal distension sets in with increase of vomiting, shifting dulness in the flanks, obliteration of liver dulness, a gradual return of i)yrexia if there has been a fall, with rapid feeble pulse, restlessness and


A streptococcus infection in typhoid is undoubtedly a very severe complication and Vincent J believes that it carries with it an extremely grave prognosis. Doubtless, considering its frequency in autopsy records of perforation, it has been present in many of the fatal cases which have succumbed after operation. Eeports by Flexner,§ Fraenkelll and others show how frequently streptococci are obtained from the peritoneal exudate at post-mortem examinations after typhoid perforations. Tavel and LanzT[ in their extensive report on peritonitis, recognize the frequency and importance of streptococcus infections, but they seem to have encountered no cases of typhoid perforation at the surgical clinic in Bern, nor has Korte** in his recent paper added any to his two previously published cases.


It is strange with the degree of ulceration found and the abundance of streptococci present, that there was no diarrhoea in this case. The steady drop in the leucocytes, after the perforation and with the onset of general peritonitis, is a most interesting feature and recalls the condition in Case II, where with the purulent peritonitis no leucocytosis was presen t, though it will be observed that no count was made in the latter case at the time of probable perforation or just before it. It is quite well recognized that in appendicitis the leucocytosis, which may be high (30,000 to 30,000) before, drops after perforation, and


Thi8 case subsequently came to autopsy and a tuberculous
enteritis was found. The appendicular perforation was probably through a tuberculous ulcer.




•Op. cit.,p. 220.


f Durham : On the Clinical Bearing of Some Experiments on Peritoneal Infections. Med. Chir. Trans., London, Vol. LXXX, p. 191, 1897.
thirst, all indicative of general peritonitis, with death supervening in 24 to 48 hours.


^Vincent, M. H.: Etude sur les resultats de 1' association du streptocoque et du bacille typhique. Annales de 1' Institute Pasteur, Vol. VII, p. 141, 1893.
Of these symptoms, especially those associated with the onset, a few remarks will be made.


^ Flexner, Simon : Certain Forms of Infection in Typhoid Fever, .lohns Hopkins Hospital Reports, Vol. V, 1895.
Abdominal pain and tenderness. — It is a well -recognized fact that the character of the symptoms in typhoid fever seems to vary in different years within considerable limits. An unusually large number of the cases which have been treated in our medical wards this fall have had abdominal pain and tenderness which have frequently been associated with diarrhoea. This has been so pronounced a feature that several cases have been seen in surgical consultation for symptoms which have subsequently disappeared. A sudden acute onset of increased abdominal pain is an all important symptom which unfortunately may be absent, or owing to a patient's stupor be overlooked. Any complaint of pain, however, of less abrupt onset, associated with tenderness, must arouse the greatest suspicion on the part of the attendant. I cannot but believe that the condition which has been spoken of above as a pre-perforative stage of ulceration often exists. A little localized inflammation of the serosa, with or without the passage of microorganisms and leading to a slight adhesive peritonitis, usually of omentum, can give rise to these symptoms and produce an associated slight leucocytosis. This is precisely analogous to what occurs in the pre-perforative stage of appendicitis which, however, is of less urgent nature because in the case of the appendix which is fixed and does not move about freely in the general cavity, as do the coils of ileum, the adhesions are less likely to be dislocated and a general peritonitis, which would result from this separation, is avoided. This is as true of appendicular perforations in typhoid as of those occurring at other times. I believe that this pre-perforative stage may be frequently recognized as in Case III reported above. Doubtless m some of the successful cases of operation for perforative peritonitis such a pre-perforative stage has been met with. This was notably so in Dr. J. B. Murphy's case,* where no perforation was found, but merely a local inflammatory reaction about one threatening ulcer. Several of the other successful cases illustrate a preextravasation stage where adliesions had reinforced the serosa before it gave way entirely and had temporarily prevented extravasation. Among such cases may be mentioned Watsou's,t Bogart'sJ and our first case at the third operation.


II Fraenkel, Euj!. : Zur Aetiologie der Peritonitis. Miinchener med. Wochenschrift, Bd. XXXVII, s. 23, 1890.
Under rare conditions when the adhesions are firm, which, for the reasons mentioned above, is more likely to occur when the appendix is the seat of threatened perforation, the base of the ulcer may completely penetrate the bowel and yet the general cavity be protected. A local abscess may result, or the adhesions may floor the ulcer and subsequent healing take place over them so that recovery follows withoitt operative intervention.


H Tavel, E. und Otto Lanz : Ueber die Aetiologie der Peritonitis. Mitteilungen aus Kliniken und medicinischen Instituten der Schweiz, 1898.
This is the usual explanation of recovery following symptoms of perforation, in cases which have not been subjected to operaration. In the case of Buhl,§ qtroted by Fitz, at an autopsy


Korte, W.: Weiterer Bericbt iiber die chirurgische Behandlung
der diffusen eiterigen Bauchfellentzundung. Mitteilungen aus den Grenzgebieten der Medizin und der Chirurgie, Bd. II, 1897, p. 145.




•Westcott's table, Case No. 41. Keen.


264
t Watson : Boston Med. and Surg. Journ., Vol. CXXXIV, 1896.


t Bogart : Op. cit.


I Zeitschr. f. rat. Med., 1857, N. F. VIII, S. 12.


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[No. 92.




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with the onset of general peritonitis often disappears completely.


I am inclined to believe that in these suspicious cases the tubs should be discontinued. The late appearance of vomiting and its single occurrence shows the unreliability of this symptom for the diagnosis of perforation.


Case IV. Surgical No. 8154. — Typhoid fever in foiirlli week during relapse. Supposed perforation. Exploratory lajxirotomy negative. Recovery.
267


Maggie P., aged 15, was admitted to the medical wards, August 8, 1898, in the first week of typhoid fever. The fever pursued a typical course (cf. Clinical chart) without abdominal symptoms, with no leucocytosis and with a positive Widal reaction. A moderately severe phlebitis of the left leg appeared unassociated with leucocytosis on the 33rd day. There was considerable swelling of the leg, and tenderness over the femoral vessels. The temperature reached 10i°, but in a few days dropped to normal, and remained down twelve days. The patient was up in a wheel-chair, and without symptoms.


On September 22nd (the 52nd day after onset) a relapse of the fever came on abruptly, the temperature rising suddenly to 103° and on the following day to 105°. There was some nausea and vomiting, without abdominal tenderness or pain, but associated with a leucocytosis of 16,000. This condition persisted for the succeeding 48 hours, and therightiliacfossa was noted as being slightly resistant. Some tenderness was noticed in the right calf.


On September 24th, the child began to complain of abdominal pain. She was seen in the evening in consultation with Dr. McCrae, but there were no objective abdominal symptoms at that time. The condition was much as on the preceding day. There was some tenderness in both calves on pressure.
following death from haemorrhage, a pre-existing perforation was found to have been closed by omentum. This was twentythree days after the occurrence of symptoms of perforation. Dr. Hare* of Brisbane, says : "At present it is an open question whether the treatment should be medical or surgical ; whether indeed laparotomy is justifiable." He reports an interesting case in which symptoms of perforation had occurred. The patient subsequently died, some time later, with dysenteric symptoms, and the ileum was found surrounded by adhesions, which were especially dense at the point corresponding to a supposed perforation. I do not think, however, that this case is at all conclusive. A threatened perforation with perhaps the escape of some organisms through an intact serosa, which Dr. Welch has proved to be possible, would have accounted for the localized peritonitis. Had the perforation been complete, doubtless the adhesions would not have long sufficed to confine the extravasation. In his second case of supposed recovery after perforation an operation, had it been offered in the first hours of symptoms, would with greater probability have insured success. Mr. Gairdner'sf interesting cases also would show that a fatal peritonitis without an absolutely complete perforation may take place. He reports five such instances.


September 25th, 1.30 A.M., the child awolfe crying out with a sudden sharp pain in the abdomen " unlike anything she had previously had." Some nausea and slight vomiting followed. Leucocytosis 11,000. Two hours later, 3.30 A. M., the patient was again seen by the writer. She was complaining of colicky pain in the abdomen. Her thighs were kept flexed. There was some slight distension present. The liver dulness did not reach the costal margin by a finger's breadth. The walls were somewhat tense, and with moderately deep pressure in the right iliac region muscle spasm was elicited and the patient would cry out with pain. The chief rigidity, however, was above the level of the umbilicus. Her leucocytes had dropped to 8200. She vomited about 20 cc. of nourishment given her just before.
The protection by adhesions in this way is too precarious a thing to be relied upon, and that they should hold for any length of time is something which can never be anticipated. The recognition of this pre-perforative stage I would emphasize as all important.^


Operation September 25th, 6 A. M., four and one-half hours after the first appearance of symptoms.
This is the period in which, if possible, an operation should be performed, and as it may endure but a short time, the opportunity should be immediately seized. Such a condition existed in Bogart's case§ in which he found a perforation of the ileum closed and the ulcer floored by the adherent tip of the appendix. He speaks of the presence of sero-puruleut fluid in the general cavity which doubtless was free from organisms as it was in our Case I, which was operated upon before extravasation of intestinal contents had taken place. An opportunity of operating in this stage was unhappily neglected in Case III.


Exploratory laparotomy. Negative findings. Closure loithout drainage.
An analogous pre-perforative stage was recognizable in the following case, one of dysentery, upon which the writer recently operated, though too late. The patient had been in the medical wards for some days with a severe amoebic dysentery. He developed considerable abdominal pain, tenderness and leucocytosis, with some rigidity of the parietes. Several


An incision was made in the right iliac region. There was no free fluid in the general cavity ; no injection of the peritoneum. The appeudi.x, ileum and ascending colon appeared normal and without adhesions. The Peyer's patches in the ileum were swollen and hard, being felt like buttons through the bowel. The gall-bladder was not distended or inflamed. The pelvic viscera were negative. No thrombi could be palpated in the internal iliac veins. There were no suppurating glands felt in the mesentery. The abdominal wound was closed. The operation lasted only fifteen minutes.


The patient showed no ill effects from the operation. There was no subsequent nausea or vomiting; her leucocytosis dis


» The Cold Bath Treatment of Typhoid Fever, 1898, p. 178.


appeared, and she passed through an uneventful relapse of fever (cf. Clinical chart).
tGairdner: Peritonitis in Enteric Fever. The Glasgow Med. Journal, Vol. XLVI, p. 114, Feby., 1897.


In the light of our previous experience with Cases II and III and with such symptoms as sudden acute abdominal pain, nausea and vomiting with increasing distension, some rigidity and tenderness and leucocytosis (especially a falling leucocytosis), the writer did not dare take the responsibility of withholding operative intervention even though there was some doubt as to the diagnosis. The possibility of an extension of the phlebitis to the internal iliac veins, thus causing some abdominal pain and tenderness, was thought of, but with the preceding phlebitis of September 23nd there had been no leucocytosis, pain or vomiting. The fact that the chief rigidity was above the level of the umbilicus suggested a gall-bladder complication, which in itself would have demanded exploration. The general appearance of the child was not that of collapse following perforation. There was no marked change in pulse, temperature or respiration with the above-mentioned symptoms. Nevertheless, I believed much less responsibility to be associated with an exploratory laparotomy than with running the risk of neglecting a i)erforation until signs of peritonitis should occur.
t Under "pre-perforative stage" let it be understood that the whole period is included between the first involvement of the serosa with the customary formation of adhesions at that point, until these adhesions, which may for a time constitute the floor of the ulcer after the serosa has given way, have themselves become broken down and general extravasation has taken place. This period as in perforating appendicitis may last a longer or shorter time and is associated with pain and tenderness and a possible rise in leucocytosis owing to the localized peritonitis. i Bogart, J. Bion : loc. cit.


The precise cause of the patient's symitoms remains undecided. She was a very nervous child, ai:d there had been some children with acute abdominal affections in the ward during her previous period of convalescence.


Similar cases have been reported. Herrington andBowlby* report an operation on a young girl convalescing from typhoid who had even more marked symptoms of perforation with collapse than those related above. There is no mention of a leucocyte count. A laparotomy revealed no peritoneal lesion. Convalescence was uninterrupted.


General Considerations on Operation for Typhoid Perforation. — In recent years several tables have appeared in which are included all of the supposed authentic cases of operation for this particular complication in typhoid, notably those of Finney, Keen and Monad and Vanverts.
days later, while having a rectal irrigation, sudden evidence of perforation and extravasation occurred with acute paiu and collapse. At the operation, three hours later, bis abdomen was full of fifices, which were pouring from a large opening in the sigmoid flexure. The autopsy revealed an extraordinary degree of ulceration of the colon with a complete loss of substance in the bowel in several places, but all of these ulcerated areas, except the one found at the operation, were completely floored by protecting omental adhesions.


Statistics, however, always misleading, are especially so when they concern a question involving so many considerations as are included under the one head of " Results of Operation for Typhoid Perforation."
As iu the three typhoid cases reported above, here too was a distinctly recognizable pre-perforation or pre-extravasation stage of intestinal ulceration which demanded operative relief before final signs of perforation with extravasation had rendered the chances of giving it most desperate.


In the first place two distinct varieties of perforation may be recognized in which the operative prognosis is widely different. In one, the appendicular form, the process takes place in a quiet corner of the abdomen usually remaining localized, owing to the formation of adhesions, for perhaps a long time. In these cases some pre-existing chronic appendicular trouble may predispose toward perforation in the same way as does an ulcer of typhoidal origin in this situation. The condition, then, is practically one of acute perforative appendicitis occurring in the course of typhoid, and has the same prognosis and surgical features as similar conditions unassociated with
Undoubtedly, signs exist which are often considered trivial, but which may aid us iu anticipating a final perforation by indicating early laparotomy.


Temperature and Pulse. — A prouounced drop in temperature is a not infrequent symptom, associated with the onset of the perforation. It must, however, be clearly distinguished from the great fall in surface temperature, which is often pronounced and gives rise to the cold and clammy extremities so characteristic of the collapse of onset. This latter condition, however, may be associated with a rise of central temperature. In some of the cases cited by Fitz this collapse was the only symptom indicative of perforation.


The suilden fall of the central temperature, wheu it occurs, is such a pronounced feature that more importance has been ascribed to it than it deserves. Dieulafoy* considered it au almost infallible sign. He says : " La perforation intestinale, au cours de la fievre typhoide se traduit dans la tres grande majorite des cas, par uue chute hru^ve de la temperature." He thinks the appendicular attacks occurring in the course of the fever show, ou the coutrar}', a rise in temperature, and may thus be distinguished. Lerebonllet.t however, takes exception to this statement in a thorough discussion, and believes it to be exceptional. Gesselewitsch and WanachJ also emphatically assert that many cases are accompanied by a rise in temperature. One can merely state that when present it is a characteristic symptom, but that it may be absent. It also, of course, frequently occurs in other conditions such as haemorrhage, and our Case I further illustrates its unreliability as there was no drop with the perforation, but a prouounced fall with the obstruction and after each operation. It may possibly be a means of distinguishing, as Dieulafoy suggested, between a perforation with extravasation into the free cavity and one protected by adhesions giving merely a local inflammatory reaction.


Herrington, W. C, and Bowlby, A. A. : Typhoid Fever Convalescence; Symptoms of Perforation, Laparotomy ; no Lesion found;
Recovery. Med. Chir. Transactions, London, Vol. LXXX, 1897, p. 127.




•Dieulafoy: De rintervention chirurgicale dans les peritonites de la fievre typhoide. Bull, de I'Academie de Medicine. Oct. 27, 1896.


November, 1898.]
tLereboullet : Sur le diagnostic et le traitement des perforations intestinales dans la fiuvre typhoide. Bull, de I'Acad. de M^d. Nov. 3, 1896.


t Gesselewitsch and Wanach : Die Perforations Peritonitis beim Abdominal Typhus und ihre operative Behandlung. Mitteilungen aus den Grenzgebieten der Medizin und Chirurgie, Bd. I, H. 1 und 2, 1898.




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typhoid which give a certain percentage of recovery in uuoperated cases.


In the other variety the perforation almost always occurs in the freely moving bowel, usually in the lower foot of the ileum.
[No. 92.


I believe that Dr. Fitz* first clea'-ly distinguished between these two varieties of perforation in typhoid, emphasizing the fact that many cases would be called appendicitis which, when occurring during typhoid fever, are classed as perforations. Undoubtedly the appendicular cases are much more common thau has been ordinarily supposed. Fitz finds, however, only 3 per cent, in 167 cases. Of the 20 cases of perforation in the pathological records of the Johns Hopkins Hospital there have been 3 appendicular perforations which, grouped with a single case out of the nine of which I am personally cognizant, makes 9.6 per cent, which have occurred in the appendix.


To further quote from Dr. Fitz's paper : " The probability of its occurrence (perforative appendicitis) furnishes the best solution to the prognosis of intestinal perforation in the latter disease (typhoid fever). Most cases of recovery from symptoms of perforation of the bowel iu typhoid fever are those in which an attack of appendicitis is most closely simulated, while the fatal cases of perforation of the bowel in typhoid fever are, in the great majority of instances, those in which other parts of the bowel than the appendix are the seat of of perforation."


It is of course important to recognize the fact that either of these conditions may be present, but a differential diagnosis can hardly be made, and were such possible, operative interference is as surely indicated as in any acute apj)endicitis. The prognosis in the appendicular varieties, for the reasons given above, is naturally more favorable, but in all cases the earlier surgical intervention is sought the better for the patient. This applies especially to the variety in which the perforation is in the free bowel. Here, also, adhesions presumably form as the nicer approaches the serosa, but inasmuch as they are attached to a movable part of the bowel they cannot be relied upon to hold, and extravasation usually soon takes place. It is with perforation of the ileum that we are chiefly concerned, and in looking for information upon this subject we are hampered because we find commingled iu the statistician's tables, two very different and widely separate conditions, one, the results of operation for typhoid perforation, the other, the results of operation for general peritonitis following typhoid perforation.
The disparity between pulse and temperature may be a marked feature, the former being small and rapid during the drop in temperature. The respiration likewise is apt to be more rapid and shallow with less marked abdominal movements.


The mortality following operation for general septic peritonitis, due to extravasation of intestinal contents, is necessarily high. Could these cases be excluded from the tables we should find that operative interference in typhoid perforation is associated with a moderately low mortality.
Of symtoms other than those associated with a threalening perforation or with its immediate occurrence little need be said. A cliill sometimes occurs, but more often with the circumscribed and appendicular varieties, when, too, the temperature is more apt to rise. Vomiting is an important symptom when present, but its frequent absence makes it an unreliable one. The acoustic phenomenon of Levaschoff, a sound caused by the passage of gas through the perlbration with each descent of the diaphragm, has not been generally confirmed. Later signs, such as siiifting dulness from free fluid, distension, obliteration of liver dulness and other indications of abundant extravasation of gas and faeces, such as were present in Case II, make the diagnosis of a long standing perforation as easy as its prognosis is unfavorable. Even many of these stereotyped indications of general peritonitis may be misleading. In Case III shifting dulness was a marked feature, and yet but little free fluid was present. Similarly a distended colon may cause partial obliteration of liver dulness, but even with perforation and extravasation too small an amount of gas may escape to produce it.


A consideration of our cases, and of some heretofore reported, emphasizes the necessity of early operation upon the first symptoms of perforation, or possibly upon recognizable pre-perforative symptoms, without waiting for the usual signs of peritonitis. It is far better to operate early, needlessly if it so
Leucocytosis. — Of great interest and of great diagnostic importance in these cases would seem to be the presence or absence of leucocytosis.


The final interpretation, however, to be given to this symptom is far from being made. Dr. Finney says: " Of all the socalled diagnostic signs of perforating typhoid ulcer most reliance is to be placed upon the development of an attack of severe, continued abdominal pain, coupled with nausea and vomiting, and at the same time a marked increase in the number of white blood corpuscles." We have seen, however, in some of our cases a fall and not an increase in leucocytes, which must receive consideration.


The fact that " there is not only no increase in the proportion of colorless corpuscles during the fever, but that on the contrary there is rather a tendency toward a diminution in number at the height of the disease," was emphasized by Thayer* in 1892. The occurrence of leucocytosis therefore is quite properly in most cases supposed to be coincident with the presence of some septic complication other than the surface ulcerations of the intestinal tract. Cabotf is inclined to the belief that in all the cases in which leucocytosis exists constantly, some complication really is present though it may be unrecognized. He cites two cases with a leucocytosis of 2i,000 and 18,000 respectively, occurring at the time of perforation. He further states: "It occasionally happens in very exhausted patients that complications fail to produce any leucocytosis, the patient (as in some cases of pneumonia or purulent peritonitis) being unable to react against the infection " (p. 170). This statement, I think, needs some qualification.


• Fitz, R. H. : latestinal Perforation in Typhoid Fever : Its Progress and Treatment. Trans, of the Assoc, of Am. Phys., Vol. VI, p. 20n, 1891.




Thayer, W. S.: Two cases of Post Typhoid Anaemia. With
Remarks on the Value of Examinations of the Blood in Typhoid Fever. Johns Hopkins Hospital Reports, Vol. IV, No. 1, p. 88.


eventuate, rather than to wait until symptoms of peritonitis appear and actually demonstrate a perforation by its dread and practically inoperable sequel of general septic infection of the peritoneal cavity.
tCabot, R. C: Clinical Examination of the Blood, p. ](!8, 1897.


Any abdominal symptoms occurring in the course of the fever are as urgent indications for a surgical consultation as is the appearance of pain and tenderness in the right iliac fossa under all occasions, and only when this is fully realized will the mortality of these cases approach the low percentage reached in operations for acute perforative appendicitis or perforating gunshot wounds of the abdomen. Delay in these two latter conditions is no longer thought of, and equally prompt intervention ou the first abdominal symptoms in the course of typhoid, without waiting for actual evidence of peritonitis, will similarly reduce its high death-rate. It is hard to understand Dr. Keen's advocating delay until symptoms of shock have passed away and his preference of the second twelve hours for operating, when one appreciates that extravasation, perhaps of virulent organisms, is with all probability continually taking place while we are waiting.


There are of course certain cases, of which Dr. Osier* makes mention, in which perforation gives rise to no signs whatever as the patients are desperately ill and the local features are masked by the severity of the toxtemia. The diagnosis is usually made at such times on the autopsy table. Hospital cases, however, are usually carefully watched and some symptoms almost invariably should give warning of the complication, if not before, certainly at the time of perforation.


The figures, however, as they are given, including cases of all descriptions, even those condemned before they reach the operating room, present a comparatively low mortality.
Using the cases above reported, in all of which careful leucocyte counts were made, we are confronted by quite a diflerent picture. In Case II the complete absence of leucocytosis was the unfortunate cause of a deferred operation. I doubt not, however, that a leucocytosis, which subsequently disappeared, was present at the onset of the peritonitis.


Westf all's statistics (1898) given by Keenf are the most recent, and show 19.36 per cent, of recoveries in 83 collected cases. Those of FinueyJ (1897) include forty-five fairly authentic cases, with eleven recoveries, making his statistics somewhat better with 26.22 per cent, of recoveries. Monad and Vanverts§ consider the mortality to be much greater, namely 88 per cent., contrasted with a supposed 95 per cent, of deaths in unoperated perforations. With this small margin, however, they strongly recommend operation.
In Case I there was an early and recognized leucocytosis appearing, however, before any signs of general peritonitis had developed; and in the peritoneal fluid comparatively few white cells were present and no micro-organisms.


It is probable that the last figures morenearly represent the truth, as there are presumably many cases lost from tardy operations, which are never reported, and in the more favorable statistics given above there are doubtless some cases included which are of questionable typhoid origin.
In Case III, a preceding leucocytosis associated with abdominal pain and tenderness, which, as has been stated, was probably indicative of a mild local peritonitis about the extensively ulcerated bowel, was completely wiped out concomitant with the occurrence of general peritonitis and the appearance of great numbers of leucocytes in the extravasated peritoneal fluid.


Only in recent years has it become possible by bacteriological examination and by the serum reaction to conclusively demonstrate the nature of certain fevers. The writer recently operated on a perforated appendix associated with a general fibrino-purulent peritonitis due to a colon infection in a patient who subsequently had for three weeks a typical typhoid
In the case of dysenteric perforation, mentioned above, the leucocytosis had previously been constantly high. A few days before the perforation it was 47,000. At the time of perforation it was 41,000. An hour later it had fallen to 30,000 and at the time of operation it was 27,000, a drop of 20,000 in three hours. At the operation the lower bowel was matted together with adherent omentum, this local inflammatory j^rocess doubtless being the cause of the preceding leucocytosis. The general cavity was full of fajcal and purulent fluid, in which were great numbers of polymorphonuclear leucocytes, eosinophiles and mononuclears in about the proportions found in the blood. Many of these cells were crowded with organisms and disintegrating. There is but one natural conclusion to be made from this sudden diminution of the number of white cells in the peripheral circulation coupled with their appearance in the peritoneal exudate.


Similarly in appendicitis the writer has frequently seen, after a high percentage of leucocytes present during the acute stage, a drop in their number occurring in association with the onset of peritonitis, as characteristic as that which occurs with the subsidence of the acute attack and recovery.


In Cabot's table XXI of counts made in general peritonitis, there are 4 without leucocytosis, the numbers varying between 4600 and 6000. Of those with leucocytosis, as well as in his cited dysenteric case with 24,000 leucocytes there is no recognition of a possible fall in number such as occurred in the cases cited above after the onset of general peritonitis.


Osier : Practice of Medicine, 3d edition, 1898, p. 26.
Cabot* says : "A steadily increasing leucocytosis is always a bad sign and should never be disregarded even when other bad symptoms are absent." I would add that a decreasing leucocytosis may be a much worse sign, and should never be disregarded. This is especially of importance in those typhoid cases in which the "other bad symptoms" are diflBcult to estimate on account of the dull condition of the patient.
•f Surgical ComplicationsandSequelsof Typhoid Fever, 1893, p. 234.


I Finney, J. M.T.: The Surgical Treatment of PerforatingTyphoid Ulcer. The Annals of Surgery, March, 1897.
From these data on leucocytosis the following conclusions may be drawn :


gMonad, Ch. et J. Vanverts : Du traitement chirurgical des p^ritonites par perforation dans la lievre typhoide. Revue de Chirurgie. T. XVII, 1897, p 169.
1. The appearance of leucocytosis in the course of typhoid fever points toward some inflammatory complications in its early stage.






266
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chart and a general typhoidal appearance without leucocytosis, and with no abdominal symptoms. This would undoubtably in former years have been considered an ajipendicular typhoid perforation. Only after persistent negative results with the Widal reaction could we believe the case to be nou-typhoidal.*
,


Another case, which would certainly have been considered a perforation in an ambulatory typhoid had not careful microscopical and bactei'iological study been made of the tissues, is as follows :


The patient, Fred. H., aged 26, having been discharged from the work-house the day previously, entered the hospital January 25, 1897, after 12 hours of acute abdominal distress. He had all the symptoms of general peritonitis, and at operation a single perforation was found in the ileum the size of a five-cent piece and about ten inches above the ileo-csecal valve. He died 6 hours later, and the necropsy revealed an acute splenic tumor, parenchymatous degeneration of the liver and kidneys, but no other intestinal lesions characteristic of typhoid. There were no focal necroses in the liver, and the bacillus typhosus was nowhere obtained in cultures.


This case of perforation of the ileum, evidently not typhoid, presents such similarity to the notable one of Miculicz, which is usually admitted to have been of typhoid origin, that I cannot but believe the latter also was due to a perforation not resulting from typhoid fever, though its exact nature must remain uncertain. Doubtless many others of the tabulated perforation cases would likewise be discarded as " not typhoid " could they be scrutinized in the light of more recent and positive methods of diagnosis.


Diagnosis. — The question of early diagnosis of typhoid perforation is unfortunately but little touched upon in the recent monographs upon the subject, which give little more than a stereotyped picture of pain, collapse, vomiting and abdominal tenderness, a symptom complex which is enough of course in ordinary cases to assure one of the condition. We have seen illustrated by the above cases, however, that this picture is but rarely complete, and the difficulties in the way of the recognition of perforation are frequently so great that it may be overlooked entirely. Two of them also show that other conditions may give the characteristics typical of perforation when this complication has not occurred.


The complete symptomatology is usually given as follows. During the course of the fever, usually in the third week of a severe attack, most often in male adults there appears, with sudden onset, abdominal pain usually in the right side, associated with more or less tenderness and rigidity. Vomiting follows with more or less irregularity. The onset may be associated with a chill and pyrexia, or with cold extremities, collapse and a drop in temperature often of several degrees. The pulse becomes small and wiry. Leucocytosis is supposed to make its appearance, and soon more or less abdominal distension sets in with increase of vomiting, shifting dulness in the flanks, obliteration of liver dulness, a gradual return of i)yrexia if there has been a fall, with rapid feeble pulse, restlessness and






Thi8 case subsequently came to autopsy and a tuberculous
enteritis was found. The appendicular perforation was probably through a tuberculous ulcer.






thirst, all indicative of general peritonitis, with death supervening in 24 to 48 hours.


Of these symptoms, especially those associated with the onset, a few remarks will be made.


Abdominal pain and tenderness. — It is a well -recognized fact that the character of the symptoms in typhoid fever seems to vary in different years within considerable limits. An unusually large number of the cases which have been treated in our medical wards this fall have had abdominal pain and tenderness which have frequently been associated with diarrhoea. This has been so pronounced a feature that several cases have been seen in surgical consultation for symptoms which have subsequently disappeared. A sudden acute onset of increased abdominal pain is an all important symptom which unfortunately may be absent, or owing to a patient's stupor be overlooked. Any complaint of pain, however, of less abrupt onset, associated with tenderness, must arouse the greatest suspicion on the part of the attendant. I cannot but believe that the condition which has been spoken of above as a pre-perforative stage of ulceration often exists. A little localized inflammation of the serosa, with or without the passage of microorganisms and leading to a slight adhesive peritonitis, usually of omentum, can give rise to these symptoms and produce an associated slight leucocytosis. This is precisely analogous to what occurs in the pre-perforative stage of appendicitis which, however, is of less urgent nature because in the case of the appendix which is fixed and does not move about freely in the general cavity, as do the coils of ileum, the adhesions are less likely to be dislocated and a general peritonitis, which would result from this separation, is avoided. This is as true of appendicular perforations in typhoid as of those occurring at other times. I believe that this pre-perforative stage may be frequently recognized as in Case III reported above. Doubtless m some of the successful cases of operation for perforative peritonitis such a pre-perforative stage has been met with. This was notably so in Dr. J. B. Murphy's case,* where no perforation was found, but merely a local inflammatory reaction about one threatening ulcer. Several of the other successful cases illustrate a preextravasation stage where adliesions had reinforced the serosa before it gave way entirely and had temporarily prevented extravasation. Among such cases may be mentioned Watsou's,t Bogart'sJ and our first case at the third operation.


Under rare conditions when the adhesions are firm, which, for the reasons mentioned above, is more likely to occur when the appendix is the seat of threatened perforation, the base of the ulcer may completely penetrate the bowel and yet the general cavity be protected. A local abscess may result, or the adhesions may floor the ulcer and subsequent healing take place over them so that recovery follows withoitt operative intervention.


This is the usual explanation of recovery following symptoms of perforation, in cases which have not been subjected to operaration. In the case of Buhl,§ qtroted by Fitz, at an autopsy






•Westcott's table, Case No. 41. Keen.
CASE


t Watson : Boston Med. and Surg. Journ., Vol. CXXXIV, 1896.


t Bogart : Op. cit.
II


I Zeitschr. f. rat. Med., 1857, N. F. VIII, S. 12.






NOVEMBEB, 1898.]






JOHNS HOPKINS HOSPITAL BULLETIN.






267






following death from haemorrhage, a pre-existing perforation was found to have been closed by omentum. This was twentythree days after the occurrence of symptoms of perforation. Dr. Hare* of Brisbane, says : "At present it is an open question whether the treatment should be medical or surgical ; whether indeed laparotomy is justifiable." He reports an interesting case in which symptoms of perforation had occurred. The patient subsequently died, some time later, with dysenteric symptoms, and the ileum was found surrounded by adhesions, which were especially dense at the point corresponding to a supposed perforation. I do not think, however, that this case is at all conclusive. A threatened perforation with perhaps the escape of some organisms through an intact serosa, which Dr. Welch has proved to be possible, would have accounted for the localized peritonitis. Had the perforation been complete, doubtless the adhesions would not have long sufficed to confine the extravasation. In his second case of supposed recovery after perforation an operation, had it been offered in the first hours of symptoms, would with greater probability have insured success. Mr. Gairdner'sf interesting cases also would show that a fatal peritonitis without an absolutely complete perforation may take place. He reports five such instances.


The protection by adhesions in this way is too precarious a thing to be relied upon, and that they should hold for any length of time is something which can never be anticipated. The recognition of this pre-perforative stage I would emphasize as all important.^


This is the period in which, if possible, an operation should be performed, and as it may endure but a short time, the opportunity should be immediately seized. Such a condition existed in Bogart's case§ in which he found a perforation of the ileum closed and the ulcer floored by the adherent tip of the appendix. He speaks of the presence of sero-puruleut fluid in the general cavity which doubtless was free from organisms as it was in our Case I, which was operated upon before extravasation of intestinal contents had taken place. An opportunity of operating in this stage was unhappily neglected in Case III.


An analogous pre-perforative stage was recognizable in the following case, one of dysentery, upon which the writer recently operated, though too late. The patient had been in the medical wards for some days with a severe amoebic dysentery. He developed considerable abdominal pain, tenderness and leucocytosis, with some rigidity of the parietes. Several






» The Cold Bath Treatment of Typhoid Fever, 1898, p. 178.


tGairdner: Peritonitis in Enteric Fever. The Glasgow Med. Journal, Vol. XLVI, p. 114, Feby., 1897.


t Under "pre-perforative stage" let it be understood that the whole period is included between the first involvement of the serosa with the customary formation of adhesions at that point, until these adhesions, which may for a time constitute the floor of the ulcer after the serosa has given way, have themselves become broken down and general extravasation has taken place. This period as in perforating appendicitis may last a longer or shorter time and is associated with pain and tenderness and a possible rise in leucocytosis owing to the localized peritonitis. i Bogart, J. Bion : loc. cit.


lOl




days later, while having a rectal irrigation, sudden evidence of perforation and extravasation occurred with acute paiu and collapse. At the operation, three hours later, bis abdomen was full of fifices, which were pouring from a large opening in the sigmoid flexure. The autopsy revealed an extraordinary degree of ulceration of the colon with a complete loss of substance in the bowel in several places, but all of these ulcerated areas, except the one found at the operation, were completely floored by protecting omental adhesions.
• 5


As iu the three typhoid cases reported above, here too was a distinctly recognizable pre-perforation or pre-extravasation stage of intestinal ulceration which demanded operative relief before final signs of perforation with extravasation had rendered the chances of giving it most desperate.


Undoubtedly, signs exist which are often considered trivial, but which may aid us iu anticipating a final perforation by indicating early laparotomy.


Temperature and Pulse. — A prouounced drop in temperature is a not infrequent symptom, associated with the onset of the perforation. It must, however, be clearly distinguished from the great fall in surface temperature, which is often pronounced and gives rise to the cold and clammy extremities so characteristic of the collapse of onset. This latter condition, however, may be associated with a rise of central temperature. In some of the cases cited by Fitz this collapse was the only symptom indicative of perforation.
s


The suilden fall of the central temperature, wheu it occurs, is such a pronounced feature that more importance has been ascribed to it than it deserves. Dieulafoy* considered it au almost infallible sign. He says : " La perforation intestinale, au cours de la fievre typhoide se traduit dans la tres grande majorite des cas, par uue chute hru^ve de la temperature." He thinks the appendicular attacks occurring in the course of the fever show, ou the coutrar}', a rise in temperature, and may thus be distinguished. Lerebonllet.t however, takes exception to this statement in a thorough discussion, and believes it to be exceptional. Gesselewitsch and WanachJ also emphatically assert that many cases are accompanied by a rise in temperature. One can merely state that when present it is a characteristic symptom, but that it may be absent. It also, of course, frequently occurs in other conditions such as haemorrhage, and our Case I further illustrates its unreliability as there was no drop with the perforation, but a prouounced fall with the obstruction and after each operation. It may possibly be a means of distinguishing, as Dieulafoy suggested, between a perforation with extravasation into the free cavity and one protected by adhesions giving merely a local inflammatory reaction.
!J






•Dieulafoy: De rintervention chirurgicale dans les peritonites de la fievre typhoide. Bull, de I'Academie de Medicine. Oct. 27, 1896.
«


tLereboullet : Sur le diagnostic et le traitement des perforations intestinales dans la fiuvre typhoide. Bull, de I'Acad. de M^d. Nov. 3, 1896.
5 5


t Gesselewitsch and Wanach : Die Perforations Peritonitis beim Abdominal Typhus und ihre operative Behandlung. Mitteilungen aus den Grenzgebieten der Medizin und Chirurgie, Bd. I, H. 1 und 2, 1898.


5 S




268
y




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[No. 92.


IJ


/


The disparity between pulse and temperature may be a marked feature, the former being small and rapid during the drop in temperature. The respiration likewise is apt to be more rapid and shallow with less marked abdominal movements.


Of symtoms other than those associated with a threalening perforation or with its immediate occurrence little need be said. A cliill sometimes occurs, but more often with the circumscribed and appendicular varieties, when, too, the temperature is more apt to rise. Vomiting is an important symptom when present, but its frequent absence makes it an unreliable one. The acoustic phenomenon of Levaschoff, a sound caused by the passage of gas through the perlbration with each descent of the diaphragm, has not been generally confirmed. Later signs, such as siiifting dulness from free fluid, distension, obliteration of liver dulness and other indications of abundant extravasation of gas and faeces, such as were present in Case II, make the diagnosis of a long standing perforation as easy as its prognosis is unfavorable. Even many of these stereotyped indications of general peritonitis may be misleading. In Case III shifting dulness was a marked feature, and yet but little free fluid was present. Similarly a distended colon may cause partial obliteration of liver dulness, but even with perforation and extravasation too small an amount of gas may escape to produce it.


Leucocytosis. — Of great interest and of great diagnostic importance in these cases would seem to be the presence or absence of leucocytosis.


The final interpretation, however, to be given to this symptom is far from being made. Dr. Finney says: " Of all the socalled diagnostic signs of perforating typhoid ulcer most reliance is to be placed upon the development of an attack of severe, continued abdominal pain, coupled with nausea and vomiting, and at the same time a marked increase in the number of white blood corpuscles." We have seen, however, in some of our cases a fall and not an increase in leucocytes, which must receive consideration.


The fact that " there is not only no increase in the proportion of colorless corpuscles during the fever, but that on the contrary there is rather a tendency toward a diminution in number at the height of the disease," was emphasized by Thayer* in 1892. The occurrence of leucocytosis therefore is quite properly in most cases supposed to be coincident with the presence of some septic complication other than the surface ulcerations of the intestinal tract. Cabotf is inclined to the belief that in all the cases in which leucocytosis exists constantly, some complication really is present though it may be unrecognized. He cites two cases with a leucocytosis of 2i,000 and 18,000 respectively, occurring at the time of perforation. He further states: "It occasionally happens in very exhausted patients that complications fail to produce any leucocytosis, the patient (as in some cases of pneumonia or purulent peritonitis) being unable to react against the infection " (p. 170). This statement, I think, needs some qualification.
:






Thayer, W. S.: Two cases of Post Typhoid Anaemia. With
Remarks on the Value of Examinations of the Blood in Typhoid Fever. Johns Hopkins Hospital Reports, Vol. IV, No. 1, p. 88.


tCabot, R. C: Clinical Examination of the Blood, p. ](!8, 1897.
?f*


!M




Using the cases above reported, in all of which careful leucocyte counts were made, we are confronted by quite a diflerent picture. In Case II the complete absence of leucocytosis was the unfortunate cause of a deferred operation. I doubt not, however, that a leucocytosis, which subsequently disappeared, was present at the onset of the peritonitis.


In Case I there was an early and recognized leucocytosis appearing, however, before any signs of general peritonitis had developed; and in the peritoneal fluid comparatively few white cells were present and no micro-organisms.
!5jss5'f


In Case III, a preceding leucocytosis associated with abdominal pain and tenderness, which, as has been stated, was probably indicative of a mild local peritonitis about the extensively ulcerated bowel, was completely wiped out concomitant with the occurrence of general peritonitis and the appearance of great numbers of leucocytes in the extravasated peritoneal fluid.


In the case of dysenteric perforation, mentioned above, the leucocytosis had previously been constantly high. A few days before the perforation it was 47,000. At the time of perforation it was 41,000. An hour later it had fallen to 30,000 and at the time of operation it was 27,000, a drop of 20,000 in three hours. At the operation the lower bowel was matted together with adherent omentum, this local inflammatory j^rocess doubtless being the cause of the preceding leucocytosis. The general cavity was full of fajcal and purulent fluid, in which were great numbers of polymorphonuclear leucocytes, eosinophiles and mononuclears in about the proportions found in the blood. Many of these cells were crowded with organisms and disintegrating. There is but one natural conclusion to be made from this sudden diminution of the number of white cells in the peripheral circulation coupled with their appearance in the peritoneal exudate.


Similarly in appendicitis the writer has frequently seen, after a high percentage of leucocytes present during the acute stage, a drop in their number occurring in association with the onset of peritonitis, as characteristic as that which occurs with the subsidence of the acute attack and recovery.
1


In Cabot's table XXI of counts made in general peritonitis, there are 4 without leucocytosis, the numbers varying between 4600 and 6000. Of those with leucocytosis, as well as in his cited dysenteric case with 24,000 leucocytes there is no recognition of a possible fall in number such as occurred in the cases cited above after the onset of general peritonitis.
4


Cabot* says : "A steadily increasing leucocytosis is always a bad sign and should never be disregarded even when other bad symptoms are absent." I would add that a decreasing leucocytosis may be a much worse sign, and should never be disregarded. This is especially of importance in those typhoid cases in which the "other bad symptoms" are diflBcult to estimate on account of the dull condition of the patient.


From these data on leucocytosis the following conclusions may be drawn :
^


1. The appearance of leucocytosis in the course of typhoid fever points toward some inflammatory complications in its early stage.


^




<0p. cit., p. 197.
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Fig. 7. Germ tubes with conidia attached, from hanging drop of bouillon. 3 days.
Fig. 7. Germ tubes with conidia attached, from hanging drop of bouillon. 3 days.


Plate II.
Plate II.
 
 
Figs. 1, 2 and 3. Sections of wall of abscess in subcutaneous tissue dog. Leitz obj. i ^Fig. 1), i (Fig. 2), and J. (Fig. 3).
Figs. 1, 2 and 3. Sections of wall of abscess in subcutaneous tissue dog. Leitz obj. i ^Fig. 1), i (Fig. 2), and J. (Fig. 3).
 
 
Fig. 4. Peribronchial lymph glands of white mouse. Carmine and Weigert's stain. Leitz obj. J inch.
Fig. 4. Peribronchial lymph glands of white mouse. Carmine and Weigert's stain. Leitz obj. J inch.
 
 
 
 
 
===Oedematous Changes In The Epithelium Of The Cornea In A Case Of Uveitis Following Gonorrhceal Ophthalmia===
(EDEMATOUS CHANGES IN THE EPITHELIUM OF THE CORNEA IN A CASE OF UVEITIS FOLLOWING GONORRHCEAL OPHTHALMIA.
 
 
DECEMBER, 1898.
 


Edward Stieren, M. D , Pittsburgh, Penna.
Edward Stieren, M. D , Pittsburgh, Penna.
Line 31,618: Line 31,463:
minute channels for transporting nutritive fluids to the individual cells and containing a small amount of viscid cement substance. Pfluger'^ and Grubor'" have also described the nutrition of the corneal epithelium through these channels.
minute channels for transporting nutritive fluids to the individual cells and containing a small amount of viscid cement substance. Pfluger'^ and Grubor'" have also described the nutrition of the corneal epithelium through these channels.


THE JOHNS HOPKINS HOSPITAL BULLETIN.
DECEMBER, 1898.
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THE JOHNS HOPKINS HOSPITAL BULLETIN.
DECEMBER, 1898.
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Line 31,683: Line 31,486:


Pl.^te II.— To face p. 2'.K).
Pl.^te II.— To face p. 2'.K).
Decembee, 1898.]
JOHNS HOPKINS HOSPITAL BULLETIN.
291




Line 31,730: Line 31,521:
Apt terms need by Klebs.
Apt terms need by Klebs.


292
JOHNS HOPKINS HOSPITAL BULLETIN.
[No. 93.




Line 31,769: Line 31,550:
Alcohol fixation, celloidin section, stained with Bende's iron hiematoxylin and with congo red. A vertical section passing through the corneal e])ithelium, from a region slightly nearer the centre of the cornea than that shown in Fig. 1. The marked alterations in the epithelial cells, described at some length in the text, are here clearly shown. A few leucocytes appear among the epithelial cells.
Alcohol fixation, celloidin section, stained with Bende's iron hiematoxylin and with congo red. A vertical section passing through the corneal e])ithelium, from a region slightly nearer the centre of the cornea than that shown in Fig. 1. The marked alterations in the epithelial cells, described at some length in the text, are here clearly shown. A few leucocytes appear among the epithelial cells.


BIBLIOGRAPH'y.
BIBLIOGRAPHY


I. Arlt: Die Krankheiten des Auges. Prague, 18.55. 3. Archiv fur mikr. Anat., Vol. XXXII.
I. Arlt: Die Krankheiten des Auges. Prague, 18.55. 3. Archiv fur mikr. Anat., Vol. XXXII.
Line 31,805: Line 31,586:




PROCEEDINGS OF SOCIETIES,
===PROCEEDINGS OF SOCIETIES===




Line 31,819: Line 31,600:




that this affection was more frequent than is generally recognized, the questions of causation, pathological anatomy, symptoms, diagnosis and prognosis were severally considered. With the exception of pistol-shot wounds, sudden flexions and extensions of the neck were the best established causes. The author believed the lesion was produced by an actual stretching of the cord, with resulting laceration of blood-vessels and to a certain extent of centrally situated nerve fibres; he rejected the explanation proposed by Thorbun that a momentary displacement of a vertebra was the immediate causative agent. The pathological anatomy of the condition consists in a focal ha?morrhage confined chiefly to the gray matter always in the cervical or upper thoracic region ; the blood sometimes burrows for considerable distances up and down the cord. The extravasa
that this affection was more frequent than is generally recognized, the questions of causation, pathological anatomy, symptoms, diagnosis and prognosis were severally considered. With the exception of pistol-shot wounds, sudden flexions and extensions of the neck were the best established causes. The author believed the lesion was produced by an actual stretching of the cord, with resulting laceration of blood-vessels and to a certain extent of centrally situated nerve fibres; he rejected the explanation proposed by Thorbun that a momentary displacement of a vertebra was the immediate causative agent. The pathological anatomy of the condition consists in a focal ha?morrhage confined chiefly to the gray matter always in the cervical or upper thoracic region ; the blood sometimes burrows for considerable distances up and down the cord. The extravasation on its absorption leaves a cavity which may remain patent or be filled up by new tissue. Secondary degenerations are usually not pronounced. The symptoms are in general those of other spinal cord traumatisms, though usually less severe and less numerous; but the motor and sensory symptoms have distinguishing characters. The distribution of the motor symptoms depends upon the extent and situation of the clot. Tiiere may thus be spinal hemiplegia, or monoplegia, or (probably) brachial diplegia, or paralysis of the legs, or paralysis of b3th arms and legs. The paralysis at first, unless the lesion is very small, is flaccid in all its characters; later it assumes the central neurone type in the legs with places in the arms of peripheral neurone type. The sensory symptoms consist, in addition to pain in the neck, of a dissociated anesthesia, that is, anesthesia for temperature or for pain or for both, with perfect preservation of tactile sensibility. A case was reported in which this peculiar clinical condition was absolutely distinct, biit in which, as shown by subsequent microscopical examination, the blood had exceeded to a certain extent the confines of the central gray niatter of the cord. The sensory anomalies of primary focal haamatomyelia from traumatism are usually transitory, unless the case is exceptionally severe. In reported cases the analgesia has disappeared before the thermoansesthesia.
 
 
THE JOHNS HOPKINS HOSPITAL BULLETIN.
 
 
 
DECEMBER, 1898.
 
 
 
 
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December, 1898.]
 
 
 
JOHNS HOPKINS HOSPITAL BULLETIN.
 
 
 
293
 
 
 
tion on its absorption leaves a cavity which may remain patent or be filled up by new tissue. Secondary degenerations are usually not pronounced. The symptoms are in general those of other spinal cord traumatisms, though usually less severe and less numerous; but the motor and sensory symptoms have distinguishing characters. The distribution of the motor symptoms depends upon the extent and situation of the clot. Tiiere may thus be spinal hemiplegia, or monoplegia, or (probably) brachial diplegia, or paralysis of the legs, or paralysis of b3th arms and legs. The paralysis at first, unless the lesion is very small, is flaccid in all its characters; later it assumes the central neurone type in the legs with places in the arms of peripheral neurone type. The sensory symptoms consist, in addition to pain in the neck, of a dissociated anesthesia, that is, anesthesia for temperature or for pain or for both, with perfect preservation of tactile sensibility. A case was reported in which this peculiar clinical condition was absolutely distinct, biit in which, as shown by subsequent microscopical examination, the blood had exceeded to a certain extent the confines of the central gray niatter of the cord. The sensory anomalies of primary focal haamatomyelia from traumatism are usually transitory, unless the case is exceptionally severe. In reported cases the analgesia has disappeared before the thermoansesthesia.


In the anther's cases thermoanaesthesia was the only sensory anomaly present.
In the anther's cases thermoanaesthesia was the only sensory anomaly present.
Line 31,888: Line 31,624:
The difference in the etiology of spinal haemorrhages and of cerebral hemorrhages is obvious from what Dr. Bailey has said. While nearly all spinal haamorrhages are due to trauma, relatively few cerebral hemorrhages are thus produced, the majority of the latter being dependent upon chronic arterial disease. A spinal hemorrhage due to vascular disease is one of the rarest of pathological findings.
The difference in the etiology of spinal haemorrhages and of cerebral hemorrhages is obvious from what Dr. Bailey has said. While nearly all spinal haamorrhages are due to trauma, relatively few cerebral hemorrhages are thus produced, the majority of the latter being dependent upon chronic arterial disease. A spinal hemorrhage due to vascular disease is one of the rarest of pathological findings.


If I understood Dr. Bailey correctly he referred in one part of his paper to the possibility of occurrence of an anesthetic area in which no painful sensations resulted on the application of heat, though pain could be elicited by ordinary methods of stimulation. 1 have been convinced myself in the study of sensations that "heat-pain " is due to the stimulation of jjain nerves and not to the stimulation of " temperature nerves," i. e. the warm points or cold points. In areas on the circumscribed area of elective sensory paralysis on my own left arm where pain sensations are the only ones which can be elicited by any method of stimulation, a test-tube heated above a certain temperature, after a certain latent period, will always cause pain not preceded or accompanied by any temperature sensation. The studies of von Frey demonstrate conclusively the existence of points in the skin which when stimulated give rise to painful sensations, but not to thermal or tactile sensations. In the case I have studied all the warm-points, cold-points and pressure- or tactile-points in certain areas are thrown out of function and the pain-points alone yield a response. Ice and heat applied to these areas cause painful sensations, but no feeling of cold or warmth. One interesting feature of the heatpain and cold-pain as studied upon surfaces supplied only with
If I understood Dr. Bailey correctly he referred in one part of his paper to the possibility of occurrence of an anesthetic area in which no painful sensations resulted on the application of heat, though pain could be elicited by ordinary methods of stimulation. 1 have been convinced myself in the study of sensations that "heat-pain " is due to the stimulation of jjain nerves and not to the stimulation of " temperature nerves," i. e. the warm points or cold points. In areas on the circumscribed area of elective sensory paralysis on my own left arm where pain sensations are the only ones which can be elicited by any method of stimulation, a test-tube heated above a certain temperature, after a certain latent period, will always cause pain not preceded or accompanied by any temperature sensation. The studies of von Frey demonstrate conclusively the existence of points in the skin which when stimulated give rise to painful sensations, but not to thermal or tactile sensations. In the case I have studied all the warm-points, cold-points and pressure- or tactile-points in certain areas are thrown out of function and the pain-points alone yield a response. Ice and heat applied to these areas cause painful sensations, but no feeling of cold or warmth. One interesting feature of the heatpain and cold-pain as studied upon surfaces supplied only with pain nerves is tlie latent period of the pain. When one carefully applies a piece of ice or a hot test-tube to such an area he has no sensation at all at first ; only after the lapse of some seconds does any sensation result. There is first disagreeableness which soon goes over into distinct pain. Ordinarily when a hot test-tube is applied to normal skin the part is jerked away quickly. This is due to the fact that there is such violent stimulation of the heat-points that we are warned that if we do not remove the arm pain will result. We say that it hurts, but as a matter of fact we are not hurt but only warned that we shall feel pain unless the heat be removed. The same is the case in applying a piece of ice. If the ice remains in contact long enough we have " cold-pain," but the first effect on normal skin is a violent stimulation of the cold-points with a startling sensation of cold. I have wondered if heat-pain and cold pain are ever really absent in areas where pain-sensations can be elicited by the application of ordinarily painful stimuli, such as pricking with a needle. I am of the opinion that the prolonged contact of ice or hot water would give rise always in such cases to the sensation of pain. May it not be that the existence of heat-pain and cold-pain is often overlooked in cases in which the cold-points and warm-points are thrown out of function. Many, of course, still hold that heat-j)ain and cold-pain are due to over stimulation of temperati;re nerves and not due to the stimulation of specific pain nerve, but this view is irreconcilable with our present physiological and pathological knowledge.
 
 
 
294
 
 
 
JOHNS HOPKINS HOSPITAL BULLETIN.
 
 
 
[No. 93.
 
 
 
pain nerves is tlie latent period of the pain. When one carefully applies a piece of ice or a hot test-tube to such an area he has no sensation at all at first ; only after the lapse of some seconds does any sensation result. There is first disagreeableness which soon goes over into distinct pain. Ordinarily when a hot test-tube is applied to normal skin the part is jerked away quickly. This is due to the fact that there is such violent stimulation of the heat-points that we are warned that if we do not remove the arm pain will result. We say that it hurts, but as a matter of fact we are not hurt but only warned that we shall feel pain unless the heat be removed. The same is the case in applying a piece of ice. If the ice remains in contact long enough we have " cold-pain," but the first effect on normal skin is a violent stimulation of the cold-points with a startling sensation of cold. I have wondered if heat-pain and cold pain are ever really absent in areas where pain-sensations can be elicited by the application of ordinarily painful stimuli, such as pricking with a needle. I am of the opinion that the prolonged contact of ice or hot water would give rise always in such cases to the sensation of pain. May it not be that the existence of heat-pain and cold-pain is often overlooked in cases in which the cold-points and warm-points are thrown out of function. Many, of course, still hold that heat-j)ain and cold-pain are due to over stimulation of temperati;re nerves and not due to the stimulation of specific pain nerve, but this view is irreconcilable with our present physiological and pathological knowledge.


I would add a few words with reference to the relation of hEematomyelia to syringomyelia and central glioma. Since the investigations of Minor, early in this decade, the attention of all neuro-pathologists has been directed towards this dissociation of sensation or elective sensory paralysis in cases of central hsematoniyelia. As Dr. Bailey has said there can be but little doubt in most cases with regard to diflerential diagnosis, for the symptoms follow so directly upon the trauma that one can scarcely make a mistake. The pathology of these cases, however, is somewhat more puzzling than their clinical history. A number of cases have been studied in which in addition to haemorrhage, or the signs of old hfemorrhage, cavity formation with gliosis (or gliomatosis) in the periphery of the cavities has been observed. Some pathologists assert that after haematomyelia not only may partial obliteration of the hajmorrhagic cavities by glia tissue occur, but tliese cavities may become lined later by glia cells and thus give lise to syringomyelia or even be the starting point of a central gliomatosis. Minor goes so far as to suggest that such cavities secondary to hemorrhage may possibly at once or later become connected with the canalis centralis, receive an ependymal lining from this and so give rise to the appearance of a malformation of the cord. One cannot help being somewhat skeptical with regard to such a point. It is certainly not to be forgotten that in so-called gliomata in which the main constituents are cells of the ependymal type multiple cavities are frequently found, and there seems to be a special tendency to haemorrhage in such cases. In a case of this kind where such multiple cavities exist with surrounding gliosis or ependymal tumor formation a slight trauma might produce a hffimorrhage, and the symptoms would be those of hsematoniyelia. Clinically this might
I would add a few words with reference to the relation of hEematomyelia to syringomyelia and central glioma. Since the investigations of Minor, early in this decade, the attention of all neuro-pathologists has been directed towards this dissociation of sensation or elective sensory paralysis in cases of central hsematoniyelia. As Dr. Bailey has said there can be but little doubt in most cases with regard to diflerential diagnosis, for the symptoms follow so directly upon the trauma that one can scarcely make a mistake. The pathology of these cases, however, is somewhat more puzzling than their clinical history. A number of cases have been studied in which in addition to haemorrhage, or the signs of old hfemorrhage, cavity formation with gliosis (or gliomatosis) in the periphery of the cavities has been observed. Some pathologists assert that after haematomyelia not only may partial obliteration of the hajmorrhagic cavities by glia tissue occur, but tliese cavities may become lined later by glia cells and thus give lise to syringomyelia or even be the starting point of a central gliomatosis. Minor goes so far as to suggest that such cavities secondary to hemorrhage may possibly at once or later become connected with the canalis centralis, receive an ependymal lining from this and so give rise to the appearance of a malformation of the cord. One cannot help being somewhat skeptical with regard to such a point. It is certainly not to be forgotten that in so-called gliomata in which the main constituents are cells of the ependymal type multiple cavities are frequently found, and there seems to be a special tendency to haemorrhage in such cases. In a case of this kind where such multiple cavities exist with surrounding gliosis or ependymal tumor formation a slight trauma might produce a hffimorrhage, and the symptoms would be those of hsematoniyelia. Clinically this might

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The Johns Hopkins Medical Journal - Volume 9 (1898)

https://archive.org/details/johnshopkinsmedi08john

The Johns Hopkins Medical Journal 9 (1898)

The Johns Hopkins Hospital Bulletin


BULLETIN OF THE JOHNS HOPKINS HOSPITAL. Vol. IX. - No. 82. BALTIMORE, JANUARY, 1898.


Contents

  • On Certain Activities of tiie Epithelial Tissue of the Skin of the Guinea-pig, and Similar Occurrences in Tumors. By Leo Loeb, M. D ,
  • The Successful Treatment of Extra-peritoneal Rupture of the Bladder, complicated by Fracture of the Pelvis, by Operation and the Continuous Bath. Report of Case. By J. F. Mitchell, M. D.,
  • The Physiological and Pathological Relations between the Nose and the Sexual Apparatus of Man. By John Noland JIacKENZIE, M.D.,
  • Proceedings of Societies : Hospital Medical Society, - On the Hfematozoan Infection of Birds [Dr. W. G. MacC'allum] ; — The Presence in the Blood of Free Granules derived from Leucocytes, and their possible Relations to Immunity [Dr. W. R. Stokes and Dr. A. Wegefaetu].
  • Notes on New Books

Books Received


ON CERTAIN ACTIVITIES OF THE EPITHELIAL TISSUE OF THE SKIN OF THE GUINEAFIG, AND SIMILAR OCCURRENCES IN TUMORS

By Leo Loeb, M. D., Baltimore.


Iq order to cause migration of the epithelial tissue in the guinea-pig the most certain method is to make a wound in the epithelium, thus, to use Weigert's expression, removing the tension on one side. Under these circumstances the whole epithelial mass in the immediate neighborhood of the injury begins to move. The boundaries between the cells become invisible, and we have one large protoplasmatic mass with nuclei. The size of this tissue increases very much, and the nuclei also become enlarged. The latter often turn to that Bide towards which the whole mass is migrating. This can sometimes be seen very distinctly in pigmented epithelium, where the pigment caj)s turn with the nuclei. The shape of the nuclei and the surrounding protoplasm becomes elongated in the direction of the wandering tissue, the granular and keratine layers disapj)ear, and instead we see a homogeneous mass, which may be called the upper protoplasmatic layer, which contains nuclei that have taken the form of rods.

These changes are seen not only at the edge of the wound, but also somewhat removed from it, throughout that extent to which the epithelium is moving. Now there soon begins

•This is to a great extent a preliminary account of a part of my investigations on the regeneration of the epithelium, the more detailed description of which will appear in the Archiv fiir Entwickelungsmechanik, Bd. VI, 3.


an increase in the number of dividing nuclei, but this does not occur before the migration has begun. The migration is certainly not the result of the increase in the nuclear divisions. In the lower layers of the epithelium the form of division is mitotic ; the form of division which occurs in the upper layers of the epithelium is amitotic. This migration may be directed sidewards in the wound or downwards, in which case a certain kind of atypical epithelial growth is thus produced. The shape of the protoplasm and of the nuclei, as described above, indicates very often the direction of the migrating tissue. We have a control for this in the wandering of epithelial tissue in blood-clots, where we are enabled to see that the epithelial tissue migrates in that direction which is indicated by the structure of the whole epithelial mass. This appearance is still more marked, in that the fibrillar structure of the epithelial tissue becomes very clear under these conditions, so much so indeed that it can easily be seen without staining. These fibres connect all nuclei, no interruption being discernible between them that could correspond to cell boundaries. It may be added that under certain conditions* it is possible to show very distinctly the connection of the epithelial protoplasm with the fibrillar network below the epithelium. Some


Arch. f. Entwickelungsmechanik, loc. cit.


2


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 82.


times the sub-epithelial fibres appear to be the direct continuation of the epithelial fibres, the epithelial cell seems to ramify, aud it is in fact impossible to determine which part of this sub-epithelial fibrillar network is of epithelial origin and which part of it originates from the connective tissue below the epithelium. According to the direction in which the tissue is wandering, which direction is indicated by the position of the foremost nuclei together with their surrounding protoplasm, traction comes to be exercised on the tissue behind by the advancing line of epithelium, aud these circumstances determine the different types of structures of the epithelium. (See Figs. 1 and 3.) In structures as indicated by Fig. 3, one can see that the protoplasm gives way between the nuclei under the influence of the traction.


^' , ,/ b ^^^




Fig. 1.


a, epithelial nuclei,

J, holes in protoplasm produced by the traction.

We have seen that all layers of the epithelium participate in the migration, the shape of the different layers becoming very similar to each other, with excejjtion of the upper protoplasmatic layer. But there is one marked difference, namely, the velocity with which the different layers are moving, in so far as the upjjer protoplasmatic layer moves fastest, the velocity gradually decreasing towards the deeper layers, the basal layer being usually the slowest. Indeed the upper protoplasmatic layer, which corresponds to those structures that seem to have lost the greatest part of their vitality, is migrating so fast that after 36 hours a part of the wound is covered by it, and the remains of this layer form a considerable part of the scab together with the rod-like nuclei found in the middle of the scab, where they seem to undergo disintegration.

The activity of the epithelial tissue goes further than merely to migrate. It can and in most cases does actually penetrate into the blood-clot, occasionally into the connective tissue; and it was even j)ossible to get microscopical specimens in which all stages of the epithelial tissue breaking through the cartilage of the ear aud dissolving it could be seen. But it must be stated that in these cases it is not to be excluded that the cartilage and connective tissue may have been lessened in their vitality, although microscopically the cartilage appeared quite normal. At some places one sees this process nearly finished; the plate of ear cartilage being divided in two parts by the epithelial tissue. There are in the nearly re-established epithelial layer still some round hyaline or granular bodies visible as the remainder of the cartilage at


the very place where it was to be expected. In other places one sees how the epithelial protoplasm with nuclei begins forcibly to break through the still nearly intact cartilage, especially in this case protoplasm and nuclei having a very elongated shape. Between these two extreme cases different phases in which the epithelial protoplasmatic masses have broken through and are fiowing around those round bodies just mentioned — which are nothing else than the cartilage cells in a swollen state — may be made out. This swollen condition of the disintegrated cartilage seems to be preparatory to its perfect dissolution. In the same way the migrating epithelial cells have the power to break through connective tissue. Not quite so rarely one can see how the protoplasmatic masses move sidewards and downwards in the infiltrated connective tissue, the different arms of the divided epithelial masses separating it in islands and at last dissolving it wholly. This process is very similar to an amoeba-like multinuclear mass flowing around a foreign body and digesting it. This process is also similar to the action of the egg-cells of Polyclades, which form later on the intestinal epithelium and which break in the same way through the yolk and dissolve it. In an apparently equal way the syncytium seems to act in what is usually called deciduoma maliguum, a malignant growth which is, according to Marchand, brought about by the activity of the syncytium. Here also protoplasmatic masses break through the tissue, the different arms of the divided masses separating it in islands ; and there is no reason to doubt that they act on the tissue in the same way as the epithelial masses do, namely, to dissolve it, the microscopical appearances and the results being in both cases very similar. In connection with this it may be mentioned that the growth of the epithelium in carciuomata of the skin shows some resemblances to the migrating epithelium produced by injuring the normal skin. The formation of keratine seems to bear often more resemblance to the upper protoplasmatic layer than to the keratine layer of the normal skin. Pianese shows, in his work on carcinoma, pictures of the same kind of arrangement of the epithelial tissue, especially of the arrangement of the epithelial fibres, and in carcinomata one sees not rarely columns of epithelial masses that have an elongated shape moving towards the connective tissue, at the ajjex of which connective tissue cells are sometimes included between the epithelial cells. At other places one sees more isolated cells advancing.

As stated above, the epithelial masses that penetrate in the scab or through the cartilage have as a rule an elongated shape. In this connection it may be mentioned that H. Driech made the interesting observation that the meseuchym cells of echinus microtuberculatus also assume an elongated shape if they begin to migrate. So we may assume that the epithelial cells of carcinomata have the same activity as the regenerating epithelium and migrate through the tissues, and that especially the elongated shape of the cells indicates active migration, especially through tissues which offer a certaiu amount of resistance. Similar pictures, so far as the structure of the whole epithelium, and especially the fibrillar structure, is concerned, are met with in different skin diseases, among which may be mentioned psoriasis. In these pathological conditions such pictures have been differently exjjlaiued.


i


January, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


The significance of those pictures observed ia experimental healing of wounds is open to little doubt; and it may be suggested that alsii the other changes in the arrangement of the epithelial masses which are met in carcinoma and in skin diseases, and which have been referred to above, are brought about by migration or the tendency to migration and the traction caused by this activity on the part of the epithelial elements.

The best proof that the epithelial tissue really breaks through the. connective tissue is found in those cases where one can see the epithelial masses migratiug beneath a hair follicle that is lying in connective tissue, this gland being so entirely separated from its surroundings.

A phenomenon more frequently observed than the foregoing is the penetration of the epithelial masses into the scab, which consists, as is well known, partly of coagulated blood. Here under one form or another one sees the epithelial masses breaking in all directions through the clot, extending in the form of arms, and dissolving fibrin and blood corpuscles. I will mention a few of the ways in which this takes place. Of all the layers, the upper ones of epithelium, which are the quickest ones to migrate, are also most active in breaking through the tissue and scab. At places where more resistance is offered to the advancing epithelium, the protoplasmatic masses of the epithelial tissue fiow around these obstacles in circles that continually become closer, and if possible dissolve them. From this there result not unusually cyst-like formations that lie, in the case that the upper protoplasmatic layer has formed them, above the newly formed epithelium. These upper protoplasmatic cysts are only of short duration. The nature of the action by which the epithelial protoplasm is able to dissolve the tissue is unknown. It is certain that phagocytosis plays no part in it, the epithelial protoplasm does not engulf the foreign body, but the close contact with it seems to be suflBcient to cause the secretion of the substance which, be it of the character of a proteolytic ferment or some other chemical agent, has this dissolving effect. The circumstance that it seems easier for this solving effect to be exerted upon injured rather than healthy tissue would favor the assumption that the hypothetical body is a ferment, for this is a well-known condition of action of trypsin. Further investigations which have already beeu started may possibly yield more certain knowledge of this question; but in any case contact with the foreign body seems to be the stimulus that brings about tlie secretion of this substa)ice, in the same way as the glands of the alimentary canal secrete their digestive substances when in contact with food. Leucocytes not improbably have the same faculty.

It is a well known fact that the cells of malignant tumors, especially of carciuomata, break through all kinds of tissue; but the precise manner of this action has been conceived by different observers in different ways. If we study experimentally the regeneration of epithelium, we see, in the course of a few days, all the changes described above. Indeed, we not only appreciate that cartilage is destroyed, but we may even follow all stages of the process, and thus really obtain a picture not only of the results, which could be explained in different ways, but also of the kind of activity of the tissue


by which this result is achieved. And if there can be no doubt that in regeneration the epithelium has the above described power, we may conclude that the carcinomatous cells which can penetrate through all tissues do so in very much the same way, that is, by actually dissolving the tissues by chemical means. This is the more probable inasmuch as the histological pictures in spreading malignant epithelial tumors ofteu show places strongly resembling the penetration of regenerating epithelium. The principal reason that this kind of activity of the carcinomatous tissue has so far not been more generally recognized, may jirobably be found in the circumstance that such a power would have been to be regarded as a new quality of the epithelial cells for which no analogy had existed. But seeing now that the regenerating epithelial tissue possesses this faculty, this objection no longer holds good. That malignant tumors act also by other means, as e. g. by pressure on the surrounding tissue, is, however, not excluded. It has long been known that endothelial and connective tissue cells have the power to penetrate into blood-clots as into thrombi, and also in foreign bodies, and to replace these by connective tissue. We have seen that the epithelial tissue replaces blood-clots quite in the same way, and the result of this replacement is, in many cases, the production of an epithelial tissue which occupies the position formerly held by the blood-clot, or even the cartilage and connective tissue. We may therefore speak of this process as ejnthelial organization, in contradistinction to the well-known connective tissue organization. The similarity between the behavior of the epithelial tissue towards a blood-clot with the action of the endothelial and connective tissue or vessels in the organization of thrombi, would probably still be more apparent if it were possible to replace the cutis by blood in such a manner that the deeper epithelial layers come to lie in close contact with the blood-clot.

Although so far only those changes of regenerating tissue have been described that occur in the skin of the guinea-pig, there seems to be little doubt that also other epithelial tissue has the same kind of activity. The account which Peipers gives of the regeneration of the kidney makes it very probable that also the kidney cells have the faculty of penetrating into the blood-clot and dissolving it. The same holds probably good of the liver and salivary glands. I have already begun experiments in order to ascertain how far there is an analogy in the activity of these cells and of the epithelial cells of the skin.

When we see the epithelial tissue thus in motion we may ask, are there any linutations as to the directions in which it may move, or is it possible to detect any kind of influence of the surroundings that determines the direction of the migration ? As to the first point, there is no limitation in the directions of migration. One might suppose that the epithelial masses are able only to move in the wound because only this movement would be of value in the healing of the injury. But this is not the case ; the epithelial masses have the faculty even to go in the directly opposite way, and indeed a part of the protoplasmatic masses may go in one direction while another part branches through another side. The whole process reminds one of an amoeba that creeps and sends protoplasmatic arms to different sides. But there is one circumstance that invariably


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determines the direction of the flowing epithelial mass, that is, the contact with a solid body. If it once toaiches a foreign body it never leaves it again, but flows all around it. One can see how it flows around the balls formed by the hair-glands, similar to what is observed in Dewitz's experiments, in which spermatozoa are seen to wander around glass balls, never ceasing to touch them. The epithelial masses follow every furrow on the lapper side of the scab, and especially of the upper side of the wounded connective tissue; and the contact with the latter especially is the cause that in wound-healing the epithelial masses are brought usually to cover the connective tissue, in this way restoring the normal epithelial layer. There is no difference in the different layers of the epithelium in regard to this irritability, and one can sometimes observe how the upper protoplasmatic layer with its characteristic nuclei migrates in contact with the edge of the deeper layer. Fig. 3 shows such an occurrence. The above-described rod-like nuclei seem to continue the basal layers. Hence we see a factor that comes into play to determine the sti'ucture of the epithelial tissue of a mammalian is the same that is active in the life of plants and of the simplest forms of invertebrate animals and of spermatozoa.*


jteS&cDO


imooo


m


a, basal layer.

b, rod-like nuclei of the upper protoplasmic layer.

The possibility of a chemotropic irritability of the epithelial cells in addition to the stereotroi3ism described, is not to be wholly excluded, especially as the epithelial masses tend to penetrate in the blood-clot. But thus far it has not been possible to prove the presence of this form of irritability.

fWe have now spoken of several different activities of the epithelial masses, but there is still another and very curious kind which can be called epithelial infiltration, by which is meant the penetration and replacement of an epithelial tissue by a neighboring one. This process of epithelial infiltration can be produced by transplanting the pigmented skin of a


The endothelial cells of a vessel which organize a thrombus seem to have the same kind of irritability. In the drawings that Cornil gives e. g. (Journal de Tanatomie, 1897) one sees how the endothelial cells migrate around the thrombus, api)lying themselves to every furrow and penetrating later on its substance. Ranvier (C. r. vol. 112) describes, in inflammation of the peritoneum that leads to adhesions, the endothelial cells, which are to become connective tissue cells, as creeping along in contact with the fibrin films. That seems to be another instance of stereotropism.

1 For a fuller account of the following part it may be referred to Arch. f. Entwickelungsmechanik, Bd. VI, 1.: Ueber Transplantation von weisser Haut etc. am Ohr des Meerschweinchens. These experiments on transplantation have been carried out at the suggestion of Prof. Ribbert in the Pathol. Institut in Zurich.


guinea-pig to a place where the original skin is unpigmented, or conversely by transplanting unpigmented skin to a pigmented area. Without discussing how far these experiments on transplantation answer questions relating to the problems of transplantation in general, it may be mentioned that after the transplantation the black skin not only keeps its own pigment, but one can see, after a variable period in different cases, even with the naked eye, that the boundaries of the transplanted skin which before were very distinct become indistinct, a darker line appearing at the margins, and gradually the pigmented area spreads in the white skin. The same happens under certain conditions when white skin is transplanted to dark, the black pigment spreading in the white skin. This behavior was also observed by Carnot and Jllle. Deflandre, who gave an account of it in the Comptes rendus (see also Carnot's report in the Bulletin scientifique). But the fact alone could be explained in different ways. It is in the first place possible that the transplantation causes an augmentation iu the production of pigment by the pigmented epithelium. The surplus of pigment would be carried away either by leucocytes or by some other means, and brought into the neighboring white epithelium, gradually causing it to become pigmented. After some time the effect of the transplantation ceases, and therefore the surjilus production of the pigment, and there would be no further progress in the pigmentation of the white skin. That this explanation is not correct is shown by the following experiment. The transplanted black skin is made to regenerate, from which one observes that the transplanted black skin regenerates wholly, like the original black skin, going through four distinct stages which need not be mentioned here. Next one makes that part of the skin regenerate which has originally been white but had afterwards become black through the influence of the neighboring transplanted black skin. Fig. 4 gives a sketch of both cases. In the latter case one sees that this secondarily black skin regenerates in precisely the same manner as the originally black skin did, namely in four stages. Now if the pigment had only been passively transferred to the white skin, this characteristic kind of regeneration could -not have taken place. The white skin would have regenerated as white skin does.



Fig. 4.


«, transplanted black skin.

A, area where transplanted skin has grown.

c, skin that was afterwards removed.


This experiment proves that the white skin in the neighborhood of transplanted black skin becomes true pigmented skin.


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This can take place only by the emigration of the black epithelial tissue into the white. Any iniluence of the underlying connective tissue could with certainty be excluded. Microscopically we see in this intermediate zone, where the white epithelium becomes black, chromatophores in the deepest layer of the epithelium. Soon afterwards the cap pigment around the nuclei appears, until at last the whole epithelium has the character of the typical pigmented epithelium. One might be tempted from the microscopical appearance to take it for granted that the pigmentation of the originally white epithelium is caused by the emigration of chromatophores which act as a kind of unicellular glands, gradually supplying the pigment to the whole epithelial tissue. But this explanation is not applicable, for there are facts that show that the chromatophores do not act as glands. There remain two other possibilities. Either the chromatophores are able in the same way as the basal cells of the epithelium to give rise by cell division to the upper layer of the epithelium and the basal cells as well, or not only are the chromatophores migrating and infiltrating, but also the other cells of the pigmented epithelium, which, however, under the changed conditions of this process lose for a short time their pigment. As strange as it may seem that the widely branched chromatophores should be equivalent to the basal epithelial cells, there are a number of facts in favor of the view that the chromatophores in the epithelium are only modified epithelial cells. Two facts, however, are in favor of the latter assumption : First, in the third stage of the regeneration of the' pigmented epithelium, the epithelium has nearly the same ajipearance as described here, that is, chromato


phores in the basal layer are the only pigmented cells present in the epithelium; and in the fourth stage the upper layers gradually gain their pigment. Hence in this situation what seems to belong still to the white epithelium, belongs in fact to the regenerating black epithelium if the second assumption is the right one. Secondly, one can sometimes see that the highest epithelial layers have pigment around the nuclei, so that these nuclei certainly must have come from the black eiiithelium.

So far it has been impossible to decide with certainty which of these two explanations is the right one, but in any case it may be taken as proved that the living white epithelium is substituted by the transplanted black epithelium by means of a process of infiltration. But it must be added that under these circumstances there are no signs of a phagocytosis by which the black cells destroy the white ones. And it results from this that we must take into account the possibility that there are also at other times in the epithelium not only growing movements upwards from below from the basal layer in the direction of the corneal layer, but that there can also be sidewards movements as in the case described. The distinction of color made it possible to recognize this kind of activity of the epithelial tissue. Without this distinction the recognition would have been very difficult, because the last described activity of the epithelial tissue is one that proceeds much slower than the migration described first.

I wish to express my especial thanks to Dr. Flexner, to whose kindness I am indebted for a carcinoma of the skin, and to Dr. Cullen for sections of a deciduonui malignum.


THE SUCCESSFUL TREATMENT OF EXTRA-PERITONEAL RUPTURE OF THE BLADDER, COMPLICATED BY FRACTURE OF THE PELVIS, BY OPERATION AND THE CONTINUOUS BATH. REPORT OF CASE.


By J. F. Mitchell, M. D., Resident Medical Officer, The Johns Hopkins Hospital.


Through the kindness of Dr. Bloodgood I am permitted to report the following case from the surgical service of the Johns Hopkins Hospital :

A. A., Lithuanian woman, age 53. Admitted May 30th, 1896, with the following history. On May 19th, about 11 p. m., 10 hours before admission, she was thrown from a wagon, the wheels passing over the hips and lower abdomen at the level of anterior iliac spines. On admission at 9 a. m., 10 hours after the accident, the pulse is 100-130; temjjerature, 100.8°. Mental condition seems to be one of stupor. There is frequent moaning, and when the left hip is moved she cries out with pain. Over the lower abdomen and thighs the skin has been scratched and is covered with gravel and dirt, the entire superficial epidermis seeming to have been brushed away, but at no point is the fat exposed. The abdomen is not distended nor tender except over the skin bruises, and there is no muscle spasm nor any evidence of intraabdominal injury.

At 10..30 a. m. catheterization yielded 140 cc. of smoky urine


with a sediment of blood corpuscles, and at 3.30 p. m., four hours later, 160 cc. of similar urine. On distending the bladder with 500 cc. of boric acid solution not more than 350-300 cc. could be withdrawn, and examination by means of a speculum showed the bladder to be quite empty, demonstrating conclusively a rupture. It was impossible to ascertain whether urine was passed befoi'e admission, but between admission and operation there was no attempt to void urine and there was no dribbling.

Operation by Dr. Bloodgood, 17 hours after the accident, under ether. On opening into the space of Ketzius through the middle line, it was found filled with a large quantity of blood-stained urine which was not ammoniacal, and there was as yet no sign of inflammation. The peritoneum was pushed up to within 4 cm. of the umbilicus, and in the lumbar regions almost to the margins of the 13th ribs. This fluid was carefully sponged out and the peritoneal cavity opened in the middle line to examine the bladder for any intraperitoneal opening. As none could be found and there was no fluid in


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the peritoneal cavity, the peritoneum was closed with a double row of silk sutures. The opening in the bladder was demonstrated by passing a silver catheter through the urethra. It appeared to be about 2 cm. to the left of the median line at the level of the pubes, that is, just behind the seat of fracture, which was in the ramus of the left pubes. The line of fracture was oblique, and two ragged points projected towards the bladder. The bladder wound was closed with silk sutures which did not include the mucous membrane. Lateral incisions were then made in both inguinal regions and the three wounds were packed with bismuth gauze, the upper half of the median incision being closed with two mattress sutures in the recti muscles and a continuous subcutaneous silver suture. There was no loss of blood, and the pulse was excellent at the end of the operation. Temperature, 100.2°; pulse, 106. Cultures and cover-slips from the extravasated fluid were negative and there were only a few leucocytes.

May 21st. Patient passed a fairly comfortable night. From 8 p. m. until noon she was catheterized 7 times, 12-35 cc. of urine being obtained each time, total amount being 162 cc. of bloody iiriue. The gauze on the abdomen is saturated with iirine, showing that the sutures of the bladder have not held or that there is another rupture. Temperature, 102.2°; pulse, 106-110 ; respiration, 30-35 ; condition of stupor more marked than on admission. 3.30 p. m., patient placed in bath of water at 100° F. 8 p. m., patient has been in bath 4 hours. The pulse is 100 and better ; respiration, 24 and decidedly improved; temperature, 100.8°. The condition of stupor has been replaced by a much brighter mental state and the patient looks a great deal better.

May 26th. The patient was taken out of the bath for 4J hours, during which time no urine leaked from the wound. There was some pain and a little hemorrhage. The removal of the packing was followed by a rise of temperature to 102°, but no discomfort.

June 8th. The patient has been almost continuously in the bath since May 21st, being removed only for an hour at a time to clean the tub, and then she cries to be returned. The pulse has been good, but there has been continuous fever from 100.5° to 101°, and yesterday after examination and removal of two small pieces of bone from the fracture the temperature reached 103.5°. The packing has been out since May 26th (7th day). The lumbar wounds closed two days later and the superficial wound has entirely healed. The abdomen is soft and there is no evidence of infiltration beyond the suprapubic sinus. Appetite and general condition good.

June 27th. There has been more or less fever during the past three weeks, and in the last four or five days several shaking chills, the temperature in one instance reaching 107°. Examination of blood is negative and there is no leucocytosis. The urine shows a faint trace of albumin and many polymorphonuclear leucocytes. The abdomen is soft and not distended, and nothing can be found indicating any accumulation of pus. Spleen and kidneys not palpable. On irrigation the opening between the suprapubic wound and bladder is not large enough to prevent distension of the bladder and 250 cc. can be retained. On examination of the suprapubic wound a small cavity was found just to the left of the sinus and com


municating with it by an opening 2-3 mm. in diameter. This was completely dilated with the index finger and packed with bismuth gauze. Extravasation of urine into this cavity may explain the chills and temperature; no other explanation has been found.

July 20th. Following the dilation of the above cavity the temperature fell rapidly and there were no more chills and no rise of temperature. The patient was removed from the bath on June 28th, 40 days after the accident. Since then the sinus and bladder have been irrigated daily with boric acid solution, and to-day gauze removed from the sinus is slightly moist with urine. The sinus is closing rapidly. Except for some swelling and pain in the left leg and hip, the patient has been fairly comfortable and for two days has been up in a wheel-chair. It is now two months since the accident.

Sept. 2d. The general condition is much improved. Her appetite is good and she rests comfortably. The suprapubic sinus is still open, its external orifice barely admitting the tip of the little finger, and a probe passed to the bottom strikes roughened bone. No mobility can be obtained at the seat of fracture. She voids urine without difiBculty and the urine is greatly improved.

Sept. 29th. The sinus is about 2 cm. deep and does not communicate with the bladder or seat of fracture. The patient has been walking without any difficulty for some time, although there seems to be some motion at the seat of fracture. The urine contains only a few leucocytes and is acid.

Oct. 8th. Discharged. Sinus closed and urine clear.

Dec. '96. Patient returns with a small reducible hernia 2 cm. long in the scar in the right groin.

Feb. 13th, '97. Operation for hernia.

Mar. 3rd, '97. Discharged cured. Patient has recovered | perfectly her normal state of health. She walks without | difficulty and there is no evidence of mobility at the seat of fracture.

Considering the great number of surgical cases of all kinds treated in hospitals, neither fracture of the pelvis nor rupture of the bladder is a frequent occurrence ; for statistics show that in Berlin in 10,867 surgical cases there were only 3 ruptured bladders, and in Loiulon in 16,711, only 2. In the Johns Hopkins Hospital among 7268 surgical patients there have been 5 ruptured bladders. It is generally stated that fractures of the pelvic bones compose about 1 per cent, of all fractures. Either is a serious lesion ; but with the two combined the prognosis is always grave. According to its relation to the peritoneum, the rupture may be one of three varieties: intraperitoneal, subperitoneal, and extraperitoneal. I To the last, in combination with fracture of the pelvis, we • will confine our attention as bearing directly on the case just shown. We have collected 90 similar cases scattered through the literature of the past century, and on an analysis of these reports base the remarks which follow. In many instances the reports are very meagre and cause the statistician much trouble in collecting and analyzing cases.

The injury is met with much more frequently in men than in women, and most commonly between the ages of 20 and 60, that is, in the most active period of man's life when his habits


January, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


and occupation expose him to violence. Harrison, of Dublin, thinks the greater size of the pelvis and the protective pad offered by the uterus account for the greater rarity of rupture of the bladder in the female. In boys the bladder is not as likely to be allowed to become distended — an important factor in the causation of rupture— while after 60 a man has usually retired from active and dangerous service.

As might be imagined, the direct cause is traumatism of some violent character, for example the passage of a wheel over the body, as in the present instance. Fully one-third of all the cases are due to this cause alone. Many are caused by a fall from a height or a crushing weight received on the lower abdomen. An interesting case is recorded in which the man was thrown from his horse, landing rather forcibly on the ground in a sitting posture. The symphysis was separated and the bladder wall torn asunder. Another man while intoxicated stepped from a second story window which he mistook for the door. He alighted on one foot and sustained a fracture of the pelvis complicated by a ruptured bladder.

As a predisposing cause alcoholic indulgence ranks high, not only on account of greater exposure to violence in intoxicated persons, but owing also to the fact of the increased liability to distension of the bladder and the consequent loss of tone, elasticity and resistance of its walls.

As to the immediate causes of the tear in the bladder walls, opinions differ. Undoubtedly many are due to a continuation of the same crushing force that fractured the pelvis; but in a great number the cause is by no means so evident. A considerable proportion can be attributed to direct penetration of the bladder by a displaced or fractured bone. In 21 cases it is stated to have occurred, though from the position of the tear and the nature of the fracture in many other cases it must be much more common. Still others are due to concussion favored by a wall distended and weakened by chronic alcoholism. The bladder when empty lies behind and wholly protected by the pubic bones, and it would be difficult to conceive of a rupture of an empty bladder caused by actual pressure without penetration by bone, as in cases where there is simply separation of the symphysis without any anteroposterior displacement. Allis explains such a rent as being due to actual tearing apart of the bladder wall by the anterior ligaments which connect the front of the bladder with the pubic bones, one on either side of the symphysis. When the bladder is distended the walls themselves are weakened by a separation of the muscular fibres, and the anatomical position is much more favorable to rupture ; for the bladder then rises above the symphysis pubis and in part loses the protection afforded by it. The opening is most often in the anterior wall communicating directly with the space of Retzius. It was situated here in 63 per cent, of the reported cases. Next in frequency comes the neck as a seat of rupture, while in a few instances the rent is in the side or base.

Fracture is oftentimes multiple, and by far the commonest location is in the pubic bones— 49 cases thus recorded. Separation of the symphysis pubis is of frequeut occurrence, while tearing apart of the sacro-iliac synchondrosis is not very uncommon. Fractures of other bones are not so numerous, the sacrum and ischium being about equally often and the


ilium rarely involved — the latter only 6 times in our collection.

The symptomatology is quite definite. After the accident the patient is usually unable to walk or even to rise from the ground, and is often rendered unconscious, though accounts are given of patients walking some distance. Peaslee reports a case of a man who, with 7 fractures and a ruptured bladder, could actually walk a few steps. The subjects often describe a sensation as of something tearing within them at the time of the accident. They are brought to the hospital in a semistupid condition, complaining of intense pain in the hypogastric region or at the seat of fracture. Many go at once into a state of collapse or coma from which they never rally, dying in a few hours. A pretty constant and characteristic symptom is great desire to micturate, with either total inability to jjass any urine, or the passage of a small amount of blood-stained urine or pure blood. Sometimes, however, urination is not interfered with and the patient voids perfectly clear urine; these are rare exceptions. Again, the patient may at first pass no urine, but after a time be able to do so. There may be one or repeated shaking chills.

The condition of the patient depends somewhat upon the time elapsed since the accident. Very commonly it is one of collapse with marked pallor, rapid and weak pulse, hurried and shallow respiration and high temperature. The body is bent forward and the legs drawn up. There may be vomiting and diffuse abdominal pain, with distension and tenderness and signs of general peritonitis ; but this picture by no means always denotes involvement of the peritoneum in the rupture. Tumefaction, due to extravasation of urine and blood, may be seen in various localities according to the situation of the rupture of the bladder or the fracture of the pelvis, and there may be localized abdominal dullness. Extravasation of urine may be absent entirely, or may be extreme and yet overlooked, because on account of the violence necessary to the production of the lesion it has not followed the classical paths. It has been known to ascend as high as the shoulders, or to follow the psoas muscle, stripping up the peritoneum as far as the kidneys. In one case at the time of the accident a rounded and fluctuating tumor appeared on the thigh not far above the knee. This on being opened some two weeks later was filled with urine, pus and blood. If seen late, there is likely to be infection, especially if the patient has been catheterized.

From the signs given the diagnosis can generally be made, but there are certain aids which make the extraperitoneal rupture plainer and distinguish it from the intraperitoneal form. Catheterization yields important information. As a rule one obtains by the catheter only a small amount of urine and this is mixed with blood. Sometimes catheterization is imjiossible. In rare instances clear urine has been obtained, and quite frequently nothing at all, which latter condition Willard explained in his case as being due to suppression of urine rather than escape from the bladder.

Sometimes the catheter will pass through the rent in the bladder and then a large amount of bloody urine may be withdrawn. The ordinary procedure, and a very useful one, is to inject into the bladder a known amount of some mild solution


8


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[No. 82.


(in the present case half-saturated boric acid solution was used), and then measure the fluid withdrawn, any considerable decrease indicating leakage through a rupture. Sometimes the patient will feel the liquid escaping immediately from the bladder. This method has been opposed on the ground of being dangerous in case of intraperitoneal rupture ; but as immediate laparotomy is here indicated, it is not an important objection, and with proper precautions the gravity of the case need not be increased. In locating the position of the tear during operation, this injection is also very useful. Walsham suggested that air be introduced by means of a hand-ball apparatus as a substitute for fluid. Kivington has advised a preliminary perineal incision and digital examination of the bladder as a means of diagnosis. Eectal, vaginal, and cystoscopic examinations occasionally give useful data in ruptures about the neck, and rectal and vaginal examinations are especially useful in the location of fractures.

The prognosis has always been grave, though with the progress of surgery the death rate has greatly lessened. Hippocrates thought rupture of the bladder necessarily fatal, while Galen admitted the possibility of recovery in extraperitoneal injuries. In 1878 liartels collected 169 cases of rupture of all varieties, with a mortality of 89.3 per cent., and at that time there was only one recorded recovery in intraperitoneal rupture. Cramer in 1896 gave the mortality for all forms as 54 per cent. Q^his drop in the death rate has been to a large extent due to the improved treatment of intraperitoneal cases. In our 90 reports there were 15 recoveries, making the mortality 83.3 per cent. Taking only those which have occurred in the last 15 years, we find 34 with 7 recoveries, i. e. a mortality of 70.8 per cent., so that under improved treatment the decrease in deaths has not been great, and it is still considered a very grave injury and one whose treatment has been rather unsatisfactory. When we consider how likely it is to have only recoveries reported it is not probable that this estimate is an exaggerated one. In the majority (55 per cent, of our collected cases) death occurred in the first four days, while in the first week 73 per cent. died. Those surviving the first few hours rally from the shock and later show signs of peritonitis or extravasation of urine ; the lingering cases die finally of sei> tica^mia.

At autopsy the space of Retzius and other seats of infiltration are found filled with a bloody urino-purulent fluid, and the tissues about are necrotic and sloughing. The sloughing may reach an extreme grade. General peritonitis may result, or the peritonitis may be more or less localized, according to the extent of the infection. Spontaneous cure is jiossible even in cases of extensive infiltration.

It is well known that perfectly sterile urine flowing over tissues has little effect except when absorbed in great amounts, and that it does not materially interfere with the repair of open wounds; but the flow, if continued for a long time, or dammed up without exit, does provoke irritation and lower vital resistance, so that we have a most favorable medium for infection. Strauss and TuflSer have done some interesting work to shed light on this point. They injected aseptic urine into the peritoneal cavity, the space of lletzius and the muscle of dogs, and found that the urine was absorbed and there


was no reaction. On repeating these injections, using urine mixed with blood, ammonium sulphide or ammonium chloride, the same result was obtained. On cutting one ureter, however, and allowing the urine to flow into the peritoneal cavity, the dogs died in 8-20 days of uraemic poisoning and peritonitis. They conclude that sterile urine in itself has no action, but that prolonged exposure so irritates and lowers the resistance of the parts as to allow organisms to pass through the intestinal wall and set up a peritonitis. Unfortunately they do not state what orgiinisms were concerned.

Urine is in itself, however, an excellent culture medium, and on account of the common practice of catheterization is rarely if ever sterile for any time after the accident with which we are concerned, and thus it acts as a carrier of infection.

The treatment therefore is plainly indicated, viz. immediate relief of the extravasated urine and prevention of reaccumulation by proper drainage and suture.

As far as the fracture is concerned little is to be done except to fix the parts, though it is sometimes necessary to remove spicules of bone or wire the fragments together. To get rid of the extravasated urine has been a simple matter, but the question of efficient drainage seems to have been a difficult one.

The earliest cases were treated by hot applications, leeches and bloodletting, and two i-ecoveries are reported in 53 cases where no other treatment save these and catheterization was employed.

In all 37 cases were treated by various operative procedures, with a resulting mortality of 64.9 per cent. In many of the recoveries the convalescence has been slow and tedious, with a history of long-continued suppuration and the existence of one or more fistulous tracts for months or years.

Statistics show nothing as to the advantage of early operation, for there were more recoveries where the operation was in the second week. But we know that it is best to operate as soon as possible, and it is a question as to whether these late cases would not have recovered spontaneously by rupture of the abscesses and formation of fistula?. The first attempt at operation amounted merely to incisions for extravasation plus a catheter retained in the urethra. Of 8 cases so treated, 3 recovered. The recoveries were cases which had gone on to abscess formation, and all that was done was to open the abscesses. In 1845, Walker, of Boston, first employed lateral perineal cystotomy in a case of ruptured bladder, and drainage through this incision was successful and the patient recovered. After that perineal incision with drainage was the favorite method, and in 16 cases there were 4 recoveries. Abdominal incision was employed 5 times with 1 recovery, and then suprapubic cystotomy with or without a counter incision in the perineum took its place and has been up to the present time the ordinary method of dealing with this injury ; but of 8 patients treated in this way only 3 recovered.

In three cases, including the present one, the continuous bath has been used to prevent absorption and for better drainage, and all of these have recovered. While the bath treatment of wounds is in itself old and has been much used both in this country and abroad, its application to such cases as the present one seems to have been gradual, and its great value


January, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


should be insisted upon. In 1878 Bartels speaks of "giving baths" to a case in which there was extensive suppuration, and the patient got well, but he does not go into particulars as to the time in which the patient remained in the bath. In 1891 Rose after doing a suprapubic operation for rupture found that ordinary dressings were not sufficient, and says that " therefore the patient was every day put in a continuous bath for several hours without any dressing." This was continued for 20 days, and then the bath was used only every 3nd or 3rd day. The second case in which it was employed was in 1896 by Wiesinger. Here on the 17th day an abscess was opened over the seat of fracture and the patient put in a continuous bath. The abscess was healed on the 42nd day.

It would seem then that whether there be merely incisions for extravasation, or whether suprapubic cystotomy or perineal section be performed, the best results can be secured by placing the patient in a continuous bath. In view of a forthcoming report we will not go into the particulars of the management of the bath, but as far as the comfort of the jiatient is concerned little can be said against it. While at first patients may object to the bath, probably more from the thought of it than from actual discomfort, they soon grow to like it. As has been said, the present patient when removed from the tub cried to be returned.

Dr. Bloodgood has already reported a case of ruptured urethra with fractured pelvis in which the bath was used with excellent result. It has been used by Schede in cases of extravasation of urine, and last year Puzey, in London, reported two cases of ruptured urethra which recovered under the bath ; so that it would seem to be especially adapted to this class of injuries, where efficient drainage is so important and so difficult.

Analysis of Cases.

Sex. — Males 84 = 94.4 per cent. Females 5 = 5.6 per cent.

Age.— 1-10 years, 4 ; 10-20 years, 8 ; 20-30 years, 20 ; 30-40 years, 18; 40-50 years, 10; 50-60 years, 11 ; 60-70, 4; total, 75. Total from age 20-60= 59 = 78.7 per cent.

Cause. — Crushed by weight falling on body, 23; run over, 25; fell from a height, 22; struck by engine or car, 4; crushed between wagons or cars, 9 ; total, 83.

Result. — Whole number of cases, 90; whole number of deaths, 75 ^ 83.3 per cent.; whole number of recoveries, 15 =: 16.7 per cent.

. Time of Death.— iBt day, 9; 2nd day, 14; 3rd day, 7; 4th day, 10 ; 5th day, 5 ; 6th day, 5 ; 7th day, 3. 1st week, 53.

8th day, 2 ; 10th day, 1 ; 12th day, 3 ; 14th day, 3. 2nd week, 9.

3rd week, 2; 4th week, 4; 5th week, 1; 6th week, 2; 6th month, 1 ; 14th month, 1.

Time of Operation. —


Time after Accident.

Within 24 hours.


Total. 11


Deaths.

7


Recoveries. 4


Mortality.

63.7 per cent.


« 48 "


3


2



100.0


" 4 days, " 2 weeks.


5

7


5 2


5


100.0 " 28.6


3 "


1


1



100.0


Bones Fractured. — Multiple fracture, 42 ; os pubis, 49 ; sacrum, 9; ischium, 9; ilium, 6; separation of symphysis pubis, 31 ; separation of sacroiliac synchondrosis, 10 ; penetration of bladder by bone, 20.

Position of Rupture. — Anterior wall, 41^63.2 per cent.; posterior wall, 1 ; neck, 13 ; side, 5 ; fundus, 3 ; base, 3.


Unoperated.


and catheterized

hot applications. . . retained catheter .


Incision for extravasation.


and retained


catheter.


Perineal incision

" " and retained catheter.

" " " drainage tube

" " " incision for extravasation

Perineal incision and incision for ex travasation and retained catheter. . . Perineal incision and abdominal incision " " " suprapubic incision


lithotomy tube and drainage.


Abdominal incision

" " and retained catheter

" " '• suprapubic inci

sion


Suprapubic incision

" " and retained catheter


Bath and incision for extravasation. . . " " suprapubic incision


Whole number operated upon.


"5.0


00.0 64 9


17


65.4


THE JOHNS HOPKINS HOSPITAL BULLETIN.

The Hospital Bulletin contains announcements of courses of lectures, programmes of clinical and pathological study, details of hospital and dispensary practice, abstracts of papers read and other proceedings ot the Medical Society of the Hospital, reports of lectures, and other matters of general interest in connection with the work of the Hospital. It is issued monthly.

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10


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 82.


THE PHYSIOLOGICAL AND PATHOLOGICAL RELATIONS BETWEEN THE NOSE AND THE

SEXUAL APPARATUS OF MAN/^=

By John Noland Mackenzie, M. D., of Baltimore, Clinical Professor of Laryngology atul Rlmiology in the Johns Hopl-ins Medical School and Laryngologisl lo the Johns Hopkins Hospital.


" Balnea, vina, Venus corrumpunt corpora nostra, Set vitam faciunt, l)(aluea), v(ina), V(enus)."t

Olvog Kal ra '/joETfja kol ij Trept KvTTfiiv Ipuij

Mr. President and Oetitlemen. — The limited time at my disposal this moruiiig precludes an elaborate discussion of the propositions which form the text for these remarks. I shall, therefore, content myself with a brief statement of the conclusions which I have reached after a careful study of the subject, and shall not weary you with the arid narrative of individual cases.

The injurious effects of undue excitation or disease of the generative apparatus upon the organs of sight and hearing are matters of ancient recognition. That immoderate indulgence in venery may lead to derangements of the former was familiar to Aristotle,§ and that the fathers of medicine recognized some mysterious connection between the ear and the rejM'oductive functions is evident from the testimony of Hippocrates.|| Over two centuries ago Eolfinc^ wrote: "Qui partihus genitalibus aiutitur, et sexto ptraccepto vim infert, male audit," a proposition which has been fully established by the clinical exj^erience of to-day.

The intimate relationship between the genital organs and those of the throat and neck seems to have attracted the special attention of the ancients. Thus Aristotle** clearly defines the changes iu the voice at puberty, and the effect of castration on its qualities. ff Its harsh, irregular and discordant character during the maturation of the sexual functions was furthermore affirmed to be more conspicuous in those who attempted the early gratification of the sexual appetite. The


Remarks made before the British Medical Association at its Montreal meeting, September, 1897.

t An old inscription found in the Campus Florae in Rome. See Buecheler's Antbolog. Latin. Carmen. Epigraphic, Fasc. II, p. 705, No. 1499, Teubner edition, 1897. Also Corpus Inscript. Latin. VI, 15258, Gruter 615, 11, Orelli 4816, etc. It is attributed, however, by Scaliger to a modern poet.

X The supposed Greek original. See Antbolog. Palatin. X, 112.

§ Aristot. Opera omnia giaeco-latin. Parisiis, 1834. De animalium generatione, lib. ii, cap. 7.

II Opera omnia. Ed. Kiihn, Lipsiae, 1827, torn, i, p. 562.

H Ordo et methodus generatione dicatarum partium, per anatomen, cognoscendi fabricam. Jenae, 1664, part i, cap. vii, p. 32.

0p. cit., De animal, historia, lib. vii, cap. i. Choking sensations in the throat and other hysterical manifestations have from time immemorial been regarded as signs of pregnancy. Shakespeare, in King Lear (sc. ii, act iv) thus gives expression to this idea :

" O, how this mother swells up towards my heart I Hysterica passio ! down, thou climbing sorrow, Thy element's below.*'

ttOp. cit., De animal, generatione, lib. v, cap. 7.


observation that, during coitus, the voice becomes rougher and less acute, led tlie phouasci or voice-trainers to infibulate their pupils, or confine the penis with bauds and fetters, to preclude indulgence in wantonness,* whilst the popular idea of the injurious effect of repeated coition upon the singing voice is reflected in the epigram of the Roman satirist:

" Cantasti male, dum fututa es, Aegle, Jam cantas bene ; basianda non e8."t

The supposed influence of sexual excitement upon the external throat is likewise apparent from the ancient nuptial ceremonial. Before the virgin retired on the wedding night it was customary to measure her neck with a tape and again on the following morning. If the neck showed an increase in size it was taken as a certain indication of defloration, whilst if the two measurements were equal she was supposed to have retained her virginity. This curious test, which has also been utilized to establish the fact of adultery, has been transmitted to us iu the Epithalamium of Catullus:

" Non illam nutrix, oriente luce revisens, Hesterno collum poterit circumdare filo."t

Whilst, therefore, the above historical facts point to the early i-ecognition of the relationship between over-indulgence of the sexual powers and morbid conditions of the eye, ear and throat, the special part which it plays in the production of nasal disease seems to have been heretofore overlooked.

My attention was first attracted to the investigation of the physiological and pathological relations between the nose and


J. Riolani Anthropographiae, lib. ii, cap. 34, p. 303, Francofurti, 1626. Riolanus quotes from the Musaeum of Albertus Magnus the case of a girl, sent to fetch wine from a public house, who was seized and ravished on the road, and who found in attempting to sing on her return that her voice had changed from acute to grave.

See also Martial (lib. ix, Epig. 28) :

"Jam paedegogo liberatus etcujus Reflbulavit turgidum faber penem."

Also lib. xiv, Epig. 215:

" Die mihi, simplicitur, comoedis et cithaedis Fibula quid praestet ? Carius ut futuant,"

See also Juvenal, sat. vi, 73.

The gladiators and athletes were also subjected to infibulation :

"Dum ludit media, populo spectante, palaestra, Delapsa est misero fibula ; verpus orat."

Martial, lib. viii, Epig. Ix-t-Tii.

f Martial, Epig. lib. i, xcv, ad Aeglen fellatricem.

} Epitbal. Pelei et Thetidos, Ixiv. Catulli op. omn., Lond., 1882, p. 230. This phenomenon was variously attributed to the dilatation of the vessels of the neck by the semen, a portion of which, according to the Hippocratic doctrine, flowed down from the brain during intercourse, and to the general agitation of the vascular system, and especially the arterial and venous trunks of the throat, during the excitement of the sexual act.


January, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


11


the genital orgians by the case of a patient in London, in 1879, wlio invariably suffered from coryza after sexual indulgence.

Stimulated by this observation I began the study of the subject, and five years later published the results of my investigations in the American Journal of the Jledical Sciences for April, 1881, in an essay entitled " Irritation of the Sexual Apparatus as an Etiological Factor in the Production of Nasal Disease." In this thesis, which was the first attempt to reduce this curious relationship to, as far as possible, a scientific basis, I advanced the series of propositions which you will find embodied in the text of these remarks.

Several years later there appeared in France a thesis by Arviset,* a critical review by Isch-Wallf and an excellent article by Joal,| which dealt in a most interesting way with the topic under consideration. In Germany, Peyer§ in Munich, Eudrissll in Goeppiugen, and, in the present year, Fliess^l in Berlin, have enriched its literature with their contributions. Fliess's elaborate monograph, written in apparent ignorance of the work done by me in this special field before him, is a model of painstaking labor, and is valuable as an independent contribution to the study of this important subject.

Before submitting for discussion the propositions which form the text for these remarks, let me briefly call attention to certain matters of historical interest which have seemed in olden times to have foreshadowed the physiological relationship between the nose and the genital apparatus.

In the Ayurveda, the sacred medical classic of the ancient Hindus, a work of fabulous antiquity, the causes of common catarrh are thus tersely defined :

"Uxoris concubitus, capitis dolor, fumus, pulvis, frigus, Vehemens calor, retentio urinae soecumque statim Catarrhi causae dictae sunt."**

Although indulgence in venery heads the list, it is highly probable that its real influence was unrecognized, and that it is given as an etiological factor simply in accordance with the seemingly prevalent idea that pervades the Indian Shastras, that venery and confinement of the bowels lay at the root of most diseases.

The earlier physiognomists laid great stress upon the size and form of the nose as an indication of corresponding pecu


Contribution a I'etude du tissu erectile des fosses nasales. These de Lyon, aoiit, 1887.

t Progres Medical, Sept. 10 et 17, 1887. Du tissu erectile des fosses nasales.

t Revue mensuelle de laryngologie, d'otologie et de rhinologie, fevr. et mars, 1888. De I'epistaxis gt'-nitale.

gUeber nervijs. Schnupfen u. Speicheliluss u. den iitiologischen Zusammenhang derselben mit Erkrankungen desSexualapparates. M'inchener Med. Wochenschrift, Jahrgang 1889, No. 4.

jUeber die bisherigen Beobachtungen von pliysiologischen u. pathologisehen Beziehungen der Oberen Luftwege zu den Sexualorganen. Inaug. Diss. Wiirzburg, 1892.

T^Die Beziehungen zwischen Nase u. weiblichen Geschlechtsorganen. Berlin, 1897.

Siisrutas Ayurvedas: id est Medicinae Systema, a venerabili D'hanvintare demonstratum a suo disoipulo compositum. Translated from the Sanscrit into Latin by Franciscus Hessler, Erlangen, tom. iii, cap. xxiv, p. 44, 1850.


liarities in the penis.* The nose, for example, that was large and firm was looked upon as an index of a penis acceptable to women, and hence it was that the licentious Emperor Heliogabalus only admitted those who were nasuti, i. e. who possessed a certain comeliness of that feature, to the companionship of his lustful practices. t

Johanna, Queen of Naples, a woman of insatiable lust, seems also to have selected, as her male companions, men with large noses, with a similar end in view. J Sterne, in Tristram Shandy, depicts with consummate humor the supposed sexuality of the nose in " Slawkenbergius's Tale," in which the city of Strasburg was captured by a handsome nose. Every one remembers the closing lines of that intensely amusing production : "Alas ! alas ! cries Slawkenbergius, making an exclamation— it is not the first, and I fear will not be the last fortress that has been either won — or lost by noses."

While the efforts of those who have selected men who were nasuti for sexual purposes were doubtless often crowned with success, history, alas ! records some cases of bitter disappointment. Thus Henry Salmuth§ relates with great solemnity a case in point.

Christian Francis Paullini in his curious work]] devotes a chapter, under the caption Nasuti non semper hene vasati,\ to the subject. After alluding to the prevalent impression that a large nose indicated a corresponding increase in volume of the virile organ, he goes on gravely to state that he has known several "noble and pious" men in whom the rule did not hold good, and relates the following mournful tale : " Nobilissima ac venustissima Virgo, sed valde petulca, duos simul habebat procos, alteram bonae vitae, fortunataeque hominum, sed macileutum; alteram quadratum, et tws/^rwi.' ?irt>o conspicuum, hirconem, ac fruges consumere natum. Ilia, temto isto, hunc sibi elegit ob peculium, quod sperabat, magnum et conditionem strenuam. Sed egregie decepta est. Hinc domi jurgia, foris risae et sunima viri aversio, ob sterilitatem quae thorum perpetuo comitatur."

It was possibly the supposed influence of an elegant and handsome nose as an incentive to illicit amours that led to the well-known custom of amputation of that organ in adulterers, " truncas inliomsto vulnere nares,"** whilst in women detected in the actft the disfigurement thereby produced was intended as a perpetual reminder of their shame.

In astrology Venus was supposed to govern the nose.


See especially Ludwig Septalius : De Naevis tractatus, sect. 26, p. 18, in Bonel's Labarynthi medic, extricati, etc. Genevae,

I'JS.

f Vide Aelius Lampridius in vita Antonii Heliogabilis, in Hist. August, etc. Beponti.

JGuidonis PanciroUi rerum memorabilium sive deperditarum pars prior, etc. Francofurti, 1646, lib. 2, tit. 10, p. m. 176.

gibid.p. 177.

llObservat. medico-physiog. Cent, i, obs. xcvii, p. m. 141 ; Lipsiae, 1706.

IF Vasatus, post-classical.

Virgil, Aeneid, vi, 497. ffVide Diodorus Siculus in Bibliothecae Historicae, Paris edition, 1854, tom. i, lib. i, cap. Ixxvii (5), p. 04. On the customs and laws of the Egyptians.


12


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 82.


According to all the astrologers, the gentry who

"... feel the pulses of the stars, To find out agues, coughs, catarrhs,"

Venus presides over generation and all the parts pertaining thereto. De la Chambre in his work UArt de Gonnoisfre les Homines* in alluding to this supposed influence, says that nothing is more convincing, at least to those who admit the influence of planets on the affairs of men, than that there is an intimate relationship (astrologically) between the genital organs and the nose. As the result of this sympathy the nose must receive the same influence which the planet Venus communicates to the genital organs and must submit to the same empire to which they are subjected. The astrological signs of the nose are reproduced in the genital organs, which, like the nose, occupy a prominent part in the center of the body.

The charlatans of those days pretended to establish the fact of virginity or defloration by astrological signs. William Lilly, the celebrated English astrologer and impostor of the seventeenth century, claimed never to have made a niistake.f It was doubtless this method of imposture that inspired the line of Butler in Hudibras, "detect lost maidenheads by sneezing,"! ill the famous poem in which he smiled the pretensions of this fraternity of quacks away.

The idea of some occult relationship between the nose and the virile member seems, in days gone by, to have crept even into the darkness of teratology. Thus we find Palfyn§ describing cases in which in place of the nose were found masses resembling the male organs of generation.

To render the relationship to which I wish to call attention more intelligible it is necessary to recall the anatomical fact that in man, covering the whole of the inferior, the under surface of the middle, the posterior ends of the middle and superior, and, what is not sufficiently insisted upon by many writers, a portion of the septum, is a structure which is essentially the anatomical analogue of the erectile tissue of the penis. Like it, this body is composed of irregular spaces, or so-called erectile cells, separated by trabecule of connective tissue containing elastic and muscular fibers, the latter element being not as prominent and well-marked as in the cavernous bodies of the generative organs. Under a multitude of various impressions erection of this tissue takes place, the dilatation of its cells being, in all probability, under the direct dominion of vaso-motor nerves derived through the spheno-palatine ganglion. It is the temporary dilatation of these bodies that constitutes the anatomical explanation of


L'Art de Connoistre les Hoinmes. Amsterdam, cliez Jacques le Jeune, 1660. De la metoposcopie, p. 259.

t Life and Times of William Lilly, written by himself. London, 1829.

tPart ii, canto iii, 285. Bartholini (Anatomica Reformata, de naso ; also Lond. ed., bk. iii, chap, x, p. l.W) tells us that Michael Scotus pretended to be able to diagnosticate virginity by touching the cartilage of the nose.

§Fortunus Licetus (Jean Palfyn), Description anatomique des parties de la femme, etc., avec un traite des monstres. Leiden, 1708, lib. ii, chap. 30, p. 142 and 144.


the stoppage of the nostrils in coryza and allied conditions, and their permanent enlargement is the distinctive feature of chronic inflammatory states of the nasal passages. This erectile area is, moreover, especially concerned in the evolution of the many curious "reflex" phenomena which are observed in connection with nasal affections. Indeed, the changes which it undergoes seem to lie at the foundation of nasal pathology, and furnish the key not only to the correct interpretation of nasal disease, but also to many obscure affections in other and remote organs of the body. For practical purposes we may consider this erectile, or contractile, area, consisting, as it does, of myriad blood-vessels and blood spaces in wonderfully exquisite correlationship, bounded on the one side by mucous membrane, and on the other by periosteum, as an important organ, certainly of respiration and probably of other physiological functions, using the term organ in its highest physiological sense. Call these bodies by whatever name we may, erectile bodies, corpora cavernosa, nasal lungs, we have a definite, peculiar anatomical arrangement of tissues endowed with specific physiological function and serving a manifest and manifold destiny in the organism.

Physiological.

That an intimate physiological relationship exists between the sexual apparatus and the nose, and especially the intranasal erectile tissue, is sufficiently evident from the following facts :

I. — (a) In a certain proportion of women whose nasal organs are healthy, engorgement of the nasal cavernous tissue occurs with unvarying regularity during the menstrual epoch, the swelling of the membrane subsiding with the cessation of the catamenial flow.

(b) In some cases of irregular menstruation, in which the individual occasionally omits a menstrual period without external flow, at such times the nasal erectile bodies become swollen and turgid as in the periods when all the external evidences of menstruation are present.

(c) The monthly turgescence of the nasal corpora cavernosa may be bilateral, or confined to one side, the swelling appearing at first in one side and then in the other, the alternation varying with the epoch.

{(l) The periodical erection may be inconsiderable and give rise to little or no inconvenience, or, on the other hand, the swollen bodies may occlude the nostril and awaken phenomena of a so-called reflex nature, such as coughing, sneezing, etc.

{e) In some cases there seems to be a direct relationship between this periodical engorgement of the nasal erectile bodies and the phenomena referable to the head that so often accompany the consummation of the menstrual act.

(/) As a natural consequence of the phenomena above described, the nasal mucous membrane becomes, at such periods, more susceptible to reflex-producing impressions, and is therefore more easily influenced by mechanical, electrical, thermic and chemical irritation.

{(j) The conditions (engorgement and increased irritability of the nasal mucous membrane) indicated above, together with the phenomena that accompany them, are also found


Jaxuary, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


13


during pregnancy at periods correspouding to those of the menstrual flow. There is also reason to believe that similar phenomena occur during lactation and the menopause.

During the period of my original investigations I was unable, from poverty of material, to come to any definite conclusions in regard to the behavior of the nasal apparatus during pregnancy. I was familiar with the fact that in some women the presence of pregnancy was proclaimed by a cokU in the head. Isolated cases, too, had led me to the belief that the changes such as I described in my first article occurred in some women, at least, during that period at intervals corresponding to those of the menstrual flow, but at the time of publication of my essay I was not as sure of the fact as I am now. Since my work first appeared I have been so busied with other things that I have given little or no time to the subject. Several cases have, however, offered themselves to me which have confirmed me in the belief that sometimes, at least, the phenomena described by me as occurring during menstruation also occur iu pregnancy at periods corresponding to those of the monthly flux. Not to mention others, I have, for example, at present under my care a young pregnant married woman, without any disease of the nasal passages, who with great regularity during the time at which her menses are due (from the 13th to the 17th of every mouth) suffers from acute and complete obstruction of both nostrils, intense sensitiveness of the nasal mucosa and violent paroxysms of sneezing. These phenomena commence on the 13th, reach their acme by the 15th, and gradually subside, to disajjpear on the 17th of the month. During the intervals between the periods there is no abnormal condition of the nose present. Indeed, it was for this peculiar, disagreeable feature of her pregnancy that she consulted me, with a very accurate voluntary description of her symptoms. This condition of affairs has continued during three pregnancies. If other proof were wanting of the fact that menstrual phenomena referable to the nose occur during pregnancy, the question has been definitely settled by Fliess, who has shown that they not only occur during that period, but also during lactation. This author also reports several cases iu which abortion was accidentally produced by galvano-caustic operations on the nose. In this connection I would call attention to the fact that Pliny* observes that the smell of a lamp which has been extinguished will often cause abortion, and that the latter ensues should the female happen to sneeze just after the sexual congress.

II. — The presence of vicarious nasal menstruation.

(rt) It is a familiar fact that women are occasionally found iu whom the menstrual function is heralded or established by a discharge of blood from the nostrils. This hemorrhage, which may be accompanied by other phenomena referable to the nose, such as sneezing, etc., may be replaced afterwards by the uterine flow, but sometimes continues throughout the menstrual life of the individual. In the latter case, some malformation or derangement of the sexual apparatus seems to be, usually, though not always, responsible for the nasal flow.


Nat. His. lib. vii, cap. 7.


(b) Epistaxis also occurs, now and then, from the suppression of the normal flux. This was considered as a favorable sign by Hippocrates,* and by Celsus,twho followed closely in his footsteps.

(c) Hemorrhage from the nose may occur as the vicarious representative of menstruation during pregnancy ; towards the close of menstrual life as the premature or normal herald of the menopause ; or it may be observed as a recurring phenomenon after the establishment of the change of life or after the removal of the uterus or its appendages.

(d) These vicarious hemorrhages are, moreover, not confined to women, but make their appearance not infrequently in boys at or near the age of puberty, upon the full development of their sexual powers.

III. — The well-known sympalhy between Ihe erectile portions of the generative tract and other erectile structures of the body.

There is uo reason why the sexual excitement that leads to congestion and erection of these organs, as for example in the case of the nipple, may not, under similar circumstances, cause engorgement of the nasal erectile spaces.

IV. — The occasional dependence of phenomena referable to the nose during sexual excitement (such as, for example, nose bleed, stoppage of the nostrils, sneezing and other reflex acts), either from the operation of a physiological process, the erethism produced by amorous contact with the opposite sex or during the consummation of the copulative act.

The nasal symptoms most commonly found associated with sexual excitement are sternutation, occlusion of the nasal passages (from erection of the corpora cavernosa), and epistaxis.

Sneezing is sufficiently common, particularly during coitus. Quite a number of such cases have come under my personal observation in persons in robust health and whose nasal organs were apparently free from disease. The reflex may occur before (from erotic thoughts), during, or after the consummation of the act. Many like cases have been since reported to me. Thus one physician of large practice, who became interested in the subject, found twelve cases among his clientele. It may be interesting to know that this form of sexual consensus, or sympathy, has been recognized for centuries. Thus in the sixteenth century, Amatus LusitanusJ reports a case of sneezing from the sight of a pretty girl ; Bonet§ and Thomas Bartholini,|| and later, Stalpart Vanderwiel,T| relate cases of sneezing during coitus. In the last century Schurig,**


0p. omn. EJ. Ktilin. Lipsiae, 1827, toui. ii, p. 174. De morbis lib. i, and Aph. sect. 5, art. 33.

t De medicina. Rotterodami, 1750, lib. ii, cap. S.

j:Curationum medicinalium cent, iv, cur. 4, Venet. 1557. See also Rahn. Exercit. phys.de causisphyeicis mirae illiustum in homine, turn inter homines, turn denique inter cetera naturae corpora sympathia, xvii, Turici 1788.

§Sepulchretuni. L. I, s. xx.

II Historiarum anatomic, et meilic. rariorum, cent, v et vi, ed. Hafniae, 1761, v, p. 184.

H Gynaecologia historico-medica, etc. Dresden and Leipsic, 1730, p. 429.

Observations rares de medecine etc. (quoted by Deschamps, Traite des maladies des fosses nasales et leur sinus. Paris, 1804, p. 88.)


14


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 82.


following Bartholini, and at the commencement of the present, Gruner,* give sneezing as one of the sigus of pregnancy. Grunert states that the nose becomes warm and red in the hysterical, in women at the menstrnal period and in the victims of onanism.

Isolated cases of sneezing at the menstrual period arefonnd scattered here and there in older medical literature. Thus GarmauusJ and Lauzonus§ report cases of this kind, Delius|| a case of sneezing following the suppression of the menses, while Petzoldlf relates one in which sneezing occurred every day during the whole of pregnancy. Paullini** records a case in which the menses were brought on by sternutatories, and quotes Fabricius Hildanus as having noted copious menstruation follow violent and immoderate sneezing.

Sudden and complete occlusion of both nostrils sometimes occurs with regularity during coitus. This phenomenon, which may be accomjjanied by so-called "reflex" phenomena, such as, for example, asthmatic attacks, is doubtless due to sudden dilatation of the erectile bodies from paralysis of their vaso-motor nerves; for as Anjelft has shown, during coitus the nervous shock is distributed to the whole vaso-motor system of nerves and is not confined to the erection center.

Cases have also been reported in which the act of coitus was accompanied by hemorrhage from the nose (Isch-Wall, Joal).

V. — The reciprocal relationship between the genital organs and the nasal apparatus is furthermore illustrated by the occasional dependence of genito-urinary irritation upon affec


Physiologische u. pathologische Zeichenlehre, etc. Jena, ISOl, p. 122.

tibid., p. 327. Several of the older writers refer to a case of " pituitous and serous catarrh " from coitus, reported by Georg Wolfgang Wedel (see Schurig, Spermatologia historico-medica etc., Francofurti ad Moenum., 1720, p. 280), but I have been unable to obtain the original account of the case. John Jacob Wepfer, Observationes medico- practicae de affectibus capitis internis et externis, Schaphusii, 1728, obs. Ivii (see my essay. The Pathological Nasal Reflex, an Historical Study. Transactions of the American Laryngological Association, 1887 ; also N. Y. Medical Journal, August 20th, 1887), mentions a case of hemicrania, tinnitus aurium and vertigo associated with uterine trouble, sneezing and a nasal discharge, but few particulars are given.

It is interesting in this connection to recall the admonition of Celsus to abstain from warmth and women at the commencement of an ordinary catarrh. (Op. cit., lib. iv, cap. 2, § 4, " ubi aliquid ejusmodi sentimus, protinus abstinere a sole, a balneo, a venere deberaus.") Hippocrates, on the otlier hand, relates the following case : " Timochari liieme distillatione in nares praecipue vexato, post veneris usum cuncta ressicata sunt, lassitudo, calor et capitis gravitas successit, sudor ex capite multus manabat." Op. cit., De morbis vulgaribus, lib. v (torn, iii, p. 574). The expression " bride's cold " would seem to indicate on the part of the laity the suspicion of a causal connection between repeated sexual excitement and coryza.

t Ephemerid. nat. cur. Dec. ii, An. viii, obs. 152.

§Ibid., Dec. iii. An. ii, obs. 32.

II Act. nat. cur., vol. viii, obs. 108.

TEphem. nat. cur. Dec. iii, An. v, vi, obs. 183. See also Rahn, op. cit., p. 34.

0p. cit., cent, iv, cap. xlviii. tt Archiv fur Psych., Bd. viii, Heft 2.


tioiis of the nasal passages. Ketarded sexual developmeut, too, may possibly depend upon the co-existence of nasal defect* Unfortunately there are no authentic cases in literature in support of this latter hypothesis, but in this connection I would like to call attention to the remarkable case reported by Heschel (Wiener Zeitschrift fiir pract. Heilkunde, Miirz 23, 1861), in which imperfectly developed genital organs were associated with absence of both olfactory lobes. The man was well developed, with the exception of the testes, which were the size of beans and contained no seminal canals, and the larynx, which was of feminine dimensions. All trace of olfactory nerves was absent, as were also the trigona olfactoria and the furrow on the under surface of the anterior lobes. There was scant perforation of the cribriform plate which transmitted the nerveless processes of the dura mater. There was also an absence of nerves in the nasal mucosa.

VI. — It is, finally, quite possible that irritation and congestion of the nasal mucous membrane precede, or are the excitants of, the olfactory imjiression that forms the connecting link between the sense of smell and erethism of the reproductive organs exhibited in the lower animals and in those individuals whose amorous propensities are aroused by certain odors that emanate from the person of the opposite sex.

Through all the centuries the season of flowers — the springtime — has been celebrated in amatory song and story as the season of love and of sexual delight. This conceit, handed down to us from the poets of antiquity, finds modern expression in the glorious verse of Tennyson:

" In the Spring a fuller crimson comes upon the robin's breast ; In the Spring the wanton lapwing gets himself another crest ; In the Spring a livelier iris changes on theburnish'd dove ; In the Spring a young man's fancy lightly turns to thoughts of love."

Woman, in all the ages, from the perfumed courtesan of ancient Babylon to her reflected image in the harem of the Sultan to-day, has appealed to the olfactory sense to bring man xrnder her sexual dominion and to fire his passionate desire.

In the Song of Solomon, in the Aries amoris of the older writers, in the fetich worship of odor, in the picture of Eichelieu surrounded by an atmosphere of dense perfume in order to stimulate his amorous feeling, is reflected the idea of the m possible power of olfactory perception in awakening sexual I thoughts. If you doubt that modern man has not forsakeh this idea, read Zola,t Lombroso, Tolstoi, Nordau.

Rousseau has aptly termed olfaction the sense of the imagi- nation, and if we reflect how intimately related it is to the I impressions we form of external objects, how it affects our emotions and influences our judgment, the clever definition of the French philosopher becomes all the more striking and felicitous. J


See Elsberg, Archives of Laryngology, Oct., 1883. f See especially a work by Leopold Bernard, Les odeurs dans lea romans de Zola. Montpellier, 1889.

tOf great interest is the influence which civilization exerts upon the development and impressibility of the olfactory sense. With


January, 1898.]


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While it is iindonbtedly true that olfactory impression iu man, under natural conditions, plays a subordinate part in the excitation of sexual feeling, while it may be also true that such intensification or perversion of the odor sense may indicate an abnormal condition and a reversion to the purely animal type, still the fact is incontestable that many persons are attracted sexually to each other through the sense of smell. Both history and fiction are full of such examples.

In connection with this part of the subject it is interesting to note the extraordinary degree of nervous sympathy that may be developed through the sense of smell. Millingen,* for example, relates the case of a pensioner iu the Hospital for the Blind in Paris, called Les quinze Vingt, who by the touch of a woman's hands and nails and their odor could infallibly assert if she were a virgin. A number of tricks were played on him and wedding rings were put on the fingers of young girls, but he never was at fault.

As in the lower animals it is possible or even probable that the alternate inflation and collapse of the erectile bodies is, to some extent at least, the means by which the grateful or ungrateful odorous particles are excluded from, or admitted to contact with, the apparatus of special sense, so in men in whom this sense is sexually excited or perverted, either normally, or from defect in the subjects themselves, the reception or rejection of the sensuous odors may be accomplished by a similar mechanism.

These facts point conclusively to an intimate physiological association between the nasal and reproductive apjjaratus, which may be partially explicable on the theory of reflex or correlated action, partially by the bond of sympathy which exists between the various erectile structures of the body. That a relationship exists by virtue of which irritation of the one reacts upon the circulation and possibly nutrition of the other, is accordingly rendered highly probable by the evidence of clinical observation.

If this excitation be carried beyond its physiological limits there comes a time sooner or later when that which is a normal process becomes translated into a pathological state, according to a well-known law of the economy. Hence it is


out enumerating, much less elaborating, the myriad conditiona that conspire to produce such a result, we may safely lay down the general proposition that the physical and moral forces of civilization — the social and intellectual environment of the subject — exert a marked effect upon the olfactory faculty by inviting or encouraging disturbance of the sentient and perceptive apparatus ; that the higher we ascend in the social scale, the more readily our judgments are unnaturally influenced or perverted by impressions derived through tlie sense of smell, and that the more we recede from the inferior orders, the less perfect and acute this faculty becomes, the more susceptible to irritation and the more predisposed to disease. In view, therefore, of the importance of olfaction as an avenue through which our mental impressibility is influenced — our imagination perverted — and in view of the relations of civilization to the sense of smell, we can readily understand why it is that this faculty is found more frequently deranged among the superior orders than in those lower down in the social scale and in the savage state.

•Millingen. The Passions, or Mind and Matter, etc. London, 1848, p. lOli.


a priori conceivable and eminently probable, not only that stimulation of the generative organs, when carried to excess, may become an etiological factor in the production of congestion and transient inflammation of the nasal passages, and especially of their cavernous tissue, but that repeated and prolonged abuse of the function of these organs may, by constant irritative influence on the turbinated tissue, become the starting point of chronic changes iu that structure.

Pathological.

The following data, derived from personal clinical observation, may possibly throw some light upon the subject.

I. — In a fair proportion of women suffering from nasal affections, the disease is greatly aggravated during the menstrual epoch or when under the influence of sexual excitement.

II. — Cases are also met with in which congestion or inflammatory conditions of the nasal passages make their ajipearance only at the menstrual period, or, at least, are only sufficiently annoying at that time to call for medical attention.

III. — Occasionally the discharge from a nasal catarrh will become offensive at the menstrual epoch, losing its disagreeable odor during the decline of the ovarian disturbance. In many cases of ozoena, the fetor is much more pronounced at times corresponding to those of the menstrual flow.

IV. — Excessive indulgence invenery sometimes seems to have a tendency to initiate inflammation of the nasal mucous membrane, or to aggravate existing disease of that structure. There are those, for example, who suffer from coryza after a night's indulgence in venereal excesses, and the common catarrhal affections of the nose are undoubtedly exaggerated by repeated and unnatural coition.

V. — The same is true in regard to the habit of masturbation. The victims of this vice in its later stages are constantly subject to nose-bleed, watery or mucous discharge from the nostrils, and perversion of the olfactory sense.

VI. — The co-existence of uterine or ovarian disease exerts sometimes an important influence on the clinical history of nasal disease. This fact has been shown in practice in cases in which the nasal affection has resisted stubbornly all treatment and in which it has only been relieved upon the recognition and appropriate treatment of the disease of the generative apparatus.

The recent researches of Fliess seem to indicate that the converse of this proposition is true.

The most commonly found conditions of the nasal apparatus following perverted sexual excitement, either from excessive venery or onanism, are: (1) coryza (generally of vaso-motor type), with or without reflex manifestations, such as asthma, paroxysmal sneezing, etc., (2) epistaxis, and (3) various forms of perversion of the sense of smell. In addition to these, Peyer has observed abnormal dryness of the nasal and pharyngeal mucous membrane, indicated by a feeling of dryness and burning in these regions and by complete cessation of secretion.

The coryza that follows intemperate venery resembles iu character that seen in the disease falsely called "hay fever,"


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[No. 82.


and, like it, is generally associated with more or less prouounced neurasthenia, or shall we say, localized hysteria. In other cases the nervous system is not apparently involved. The predominant temperament, however, in individuals thus affected is the neurotic. While they may not necessarily in some instances belong to the so-called "nervous " or "hysterical " individual, while they may give no outward and visible sign of a deranged nervous system, there will generally be found, on careful examination, a delicacy or sensitiveness of the nervous apparatus either in whole or in part.

It is conceivable that this sexual coryza may be associated with almost any of the so-called reflex neuroses. In one of my cases asthma was the central symptom. A young married woman, twenty-three years old, in otherwise apparently perfect health, consulted me for the relief of attacks of asthmatic breathing associated with stoppage of the nostrils. I could find nothing wrong at the time of consultation with the respiratory apparatus, and her other organs were in perfect condition. Keluctantly she confessed that every night for five years she and her husband had indulged in intemperate venery. Moderation in their sexual relations caused rapid disappearance of the symptoms, and in the nine years that have elapsed since she consulted me there has been no return of the disorder.

Interesting cases of asthma of nasal origin associated with, and due to sexual excitement have also been reported by Joal and Peyer. In this connection I would recall a case of periodic vaso-motor coryza reported by me at length elsewhere,* in which the attacks invariably appeared and were most severe at the menstrual period, appearing sometimes at its commencement, sometimes at its close. In the attacks coming on in the interval between the monthly periods pain was always felt in the left ovary. Residence at the seashore invariably gave relief, except during menstruation, when the attacks were as bad as when at home. The outbreak of the disease at the menstrual epoch in this case is readily explained by the physiological erection of the corpora carveruosa which occurs at that period. In this particular case the chief, and under certain circumstances the sole excitant of the paroxysm was the utero-ovarian excitement of the menstrual epoch.

Nose-bleed is not infrequently the result of onanism. Years ago Du Saulsayf called attention to the fact that enormous quantities of blood can be lost from the nose from the practice of this vice, and the accuracy of his observation is borne out by the experience of subsequent observers. Among others, Joal| has collected several such cases and reports three of his own. One of his patients informed him that he masturbated to excess to provoke nose-bleed, which relieved him from violent headaches from which he suffered.

AVhether the hemorrhages in these cases — which by the way are not confined to the male sex§— come from simple acute


A contribution to the study of coryza vasomotoria periodica, or so-called " hay fever." N. Y. Med. Rec, July 19, 1884.

t Comment, de rebus in med. etc., vol. xviii, p. 213. Michell, in Schlegel's "Sylloge selectiorum opusc. de mirabile sympathiae quae partes inter diversas corporis humani intercedit." Lipsiae, 1787. Jl. c.

§See case of Lemarchand de Trigon (girl of 10), quoted by Joal.


distension of the intra-nasal blood-vessels, or whether definite chronic structural changes have taken place in the mucous membrane and in the vessel walls, are points which are as yet undetermined. The probability is that some intra-nasal lesion is responsible for them, for, as I have pointed out elsewhere,* the discharge from the nostrils and the perverted olfactory sense found in the later stages of onanism are often simply the outward expression of chronic nasal inflammation.

The nature of the perversion of the olfactory sense in onanists will vary with the character of the nervous condition produced by the vice — hyperosmia, hyposmia, parosmia andallotriosmia have all been observed in cases of immoderate sexual excitement.

The investigations of Fliess would seem to indicate that painful, profuse and irregular menstruation may in some instances depend upon an intra-nasal cause. He cites a number of cases to show that the pain of certain forms of dysmenorrhcea may be temporarily dissipated by the application of cocaine to the nasal mucous membrane, or permanently controlled by cauterization. According to him, only the inferior turbinated body and the tuberculumsepti possess a special relation to the dysmenorrhoeic pains. These two localities he accordingly designates as xar' i^nyrj-, genital zones (Genitalstellen). If the tuberculum septi be cocainized, the sacral, if the inferior turbinated bodies be cocainized, the hypogastric, pains disappear. Cocainization of the right nostril causes disappearance of the pain on the left side of the body and vice versa.

In answer to the objection that these phenomena may be due to the general auassthetic action of the drug, he points out the fact that cocaine absorbed into the blood does not produce a general analgesic effect, as is produced in the case, for example, of morphia. On the contrary, in small doses it acts as a stimulant. The fact that the pain ceases 07ily when the genital zones are cocainized and that it may be permanently dissipated by cauterization of this area, does away, he thinks, with the assumption that the subsidence of the pains is a part of the euphoria produced by the drug. The fact alluded to above, that in cocainization of certain parts of the genital zones only individual pains disappear from the symptom complex, militates against the supposition of a simple, general narcotic effect.

I cannot vouch for or deny the accuracy of the above statements, as Fliess's monograph has just come into my possession and I have had neither time nor opportunity to put them to the test. Curiously enough, the genital zones of Fliess correspond exactly with the most sensitive portions of the sensitive reflex area mapped out by me in ISSS.f


•1. c.

tOn Nasal Cough and the Existence of a Sensitive Eetlex Area in the Nose. American Journal of the iMedical Sciences, July, 1883. The results of these experiments were first brought before the Baltimore Medical Association in the early part of 1SS3, and subsequently before the Medico-Chirurgical Faculty of Maryland (April, 1883, vide Transactions), and the American Laryiigological Association (May, 1883, vide Transactions). The conclusions reached from these investigations were as follows :

"(1) That in the nose there exists a definite, well-defined seusi


January, 1898.]


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17


I have ou innumerable occasions* shown that phenomena widely different in character and anatomical sphere of opera


tive area, whose stimulation, either through a local pathological process, or through the action of an irritant introduced from without, is capable of producing an excitation which finds its expression in a reflex act or in a series of reflected phenomena.

(2) That this sensitive area corresponds in all probability with that portion of the nasal mucous membrane which covers the turbinated corpora cavernosa.

(3) That reflex cough is produced only by stimulation of this area, and is only exceptionally evoked when the irritant is applied to other portions of the nasal mucous membrane.

(4) That all the parts of this area are not equally capable of generating the reflex act, the most sensitive spot being probably represented by that portion of the membrane which clothes the posterior extremity of the inferior turbinated body and that of the septum immediately opposite.

(5) That the tendency to reflex action varies in different individuals, and is probably dependent upon the varying degree of excitability of the erectile tissue. In some the slightest touch is sufiicient to excite it ; in others, chronic hypersemia or hypertrophy of the cavernous bodies seems to evoke it by constant irritation of the reflex centers, as occurs in similar conditions of other erectile organs, as for example the clitoris.

(6) That this exaggerated or disordered functional activity of the area may possibly throw some light on the physiological destiny of the erectile bodies. Among other properties which they possess, may they not act as sentinels to guard the lower air passages and pharynx against the entrance of foreign bodies, noxious exhalations and other injurious agents to which they might otherwise be exposed ?

Apart from their physiological interest, the practical importance of the above facts from a diagnostic and therapeutic point of view is sufiiciently obvious. Therein lies the explanation of many obscure cases of cough which heretofore have received no satisfactory solution, and their recognition is the key to their successful treatment."

In calling attention to this area as containing the spots most sensitive to reflex-producing impressions, I did not, nor do I now (as lias been wrongly inferred), desire to maintain that pathological reflexes may not originate from other portions of the nasal mucous membrane. Indeed, wherever there is a terminal nervous filament it may be possible to provoke sneezing, lachrymation and other reflex movements. My contention is simply this, that the area indicated in my original paper represents by far the most sensitive portion of the nasal cavities, and that pathological reflex phenomena are in the large majority of cases related to diseased conditions of some portion of this sensitive area. That all pathological nasal reflexes arise from irritation of this particular area is a proposition which I do not, and never have maintained. The determination of these sensitive areas is of special importance and interest in the solution of the pathology of the so-called nasal reflex neuroses. Whether a special sensitiveness in certain portions of the nasal mucous membrane exists or not, the agitation of the question has led to more rational methods of procedure in the treatment of a large class of nasal affections, and to more conservative methods in intranasal surgery. Before the location of the sensitive area or areas, the nasal tissues were destroyed with an almost ruthless recklessness that bade fair to bring intra nasal surgery into the worst repute. (For an elaborate discussion of this whole subject see article by the author in Wood's Reference Handbook of the Medical Sciences, edited by Buck, Wm. Wood & Co., N. Y., 1887, vol. V, pp. 222-242.)

My views upon this subject may be found in the following publications: A contribution to the study of coryza vasomotoria


tiou may be produced at will by artificial stimulation of this area, and that they may be dissipated by local applications to, or removal of, the membrane covering the diseased surface. It is therefore not difficult to conceive that the phenomena referable to the uterus and ovaries during menstruation may be influenced in a similar manner. The specific relations of the two zones and the crossed action of the reflex, if such it be, are much more difficult of explanation. If such a condition of affairs exists, it is certainly a remarkable phenomenon.

These observations, therefore, encourage the belief, if they do not establish the fact, that the natural stimulation of the reproductive apparatus, as in coitus, menstruation, etc., when carried beyond its normal physiological limits, or pathological states of the sexual apparatus, as in certain diseased conditions, or as the result of their over-stimulation from venereal excess, masturbation, etc., are often the predisposing, and occasionally the exciting causes of nasal congestion and inflammation and perversion of the sense of olfaction. Whether this occur through reflex action, pure and simple, or as a sequel of an excitation in which several oi' all of the erectile structures of the body participate, the starting point of the nasal disease is, in all probability, the repeated stimulation and congestion of the turbinated erectile tissue of the uose. It is highly probable that this erectile area, or organ, so sensitive to reflexproducing impressions, is the correlative of certain vascular areas in the reproductive tract, and that the phenomena observed may therefore be explained by the doctrine of what we may call, for want of a better name, reflex, correlated action.

In these remarks I have attempted no thoroughgoing exposition of the subject, but simply laid before you the results of my personal labors. These no longer represent, I am glad to say, the result of solitary observation and isolated experience. I have not attempted, as Fliess has done, to touch upon the biological side of the question.

The study of the relations between the nose and the sexual apparatus opens up a new field of research, of pleasing landscape and almost boundless horizon, which bids to its exploration not only the physiologist and pathologist, but also the biologist. Above all it brings us face to face with a serious problem of life, an interesting enigma, whose significance it will be the task of the future to divine.


periodica, or so-called " hay fever," N. Y. Med. Record, July 19, 1884. Coryza vaso-motoria periodica in the negro, with remarks on the etiology of the disease, N. Y. Med. Record, Oct. 18, 1884. Rhinitis sympathetica, essay read before Clin. Soc. of Md. ; see brief abstract in Md. Med. Journal, April 11th, 1885, and in Internationales Centralblatt f. Laryngologie, etc., Sept., 188.5. Observations on the origin and cure of coryza vaso-motoria periodica. Trans. Medico-Chir. Faculty of Maryland, 1885. Review of Morell Mackenzie's essay on hay fever, etc.. The American Journal of the Med. Sciences, Oct., 1885, pp. 511-528. See also discussion of the subject before the American Laryngological Association (May 14th, 1884, vide Transactions, p. 113 et seq.). See also cases of reflex cough due to nasal polypi, Trans, of the Medico-Chirurgical Faculty of Md., 1884, and articles in Wood's Handbook already referred to


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[No. 83.


PROCEEDINGS OF SOCIETIES


THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Meeting of October 18, 1897.

On the Hiematozoan Infection of Birds.— Dr. W. G. MacCallum.

(See Bulletin, Vol. VIII, p. 235.)

Discussion.

Dr. Welch. — Everybody familiar with the literature of the subject knows that this communicatiou is of the very first importance, not only of interest with reference to this particular organism, but of general biological interest. It clears up one of the most obscure questions in the biology of the malarial parasites. I have had the opportunity of seeing Dr. MacCallum's demonstration of the phenomena which he has described in the blood of the crow. I should like to ask Dr. MacCallum if he has any evidence that in the regular sporulating cycle of development any differences can be observed between male and female organisms.

Dr. Thayer. — Dr. MacCallum's communication is most refreshing. For nearly 20 years the question of the nature of the flagellate bodies has been one of the most keenly studied points in connection with the malarial parasite, and that this important discovery should have come from our laboratory is an honor to the institution.

Owing to my absence from America I have not seen the whole process as it takes place in birds, but a part of the process I have been able to follow out in man. The specimen was that which Dr. MacCallum has described, and the body which I observed was one which had just been penetrated by a free flagellum. This body was a large round form of the aistivo-autumnal parasite without evidence of any surrounding corpuscle. It contained a central ring of pigment. About this body there were two flagella which, though actively motile, did not disturb or agitate the round body. On careful observation, however, it was easy to observe that the flagella were quite free from the organism. These flagella which were very active would draw away from the parasite and then attack it, butting their heads against its periphery, struggling around it, and apparently making every effort to jjenetrate into the interior. Now this parasite represented a form which we have been looking at quietly off and on for these last seven years, considering it to be a flagellate body which for some reason or other was not agitated by the surrounding filaments, as is ordinarily the case. And yet after being taught by Dr. MacCallum to observe the picture before us, how perfectly simple it was to realize that the organism was not really possessed of motile filaments, but was a separate body attacked by free flagella.

These observations are, as I said, most refreshing and encouraging, and may well lead us to hope for more. It is particularly satisfactory to realize that Dr. MacCallum's discovery was not accidental, but was the result of intelligent and well-directed observations. It bids fair to be the most important contribution to our knowledge of the malarial parasite since the discovery by Golgi in 1885 of the ordinary cycle of development.


Dr. Barker. — The observations reported by Dr. MacCallum are of interest not only as settling the fact that fertilization occurs in connection with the life-history of the malarial parasites, but they also give ns some information concerning the exact nature of the fertilizing process in its different stages. The processes of fertilization in the protozoa have been studied by many observers, and one naturally inquires in how far does the phenomenon as observed in the malarial parasite agree with the findings heretofore recorded concerning protozoan organisms in general. All zoologists believe that the important material substances underlying the process of fertilization are situated in the nuclei of the cells concerned. It would seem very likely then that the flagella of the malarial parasite contain nuclear substances, a view which is quite in accord with the ideas of Sacharov.

If the flagella do contain nuclear substances we have beautifully exemplified in the process of fertilization in the malarial parasite the well-known phenomenon of reduction-division. In the fertilization of all animals and plants, as far as the process has been studied exactly, reduction-division of some sort appears to be constant. Dr. MacCallum has shown that one only of the flagella of the aggressive organism enters the passive parasite. It will be of very considerable interest to find out whether or not any analogous process of reduction of nuclear substances occurs in the parasite into which the flagellum goes. In most instances in other organisms the reduction-division in the female element occurs before the entrance of the spermatozoon. In a few instances it is stated that the directive corpuscles are extruded after fertilization. Dr. MacCallum tells me that thus far he has been unable to make out any bodies resembling directive corpuscles thrown off from the passive parasite.

Dr. MacCallum. — I can hardly answer Dr. Welch's question because in the particular form which I examined, segmentation takes place only in the bone marrow, I believe. I recorded the temperature of an infected crow every three hours day and night for three weeks and found a rise in temperature of three to five degrees daily. There is, however, a similar daily rise in temperature in the normal crow. There seemed to be a higher rise about every fifth day in the infected crow, but I could not determine this definitely. The temperature of the crow is from 103° to 109°.

The Presence in the Blood of Free Grannies derived from Leucocytes, and their Possible Relations to Immunity.— Dr.

W. R. Stokes and Dr. A. Wegefaeth. (See Vol. VIII, p. 246.)

Discussion. Dr. Welch. — This has been a very painstaking research. Dr. Stokes' view that free granules in the blood are identical with or derived from the specific granules in the leucocytes is very suggestive, and he brings valuable, although not wholly conclusive, evidence in its support. Especially significant is his observation that free granules exist in the horse's blood apparently identical with the unusually large and characteristic granules in the eosinophiles of this animal. Dr. Stokes,


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it will be observed, does not identify with the granules which he has studied the blood-plates, concerning whose structure and origin there is still much difference of oj^iniou.

As to whether the bactericidal properties of blood are in fact derived from the free granules cannot be said to be demonstrated beyond all doubt. It is well known that tiltratiou through porcelain not only filters out particulate matter, such as these granules, but likewise affects the composition of the fluid. Still the theory of immunity proposed by Dr. Stokes is supported by other observations, such as those of Kanthack and Hardy, and is a legitimate one to use as a working hypothesis.

Dr. Barker. — When Dr. Stokes replies I should like him to state whether or not he has observed the granules in rows outside of the leucocytes. Many histologists believe that the granules in the leucocytes are really the cytomicrosomes embedded in the cytolinin threads of the cytoplasm.

Dr. Stokes. — In answer I would say that you can stain the free eosinophilic granules both by eosin and the triple blood stain in horse's and frog's blood. We have found numerous large granules in the horse's blood, but have not been very successful in staining the free granules of either variety in human blood. I have not seen the granules in rows.

I simply used the term neutrophilic to designate a leucocyte containing fine granules and having a polymorphous nucleus.


NOTES ON NEW BOOKS.

An Epitome of the History of Medicine. By Koswkll Park, M. D.

(Philadelphia : F. A. Davis Co., 1896.)

As Dr. Park in his introduction states, "the following pages represent an effort to bring the most important facts and events comprised within such a history into the compass of a medical curriculum, and at the same time to rehearse them in such a manner that the book may be useful and acceptable to the interested layman,— J. e. to popularize the subject." The work represents a series of lectures delivered to the medical students at Buffalo, and is interesting and thoughtful, as are all the writings of this author. There is no satisfactory history of medicine in the English language — perhaps there is none in any language — for the difficulties in writing it are very great. In this epitome Dr. Park has succeeded in presenting his subject in as attractive a way as possible, we think, and we have found it agreeable reading, although frequently, from the very necessity of the case, it is too encyclopedic in form to be altogether easy reading. To cover the entire history of medicine in 350 octavo pages and make it readable at all is a task in itself, but Dr. Park has done more than this. He has not only given us a history of medicine, but has shown us its connections with the other arts, and the influences brought to bear upon it through all time. And in addition he has set the example to other medical schools of giving a course in medical history, which, spite of the many branches of medicine that have to be studied, should certainly not be left by the leading medical schools entirely out of their curriculum. The only unsatisfactory part about the book is its index, which should be more complete.

It is perhaps in just such an epitome of history that one can grasp the whole subject better than in a larger history ; in a certain sense it brings the different periods in the development of medicine into closer union, and one is able to judge more readily of the advances made in medicine since our earliest knowledge of it. There are many points of similarity between the conditions of medical prac


tice to-day and those of the middle ages and later — we are no more free of false schools now than then — even to-day when the hold of pure science on the minds of men is greater than ever before, we find schools of homeopathy, osteopathy, bone-setters, faith-curists and Christian-scientists. Then again we have no doubt that when the history of medicine of the present era is written several hundred years hence, it will be shown that we shall have missed making discoveries, to which we are as close, as those discoveries made by us, which the practitioners of the 16th, 17th and 18th centuries almost made— they helped us to them. In fact most of our discoveries are not due to greater intellectual discernment, but to added tools of trade, which make the study of medicine easier for us every day, and at the same time tend to make most of us superficial thinkers — we rely on our instruments and not on our brains. It may fairly be argued whether we have any as great men-thinkers as existed during the middle ages. The breadth of knowledge attained by the leading men of those times is something very remarkable. True, there was not so much to know, not so many book* to read, but nevertheless the great men were better informed for their times than those of today. Their very breadth of knowledge may have made them less able practitioners than are the physicians of to-day ; it is certain that great knowledge in many branches of science often leads to a questioning spirit of mind, to one of less positiveness and directness, and thus to less readiness to act. We have advanced far in medicine during the past ICO years, but with all our new tools is the advance so great after all when in addition we take into consideration the enormous increase in workers? It is certainly an interesting comment that in the past 2500 years only two specifics for diseases have been found, quinine and mercury, and the latter is not so sure a specific as the former. Let us hope for better times to come in therapeutics.

Unscientific as Rademacher's doctrine was of three primary diseases with three universal medicaments, in its development it came closer than appears at first sight to a doctrine of the present day. He and his followers believed that besides universal diseases there were diseases of organs to be diagnosed by the efficacy of organ remedies, "thus abdominal diseases must be relieved by corresponding abdominal remedies," head diseases with "head remedies," etc. Are we not to-day doing just this with such remedies as cerebrine, ovarine, thyroidine, pancreatine, pepsin and many others, and, what is more, do we not believe to a greater or less extent in their efiicacy, and are we not justified in our belief? Is it quite fair when Dr. Park says : "What is the most surprising about this absurd doctrine is that it found followers, some even quite capable in their way." Rademacher may have been a "quack," so to speak, but oftentimes the difference between the " quack " and the " regular practitioner " is rather in words than in deeds.

Have we any much better definition of hysteria than that of Thomas Willis (l(i22-1675), who accounted for this condition "by the union of the spiritus with imperfectly purified blood "; a most accurate definition of the cause in many cases of hysteria.

We cannot go further on this line. We merely wish to show how nearly connected we are with the past in many respects, and . how interesting it is to follow the steps which have led us on so far ; there are few broken links in the chain of gradual growth in medicine, although its development has been hindered at all times by various false doctrines.

Before we close this review there are still one or two points to which we would like to draw attention. The easiest way, we think, to make such an epitome interesting is to connect as many stories or discoveries with the names of the men introduced. Dr. Park has given us many, but there are others we miss which would add to the value and attractiveness of the volume without increasing its length materially. Although Scarpa, Pott, and Bigelow are mentioned, there is no mention of the triangle, disease of the spine, and y-ligament so closely associated with these names. The


20


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 82.


discovery of the y-ligament is one which has quite revolutionized the treatment of dislocations of the hip and shouKl certainly not be omitted. Other omissions of a like character might be spoken of, but these are enough to mark our point. One of the most striking stories in medicine, itseemstous, is theone connected with Boerhaave's name, of which we find no mention in Dr. Park's work. When he died he left behind him an elegant volume, the title-page of which declared that it contained all the secrets of medicine. On opening the volume every page except one was blank. On that one was written : " Keep the head cool, the feet warm, and the bowels open." We miss also the amusing verse connected with I. Lettsom's name (there are a number of variations of this stanza) :

" When patients come to me I physics, bleeds, and sweats 'em. If after that they choose to die, Why then of course

I. Lettsom."

We are surprised, too, at the slighting mention of Sir Thomas Browne, who is one of the very few literary lights in medicine. His work, the " Religio Medici," should be read by every student of medicine, and is a book which will always live ; there is none other like it ; it is a classic. Surely, too, the student of medicine should know that Thomas Dover (Dover's powder) was a buccaneer, and the discoverer of Alexander Selkirk, the original of Robinson Crusoe. There is a delightful paper by Dr. Osier on Thomas Dover. And, finally, the name of James Cesdaile, M. D., should not be entirely omitted. He wrote two works, one entitled " Mesmerism in India," 1850, and the other, "Clairvoyance and Practical Mesmerism," 1852. He peiformed a large number of major operations in India on patients under the influence of mesmerism or hypnotism, and had it not been for the discoveries of ether and chloroform just at this time, his work, which was admirable, would have obtained greater reputation than it has. He was an able surgeon and used mesmerism merely as a means of doing away with pain. He was not a believer in mesmerism in any false sense ; he used it purely from a humanitarian point of view, and more extensively than any one who preceded him, and with very brilliant results.

In final conclusion we wish only to congratulate Dr. Park on this last work of his, which deserves much praise.


Practice of Medicine. By James M. Anders, M. D. {Philadelphia :

W. B. Saunders, 1898.)

Witliin the past eigliteeu months three books on the practice of medicine have appeared written by Philadelphia physicians ; first came Dr. Tyson's, then the combination work of Drs. Wood and Fitz, and finally this one by Dr. Anders. In addition to these volumes from Philadelphia, a number of systems of medicine have appeared, so that there is at present no lack of text-books on medicine. These are the days of cheap printing and of superabundant writing. Tliere have been many advances in the past ten years in diagnosis and treatment of diseases, but we do not think there is any call for this multiplicity of books on practice ; and we hope that there will soon be a reaction against the production and publication of works all treating the same subject.

This last book compares favorably with its predecessors; it is about the same size as Dr. Tyson's, but larger than that of Drs. Wood and Fitz. Every author necessarily has views of his own on diagnosis, prognosis, treatment, etc., but these may not be either truly novel or suggestive. Much space in this work — too much, we think— is given to treatment ; and with it all we have found important matters left out, and treatment suggested that we do not believe to be good. For instance, in typhoid fever Dr. Anders seems to be a strong advocate of rectal feeding and rectal irrigation, in spite of the fact that, as he states, ulcerations in the large intestine are found in nearly 33 per cent, of all cases; the dangers of perforating


an ulcer with a rectal tube are not slight, and we believe such treatment should only be resorted to in the very gravest cases. We find no mention of the use to which the Roentgen rays may be applied in the diagnosis of obscure thoracic cases ; the value of these rays has been ably demonstrated by Dr. Francis H. Williams, of Boston, and others. And again the author does not speak of the use of antistreptococcus treatment in ulcerative endocarditis. The value of this last method of procedure may be questioned, but it deserves to be noted, and has already proved eflScacious in certain cases. Nothing is said also of the palliative treatment by hypodermoclysis in diabetic coma. This brings up one of those subjects of perennial interest to all practitioners, and one which was much discussed at the late meeting of the British Medical Association in Montreal, that is, the treatment of diabetes mellitus. Anders' treatment is practically that advised by the men who took part in the discussion, to cut off all starches at first, and then to admit them little by little to the dietary as the patients prove that they can digest them without harm, or prove as in some cases to be doing worse without them. We are glad to note that he advocates the free use of fats, which oftentimes are readily digested in large quantity, while the patient gains in strength and weight.

Another subject which was much discussed at Montreal was that of arthritis deformans ; and here Dr. Anders differs from the general consensus of opinion as expressed at that meeting. He believes in the neuro-trophic theory as a cause of this disease, which it seems to us is a theory which does not stand a very thorough examination. As Dr. James Stewart, of Montreal, said in closing his paper on this subject, " the result of recent investigations points very strongly to its infectious nature." He also very strongly advocated the Tallerman method of treatment, i. e. baths of superheated dry air. This means is not spoken of by Dr. Anders.

In the chapter on malaria there are several confusing statements ; speaking of the evolution of the aestivo-autumnal parasite the author saj'S, p. 83 : " For the differences in the period of evolution there is no satisfactory explanation, though the variation may be connected with the circumstance that it frequently (though by accident) penetrates into the red blood corpuscle." We do not understand what the author means by this. Again on p. 91, in speaking of malarial hsematuria, he states : " The blood shows non-pigmented parasites (forming rosettes)"; the rosette-shaped figures are always pigmented, and we do not comprehend exactly what form of organism he means. On p. 93 we regret to note the term typho-malaria, — the author says " remittent fever must not be confounded with typho-malaria "; it is the use of this word which has already led to so much distracting confusion between typhoid fever and malaria, and it ought not to be used any longer. There is no mention in the differential diagnosis of malarial and other diseases of syphilis. Every now and then cases of syphilis will develop intermittent chills, almost identical to those seen in malaria. We have lately had under observation a very interesting case of right apical lobar pneumonia ; the patient had contracted syphilis about a year previously for which he had received irregular treatment. On three successive occasions, on alternate days, during the height of the pneumonic fever, at about 4 o'clock in the afternoon there was a rise of from one to two degrees in the temperature, and this wasseenon twooccasions after the temperature was practically normal. The blood was examined on two occasions for malarial parasites, but none were found ; the patient was treated with both quinine and mercury, so that no conclusions can be drawn from the effects of the medicine. It yet remains in doubt as to whether these peculiar rises of temperature were due to syphilis or malaria. We are inclined to attribute them to the former.

On page 602 it is stated of the diastolic murmur heard in aortic incompetency, that "from the xyphoid it is transmitted to the left as far as the spinal column." We believe there is some slip here.


January, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.




There are many other points we should like to iliscuss in this review, but they would take up too much space. It seems to us that the prognosis of valvular lesions of the heart is too favorable as given by Dr. Anders, and that the relationship between increased tension in the arterial system, arterio-sclerosis following it, and disease of the valves of the heart is not clearly stated.

There are a few typographical errors, and while most of the illustrations seem to us satisfactory, yet there are some which might quite as well be omitted, for instance those on pp. 467, 472 and 476.

Notwithstanding all our criticisms the book is a good one, and for the average general practitioner will be of distinct service from its detail of treatment. It is not a great book. We could have got on without it, but we are glad to have it on our shelves. There is little that is new in it, but it is well to have the opinions of any man of large experience. The reliance of the author on Osier's work is marked by numerous references to his practice of medicine.

A Text-Book of Diseases of Women. By Charles B. Penkosk,

M. D., Ph.D. 8vo, 529 pages. {W. B. Saunders, Philadelphia,

1897.)

After a brief introductory chapter, the author treats in detail the methods of examining the uterus and bladder, and in the examination of the rectum lays especial stress on the value of the kneechest posture.

The illustrations demonstrating Emmit's operation for repair of a lacerated perineum are the best that have yet appeared, but theuse of silk ligatures and shot instead of catgut in the angles is rather antiquated, as there is usually considerable danger of a breaking down of the external portions of the perineum during the removal of the deeply-seated sutures in the angles.

It is pleasing to see the word of warning against the stem pessary noted on page 119. On page 127 it is said, " in all old cases of retrodisplacement, endometritis is an accompaniment." This is very doubtful. In a number of cases of retroflexion where the uterus was densely adherent posteriorly and where both tubes were the seat of pyosalpinx, we have found a perfectly normal endometrium. On page 137 a very opportune warning is given against the use of pessaries where the uterus is bound down or the appendages are the seat of inflammation.

The operation for suspension is accurately described, and the author fully agrees with the lines previously laid down by Kelly when he says, " we do not wish to make a fixation of the uterus to the anterior abdominal wall."

Figure 98, labeled " left lateral laceration of the cervix with erosion," is misleading, resembling much more a typical early carcinoma of the cervix. It is refreshing on page 166 to note: "If the advice here given — to seek for the primary cause of the cervical catarrh and to cure it — is followed, it will be found that there are very few cases that depend for a cure upon local applications."

The articles on cancer of the uterus are well written, but we cannot agree with the writer when on page 212 he says that cancer of the body is rare in comparison with cancer of the cervix. Figure 118, which is marked Glandular Endometritis, shows an intact surface epithelium, typical glands lined by characteristic epithelium, and a normal stroma between the glands. Although this might according to general usage be called endometritis, there is not the slightest sign of any inflammation.

On page 205 one is advised to carefully wash out the uterus with a bichloride solution should the organ be perforated by the curette. This is hardly to be recommended, as the fluid would naturally flow out into the abdominal cavity. The author on page 247 claims that myomectomy is a dangerous operation and that it is applicable only when one fibroid is present. The experience of others has shown conclusively that several may be removed with little danger, and Kelly has removed as many as eighteen at one time.


The chapters on diseases of the tubes are clear and forcible, especially chapter xxvi, on tubal pregnancy.

Ovarian tumors are well handled, but it is surprising to learn that ovarian fibromata are very rare, as the literature contains reports of numerous cases ; also to learn that the majority of solid tumors of the ovary are sarcomatous in character, in view of the fact that they are sparsely scattered throughout the bibliography.

Primary carcinoma of the ovary is by no means a rarity. Diseases of the urethra and bladder are brought up to date and due credit is given to Kelly for the work he has done.

The chapters on technique are to the point, but we believed that the glass drainage tube was a thing of the past.

The majority of operators will fully agree with the author when he says " more discomfort may be experienced after ventrosuspension of the uterus than after a hysterectomy," and with a subsequent remark, "catheterization should never be performed under any circumstances by the aid of the tactile sense alone. The nurse should always see what she is doing."

Preceding the discussion of each organ, a brief review of its anatomy is given. The illustrations both of the gross and microscopical specimens are well executed and the text concise and clear. The book was written for students and to them it can be recommended as the best we possess. T. S. C.

Crimeand Criminals. By J. Saxdersox CnnisTisoN, M. D. (Chicago:

W. T. Keener Co., 1897.)

It is very seldom that a series of newspaper articles are worth reprinting in book form, and this work is no exception to the rule. It is composed of a series of articles which appeared in the Chicago Tribune under the caption of "Jail Types," and we believe that they were undoubtedly meant to be " popular" articles. They are certainly not in any strict sense " scientific" papers, and are practically of no value to the thorough student of criminology. The histories of the cases as presented are very superficial, and no fair deductions can be made from the majority of them. We think that the book is practically useless, and that the moral tendency of such papers in daily journals is bad.

Transactions of the Chicago Pathological Society, from December, 1895, to April, 1897. Vol. II. [Chicago: American Medical Association Press.)

There are many cases of interest to both physicians and surgeons reported in this volume — too many, one may fairly say. The mere collection of cases or specimens at the present time is of comparatively little value; both must be "worked up" by all the many methods we have at our command. Especially is this true of pathological specimens, which without a most thorough microscopical examination are practically worthless. The value of such volumes of transactions lies wholly in their being books of reference for strange and rare cases. We have no doubt Volume II is an improvement on Volume I, but if the editors of Volume III would use more supervision in the selection of cases to be published next time, the third volume would be an improvement on its predecessors. Fewer cases should be reported, and more in greater detail ; then the volume would become of permanent value.

Transactions of the Indiana State Medical Society. Forty-sixth Annual Session held in Indianapolis, Ind., June 6th and 7th, 1895. {Indianapolis : Carlon and Uollenbeck.) This is a large volume of over 500 pages, nearly 400 of which are devoted to papers on medical and surgical topics, but there is little of permanent value to be found in this mass of material. A number of interesting cases are reported, but few of them with sufficient detail to make them of real value, and the papers on general topics, such as litha;mia, immunity, hypnotism, alcoholism, etc., present no original ideas. The volume can only be of importance to the members of the society and their immediate friends.


22


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 82.


Compatibilities in Prescriptions. By Edsel A. Ruddiman, Ph. M.,

M. D. {New York : John Wiley & Soiis, 1897.)

This work is divided into two parts as described by the author in his preface : " The object of the first part of this book is to present to liim [the busy practionist] in a convenient and condensed form the more common incompatibilities .... The second olg'ect of t' e writer is to furnish the student of pharmacy with a list of incompatible prescriptions in such form that he may find out for himself what the trouble is and the best means of avoiding or overcoming it." The book is well arranged, the more ordinary drugs being taken up in alphabetical order, and in fact no fault can be found with it. But it requires very careful study, and is hardly adapted for the general practitioner unless he has a well-grounded knowledge of chemistry. As an exercise book for the student it will undoubtedly prove itself of value. We doubt whether any one but an expert pharmacist or chemist would recognize the errors in a number of the prescriptions given, which only go to show the numberless difficulties to be met with in combining drugs, and the gratitude which the ordinary practitioner should have for the makers of tablet triturates and other compounded drugs, which we believe have eaved many errors in prescription writing, and also many lives. The multiplicity of new chemical compounds has added immensely to the probabilities of making errors in combining two or more drugs in a prescription, and we rejoice that it is becoming less and less the fashion to use more than two or three medicines in combination. It is better to use the active principles alone, if possible.

Exercises in Practical Physiology. By Augustus D. Waller, M. D., F. R. S. Part III. Physiology of the Nervous System. ElectroPhysiology. (New York: Longmans, Oreen cC Co., 1897.)

In this volume, which forms the third in a series of exercises and demonstrations in physiology for medical students, the author has dealt with that difficult branch of medicine, the " electrophysiology " of the nervous system. The experiments are only intended foraJvanced students, and seem to us to coverthe ground well. Every instructor would probably modify these exercises, or build up a new series for himself, but any student who has done these experiments should have a good understanding of this subject. The author takes up in order first some of the ililferent kinds of electric cells and their adjuncts, as commutators, galvanoscope, rheostat, etc. ; then follow a number of experiments on the stimulation of the muscle, its fatigue and contractions ; on muscle and nerve currents ; on the secondary currents ; and these experiments in turn are followed by others on reflex time and action. In this manner Dr. Waller covers a broad ground with a comparatively small number of well-chosen exercises.

Rheumatism and its Treatment by the Use of the Percusso-Punctator. By J. Brindley James. {London : Rebman Publuhiitg Co. Ltd., 1897.)

The title of this work is both misleading and ambiguous. We opened the book thinking that the author had found a new treatment for acute articular rheumatism, but found ourselves entirely mistaken. The treatment is not new, and by " rheumatism " the author means all those vague pains which are included in such terms as " lumbago," "vertigo," " hemicrania," " brow-ague," etc. The " percusso-punctator " is nothing more nor less than a modified form of acupuncture, and an instrument very like many of the old "wet-cups." The cures which the author professes to have wrought by means of this tool are frequently obtained by other physicians with simpler methods ; we have seen the insertion of a long hat-pin in the lumbar muscles rapidly relieve an attack of lumbago. Another chapter in this superficial work is taken up with the treatment of sciatica by hypodermatic injections of sulphuric ether; the writer states that he has cured a number of cases by this


method, and we have no doubt of its use in certain cases, but bis treatment was supplemented by the daily use of salicylate of soda, so that it is quite impossible to judge to which of these two drugs the honor is due. There are two chapters given to " nevrose" or neurasthenia which deserve special condemnation ; the use of numerous French words and italics is resorted to most unnecessarily and lends no strength to an otherwise feeble production.

The conceit of the author is astonishing, as may be judged from the following: "It is, however, only in strict accordance with this sublunary world's order of things that the discoverer and inventor, from Galileo with his telescope to Stephenson with his locomotive, should at first — often a terribly prolonged 'at first' — resign themselves to encounter, not active persecution in our times, but at all events hostile opposition, scepticism and contemptuous derision." The author believes he has been most unjustly treated by the world at large, but when he compares his discovery (?) to those of Galileo and Stephenson we can but smile and leave him to his merited fate.

Transactions of the Jlichigan State :Medical Society. 1897. Vol.

XXI. {Grand Rapids : Published by the Society.)

Were it not for the address on surgery in this volume by Roswell Park, these transactions might be laid on a back shelf. But this address, like all of Dr. Park's, contains thoughts of more than passing value. The subject of it is " the problems which most perplex the surgeon," but it is devoted almost entirely to a very interesting discussion of the question of cancer in many of its various relations. Besides this paper there are only two or three to which attention might be drawn — one on a case of purulent pericarditis, by F. AV. Garber ; a second on cancer of the stomach, by J. H. Kellogg, and thirdly, report of a case of lead-poisoning, by H. Gibbes; but except as cases they deserve no special mention — the histories are meagre.

The Diseases of Women. A handbook for students and practitioners. By J. Bland Sutton, F. R. C. S. Eng. , and Arthur E. Giles, M. D. {Philadelphia: W. B. Saunders. London : Rebman Publishing Co. Ltd., 1897.) This little book of 436 pages is written in a way to be " useful to

students for examination purposes," and is not calculated to increase

the reputation of its distinguished authors. It contains nothing

new. It is well printed and profusely illustrated.


BOOKS RECEIVED.


Crime and Criminals. By J. Sanderson Christison, M. D. 1897. 12mo. 117 pages. The W. T. Keener Co., Chicago.

Rheumatism and its Treatment by the Use of the Perciisso-Pnnctatur.

By J. Brindley James, M. R. C. S. Eng. Second edition. 1897.

12mo. 39 pages. The Rebman Publishing Co. Ltd., London. Transactions of the Michigan Slate Medical Society for the Year 1897.

Vol. XXI. Svo. 526 pages. Published by the Society, Grand

Rapids.

A Practical Treatise on Scvual Disorders of the Male and Female. By Robert W. Taylor, A. M., M. D. 1S97. Svo. 451 pages. Lea Brothers & Co., New York and Philadelphia.

Selected Essays and Monographs. Translations and reprints from various sources. 1897. Svo. 436 pages. The New Sydenham Society, London.

Thirty-third Report of the Trustees of the Boston City Hospital, with Report of the Superintendent, etc., for the year Feb. 1, 1896, to Jan. 31, 1S97, inclusive. Svo. 194 pages iMunicipal Printing Office, Boston.


January, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


23


PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.


THE JOHNS HOPKINS HOSPITAL REPORTS. Volume I. 423 pages, 99 plates.

Report In Fntliologrr The Vessels and Walls of the Dog's Stomach; A Study of the Intestinal Contraction;

Healing of Intestinal Sutures; Reversal of the Intestine; The Contraction of the

Vena Fortae and its Influence upon the Circulation. By F. P. Mall, M. D. A Contribution to the Pathology of the Gelatinous Type of Cerebellar Sclerosis

(Atrophy). By Henry J. Berkley, M. D, Reticulated Tissue and its Relation to the Connective Tissue Fibrils. By F. P.

Mall, M. D.

Report in Dermatology. Two Cases of Protozoan (Coccidioidal) Infection of the Skin and other Organs. By

T. C. Gilchrist, M. D., and Kmmet Risford, M. D. A Case of Blastomj-cetic Dermatitis in Man; (Tomparisons of the Two Varieties of

Protozoa, and the Blastomyces found in the preceding Cases, with the so-called

Parasites found in Various Lesions of the Siiin, etc. ; Two Cases of MoUuscum

Fibrosum; The Pathology of a Case of Dermatitis Herpetiformis (Duhring). By

T. C. GiLCBKIST, M. D.

Report in Pathology. An Experimental Study of the Thyroid Gland of Dogs, with especial consideration

of Hypertrophy of this Gland. By W. S. Halsted, M. D.


Volume II. 570 pages, with 28 plates and figures.

Report in Metliclne.

On Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with

Gallstones. By William Osler, M. D. Some Remarks on Anomalies of the Uvula. By John N. Mackenzie, M. D. On Pyrodin. By H. A. Lafleur, M. D. Cases of Post-febrile Insanity. By William Osler, M. D, Acute Tuberculosis in an Infant of Four Slonths. By Harry Toitlmin, M. D. Rare Forms of Cardiac Thrombi. By William Osler, M. D. Notes on Endocarditis in Phthisis. By William Osler, M. D.

Report in Medicine.

Tubercular Peritonitis. By William Osler, M. D.

A Case of Raynaud's Disease. By H. M. Thomas, M. D.

Acute Nephritis in Typhoid Fever. By William Osler, M. D.

Report in Gynecology.

The Gynecological Operating Room. By Howard A. Eellt, M. D.

The Laparotomies performed from October 16, 1889, to March 3, 1890. By Howard

A. Kelly, M. D., and Hunter Robb, M. D. The Report of the Autopsies in Two Cases Dying in the Gjrnecological Wards without Operation; Composite Temperature and Pulse Charts of Forty Cases of

Abdominal Section. By Howard A. Kelly, M. D. The Management of the Drainage Tube in Abdominal Section. By Hunter Robd,

M. D. The Gonococcus in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Peritoneum;

Ovarian Tumor; General Gynecological Operations from October 15, 1889, to

March 4, 1890. By Howard A. Kelly, M. D. Report of the Urinary E.xamination of Ninety-one Gynecological Cases. By Howard

A. Kelly, M. D., and Albert A. Ghriskey, M. D. Ligature of the Trunks of the Uterine and Ovarian Arteries as a Means of Checking

Hemorrhage from the Uterus, etc. By Howard A. Kelly, M. D. Carcinoma of the Cervix Uteri in the Negress. By J. W. Williams, M. D. Elephantiasis of the Clitoris. By Howard A. Kelly, M. D. Myxo-Sarcoma of the Clitoris. By Hunter Robb, M. D. Kolpo-Ureterotomy. Incision of the Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gynecological Operations. By

Howard A. Kelly, M. D.

Report in Snrgery, I.

The Treatment of Wounds with Especial Reference to the Value of the Blood Clot in the Management of Dead Spaces. By W. S. Halsted, M. D.

Report in Nenrolosy, I.

A Case of Chorea Iiisanicns. By Henry J. Berkley, M. D. Acute Angio-Neurntic Oedema. By Charles E. Simon, M. D. Haematomyelia. By August Hoch, M. D.

A Case of Cerebrospinal Syphilis, with an unusual Lesion in the Spinal Cord. By Henet M. Thomas, M. D.

Report in Pathology, I.

Amoabic Dysentery. By William T. Councilman, M. D., and Henri A. Lafleue, M. D.


Volume III. 766 pages, with 69 plates and figures.

Report in Pathology.

Papillomatous Tumors of the Ovary. By J. Whitridqe Willlaus, M. D. Tuberculosis of the Female Generative Organs. By J. Whitridqe Williams, M. D.

Report in Pathology.

Multiple Lympho-Sarcomata, with a report of Two Cases. By Simon Flexner, M. D.

Tlic Cerebellar Cortex of the Dog. By Henry J. Berkley, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman, M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Russell, Ph. D.

Heart Hypertrophy. By Wm. T. Howard, Jr., M. D.

Report in Gynecology.

The Gynecological Operating Room; An External Direct Method of Measuring the Conjugata Vera; Prolapsus Uteri without Diverticulum and with Anterior Enterocele; Lipoma of the Labium Majus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Source of Error in Gynecological Diagnosis; Operation for the Suspension of the Retroflexed Uterus. By Howard A. Kelly, M. D.

Potassium Permanganate and Oxalic Acid as Germicides against the Pyogenic Cocci. By Mary Sherwood, M. D.

Intestinal Worms as a Complication in Abdominal Surgery. By A. L. Stately, M. D.


Gynecological Operations not involving Coeliotomy. By Howard A. Kelly, M. D. Tabulated by A. L. Stavely, M. D.

The Employment of an Artificial Retroposition of the Uterus in covering Extensive Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdominal Pelvic Operations. By Howard A. Kelly, M. D.

Photography applied to Surgery. By A. S. Murray.

Traumatic Atresia of the Vagina with Hxmatokolpos and Haematometra. By Howard A. Kelly, M. D.

Urinalysis in Gynecology. By W. W. Russell, M. D.

The Importance of employing Anaesthesia in the Diagnosis of Intra-Pelvic Gynecological Conditions. By Hunter Robb, M. D.

Resuscitation in Chloroform Asphyxia. By Howard A. Kelly, M. D.

One Hundred Cases of Ovariotomy performed on Women over Seventy Years of Age. By Howard A. Kelly, M. D., and Mary Sherwood. M. D.

Abdommal Operations performed in the Gynecological Department, from March 5, 1890, to December 17, 1892. By Howard A. Kelly, M. D.

Record of Deaths occurring in the Gynecological Department from June 6, 1890, to May 4, 1892.


Volume IV. 504 pages, 33 charts and illustrations.

Report on Typhoid Fever.


Report in Nenrology.

Dementia Paralytica in the Negro Race; Studies in the Histology of the Liver: The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of the Submaxillary Gland of ihs musculiis; The Intrinsic Nerves of the Thyroid Gland of the Dog; The Nerve Elements of the Pituitary Gland. By Henry J. Berelet,

Report In Snrgery.

The Results of Operations for the Cure of Cancer of the Breast, from June. 1889. to January, 1894. By W. S. Halsted, M. D.

Report in Gynecology.

Hydrosalpinx, with a report of twenty-seven cases; Post-Operative Septic PeritonitisTuberculosis of the Endometrium. By T. S. Collen, M. B.

Report in Pathology.

Deciduoma Malignum. By J. Whitridqe Williams, M. D.


Volume V. 480 pages, with 32 charts and illustrations.

CONTENTS

The Malarial Fevers of Baltimore. By W. S. Thayer, M. D., and J. Hewetson, M. D. A Study of some Fatal Cases of Malaria. By Lewellys F. Barker, M. B.

Stndies in Typhoid Fever. By William Osler, M. D., with additional papers by G. Blumer, M. D., Simon Flexner, M. D., Walter Reed, M. D., and H. C. Parsons, M. D.


Volume VI. 414 pages, with 79 plates and figures.

Report in Nenrology.

Studies on the Lesions produced by the Action of Certain Poisons on the Cortical Nerve Cell (Studies Nos. I to V). By Henry J. Berkley. M. D.

Introductory.— Recent Literature on the Pathology of Diseases of the Brain by the Chromate of Silver Methods; Part I.— Alcohol Poisoning.— Experimental Lesions produced by Chronic Alcoholic Poisoning (Ethyl Alcohol). 2. Experimental Lesions produced by Acute Alcoholic Poisoning (Ethyl Alcohol) ; Part Il.-^erum Poisoning.— Experimental Lesions induced by the Action of the Dog's Serum on the Cortical Nerve Cell; Part III.— Ricin Poisoning.— Experimental Lesions Induced by Acute Ricin Poisoning. 2. Experimental Lesions induced by Chronic Ricin Poisoning; Part IV.— Hydrophobic Toxaemia.— Lesions of the Cortical Nerve Cell produced by the Toxine of Experimental Rabies; Part V.— Pathological Alterations in the Nuclei and Nucleoli of Nerve Cells from the Effects of Alcohol and Ricin Intoxication; Nerve Fibre Terminal Apparatus; Asthenic Bulbar Paralysis. By Henry J. Berkley, M. D.

Report in Pathology.

Fatal Puerperal Sepsis due to the Introduction of an Elm Tent. By Thomas S.

Cullen, M. B. Pregnancy in a Rudimentary Uterine Horn. Rupture, Death, Probable Jligration of

Ovum and Spermatozoa. By Thomas S. Cdllen, M. B.. and O. L. Wilkins. M. D. Adeno-Myoma Uteri Diifnsum Benignum. By Thomas S. Cullen, M. B. A Bacteriological and Anatomical Study of the Summer Diarrhoeas of Infants. By

William D. Booker. M. D. The Pathology of Toxalbumin Intoxications. By Simon Fle.xner, M. D, Tlie prirf of a si-t hrmnil in riolli [Tnls. I-VT] of the TTospittil Ittports is

$30.00. Vols. I, II and III are not sold senai-atelii. Tlir price of

Vols. IV, r and TI is $B.O0 each.


Monographs.

The following papers are reprinted from Vols. I, IV, V and VI of the Reports, for those who desire to purchase in this form : STUDIES IN DERMATOLOGY. By T. C. GiLCiiRisT, M. D.. and Emmet Rixforo,

M. D. 1 volume of 164 pages and 41 full-page plates. Price, bound in paper,

$3.00. THE MALARIAL FEVERS OF BALTIMORE. By W. S. Thayer, M. D., and J.

Hewetson, M. D. And A STUDY OF SOME FATAL CASES OF MALARIA.

By Lewellys F. Barker, M. B. 1 volume of 280 pases. Price, in paper, $2.7.5. STUDIES IN TYPHOID FEVER. By William Osler. M. D., and others. Extracted

from Vols. IV and V of the Johns Hopkins Hospital Reports. 1 volume of 481

pages. Price, hound in paper. $a.00. THE PATHOI.OOr OF TOX.M.ItUMIN INTOXICATIONS. Rv Simon Flexner, M. I). 1

volume of 150 paees with I full-paKe lilliricraphs. I rice, bound in paper, J'i.OO. Subscriptions for the above publications may be sent to

The Johns Hopkins Press, Baltimore, Md.


24


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 82.


THE JOHNS HOPKINS MEDICAL SCHOOL. SESSION 1897-1898.


FACULTY.


Daniel C. Oilman, LL. D., President.

William H. Welch, M. D., LL. D., Dean and Professor of Pathology.

Ira Rehsen, M. D., Ph. D., LL. D., Professor of Chemistry.

William Osler, M. D., LL. D., F. U. C. P., Professor of the Principles and Practice

of Medicine. Henrt M. Hurd, M. D., LL. D., Professor of Psychiatry, William S. Halsted, M. D., Professor of Surgery. Howard A. Kelly, M. D., Professor of Gynecology and Obstetrica. Franklin P. Mall, M. D., Professor of Anatomy. John J. Abel, M. D., Professor of Pharmacology. William H. Howell, Ph. D., M. D., Professor of Physiology.

William K. Brooks, Ph. D., LL. D., Professor of Comparative Anatomy and Zoology. John S. Billings, M. D., LL. D., Lecturer on the History and Literature of Medicine. Charles Wardell Stiles, Ph. D., M. S., Lecturer on Medical Zoology. Robert Fletcher, M. D., M. R. C. S., Lecturer on Forensic Medicine. William D. Booeer, M. D., Clinical Professor of Diseases of Children. John N. Mackenzie, M. D., Clinical Professor of Laryngology and Rhinology. Samdel Theobald, M. D., Clinical Professor of Ophthalmology and Otology. Henry M. Thomas, M. D., Clinical Professor of Diseases of the Nervous System, Simon Flexner, M. D., Associate Professor of Pathology. J. Whitridge Williams, M. D., Associate Professor of Obstetrics. Lewellvs F. Barker, M. B., Associate Professor of Anatomy. William S. Thayer, M. D., Associate Professor of Medicine. John M. T. Finney, M. D., Associate Professor of Surgery.


Georoe P. Dreter, Ph. D., Associate in Physiology.

William W. Russell, M. D., Associate in Gynecology.

Henry J. Berkley, M. D., Associate in Neuro-Pathology.

J. Williams Lord, M. D., Associate in Dermatology and Instructor in Anatomy.

T. Caspar Gilchrist, M. R. C S., Associate in Dermatology.

Robert L. Randolph, M. D., Associate in Ophthalmology and Otology.

Thomas B. Aldrich, Ph. D., Associate in Physiological Chemistry.

Thomas B. Futcher, M. B., Associate in Medicine.

Joseph C. Bloodgood, M. D., Associate in Surgery.

Thomas S. Cullen, M. B., Associate in Gynecology.

Ross G. Harrison, Ph. D., Associate in Anatomy.

Frank R. Smith, M. D,, Instructor in Medicine.

George W. Dobbin, M. D., Assistant in Obstetrics.

Walter Jones, Ph. D., Assistant in Physiological Chemistry.

Adolph G. Hoen, M. D., Instructor in Photo-Micrography.

Sydney M. Cone, M. D., Assistant in Surgical Pathology,

Louis E. Livingood, M. D., Assistant in Pathology.

Henry Barton Jacobs, M. D., Instructor in Medicine.

Charles R. Bardeen, M. D., Assistant in Anatomy.

Stewart Paton, M. D., Assistant in Nervous Diseases.

Norman McL. Harris, M. B., Assistant in Pathology,

Harvey W. Cushing, M. D., Assistant in Surgery.

J. M. Lazeab, M. D., Assistant in Clinical Microscopy,

J. L. Walz, Ph. G., Assistant in Pharmacy.


GENERAL STATEMENT.

The Medical Department of the Johns Hopkins University was opened for the instruction of students October, 1803. This School of Medicine is an integral and coordinate part of the Johns Hopkins Universit}', and it also derives great advantages from its close affiliation with the Johns Hopkins Hospital.

The required period of study for the degree of Doctor of Medicine is four years. The academic year begins on the first of October and ends the middle of June, with short recesses at Christmas and Easter.

Men and women are admitted upon the same terms.

In the methods of instruction especial emphasis is laid upon practical work in the Laboratories and in the Dispensary and Wards of the Hospital. While the aim of the School is primarily to train practitioners of medicine and surgery, it is recognized that the medical art should rest upon a suitable preliminary education and upon thorough training in the medical sciences. The first two years of the course are devoted mainly to practical work, combined with demonstrations, recitations and, when deemed necessary, lectures, in the Laboratories of Anatomy, Physiology, Physiological Chemistry, Pharmacology and Toxicology, Pathology and Bacteriology. During the last two years the student is given abundant opportunity for the personal study of cases of disease, his time being spent largely in the Hospital Wards and Dispensary and in the Clinical Laboratories. Especially advantageous for thorough clinical training are the arrangements by which the students, divided into groups, engage in practical work in the Dispensary, and throughout the fourth year serve as clinical clerks and surgical dressers in the wards of the Hospital.

REQUIREMENTS FOR ADMISSION.

As candidates for the degree of Doctor of Medicine the school receives :

1. Those who have satisfactorily completed the Chemical-Biological course which leads to the A. B. degree in this university.

3. Graduates of approved colleges or scientific schools who can furnish evidence : (a) That they have acquaintance with Latin and a good reading knowledge of French and German ; (ft) That they have such knowledge of physics, chemisti'y, and biology as is imparted by the regular minor courses given in these subjects in this university.

The phrase "a minor course," as here employed, means a course that requires a year for its completion. In physics, four class-room exercises and three hours a week in the laboratory are required; in chemistry and biology, four class-room exercises and five hours a week in the laboratory in each subject.

3. Those who give evidence by examination that they possess the general education implied by a degree in arts or in science from an approved college or scientific school, and the knowledge of French, German, Latin, iihysics, chemistry, and biology above indicated.

Applicants for admission will receive blanks to be filled out relating t p their previous courses of study.

They are required to furuish certificates from officers of the colleges or scientific schools where they have studied, as to the courses pursued in physics, chemistry, and biology. If such certificates are satisfactory, no i xamination in these subjects will be required from those who possess a degree in arts or science from an approved college or scientific school.

Candidates who have not received a degree in arts or in science from an approved college or scientific school, will be required (1) to pass, at the beginning of the session in October, the matriculation examination for admission to the collegiate department of the Johns Hopkins University, (2) then to pass examinations equivalent to those taken by students completing the Chemical-Biological course which leads to the A. B. degree in this University, and (3) to furnish satisfactory certificates that they have had the requisite laboratory ti'aining as specified above. It is expected that only in very rare instauces will applicants who do not possess a degree in arts or science be able to meet these requirements for admission.

Hearers and special workers, not candidates for a degree, will be received at the discretion of the Faculty.

ADMISSION TO ADVANCED STANDING. ; ,

Applicants for ailinlsslon to advanced standing must turnish evidence II) that the foregolug terms of admission as regards prellmluary training have been fulOUed, 1 (2) that courses eqiilvaleut In kind and amount to those given here, preceding that ye.ir of the course tor admission to which application Is made, have been satisfactorily ' completed, and (3| must pass examinations at the beginning of the ses.slou In October In all the subjects that have been already pursued by the class to which admission Is sought. Certificates of standing elsewhere cannot be accepted in place of these exainlnationa.

SPECIAL COURSES FOR GRADUATES IN MEDICINE.

Since the opening of the Johns Hopkius Hospital in 1880, courses of instruction have been offered to graduates in medicine. The attendance upon these courses has steadily increased with each succeeding year and indicates gratifying appreciation of the special advantages here afl'orded. With the completed organization of the Medical School, it was found necessary to give the courses intended especially for physicians at a later period of the academic year than that hitherto selected. It is, however, believed that the period now chosen for this purpose is more convenient for the majority of those desiring to take the courses than the former one. The special courses of instruction for graduates in medicine are now given annually during the months of May and June. During April there is a preliminary course in Normal Histology. These courses arc in Pathology, Bacteriology, Clinical Microscopy, General Medicine, Surgery, Gynecology, Dermatology, Diseases of Children, Diseases of the Nervous System, Genito-Urinary Diseases, Laryngology and Rhinology, and Ophthalmology and Otology. The instruction is intended to meet the requirements of practitioners of medicine, and is almost wholly of a practical character. It includes laboratory courses, demonstrations, beside teaching, and clinical instruction in the wards, dispensary, amphitheatre, and operating rooms of the Hospital. These courses are open to those who have taken a medical degree and who give evidence satisfactory to the several instructors that they are prepared to profit by the opportunities here offered. The ntimber of students who can be accommodated in some of the practical courses is necessarily limited. For these the places are assigned according to the date of application.

The Annual Announcement and Catalogue will be sent upon application. Inquiries should be addressed to the

KEGISTR.\R OF THE JOHNS HOPKINS MEDICAL SCHOOL, BALTIMORE.


The Johns Hopkins Hospital BiiJIrtins fire issued monthly. They arc printed by THE FRIEDENWALD CO., Baltimore. Single coplet may he procured from Messrs. GUSHING <f CO. and the BALTIMORE NEWS COMPANY, Baltimore. SubsaHptions, $1.00 a vear, may be addressed to the publishers, THE JOHNS HOPKINS PRESS, BALTIMORE; sinyle eopie^ uHll be sent by mail for fifteen cents each.


BULLETIN


OF


THE JOHNS HOPKINS HOSPITAL.


Vol. IX.- No. 83.]


BALTIMORE. FEBRUARY, 1898.




co:N"TEisrTS


Inflated Rubber Cylinders for Circular Suture of the Intestine. By W. S. Halsted, M. D., - - - 25

Cerebro-Spinal Meningitis. By W. T. Councilman, M. D., - 27 The Diaphragm Phenomenon— The So-called Litten's Sign.


By NoEMAN B. GwYN, M.B.,


35


PAGE.

Proceedings of Societies :

Hospital Medical Society, - - - ZS

Cases of Aneurism [Dr. Hunner] ;— Diabetes in the Negro [Dr. Pancoa.st] ; Exhibition of Specimen of Round Ulcer of the Stomach. Erosion of Gastric Artery ; Post-mortem Perforation [Dr. Flexner].

Notes on New Books, 42

Books Received, ---------- 44


INFLATED RUBBER CYLINDERS FOR CIRCULAR SUTURE OF THE INTESTINE.*


By W. S. Halsted, M. D., Professor of Surgery in the Johns Hopkins University.


Until ten years ago every oue who had written on the subject of intestinal suture believed that the Lembert stitches, which were then almost universally used in circular and other sutures of the intestine, included only the jjeritoneal coat of the intestine ; and many surgeons evidently still believe this. The notions of Jobert and Lembert as to the structure of the intestinal wall were still accepted by all surgeons. The submucous coat of the intestine, the coat which, I am convinced, should most concern the surgeon when he is sewing the intestine, was ignored or unknown. In my first article on suture of the intestinef in 1887 I quoted from MadelungJ as follows: " The needle now penetrates in the usual manner the two ends of the intestine, passing between serosa and muscularis"; and from Reichel,§ who insists upon the " accurate adaptation of the two edges of the wound, particularly of the two serous coats," and having described the mannerof taking the first row of stitches, continues, "over this then comes the external suture, which includes only the serosa." Maydl, Kocher, Czerny and others were quoted to show that the submucous coat had not been recognized, and how universal was the opin


Remarks before the Johns Hopkins Hospital Medical Society, December 13, 1897.

t Halsted: Circular Suture of the Intestine. An Experimental Stuily. Am. Jour. Jled. Sciences, October, 18S7.

X Madelung : Arch. f. klin. Chirurgie, Bd. xxvii, p. 321.

§Reichel: DeutscheZeitschr.f. Chirurgie, Bd. xiv, pp. 268 and 270.


ion that intestinal suture should be performed by stitches which included only the peritoneal coat. When we know that the wall of the intestine must be magnified to a thickness of 4 cm. to enable us to represent the peritoneal coat by a fine pencil-stroke, we find it hard to understand that surgeons should ever have supposed that they were including nothing but peritoneum in their stitches. Hardly less remarkable is the fact that the intestinal wall had, for the surgeon, only three coats : the serous, muscular, and mucous coats. Not only were the qualities of the submucosa unknown to surgeons, it was also an unknown quantity. Only five years ago Schimmelbusch,* describing with some detail the manufacture of the so-called catgut, tells us that it is made from the longitudinal muscular coat. He says, " If the intestine be laid ou a towel and scraped with a dull instrument like the back of a knife, the muck (' Schmutz '), so called by the artisans, is removed. This is nothing else than the mucous membrane of the gut. In the same manner the circular muscular coat is rubbed off, so that only the very thin tube composed of longitudinal muscle-fibres remains, an intact, very delicate and pipelike structure which may be distended with air. The threads are manufactured from this by twisting, and conformably to the thickness desired, either the entire tube or only strips of


Schimmelbusch: Anleitung zur aseptischen Wundbehandlung Berlin, 1892, p. 104.


20


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 83.


it are twisted together like heuiiieu cords." The muscular pipe referred to is, of course, the tube of the submucosa, the sausage-skiu, etc.

The following suggestions, emphasized among others, in my article on intestinal anastomosis,* are equally relevant to circular suture of the intestine :

"1. It is bad surgery to employ stitches which enter the lumen of the intestine.

" 2. It is impossible to suture the serosa alone.

"3. It is impossible to suture unfailingly the serosa and niuscularis alone, unless one is familiar with the resistance offered to the needle by the submucous coat of the intestine; furthermore, stitches which include nothing but the serous and muscular coats tear out easily and are not to be trusted.

"4. Each stitch should include a bit of the submucosa. A fine thread of this coat is much stronger than a considerable shred of the entire thickness of the serosa and muscularis. It is not difficult' to familiarize one's self with the resistance offered to the needle by the submucosa, and with a very little practice one learns to include a bit of this coat in each stitch.

" 5. The mattress-stitches are to be preferred to Lembert's, because one row of them is siifficient, because they tear out less easily, oppose larger surfaces and more evenly, and constrict the tissues less than the Lembert stitches do."

6. lu circular suture of the intestine, only one row of stitches should be taken, and the entire row should be applied before a single stitch is tied ; othej-wise it is impossible to preserve a straight line in the taking of the stitches, and the stitches taken last may be never so much farther from the cut edge than those taken first, and the flange turned in may be so broad as to occlude the intestine's lumen.

7. Before the intestine is resected, its blood-supply should be most carefully studied, with reference not only to the placing of ligatures, but also of the stitches, and the stitches should be so placed that the circulation, up to the very edge of the parts to be sewed, shall be as perfect as possible.

The results obtained by adhering strictly to the foregoing rules have been so perfectf that we have employed no other methods in our practice.

Edmunds aud Ballance in their valuable coutributionj to intestinal surgery, give the results of their measurements to determine the relative thickness of the submucous and muscular coats in the dog and in man. They state that the muscular coat is very much thicker in the dog than in man, but that the submucous coat is somewhat thicker in man than in the dog, and they too find it perfectly feasible to engage a thread of the submucosa in each stitch without perforating the lumen of the intestine.


Halsted : I otestinal Anastomosis. Demonstration at a meeting of the Johns Hopkins Hospital Meiiical Society, December 1, 1890. Johns Hopkins Hospital Bulletin, January, 1891.

fAmer. Journ. Med. Sciences, October. 1887.

t W. Edmunds and Charles A. Ballance: Observations and Experiments on Intestinal and Gastro-intestinal Anastomosis. Medico-Chirurg. Trans,, Vol. 78. London, 1S9G.


The objection to Neuber's* decalcified bone-bobbins, Senn's decalcified bone-plates, and Murphy's button, probably the best of the mechanical aids to intestinal suture, I will not dwell upon at this time. The method of each of these surgeons has its advantages, particularly in the hands of those who have not practised the intestinal sutures on animals.

I believe that the license to practice general surgery should be withheld from those who have not practiced on animals the operations for circular suture of the intestine and intestinal anastomosis.

Not so very long ago a surgeon requested me to assist him to perform a circular suture of the intestine (end to end anastomosis) upon one of his patients. He readily consented to practice the ojjeration upon dogs. At first his dogs died. He finally succeeded in saving more than 50 per cent, of the dogs operated upon. The operation upon his patient required five hours, but was successful. It is not difficult to predict what the result would have been if the practice on dogs had been omitted.

Experts in intestinal surgery, almost without exception, prefer to jserform circular suture of the intestine without the use of mechanical devices.

But my operation was not by any means a satisfactory one, notwithstanding the very perfect results which attended its employment in the bands of others as well as myself.

The disadvantages of my original method aud of all similar methods (methods without mechanical aids) were as follows:

1. They required about twenty minutes to perform the operation.

2. One or two assistants at the wound were indispensable.

3. Clamps or the fingers of an additional assistant were necessary to prevent the escape of intestinal contents.

4. The vermicular action of the intestine (particularly in dogs) was a great annoyance, for it prevented an accurate disposition of the stitches; stitches applied as near together as possible during intestinal contraction might be too far apart in the stage of relaxation.

5. If the j)ieces of intestine to be united were not of the same size their adjustment might be very difficult.

6. The rolling out of the cut edges of the intestine prevented in places recognition of the precise edges, and hence


A few weeks ago Dr. ^Mitchell discovered in the Medical and Surgical Iieporter for July, 1S96, a description b}- Dr. A. J. Downes, of collapsible rubber bobbins for all forms of intestinal approximation. These bobbins resemble Neuber's bobbins very closely and were designed with the same end in view, viz. to accommodate the inverted ends in circular suture of the intestine. My rubber cylinders were made in June, 1S97, and were suggested to me by the success attending the employment, experimentally, of aluminum rods in suture of the common bile-duct. I intend to describe these rods at another time. Dr. Downes' bobbins have spherical ends, which are filled with water. When a larger is to be sutured, end to end, to a smaller intestine he uses a bobbin especially designed for the purpose, with a large sphere at one end and a small sphere at the other end of the connecting shank. I should suppose that this modification of the bobbin would defeat the very end for which it was constructed.


Presection-siitches —Left.


Prese^tioQ-stikhes — Right.



Presection-siitches.



The Johns Hopkins Hospital Billetix No. 83. See page



FIG. 3



FIG.



FIG. 5



FIG. 6.



FIG. 7.



The Johns Hoprivs Hn


February, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


27


the operator might not know just how far from the edge he was phicing his stitches nor just how much intestine he was turning in.

7. The handling of the intestine by assistants who act as clamps or who hold parts in place during the stitching must be injurious to the tissues and predispose to infection.

Every one of these objections is disposed of by the employment of the rubber cylinders in the manner indicated in the plates. The drawings are so excellent and illustrate the method so graphically and accurately that a description of the procedure is almost superfluous.

Figs. 1 and 3 show the presection-stitches applied. It is immaterial whether these stitches perforate the wall of the intestine or not, for they are cast off eventually into the bowel. The method of ligating the mesenteric vessels is also accurately shown in Figs. 1 and 2, which were drawn from life. The intestine should be divided carefully with scissoi-s as close to the presection-stitches as possible. No visible blood-vessels are occluded by these stitches.

Fig. 3. The rubber cylinder inflated. For the human small intestine the diameter of the cylinder is from li to IJ inches. It would be better to have cylinders larger than necessary rather than too small.

In Fig. 4 two of the presection-stitches have been tied, and the collapsed rubber cylinder is being pushed into the bowel with a forceps.

Fig. 5. The three presection-stitches have been tied. They are supplemented by a fourth stitch, b, which is removed later to facilitate the withdrawal of the bag. The bag has been inflated with air by the syringe. Water might, of course, be used instead of air ; but a bag distended with air would, perhaps, more quickly reveal a prick from a faulty stitch than a bag distended with water.

The stitch a (Fig. 6 and also Figs. 5, 7 and 8) is the first and most important of the mattress or permanent stitches. The submucosa is picked up four times by this as by all the mattress stitches, and the mesentery is twice perforated by it (Fig. 6). This stitch insures the proper turning in of the mesenteric border. It was devised by Drs. Mitchell and Huuner, and I shall call it the Mitchell-Hunner stitch.

Fig. 7. The bag is still distended, and all of the mattress stitches have been placed. From seven to nine of these


stitches suflBce in operations upon the small intestine of the dog, and from ten to twelve in operations upon the human subject. The first stitch to be drawn home and tied is a. The mesenteric border is turned in by it infallibly. Not.a single visible vessel is occluded by the stitches (Figs. 7 and 8). On the right side the stitches pass under one vessel and over another, without interfering with either, and on the left side a vessel lies under the stitches, uninjured.

Fig. 8. Two mattress stitches drawn aside on a hook ; the temporary stitch has been removed and the collapsed bag is being withdrawn.

Fig. 9. The circular suture is completed; the slit in the mesentery is being sewed in such a way that its circulation is not interfered with.

Advantages of the Inflated Eubbeu Cylinder in Circular Suture of the Intestine.

1. The vermicular action of the bowel is arrested over the bag, and the stitches can, consequently, be placed at regular and proper intervals.

2. The distended bag unrolls and spreads out to a fine edge the everted raw edge of the intestine (Fig. 4), and enables the operator to place the stitches with great precision at the desired distance from this edge.

3. If distended intestine is to be sutured to collapsed intestine (in strangulated hei-nia, ilius, etc.), or intestine of larger to intestine of smaller lumen (jejunum to ileum, duodenum to esophageal end of the stomach, etc.), the smaller may easily be expanded to fit the larger piece.*

4. Very little handling of the intestine itself by the operator is necessary. The tube from bag to syringe is used as a handle to rotate and elevate the parts to be united.

5. The cylinder takes the place of at least two assistants. The operation could readily be performed without an assistant.

6. It prevents escape of intestinal contents and hence dispenses with the injurious clamps or the fingers of assistants.

7. The entire operation, exclusive of suture of the abdominal wall, can be performed on dogs in five or six minutes and probably in less time.

The results should, I believe, be better than by any method hitherto devised.


CEREBRO-SPINAL MENINGlTIS.t

By W. T. Councilman, M. D., Harvard University.


Cerebro-spinal meningitis has prevailed in Boston iu the form of an epidemic during the past winter and spring. One hundred and eleven cases of the disease were treated in the Boston City Hospital, the Massachusetts General Hospital, and the Children's Hospital, between June, 1896, and October 1, 1897. At the time of the appearance of the first case in June there had been no case of this form of meningitis in the hospitals for a number of years. The first case occurred in June, 1896, one in the following September, and three cases in December. In 1897 there was one case in January, ten in


February, 33 in March, 39 in April, 21 in May, 14 in June,


I have recently had occasion to unite a distended paper-thin jejunum to a collapsed ileum. The rubber cylinder worked like a charm. The patient, a very old and feeble woman, convalesced without interruption for 16 days. She died quite suddenly from peritonitis due to complications which cannot at this time be discussed. So far as the stitching was concerned the result was perfectly satisfactory.

t Presented to the Johns Hopkins Medical Society, November 15, 1897.


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7 iu July, aud 3 in September. At the present time the disease contiunes to prevail aud many more cases have been seen this autumn than in the autumn of 189G.

The disease has been epidemic iu Boston a number of times. The first appearance of the disease iu Massachusetts was in 180G, one year after its apjjearance in Geneva in 1805. It has been generally supposed that this was its first appearance, but it is more than possible that many of the early epidemics were this disease, although iu the absence of clear clinical records aud post-mortem examinations it is impossible to be certain of this. The first epidemic of the disease prevailed in the New England States and lasted until 1816. There was another epidemic between 1864 aud 1860, and still another in 1874.

A table of the ages of the 111 cases shows that the disease prevailed principally in young adults. Only oue case was seen iu a child under one year of age. A table of ages of our 111 cases agrees almost exactly with the table of the same number of cases given by Leichtenstern in his report of the epidemic in Cologne in 1885. A great deal of stress should be laid on the rarity not only of epidemic meningitis but of all forms of meningitis in children under one year of age. Nothing more clearly shows the inaccuracy of general mortality tables than the ages given iu the cases of meningitis. In nearly all of these tables a large percentage of cases are attributed to children under one year of age. In looking over these mortality tables one receives the impression that errors iu the diagnosis of meningitis are not uncommon.

The mortality of the 111 cases was 68 per cent., which is comparatively high. Hirsch gives the mortality as varying from 20 to 75 per cent. The greatest actual and relative mortality was found iu the cases iu April aud May. Most of the epidemics of cerebro-spinal meningitis reported in the literature have appeared in the late winter and spring, although there have been a number of exceptious to this general rule. A map of the city giving the distribution of the cases shows them to have been pretty well scattered over the city, there being only two localities where they were esjjecially numerous. Generally but a single case came from the same family, although there were several exceptions to this, in oue case three coming from the same family, and in another two.

A great deal of interest attaches to sporadic cases of cerebro-spinal meningitis. We can only be certain that these sporadic cases are the same as the epidemic form when the organism associated with the epidemic form has been found in them. So far we have only been able to find one instance in which the diplococcus intracellularis of Weichselbaum, the organism of epidemic cerebro-spinal meningitis, was found in a sporadic case. In most of the sporadic cases no cultures have beeu made, but so far as we can judge from the clinical and anatomical descriptions many of these represented the true epidemic form. Almost all observers who have been acquainted with the epidemic form of the disease speak of the presence of spoi-adic cases occurring both before and after the epidemics. The single cases seen here in June and September may be considered as sporadic. We think it maybe generally assumed that cases of sporadic meningitis which recover are of the epidemic variety. So far we have not beeu able to find


a case which from its association with other conditions could be regarded as dne to the pneumococcus or streptococcus which has recovered. Certainty with regard to the sporadic cases can only be known by careful anatomical and bacteriological investigation. The bacteriological examination of the fluid removed by spinal puncture is of special importauce.

The first description of an organism which might be regarded as the diplococcus intracellularis was given by Leichtenstern in 1885. He found in the exudation iu the meninges a few diplococci, sometimes single, sometimes in group?, similar in arrangement togonococci, enclosed iu white corjiuscles. Schwabach found diplococci in the pus cells in a case of otitis media secondary to meningitis.

Most of the bacteriological examinations made on cases of meningitis up to the past few years have seemed to show that the pueumococcus was the cause both of the epidemic aud most of the sporadic cases. This was probably due to the fact that the pueumococcus is very frequently found in sporadic meningitis, aud in the ejiideniic form the diplococci may either be mistaken for the pueumococci, or an accompanying pneumococcus infection mask the diplococci.

The first definite description of this organism was given by Weichselbaum in 1887. The organism was described by him as a diplococcus which in the lesions is found almost solely vvithiu the cells. In cultures the organisms grow singly, in pairs and in tetrads. Both in cultures and in the tissue they were decolorized by Gram. There were few confirmations of the discovery of Weichselbaum until 1895, when Jiiger found the same organism in 13 cases of epidemic cerebro-spinal meningitis which occurred iu the garrison at Stuttgart. Jiiger's description added but little to the previous description of Weichselbaum.

Post-mortem examinations were made iu 35 of the 111 cases, aud the diplococcus intracellularis was found in cultures, on microscopic examination of the exudation, or in sections of the tissues, iu all but four cases. In most of the cases they were found iu all three methods of examination.

In one of the four negative cases they had previously been found iu the fluid withdrawn during life by spinal puncture. Two of the other cases were very chronic, aud the fourth was a chronic case of mixed infection with tuberculosis. In a certain number of cases cultures failed to give the organisms, | although they were abundantly present, as shown by cover-slip B examination of the meninges and microscopic sections. The organism is very difficult to grow, and from a number of tubes inoculated, in many cases only one or two tubes would show a | few single colonies. We have found the Loeftler's blood serum | mixture best adapted for its growth. Hud agar been used for the primary cultures there is no doubt that iu nuiuy cases no growth would have beeu obtained. There is considerable irregularity in staining, some organisms being brightly stained, others more faintly. Sometimes these differences in staining tl are seen in a single pair of organisms, one being more brightly I stained than the other. There may also be considerable variation in size, and the larger organisms stain more imperfectly. In these swollen organisms there is often a brightly stained point iu the centre, while the remainder of the cell is but slightly colored. This condition may have been mistaken by


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Jiiger for a capsule around the organism. These variations in size aad staining appear to be due to degeneration and are more common in old than in fresh cultures. In the tissues the diplococcus is almost strictly confined to the interior of polyuuclear leucocytes. It has no definite position in the cell and is never found in the nucleus. The number of organisms found in the cells varied from a single pair to such numbers that the nuclei of the cell were frequently obscured. In no case were the diplococci found except in connection with the lesions of the disease. So far as could be learned from cultures of the blood, liver, spleen and kidneys, the organism does not produce septicffimia.

Lumbar puncture was iierformed in 55 cases, and in a few cases several punctures were made in the same individual. In the fluid obtained diplococci were found on microscopic examination or in cultures in 38 cases; in 17 of the cases they were absent. The average duration of time from the onset of the disease before spinal puncture was made was 7 days in the positive cases and 17 days in the negative. The longest time after onset in which a positive result was obtained was 29 days.

The character of the fluid obtained by spinal puncture varied greatly. In some cases, even when diplococci were found in it, it was almost clear, showing only a slight turbidity when examined against a dark background. In most cases where the puncture was made early in the disease the fluid was turbid, and in 3-1 hours a large amount of sediment formed at the bottom of the tube. The amount of fibrin in the exudation varied greatly. In a few cases so much was present that the fluid coagulated and the tube could be inverted. In one chronic case of marked intermittent character three punctures were made, one before, one after and one during the exacerbation. In the fluid obtained before and after the exacerbation no diplococci were found. The fluid obtained during the exacerbation was more cloudy and contained diplococci. This would seem to show that in the intermittent cases the exacerbations are due either to a fresh, growth of the organisms or to a fresh invasion of the j^arts which had been previously comparatively free. In the fluid obtained in the early punctures almost the only cellular elements were polynuclear leucocytes. Later, large epithelioid cells and lymphoid cells were found among the pus cells. No ill effects were seen from spinal puncture.

Too much cannot be said of the importance of spinal puncture in making the diagnosis of the disease. As a diagnostic measure it ranks in value with the examination of the sputum. A microscopical and bacteriological examination of the fluid should always be obtained in order to ascertain what organism is present. In no other way will it be possible to arrive at certainty with regard to the nature of the sporadic cases.

In all of the post mortem examinations careful microscopic examination was made of the tissues. For general histological purposes portions of the brain and cord and other organs were hardened both in Zenker's fluid and in alcohol. For the study of nerve degeneration small pieces of tissue were hardened in Jliiller's fluid, or in formaldehyde followed by Miiller's fluid, preparatory to staining by Marchi's method. The amount of the exudation varied in the acute and chronic cases.


In the most chronic cases there was general thickening of the meninges and only small masses of degenerated cells were found in the place of the former exudation. In cases dying two or three days after the onset but a slight amount of purulent exudation was found. The amount of fibrin in the exudation varied and was never so great as is found in cases of meningitis due to the pneumococcus.

In addition to the acute inflammation found in the meninges of the brain and cord, lesions of the tissue were found. In places there was a circumscribed infiltration of the tissue with pus cells which extended from the infiltration in the meninges. The vessels were dilated, and the spaces around the vessels filled with pus cells which extended into the surrounding tissue. In two cases there was extensive softening with purulent infiltration and hemorrhage in the cortex of the cerebellum, l^esions were foiind in both the white and gray matter, consisting principally in foci of fine hemorrhages with some purulent infiltration. There was a definite increase in the cells of the neuroglia both in connection with the acute lesions and at a distance from them. The neuroglia cells were swollen, their nuclei large and vesicular and contained much chromatin. Around these large nuclei there was a faintly stained irregular mass of granular protoplasm. Many of the cells contained two nuclei, and in places thei'e were groups of four or more nuclei with a considerable amount of protoplasm around them. In all of these places nuclear figures were found. They presented the same form as other nuclei, and in some cases both spindles and centrasomes were distinguished. In addition to the changes in the neuroglia, proliferation was found in the connective tissue of the brain and cord around the blood-vessels. The inflammation of the meninges extended along the cranial nerves and along the anterior and posterior spinal nerve roots.

The cranial nerves most affected were the 2nd, 5th and 8th. The examination of the eyes in two cases showed a choroidoiritis which was due to a direct extension along the sheath of the optic nerve. Diplococci were found here and in the purulent exudation within the eye. The same thing was true of the ear. Secondary otitis media was found in a number of cases, some of which recovered. In all of these nuntliers of diplococci were found in the pus.

The nasal secretion in 19 of our cases was examined, by means of cover-glass preparations, the material being taken from high up in the nasal cavities with the aid of a platinum loop. Of the 19 cases 10 showed the presence in the nasal secretion of diplococci, decolorized by Gram's method and identical in morphology with the diplococcus from the brain. Similar Gram decolorizing diplococci were also found within leucocytes in the nasal secretion of two cases of convalescing meningitis. Attempts were made to isolate this organism in cultures in 10 cases in which microscopic examination showed them to be present, but without success.

With reference to the occurrence of this organism in the nasal secretion of patients not affected with meningitis twelve hospital patients chosen at random were examined. In the nasal secretions of two among these twelve, diplococci like the preceding were found by cover-glass examination. They were not cultivated. From the results of these examinations it


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would seem either that the diplococcus intracellularis may be met with in the nasal secretion of patients who have not meningitis, or that other species of diplococci identical with this morphologically and in staining peculiarities may be found.

It is greatly to be regretted that it was not possible to obtain cultures of the organisms from this locality, for their identity can only be established by this method combined with inoculations. At any rate it is impossible to regard the presence of diplococci in the nose, decolorizing by the Gram stain, as of much diagnostic value as claimed by Scherrer.

Degenerations were shown by the Marchi method in the nerves of both the brain and cord. The spinal ganglia were affected iu all cases, and in four cases in which the Gasserian ganglion was examined an acute inflammation, sometimes to an intense degree, was found in this. Degeneration was shown by the Nissl method in the ganglion cells of the brain and cord. The studies of this degeneration have not been completed.

The condition of the lung is interesting on account of the relation which has very generally been supposed to exist between epidemic cerebro-spinal meningitis and pneumonia. In 13 cases there was merely congestion with more or less adema. In 7 cases there was broncho-pneumonia, more marked in the lower posterior portion of the lung. In two cases there was characteristic croupous pneumonia ; one in the stage of red hepatization bordering on gray. Pueumococci were found in these cases in cultures and on microscopic examination. In 8 cases pneumonia due to the diplococcus intracellularis was found. Nearly all of these cases came from the last part of the epidemic. It is very possible that some of the earlier cases in which the lesions were described simply as broncho-pneumonia, were really due to the diplococcus intracellularis.

These lesions consisted microscopically of areas of consolidation in various parts of the lung, more particularly in the lower lobe, and they were most numerous beneath the pleural surface. The foci varied in size from a pin's head up to that of a pea, and on section some of them resembled small hemorrhages in the tissue. In other cases the periphery of the area was distinctly hemorrhagic and the centre opaque and yellowish. In one case the consolidation of the lung was so extensive that it might easily have been regarded as croupous pneumonia, particularly as the pleura over it was covered with a definite fibrinous exudation. On section this large area was composed of a number of irregular grayish foci, with softened centres, and with hemorrhagic and cedematous tissue between them. The lung tissue in the yellowish centres was frequently broken down and pus oozed from it. On microscopical examination the central areas showed in most cases a purulent infiltration of the tissue, with beginning abscess formation. The alveoli contained large numbers of pus cells ; their walls were found infiltrated with pus and iu places entirely broken down. The foci of consolidation did not appear to be bronchial in origin. The bronchi in the vicinity often contained pus cells, but their walls were not infiltrated.

The duration of the disease in the cases in which diplococcus pneumonia was found was: iu 2 cases, 3 days; in 2


cases, 2 days ; in 2 cases, 5 days ; in 1 case, 9 days ; in 1 case, 23 days, and in 1 case, 74 days. It will be seen from this that the lung complications due to the pneumococcus can take place in almost any period of the disease. In the case of 74 days' duration the lesions in the brain and cord could be regarded as almost completely healed and the lesions in the lungs were acute. In one case in which the apparent history of the disease was of only two days' duration, the lesions were so advanced that they seemed possibly to antedate those of the brain, providing the history as given by the patient's relatives was correct. Immense numbers of diplococci were found in the pus cells in the lung. They were most numerous in the cells in the centres of the foci where softening was taking place. In the centre of one of the foci a small branch of the pulmonary artery occluded by a thrombus formed of pus cells containing large numbers of diplococci was found. It seems probable that this thrombus may have come as an embolus from the meninges and may have produced an infection of the surrounding tissue.

There was great variation in the size of the spleen. In general it was not much enlarged and was probably smaller than in most of the acute infectious diseases. In only three cases it was found considerably enlarged. The average weight in the adult cases was 163 grms. The lymphatic glands in the uncomplicated cases were never found enlarged.

The liver presented no change beyond acute degeneration. In two cases extensive acute lesions were found in the kidneys. In one of these the acute lesions had no connection with the meningitis, but were due to an accompanying infection with diphtheria. In the other case there was an acute hemorrhagic nephritis. In this there was an accompanying acute pericarditis, the organism causing which could not be ascertained. The only lesions found in the kidney which could be properly attributed to the meningitis were acute degenerative lesions which were always present.

The intestinal canal was found normal iu every case.

In two cases there was acute pericarditis, accompanied in one case with foci of necrosis and jjuruleut infiltration of the myocardium. In several other cases in which the myocardium was examined histologically it was found normal.

Lesions of the skin were found in but one of the cases on which an autopsy was made. In this case, over upper and lower extremities, chest and abdomen, there were numerous small dark purplish spots in the skin, varying in size from a pin's head up to that of a pea. On microscopic examination of these areas there was intense congestion and dilatation of the blood-vessels of the skin, with small and diffuse hemorrhages immediately beneath the epithelium. In some of the larger areas there was some purulent infiltration in the centre. No diplococci were found in these lesions.

There is no doubt that acute meningitis may be produced by the entrance into the meninges of a number of infectious organisms. These forms are rarely primary. The organisms enter the meninges either by the formation of a communication between the meninges and some cavity where they may be accidentally present (as in the middle ear and nose), or by the extension to the meninges of an infectious process in the vicinity (mastoiditis, erysipelas), or they are brought to the


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meuinges by the blood from some other focus iu the body (pneumonia, endocarditis). In tuberculous meningitis we have never found a single case in which the lesions iu the meuinges could be regarded as primary. We believe that all infections of the meninges other than the diplococcus intracellularis are fatal, but this cau only be determined by microscopic and bacteriological examination of the exudation obtained during life by spinal puncture. If tubercle bacilli, pneumococci or streptococci are found with the evidences of meningitis iu a case which recovers, it would settle the point; clinical evidence, without spinal puncture, will not.

Discussion.

Dr. Welch. — It is a great pleasure to have Dr. Councilman with us upon this occasion, and we are all very much indebted to him for his instructive presentation of this subject and the report of his extensive and valuable studies. As he has not dwelt upon the historical development of our knowledge concerning the meningococcus iutracellularis, I maybe permitted to say a few words about the steps leading to the recognition of this organism as the cause of epidemic cerebro-spiual meningitis.

It is not a little remarkable that the organism first described by Weichselbaum in 1887 as the diplococcus iutracellularis meningitidis did not come to be accepted as associated especially with epidemic cerebro-spinal meningitis until the publication of Jaeger's article iu 1895. This was not due to an imperfect or faulty description of this micrococcus by Weichselbaum, for its essential morphological and biological characters were fully and correctly described by him. Weichselbaum, iu the article referred to, reported the results of his bacteriological examination of eight cases of cerebro-spiual meningitis not secondary to pneumonia. All of these cases he regarded as sporadic forms of meningitis. In two he found the lanceolate pneumococcus and in the remainiug six the diplococcus iutracellularis meningitidis. He concluded that each of these two bacterial species may be the cause of primary acute cerebro-spinal meningitis, but he expressed no definite opinion as to whether either was concerned with epidemic cerebro-spinal meningitis, although he thought it probable that the jjueumococcus might cause epidemic forms of cerebro-spiual meningitis with or without pneumonia. With the exception of the confirmation in 1887 in a single case by Goldschmidt of Weichselbaum's discovery, and of Edler's microscopical examinations in 1888, nothing more is heard of the presence of the meningococcus iutracellularis of Weichselbaum in meningitis until Jaeger's report already mentioned.

During these eight years the results of bacteriological examinations of cases of meningitis were reported by a number of observers. In 60 to 70 per cent, of these cases the pneumococcus was reported as present, and in about 13 per cent, the streptococcus pyogenes. Some of the cases in which the pneumococcus was reported as present were of epidemic cerebrospinal meningitis. The attempts of Bouome and of FoA to separate as distinct varieties or species from the pneumococcus cocci which they found in cerebro-spinal meningitis received merited criticism from Bordoni-Uffreduzzi, who


showed that these organisms were in all probability genuine pneumococci. Bordoni-UfEreduzzi at the same time expressed the opinion that not only Bonome's streptococcus meningitidis and Foa's meningococcus, but also Weichselbaum's diplococcus iutracellularis meningitidis, are varieties of the diplococcus pneumouise. This opinion acquired support as we became familiar with the remarkable variations in all of the characters, morphological, cultviral aud pathogenic, of the pneumococcus. Hence the view came to be generally entertained that, although various species of bacteria may be the cause of cerebro-spiual meningitis, the pneumococcus is the most common cause not only of meningitis secondary to pneumonia but also of primary cerebro-spinal meningitis, including the epidemic form.

The great merit of Jaeger's publication in 1895 lies, not in adding materially to Weichselbaum's description of the meningococcus iutracellularis, but in directing attention to the special association of this coccus with epidemic cerebro-spinal meningitis. He denies any relationshij) between the pneumococcus and this disease. Most of those who have investigated the subject during the two years following the appearance of Jaeger's article have come to the same conclusion, and the confirmation of this view by Dr. Councilman in his report of a larger number of cases of epidemic cerebro-spinal meningitis than have been previously studied bacteriologically by a single observer is an importaut contribution to our knowledge.

The question naturally arises whether those who before Jaeger's publication reported the presence of the j)neumococcus in the exudate of epidemic cerebro-spinal meningitis have all been mistaken in the diagnosis of the organism. As some of these reports are by highly competent bacteriologists, it is difficult to admit this supposition. Several possibilities suggest themselves : (1) It is possible that the meningococcus iutracellularis is not the sole specific cause of epidemic cerebro-spinal meningitis, but that the pneumococcus is likewise the cause of a certain number of cases. (2) There may have been mixed infection or secondary infection with the pneumococcus; the intracellular meningococcus, on account of its scarcity or failure to grow iu the cultures, or absence of pathogenic power by subcutaneous inoculation, being overlooked. (3) It is probable that in some cases at least the intracellular meningococcus has been mistaken for the pneumococcus. Further investigations are needed in order to determine how much value attaches to these various suppositions.

Another question of interest is as to a possible relationship between the meningococcus iutracellularis and the micrococcus lauceolatus, in the sense that the former may be a variety of the latter. All of those who have worked with the meningococcus appear to agree upon the independence of this organism as a bacterial species, and especially upon its separation from the micrococcus lauceolatus. This view seems to me probable. Nevertheless, the great variability of the lanceolate coccus as to form, cultural characteristics and pathogenic properties renders this question still a debatable one, as is shown by the position assumed by Lubarsch in his discussion of the relations of this organism to the streptococcus pyogenes


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on the one hand and to the meningococcns intracellularis on the other hand.*

Baltimore seems to have enjoyed remarkable immunity from epidemic cerebro-spinal meningitis. In New York I used to see every year at least a few sporadic cases of primary cerebrospinal meningitis.

It may not be out of place if I say a word in this connection concerning the disease in horses commonly called cerebrospinal meningitis. Through the kindness of Dr. Clement I have had the opportunity of making autopsies upon horses in Maryland which have died with the symptoms commonly attributed to this disease, and I have been informed by him of his investigations upon the same disease which has prevailed in this State during the past summer and autumn. In none of the cases which we examined was there any meningeal exudate. The disease was not cerebro-spinal meningitis in the anatomical sense, nor were we able to find any lesions competent to explain the symptoms. While I would not be understood to deny the occurrence of genuine cerebro-spinal meningitis in horses, I believe that the disease which usually passes by that name among veterinarians is not a true meningitis. We did not obtain evidence even of a meningitis serosa, as claimed for these cases by Siedamgrotzky and Schlegel.

Dr. Flexner. — One appreciates all the more what the investigations of Dr. Councilman have involved if he has had an opportunity of studying an epidemic of cerebro-spinal meningitis. Many of you will recall that Dr. Barker and myself, through the courtesy of the State Board of Health, were permitted to study an epidemic of this disease which prevailed in the year 1893 at Lonacouing and other places in the George's Creek valley in this State. As Dr. Councilman proceeded to develop the symptomatology and the pathological anatomy of his cases I was impressed more and more with the idea that we had been working with the same disease-process. In one respect only do onr results differ; Dr. Councilman has become convinced through the study of the large material at his command that the causative micro-organism is the meningo-coccus inti-acellularis of Weichselbaum, while we believed that we isolated from our cases the diplococcus pneumoniiE. In regard to this disparity, of which I shall speak more at length, it is worth while noting that Dr. Councilman stated that he did not distinguish the two organisms in his first post-mortem examinations.

The epidemic at Lonaconing was perhaps larger than the one at Boston, but its investigation was much more difficult. Dr. Barker and I spent some days in this place and the adjacent country in which the disease' prevailed, at a time when the epidemic was on the decline. We had therefore to rely for our statistics upon the reports of the local profession scattered over twenty miles of rough mining country. Our conclusions were that there had occurred within this area about 200 cases of cerebro-spinal meningitis and the mortality had been about 48 per cent., a figure somewhat lower than the Boston epidemic and somewhat higher than some of the reported European epidemics.


Lubarsch-Oestertag. Ergebnisse der allg. Pathologie u. path. Anat., 3ter Jahrg. I, p. 169.


Our studies were both clinical and pathological. While we had the opportunity of visiting many cases, we succeeded in obtaining two autojjsies only. These were of great interest to us as they were examples of two different types of the disease. I wish to recall to you briefly these cases.*

Case 1. Girl 9 years of age; died on 3rd day of disease; autopsy two hours post mortem. There were no adhesions between the dura and skull-cap, the dura and pia arachnoid were free from adhesions to each other. The soft meninges were swollen, but no considerable quantity of fluid escaped from them ; they were opaque, especially over the convexity of the brain, and in the depressions between the sulci heavy opaque white streaks and bands were visible. The exudation into the meninges was confined to the convex surface of the brain, the base being free from it ; but the ventricles were dilated and contained an excessive amount of clear serum.

The dura covering the spinal cord, especially in its inferior part, was wide and bulging. On incising it near the middle of the lumbar region about 40 cc. of turbid fluid escaped. In the meshes of the pia arachnoid was an exudate which was not uniformly distributed, but was most abundant posteriorly, and corresponded for the most part with the lower cervical and dorso-lumbar region. The exudate resembled that present in the brain.

The bacteriological examination by means of cover-slips showed the presence of what was regarded as the micrococcus lanceolatus without admixture with any other organism. The micrococci occupied pus cells and were also present in the fluid among the cells.

Case 2. Girl 16 years old; death in third week of disease; autopsy 12 hours after death. The dura was strongly adherent to the skull-cap, and on removing it about 200 cc. of turbid fluid containing white flakes escaped from the posterior fossa. The fluid in the pia over the cortex, which was increased in amount, was turbid. In the membrane covering the pons and upper part of medulla was a firm white deposit which was intimately adherent to the underlying tissues. Over the base, from the pons to the optic chiasm inclusive, there was a turbid fluid exudate. The fourth ventricle and the lateral ventricles contained greenish-yellow, gelatinous pus; indeed the former was completely filled with it. Both the lateral ventricles were dilated, and the choroid plexuses covered with an opaque exudate. A similar exudate extended along the sheath of the auditory nerve into the bony canal. The pia arachnoid, throughout the whole length of the cord on the posterior surface, contained an opaque exudate fully two millimetres in thickness, the exudate on the anterior surface I being less marked. From the pus in the ventricles and from the exudate over the base of the brain diplococci were obtained on cover-slips. The organisms were present in much smaller numbers than in the previous case. I

The cultures made from the brain and other organs did not ' grow. Those made from the first case, which was most promising, included the cerebro-spinal exudate and organs


Ab8tracted from report in American Jourual Jledical Sciences, 1S94.


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generally. Cultures from the exudate were made at once on exposing it by drawing back the dura. Additional cultures were made an hour or so later. It is necessary to state that the second set was made in a carriage-house next a stable in which horses were kept. The first cultures, made at the time of the autopsy, showed a very feeble growth of diplococci ; but on transplantation no further growth could be obtained. All other tubes from the brain or cord showed either no growth or an abundant one, a tolerably coarse bacillus, doubtless a contamination. Culture tubes from the organs remained sterile with the exception of those from the spleen. From this a pure growth was obtained of streptococci. The cultures from the second case could not be made until Baltimore was reached, 14 hours after the autopsy. Various media inoculated from the exudate and solid organs remained without growth ; mice and rabbits were inoculated without effect. In view of the negative results in cultivations and animal experiments, we regarded it as questionable whether the organism found by us in the exudate was really the micrococcus lanceolatus. But as it is regarded as characteristic of the lanceolate diplococci to show a variable vitality and great variation in pathogenic effect on animals, we were therefore the more disposed to consider the bacteria found by us as probably identical with this organism. In interpreting the studies of Dr. Councilman and comj^aring them with those of Dr. Barker and myself, it must be remembered, as Dr. Welch has just pointed out, that it was not until Jaeger's studies, which appeared in 1895, that the meningococcus intracellularis was sharply differentiated from the pneumococcus. There remains, moreover, the disparity in behavior of the bacteria found by us and the organism obtained by Dr. Councilman towards Gram's stain. Kecent studies have shown the Gram's method of staining to be a feeble reed and one perhaps unworthy of the confidence placed in it as a means of differentiation of bacterial forms. All these facts taken together, and especially the histological details of Dr. Councilman's study, which agree so well with our findings, dispose me to the belief that the Lonaconing and Boston epidemics have not improbably been caused by the same micro-organism.

In our studies of the histological changes in the central nervous system. Dr. Barker and myself were impressed with the large phagocytic cells which Dr. Councilman also found, and we regarded them as forming a considerable portion of the exudate in the acute case. The figure No. 3 in the reprint (passed around) which I brought with me will show you the relative size and numbers of these cells in a portion of the exudate in the meninges of case 1. These cells were regarded as being derived by proliferation from the pia mater. In the chronic case the exudate looked more like the caseation of a tuberculous meningitis than an ordinary inflammatory exudate, and the stained preparations showed extensive degeneration of all the morphological elements composing the exudate. We found in our cases a tendency for the exudate to pass along the sheaths of the nerves (optic and auditory ; spinal nerves) leaving the cerebro-spinal cavity, and we attributed the disturbances of sensation in part to the involvement of the posterior roots of the spinal nerves. Dr. Councilman has not mentioned the occurrence of abscesses within


the substance of the brain and spinal cord; we encountered several small accumulations of leucocytes in the spinal cord, and it maybe recalled that Zenker, Klebs and Striimpell have shown that abscesses of comparatively large size may exist.

I have been most interested and instructed by Dr. Councilman's presentation of the subject, and I desire to add to the sentiments already expressed my sense of obligation to him.

Dr. Barker. — I was much impressed with what has been said with reference to the presence in the nose in cerebrospinal meningitis of the organism which gives rise to the disease. It is certainly anatomically proven that relatively free communication exists between the nose and the intracranial cavity, but it is just as reasonable to assume that the organisms pass from the cerebral meninges to the nose as to believe that the path followed is in the opposite direction.

Concerning the lesions in the nervous system Dr. Councilman states that he has found marked alteration in the ganglion cells and in the white matter of the spinal cord and brain. In the report made by Dr. Flexner and myself of the autopsies at Lonaconing, considerable attention was paid to the nerve lesions. Since then better methods of studying alterations in the nerve tissues have been developed. In view of this fact I undertook last year to restudy the spinal cords of our cases, some portions of which had been preserved, and in them it has been possible to make out some interesting changes not referred to in our article. The results were communicated to the Pathological Section of the British Medical Association, held this autumn in Montreal, but it may not be out of place to refer briefly to the main points.

As is now well known, the cells of the anterior horn of the spinal cord, when stained by the method of Nissl, show inside them what appear to be three distinct substances: (1) In the dendrites and cell body (except in the area whence the axone arises) the stainable substance of Nissl, here arranged chiefly in the form of spindle-shaped masses, the latter in turn tending to be arranged in stripe-like rows; (2) the achromatic substance occupying the regions between the Nissl bodies, and constituting the whole of the axis cylinder process and its hillock of origin ; (3) the so-called " pigment " of the anterior horn cells.

In the Lonaconing material, though the tissue was not. perfect for work with Nissl's method, it was easy to make out two distinct types of change. The first, briefly stated, consisted in a disintegration in the stained section of the individual Nissl bodies, especially in those of the dendrites and of the periphery of the cell body. In the second tyjie the anterior horn cell presented an entirely different appearance. Whereas the Nissl bodies at the perijjhery of the cell and in the dendrites were sometimes tolerably well preserved, in the centre of the cell the achromatic substance was entirely broken down, this portion of the cell being either pale in sections stained by Nissl's method, or pervaded by minute dust-like particles of the stainable substance. In addition, the nucleus of the cell was displaced to the periphery, sometimes to such an extent as to cause a distinct bulging at the margin of the cell.

In the light of the more recent work bearing upon the patholoo-y of the nerve cells it is not difficult to bring forward plausible


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explanations of these lesions. The researches of Nissl, Marinesco, Flatau, Liigaro, van Gehuchten and others have demonstrated that in many forms of poisoning the action of the toxic snbstauces upon the cells tends to be exerted chiefly upon the periphery. It is but natural that poisonous substances circulating in the blood and lymph should affect the dendrites and periphery of the cell before leading to alterations in its central portion. My own studies on ricin poisoning and diphtheric intoxication support the observations just mentioned. On the other hand Nissl was the first to call attention to the fact that if a given axis cylinder be severed or seriously injured, the cell body of the neurone to which it belongs undergoes curious and typical alterations, and the nucleus is dislocated from its usual position. Thus if the root of the n. facialis be cut, the cells in the nucleus of origin of the same side situated in the pons undergo the alterations described; the nucleus is displaced to the side of the cell ; the Nissl bodies in the ceil, more particularly in the central regions and especially near the axone hillock, are disintegrated or even wiped out. Nissl further proved that the application of common salt to the nerve trunk without actual section of the fibres would yield the same result. The experiment has been repeated by many neurologists and in the Anatomical Laboratory here by J. Erlanger. Nissl's results have received manifold confirmation.

It is obvious, if you compare the two types of changes which I have described as occurring in the anterior horn cells in cerebro- spinal meningitis, with the two classes of changes mentioned in the bibliography, that there is a striking agreement. The first type corresponds to the primary alteration consequent upon direct insult of the cell bodies and dendrites by a poisonous solution bathing them, while the second type corresponds to the secondary changes occurring in the cell body after insult to its axone at any point between the cell and the peripheral ramifications of the nerve fibre — in other words, to the "reaction at a distance" of Mariuesco.

The first series of lesions, not strongly marked in the specimens, are probably to be accounted for by the slight tox£emia which we may assume accompanies a meningitis ; for although the causative micro-organism does not lead to a severe general .intoxication of the body, at least under ordinary circumstances, there is evidence (from the occurrence of leucocytosis and changes in the urinary secretion) that some poison is absorbed. That the lesions of the first type are so little marked is probably directly attributable to the fact that the disease is relatively non-toxic.

The other lesions, those designated as " secondary," were in contrast with the "primary" or "toxic" lesions very marked in the anterior horns. The explanation is not far to seek. In the Lonaconing cases, and as Dr. Councilman has stated in those coming to autopsy in Boston, a very common finding was involvement, in the meningeal inflammation, of the anterior and posterior roots of the spinal nerves. Swollen axis cylinders, accumulations of small round cells and of leucocytes were met with, the changes varying in degree and extent in different nerve roots. That the cells in the anterior horns then should show the alterations so characteristic of axone lesion is not surprising; indeed, from what we now know their


existence could have been prophesied, and their absence would have been extremely difficult to account for. The variation in the number of cells affected in different segments of the cord doubtless depends upon the varying degree of involvement of the corresponding nerve roots.

The explanation of the condition of the cells of the nucleus dorsalis Clarkii met with on studying the thoracic cord was temporarily puzzling. An examination of sections showed that almost every cell in this nucleus on each side showed alterations quite like those following axone lesion. The axones of these cells enter neither the anterior nor posterior roots of the spinal nerves. Some other explanation than nei've root involvement had to be sought; for although the experiments of Warrington in England and van Gehuchten in Belgium make it seem probable that a lesion apparently precisely similar can be called forth in a nerve cell by depriving it of the cellulipetal impulses reaching it, it is scarcely conceivable that there could have been, through the irregular involvement of the posterior roots, sufficient interference with the passage of impulses along collaterals and terminals into the nucleus dorsalis to account for the involvement of almost every one of the cells contained within it. If, on the other hand, one inquires as to the course followed by the axones of the cells of this nucleus, there comes into view a much more plausible explanation for the lesions. While, so far as I know, no one has ever actually demonstrated the connection of the axones in the tract with the cell bodies of the nucleus by means of the method of Golgi, still the study of secondary degenerations by Mott and of the embryonic cord by Flechsig leave but little reason for doubting the view now generally held that the axones of the cells of the nucleus dorsalis Clarkii are also the constituent axis cylinders of the fibres in the fasciculus cerebellospinalis (direct cerebellar tract).

The exact position of the direct cerebellar tract in the spinal cord, and in the medulla oblongata where it passes into the corpus restiforme, is well known. The fibres occupy an extensive area immediately adjacent to the surface of the cord, being intercalated between the lateral pyramidal tract and the periphery. A reference to the description of the gross appearances of the cord in cerebro-spinal meningitis will show that it is precisely in this region that the meningeal exudate is most abundant. Is it any wonder then that axones running practically on the surface of the cord all the way from the thoracic region to the corpus restiforme, exposed throughout this whole distance to the direct action of the meningeal inflammation, should undergo inj ury ? AVould it not be more surprising to learn that some fibres had escaped insult? I am of the opinion therefore that the lesions of the second type met with in the nucleus dorsalis in cerebro-spiiuil meningitis are in reality "secondary" to injuries of the axones in the direct cerebellar tract, and afford another example of the so-called " reaction at a distance."

Dr. Theobald. — There are two points I would like to allude to. Dr. Councilman has spoken of the belief that the disease is comparatively rare in young children. I have seen from time to time a great many cases of deaf-mutism from cerebro-spinal meningitis, at least the history indicated this, and most of these had the disease in infancy or early childhood. So it


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would seem, if this view is correct, that when the attack occurs in early childhood it is more apt to affect the ears than it is later in life. Again, Dr. Councilman spoke of the labyrinth being involved through extension of the inflammatory process along the auditory nerve. While this is one way by which the labyrinth may be reached, another, not improbable, route would be through the aqueductuscochleas and the aqueductus vestibuli which connect the lymph spaces of the labyrinth with those of the brain.

Dr. Randolph. — I had the opportunity of examining the eyes of about forty cases in the epidemic of cerebro-spinal meningitis which has just been described by Drs. Flexner and Barker, and of these the fundus was normal in only seven cases, and out of these seven cases one had divergent strabismus and dilated pupils, another had marked nystagmus, and still another had greatly dilated pupils. I found neuritis optica in six cases. There was one case of retinitis with which was associated thrombosis of the central vein of the right eye. The other cases were (as regards the fundus of the eye) characterized especially by great venous engorgement and tortuosity, and more or less congestion of the optic disk. In the eight cases of divergent strabismus it was the right eye that diverged. In four cases the right pupil was dilated and the left unchanged. In three cases the neuritis was more marked in the right eye. I can give no satisfactory reason why the right eye more often showed abnormal conditions than the left.

The type of eye symptoms peculiar to this epidemic seems to have been a remarkable tortuosity and distension of the retinal veins and more or less congestion of the oj^tic disk. The degree of venous engorgement in some of the cases was, in my experience, a unique condition, the blood appearing almost black and as though actually stagnant. The tortuosity of the veins, too, was striking. The turning points of


the veins were so abrupt that they resembled small hemorrhages, and as such I regarded them in one case till I was enabled later to make a more thorough examination, when I found that what I took to be hemorrhages were very abrupt tui-ns in the veins where the circulation must have been almost at a standstill. These conditions are quite analogous to what was discovered in the brain in every case where a post-mortem was made. I regard the existence of eye symptoms, especially those where the fundus is involved, as indicating a particularly grave case. Wherever I found the condition I have described very pronounced I felt justified in speaking positively as regards the prognosis. I think that this type of eye symptoms is of more value as indicating the condition of the brain than the symptoms described by other writers, such as panophthalmitis, suppurative choroiditis and keratitis, affections which in my opinion would be likely to have their origin in general infection, and not likely to be the direct result of purely cerebral changes.

I have been interested in Dr. Councilman's account of the bacteriology of the disease, and it may be worth while mentioning that the Fraenkel-Weichselbaum diplococcus, which has been regarded till lately the specific organism of epidemic cerebro-spinal meningitis, has been identified as the causative agent in more than one eye affection. Recently Uhthotf and Axeufeld have reported 34 cases of serpent ulcer of the cornea, where they found this diplococcus in every case, and in the majority of cases in pure culture. These observers go so far as to call this affection of the cornea the pneumococcus ulcer. Not a year ago Gifford reported an extensive epidemic of "pink eye" in Omaha and its vicinity, and he was able to identify the pneumococcus of Fraenkel-Weichselbaum as the specific organism. In conclusion it may be said that this same organism is the predominating one in the majority of cases of chronic suppurative inflammation of the middle ear.


THE DIAPHRAGM PHENOMENON-THE SO-CALLED LITTEN'S SIGN.

By Norman B. Gwyn, M. B., Assistant Resident Physician.


In an indirect way the movement of the diaphragm is well recognized by its displacement of underlying organs or masses, and in this direction its value in the diagnosis of certain conditions is thoroughly established ; but the fact that this movement normally gives indication of itself seems until lately to have escaped the observation of clinicians.

Stokes first, in 1837, incidentally mentions that in some cases of emphysema the diaphragm stood so low that its line of contact could be seen as a transverse furrow, moving downwards with inspiration, between thew hypochondria, and that there was a similar occurrence in pleurisy.

Gerhardt, in the second edition of his " Lehrbuch der Auscultation," quotes these words of Stokes, and adds that in similar cases at the beginning of a short and deep inspiration he has seen this furrow move first a little upwards, then downwards. Gerhardt further states that "occasionally the movement of the diaphragm at a higher level can be seen on the intercostal spaces of very wasted people, a slight horizontal furrow


separates in these cases the upper concave part of the diaphragm from the lower flatter part, and moves up and down. Artificially overfed sucklings give the first sad examples for the demonstration of this occurrence."

The deformity known as Harrison's groove, marking the early position of the point of contact of the diaphragm with the chest wall, may be mentioned as one way of determining by inspection alone where this muscle stands or has stood in earlier years.

Except Stokes and Gerhardt, physicians do not seem to have observed any direct visible movement of the diaphragm, and they definitely limited it to certain abnormal conditions, and seem to have regarded it as an accidental occurrence. Stokes says " in some cases of emphysema." Gerhardt expressly says " in similar cases," and " in extremely wasted conditions." These references do not take into consideration a constantly visible movement, which was first recognized and described bv Litten in 1892.


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His account appears under the title of "The visible movements of the diaphragm which are normally seen on the thorax with every respiration," and he states particularly that it is a description of a constantly visible movement of the diaphragm, which up to this time had been described as a very rare condition, or as one occurring only in pathological conditions. As a preliminary he dwells upon the action of the diaphragm, its position as determined by pei-cussion, and the extreme value of the ascending and descending movements of this muscle in the physical examination, and in contrast to all previous methods of estimating the movements he insists upon the possibility of so doing by direct inspection of the thoracic walls.

Previous to a full description the references of Stokes and Gerhardt are discussed, which are altogether to pa(7wlogical conditions; then the statement is made that "in contradistinction to these the author has made this observation," namely, "that one can see the movements of the diaphragm as a constant physiological appearance, returning with every respiration on the thorax of every sound person, and also on those patients who have no grave respiratory disturbance."

The phenomenon is described as an undulating movement or shadow which begins on both sides at about the level of the sixth intercostal sjDace, and descends with inspiration as a distinct line or furrow for several spaces, reaching sometimes the costal margin, returning to its point of origin with expiration, and crossing the ribs at an acute angle.

With a deep inspiration the visible movement or play of the diaphragm travels 2-3 s^mces. In superficial, this is reduced to 1-1 J. The movement may cover the whole width of the side of the thorax, so that the visible line of departure of the diaphragm reaches from axillary line to the sternal margin on same side. In other cases one may not see it in this full extent, but perhaps only between the axillary and parasternal or mammillary lines, or only in one or other intercostal space. The movement on the right side is usually more marked than on the left, but often the reverse is true ; it can also be well demonstrated on the back. The costo-abdominal type of resjiiratiou seen in men favors the occurrence of the movement, which is not so constantly present or so well marked in women and children.

To see well this movement of the diaphragm the recumbent position, either on back or abdomen, is required. The lateral position is unfavorable. A thick chest wall does not necessarily hide the movement. Pull daylight, with the bed near a window, the observer in front and to the side, complete the requirements. Artificial light is useless unless concentrated on the side examined.

This comprises the description of Litten's sign, as it is now commonly called. Litten mentions that he has known of its occurrence for some time, and that so far he has not failed to find it in any case, provided there was no marked respiratory disturbance. The principal importance attached by him to this movement is that it gives an absolute method for determining at a glance the exact position of the diaphragm and its mobility, and having fixed the position of this muscle the inferior border of the lungs is also found. It gives also an idea of the depth of respiration, and finally in the left front the heart's lower limits can be mapped out by this movement.


Chief among respiratory disturbances which interfere with the production of this movement are emphysema and pleural effusions; other processes are pericardial adhesions, tumor masses underlying the diaphragm, and paralysis of the diaphragm itself. Litten states that pleural effusions cause partial obliteration of the movement on the affected side, and in addition that the level of the effusion may be influenced by the rise and fall of the diaphragm. Emphysema and hypertrophy of the right ventricle, by depressing the diaphragm, may give indication of its visible movement as a transverse furrow below the xiphoid between the costal margins.

A year after the appearance of Litten's article, Becher of Berlin admitted the normal character and value of the sign and sought to determine its cause. This was the first notice of Litten's original communication, which seemed to have attracted so little comment that in 1894 he again called attention to the subject. Following this second article came a statement from Martins that Litten had entirely overlooked the fact of Gerhard t's description several years before, to which Litten replied, pointing out the differences already referred to.

In the Wiener Klin. Wochenschrift, 1895, Litten returned to the question, and deplored the fact that so little attention had been given to his original paper. In this article he added several points of interest. The cause is stated to be the peeling of the vertical portion of the diaphragm from the chest wall by the inspiratory contraction, and the subsequent replacement in expiration. In looking for the sign behind, the knee-elbow position is recommended. The observer should stand three or four feet away from the patient, at an angle of 45 degrees with his body. Both patient and observer should be turned from the light, which should come from a window directly adjacent to the bed. Three essential requirements are given : horizontal position, good light and full deep breath. From 6 to 7 cm. are given as the normal limit of descent of the movement ; anything less than this is considered abnormal. By comparing the descent of the abdominal organs during the descent of the diaphragm it is considered that we have a valuable confirmatory accessory sign. Should the diaphragmatic movement not be observed on one side or other, palpation should show that underlying organs are not depressed as they normally are.

The sign is valuable in differentiating subphrenic abscess from a small pleural effusion. In the former the line at which the movement begins is elevated, while in the eft'usiou the line of movement, if present, is depressed. In the Verhandluug der Berliner Med. Gesellschaft a case of subphrenic abscess is reported in which the line of origin was pushed up to the third rib.

According to Litten, small pleural effusions do not obliterate tlie movement entirely,-but show it at a lower level, which indicates that a small effusion does not sink into the complementary sjjace, or that it is unable to separate the adjacent diaphragm and chest wall. Tumors in the thorax also depress tlie line of origin, while abdominal tumors elevate it, but do not obliterate it; only one case of sarcoma of the liver, thirtysix pounds in weight, having been observed to do so. With tumors are included jiregnancy, tympanites, moderate ascites. Litten furtlu'r states tliat if the visible niovenieiit reaches thi


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costal margin (an occurrence which is never normally the case) one must consider the existence of emphysema.

Generally speaking, processes which limit the breathing to the costal type obscure the diaphragm phenomenon ; with these is to be included pneumonia of the lower lobe, a point not- mentioned in the first article. Pleural adhesions and retraction of the chest give an impaired or restricted movement.

From this review of the 1895 article it is seen that Litteu not only confirms his previous views, but elaborates them, and insists on the physiological and clinical value of the sign. His observations, which dated from 1891, numbered nearly 6000, and he asserts that nothing has so far come up to disprove the occurrence of the diaphragm phenomenon in every normal chest.

There are very few confirmatory references to Litteu's sign. Eichhorst* says "the movements of the diaphragm are often visible in people not too fat, as a light shadow which especially on the right side descends with inspiration, ascends with expiration; the extent of this shadow is 5-7 cm. Litten has called this the diaphragm phenomenon, and places much value thereon as marking the lower border of the lungs." In the second edition of Musser's diagnosis there is also a note upon it.

Elkanf reviews the subject and insists on the value of the sign in diaphragmatic hernia ; its retention at a higher level than normal, and the tympany above it from the distended intestines being the marked features.

Stabyl gives the diajihragm phenomenon considerable diagnostic value.

Rumpf § in studying the diaphragm phenomena in beginning pulmonary apical tuberculosis, shows that when the apex is involved to a certain extent the sign is lessened perceptibly on the affected side.

The diaphragm phenomenon is generally held to represent the peeling oif of the vertical part of the diaphragm from the chest wall and its subsequent replacement. This is Litten's view, and it seems most reasonable. Two other views are advanced in Becher's article of 1893. Gad thinks it due to the atmospheric pressure around the infundibula of the lungs, which is increased by the beginning descent of the diaphragm, the negative pressure not being immediately neutralized from the upper air passages. As the lungs descend, the diaphragm preceding them, this line of atmosjjheric pressure follows the line of the lower border of the lungs downward, and makes the shadow or undulation of descent. He does not explain the shadow of ascent.

Becher holds that the abdominal contents, feeling the direct pressure of the diaphragm downwards, attempt to neutralize the negative pressure at the point where it is most marked, i. e. at the meeting of the horizontal with the vertical part of the diaphragm. The pressure to which the contents are subjected


Lehrbuch Klinische XJntersuchungen Methoden innere Krankheiten, Ed. 1896. t Berlin Thesis, Aug. 1896. t Berlin Thesis, February, 1896. § Berliner Klin. Wochenschr., Feb. 8tb, 1897.


and their attempts to neutralize the negative pressure result in a protrusion against the point of meeting, making the visible sign descending with inspiration. As reason for this view Becher gives Hinke's description of the diaphragm. This is that the diaphragm has two parts, a vertical, rising from the attachment at the costal margin and lying in contact with the chest wall as high as the sixth or seventh rib, and a horizontal part stretching directly across, meeting the vertical at a distinct angle. The close apposition of the vertical to the chest wall allows the pressure results to be easily transmitted through it.

We might well question whether, as Litteu supposes, the mere separation of one smooth surface from another is capable of producing the phenomenon. Could we include the influence of atmospheric pressure, Litten's view would be strengthened, for often the phenomenon is marked as a distinct narrow furrow, a depression which looks as if pressure were exercised from without. One can see in many chests on sudden stoppage of inspiration a similar furrow momentarily made along the lower pulmonary borders. Harrison's groove, which represents this in a chronic form, seems to jjoint to the occurrence of a negative pressure within and a counteracting external pressure.

Against Becher's view it can be primarily said that the phenomenon does not appear in the form of bulging, but, as has been stated, is more to be compared to a furrow ; the result seen in sudden stoppage of inspiration and in Harrison's groove both seem at variance with his idea.

The result of increased abdominal pressure on the right side must act directly through the liver. One would expect some modification therefrom ; the reverse, however, is more often found.

The descent of the expanding lung is not considered especially as being a factor in producing the diaphragm phenomenon, though it must be in very close relation thei'eto; one could look for a sign produced thus wherever the free border of the lung is inflnenced by inspiration, as, for example, the covering of the cardiac area.

The production of the shadow seen returning with expiration seems more in accordance with Litten's idea of the replacement of the diaphragm against the chest wall. Neither Gad nor Becher discusses this part of the phenomenon.

To study and familiarize myself with the sign I have made observations upon 100 consecutive cases in the wards, seeking to confirm Litten's statements.

The patients were all examined in the recumbent posture. Ths position in every case was such that daylight fell directly upon the side to be examined, forming an angle of 90 to 130 degrees with the line of the observer's vision. The observations were made on clear days before 4 p. m. There was no selection of the cases. In order to expose the sides fully the hands were placed on the head and the jiatient brought to the edge of the bed, and the examination made first during quiet breathing and then during deep inspiration. The limits of the movements were marked in pencil on the chest wall, and the depth of the excursion measured in centimeters. To clearly make out the movement an ordinary deep inspiration is necessary, as only in very thin subjects does a quiet respiratory movement bring out the sign. In very stout subjects


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[No. 83.


deep iuspiratiou is always necessary. The following are the results in 100 cases examined :

In every patient not too fat or excessively developed, or who had had no serious pulmonary disorder, the sign was fouud. In one very fat subject. Case 52, thei'e was only a suspicion of the phenomenon on one side. In five cases there was no indication of the sign on either side. In four cases the phenomenon was present on only one side. In the cases in which it was absent one was a colored boy of eleven, with double adhesive pleurisy, the autopsy showing a diaphragm firmly attached to chest wall on both sides. Case 62 was a short, stout, well developed man. Case 38 was a colored man with ascites and general anasarca. Case 49 was a man with extreme emphysema. Case 6, a very stout woman.

Of those showing the sign on one side only, Case 39 was a well built negro with much effusion into the left pleura, on which side the sign was absent. Case 46 had pneumonia of the right lower lobe. Case 52 was the very stout man above referred to. Case 85 was a colored man with chronic pleurisy on the right side.

The remaining 91 cases showed the phenomenon more or less equally on both sides. Thin subjects furnished the most satisfactory examples, giving usually more sharply defined and regular outlines to the shadow. The most favorable field of motion for the shadow lay between the parasternal and posterior scapular lines. It sometimes reached as far as the spine behind and the nipple line in front. In the axilla the sign was always the most marked. The extent of visible movement from behind forwards measured from 2 to 29 cm., the average being about 15 cm. In all instances it was a continuous line without interruption. The vertical excursion varied from 1 to 9 cm., the average distance being about 4* cm. It did not reach the costal margin in any case. The beginning of the descent does not coincide accurately with the beginning of the movement of inspiration. One can see the shadow begin a fraction of a second after one has perceived the inspiration to have begun. Erect posture occasionally gave a small sign, while the line of origin would often be seen as an oblique line approaching the costal margin behind, and sometimes reaching it at the finish, when the subject lay on his side. The light seems to be the essential condition. Two cases in which the absence of the sign on one side could not be explained showed on re-examination that the sign was present. Artificial light under some conditions of j)osition gave fair results.


The shadow ascending with expiration moved accurately in the same field as the descending shadow, ending quite abruptly at the line of origin. It was never so marked as the descending shadow, and never showed the marked furrow-like appearance observed often in this.

On either side the lines of origin as determined by insi^ection were at a very nearly equal distance from the costal margin ; a difference of J to 1 cm., however, was quite common. It was not apparent that the line stood higher on the right side over the liver. The descent on both sides was never so equally marked, differences of 2 to 3 cm. being quite often seen where no affection of respiration was suspected or found. This difference was noted both on right and left.

The position and extent of the phenomena in a majority of the cases was within the same lines, but occasionally one side would show a sign several centimeters longer from behind forward, and perhaps situated more towards the back or front than the other.

Litten's sign may be regarded as a normal phenomenon. The absence in 9 of the 100 cases in this series could be reasonably accounted for. Litten states that in his enormous number of observations, amounting now to many thousand cases, it was present in every normal thorax. It is certainly a matter of very great value to be able to see at a glance the inferior border of the lung, and it is certainly true, as Litten says, that the student has now a valuable and accurate method of proving the correctness of his percussion, and a rapid and easy way of ascertaining a fact that previously had to be laboriously and jjerhaps only indefinitely determined.

As yet the value of the jihenomenou in diagnosis is unsettled. So long as one may see in apparently normal chests differences of several centimeters, it would be hard to say what might be considered abnormal. The complete absence of the sign in large effusions and emphysema is an interesting and natural fact, but the presence in small effusions might be misleading. Cases of subphrenic abscess and diaphragmatic hernia, in which rather striking modifications of the phenomenon have been observed, are rather few to establish any fixed rule. Only adhesions of the diaphragmatic and costal pleural layers directly below the infundibula of the lungs would interfere with the diaphragm's descent enough to obliterate the sisrn.


PROCEEDINGS OF SOCIETIES,


THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Meeting of November 1, 1897.

Dr. Baekee in the Chair.

Cases of Aneurism.— Dr. Hunnee.

Case I. — "W. T. G., a3t. 27, a printer, with a definite family history of tuberculosis, was sent to the hospital on October 26 by Dr. Norton of Washington, with the diagnosis of abdominal aneurism.


Since a boy he has always been accustomed to holding type in his mouth. He has carried heavy " forms " of type resting against his abdomen, and has lifted heavy weights in the gymnasium. He has had several attacks of gonorrhcea, and about seven years ago an attack of acute arthritic rheumatism which he thinks was synchronous Avith one. No definite history of syphilis. He has been a pretty heavy drinker of alcoholics since a boy.

His present trouble dates since May or June of this year, when he began having a "dull dragged-out feeling" and


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occasionally sharj) pains across the abdomen, which caused him to lie doubled across his printer's stool for the pressure benefit. At this time he often vomited after eating, but has not vomited for the past two months.

The paiu and weakness have increased since May and he has lost about forty pounds in weight. During the past mouth he has been obliged to sleep on the left side or in the erect posture, because of j)ain when in any other position. Pain is referred to the pelvic region, at times shooting into scrotum, at times extending even to the knees. In walking the street a sudden jar gives great pain. He walks slightly bent forward to avoid pain. He first noticed pulsation in abdomen one month ago.

On physical examination he is found to have greatly sclerosed arteries ; a markedly accentuated second aortic sound ; no blue line on the gums or other evidence of plumbism.

On inspection of the abdomen a diffuse pulsation over the whole upper abdominal region, most marked in the left epigastrium, is seen. This region is prominent, and the left costal margin over the sixth and seventh cartilages is bulged slightly forwards. The pulsation is felt to be limited to the upper half of the abdominal aorta, over which a globular exj^ausile mass the size of a very large orange can be outlined. A purring systolic and diastolic thrill is felt over the mass. Percussion gives dullness everywhere over the mass, but later, during observation, stomach tympany is found on percussion over its lower left quadrant. On auscultation a loud double murmur — a systolic, loud, harsh, and short — a diastolic, fainter, prolonged, and almost musical in character — is heard. In the back a soft blowing systolic murmur is heard over an area to the right of the vertebras extending from the eleventh dorsal to the first lumbar. The knee kick is greatly exaggerated.

Case II. — 0. G., a German, set. 47, was first admitted to hospital, Oct. 23, 1896, complaining of pain in the back and left side. He has an excellent family history and has always been a healthy and hard-working man. He served through the Franco-Prussian war in the artillery ; has always been a steady drinker of alcoholics ; twenty years ago he had a hard chancre, and one year later was treated five weeks for secondary symptoms at the Konigsberg hospital. In 1894 he was at the Johns Hopkins dispensary for eye trouble; was told that it was syphilitic in origin, and after two or three weeks' treatment he was well.

His present trouble began in March, 1896, with paiu in the right side under the costal margin extending down to hip. This grew gradually worse, and about August, 1896, the pain began in the mid-lumbar region, and on first admission in October, 1896, it was described as only on the left side, beginning ill the left iliac region and running back to the spine. The pain was of varied character, a dull aching being almost always present, and several times a day, lasting for a second or two, very sharp pains like the cutting of a knife ran across the abdomen.

The patient improved greatly during a three months' rest in the Hospital, and in February, 1897, went to work, at first doing light work on a dairy farm, and then heavy work grading roads. He soon had to cease work because of great


jjain in the left side beneath the ribs, and returned to the Hospital in March, 1897.

His pains grew more severe and frequent during a second stay of three months, but being ambitious to get to work he left the Hospital in June and was able to work about halftime during the summer. He remained under supervision of the Hospital and kept up treatment with iodide of potassium, nitroglycerine, and cathartics, being obliged to take as high as four grains of morphia per diem for pain. He lost weight and grew weaker, and on October 23 was obliged to enter the Hospital for the third time.

Physical examination on his first admission revealed an aortic and a mitral insufficiency. On careful inspection there was seen a good deal of throbbing over the manubrium. No localized pulsation. The epigastrium showed a marked pulsation, and on palpation a heaving up and down stroke with an occasional palpable thrill. No positive tumor could be outlined. On auscultation a very loud systolic bruit was heard over the course of the abdominal aorta. This thrill was intense and rough in the left upper quadrant of the epigastrium. In the back a murmur could be faintly heard about opposite the tenth dorsal vertebra and for a distance of six centimeters below.

On his second admission in March, 1897, the pulsation, the thrill and bruit were all increased in intensity, and on deep pressure just below the ensiform it was thought that a throbbing expansile tumor could be f elt ; not, however, as a globular mass.

Before his discharge in June a pulsation could occasionally be detected in the back ; and during a paroxysm of pain, with one hand under the ribs in front and one under the ribs behind, a definite expansile pulsation could be obtained. On his last admitsion in October a diffuse epigastric pulsation is seen, although the region shows a depression rather than an elevation as before. The pulsation and displacement of the hand is limited to the upper half of the abdominal aorta. On auscultation over this area a loud blowing systolic murmur is heard, followed at times by a higher pitched blowing diastolic.

Inspection of back shows a widely diffuse pulsation at the outer edge of the erector spinte muscle just below the twelfth rib. This is more evident on palpation. On auscultation over this area a very faint distant systolic murmur, followed by a sudden diastolic shock, is heard. Examination of the tendon reflexes shows that of the right rectus femoris to be apparently normal, while the left seems diminished.

Dr. Barker. — The possibility of the healing of aneurisms has interested me especially, for I have met with one case in which an aneurism of the aorta of considerable size healed spontaneously. In 1891 a colored man applied to the dispen sary for treatment, complaining of cough, shortness of breath and some swelling of the legs. His personal history showed that he had been a hard worker and had seen the rough side of life; he had indulged in alcohol to excess and gave some evidence of having had lues. On examination of the chest a globiilar swelling was found in the parasternal region on the right side, extending from above the sternal clavicular articulation to the level of the third rib. The swelling pulsated


40


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[No. 83.


with the heart's beat, yielded a marked systolic impulse aud evident diastolic shock. It was dull ou percussion, aud the aortic second sound over the area was accentuated. Tracheal tugging was well marked. No difference could be appreciated in the pulse at the two wrists ; the radials were thickened. There was no distinct bruit over the tumor, nor was there any valvular lesion of the heart. A diagnosis was made of general arterio-sclerosis with aneurism of the ascending portion of the aortic arch. In*1893, a little less than two years after I had first seen him, he entered the medical ward with oedema of the legs, complaining of shortness of breath ; the urine was albuminous, and a few granular and hyaline casts together with blood corpuscles were present in it. In the thorax there was found an area of dulness, and ou deep palpation a firm resistant mass could be felt in the episternal notch. There was no pulsation of the tumor nor was there any distinct tracheal tugging. The character of the thoracic lesion was puzzling until his previous history in the dispensary was consulted, when it seemed clear that the aneurismal sac had been slowly filled with clots. Dr. Osier suggested that the case be shown at that time to the medical society as one of healed aneurism, and a description of it is to be found in the proceedings of this society published in the March number of the Bulletin for 1894. Some hesitation was felt in concluding during the life of the patient that his aneurism had really healed. The case, however, came later to autopsy in the pathological laboratory, when it was found that the diagnosis made intra vitani was correct. The aneurism was filled with firm lamellated clots and presented as jjerfect a picture of healed aneurism as one is likely to meet with. The individual died from causes entirely independent of the aortic disease.

Dr. Flexner. — I recall the case of aneurism of the abdominal aorta which was operated upon by Dr. Halsted. The condition found at autopsy was a very interesting one, and the case as a whole is impressed upon my mind because it served as an example of rapid post-mortem development of the bacillus aerogenes capsulatus, the source of which was easily traced to the intestinal contents.

The autopsy was made 21 hours post mortem in the last week of April, 1896. Man set. 33, well nourished. The peritoneal cavity contained blood-stained fluid in the dependent parts. On the left side a large swelling existed which proved to be a hffimatoma. It occupied one-half of this side of the peritoneal cavity. The serous covering of the splenic flexure of the colon, the meso-colou and the tissues about the pancreas were all deeply infiltrated with blood and contained numerous gas blebs. The meso-colou of the sigmoid flexure, the meso-rectum and the sjjlenic portion of the transverse colon were enormously thickened by recently clotted blood and measured ou an average 3 to 3.5 cm. in thickness. The mesentery of the descending colon and sigmoid flexure formed a part of the anterior wall of a large aneurismal sac, the lower boundary of which was formed by the infiltrated cul-de-sac between the bladder and the rectum, which had about the same thickness as the meso-colon. The infiltration extended posteriorly to the vertebral column. The posterior boundaries of the sac were formed by the sheaths of the psoas and iliacus muscles, the infiltration with blood having extended below


Poupart's ligament into tlie thigh along the sheaths of these muscles and the tissues of Hunter's canal. The sac of the false aneurism, which in its extreme dimensions measured 22 cm. in length and 26 cm. in transverse circumference, was filled with dark, fairly recent clots. fSimilar clots gave to the wall of this sac its thickness, upon removing which the anterior portion of the sac was shown to be covered by the peritoneal layer alone. The infiltration with blood passed upwards into the diaphragm aud left peri-renal tissues.

The oiDening in the aorta which communicated with the large sac was nearly circular and measured 2.5x3 cm. in size. This opening led directly into the true sac of the aneurism, which was situated posteriorly, extending to and eroding the vertebral column, aud reached a pool-ball in size. The communication with the larger sac already described was through this sac, the opening in the latter admitting four fingers.

The aneurism sprang from the aorta to the right of and about on a line with the creliac axis ; all the vessels leading from the abdominal aorta were preserved intact. The iutima of the aorta generally was smooth, but in the beginning of the ascending arch and in the transverse portion several elevated nodular patches free from calcification existed.

There can be, I think, uo doubt that at some time, perhaps a week or more jirior to the operation, the rupture of the aneurism took place, permitting a gradual escape of blood into the tissues described. Death followed the rupture of the secondary sac thus formed at the tiiue of the operation.

The bacteriological examination of the frothy, blood-stained fluid in the peritoneal cavity showed many capsulated bacilli agreeing in morphology with the bacillus aerogenes capsulatus. The liver, pancreas and heart's blood yielded small numbers of similar micro-organisms. Cover-slip preparations made from the large intestine (colon and caecum) showed among many bacteria having the morphology of the bacillus coli communis, not a few of the larger forms agreeing with the gas bacillus ; while films from the small intestine showed the presence of the latter in practically pure culture. The bacillus aerogenes cajjsulatus was isolated in pure culture and shown by inoculation of a pigeon to be pathogenic.

Diabetes in tlie Negro.— Dr. Pancoast.

Dr. Osier has asked me to report the following case: Henry Roy; colored; aged 50 years; driver. On admission he complained of a severe cough aud of weakness and pain under the sternum. His family history is unimportant. Excepting diphtheria and whooping-cough he has had no severe acute infectious diseases. He had a sore about 25 years ago and apparently no secondary symptoms. The patient has had a slight hacking cough at intervals for years, and says that eight years ago he had night sweats for two weeks. Until five years ago he drank whiskey to some excess. He had noticed no change in frequency of micturition or in amount of urine voided, but as long as he can remember he has risen once or twice at night to pass his water.

About nine weeks ago he was taken with a severe paroxysmal cough which has increased in severity. His appetite has gradually failed and he has lost in strength and weight. He then weighed 188 pounds aud now weighs 139. For a week


February, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


41


before admission his scanty expectoration has at times been blood-tinged, and he has suffered from dull pain beneath the sternum. He has had some shortness of breath ; has vomited once and has been quite thirsty after meals. His skin has been dry.

Examination shows a rather light-colored negro, much emaciated. In the left axilla we found quite evident dullness on percussion and increased transmission of vocal fremitus and voice sounds. Moist crackles were found at the left apex. He has the Argyle-Eobertson pupil and has lost the patellar reflex. He has congenital phimosis and a large scar on the penis. The sputum is moderate in amount and shows numerous tubercle bacilli and bands of elastic tissue.

Urine in 34 hours, 2300 cm.; specific gravity 1028; a trace of albumin ; 122 grams of sugar. On the ward diabetic diet, which is not sugar-free, he passed fi'om 20 to 50 grams of sugar in 24 hours. After three days of Van Noorden's standard diet the urine was sugar-fi'ee.

The patient is shown because diabetes in the negro is rather rare and becaiise he illustrates a common complication (pulmonary tuberculosis). Of particular interest, however, is the fact that his blood and urine give the reactions described by Bremer of St. Louis as diagnostic of diabetes. The slides I exhibit were prepared by Mr. Herrick of the Fourth Year Class and show the difference in staining by Congo red very well indeed. I also exhibit two specimens of urine, the patient's and a control specimen. Mr. Herrick has added eosin and gentian violet to each and the difference in color is very marked. The articles of Dr. Bremer which describe this reaction are in the New York Medical Journal, Vol. 63, page 301 (1896) and Vol. 6.5, page 360 (1897); also in the Medical Kecord, Vol. 52, page 495 (1897).

Dr. FuTCHER.— Diabetes is a rare disease in the colored race. This is the sixth case we have had in the Hospital. Up to May, 1897, there had been 69 cases of diabetes, five of which were in the colored race, making a percentage of 7.2. Saundby credits Dr. Tyson with saying that he had never met with a case of diabetes in the colored race in America, which shows that it is very rare. Tyson, however, in his Practice of Medicine, 1896, states that the disease is rare in the negro race, but that he has seen several cases.

The proportion of males and females in the white race who suffer from diabetes is about 3 to 2. In children, however, the ratio is not the same ; girls have it more frequently than boys. In the colored race our experience has been that the cases occur more frequently in women than in men, four of the six cases being in women.

In regard to Bremer's reaction in the urine he claims that it is also present when the urine is temporarily free from sugar. This case is contrary to that belief. It has been claimed by Lepine and Lyonuet that the blood reaction is due to the variable alkalinity of the blood serum. Bremer believes that it is due to qualitative changes in the corpuscles, and thinks that the test supports Spitzer's view that the glycolytic ferment is contained within the red blood corpuscles. Lepine and Lyonnet have found that the reaction is present in leucffiniic blood, while Bremer claims that if his technique is strictly adhered io leucajmic blood reacts like normal blood.


He has found it present in cases of experimental phloroglucin

diabetes.


Exhibition of Specimen of Round Ulcer of the Stomacli. Erosion of Gastric Artery; Post-mortem Perforation.—

Dr. Flexner.

The specimen which I present this evening came from a negro man about 60 years of age who came to the Hospital for tuberculosis of the elbow joint. The clinical notes state that on October 24th, while in the hospital for the above trouble, he was seized with hasmatmesis. There is no record of a previous attack of this sort. The patient, who was already very weak and much emaciated, died on October 27th. The autopsy was performed six hours post mortem.

The peritoneal cavity contained about 200 cc. of dark, turbid fluid which was collected in the fossae. The omentum was almost devoid of fat ; no unusual adhesions between the several viscera.

The stomach itself was moderately dilated and its contents were fluid and dark in color. The mucous membrane was covered with sticky mucus which was streaked with dark lines, the surface presented a coarsely mammillated appearance and there was absence of the normal velvety surface. There existed on the posterior wall, 6 cm. from the pylorus, just at the limits of the lesser curvature, a deep almost circular ulcer 4.5 x 3 cm. in extent, the edges of which were for the most part rounded in form. The ulcer extended to the peritoneal coat, and at one place (perhaps two places) it had penetrated this coat and communicated with the peritoneal cavity. Through this break fluid passed from the interior of the stomach into the abdominal cavity.

The base of the ulcer, as you can see, is not quite smooth, but it jjresents a somewhat convoluted appearance. This is brought about chiefly by its relation to the branches of the right gastric artery over which it lies. It may be seen that the elevated lines in the under (widest) part of the ulcer correspond to the secondary and tertiary branches of this vessel. Over one such prominent ridge there was a small dark clot; on I'emoving this a slightly elongated erosion was brought to view in a secondary branch of the right gastric artery. A probe can be passed through this opening into the main vessel. All the branches and the main stem of the artery show thickening of the intima.

Between the ridges described the ulcer, in its lower part, extends to the serous coat ; the upper half has not passed beyond the muscular tunic. The least manipulation brings about breaks in the thin tissue mentioned.

My object in bringing this specimen before you is as follows : In the first place, ulcer of the stomach is not a common condition with us. As you know, the large statistics collected by Drs. Welch and Brinton would seem to prove that simple ulcerations or cicatrices are found at autopsy in about 5 per cent, of persons dying from all causes. Our experience is quite different, and while I have not collated our autopsies from this point of view, yet I venture to say that our percentage is far below this estimate. The present instance cannot be said to shed any new light on the cause of such round ulcers, but as the sclerosis of the gastric arteries was so


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[No. 8.3.


much more marked than of the other arteries of the body, it teuds to support the vascular origin of the condition. But I wish to ask your attention especially to the possibility of rapid post-mortem digestion of the stomach, with the production of perforation in places where the walls are already greatly thinned, which is not to be confounded with antemortem perforation. In this case the evidences of perforation were found at once on opening the abdominal cavity ; the dark fluid was evidently derived from the stomach contents ; but the absence of all signs of inflammation is taken to indicate that, although the autopsy was made only sis hours after death, yet the remaining barrier between the cavity of the stomach and that of the peritoneum was in this time digested away.


NOTES ON NEW BOOKS

A Treatise on Surgery by American Authors. Edited by Roswell Park, A. M., M. D , Professor of Surgery in the Medical Department of the University of Buffalo, etc. Volume II. 804 pp., 451 engravings, 17 plates. (Lea Brothers & Co ., Philadelphia and

New York, ISg?.)

The second volume of this interesting work fully sustains the high expectations raised by the appearance of the first, the only disappointment being the smaller extent to which the hand of the editor appears in its contents, and the further extension of that process of condensation which, impossible as it is of dissociation from a work of this encyclopediac range nowadays, interferes with the flow and beauty of the style and diminishts our pleasure in reading it. The illustrations are again remarkable both for their abundance and freshness, although a few of them again show the " defects of the virtues " of the camera.

Of the twenty chapters, three are by the editor, the one upon Surgical Diseases and Injuries of the Head being especially notable as an eminently concise and practically helpful treatment of an extremely complicated subject. His brief chapter at the close upon Skiagraphy, with its full description of apparatus and methods and its interesting series of radiographs, adds much both to the completeness and to the interest of the volume.

The names of Bradford, upon Diseases and Injuries of the Spine ; of Dennis, upon the Surgery of the Chest ; Gerster, upon Plastic Surgery ; and Blake, upon the Surgery of the Ear, are sufficient guarantees for the ability and authoritativeness of the treatment of these subjects. And the method of presentation is equally admirable, with the exce|ition of those omissions which are of course absolutely necessary for reasonable brevity in chapters of a general work, and the occasional baldness and disjointedness of style which almost necessarily accompany this.

The question, however, suggests itself most forcibly whether in this twentieth century age it is any longer necessary to cumber a work of this description with even a nominally complete discussion of such liighly specialized subjects as the diseases of the eye, the ear, and the female reproductive organs. Nearly every practitioner, and certainly every graduate nowadays, is compelled to have in his library at least one work treating upon each of these subjects. Works are written upon these subjects especially intended to meet the needs of the general practitioner, who is beyond the reach of a specialist, and such treatment as can possibly he afforded to them in from thirty to sixty pages of a work upon general surgery can from the very nature of the case and the necessity of naming and classifying all the more important disturbances, hardly have that degree of preliminary detail and logical connection which is absolutely indispensable to a rational


introduction to the subject, while as a work of reference it would be mainly a source of irritation if not of exasperation.

Of course we are well aware of the long-standing feud which exists between the general surgeon upon the one hand and the gynecologist proper upon the other, and it is unquestionably fully within the rights of the former to have a chapter upon this subject inserted in his formal text-book, as a sort of assertion of his rights within this domain. But we think that any one who would attempt to perform any of the special operations, particularly inthe region of the eye or ear, without any further knowledge than that which could be obtained from the chapters upon this subject, admirably definite and condensed as they are, would be a man to whose boldness a somewhat less complimentary term might not be improperly applied. As extracts and condensations they are admirable, but life cannot long be maintained upon Liebig.

The absence of our old friend " the opisthotonos man," of which we complained in the former volume, is more than compensated for by the group of old friends which greet us in the chapter upon the diseases of the eye. But with that exception, as we have before stated, the illustrations are striking for both their freshness and appropriateness.

One of the most admirable and interesting features of the entire volume is the full treatment accorded to those deformities and disturbances which result from errors and defects in embryonic development. This is particularly noticeable in the editor's own chapter, and also in the excellent chapter by Arthur Bevan upon the Mouth, Teeth and Jaws, in which a brief but admirably clear and vivid description is given of the development of these parts, without which, as the author very happily says, no rational understanding of their deformities can possibly be had. It is one of the most suggestive and promising signs of the times that we are beginning to trace a developmental and morphological basis for such a large and rapidly increasing class, not merely of surgical hut also of medical disturbances. The cysts and bronchial fistulje of the neck, the forms of hare-lip and cleft-palate, the coccygeal sinus, the dermoids of the tongue, and many other conditions are treated here from this point of view, and with a most refreshing gain in point of clearness and interest. We regret, however, that in his otherwise excellent chapter upon the Surgery of the Abdomen, Maurice Richardson has not seen fit to distinctly class the appendix in this group and to treat its etiology and pathology from that point of view. Etiology is dismissed in a single ten-line paragraph which is characterized by the last sentence, namely, []

that it is obscure. And this we are the more surprised at because from the pen of the editor have come some of the clearest and most convincing statements of the essentially morphologic and ancestial basis of this interesting disturbance. The human appendix is clearly an atrophying vestige of a more voluminous and functional, intestinal pouch, such as is seen in some of tlie herbivora, and is intermediate between these and the small rounded csecum of the carnivora, in which 'the distal two-thirds, or 'appendix," as we term it, has entirely disappeared. Noi only is it degenerate ancestrally, but it rapidly undergoes involution in the individual, from a direct continuation of the crecum in early foetal life up to its occlusion after adult life, which, as Ribbert has shown, is completed in no less than twenty-five per cent, of all persons by the age of forty, so that the diminishing frequency of appendicitis after this age is to be accounted for upon developmental grounds. In short, we tliink that a full recognition of the fact that appendicitis is simply a " short-circuiting " or accelerating of a process of elimination and atrophy which is normally being carried out in the liuman species, to reach its completion somewhere about the fortieth year, will of itself afford an almost complete rational basis for the etiology and jiathology of the disease.

Dr. Bradford's brief but adequate treatment of the coccygeal dimple and sinus is not only interesting and thoroughly scientific, but of great practical importance, as disease of this structure is fw


February, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


43


commoner than is generally supposed. We have seen three or four

cases which have been mistaken for Jisitilm in ano and determined efforts made to cause the probe to pass through into the rectum.

The p.itholog,v, as a rule, throughout the volume is admirable, clear, and up to date. We cannot help regretting, however, that at some point in the treatment of cancer the editor's well-known and most interesting views upon its dependence on the ancestral or individual senility of epithelial tissue could not have been developed. This view, it appears to us, throws such a valuable light upon the carcinomata of the uterus and breast, organs which are functionally senile long before the remainder of the body tissues, and which are in consequence the site of nearly seventy per cent, of all cases of carcinoma in the female sex. The atrophying lips of the toothless old man, the remains of the invertebrate grinding stomach at the pylorus, and the vestiges of the crop in the middle third of the oesophagus, seem to display the same fatal tendency.

In fine, the entire volume displays, with the exception of a few chapters, that combination of scientific thoroughness with concise and eminent practicality in treatment which so favorably impressed us in the former part of the work. And our chief criticism takes the form of regret that in some instances the "boilingdown " process has been carried so far as to result in the precipitation of a rather irritating mass of crystalline facts. Especially is this the case with the chapter upon Injuries of the Face, anywhere in the first five or six pages of which paragra])h8 may be picked out which contain a description of a new condition to every line. The result is that the pages read like quotations from a medical dictionary, and are just about as interesting and satisfactory, while they fall short of it in point of accuracy. For instance, the extraordinary statement is made that 'long-continued proper specific treatment will improve" the opacities of the cornea, malformations of the permanent teeth and fissures at the angles of the mouth due to hereditary syphilis, all of which well-known symptom group is dignified with the extraordinary title of "congenital syphilitic hypertrophy of the face," while the changes due to leprosy are persistently referred to under the title of " elephantiasis."

The paragraphing of the work and the use of display type have been most skilfully carried out, and with the admirable index, make the tracing down of any particular subject or paragraph a positive pleasure. W. jj.

A Manual of Clinical Diagnosis by Means of Microscopic and Chemical Methods, for Students, Hospital Physicians and Practitioners. By CiiAKLES E. Simon-, M. D , Baltimore. Second edition, revised and enlarged. Philadelphia and New York, Lea Bros. & Co., 1897. Pp. i to xx and 17 to 563, with 133 illustrations on wood, and 14 colored plates.

The fact that a second edition of this book has been called for within one year is the best index to the reception given it by the profession. It differs from the majority of text-books on clinical diagnosis in that it limits its sphere almost entirely to the consideration of microscopical and chemical methods as applied to diagnosis and the results yielded by these. The exact ground which it attempts to cover may perhaps be best understood if we say that it deals with those materials (other than excised portions of tissue) which can be obtained from a living patient and can be removed from his bedside for careful examination. It is in fact a manual for the clinical laboratory of the diagnostician.

The book consists of 13 chapters with the following headings : (I) The Blood; (2) The Secretions of the Mouth ; (3) The Gastric Juice and the Gastric Contents; (4) Fseces; (.5) The Nasal Secretion ; (8) The Sputum ; (7) The Urine ; (S) Transudates and Exuilates; (9) The Examination of Cystic Contents; (10) The Examination of Cerebrospinal Fluid: (11) The Semen; (12) The Vaginal Discharge ; (13) The Secretion of the Mammary Glands.


Under each of these headings the general characters, chemical constitution and microscopical appearances in health and disease are discussed at considerable length. One has only to consult the list of sub-headings in the table of contents to realize the dimensions which the subject has in recent times assumed.

The second edition of this book has been revised and extended. It is not, however, entirely free from error. The illustrations of stained malarial parasites, for example, are not In accord with what one actually sees in the preparations, and we have noticed a few other mistakes which we hope will be corrected when another edition appears.

It is now a matter of general recognition that the successful penetration of research into new fields in almost every department of knowledge is dependent in large measure upon the invention of methods which supplement the activities of our sense organs ; that is to say, methods which extend the domains in which the eye, the ear and the tactile surfaces can be utilized in gaining information concerning the objects to be studied. Whereas, with regard to the urine, for example, the physician of the olden time gathered what information he could from the naked eye appearances, odor, and possibly the taste, the modern clinician helps out his eyes by means of (1) chemical tests yielding color reactions or visible precipitates, and (2) images obtained by the intercalation of microscopic lenses, and the prisms of the spectral apparatus and the polariscope, between his eye and the object. Instead of judging of the condition of the blood solely by a glance at the color of the visible mucous membranes, the latter supplies himself with accurate data concerning the exact holding in haemoglobin, the presence of abnormal hemoglobin compounds, the number of red and white blood corpuscles, the relative proportions of the different varieties of the latter, the presence of protozoa or of bacteria, the existence of chemical abnormalities and of certain specific qualities sometimes possessed by the serum, by using the hfemoglobinometer, the spectroscope, the htemocytometer or the hasmatokrit and the microscope, and by chemical and bacteriological technique. Nowadays rather than rely upon shrewd guesses as to the condition of the cerebrospinal meninges founded upon the symptoms manifested by the patient, the examiner prefers in many instances to study the cerebrospinal fluid directly in order to determine the presence or absence of pus, blood, the tubercle bacillus, the meningococcus or other abnormal element.

It may be urged by the " ultra-practical man " that these methods are of but little service and that he gets along very well without them. He would relegate such refinements with the sphygmographs, sesthesiometers, phonendoscopes, and perhaps also the stethoscopes, to the limbo in which he mentally confines all physicians who strive for scientific accuracy, or what he would probably choose to designate " liighfalutin poppycock."

In sciences as new as clinical bacteriology and clinical chemistry, the doors to which may scarcely be said to be fully open, the threshold barely crossed, very many experiments have to be made, and often enormous numbers of new methods tried before one is found which is really of permanent practical value. Undoubtedly in books like those of Simon and von Jaksch, procedures are described which are of no practical significance and which will sooner or later be discarded. On the other hand, a knowledge of the principles which underlie them and the power of intelligently applying the majority of them to the study of clinical cases is just what distinguishes the physician of the " better sort" from the " ordinary " practitioner.

The scientific physician takes advantage of every possible means to establish his diagnosis on a firm basis; he is analytical; he seeks an explanation for every symptom ; he takes account of all likely complications ; he endeavors to avoid every source of error. He may sometimes, it is true, be led astray. A well marked WIdal reaction may, if he forgets that its presence does not necessarily indicate typhoid ulceration of the intestine, lead him to overlook a local infection of some part in which the typhoid bacillus is the


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[No. 83.


exciting cause. Or again he may be trapped into making too favorable a prognosis on finding malarial parasites in the blood should he chance to deal with a case in which the malarial invasion is associated with general streptococcus infection, with amoebic abscess of the liver or with typhoid fever. But he learns by his mistakes ; another time he avoids them. If he is magnanimous he acknowledges them and warns his fellow-practitioners of possible pitfalls. The true significance of new tests by this means gradually comes to be understood and medicine is advanced.

Tlie "ordinary" doctor says he " does very well without these tests," and indeed he does probably better without them than with them. If he attempted to apply many of them, having no knowledge of the principles upon which they rest, he would obtain false results, or, to be more accurate, falsely interpret the results he obtains and deceive not only his patient but also possibly himself. The only methods which he is capable of using satisfactorily are those so reduced to a " rule of thumb" that mistake is practically impossible. When a test has been so thoroughly sifted by trained men that it comes in this category it is said to have undergone the "crucial test of clinical experience." It is then on a par with the examination of measly pork by factory girls, or the making of ordinary agar-agar by the laboratory Biener.

The newer researches of the clinical laboratory are and must continue to be based upon advances in anatomy, physiology and pathology in the same way that these three sciences are in turn dependent for their progress upon the application of the newer results in chemistry and physics. It is almost trite to say that the better founded the physician is in these fundamental branches the further he can extend his clinical researches. The clinical investigator of fifty years from no-w will be sadly at a loss if he depend upon the anatomy and physiology, the chemistry and physics of to-day. The clinician of ten or twenty years from now must be well versed in these subjects, at least as they are at present understood. But how many students beginning the study of medicine have any adequate knowledge of modern physics and chemistry ? Relatively few of them know enough to read intelligently even the articles of Gruetzner, WUtrich, Hamburger, Kahlenberg and True, Loeb, Heald, Krunig and Paul and Koranyi, to mention some of those who have been writing recently upon the application of physical chemistry to the solution of certain problems in medicine and biology. And what is worse, they do not know enough mathematics to permit them to familiarize themselves with the laws to which the processes of electrolytic dissociation, the velocity of anions and kations, or the passage of substances through semi-permeable membranes conform.

A student contemplating medicine as a career and capable of looking ahead will shape his course very differently from that generally followed. He will lay a foundation in mathematics which reaches wider than arithmetic, two books of Euclid and simple quadratic equations. It will be all the better for him if do not stop short of Calculus and the Theory of Equations. He will study physics and chemistry until he is not only capable of understanding the forward movements going on in these branches, but until he is capable of taking part in their advance. He will especially thoroughly master the principles of the new physical chemistry, seeing that the human body itself consists of a mass of units bounded apparently (the majority of them at any rate) by semi-permeable membranes, and bathed by fluids in which not only simple but extremely complex substances are present in aqueous solution. The manuals of clinical chemistry and microscopy such as that of Dr. Simon may seem complex to-day ; their contents are, however, only fragments of an alphabet out of which the textbooks of coming generations will be constructed. L. F. B.

High Altitudes for Consumptives. By A. Edgar Tussey, M. D.

{Philadelphia: P. Blakialon, Son & Co., 1S96.)

Although the author seems to have but little belief in the bacillus tuberculosis as a cause of phthisis, yet there is much good


sense in this volume, and had it been cut down one-half or more we would praise it without hesitation. Its fault lies in an unbounded tendency of the author to moralize. This is all very well in its place, but its place is not properly in what is meant to be a scientific production addressed to the medical profession. There are too many quotations which seem to us out of place and merely an effort to impress the reader ; the author's style is verbose, and the attempt to write "elegant" English is continually thrust before one.

The object of the author to impress on the general practitioner the use of much greater care than is ordinarily employed in the selection of climates for consumptives is a worthy one, and the end would have been much better attained were the work more condensed. The general practitioner is oftentimes criminally careless in sending phthisical patients away to high climates without a previous careful examination of them. Many a practitioner thinks that a patient with the tubercle bacilli in his sputa should at once be sent off to Colorado. No more serious mistake could be made ; such advice may cause much distress in many ways, or may hasten the death of the patient. If more care was exercised in these cases, the medical profession of this country would to-day have less slurs cast upon it by the middle class (if such a class exist in America) and there would be less heard of quack consumptive cures.

The work which the author has done in estimating the capacity of the chest is valuable, and spite of its defects we recommend this work to all interested in the proper treatment of consumptives.

Guy's Hospital Reports, Vol. LI. {London: J. & A. Churchill, 1895.) No volume of reports ever appears from this hospital without containing one or more articles of real value, and this volume has a number of special interest both to the surgeon and physician. The paper by Theodore Fisher on "Hypertrophy of the Heart without Gross Organic Lesion," is one we were very glad to see, for although this condition has been recognized by the leading medical men in all countries within the past few years, it has not yet met with the general recognition which it deserves. The question of alcohol and overwork as productive causes of this lesion is here well discussed. There are other interesting papers on empyema following lobar pneumonia, in which the value of the course of the temperature curve is specially noted; on scarlatinal nephritis and its complications — this paper brings out clearly the difficulty in making a proper classification of the various forms of nephritis which may occur in scarlatina, in spite of the numberless articles on just this topic. There is a long and important paper on the question of amputation in senile gangrene, and another on the extremely rare lesion of bilateral paralysis of the facial and auditory nerves.

BOOKS RECEIVKO.

Genilo-urinary Surgery and Venereal Diseases. By J. W. White, M. D., and E. Martin, M. D. 1898. 8vo. 1061 pages. J. B. Lippincott Co., Philadelphia.

Index-Catalogue of the Library of the Surgeon-General's Office, United States Army. Authors and Subjects. Second Series. Vol. II, B-Bywater. 1897. 4to. 954 pages. Government Printing Office, Washington.

A Clinical Text-book of Surgical Biagnosis and Treatment. By J. W. Macdonald, M. D. 1898. 8vo. 798 pages. W. B. Saunders, Philadelphia.

The Physiology and Pathology of the Cerebral Circulation. An Experimental Research. By Leonard Hill, M. B. 1896. 8vo. 208 pages. J. & A. Churchill, London.

Saint Thomas's Hospital Reports. New Series. Edited by Dr. Hector Mackenzie and ]\Ir. G. H. Makins. Vol. XXV. 1897. 499-1-119 pages. J. & A. Churchill, London.

The British Quiana Medical Annual. Edited by J. S. Wallbridge and C. W. Daniels. Ninth year of issue. 1897. 8vo. S7-f73 pages. Printed by Baldwin & Co., Georgetown, Demerara.


Febkuary, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


45


PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.


THE JOHNS HOPKINS HOSPITAL REPORTS. Volume I. 423 pages, 99 plates.

Report in Patliology.

The Vessels and Walls of the Dog's Stomach; A Study of the Intestinal Contraction;

Healing of Intestinal Sutures; Reversal of the Intestine; The Contraction of the

Vena Portae and its Influence upon the Circulation. By F. P. Mall. M. D. A Contribution to the Pathology of the Gelatinous Type of Cerebellar Sclerosis

(Atrophy). By Henkt J. BERKiEr, U. D. Reticulated Tissue and its Relation to the Connective Tissue Fibrils. By F. P.

Mall, il. D.

Report in Dermntolo^y. Two Cases of Protozoan (Coccidioidal) Infection of the Skin and other Organs. By

T. C. Gilchrist, M. D., and Emmet Eixford. M. D. A Case of Blastomycetic Dermatitis in Man; Comparisons of the Two Varieties of

Protozoa, and the Blastomyces found in the preceding Cases, vdth the so-called

Parasites found in Various Lesions of the Skin, etc. ; Two Cases of Moliuscum

Fitjrosum; The Pathology of a Case of Dermatitis Herpetiformis (Duhring). By

T. C. Gilchrist, M. D.

Report in Pathology. Ad Experimental Study of the Thyroid Gland of Dogs, with especial consideration

of Hypertrophy of this Gland. By W. S. Halsted, M. D.


Volume II. 570 pages, with 28 plates and figures.

Report In Medicine.

On Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with

Gallstones. By William Osler, M. D. Some Remarks on Anomalies of the Uvula. By John N. Mackenzie, M. D. On Pyrodin. By H. A. Lafleur, M. D. Cases of Post-febrile Insanity. By William Osleb, M. D. Acute Tuberculosis in an Infant of Four Months. By Harry Toulmik, M. D. Rare Forms of Cardiac Thrombi. By William Osler, M. D. Notes on Endocarditis in Phthisis. By WiLLiAit Osler, M. D.

Report in Aledleine.

Tubercular Peritonitis. By William Osler, M. D.

A Case of Raynaud's Disease. By H. M. Thomas, M. D.

Acute Nephritis in Typhoid Fever. By William Osler, M. D.

Report in Gynecology.

The Gynecological Operating Room. By Howard A. Kellt, M. D.

The Laparotomies performed from October 16, 1689, to March 3, 1890. By Howard

A. Kelly, M. D., and Hitnter Robs, M. D. The Report of the Autopsies in Two Cases Dying in the Gynecological Wards without Operation; Composite Temperature and Pulse Cliarts of Forty Cases of

Abdominal Section. By Howard A. Kelly. M. D. The Management of the Drainage Tube in Abdominal Section. By Hunter Robb,

M. D. The Gonococcus in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Peritoneum;

Ovarian Tumor; General Gynecological Operations from October 15, 1889, to

March 4, 1S90. By Howard A. Kelly, M. D. Report of the Urinary Examination of Ninety-one Gynecological Cases. By Howabd

A. Kelly, M. D., and Albert A. Ghriskey, M. D. Ligature of the Trunks of the Uterine and Ovarian .\rteries as a Means of Checking

Hemorrliage from the Uterus, etc. By Howard A. Kelly, M. D. Carcinoma of the Cervix Uteri in the Negress. By J. W. Williams, M. D. Elephantiasis of the Clitoris. By Howard A. Kelly, M. D. Myxo-Sarcoma of the Clitoris. By Hunter Robb, M. D. Kolpo-Ureterotomy. Incision of the Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gynecological Operations. By

Howard A. Kelly, M. V.

Report in Surgery, I.

The Treatment of Wounds with Especial Reference to the Value of the Blood Clot in the Management of Dead Spaces. By W. S. Halsted, M. D.

Report in Neurology, I.

A Case of Chorea Insaniens. By Henry J. Berkley, M. D. Acute Angio-Neurotic Oedema. By Charles E. Simon, M. D. Haematomyelia. By Auodst Hoch, M. D.

A Case of Cerebro-Spinal Syphilis, with an unusual Lesion in the Spinal Cord. By Hehby M. Thomas, M. D.

Report in Pathology, I.

Amosbic Dysentery. By William T. Councilman, M. D., and Henri A. Lajleub, M. D.


Volume III. 766 pages, with 69 plates and figures.

Report in Pathology.

Papillomatous Tumors of the Ovary. By J. Whitridge Williams, M. D. Tuberculoaia of the Female Generative Organs. By J. Whitridge Williams, M. D.

Report in Pathology.

Multiple Lympho-Sarcomata, with a report of Two Cases. By Simon Flexnee, M. D.

The Cerebellar Cortex of the Dog. By Henry J. Berkley, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman, M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Russell, Ph. D.

Heart Hypertrophy. By Wm. T. Howard, Jr., M. D.

Report in Gynecology.

The Gynecological Operating Room; An External Direct Method of Measuring the Gonjugata Vera; Prolapsus Uteri without Diverticulum and with Anterior Enterocele; Lipoma of the Labium Alajus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Source of Error in Gynecological Diagnosis; Operation for the Suspension of the Retroflexed Uterus. By Howard A. Kelly, JI. D.

Potassium Permanganate and Oxalic Acid as Germicides against the Pyogenic Cocci. By Mary Sherwood, M. D.

Intestinal Worms as a Complication in Abdominal Surgery. By A. L. Stavely, M. D.


Oj-necological Operations not involving Cosliotomy. By Howard A. Kelly, M. D.

Tabulated by A. L. Stavely, M. D. The Employment of an Artificial Retroposition of the Uterus in covering Extensive

Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdo minal Pelvic Operations. By Howard A. Kelly, M. D. Photography applied to Surgery. By A. S. JIurray. Traumatic Atresia of the Vagina with Ha:matokoIpos and Hsmatometra. By Howard

A. Kelly, M. D. Urinalysis in Gynecology. By W. W. Russell, M. D.

The Importance of employing Anesthesia in the Diagnosis of Intra-Pelvic Gynecological Conditions. By Hunter Robb, M. D. Resuscitation in Chloroform Asphyxia. By Howard A. Kelly, M. D. One Hundred Cases of Ovariotomy performed on Women over Seventy Tears of Age

By Howard A. Kelly, M. D., and Mary Sherwood, M. D. Abdominal Operations performed in the Gynecological Department, from March 5.

1890, to December 17, 1892. By Howard A. Kelly, M. D. Record of Deaths occurring in the Gynecological Department from June 6, 1890, to

May 4, 1892.


Volume IV. 504 pages, 33 charts and illustrations.

Report on Typhoid Fever.

By William Osler, M. D., with additional papers by W. S. Thayer, 51. D , and J Hewetson, M. D.

Report in Neurology.

Dementia Paralytica in the Negro Race; Studies in the Histology of the Liver; The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of the Submaxillary Gland of Mw musrulus; The Intrinsic Nerves of the ThvToid Gland of the Dog; The Nerve Elements of the Pituitary Gland. By Henry J. Berkley,

Report in Surgery.

The Results of Operations for the Cure of Cancer of the Breast, from June, 1889. to January, 1894. By W. S. Halsted, M. D.

Report in Gynecology.

Hydrosalpinx, with a report of twenty-seven cases; Post-Operative Septic PeritonitisTuberculosis of the Endometrium. By T. S. Ccllen, M. B.

Report In Pathology.

Deciduoma Malignum. By J. Whitridge Williams, M. D.


Volume V. 480 pages, vnih 32 charts and illustrations.

CONTENTS

The Malarial Fevers of Baltimore. By W. S. Thayer. M. D., and J. Hewetson, M. D. A Study of seme Fatal Cases of Malaria. By Lewellys F. Barker, M. B.

Studies in Typhoid Fever. By William Osier, M. D., with additional papers by G. Bluuer, M. D., Simon Flexnek, M. D., Walter Reed, M. D., and H. C. Parsons, M. D.


Volume VI. 414 pages, Avith 79 plates and figures.

Report in Neurology.

studies on the Lesions produced by the Action of Certain Poisons on the Cortical Nerve Cell (Studies Nos. I to V). By Henry J. Berkley, M. D.

Introductory.— Recent Literature on the Pathology of Diseases of the Brain by the Chromate of Silver Methods; Part I.— Alcohol Poisoning.— Experimental Lesions produced by Chronic Alcoholic Poisoning (Ethyl Alcohol). 2. Experimental Lesions produced by Acute Alcoholic Poisoning (Ethyl Alcohol); Part 11.— Serum Poisoning.— Experimental Lesions induced by the Action of the Dog's Serum on the Cortical Nerve Cell; Part III.— Ricin Poisoning.— Experimental Lesions induced by Acute Ricin Poisoning. 2. Experimental Lesions induced by Ciironic Ricin Poisoning; Part IV.— Hydrophobic Toxaemia.— Lesions of the Cortical Nerve Cell produced by the Toxinc of Experimental Rabies; Part V.— Patliological Alterations in the Nuclei and Nucleoli of Nerve Cells from the Effects of Alcohol and Ricin Intoxication; Ner\-e Fibre Terminal Apparatus; Asthenic Bulbar Paralysis. By Henry J. Berkley, M.D.

Report in Pathology.

Fatal Puerperal Sepsis due to the Introduction of an Elm Tent. By Thomas S.

Cullen, M. B. Pregnancy in a Rudimentary Uterine Horn. Rupture, Death. Probable Migration of

Oram and Spermatozoa. By Thomas S. Cullen, M. B., and G. L. Wilkins, M. D. Adeno-Myoma Uteri Diffusum Benignum. By Thomas S. Cullen, M. B. A Bacteriological and Anatomical Study of the Summer Diarrhoeas of Infants. Bv

William D. Booker, M. D. The Pathology of Toxalbumin Intoxications. By Simon Fleinbr, M. D. Thf price of n .ii-l hoiitid in cloth {Vols. I-VI] of tin- Uospitnl Jtejiorts i.i

$30.00. Vols. I, II and III are not sold separntelii. The nrice of

Tola, ir, r and Tl is $3.00 each. -^ ± i


Monographs.

The following papers are reprinted from Vols. I, IV, V and VI of the Hcports, for those who desire to purchase in this form: STUDIES IN DERMATOLOGY. By T. C. Gilchrist, M. D., and Emmet Rixford,

M. D. 1 volume of 164 pages and 41 full-page plates. Price, bound in paper,

$3.00. THE MALARIAL FEVERS OF BALTIMORE. By W. S. Thayer, St. D., and J.

Hewetson, M. D. And A STUDY OF SOME FATAL CASES OF MALARIA.

By Lewellys F. Barker, M. B. 1 volume of 280 pages. Price, in paper, ?2.75. STUDIES IN TYPHOID FEVER. By William Osler. JI. D., and others. Extracted

from Vols. IV and V of the Johns Hopkins Hospital Reports. 1 volume of 481

pages. Price, bound in paper, $3.00. THE P.VTIIOLOGV OF rnXALBUMIN ISTOXICATIflNS. liv Pimon Flexner, M. D. I

volume of Inii puLre.a with 1 fuli-pace lltliosraplis. 1 rice, bound in paper, $i.O(i. Subscriptions for the above publications may be sent to

The Johns Hopkins Press, Baltimore, Md.


46


JOHNS HOPKINS HOSPITAL BULLETIN.


[Xo. 83.


THE JOHNS HOPKINS MEDICAL SCHOOL. SESSION 1897-1898.


FACULTY.


Daniel C. Gilman, LL. D., President.

William H. Welch, M. D., LL. D., Dean and Professor of Pathology.

Ira Uemsen, M. D., Ph. D., LL. D., Professor of Chemistry.

William Osler, M. D., LL. D., F. R. C. P., Professor of the Principles and Practice

of Medicine. Henrv M. Hurd, M. D., LL. D., Professor of Psychiatry. William S. H.\lsted, M. D., Professor of Surgery. Howard A. Kelly, M. D., Professor of Gynecology and Obstetrics. Franklin P. Mall, M. D., Professor of Anatomy. John J. Abel. M. D., Professor of Pharmacology. William H. Howell, Ph. D., M. D., Professor of Physiology.

William K. Brooks, Ph. D., LL. D., Professor of Comparative Anatomy and Zoology. John S. Billings, M. D., LL. D., Lecturer on the History and Literature of Medicine. Charles Wardell Stiles, Ph. D., M. S., Lecturer on Medical Zoolog}-. Robert Fletcher, M. D., M. R. C. S., Lecturer on Forensic Medicine. William D. Cooker, M. D., Clinical Professor of Diseases of Children. John N. Mackenzie, M. D., Clinical Professor of Larj'ngology and Rhinology. Samuel Theobald, M. D., Clinical Professor of Ophthalmology and Otology. Henry M. 1'homas, M. D., Clinical Professor of Diseases of the Nervous System. Simon Flexneb, M. D., Associate Professor of Pathology. J. Whitridoe Williams, M. D., Associate Professor of Obstetrics. Lewkllys F. Barker. M. B., Associate Professor of Anatomy. Wiluam S. Thayer, M. D., Associate Professor of Medicine. JoH.v M. T. Finney, M. D., Associate Professor of Surgery.


George P. Dbeyer, Ph. D., Associate in Physiology.

William W. Russell, M. D., Associate in Gynecology,

Henry J. Berkley, M. D., Associate in Neuro-Pathology.

J. Williams Lord, M. D., Associate in Dermatology and Instructor in Anatomy.

T. Caspar Gilchrist, M. R. C. S., Associate in Dermatology.

Robert L, Randolph, M. D., Associate in Ophthalmology and Otology.

Thomas B. Aldrich, Ph. D., Associate in Physiological Chemistry.

Thomas B. Futcher, M. B., Associate in Medicine.

Joseph C. Bloodgood, M. D., Associate in Surgery.

Thomas S. Cullen, M. B., Associate in Gynecology.

Ross G. Harrison, Ph. D., Associate in Anatomy,

Frank R. Smith, M. D., Instructor in Medicine.

Georgia W. Dobbin, M. D., Assistant in Obstetrics.

Walter Jones, Ph. D,, Assistant in Physiological Chemistry.

Adolph G. Hoen, M. D., Instructor in Photo-Micrography.

Sydney M. Cone, M. D., Assistant in Surgical Pathology.

Louis E. Livingood, M. D., Assistant in Pathology.

Henry Barton Jacobs, M. D., Instructor in Medicine.

Charles R. Bardeen, M. D., Assistant in Anatomy.

Stewart Paton, M. D., Assistant in Nervous Diseases.

Norman McL. Harris, M. B., Assistant in Pathology.

Harvey W. Cubhing, M. D., Assistant in Surgerj'.

J. M. Lazeab, M. D., Assistant in Clinical Microscopy.

J. L. Walz, Ph. G., Assistant in Pharmacy.


GENERAL STATEMENT.

The Medical Department of the Johns Hopkins University was opened for the instruction of students October, 1803. This School of Medicine is an integral and coordinate part of the Johns Hopkins University, and it also derives great advantages from its close affiliation with the Johns Hopkins Hospital.

The required period of study for the degree of Doctor of Medicine is four years. The academic year hegins on the first of October and ends the middle of June, with short recesses at Christmas and Easter.

Men and women are admitted upon the same terms.

In the methods of instruction especial emphasis is laid upon practical work in the Laboratories and in the Dispensary and Wards of the Hospital. While the aim of the School is primarily to train practitioners of medicine and surgery, it is recognized that the medical art should rest upon a suitable preliminary education and upon thorough training in the medical sciences. The first two years of the course are devoted mainly to practical work, combined with demonstrations, recitations and, when deemed necessary, lectures, in the Laboratories of Anatomy, Physiology, Physiological Chemistry, Pharmacology and Toxicology, Pathology and Bacteriology. During the last two years the student is given abundant opportunity for the personal study of cases of disease, his time being spent largely in the Hospital Wards and Dispensary and in the Clinical Laboratories. Especially advantageous for thorough clinical training are the arrangements by which the students, divided into groups, engage in practical work in the Dispensary, and throughout the fourth year serve as clinical clerks and surgical dressers in the wards of the Hospital.

REQUIREMENTS FOR ADMISSION.

As candidates for the degree of Doctor of Medicine the school receives:

1. Those who have satisfactorily completed the Chemical-Biological course which leads to the A. B. degree in this university.

2. Graduates of approved colleges or scientific schools who can furnish evidence : (a) That they have acquaintance with Latin and a good reading knowledge of French and German ; (6) That they have such knowledge of physics, chemistry, and biology as is imparted by the regular minor courses given in these subjects in this university.

The phrase "a minor course," as here employed, means a course that requires a year for its completion. In physics, four class-room exercises and three hours a week in the laboratory are required; in chemistry and biology, four class-room exercises and five hours a week in the laboratory in each subject.

3. Those who give evidence by examination that they possess the general education implied by a degree in arts or in science from an approved college or scientific school, and the knowledge of French, German, Latin, physics, chemistry, and biology above indicated.

Applicants for admission will receive blanks to be filled out relating to their previous courses of study.

They are required to furnish certificates from officers of the colleges or scientific schools where they have studied, as to the courses pursued in physics, chemistry, and biology. If such certificates are satisfactory, no examination in these subjects will be required from those who possess a degree in arts or science from an approved college or scientific school.

Candidates who have not received a degree in arts or in science from an approved college or scientific school, will be required (1) to pass, at the beginning of the session in October, the matriculation examination for admission to the collegiate department of the Johns Hopkins University, (2) then to pass examinations equivalent to those taken by students completing the Chemical-Biological course which leads to the A. B. degree in this University, and (3) to furnish satisfactory certificates that they have had the requisite laboratory training as specified above. It is expected that only in very rare instances will applicants who do not possess a degree in arts or science be able to meet these requirements for admission.

Hearers and special workers, not candidates for a degree, will be received at the discretion of the Faculty.

ADMISSION TO ADVANCED STANDING.

Applicants for admission to advanced standiug must furnish evidence (1) that the foregoing terms of admission as regards prelirniu.iry training have beeu rulfllled, (2) ibat courses equivaleut lu liiud and amount to those given here, preceding that year of the course for admission to which appiicatiou is made, have been satisfactoriiy completed, and (3i must pass examinations at tlie beginning of ttie session in October In all the suljjects thai have beeu already pursued by the class to wlilch admission is sought. Certiflcales of standing elsewhere cannot be accepted in i)lace of these examinations.

SPECIAL COURSES FOR GRADUATES IN MEDICINE. \

Since the opening of the Johns Hopkins Hospital in lS8!t, courses of iustruction have been offered to graduates in medicine. The attendance upon these courses has steadily increased with each succeeding year and indicates gratifying appreciation of the special advantages here afforded. With the completed oi-ganization of the Medical School, it was found necessaiy to give the courses intended especially for physicians at a later period of the academic year than that hitherto selected. It is, however, believed that the period now chosen for this purpose is more convenient for the majority of those desiring to take the courses than the former one. The special courses of instruction for graduates in medicine are now given aunually during the months of May and June. During April there is a preliminary course in Normal Histology. These courses are in Pathology, Bacteriology, Clinical Microscopy, General Medicine, Surgery, Gynecology, Dermatology, Diseases of Children, Diseases of the Nervous System, Genito-Urinary Diseases, Laryngology and Rhinology, and Ophthalmology and Otology. The instruction is intended to meet the requirements of practitioners of medicine, and is almost wholly of a practical character. It includes laboratory courses, demonstrations, beside teaching, and clinical instruction in the wards, dispensary, amphitheatre, and operating rooms of the Hospital. These courses are open to those who have taken a medical degree and who give evidence satisfactory to the several instructors that they are prepared to profit by the opportunities here offered. The number of students who can be accommodated in some of the practical courses is necessarily limited. For these the places are assigned according to the date of application. I

The Annual Announcement and Catalogue will be sent upon appiicatiou. Inquiries should be addressed to the J

REGISTRAR OF THE JOHNS HOPKINS MEDICAL SCHOOL, BALTIMORE. ^


The Johns Hopkins Hospital Bulletins are issued monthly. They are printed by THE FRIEDENWALD CO., Baltimore. Single copitt may be procured from Messrs. CUSHINO £ CO. and the BALTIMORE NEWS COMPANY, Baltimore. Subscriptions, $1.00 o year, may be iddrr.'ified to the publishers, THE JOHNS HOPKINS PRESS, BALTIMORE; single copies will be sent by mail for fifteen cents each.


BULLETIN


OF


THE JOHNS HOPKINS HOSPITAL.


Vol. IX.- No. 84.]


BALTIMORE, MARCH, 1898.




OOlSTTlBISrTS.


Leprosy in the United States, with the Report of a Case. By Wm. OSLEK, M. D.,

Secondary Melano-Sarcoma of the Liver following Sarcoma of the Eye. By Louis Philip Hambukqer, M. D., . - On Infection with a Para-Colon Bacillus in a Case with all the Clinical Features of Typhoid Fever. By Norman B. Gwyn, M.B.,

The Management of Solid Tumors of the Ovaries complicating Pregnancy, with Report of a Successful Case. By William E. Swan, M. D., - - -


The Catheterization of the Ureters in the Male through an Open Cystoscope with the Bladder distended with Air by Posture.

By H. A. Kelly, M.D., - 62

Proceedings of Societies :

Hospital Medical Society, 62

On Super-Arterial Pericardial Fibroid Nodules [Mr. Knox] ; —Discussion of Dr. Hunner's Cases of Aneurism [Dr. Oslek] ; — Discussion of Dr. Pancoast's Diabetes in the Negro [Dr. Osler].

Notes on New Books, ----64

Books Received, - ---65


LEPROSY IN THE UNITED STATES, WITH THE REPORT OF A CASE.

By William Osler, M. D., Professor of Medicine in the Johns Hophins University. [Clinical Lecture delieered at Ike Johns Hopkins Hospital, Wednesday, Feb. 2, 1S98.]


To no disease perhaps has attention been more actively called of late years than to leprosy, one of the oldest and most dreaded scourges of the race. In great part this has been due to the activity in England of a Leprosy Commission, and to the establishment of a National Leprosy Fund. Through the energy of Dr. Lassar a Leprosy Conference has recently been held in Berlin, two volumes of the proceedings of which I pass about for your inspection. They contain an immense amount of valuable information with reference to the present status of the disease throughout the world, and the best means for its prevention.

I take this opportunity of again showing to you the case which has been in Ward I for some mouths, and of speaking upon the present condition of the disease in the United States and the prospects of its spreading. First let me refresh your memories about the patient before you. Her history is as follows : She is now 30 years old. She was born in Baltimore, of French-German parents; her father was a native Frenchman who came here when young; he served in the army, was a very healthy man and had no skin eruption. He died at the age of 50. Her mother, who died at the age of 40, appears to


have been a healthy woman. When 16 years old the patient visited an uncle in Demerara, remaining only a few months. This uncle, a native American, is at present in Baltimore, and neither he nor any member of his family has ever had a serious skin disease. On returning to this country she lived in Baltimore, one year in Norfolk, and for the last five years in Alleghany City, Pa. She returned to this city in April, and was admitted to the hospital as a case of obstinate lues.

Her personal history is as follows. She was healthy as a young girl ; she married when 20 years old, had one child at 23, which died shortly after birth ; she has had one miscarriage since. Her present illness began six years ago. Here is a photograph taken two years prior to the onset of the trouble, from which you can judge of the terrible changes the disease has wrought. She noticed first two brown spots over the elbow, and then several spots on the wrist. She was pregnant at the time, and had with their appearance a little fever and slight indisposition. These spots remained stationary until after her confinement, when they increased in size and became nodular. The disease spread rapidly, the feet being attacked next, beginning on the ankles nearly five years ago. Ever


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since there has been a steady appearance of lumps and nodules on the skin of the face, legs and arms. Only during the past year have they appeared above the elbows. Two years ago she lost the eyebrows and lashes ; the hair of the head is not falling out. The voice began to get hoarse a few months ago, and eight months since she noticed the formation of scabs in the nose.

Her condition at present is very characteristic of tubercular leprosy. She looks a great deal older than her age ; the swollen appearance of the eyebrows and cheeks, the rounded outlines of the nose and of the ears, the absence of eyelashes, and the brownish pigmented discoloration, give a picture that is perfectly characteristic. The neck is only slightly involved, showing only a few pigmented areas. The hands, feet and legs are very much involved, the hands showing scars of erosion and ulceration ; the finger-nails are not attacked, but in the left hand are fresh punched-out ulcers. On the arms are scars of several very deep nlcers. On the upper arm the earlier stages are shown, the brownish discoloration, and the skin looks raised and infiltrated, and on palpation one can feel that beneath the skin there is a nodular infiltration. The forehead shows a uniform infiltration. She has little or no disturbance of sensation; she feels touch everywhere and feels pain.

She has been under our care since April last, and has improved in very many ways. The general nutrition is much better. The open ulcers and sores which were present on admission have, as you see, almost entirely healed. During the months of June, July and August she had a great deal of fever, but now for some time the temperature has been normal. She has gained in weight, and is in every way very much more comfortable. She is a very tidy, neat woman, and now is able to look after her own room. I may add that it has been to both physicians and nurses of our staff a great pleasure to be able to care for her and make her comfortable.

Where did this patient contract leprosy ? You noticed in the history that she had resided in Demerara in the West Indies, a colony much alBicted with the disease. True, it is now fifteen years since she left there, and it was eight years before the first appearance of the disease. It is well known that the period of incubation may be very much longer, even as long as twenty or thirty years. It may be said that without exception all cases of leprosy met with in the Eastern States are persons who have lived for a shorter or a longer time in countries where the disease prevails. The experience in Great Britain is very instructive in this respect. Abraham estimates that within the past ten years the number of cases has been about one hundred, and so far as is known there has been but one instance in which the disease has been transmitted. This was the well known case reported by Benson, of an Irish soldier who returned from India with leprosy. His brother slept in the same bed with him for at least a year and a half, and after his death he wore the leper's clothes. Three years later the brother became leprous.

You will find in these volumes of the Transactions of the Leprosy Conference — of which by the way there is a very good abstract in Nos. 2 and 4 of the Philadelphia Medical Journal by Dr. Nuttall — a very full discussion of all the problems


relating to the disease. Of these by far the most important relates to the method of infection, whether by inoculation, contagion, or hereditary transmission.

The possibility of successful inoculation must be recognized, though Hansen, the leading living expert on leprosy, declares that as yet all attempts at reproducing the disease by direct inoculation have been unsuccessful. He does not regard Aruing's experiment on the Honolulu convict as satisfactory, since this man had leprous relatives. A number of observers, including some of the best students of the disease, have inoculated themselves with negative results. The direct hereditary transmission must be excessively rare, more so indeed than in tuberculosis. As lepers have, as a rule, very few children, heredity can only play a very small part in the spread of the disease. Alverez stated at the recent Congress that he had never seen a new-born leper child; the youngest patient he had met with was three and a half years old.

The highly contagious character of leprosy has been a fixed belief for centuries, and much of the popular dread is based upon the highly colored views as to the extreme risk of contact with the disease. For a full discussion of the question I must refer you to the Proceedings of the recent Congress. The opinion was universally in favor of its contagious nature, though the greatest difference of opinion existed as to the methods by which the disease is conveyed, and on this question we really need much more information. An important point was brought out at the Congress as to the much more widespread distribution of the lepra bacilli, particularly in the secretions. In modern times one of the strongest points in favor of the contagious nature of the disease is the manner in which it has spread in the Sandwich Islands. Europeans residing in leprous regions occasionally contract the disease, and with scarcely an exception, as in the patient I have jbst shown you, cases occurring in leprosy-free regions have a history of a residence for a longer or shorter time in localities in which the disease prevails. On the other hand there are a great many facts which would indicate that it is very difficult to catch the disease. It is true that Father Damien at the leper settlement at Molokai, and Father Boglioli (whose portrait I here show you) in Kew Orleans, contracted the disease in the discharge of their ministerial duties, but it has been the almost universal experience in the leper settlement* | and lazarettos that the nurses, physicians and attendants are n not attacked. At the Tracadie settlement, which I visited a few years ago, the head Sister told me that during the forty years no Sister or servant had contracted the disease, though the accommodations are rather contracted. Not one of the Sisters who have nursed in the Trinidad Asylum, for now nearly thirty years, has contracted the disease.

A very important question is whether there is any possi- I bility that leprosy will again spread in the more civilized dis- I tricts of the earth. A good deal of uneasiness has beeu fostered by sensational newspaper reports. The practical question for us here is, is leprosy spreading in the United States? I have here letters from most of the infected districts, the contents of which I will briefly summarize. Including the two districts in the Dominion of Canada, there may be said to be five foci in which the disease at present prevails.


March, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


49


lu the northeru part of New Brunswick leprosy lias existed iu a couple of counties since tlie early j)art of the century. The cases as recognized are segregated in thelazarette at Tracadie. Dr. Smith, the physician in charge, writes under date of January 17, 1898: "The number at present in the hospital is twenty-four, eighteen males and six females. ... Of the above number three are Icelanders whom I brought from Manitoba. Leprosy in Cape Breton has almost died out. With us iu New Brunswick segregation is stamping out the disease. The cases have dwindled from about forty in the early history of the disease to about half that number. One of our inmates is a negro I brought recently from St. John, N. B. He had strayed from Bermuda. Leprosy is not on the increase iu Canada." In British Columbia the disease has been introduced by the Chinese, but I have recently heard from Dr. Hanniugton, of Victoria, that there are only eight cases at present iu the settlement on Darcy Island. Dr. Hanningtou does not think that the disease is spreading. Among the Icelandic immigrants in Manitoba there are a few cases, but the strong probability is that it will gradually die out.

In the United States there are three important centres. To "New Scandinavia," as parts of Minnesota and Wisconsin have been called, the disease was introduced by the immigrant Swedes and Norwegians. Altogether more than 150 cases were known. The disease has not spread, and Dr. Bracken, the Secretary of the State Board of Health, wrote January 19, 1898, that there are in Minnesota, so far as is known, only twenty-seven cases, and some of these have probably died since the last return. All of them contracted the disease before coming to America. A very encouraging fact is that no instance of leprosy has been known to be contracted from any of these Norwegian settlers. In California leprosy has been introduced by the Chinese, and in a few instances by native Americans returning with the disease from the Sandwich Islands. The total number of cases, however, is not large, certainly not more than a dozen, and the likelihood of the disease progressing in the native American population is very slight.

By far the most extensive focus of leprosy is in Louisiana. Dr. Isadore Dyer, who was the delegate from Louisiana to the Leprosy Conference in Berlin, has reported fully on the history of the disease iu that State, where it has been known since 1785. Dr. Dyer writes under date of January 12, 1898: "My paper on endemic leprosy in Louisiana, read before the Lepra Conference in Berlin, has not yet been published. It is to appear iu the third or fourth volume of the Transactions of this meeting. Full tables are given of all recorded leprosy in Ijouisiana since 1785, the existing acknowledged cases being separately tabulated. This last table contains 118 cases, in addition to which I have seen six within the past four months, making a total of 124 positive living cases to-day." Dr. Dyer thinks that this does not represent by any means all the cases, bnt says he believes it is quite justifiable to calculate the number of lepers in this State as not less than 300.

A few cases of leprosy are met with in Florida, South Carolina and in others of the Southern States. Now and again cases occur in the eastern cities, invariably imported, as in the patient at present in the hospital. So far as we know.


with the exception of the single case recorded by Dr. I. B. Atkinson of this city, there has not been an instance in which the disease has been transmitted from one of these imported cases to a natire American.

I believe the danger of the disease spreading and becoming in any way a serious menace to the country is entirely fanciful. In the question of the annexation of Hawaii the danger of leprosy has also come up. This really would not be a serious objection. I have seen a letter from Dr. Day, from Honolulu, iu which he claims that the disease is progressively diminishing, and that the statement made by Dr. Prince A. Morrow, 'of New York, that every one in ten individuals in the Sandwich Islands is leprous is entirely unwarranted. He quotes figures to show that the number of cases segregated in Molokai has progressively diminished in the past few years. In a recent letter to the San Francisco Chronicle the President of the Board of Health states that barely one per cent of the population of the Sandwich Islands has leprosy.

The means for combating the existing cases of the disease are perfectly plain and well understood. The Norwegian method of segregation should be enforced in Louisiana and in the State of California. Remarkable results have followed this plan in Norway. In 1856 there were nearly 3000 lepers in Norway ; now there are not more than 700, and most of them are iu asylums. The segregation should be compulsory iu all instances except when the friends can show that they have ample provision in their own home for the comjilete separation and proper care of the patient.

In the case of the patient you have just seen, as her husband is not in a position to look after her, it is the duty of the city to care for her in a proper way. She should be removed to Bay View, where a room should be provided with a separate arrangement for washing the clothes and disinfecting the body linen. From a humanitarian standpoint we have been very glad to care for her and to do what we could to check the disease in its active and progressive state. Now that she has improved so much I feel that we are no longer bound to keep her, and as she is a free agent, I shall take an early opportunity to discharge her from my care.


NOTICE.

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

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

Under the directions of the founder of the Hospital the free beds are reserved for the sick poor of Baltimore and its suburbs and for accident cases from Baltimore and the State of Maryland. To other indigent patients a uniform rate of $.5.00 per week has been established. The Superintendent has authority to modify these terms to meet the necessity of urgent cases.

The Hospital is designed for cases of acute disease. Cases of chronic disease are not admitted except temporarily. Private patients can be received irrespective of residence. The rates in the private wards are u-overned by the locality of rooms and range from $30.00 to $35.00 per week. The extras are laundry expenses, massage, the services of an exclusive nurse, the services of a throat, eye, ear and skin or nervous specialist, and surgical fees. Wherever room exists in the private wards and the condition of the patient does not forbid it, companions can be accommodated at the rate of $15.00 per week.

One week's board is payable when a patient is admitted.


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[No. 84.


SECONDARY MELANO-SARCOMA OF THE LIVER FOLLOWING SARCOMA OF THE EYE.


Br Louis Philip Hamburgjpr, M. D., Resident Medical Officer, The Johns Hopkins Hospitcd.


lu au article written in 1889 Litten called attention to the inadequacy of the accounts of melano-sarcoma of the liver following a primary growtli in the eye. With the exception of Virchow's classical work on tumors, the condition had not been presented in the text-books of medicine or of pathological anatomy in a manner befitting its importance, and Litten writes, " Even the best special works on diseases of the liver, in German, French, and English, scarcely mention it."

Litten's case was that of a man aged 34 years, whom he saw in November, 1884, with a tumor of the liver. He did notsee him again until March, 1888. The man was then cachectic, the tumor had increased iu size, and in some places showed fluctuation. The possibility of echinococcus cysts was discussed and one of the fluctuating points was aspirated. A black fluid was withdrawn containing polymorphonuclear cells filled with pigment and many pigmented polygonal cells — the pigment being dark brown and even black in some cells — and finally, a few red blood corpuscles. The patient wore a glass eye, and upon referring to the ophthalmological records it was discovered that the right eye had been removed in January, 1884, for a melanotic sarcoma of the choroid. Thereupon the urine was carefully examined and melannria was demonstrated. The history of a choroidal tumor, au enlarged and nodular liver and melanuria rendered the diagnosis clear; it was subsequently confirmed at the autopsy.

Since the publication of the above-mentioned paper many cases of liver metastasis following primary melanotic tumor of the eye have been reported, but even now the clinical picture has not received the attention which it deserves. Within a year two patients have presented themselves at the Johns Hopkins Hospital with this condition.

Case I. C. B., male, white, age 42; admitted August 21, 1896, complaining of pain in right side.

Family liistory unimportant. Patient has never had any serious illness. Five years ago, upon the day he sailed from England to this country, his right eye witliout apparent cause became inflamed. He received no medical attention and at tlie end of the voyage the eye was quite blind.

His present illness began six weeks ago with a sAabbing pain in right side. He then for the first time noted a small lump over the lower ribs on the right side, wliich was so painful upon any exer. tion that he gave up work.

There is anorexia ; no Vomiting ; bowels irregular ; he has lost 35 pounds in weight since onset.

Physical Examination. Patient is sparely nourished and rather pale. Right eye atrophied ; on seventh rib just outside the right maramillary line there is a hard fusiform enlargement 6>^x4 cm. and a'. out 1 cm. in depth. It is firm and seems attached to the rib; the overlying skin is not discolored. Examination of heart and lungs negative.

Abdomen. With the exception of a slight bulging in the right hypochondrium, the abdomen looks natural. Liver flatness begins at the sixth rib in right mammillary line ; its edge is palpable 10 cm. below the costal margin ; it is less distinctly felt as one reaches tlie median line. Surface is smooth and firm ; edge a little irregular. In the epigastrium are four small flattened prominences which feel like subcutnneus flbro-cartilaginous nodules. Spleen not pal


pable ; no general glandular enlargement. Rectal examination negative. Urine, light amber, acid ; specific gravity 1(20-26; no albumin or sugar ; diazo-reaction present.

September 4th, Dr. Mills removed the atrophied glebe, and at ita posterior portion a small melano-sarcoma, evidently arising from the choroid, was discovered. The patient remained in the hospital a month. Subsequently, on October 8, 1896, he was readmitted, looking paler and more emaciated, and com plaining of pain in right and left sides, epigastrium, right shoulder.

The lower right chest is bulging; abdomen is markedly distended, especially in right hypochondrium. On palpation the edge of the liver is felt about 14 cm. below costal margin in riglit mammillary line ; in right and left hypochondrium the edge feels sharp and normal, but below and to the right it is very hard and nodular. Surface is slightly irregular. The patient remained under observation two weeks, and at his own request was discharged ; his subsequent history is not known. During these weeks theliver rapidly increased in size; a small swelling similar to the one on the seventh rib, but about one-third its size, appeared on the fifth rib, riglit side, at junction of its osseous and cartilaginous portions ; lymphatic glands became palpable in right inguinal and left prsterior cervical regions.

The second case we were able to study more thoroughly.

Case II. P. W., male, white, age 38 years, admitted July 26, 1S97, complaining of pain in the lateral regions of abdomen and in the back on right side. Family history unimportant. Patient has bad smallpox and rheumatism, otherwise always healthy. About December, 1890, he was struck in the right eye by the branch of a tree. At the time he paid little attention to the incident, but in the course of the winter the eye began to give him pain and his head ached a great deal. During 1891 his vision began to fail, and in January, 1892, a physician whom he consulted enucleated the eyeball.

Present Illness. Began between two and three years ago, that is, about three years after the enucleation, with pain in the abdomen. For the past year has not been able to do much work, for the pain, which extends all over the abdomen and is of a ' burning " character, is rendered more severe by any exertion. During last six months little nodules have appeared over the chest. Does not think complexion is darker than formerly ; no jaundice ; appetite variable ; vomited once last week ; three years ago weighed 185 poundp, now 117 pounds ; has grown weak. At present he has a great deal of frontal headache. He has had cough for three or four days; slight whitish expectoration.

Physical Examination. Patient is an emaciated man ; swarthy complexion ; lips and mucous membranes of fair color. He wears a glass eye in the right orbit, and when it is removed a moist glistening brown mass is visible in the posterior portion of orbital cavity. Scattered over arms, thorax, abdomen and back are noilules varying in size from one-half to three and a half cm. in diameter, bluish-green in color, and not adherent to the skin or deep tissues. Percussion note over front of chest resonant. In the supra-clavicular fossiB expiration is prolonged, elsewhere of normal relative length. Percussion note over right half of back below middle of scapula lacks resonance ; in this area many medium-sized r;iles are heard ; a few over base of left lung. Elsewhere the lung isclearon percussion and auscultation. Heart sounds feeble but free from murmurs.

Abdomen. Full; costal grooves obliterated. Right costal margin considerably more prominent than left; right half of abdomen is more distended than left ; veins are prominent over its suiface.


March, 1898.]


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51


Respiratory movements slight. On deep inspiration a large mass descends in the right half of abdomen. Hepatic flatness begins at the sixthribin the right mammillary line and extends 5;i cm. below costal margin and 13}i cm. below ensiform cartilage in the median line. On palpation a large firm mass occupies an area the limits of which correspond to those obtained on percussion. The mass (evidently the enlarged liver) is extremely firm and distinctly nodular; its edge is rounded. There is general tenderness over abdomen. Spleen not palpable. No general glandular enlargement. Rectal examination negative ; urine showed reactions of melanuria. One of the subcutaneous tumors was removed and proved to be a spindle-cell sarcoma with brown pigment within the cells as well as about them ; there was some alveolar arrangement.

Blood. Red blood corpuscles 4,480,000 ; white blood corpuscles 10,300 ; hfemoglobin 40 per cent. Differential count : Polymorphonuclears 71.6 per cent.; small mononuclear8^17.4 per cent.; large mononuclears 9 per cent.; eosinophiles 2.8 per cent.

After admission the patient had attacks of vomiting and diarrhoea, occasional elevations of temperature, now and then paroxysms of coughing during which he expectorated frothy bloodstained sputa. The abdominal tumor and the growth in the orbit rapidly increased in size, new subcutaneous nodules appeared here and there, he suffered great pain in the abdomen, especially on defecation, became progressively weaker and more emaciated, and finally died on October 13, 1897.

Autopsy. The autopsy, performed by Dr. Flexner, showed the most extensive metastases involving the liver, kidneys, lungs, pancreas, thyroid gland, stomach, intestine, gall-bladder, the abdominal, mediastinal and thoracic lymph glands. The right optic nerve showed a grey degeneration and was atrophied ; the meninges were cedematous.

The first case is evidently one of primary sarcoma of the choroid with liver metastases; the second, one of general dissemination following what was presttmably a melano-sarcoma of the nveal tract, although an account of the condition of the eye at the time of enucleation could not be obtained.

In each case the loss of an eye, the subcutaneous tumors and enlarged liver contributed to form the characteristic picture of melano-sarcoma; indeed, in the second patient the loss of an eye, the pigmented nodules and the colossal nodular liver descending visibly with each inspiration, enabled one to make the diagnosis de visu. In addition to emphasizing the clinical aspect of this condition, the cases serve to illustrate many features of pigmented sarcoma of the eye and its sequelffi.

Following the classification of Virchow, pigmented sarcomata of the eye are divided into three classes: 1. Primary external melauo-sarcomata which arise at the scleral border. 2. An orbital variety, springing most probably from the adipose tissue of the orbit. 3. Primary internal melanosarcomata. It is to this division that the first and probably the second of the present series belong. These are the sarcomata arising from the uveal tract; the great majority have their point of origin in the choroid, and as in our case most frequently from its posterior portion. They are composed of spindle cells, or they may contain besides spindle, round and stellate cells.

. The disease is not a common one. With the exception of early childhood, it occurs at all ages. Most of the patients are between forty and sixty years of age; a case has been observed as late as the 8ith year.

In each of the above histories one's attention is attracted


to certain incidents preceding the development of the tumor. It will be recalled that in the one case there is an account of a trauma one year preceding removal of the globe, and in the other, of an inflammatory trouble coming on five years before the new growth was detected, which had caused meanwhile an atrophy of the eyeball. Now, the association of simple inflammatory conditions, with or without antecedent trauma, and the development of melanotic sarcoma of the eye, has often been commented upon and is frequently so striking that it cannot be dismissed as a chance coincidence. Virchow quotes a number of examples. Thus, Rosas reports the case of a woman who lost her sight through an injury received four years previously while splitting wood. Cooper narrates the case of a woman whose cornea had been cloudy two years as the result of an inflammation. Bowman and Mackenzie each gives an example of the growth developing in an eye in which there was present a condition quite similar to that found in our first patient, namely, atrophia lulbi. Particularly instructive is a ease reported by Raab, inasmuch as imbedded in the tumor could still be demonstrated a portion of the splinter of wood which a year previously had caused the trauma. In 103 cases LaAvford and Collins obtained the history of injury in 6.79 per cent.

Perhaps no other astiological factors in the domain of new growths have been more discussed than those we have just been considering; the details of this discussion need not be rehearsed. It is particularly interesting, however, in this connection to note the recent endeavor to associate the development of malignant growths of the alimentary tract with trauma.* Once the ocular sarcoma becomes established a metastasis sooner or later occurs. All the organs may contain tumor masses, but certain of them are more prone to involvement than others. When there is a widespread dissemination, the distribution is much the same as that presented by our autopsy.

Almost all of the organs as above stated were involved. The spleen, bones, bladder, prostate and testicles were free from metastases. The pleurae were extensively involved, but in the parenchyma of the lungs there were only two or three nodules about the size of a walnut and a few smaller masses just beneath the pleura. The tumor masses varied in color from a mottled grey to a deep black ; the former usually firm, the more deeply pigmented portions almost diffluent.

Sections prepared from the abdominal lymph glands showed microscopically a pigmented large cell sarcoma.

The liver seems to offer a most favorable soil for the development of secondary growths, and it may be the only organ affected. Some of the largest livers on record belong to this group.

The liver of Litten's patient weighed about 10 kilo (27 pounds). In our second case the organ weighed 8.3 kilo (22 pounds). The capsule was tense and congested. Pigmented nodules projected from its surface, pushing the capsule out. At about the level of the umbilicus there was a fresh deposit of fibrin as well as old adhesions between the liver and the abdominal walls. There were similar deposits on the superior


'Boas. Deut. med. Wochenschr., No. 44, Oct. 1897.


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[No. 84.


surface of the right lobe and adhesions to the CBSophagus. Projecting from the inferior surface of the right lobe near its lower margin was a pedunculated tumor 5x4x6 cm.; soft, lobulated and grey on section. Many nodules of various sizes were scattered through the substance of the liver ; the largest about the size of an orange, black, and almost diffluent • the smaller variety usually greyish or slate color. Microscopically the pigmented tumor cells had an alveolar arrangement with scanty stroma intervening.

Assuming as we do that dissemination takes place through the blood, what determines the localization of metastases in certain organs and the escape of others is not at all clear. The same difficulty is met with in some cases of multiple lympho-sarcomata, and here it has been suggested that the process is really not to be regarded so much as a metastasis in the nsual sense, but rather as an infectious disease, the result of the diffusion of a virus through the body (Schulz, Flexner). Efforts have been made to detect the materies morbi in the blood, but the results have r,ot been encouraging. Pigment granules and pigmented leucocytes have been found, but actual tumor cells, as far as I know, have not been discovered.

The urine in cases such as we have been discussing often presents the condition known as melanuria. The urine of the second of our patients may be taken as an illustration of these phenomena.

On an average 1100 cc. were voided daily, of a brandybrown color, with a specific gravity varying from 1008-1027; reaction, acid ; neither albumin nor sugar present. At times polymorphonnclear cells and calcium oxalate were present in the flocculent sediment. Allowed to stand exposed to the air the iirine became much darker, and the same change immediately ensued on the addition of an oxidizing agent (nitric acid, potassium bichromate). A solution of ferric chloride added to a specimen also caused it to turn black; diazoreaction present.

The fact that the urine in melanosis is occasionally black has been long known, but it was not until 1858 that Eiselt accurately described the condition of melanuria in the case of a man suffering with " carcinoma " of the liver and eye. The urine darkened on standing, and the same change was produced by addition of nitric acid. The observation was veritied, and from the character of the ui'ine the opinion was ventured that the neoplasm was of a melanotic variety, an opinion which was later confirmed at the autopsy. To the hypothetical pigment the name melanin was given. The subject at once engaged the attention of the Prague school and many publications followed Eiselt's. In 1865 Dressier obtained an iron containing pigment from a melanotic growth of the liver, and about the same time Pribram separated by precipitation with neutral lead acetate a similar pigment from a melanuric urine. He concluded that the two pigments were probably identical. But later, in a brown pigment isolated from the urine of a patient with a melanotic growth in the orbit, Hoppe-Seyler could not demonstrate iron. In 1889 V. Jaksch added another reaction for melanuria, showing that ferric chloride even in dilute solution colored the urine black. He, like Pribram, found iron and also sulphur in the lead acetate precipitate. Almost simultaneously and inde


pendently of V. Jaksch, PoUak recommended a solution of ferric chloride as a delicate test for melanin. His analysis of tiie precipitated pigment showed besides sulphur and nitrogen, iron.

While melanuria was being investigated, attentidn had also been directed to the pigments of the sarcomata themselves. The results are not entirely in accord. The presence or absence of iron in the pigment is considered to have an important bearing on the question as to whether they take their origin from the blood. Whereas Berdez and Nencki report the pigment of sarcoma of liver and spleen as free from iron (phymatorhusin), Morner reports an appreciable quantity. In this connection it is of interest to note that in their recent work on the pigment of negro's skin and hair, Abel and Davis jioint out that the difference of opinion regarding the iron content of melanin may be due to the fact that the distinction between the pigmentary granule and the pigment itself has not always been made. The granule contains iron, the pigment a steadily diminishing amount as it is more and more purified, so that finally only the faintest trace remains; from which they conclude that iron is not a constituent part of the melanin derived from the negro's skin. A priori, knowing that the choroid is so often the primary seat of melanotic sarcoma, one might expect a correspondence between the composition of " phymatorhusin " and the melanin of the choroid. But the fact is that while the former is rich in sulphur, in the pigment of the choroid there is neither sulphur nor iron.

Whoever has approached the subject of the melanins must have been impressed with the jiresent unsatisfactory state of our chemical knowledge regarding them. In composition they approximate the proteids, and like them they present similar difficulties in separation and purification. The point of clinical importance, however, is that in melano-sarcomatosis the urine, as in Finkler's case, is sometimes black. More often, as in our case, it is clear when voided and becomes dark on exposure to air or on the addition of oxidizing agents. lu the first class a melanin is excreted ; in the latter group it is assumed that the melanin or phymatorhusin of the neoplasm is absorbed into the blood, is converted in the tissues into a colorless body melanogen, which is then excreted only to be reconverted into a melanin by oxidation. At what period in the course of the disease melanuria appears is not certain, but it is usually stated that a previous metastasis is necessary. We must look to the ophthalmologists for further information. Its diagnostic value, which might be considerable in an obscure case, is somewhat lessened by the fact that reactions similar to that of melanin-containing urine have been observed in some cases of peritonitis, of simple carcinoma of the stomach and liver, and following administration of tannic acid.

Finally, the question of the prognosis of melano-sarcoma of the uveal tract demands consideration. Left untreated, a metastasis sooner or later occurs. It is difficult to estimate the duration of the disease, for the ocular tumor is characterized at first only by ophthalmoscopic changes and its presence is not evident. Usually, after a period of one or two years, during which there have been more or less pain and functional disturbance of the eye, the tumor ruptures externally


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and a metastasis occurs. The secondary deposits often grow with frightful rapidity and death soon ensues. Litten's case, in which the patient with a metastasis survived four years, is probably unique. The average duration of life is about three vears. Widespread dissemination may have taken place before the neoplasm of the eye is suspected, and tumor masses in the liver, as in Litten's case and in Case I, may for the first time lead to a careful examination of the bulb. Early enucleation of the diseased globe has a certain prognostic import. In a study of 79 cases of sarcoma of the uveal tract whose after history could be followed, Lawford and Collins regarding patients apparently free from the disease more than three years after operation as well, report 25 per cent, of recoveries. Unfortunately, as they point out, no such limit can be fixed. Thus in Case II, although there was some evidence (abdominal pain) that metastasis may have taken place three years aftei' the enucleation, yet it was not until nearly five years had elapsed that the patient presented himself with a local recurrence and an enlarged and nodular liver. Jonathan Hutchinson, Jr., cites a case in which the first evidence of metastasis appeared eleven years after the diseased globe had been removed. Such cases illustrate the gloomy outlook in melano-sarcoma of the eye, even when early enucleation is carried out; they make it impossible to say when an individual having had a primary ocular sarcoma can be considered safe from future trouble. It is comforting, however, to know that patients have been followed as long as sixteen and eighteen years after early removal without presenting signs of the disease.

BiBLIOGKAPHY.

Abel and Davis: The Journal of Experimental Medicine, Vol. I, No. 3, 1890.

Berdez and Nencki : Archiv f. experiment. Path., Bd. 20, S. 346, 1886.

Dressier : Prager Vierteljahrschrif t, 1869.

Eichorst: Handbnch d. spec. Path. u. Therap., Bd. 2, S. 491, S. 575.

Eiselt: Prager Vierteljahrschrift f. prakt. Heilk., 1858, III, S. 190; 1863.

Finkler: Centralblatt f. klin. Med., Bd. I, 1880-81.

Fuchs: Text-book of Ophthalmology.

Ganghofer and Pribram : Prag. Vierteljahrschrift f. prakt. Heilk., 1876, CXXX.

Graefe and Saemisch : Haudb. d. Augenheilk., Bd. 4.

Hutchinson: Brit. Med. Jour., Vol. I, 1893, p. 291.

Lawford and Collins: Eoyal Loud. Ophth. IIosp. Keports, Dec. 1891.

Litteu: Ueber einen Fall von Melanosarcoma der Leber, Deut. med. Wochenschr., 15, S. 41, 1889.

Michel: Lehrb. d. Augenheilk., 1890.

Morner: Zeitschr. f. iihysiolog. Chemie, XI, 1887; XII, 1888.

Nepveu : Gaz. med. de Paris, 1872, 335, 385.

PoUak: Wiener med. Wochenschr., 1889, 39, 40, 41.

Pribram : Prager Vierteljahrschr., 1865, LXXXVIII, 16-23.

llaab: Beitrilge z. path. Anat. d. Augen, Klin. Monatsbliitter, Juli, 1875.


Sieber: Ueber die Pigmente der Choroidea n. der Haare. Arch. f. experiment. Path., XX, 1886.

Stevenson : Note on a Case of Melannria (? L. P. H.), Guy's Hosp. Keports, XIII.

Sutton : Tumors, 1893.

Virchow: Die krankh. Geschwiilste, Bd. 2.

von Jaksch: Zeitschr. f. physiol. Chemie, XIII, 385.

Discussiosr.

Dr. Abel. — The melanin, or black pigment, making up so large a part of the tumors in the case presented by Dr. Hamburger, is a substance of no little chemical interest. I wish merely to bring out two points relative to this pigment. First, the term melanin should be applied only to the black or brown pigments of the melano-sarcomata of the retinal and choroid coats of the eye, of the hair and skin, of the secretion of the cuttle-fish, etc.; in short, to a large class of substances which have been isolated by chemists, which are known to be stable and highly resistant compounds, possessing certain definite characteristics. The term should not be applied, as it sometimes is by histologists, to every brown or black particle which may be seen as a more or less temporary stage in the breaking down of red corpuscles in pathological conditions. A true melanin has not yet been isolated from an area where there has been an extensive disintegration of red corpuscles. AVe have no proof that the dark particles in such an area contain a genuine black ])igment like the melanins.

My second point concerns itself with the origin of the melanins. Are they derivatives of hfemoglobin or of some other substance? Histologists have laid great stress on the iron content of a melanotic pigment, holding that the presence of iron lends great probability to the view that the pigment in question is derived from haemoglobin. Now a micro-chemical iron reaction merely shows that iron is present in or on the little particle examined; it does not prove that iron is present in the molecule of the pigmentary substance to which the color of the particle examined is due. Iron may be present in the molecule of a pigment and yet micro-chemical methods may not be able to detect it, as in hsematin, for example. Again, the pigmentary granule as deposited in cells is a very different thing from the pigment considered as a chemical individual; the former is a complex anatomical unit, containing many other substances in addition to the pigment. Confusion has resulted because this point has not been borne in mind. Davis and I showed that the pigmentary granules in the negro's skin and hair contained much iron, while the isolated and purified pigment contains none, and we have every reason for believing that this holds for every particle of melanotic pigment in the body. The fact is that much more than the presence of iron must be established before we can say that a pigment is derived from haemoglobin. Some of the colored derivatives of haemoglobin, as haamatoidin, hfematoporphyrin and biliribin, contain no iron, while the well-known hsematin contains this element. Now all of these natural derivatives of haBmoglobm differ so widely in both their physical and chemical characteristics from the melanins, as thus far isolated, that no chemist can suggest a plausible theory for the derivation of these latter from the color-yielding complex of atoms in the hemoglobin


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molecule. To point out only one great obstacle, the melanins, with few exceptions, contain sulphur, the amount varying from 2 to 12 per cent., while the colored derivatives of hjemoglobiu, like those already referred to, contain no suljihur. A theory of the origin of melanins must account for this difference and also for the difference in the carbon, hydrogen and nitrogen content, not to speak of physical differences as shown by the spectroscope. My own observations have led me to think of the sulphur-containing melanins, such as the sarcomelanin of this case, as highly altered proteids, as compounds that must still be classed in a broad way with the proteids. If, therefore, hfemoglobin is to be made the precursor of these pigments, it is the proteid part, or globin of the blood pigment, from which they are derived. Bnt we can as easily suppose some proteid of the parenchymatous juices to be decomposed as that the proteid moiety of hEemoglobin should serve this purpose. We could assert with equal force that all the keratin in the body is derived from hemoglobin.

Schmiedeberg has recently published the results of an elaborate research on the nature and origin of the melanins which bear out this view. I cannot go into the chemical details of


the question, but can only give you bis conclusions, to which I subscribe most heartily. The immediate precursor of the melanin is a product derived from a genuine proteid, say serum albumin, by a fermentative process ; it is a highly resistant, modified proteid of the character, we will say, of an antipeptone which has lost carbon-containing groups, perhaps also leucin and tyrosin. This substance would therefore be richer iu sulphur than the original proteid. It is further modified by having ammonia and water split off from it, its hydrogen content being further diminished by oxidation. These deductions are based on a careful comparison of the elementary formula3 of many proteids and of all of the melanins hitherto isolated and analyzed, and they harmonize entirely with the chemical processes known to occur in the body. No other rational theory of the origin of the sulphur-containing melanins, like those found in these tumors, in the hair and skin, etc., can be offered at present. I may remark in closing that the formation of the dark pigments seen in decaying vegetable matter, and which are called humus substances, presents many points of analogy.


ON INFECTION WITH A PARA-COLON BACILLUS IN A CASE WITH ALL THE CLINICAL

FEATURES OF TYPHOID FEVER.


By Norman B. Gwyn, M. B., Assistant Resident Physician, Johns Hopkins Hospital


Baeberial infection, or the intoxication caused by bacteria, gives to the blood the property of paralyzing and clumping the specific organisms. This is the principle of the Widal reaction, now so well known iu connection with typhoid fever, and the same applies to other well-known organisms, such as the pyocyaneus and the bacillus of hog cholera. From this we may infer that a serum test is a valuable or certain proof of an organism's specificity. No better suggestion of this can be found than that shown by the colon family, in which Durham has shown that the serum of an immunized animal agglutinated decidedly only the organism used for the immunization, other colon organisms being but feebly affected. Widal infers from this that, especially in an infection caused by one of a group like the colon, the serum reaction is only of value as affecting that particular colon organism which has produced the infection.

For the production of this serum reaction in the blood of an individual, something more than the mere presence of the organism in the body is required. There must be a definite infection or intoxication produced before the blood will acquire its specific property. The presence of the colon bacillus in the normal intestine does not make it presumable that the blood of all persons will agglutinate the colon bacilli.

Based on the theory of specificity of the serum reaction, Widal* reports a case which he thinks (from the behavior of the patient's serum towards the organism isolated from his


' Semaine Medical, Aug. 4, 1897


body) must be considered as an instance of infection by a || para-colon bacillus, and the case he considers as one of para- ^ colon infection.

The name para-colon is given to the organism as showing its resemblance to the colon family, but Widal gives it a place I more properly between the bacillus typhosus and the colon I bacillus, as its properties are closely allied to both.

I'he history of his cas3 of so-called para-colon infection is as follows: A phthisical patient developed, after three weeks 9 in the wards, an abscess in the neck about the oesophagus, I showing at the same time some slight constitutional symptoms. From the pus at operation an organism was obtained in pure culture, actively motile, decolorizing by Gram ; it did not liquefy gelatine, clouded bouillon without making a film, and formed a few gas bubbles in glucose agar ; grew on potato as a yellowish green film.

The two most essential points distinguishing it from the colon family were that it produced no iudol and did not ferment lactose, while the fermentation of glucose distinguishes it from the typhoid bacillus. Further reactions confirmed the fermentation of glucose and mannite, and the absence of the same in lactose and saccharose.

The main feature of the organism, however, was its serum reaction, and on this its claim of specificity rests. The serum of the patient had a marked agglutinative action on the organism in as high dilutions as 1-1000, the reaction diminishing steadily with convalescence.

To confirm this result various other orsfauisms were com


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pared. The different cultures of colon bacillus were affected by the patient's serum no more than by normal sera. Another para-colou bacillns isolated from the mouth agglutinated at 1-150; the bacillus psittacosis responded at 1-50. The serum of a guinea-pig inoculated with the particular para-colon organism gave no result with two colon bacilli, a typhoid bacillus and the other para-colou organism mentioned above. Conversely various normal sera and sera from patients with various affections. Sera of animals inoculated with different organisms had little or no effect upon Widal's para-colon bacillus, with the exception of typhoid sera of very high agglutinative power obtained by experimental inoculation. The sera of animals inoculated with colon bacilli, with the psittacosis organism and the other para-colou, gave little or no reaction on the organism.

Widal concludes from these serum reactions that the bacillus isolated was the cause of the patient's infection. The other para-colon bacillus referred to, isolated from a person's mouth, differed from that isolated from the abscess in fermenting saccharose in addition to glucose and mannite.

These two so-called para-colon bacilli, the psittacosis organism, a bacillus called the bacillus of calf septicemia of Thomasson, Widal considers to form a family or group, in much the same way as the colon organisms are classified as a family. The individuality of the members is shown suggestively, though not absolutely, in the serum reactions mentioned above, and by differences in fermentation of the various sugars.

Kecently we have isolated an organism which from its cultural properties seems to belong to this so-called para-colon group, and is possibly identical with one of Widal's para-colon organisms. It was found, moreover, that the patient's serum had a specific agglutinative power on the organism, and the conclusion was reached that the organism isolated had caused the infection. The case is of further interest as one of typical typhoid fever, and the question arises whether or not the organism found had produced a secondary infection during the disease.

Louis S., admitted Oct. 11th, 1897, had been ill since Sept. 17th with headache, fever and weakness, and later with vomiting, diarrhoea and pain in abdomen. On Oct. 14th noisy delirium set in ; on Oct. 16th the patient had three hemorrhages from the bowel ; he slowly rallied and went out in five weeks.

Kose spots were present; the spleen was palpable; the urine showed the diazo reaction ; there was no diarrhcea. The temperature was that of a severe typhoid fever. There was never any Widal reaction found. Blood cultures on Oct. 12th gave a small, actively motile bacillus suggesting the bacillus typhosus. It decolorized fairly well by Gram, grew on agar as a grey blue moist raised film, clouded bouillon, giving no scum on surface and no precipitate. Milk was only faintly acidified, resuming original tint in course of ten or twelve days. Potato showed a brown yellow moist layer of growth. There was no liquefaction of gelatin, slight stab and surface growth. Plates of gelatin and of gelatin diluted with bouillon gave same circumscribed blue grey colonies, about i mm. in diameter; by microscope light brown regularly outlined


granular colonies with no nucleus. The fermentation reactions showed fermentation of glucose, slight in saccharose, Ifevulose and mannite, but none in lactose. Sugar-free bouillon, to which in tubes 3 per cent, of various sugars was added, was used. There was no production of indol. By Van Ermengeu's flagellar stain, from two to four flagellae could be made out. No peritrichal arrangement as in the bacillus typhosus was seen.

The serum reactions were as follows : The patient's serum at different dates during his illness gave a rapid, complete agglutination in low dilutions, and showed reaction in dilutions up to 1-150 to 1-200, the highest being at date of discharge. On Dec. 18th, two mouths after date of culture, there still remains a slight reaction.

The same serum was without action on the bacillus typhosus in any dilution above 1-1 or 1-5.

Two varieties of colon were agglutinated by patient's serum as high as 1-50 and 1-60, but two normal sera agglutinated the same organisms in dilutions running from 1-60 to 1-100.

Typhoid sera of agglutinative strength ranging from 1-300 to 1-1100 were without effect on the bacillus in dilutions over 1-1 and 1-5. One typhoid serum, strength 1-900, with bacillus typhosus, gave an incomplete reaction as high as 1-30. Several of these sera had little or no effect even in dilution 1-1. One normal serum affected the bacillus rapidly at 1-1, failing at 1-5. A typhoid bacillus was affected similarly ; a colon was agglutinated as high as 1-120 ; another normal serum had little or no effect at 1-1, while rapidly aad completely agglutinating the colon organisms.

One other test mentioned by Widal for the distinction of the para-colou organism, is that called the scraped tube reaction, which consists in scraping off the surface growth of an organism from an agar slant and reinoculatiug with other or the same organisms. A fresh transplant of the same organism will not grow on the scraped surface ; other different organisms will. Both colon and typhoid grow on the supposed paracolon tubes, and the para-colon grow on scraped tubes of them. Widal considers this an absolute distinction, stating that by it the different colon members can be distinguished.

The approach of the organism on the one hand to the typhoid bacillus and on the other to the colon family is well shown by the cultural properties. The effect on milk and the non-production of indol are like the typhoid bacilli; in the fermeutation of glucose it resembles the colon family, from which again the non-fermentation of lactose and the negative indol test clearly exclude it. Its place really seems to lie between these two important organisms.

By comparing the cultural properties of our bacillus with those previously described, it can be seen that with the exception of the fermentation of saccharose the organism is precisely similar to Widal's para-colon isolated from the abscess; the resemblance to the one isolated from the mouth is more exact, as the latter had some effect upon saccharose. In the colon family, however, the fermentation of saccharose is a variable characteristic and may not occur with every member, so that this slight difference in fermentative quality may perhaps be a feature in the para-colou family as well. From these reactions and characteristics we think that the organism


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here described may be considered a para-colon bacillus and may be identified with Widal's organism. Our infection unfortunately cannot be so clearly defined as his, occurring as it did in the course of typhoid, but if a serum reaction is a specific test, such an infection must have undoubtedly occurred. Of great interest, we think, is the fact that at no


time, even up to the present, Dec. 18th, 1897, has the patient's serum given a Widal reaction, he being the only typical typhoid of 48 cases to fail therein, while his serum still shows after two months the result of the infection by the supposed para-colon organism.


THE MANACtEMENT OF SOLID TUMORS OF THE OVARIES COMPLICATING PREGNANCY, WHH

REPORT OF A SUCCESSFUL CASE.

By William E. Swan, M. 1)., Assistant Resident Gyncecologist in the Johns Hopkins Hospital.


A careful examination of the literature shows that although solid tumors of the ovaries are not uncommon, their occurrence as a complication of pregnancy is sufficiently rare to justify a detailed report of every additional instance. Inasmuch, also, as the proj^er treatment of this condition is of the utmost importance, the following case offers certain points of interest.

A. R., single, white, domestic servant, aged 22, born in the United States, was admitted to the gynecological wards of the Johns Hopkins Hospital, June 13, 1893. In the February previous (five months before) she had noticed an increase in size of the abdomen, which had gradually increased. Except for this enlargement of the abdomen, and amenorrhcea since January 1st, she had had no cause for complaint.

Family History. Paternal grandmother died of a new growth in lower abdomen. Maternal grandfather had a cancerous growth on arm; family history otherwise negative.

Personal History. Does not remember having had any serious sickness before. Menstruation began at fifteen ; was irregular up to the 17th year, since then regular till 5i mouths ago, of the 38-day type and of 5 to 6 days' duration ; flow free; slight dysmenorrhoea.

Present Illness. Has always been healthy up to January, 1893. Early in February she first noticed a slight increase in the size of the abdomen, and absence of the menses, which have not returned since. The enlargement progressed in a symmetrical manner, and at the present time (June 3) the abdomen presents the appearances belonging to a five months pregnancy. The patient has had no morning sickness and has not noticed anything which could be interjjreted as fcetal movements. There has been no increase in the size of, or pain in the breasts; no swelling of the feet or ankles. Sleeps well ; appetite good ; bowels constipated ; slight giddiness ; some dyspnoea on exertion ; otherwise no inconvenience. No pain anywhere.

Physical Examination. General condition good. The patient is a well nourished, healthy-looking young woman; eyes clear, tongue slightly coated, mucosas of a good color. Heart and lungs negative.

Abdomen symmetrically distended. Line of pigmentation from umbilicus to pubes marked. On light palpation a rather yielding, slightly resistant mass is felt extending from two inches above the umbilicus to the symphysis pubis, and from 3 to 4 inches to either side of the median line. (Jn palpat


ing deeply and quickly ballottement is obtained over this area, showing the presence of a layer of fluid. The abdomen over the same area is dull ou percussion ; on auscultation a placental bruit is heard in the right lower quadrant of the abdomen ; no fcetal heart sounds are heard ; no actual movements made out, but indefinite "lumps" are felt through abdominal wall which "retreat" from the examining hand.

The measurements of the abdomen were as follows: Girth at umbilicus, 30 inches ; girth midway between umbilicus and symphysis, 31 inches ; from the ensiform cartilage to umbilicus, 74 inches; from the umbilicus to the symphysis, 71 inches ; from anterior spine of ilium on either side to umbilicus, 6 J inches.

Vaginal Examination. Vaginal mucosa dusky violet in color; outlet considerably relaxed; cervix high up, soft, shortened, patulous. Behind the cervix and occupying a large part of the pelvis is a hard, nodular, fixed mass, about 5x7 cm. in diameter, adherent to sacrum postei'iorly. The breasts contained colostrum.

Diagnosis. Pregnancy, associated with solid tumor of the left ovary.

Abdominal section by Dr. Kelly, June 21, 1893.

Incision 18 cm. long through stretched and thinned abdominal walls. The uterus, which was of the size belonging to a five months pregnancy, was forced out by compression made on the sides of the abdomen by the hands of an assistant, the operator meanwhile making direct traction ou it and throwing it forward so that the body rested ou the pubes. By these means there was brought into view a tumor of the left ovary, lying behind the uterus in the pelvis but not attached to it. It presented a whitish appearance, was hard, irregularly oval, and about the size of two clenched fists placed closely together. Pressure upon it had caused some flattening of the surface adjacent to the sacrum. The tumor, which was attached to the left broad ligament by a narrow pedicle, was raised and tied off together with the left tube by means of four intermediate silk ligatures, a few extra silk ligatures being inserted to stop some slight oozing from the severed pedicle. The uterus, which had all this time been protected by means of a large piece of gauze kept constantly saturated with warm salt solution, was now returned to the abdomen. The peritoneum was united by means of a fine silk suture; the remaining layers of the abdominal coverings with silk


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worm gut and silk; gauze dressing, edges rendered adherent with collodion ; iodoform and boric acid powder dusted over same; cotton; Scultetus' bandage.

Time of operation 46 minutes.

The convalescence was rapid and uneventful; the highest temperature reached was on the second day, when it rose to 101° F., after which it soon became normal ; the bowels moved on the fourth day. On July 2, 1893 (13th day), note reads: '•For the first few days after operation a slight bloody vaginal discharge was observed ; patient complained of sharp pains through the abdomen. This symptom soon subsided under a moderate use of morphine. Abdominal dressings removed ; wound united throughout jjer 2^1'imavij general condition excellent."

July 10, 1893 (20th day}, " Patient sat up in bed ; did not fee] weak nor tired afterwards."

July 2i, 1893 (4 weeks after operation), " Patient discharged; has had no setbacks ; wound nicely healed; patient feels well ; abdomen increased in size."

Pathological Report. Mass consists of a large tumor developed from left ovary, with about 4 cm. of normal tube, with clear mesosalpinx; tube patulous. Tumor 13x7 cm., density of cartilage, with clear smooth fibrous capsule, which strips off moderately easily. On outer surface is an umbilication about 3 cm. deep, containing a small mass of similar consistence, with broad flat pedicle. Vessels on surface small but injected. Section of mass reveals a dense fibrous structure, yellowish and translucent, with numerous deeper pinkish areas corresponding to umbilication on surface ; tissue much softened, and upon pressure exudes a clear fluid.

Frozen sections reveal fibrous tissue with fine points of fatty degeneration.

Sections hardened in alcohol. The specimen consists of dense fibrous tissue with spindle-shaped nuclei. The tumor is richer in cells in the larger portion. The cajjsule is much thickened. Vascular sujjply scanty, esjjecially around the umbilication. Diagnosis: Fibroma of ovary.

From the after-history it would seem clear that premature labor was artificially induced after the patient returned home. When she left our care she was certainly well, and had nature been left to herself there was nothing in the patient's condition to prevent the continuance of the pregnancy to term, and there was no indication that in this case delivery would have been accompanied with any more danger than that belonging to a normal labo)'.

Considerable confusion seems to exist in the minds of authors regarding the classification of tumors of the ovaries associated with pregnancy. In many reports of cases of ovariotomy during pregnancy, only incidental reference or none at all is made to the nature of the growth removed. Thus, J. Dsirue' (Liveland) collected from the literature 135 cases of pregnancy associated with ovarian tumors in which ovariotomy was performed, the diagnosis in 43 of these being tumor ovarii, and in the remainder cystoma. None are distinctly specified as being solid tumors.

Most tumors of the ovary, including those complicating pregnancy, are cystomata, and of these dermoids form a considerable number, as is shown by the following table :


Total num- Cysts, in- Number

ber of cases eluding of solid Fibro- Sarco- Carcino Name of operator, operated on. dermoids, tumors, mata. mata. mata.

1. Billroth 86 78 8 .. 3 5

2. Schroeder .... 102 97 5 . . 5

3. Thornton 338 328 10 3 .. 7

4.Hildebrandt.. 37 27 10

5. Weber 123 72 51

6. Krassowoski.. 128 128

7. K. VonBrann. 81 71 10 1 2 5

8. Thos. Keith . . 200 183 17

9. Olshausen 193 267 26 6 9 5

Totals 1388 1251 137 10 19 22

The figures iu the above table give, as we see, 9.9 per cent, solid tumors. But Olshausen" holds that this is too large a proportion. Weber, whose statistics tend materially to raise this percentage of solid neoplasms, has probably counted as solid tumors many which other authorities would class among the cystic variety. With Weber's cases omitted we should have only 6.8 per cent, of solid tumors, which is probably more correct.

The same table shows the relative frequency of the different varieties of solid tumors to be as follows : Fibromata are present in the proportion of .73 per cent. Sarcomata " " " " " " 1.36 "

Carcinomata " " " " " " 1.58 "

All others " " " " " " .057 "

The investigations of Jetter' have shown that any form of ovarian tumor may complicate pregnancy. Of his collection of 166 cases, 97 were cystomata, 37 dermoids, 11 carcinomata, and 31 uncertain. In this small number of cases the proportion of undoubted solid tumors to all others is only 6.6 per cent.

Solid tumors of the ovaries may be classified as follows :

Fibromata,

Sarcomata,

Desmoid { Mysomata,

Endotheliomata, Solid -j Enchondromata.

Carcinomata, illomata.


Epithelial I *^^'"" I- ^ I Papil


The lines between these several varieties of tumors are not always distinctly drawn, and almost any two forms may be found associated. The benign forms of epithelial tumors of the ovary are always cystic in nature (Olshausen').

Ovarian neojjlasms do not preclude the possibility of conception so long as the ovaries contain healthy ovarian tissue. Indeed, rare instances have shown that the removal of both ovaries is not an absolute safeguard against conception. In such cases there are undoubtedly rudimentary masses of ovarian tissue or supplementary ovaries left behind (Montgomery").

It is diflScult, if not wholly impossible, to arrive at any accurate conclusions as to the frequency of conception in women who are the subjects of ovarian neoplasms. S. Kemy° finds, however, that in 357 women with tumors, 331 pregnancies occurred, with 366 normal delivei'ies; so that some of the


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mothers became pregnant at least twice during the existence and probable growth of the same tumor.

Montgomery, in commenting on the frequency of ovarian tumors complicating pregnancy, says he is able from a very cursory investigation of the literature to present tables of over 150 cases. It is evident that he refers to cysts of the ovary associated with pregnancy.

Several authors, as Kleinwiichter, Spencer AVells and Eokitansky, have observed pregnancy in connection with unilateral ovarian fibromata. During labor the tumor may obstruct the biith canal, and thus render Csesarean section necessary, as happened in Kleinwiichter's case; the tumor may be contused and become gangrenous, as has been described by Rokitansky.'

After a careful examination of the literature we have been able to find but fourteen cases of undoubted solid growths of the ovary in association with pregnancy. These are here presented in chronological order with brief histories.

Case I. Breit". In this case an ovarian tumor of stony hardness and adherent to the rectum was removed ; no details given.

Case II. Sp'.egelberg' (reported by Bourgonin). Patient was aged 37 and had borne two children. Immediately after the birth of the second child a rapid enlargement of the abdomen was noticed, which pursued a slowly progressive course and ended in death. At autopsy a fibroma of the left ovary weighing 60 pounds was found, with considerable ascites. Size of tumor 51x23 cm.

Case III. Spiegelberg'" (reported in 1867). The woman died nine days after her second labor, aged 36. Tumors of both ovaries were found at autopsy which microscopic examination showed to be myxosarcomata which had undergone cystic degeneration. One tumor measured 20x12x4 cm.; the other 15x10x4 cm. Death was due to rupture of one of the tumors, apoplexy of both, and peritonitis.

Case IV. Kleinwiichter" reported in 1872 the following case. Age of patient 31 years ; month of pregnancy not stated, probably full term ; pains began on May 25, and on May 29 were very severe. Patient was brought to the hospital by midwife, who got away before giving any further information. Head presenting. Examination revealed a bony tumor, about the size of a fist, in tlie pelvis. Cfesarean operation performed on May 31, 1868, and a healthy female child weighing 3010 grammes safely delivered. Twentyfive hours afterwards the mother died of general peritonitis.

Diagnosis. Peritonitis after Caesarean section ; ossified fibroma of the right ovary.

Case V. Spencer Wells (reported by Cayla). The patient, aged 29, who had had one child, presented herself in March, 1872, with a tumor in right suprapubic region. She was three months pregnant. One month later laparotomy was performed, and a tumor weighing five kilograms was removed. This tumor had been held in place by the epiploon to which it was adherent. The structure of the tumor was that of an ceJematous fibroma. The patient recovered and the child was born at term.

Case VI. Hem pel" in 1875 reported the case of a patient aged 42 who died four weeks after her 11th labor. At autopsy both ovaries were found enlarged to more than the size of a child's head. The surfaces of the tumor masses were hard and irregular. The tumors proved to be carcinomata, probably secondary to cancer of the stomach.

Case VII. Schroeder" (reported by Cayla). Woman aged 22, six montlis pregnant ; operation May 25, 1876 ; solid tumor removed from left ovary. Labor at term ; cure.

Case VIII. Spencer Wells" (reported by Cayla.) Woman aged 41, four months pregnant ; operation October, 1876 ; tumor weighed 7 pounds. Labor at term ; cure. Diagnosis: Round cell sarcoma of left ovary.


Case IX. Spencer Wells" (Cayla). Woman aged 28, four months pregnant; operation November, 1877. Fibroma of right ovary removed, weighing 10 pounds. Labor at term ; cure.

Case X. Casati". Large fibro-sarcoma of left ovary. Pregnancy at fourth month. Ovariotomy ; abortion, partial suppurative peritonitis ; cure. Patient was 2!i years old. Menstruated at 18 ; married at 25 ; ten months later had first child. In March, 18SI, had second chilJ ; labor normal. Two months after this noticed tumor in left groin. Four months after labor menses recommenced ; milk stopped at 5th month. On January 4, 1882 (ten months after birth of last child), the patient vras examined and the following diagnosis made :

Completely solid tumor (probably sarcoma) of left ovary ; partial peritonitis and pleurisy. At operation the woman was found to be four months pregnant. The tumor weighed 1850 grammes, and measured 13x48x36 cm.

Case XL Dr. .7. H. Carstens,'^ of Detroit, Michigan, in 1889 reported a case almost identical with our own. The patient, aged 26, white, four years married, without having had children or miscarriages, had had frequent micturition and pain for the year previous. She had noticed a hard lump in lower abdomen, which had increased rapidly during ihe last four weeks. The menses, which had formerly been regular, ceased February "4, 1889. General health and family history good. Examination showed the pelvis to be filled with a hard growth which seemed movable. The uterus was found a little to the left of the growth. The os was soft, velvety. Pregnancy suspected. Examination under ether warranted a diagnosis of pregnancy of two months duration and a pelvic tumor, which was thought to be a uterine fibroid with a long pedicle, a sarcoma, or some other hard tumor of the ovary. Operation !May 27, 1889. When the peritoneum was opened a very hard nodular tumor came into view. It was movable, slightly adherent to the bladder, intestines and omentum, but not adherent to the uterus. The long narrow pedicle was tied off together with the right Fallopian tube, which was also removed. The left ovarj- was found to be healthy and was left untouched. Patient made a good recovery. The pregnancy continued and was of seven months duration at the time the case was reported. The tumor was very hard and nodular, i.0 cm. long and 12 cm. in diameter; in the middle was a constriction in which the uterus had rested. A microscopical examination by Dr. George Duffield showed only pure fibrous structure. The ovary had entirely disappeared in the growth.

Case XII. Miinchmeyer" (reported in 1890). Patient aged 30. Thir(J pregnancy. Month of pregnancy not stated, probably full term. Normal but small pelvis. Enormous elastic tumor(spindlecell sarcoma) occupied the pelvis. Head presenting. Shortly before the delivery of foetus the colossal swelling of the tumor was noticeable. The absence of any symptoms pointing to malignancy of the tumor was noted. The child being already dead, the skull was crushed and the fcetus delivered. The tumor remained for four weeks after the delivery, but shrunk to about the size of a goose egg(?). Ovariotomy was then performed ; the patient made a good recoverj', and was discharged three weeks subserjuently.

Case XIll. 3. Murphy. " Abdominal section during pregnancy (reported in 1895).

"A lady 32 years old was sent into the Sunderland Nursing Institute, under my care, to have an ovarian tumor removed, she beirg about six months pregnant. The operation was performed at noon, April 20, 1803. The tumor proved to be a solid round-cell sarcoma, weighing two pounds, with somewhat numerous adhesions. The labor pains commenced 24 hours after the operation and became severe at 10 a. m. The patient soon gave birth to a boy, who lived for 12 hours. The convalescence was uneventful. She If ft the Institute in three weeks. Her highest temperature was 99.5° F."

Case XIV. P. Ruge."' Woman aged 36; six months pregnant. !Myxo sarcomata of both ovaries ; no details.


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From au examination of the results iu the above fourteen cases we find that eight of the patients were submitted to operation before labor, with the death of one mother and with loss of but two children from miscarriages and one by craniotomy, four children going to full term and one being delivered by Cajsarean section. Three mothers were not operated on ; of these, two died soon after labor as a result of complications due to the tumors, and one lived ; in three cases no details are given.

The incompleteness of the above collection of cases is painfully apparent. A glance at the various dates of their publication — 1861 to 1895 — would suggest at once that many similar cases must have occurred previous to the former and probably also subsequent to the latter date. Their non-appearance either in the Index Catalogue of the Surgeon-General's Library or the Index Medicus, would lead to the conclusion that such instances were either not reported at all, or that the accounts of them did not possess suflRcient detail and clearness to enable the cases to be recognized as belonging to this category. So called solid dermoids and all other tumors not distinctly specified to be solid have been rejected from our list.

Influence of Pregnancy on the Growth of Ovarian Tumors.

In this connection two main theories may be cited: (1) That the increased blood flow increases the growth of the tumor (Spiegelberg and Olshausen). (2) That a decrease in the size of ovarian tumors during pregnancy occurs, owing to lack of space and inactivity of the ovaries (Koeberle). The former of these two views is generally accepted (Dsirne)."

Wernicke suggested that benign tumors are apt to become malignant during pregnancy. There are no observations which tend to support this view (Olshausen).

Luhlein" in 189.5 published a comprehensive article dealing with ovarian tumors complicating pregnancy. His views may be summarized as follows:

(1) He dissents from Wernicke's view and holds that benign tumors of the ovary do not tend to become malignant during pregnancy. (2) He doubts if tumors enlarge much during pregnancy and cites cases to support this position. He quotes many observations to show that the ovaries are in a state of rest during pregnancy.

The recognition of the co-existence of pregnancy with a solid ovarian tumor or tumors is of the greatest importance, and often presents a difficult problem. The limits of this paper forbid more than a brief discussion of the main characteristics of this condition.

Solid tumors of the ovaries are often bilateral, though there are many exceptions to this rule ; they are seldom larger than a man's head ; the general form of the ovary is maintained ; adhesions are rare, but ascites is usually present (Olshausen)."'

Although the signs and other evidences of pregnancy, in association with solid tumors of the ovaries, are sufficiently characteristic, it is a noteworthy fact that many experienced and able operators have recognized the pregnancy only after the abdomen has been laid open. It is therefore not out of place to emphasize the importance of keeping in mind the


possibility of the existence of such a condition in making our examinations.

In this connection it is interesting to note that Napier," after reporting a case of ovarian cyst in which he successfully performed cystectomy at the third month of an unsuspected pregnancy, quotes from Barnes' "Diseases of Women," as follows: "Ovariotomy during pregnancy has been performed several times, the operatornot suspecting theexistence of pregnancy before the operation. What should be done when a pregnant uterus is discovered during some stage of ovariotomy ? Wells says let it {i. e. the uterus) alone. Dr. Atlee performed ovariotomy in the second month of an unsuspected pregnancy. Dr. Marion Sims performed ovariotomy in the third month of pregnancy, not suspecting its existence, with good results to mother and child."

The prognosis in cases of ovarian tumor complicating pregnancy is by no means favorable. The great danger to the mother will be appreciated from the figures in the following statistics.

Litzmann has collected 54 cases with 24 maternal deaths ; Jetter, 215 deliveries in 165 mothers with 64 deaths ; Playfair, 57 deliveries with 23 deaths; Braxton Hicks, 6 deliveries with no deaths ; Kogers, 5 deliveries, no deaths ; Spencer Wells, 11 deliveries, one death ; Fritsch, 4 deliveries, one death. In all, 355 deliveries are reported with 114 maternal deaths, or a maternal mortality of about 32 per cent. The mortality to the children from either abortion or premature labor is, according to Engstrom, much greater. In 216 cases he finds it to be about 48 per cent. (Fenger).'"i

Heiberg'" has collected 271 cases of pregnancy with ovarian tumors and found that over one-fourth of the mothei-s and two-thirds of the children perished ; while Dsirne" says that only 60 per cent, of the pregnancies complicated by ovarian tumors terminated without accident to mother or child.

The situation and size of the tumors are of marked significance in determining the prognosis. Most solid tumors, especially during their early growth, remain in the true pelvis. When small they may be overlooked, and the hindrance which they offer to delivery may be unsuspected or attributed to pelvic narrowing (Montgomery)." Large tumors rarely hinder the engagement of the fcBtal head, unless a part of them occupy the pelvis; whereas small tumors, especially dermoids, often retard the descent of the head, so that 02ieration is necessary (Hohl)."^"

Greigg," from his post-mortem researches upon puerperal septicemia, shows that it is possible that some cases of this disease arise from injury, during parturition, to unrecognized ovarian tumors. We must consider not only the mechanical difficulties in the way of delivery, but also the cachexia due to the presence of malignant new grow'ths (Miiller)."

Complications of pregnancy may arise owing to the presence of solid ovarian tumors.

1. The stem of the tumor may become twisted and thus give rise to the presence in the abdominal cavity of a necrotic foreign body. This accident occurs in 9.1 per cent, of all cases (Dsirne)."

2. Infection of the peritoneum is more likely to occur.

3. The tumor by direct pressure on the intestines may


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cause intestinal obstruction, or indirectly twists of the gut or hemorrhoids (Barsouy)."

The mortality in ovarian tumor cases complicating pregnancy, treated by the expectant plan, is frightful. In 75 cases (cysts included) collected from the literature, 31, or 41 per cent., were fatal to the mothers, while but 32 children, or 29 per cent., are reported as having been saved (Montgomery)."

Litzmanu" gives the maternal mortality as 43 per cent., and the fffital as 83 per cent.; while Dsirne, as stated above, reports that but 60 per cent, of these cases when left alone terminate without accident to mother or child.

Such a death rate urgently demands renewed investigation and the adoption of a definite plan of treatment. When we come to the consideration of ovariotomy during pregnancy, we find far better results.

Of cases of ovariotomy during pregnancy, Dsirue finds that abortion followed in 23 per cent., and death in only 5.09 per cent. Breit'° (1861) reports results of operation on tumors of the ovary in pregnancy during labor, or the puerperium, as follows : In 315 cases, 140 mothers recovered, 64 died ; in 11 the results were unrecorded. Of the children, 81 lived, 53 died, of 61 there was no record ; 21 abortions occurred.

So far as the chances of maternal recovery from ovariotomy during pregnancy are concerned, they are fully as good as when no pregnancy exists. As regards the continuance of gestation, if the operation is performed in the early months the prospect is usually also favorable (Munde) "

In this connection Kreutzmann* states the facts clearly when he says : "The bringing about of abortion would be in order (1) if it is proved that ovariotomy during pregnancy is always followed by abortion; and (3) if the statistics show that the results of ovariotomy in pregnant women are much less favorable than in non-pregnant women. The fact that the percentage of abortions following operation is only about 20 per cent, is an answer to the first proposition. As concerns the second, statistics have demonstrated that with most operators the mortality in ovariotomies performed during gestation is less than those in non-pregnant women."

Since ovariotomy, then, can give such good results, the advisability of operative procedures must be taken into consideration in each individual case. Surgeons of wide experience, as Spencer Wells, Tait, Cauchois, Olshausen, and the late Carl Schroeder, are agreed in commending ovariotomy as the best means of dealing with all cases of ovarian neoplasms associated with pregnancy. Again, in view of tlie fact that Cohn" has proved every sixth ovarian tumor to be probably malignant, the early removal of the diseased structures is of vital importance.

The most favorable time for operation is at some period during the first half of pregnancy. In the later mouths the increased hyperasmia and engorgement of the broad ligaments increase the danger of untoward results (Montgomery)."

Kelly has published statistics which go to show that all tumors of the ovary should be extirjiated as soon as recognized, no matter how small or inoffensive they may appear. His experience with cysts of the ovary has clearly demonstrated that it is not safe to allow them to remain, inasmuch


as many apparently innocent cysts (papillary cystomata) may at any time become highly malignant, and if not removed sufficiently early, may prove rapidly fatal.

According to Olshausen,'- from 60 to 70 per cent, of all patients with proliferating cystomata (cystoma ovarii proliferans papillare) die within three years from the time of the first symptoms, and a further 10 per cent, die during the fourth year.

This surgical law which insists upon the early extirpation of all ovarian tumors applies with still more force in cases of solid ovarian neoplasms associated with gravidity.

Time for Operatmi. The elective time for the operation seems clearly defined, as all agree that the lowest mortality to both mother and child is secured by operating between the second and fourth months of gestation. There is one apparen t exception to this rule. Dsirne" states that in intra-ligameutary tumoi'S, owing to the danger of hemorrhage, it is often better to produce abortion before extirpating the tumor. It may, however, be asserted that the results in these particular cases will be determined largely by the skill and operative dexterity of the surgeon, and that under favorable conditions these cases can also be successfully operated on without previous interference with gestation.

When the case is not seen before labor, and when the tumor interferes with the engagement of the head in the true pelvis, one or both of the following procedures are indicated :

(a) Attempts may be made to replace the tumor in the abdominal cavity under anesthesia.

(b) As a last resort, celiotomy.

In the puerperium Hohl" says that we should operate not later than the second week. Others hold that if the labor is normal it is better to wait several weeks longer.

In summarizing the results of a thorough search of the literature dealing with the subject the following deductions would appear to be justifiable:

I. Solid neoplasms of the ovary complicating pregnancy are exceedingly rare.

II.- The diagnosis of this rare combination of a physiological and pathological process may be very diflBcult. In certain cases much help can be obtained from recto-abdominal palpation under narcosis, using Kelly's method to gently produce artificial descensus of the uterus. The physical examination with the signs of pregnancy, and those which belong more particularly to solid ovarian growths, will generally enable us to make at least a probable diagnosis and one sufficient to warrant .in exploratory section.

III. The prognosis in cases of solid growths of the ovary complicating pregnancy is much worse, both for mother and child, than in those of cystic neoplasms of these organs. This is to be explained by the fact that the former are usually smaller and remain in the true pelvis and obstruct the parturient canal, while the latter, owing to their bulk and consistence, rise above the pelvis, and the dystocia, if produced at all, is of a less serious nature.

Abdominal section and. extirpation of solid tumors during the early months of pregnancy produce equally good results, so far as the life of the fa?tus is concerned, as in the case of cysts ; the ultimate I'esult in the case of the mother depending.


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of course, ou the malignant or benignant nature of the new growth.

IV. In the management of these cases we have seen that if the extirpation is undertaken during the elective period of gestation (second to fourth month) the maternal mortality was but 5 per cent., due to hemorrhage, shock, sepsis, and other causes ; whereas the foetal mortality due to abortion is only 20 to 22 per cent, as compared with 40 per cent, for the former and 80 per cent, for the latter when these cases are left to unaided nature.

The general rule, then, should be to operate on all cases between the second and fourth months of gravidity. It would be hard to find a stronger argument in favor of the elective operation for e.xtirpation of these ovarian neoplasms than is furnished by a comparison of the statistics of the best authorities.

V. The compulsory operation (during the latter half of gestation, during labor, or the puerperium) will rarely be required. One then should be guided by the suggestions of Hohl, preference being given to the procedures in the order above mentioned.

In conclusion I desire to express my deep sense of obligation to Professor Kelly for permission to report this unusual case ; to Dr. Cullen for much encouragement and assistance in obtaining references; and to Dr. Bardeeu for valuable aid in abstracting literature.

Bibliography.

1. Dsirne, J.: Arch, fiir Gyniik., 1893, V0I..XLIII.

2. Olshausen : Billroth's Handbuch.

3. Jetter : Billroth's Handbuch.

4. Olshausen : Die Krankheiten der Ovarien. Stuttgart, 1886.

5. Montgomery: Med. Times, Phila., 1886-7; XVII, 693, 698.

6. Eemy, S. : Quoted by Miiller in his Handbuch der Geburtshiilfe, p. 819.

7. Rokitansky : Winckel's " Diseases of Women," p. 577.

8. Breit, F. : Dissertation, Tubingen, 1861. Case from Lachapelle (Puchelt, S. 173).

9. Spiegelberg: Monatsschriftf. Gebiirtsh. (1866), XXVIII, p. 73.

10. Spiegelberg : Monatsschrift f. Gebiirtsh. (1867), XXX, p. 380.

11. Kleinwiichter: Arch, fiir Gyniik., Berlin (1873), IV, p. 171.

12. Spencer Wells : (Reported by Cayla), see 15.

13. Hempel : Arch, fiir Gyniik., VII, p. 556, 1875.


14. Schroeder: (Quoted by Cayla), see 15.

15. Spencer Wells: Contribution a I'etude de I'ovariotomie pratiquee pendant la grossesse. Paris, 1882.

16. Spencer Wells : See 15.

17. Casati, L. : Raccoglitore Med. Forli., 1883-4, XIX, 277, 292.

18. Carstens, J. H. : Tr. Am. Assn. Obst. and Gynfficol., Phila., 1889, Vol. II, pp. 151, 167.

19. Miinchmeyer: Centralb. f. Gyniik. (1890), XIV, p. 186.

20. Murphy, J. : Lancet (1895), I, p. 148.

21. Ruge, P. : Reported by Olshausen in " Die Krankheiten der Ovarien," 1886.

22. Dsirne: Hegar and Kaltenbach, Op. Gyniik., 1886, p. 248.

23. Olshausen, R. : Die Krankheiten der Ovarien. Stuttgart, 1886.

24. See 23.

25. Napier : Tokyo Med. Jour., Feb., 1888, p. 23.

252. Fenger: American .Journal of Obstetrics, New York, 1891, XXIV, pp. 1097, 1107.

26. Heiberg: Quoted by Olshausen in "Die Krankheiten der Ovarien," 1886.

27. Dsirne: Hegar and Kaltenbach, Operativ Gyniik., 1886, p. 248.

28. Montgomery : Med. Times, 1886-7, XVIII, p. 693.

29. Hohl: Arch. f. Gyniik., Berlin, 1896, LIII, 410, 427.

30. Greigg : Quoted by Montgomery ; see 28.

31. Miiller: Handbuch der Geburtshiilfe, p. 819.

32. Dsirne : See 27.

33. Barsony: Centralbl. fur Gyniik., Leipzig, 1897, XI, 139, 144.

34. Montgomery: See 28.

35. Litzmauu: Quoted by Montgomery; see 28.

36. Breit: See 8.

37. Munde, P. F.: New York Med. Journal (1887), p. 11.

38. Kreutzmann, H. : Am. Journal of Obstetrics, XXVI, p. 204.

39. Cohn : Winckel's " Diseases of Women," p. 541.

40. Montgomei-y : See 28.

41. Kelly: Lectures, Johns Hopkins Univ., 1896-7.

42. Olshausen : Winckel's " Diseases of Women," p. 542.

43. Dsirne: Arch, fiir Gyniik., Berlin (1892), XLII, 415, 456.

44. Hohl : Archiv fiir Gyniik. (1896), Berlin, LII, pp. 410, 437.

45. Lohlein, H.: Gyniik. Tagesfr., Wiesb., 1895, Hft. IV, 1, 31.


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THE CATHETERIZATION OF THE URETERS IN THE MALE THROUGH AN OPEN CYSTOSCOPE WITH THE BLADDER DISTENDED WITH AIR BY POSTURE.

By H. A. Kelly, M. D., Gi/necolor/ist-in-Chief to The Johns Hop/cins Hospital.


The difficulties and the dangers of the various devices for electric cystoscopy with the source of illumination introdiiced within the bladder are so great that I feel sure urologists everywhere will welcome and test carefully any new method of examination which bids fair to limit or to supplant these methods by one which is simpler, more direct and more satisfactory in its results.

I have succeeded in devising such a method and in demonstrating its utility in the presence of an audience of expert urologists and surgeons at St. Luke's Hospital, New York City, Feb. 4th, 1898, through the kind invitation of Dr. L. Bolton Bangs, consulting surgeon, and the courtesy of Dr. Robt. Abbe, visiting surgeon, who oflered me his clinic hour.

Among the visitors present were Drs. Eobt. F. Weir, Willy Meyer, Clement Cleveland, Kobt. A.Murray, Faiquhar B.Curtis, F. Tilden Brown, and others.

I was greatly indebted to the house staff of the hospital for their warm, intelligent interest and assistance throughout.

Dr. Otto G. Kamsay accompanied me from the Johns Hopkins Hospital and aided me skilfully at every step of the investigation.

The cystoscope used was a straight metal nickel-plated tube 15.5 cm. long, 7 mm. in diameter, the caliber being equal from end to end, except at the conical external orifice, which measured 3.7 cm. at its outer border and was blackened on the inside to prevent the reflection of the light from obscuring the field. A stout handle 10 cm. long was attached to the outer end.

The source of illumination was a small electric headlight, deriving its current from the house supply, reduced by a Vetter controller.

The patient, a young man, was put under Schleich's anesthetic, when I introduced the cystoscope armed with its obturator as far as the prostate, and then guided it easily over the prostate and into the bladder by raising and guiding the end with one finger introduced into the rectum. The penis, of


average size, shortened on the cystoscope to a length of about 5 cm.

He was then carefully turned over and placed in the kneechest posture and brought to the edge of the table and the obturator withdrawn ; air at once entered the bladder and the investigation was made.

The light was good and the base of the bladder at once came clearly into view; the posterior wall was seen by elevating the handle a little, then by turning it to the right and to the left the left and right lateral walls were clearly seen. I then withdrew the speculum until the internal urethral orifice began to close over it, and then pushed it in a little, turned it about 30 degrees to the left and dropped the handle, when the right ureteral orifice came clearly into view, as clearly as I have ever seen it in a woman.

Dr. Willy Meyer looked through the cystoscope and agreed it could not have been seen clearer or more unmistakably if it had been on the surface of the body.

Dr. Eamsay then handed me one of my renal catheters, 50 cm. long and 2 mm. in diameter, armed with a stylet, and this was guided, after two attempts, up into the ureteral orifice, and easily stripped of the stylet, into the ureter, ascending up to the pelvis of the kidney. Dr. Abbe now looked through the cystoscope and saw the catheter entering the bladder wall.

The patient was then put to bed with the catheter in position, and before leaving the hospital I had the satisfaction of knowing that half a test-tube full of slightly cloudy urine had been collected.

By this method of cystoscopy not only is the diagnosis of vesical lesions simplified, but simpler and direct plans of treatment, such as curetting, cauterizing and making applications to localized areas are made possible. Small tumors may also be easily excised or snared.

A preliminary note has been published in the Annah of Surgery (Jan. 1897), where a fuller account will shortly appear.


PROCEEDINGS OF SOCIETIES.


THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Meeting of December 20, 1897.

Dr. Barker in the Chair.

On Super-Arterial Pericardial Fibroid Nodules.— Mr. Knox. In 1866 Kussmaul and Maier reported an instance of the development upon many of the smaller visceral arteries, of nodules, to which condition they applied the name of peri-arteritis nodosa. Since this time additional cases of a similar disease have been described by Chvostek and Weichselbaum,


Meyer, Fletcher and Von Kahlden. This rare condition is characterized by the presence upon the smaller arteries, except those of the brain and spinal cord, of small grayish-white nodules, which microscopically are found to be associated with hypertrophy of the internal and adventitial coats of the affected vessels, and with weakening or even rupture of the middle coat. The origin of this affection is conceived to be either some form of infection or intoxication.

Some months ago my attention was directed, through the kindness of Dr. Flexner, to a heart which showed upon its surface, over the arteries, opaque elevations suggesting those of


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peri-arteritis nodosa. Later, at the autopsies, several other hearts affected in like manner were fonud, and I was permitted to study the specimens in the Pathological Laboratory.

The extent of the process varied, from tortuous, more or less uniform elevations over the arteries, to whitish dots, minute in size and few iu number, which almost escape attention.

The elevations may be separated from each other by wide intervals, may be quite close, resembling beads strung along the vessel, or they may coalesce throughout the entire length of the artery.

The nodules were found exclusively upon the ventricles and the interventricular septa; never within the heart muscle, upon the auricles, nor over the veins. They were never noticed elsewhere in the body.

Ou microscopical examination there were no constant alterations to be made out in hfematoxyliu and eosin stained specimens in any of the arterial coats, but between the adventitia of the vessel and the surface there was a marked fibrous thickening projecting beyond the level of the pericardium and producing the nodules seen in gross specimens. At the base of the nodule and at the sides lymphocytes and a small number of polymorphonuclear leucocytes were accumulated.

The appearance in cross-section was as though a compact mass of firm connective tissue, convex on its inner surface, had been placed upon the artery in the loose pericardial tissue.

The nodule may be only a small oval patch over a portion of the artery, or it may extend a considerable distance upon each side.

The earliest stages of the process met with showed simply a serous infiltration and an accumulation of small round cells superficial to the artery on its outer side.

In no case was any tendency to fibrous formation noticed on the inner side of the vessel, next to the heart muscle, nor in the heart muscle itself.

The constant relationship of the fibrous thickenings to the arteries suggested that the nodules were in some way associated with changes in the arterial walls not brought out by the stain in hematoxylin and eosin, and a representative number of the sections were stained for elastic tissue by the fuchsin method described by Manchot.

There were of course variations in the sections, but the results were sufficiently uniform to be quite suggestive. In a few sections there were distinct breaks in the inner elastic coat just opposite the nodule, but the most noticeable alteration and the one present in most of the preparations was a diminution in the strength of the order elastic coat between the muscle and the adventitial layers.

This membrane was well reiiresented on the inner side of the artery often by a heavy dark red band, but as one approached tlie outer half it became thinned, the fibers looser and separated from each other until usually just beneath, at times a little to one side of the fibrous thickening, only a few straggling strands of the elastic fiber remained.

In no instance was this change accompanied by an increase in the thickness of the inner elastic coat. Occasionally only were defects in either elastic layer seen on the inner side of an artery. Iu these cases no alterations corresponding to the


nodule under discussion were present in the remaining layers nor in the surrounding tissue.

The change described was not seen in arteries not surmounted by the fibrous patch.

These findings would suggest at least some association between the nodules on the surface and the weakening in the arterial wall beneath.

The affection, as far as can be ascertained, was discovered incidentally in every case, and produced no symptoms as far as can be known.

From the above description there can be nodoubt that the condition found in the epicardium of these cases is entirely distinct from peri-arteritis nodosa. There was, too, nothing in the histological appearances that was suggestive of a primary bacterial or toxic action upon the tissues leading to the fibrous formation, and the bacteriological studies of the cases at autopsy did not support such an assumption.

In considering the histological appearances one is tempted to regard the changes in the elastic coat as the primary alteration. Moreover, a number of facts iu the protocols lend support to this idea, for the individuals in whom the condition was found were subject to unusual strains put upon their cardio- vascular system.

Of four cases in which the nodules were present, three showed heart hypertrophy. In one, lesions of the valves existed ; in another, arterio- sclerosis. Three of the cases suffered from nephritis; in three there was oedema, and in one case aneurism. Three of the four patients gave histories of heavy work, irregular life, and the ingestion of large amounts of alcoholic beverages.

Discussion of Dr. Huiiner's Cases of Aneurism [continued). See February Bulletin, p. 38.

Di\ OsLER. — The most interesting thing about this case relates to the diagnosis. This patient was under observation last year, and there were several points of great interest at first which made us doubt whether he really had aneurism of the aorta. We could not grasp a very positive tumor. There were well-marked pulsation and a definite thrill and murmur, but these, in the absence of a tumor, when you have reached a certain grade in your experience, are insufficient. He had aortic regurgitation, but that also made us hesitate, for you know how frequently, particularly in young persons, great dynamic pulsation is present. He was under observation for many months, and several additional features came out which made the diagnosis of aneurism of the aorta reasonably certain. In the first place the characters of the pains, that had kept up in a very persistent way aud required a great deal of morphia to relieve. Then he developed a loud bruit at the back ; but what really clinched the diagnosis was a pulsation at the back which could be both seen and felt. Another suggestive point was the fact that the abdominal pulsation was altogether above the infra-costal line. It did not extend the entire length of the abdominal aorta. You can feel the thrill, but you do not feel a very positive tumor, which is evidently deep-seated, probably in the ciliac axis.

In the second case the pulsation is more evident and very visible. Here the tumor is much more evident, the thrill is


64


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 84.


very intense, and there is a loud systolic and also a diastolic murmur. He has no bruit behind. His pains are not nearly so intense. The situation of the pulsation, its very wide area, the very pronounced character of the tumor, and its expansile pulsation, are features that make the diagnosis certain. One of the most important points in this case is its onset in early life; he is only 27, very early for aneurism.

The possibility is that lead, in which he worked for so many years, had caused the sclerosis of his arteries. In the first case the aneurism is probably in contact with the lower ribs on the left side. In this case I do not think the aorta has eroded the vertebrae to any great extent. He has not had the boring pains such as are almost always present when the aneurism is eroding the vertebrse.

We have had five instances of abdominal aneurism in the Hospital, out of a total of 57 aneurisms of the larger vessels. It is very much less common than aneurism of the thoracic aorta.

Some of you remember the man, Lee Kenny, who had a singularly movable tumor in the upper part of the abdomen, which was aneurismal, which pulsated with considerable force and which you could grasp in the hand. Dr. Halsted did a laparotomy, thinking it was possibly not in the aorta but in one of the branches, but it proved to be in the aorta. He was somewhat improved after the operation, but we lost sight of him.

In a certain number of aneurisms of the abdominal aorta a cure has been effected. The celebrated case of Murray was the first; the aneurism was seated low, just above the bifurcation, and digital compression for an hour caused cessation of pulsation in the sac, and patient lived for nine or ten years. The autopsy showed a healed aneurismal sac. There have been several other instances where compression either by fingers or the clamp cured the aneurism by filling the-sac and securing consolidation.

In this first case I think operative procedures would be out of the question. In the second one the possibility of wiring has to be considered. In several cases this has been done successfully. In this man the operation would be justifiable.

Discussion of Dr. Paiicoast's Diabetes in the 'Se^ro {continved). See February Bulletin, p. 40.

Dr. OsLER. — This case illustrates a point that was brought to my mind a few weeks ago. A woman with diabetes went to Europe in the middle of June. She had a slight cough at the time which had not attracted the attention of her physicians. In .July the cough became worse, and her doctor in Ireland found extensive disease of one lung. On her return she refused to see her old physicians, as she blamed them for overlooking a serious condition of affairs and permitting her to go abroad. She persisted in this point, though I tried to explain that her trouble had developed very rapidly.

Here is a case in point. This man developed tuberculosis within a period of nine weeks and lost in weight from 180 to 130 pounds. The loss of weight and the rapid downward progress are well recognized features in some cases of diabetic phthisis.


NOTES ON NEW BOOKS.

Pathological Technique. A Practical Manual for the Bacteriological Laboratory. By Frank B.\ke Mallory, A. M., M. D., and James Homer Wright, A. M., M. D. [W. B. Saunders, Philadelphia, 1897.)

The manual wliich bears the above title comes to us from the pathological laboratories connected with the Harvard Medical School, and while it is offered as a practical guide for workers in pathological laboratories, we shall be much mistaken if it does not find a much wider sphere of usefulness. The volume, which is well made and of convenient size, is subdivided into three i)art8; the subject-matter of each, while closely connected with that of the other two, being treated in detail separately.

Part I, in which the technique of autopsies is outlined, contains a full and satisfactory presentation of the best recognized procedures in making post-mortem examinations. The authors have adhered to no one authority, but have chosen from several sources methods which they regard as the most useful and practical. While, as might naturally have been expected, the Virchow method is mainly followed, the authors have not felt themselves bound to follow it in all its details and do not hesitate to recommend the employment of certain procedures which have emanated from the Austrian school of pathologists. Many of the illustrations in this part of the work are borrowed from the little manual of Nauwerck, and the authors are to be commended for reproducing and making available for the English-speaking student these excellent drawings. In the part devoted to the section of the brain the method of Virchow is justly criticized as causing too much disturbance of the relations in the cortex, while that of Pitre, which is also given in detail, is not commended. In the light of our present knowledge the authors would seem to consider the hardening of the entire organ in formalin as affording the best means for future accurate study of the topography of focal lesions, while at the same time the tissue is preserved so as to be available for the finer histological methods. The demands of modern neurology, the growth of the knowledge of cerebral localization and the importance of following closely the various tracts have rendered it evident that the customary time which can be devoted to an autopsy is every day becoming more and more unsuitable for the examination and description of lesions in this organ.

On page 20 a typographical error has slipped into this part of the work. The statement that "The greenish discoloration seen earliest over the abdomen is due to sulphate of iron," is evidently intended to read, stdphide of iron.

Part II, which treats of the general methods of bacteriological examinations, is subdivided into (1) Bacteriological apparatus ; (2) Culture media; (3) Bacteriological examinations at autopsies ; (4) The methods of studying bacteria in cultures; (-5) Bacteriological diagnosis ; (6) Clinical bacteriology.

This section of the work is all that can be desired in a book of the scope of the present one. The directions for the preparations of media and cultures and the isolation of micro-organisms in pure culture and their identification, which is the ultimate purpose of bacteriological study, are clearly and succinctly stated. AVe fail, however, to notice any allusion to the autoclave for the sterilization of culture media. There is, in our opinion, no more valuable piece of apparatus for the bacteriological laboratory. Besides its other advantages it enables the time element in the preparation of such media to be greatly reduced. But, however convenient it may be to obviate the loss of time consumed in fractional sterilization, and whatever the advantages in having the media ready to use at once after their preparation, the chief value of the autoclave lies in the certainty with which, at a single exposure, even the most resistant spores («. g. of the bacillus subtilis) are destroyed. The atmosphere of Boston or its climate may be unfavorable to the prevalence of epidemics of hay-bacillus infection, or perchance the city water


March, 1893.]


JOHNS HOPKINS HOSPITAL BULLETIN.


65


supply is free from contamination with this organism ; but in the latitude of Baltimore, especially in the fall season, it constitutes a pest to the bacteriologist, against the ravages of which the autoclave alone has been found to furnish a sufficient protection. With the exception of blood serum we do not hesitate to put all culture media, including even gelatine (which is exposed for 6 or 8 minutes), through the autoclave at a uressure of two atmospheres and at a temperature approaching 120° C.

The routine examination by cultures and films or cover-slips is recommended in post-mortem examinations. We are glad to find this point emphasized. The day is perhaps not far distant when this procedure will be regarded as essential to the proper conduct of an autopsy, so that every examination will be deemed incomplete unless the bacteriological study has been carried out. Not a few problems in the causation of disease and of death have already received their solution through the systematic search for pathogenic bacteria in human post-mortem examinations. No modern physician, and still less a pathologist or bacteriologist, regards bacteria as the only living agents which cause the infectious diseases, and we are therefore bound to exercise due caution and a chariness in drawing conclusions based upon negative results from the bacteriological study in suspicious cases. It is not too much to hope that the near future will make amenable to cultivation and study the group of protozoa, just as the bacteria, by the introduction of solid culture media and the invention of a few simple mechanical processes, have been rendered so easy of observation. And when this feat shall have been accomplished, may not the whole group of exanthematous fevers be " resolved " and fall into their natural nosological places?

It is quite natural that differences of opinion should arise, especially regarding details, as to the best or most generally useful method to be employed in the systematic bacteriological study of autopsies. The authors of this manual advise as the best medium coagulated blood serum, which by their method of preparation is easily accessible for routine work. Of its suitableness as a culture medium there can be no question, but there remains the objection that where a mixture of bacterial forms or species prevails in the original material, their isolation can be most easily effected before the existing proportions are disturbed, and data of the relative numbers of each species present can be obtained only by an immediate separation. For this purpose the "plate" method, using preferably agar-agar, would seem to be the only one applicable. In the end, special cases will dictate special methods of procedure, and the rarity or frequency of departures from the rule will depend on circumstances, among which should perhaps be placed first the readiness with which the operator appreciates the unusual and his capacity to deal quickly with special problems as they arise. In carrying out a post-mortem examination in what is now regarded a proper manner, so many details have to be considered, that unless the time factor is to be entirely neglected, dexterity in operation and quickness in decision are faculties which are especially to be cultivated and by no means to be despised.

As regards the " time factor" the improvements in histological technique allow no free latitude. If the pathological histology of the future is to keep pace with its younger brother histology, and is to advance beyond the achievements of the period which ended with the semi-centennial just celebrated by Virchow's Archives, and which marks the era of the influence upon medical science of the cellular doctrine of organized nature, then minutes must replace hours in the time elapsing after death before autopsy in order that the organic tissues may be suitable for histological research.

The statement that the micro-organism causing actinomycosis has not as yet been proved to belong to the bacteria (fission-fungi) is made with due conservatism, but it seems hardly justifiable to place it provisionally among the cladothrices. If it is a bacterium it belongs, according to our present classification, among the streptotbrices.


The differentiation of the smegma bacilli from the bacillus of tuberculosis is not quite so simple a matter as one little experienced in this undertaking might conclude from the remarks on pages 92 and 93. As the question is often an important one in diagnosis, it might not have been out of place to mention some of the difficulties and to have supplied other methods of distinction, especially the use of an alcoholic solution of methylene-blue, as recommended by Grethe.

Part III, which is devoted to the enumeration and description of histological and clinical microscopic methods, gives an excellent account of tlie processes employed in hardening, imbedding, sectioning, staining and mounting microscopic sections of tissues. The examination of sputa, blood, fwces, gastric contents and urine is also ilealt with. Where so much is attempted it is not to be expected that all the headings will be treated of with equal completeness. The chief value of this chapter will be found in the paees devoted to histological methods, and it goes without saying that the special works dealing with clinical microscopy will need to be consulted by those who require more than a brief outline of matters relating to any one subject, for the minute details of which the authors could not spare space.

Drs. Mallory and Wright have given to the English-speaking student an excellent laboratory guide in the methods of modern pathological, histological and clinical study and research.

S. F.


BOOKS RECEIVED.


Twentieth Century Practice. An International Encyclopedia of Modern Medical Science, by Leading Authorities of Europe and

America. Edited by Thomas L. Stedman, M. D. Vol. XIII.

Infectious Diseases. 1898. 8vo. 621 pages. W. Wood & Co. Biennial Rejmrt of the Department of Health of the City of Chicago,

being for the Tears 1S95 and 1896. 1897. 8vo. 397 pages -f 51 + 30.

Press of Cameron, Amberg & Co., Chicago. Case of Carcinoma of Descending Colon; Excision and Anastomosis;

Recovery. By John H. Musser, M. D., and Thomas S. K. Morton,

M. D. Reprinted from the University Medical Magazine, July,

1896. Angina Pectoris : Its Relation to Dilatation of the Heart. By John

H. Musser, M. D. Reprinted from the American Journal of

the Medical Sciences, September, 1897. A Case of Luccemia. By John H. Musser, M. D., and Joseph Sailer,

M. D. Reprinted from the Transactions of the Association of

American Physicians, 1896. On the Disappearance of Endocardial Murmurs of Organic Origin. By

John H. Musser, M. D. Reprinted from the British Medical

Journal, October 16, 1897. A Clinical Study of Widal's Serum Diagnosis of Typhoid Fever. By

John H. Musser, M. D., and John M. Swan, M. D. Reprinted

from the Journal of the American Medical Association, August

14, 1897. A TeH-Bookof the Diseases of Women. By Henry J. Garrigues, A.M.,

M. D. Second Edition. Thoroughly Revised. 1897. 8vo. 728

pages. W. B. Saunders, Philadelphia. Elements of Latin. For Students of Medicine and Pharmacy. By

George D. Crothers, A.M., M. D., and Hiram H. Bice, A.M.

1898. 12mo. 242 pages. The F. A. Davis Co., Philadelphia.


ERRATA-JANUARY BULLETIN.

In footnote, page 12, read 1629 instead of 1829.

In footnotes on page 13, the references to Vanderwiel and Schurig should be reversed.

On page 16, line 12, the word nasal should be inserted before reflex neuroses.


m


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 84.


THE JOHNS HOPKINS MEDICAL SCHOOL. SESSION 1897-1898.


FACULTY.


Daniel C. Oilman, LL. D., President.

William H. Welch, M. D., LL. D., Dean and Professor of Pathology.

Ira Kemses, M. D., Ph. D., LL. D., Professor of Chemistry.

William Osler, M. D., LL. D., F. R. C. P., Professor of the Principles and Practice

of Medicine. Henry M. Hurd, M. D., LL. D., Professor of Psychiatry. William S. Halsted, M. D., Professor of Surgery. Howard A. Kelly, M. D., Professor of Gynecjlogy and Obstetrics. Franklin P. Mall, M. D., Professor of Anatomy. John J. Abel, M. D., Professor of Pharmacology. William H. Howell, Ph. D., M. D., Professor of Physiology.

William K. Brooks, Ph. D,, LL. D., Professor of Comparative Anatomy and Zoology. John S. Billings, 51. D., LL. D., Lecturer on the History and Literature of Medicine! Charles Wardell Stiles, Ph. D., M. S., Lecturer on Medical Zoology. Robert Fletcher, M. D., M. R. C. S., Lecturer on Forensic Medicine. William D. Cooker, M. D., Clinical Professor of Diseases of Children. John N. Mackenzie, M. D., Clinical Professor of Laryngology and Rhinology. Samuel Theobald, M. D., Clinical Professor of Ophthalmology and Otology. Henry M. 1'homas, M. D., Clinical Professor of Diseases of the Nervous System. Simon Flexner, M. D., Associate Professor of Pathology. J. Whitridoe Williams, M. D., Associate Professor of Obstetrics. Lewellys F. Barker, M. B., Associate Professor of Anatomy. William S. Thayer, M. D., Associate Professor of Medicine. JoHM M. T. FiNKET, M. D., Associate Professor of Surgery.


r.EonoE P. Dreyer, Ph. D., Associate in Physiology.

William W. Russell, M. D., Associate in Gynecology.

Hesuv J. Berkley, M. D., Associate in Neuropathology.

J. Williams Lord, M. D., Associate in Dermatology and Instructor in Anatomy.

T. Caspar Gilchrist, M. R. C. S., Associate in Dermatology.

Robert L. Randolph, M. D., Associate in Ophthalmology and Otology.

Thomas B. .\ldrich. Ph. D., Associate in Physiological Chemistry.

Thomas B. Futcher, M. B., Associate in Medicine.

Joseph C. Bloodoood, M. D., Associate in Surgery.

Thomas S. Cullex, M. B., Associate in Gynecology.

Ross G. Harrison, Ph. D., Associate in Anatomy.

I'RANK R. Smith, M. D., Instructor in Medicine.

Georoe W. Dobbin, M. D., Assistant in Obstetrics.

Walter Jo.ves, Ph. D., Assistant in Physiological Chemistry.

Adolph G. Hoen, M. D., Instructor in Photo-Micrography.

Sydney M. Cone, M. D., Assistant in Surgical Pathology.

Locis E. Livincood, M. D., Assistant in Pathology.

Henry Barton Jacobs, M. D., Instructor in Medicine.

Charles R. Bardeen, M, D., Assistant in Anatomy.

Stewart Paton. M. D., Assistant in Nervous Diseases.

Norman McL. Harris, M. B., Assistant in Pathology.

Harvey W. Cushino, M. D., Assistant in Surgery.

J. M. Lazear, M. D., Assistant in Clinical Microscopy.

J. L. Walz, Ph. G., Assistant in Pharmacy.


GENERAL STATEMENT.

The Medical Department of the Johns Hopkins University was opened for the instruction of students October, 1893. This School of Medicine is an integral and coordinate part of the Johns Hopkins University, and it also derives great advantages from its close affiliation with the Johns Hopkins Hospital.

The required period of study for the degree of Doctor of Medicine is four years. The academic year begins on the first of October and ends the middle of June, with short recesses at Christmas and Easter.

Men and women are admitted upon the same terms.

In the methods of instruction especial emphasis is laid upon practical work in the Laboratories and in the Dispensary and Wards of the Hospital. While the aim of the School is primarily to train practitioners of medicine and surgery, it is recognized that the medical art should rest upon a suitable preliminary education and upon thorough training in the medical sciences. The first two years of the course are devoted mainly to practical work, combined with demonstrations, recitations and, when deemed necessary, lectures, in the Laboratories of .\natomv, Physiology, Physiological Chemistry, Pharmacology and Toxicology, Pathology and Bacteriology. During the last two years the student is given "abundant opportunity for the personal study of cases of disease, his time being spent largely in the Hospital Wards and Dispensary .^nd in the Clinical Laboratories. Especially advantageous for thorough clinical training are the arrangements by which the students, divided into groups, engage in practical work in the Dispensary, and throughout the fourth year serve as clinical clerks and surgical dressers in the wards of the Hospital.

REQUIREMENTS FOR ADMISSION.

As candidates for the degree of Doctor of Medicine the school receives :

1. Those who have satisfactorily completed the Chemical-Biological course which leads to the A. B. degree in this university.

3. Graduates of approved colleges or scientific schools who can furnish evidence : (a) That they have acquaintance with Latin and a good reading knowledge of French and German ; (6) That they have such knowledge of physics, chemistry, and biology as is imparted by the regular minor courses given in these subjects in this university.

The phrase "a minor course," as here employed, means a course that requires a year for its completion. In physics, four class-room exercises and three hours a week in the laboratory are required; in chemistry and biology, four class-room exercises and five hours a week in the laboratory in each subject.

3. Those who give evidence by examination that they possess the general education implied by a degree in arts or in science from an approved college or scientific school, and the knowledge of French, German, Latin, physics, chemistry, and biology above indicated.

Applicants for admission will receive blanks to be filled out relating to their previous courses of study.

They are required to furnish certificates from officers of the colleges or scientific schools where they have studied, as to the courses pursued in physics, chemistry, and biology. If such certificates are satisfactory, no e.vamination in these subjects will be required from those who possess a degree in arts or science from an approved college or scientific school.

Candidates who have not received a degree in arts or in science from an approved college or scientific school, will be required (1) to pass, at the beginning of the session in October, the matriculation examination for admission to the collegiate department of the Johns Hopkins University, (3) then to pass examinations equivalent to those taken by students completing the Chemical-Biological course which leads to the A. B. degree in this University, and (3) to furnish satisfactory certificates that they have had the requisite laboratory training as specified above. It is expected that only in very rare instances will applicants who do not possess a degree in arts or science be able to meet these requirements for admission.

Hearers and special workers, not candidates for a degree, will be received at the discretion of the Faculty.

ADMISSION TO ADVANCED STANDING. Applicants tor admission to advanced standing must furnish evidence 11) that the foregoing terms of admission as regards preliminary training have been fulfilled, (2) that courses equivalent In kind and amount to those given here, preceding that year of the course for admission to which application is made, have been satisfactorily completed, and 13) must pass examinations at the beginning of the ses.slon in October in all the subjects that have been already pursued by the class to which admission is sought. Certificates of standing elsewhere cannot be accepted in place of these examinations.

SPECIAL COURSES FOR GRADUATES IN MEDICINE.

Since the opening of the Johns Hopkins Hospital in 1883, courses of instruction have been olTered to graduates in medicine. The attendance upon these courses has steadily increased with each succeeding year and indicates gratifying appreciation of the special advantages here afforded. With the completed organization of the Medical School, it was found necessary to give the courses intended especially for physicians at a later period of the academic year than that hitherto selected. It is, however, believed that the period now chosen for this purpose is more convenient for the majority of those desiring to take the courses than the former one. The special courses of instruction for graduates in medicine are now given annually during the months of May and Jnne. During April there is a preliminary course in Normal Histology. These courses are in Pathology, Bacteriology, Clinical Microscopy, General Medicine, Surgery, Gynecology, Dermatology, Diseases of Children, Diseases of the Nervous System, Genito-Urinary Diseases, Laryngology and Rhinology, and Ophthalmology and Otology. The instruction is intended to meet the requirements of practitioners of medicine, and is almost wholly of a practical character. It includes laboratory courses, demonstrations, beside teaching, and clinical instruction in the wards, dispensary, amphitheatre, and operating rooms of the Hospital. These courses are open to those who have taken a medical degree and who give evidence satisfactory to the several instructors that they are prepared to profit by the opportunities here offered. The number of students who can be accommodated in some of the practical courses is necessarily limited. For these the places are assigned according to the date of application.

The Annual Announcement and Catalogue will be sent upon application. Inquiries shonid be addressed to the

REGISTRAR OF THE JOHNS HOPKINS MEDICAL SCHOOL, BALTIMORE.


The Johns Hopkim Hospital Bulletins are issued monthly. They are printed by THE FRIEDENWALD CO., Baltimore. Single copies may be procured from Messrs. CVSHING & CO. and the BALTIMORE NEWS COMPANY, Baltimore. Subscriptions, $1.00 a i/ear, may be addressed to the publishers, THE JOHNS HOPKINS PRESS, BALTIMORE; single copies trill be sent by mail for fifteen cents each.


BULLETIN


OF


THE JOHNS HOPKINS HOSPITAL.


Vol. IX.- No. 85.]


BALTIMORE. APRIL, 1898.




oolsrTiBisrTS.


Miniature Hammers and tlie Suture of tlie Bile Ducts. By W.

S. Halsted, ]\I. D.,

University Education. By Michael Fcster, . - - . The Results of the Intra-trarheal Inoculation of the Bacillus

Diphtheriae in Rabbits. By Simon Flexner, M. D.,and H.

B. Anderson, M.D.,

The Bacti-riology of Pertussis. By Henrv Koplik, M. D.,


Supplementary Report on the Sterilization of Instruments by Formaldehyde. By H. O. Reik, M. D.,

Correspondence : Does Wilhite's Story of the Negro Boy Incident in the Discovery of Ansesthesia lack Probability"? Letters from J. (>. Wilhite, M. D., and Hugh H. Young, M. D.,

Notes on New Books, --------


MINIATURE HAMMERS AND THE SUTURE OF THE BILE DUCTS.*

By W. S. Halsted, Professor of Surgery in the Johns Hopkins University a)id Sm-yeon-in-Chief to the Johns Hopkins Hospital.


The surgery of the common bile duct is still in its infancy. "Suture of the thickened duct is difficult enough, and suture of the normal duct out of the question," says one. " It is not worth while to exercise such great care in sewing up a slit in the common bile duct, for it is almost impossible to prevent leakage, and a little additional leakage can do no harm if one drains," says another. " Wait until the common bile duct dilates and thickens before venturing to open it," say all surgeons.

"Ein normaler Ductus choledochus ist ein ausserordentlich dilunwandiges Gebilde; eiue Liingswunde in demselben exakt zu verniihen, durfte techniscb ausserordentlich schwierig sein, zumal man durch Einstiilpung der Wundrixnder leicht das Lumen des Kanales zu sehr verengen kann. Zum Gliicke erweitert sich der Ductus choledochus bei Eintritt von irgendwie grosseren Steinen alsbald, seine Wandung wird dicker, so dass Incision und Naht ineist leicht gelingen."f

"Beim dritten Act, habe ich die Schwierigkeit des Nahtverschlusses der Incision des Choledochus, welche in 2 Fiillen iiberhaupt uiimoglich war, keiinen gelernt, die Niiizlichkeit der Tumponnade eiugeseheu, sobald die Choledochotomie fiir sich allein ausgefiihrt oder mit der Cystectomie verbunden


♦ Presented at the Johns Ho|ikin8 Hospital Medical Society, December 13, 1897.

tRiedel. Chirur»ische Behandlung der Galiensteinkrankheit, p. 115. Handbuch der Speciellen Therapie innerer Krankheiten, , Bd. iv.


wurde."* "Eine Choledochotomie rechnet er [Kiimmellf] zu den technisch schwierigsten Operatioi en. "J

To close an incision in the normal ductus communis choledochus has been considered so impracticable, not to say impossible, and the result of the suture, so far as the suture itself is concerned, even of the abnormally thickened duct so uncertain, that it is the practice of all surgeons to wait weeks or months or even years for the duct to dilate and thicken rather than interfere promptly in cases of obstruction of the common bile duct by stone.

It is perhaps justifiable to "give nature a chance" to e.xpel the stone, but the operation should never be postponed solely for the sake of giving the duct time to become thicker. I know from operations upon dogs and man that the normal bile ducts can be sutured easily, accurately, almost infallibly, and without danger of leakage or constriction.

We are all more or less acquainted with the more evident dangers of postponing choledochotomy when it is indicated; the deep jaundice, the retarded blood coagulation and the consequent danger from hemorrhage, whether an operation is performed or not; the cirrhotic hypertrophy of the liver and the concomitant hemorrhages into stomach and intestines, the


K-lir. Ein Ruckblick auf 209Gallen8teinlaparotomieen. Arch, fiir Klin. Chirurgie, Bd. liii, Heft 2, p. 375.

fMittheilungen aus den Hamburgischen Staatskrankenanstalten, 1897, Bd. 1, Heft 2.

|Ref Tschmarke, Centralblatt fiir Chirurgie, 1898, No. 5, p. 134.


68




acute or chronic inflammation of the bile passages ; toxaemia, cholaemic or infectious, and the interfei'ence with metabolism, more serious, perhaps, in its remoter consequences than we have estimated. And when at last the operation is resorted to the patient is perhaps so weak that the surgeon might well wish that he had interfered earlier.

The duct lies in a deep hole, at a great distance from the surface, and is covered by the liver, which is usually enlarged in the cases which we are considering, and which, if very large or very small, may embarrass the operator exceedingly. The suggestion of Dr. Fred. Lange to cut through one or two ribs and the diaphragm when the liver is very large we have found invaluable. And not only when the liver is large have we profited by this hint; for once when it was small and high up under the ribs, the duct, carried up with it, was perhaps even less accessible than in the cases complicated with large liver.

Once then because of a small liver, and several times because the livers were large, have I divided ribs and diaphragm, and each time with gratifying results. When operating upon the bile passages of dogs I divide two or three ribs and the underlying diaphragm as a matter of routine. Cutting through a few ribs and the diaphragm on the left side enabled me to remove a large and very adherent tuberculous kidney.

With the little hammers which I am describing, or with a similar contrivance, I have five times sutured the common bile duct in dogs, and twice the common duct and once the cystic duct in the human subject. Two of the dogs referred to were operated upon last spring and observed during the summer and part of the autumn.

Dog 1. June 24, 1897. Long incision in common bile duct sutured over an aluminum rod with six mattress sutures of fine black silk. The wall of the duct was so thin that all of the stitches necessarily penetrated it. The silk itself was thicker than the wall. I intentionally turned in a great deal of the wall, wishing to temporarily occlude the lumen of the duct ; and having withdrawn the rod and tied the sutures, I was impressed with the thread-like appearance of the duct and thought that I had perhaps totally occluded it. The dog was apparently as well as usual in a day or two and was observed all summer. At no time was he jaundiced, nor did he seem to be in the least inconvenienced by the operation.

Oct. 1st. Dog killed with ether. Autopsy. Except for the few silk threads in the tissues there was little to evidence the operation.

Dog 3. June 34, 1897. Through an incision into the ductus communis choledochus a small shot not quite large enough to occlude the lumen of the duct was introduced. The duct was sutured with mattress sutures over an aluminum rod as in the preceding case.

The aluminum rods, of several sizes, were flexible and were bent to suit the case just before using. I was very much pleased with the rods, because they made not only possible but very easy what hitherto had been considered too ditticult to attempt. The rods suggested to me the rubber bags for intestinal suture which I have already described.*


Philadelphia Med. Journ., Jan. 8, 1898, and The Johns Hopkins Hospital Bulletin, Feb., 1898.


The little hammers which I now use answer the purpose better than the rods. Within the past three weeks I have twice used the hammers on the human subject. If properly employed they convert one of the most difficult operations in surgery into quite a simple one. The hammers are of sizes (vid. Figs. 4 and .5) to meet all cases, from the normal duct in a dog to a much dilated human duct.

To Use the Hammer in Suture of the Common Bile Duct.

It is not necessary to dissect the duct from its bed, but the wall of the duct should be clearly exposed at the site selected for the incision. I usually incise the common bile duct near its duodenal end because the diverticulum of Vater can be more thoroughly explored through an incision at this end of the duct, and because it is easier to suture this end than the other or cystic end of the common bile duct.

Before incising the duct, two presectiou stitches, to serve as retractors, should be taken. These stitches, which are subsequently removed, should enter the lumen of the duct. They are placed close together and the incision into the lumen of the duct is carried between them (vid. Fig. 1).

The stone having been removed and the gall passages thoroughly searched with probe and fingers, the retractor threads are drawn apart and a hammer of the proper size introduced (vid. Fig. 3).

The duct is then gently raised from its bed and drawn towards the operator (vid. Fig. 3) by the hammer, the head of which is of course longer than the incision.

Mattress stitches are then applied as shown in Fig. 3 ; one over the heel behind the handle of the hammer, and the others in front of the very delicate handle. This beautiful drawing was made from the subject and depicts accurately the parts concerned in this stage of the operation.

Although the finest possible needles and silk are used the stitches necessarily perforate the wall of the normal duct. No harm results from this perforation, however, for the normal duct practically always and the thickened duct usually is sterile, and the stitches very soon cut their way out of the lumen and out of the wall of the duct and lie free in the adventitious tissues.

The silk which we use is very much finer than the artist supposed when he made the drawings, and the needles, made for us by Wiilfing-Luer, of Paris, have a split eye and are almost as fine as the silk itself. One should have a needleholder especially made and reserved for these needles. If such a needle-holder is used for coarser work it will soon be ruined.

I have been asked why the handle is not placed in the middle of the hammer. It is placed as near one end as practicable, to enable the operator to introduce the hanmier through as small an incision as possible, an incision not longer than about half the circumference of the hammer.

The Advantages of the Hammer.

1. The duct to be sutured can be drawn towards the incision in the anterior abdominal wall and within easy reach of the operator ; it can also be manipulated nicely by the hammer.


RETRACTOR THREADS.



SUSPENSORY LIG OF LIVER.


GALL BLADDER


HEPATIC

FLEXURE OF

COLON.



PYLORUS.

Fig.


lloruiss IIosriTKi, IUu.i.ktin No. fir-,. Sec piige CR.


MILLIMETERS.


O O

O

o


actual length. Fig. 4.




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2 The duct, whetlier normal or thickened and dilated, is gently expanded by the hammer ; hence the stitches can be taken with great accuracy and without fear of including the opposite wall or of occluding the lumen of the duct.

3. The operation is a very clean one, because the hammer blocks the duct and this prevents the escape of its contents and the contents of the gall bladder.


i. With the hammer, wounds of thin normal ducts can be easily and almost infallibly sutured, and hence the surgeon may, if he chooses, fearlessly operate upon the common duct as soon as the obstruction takes place.

The sewing of the thickened and dilated ducts is also greatly facilitated by the employment of the hammer.


UNIVERSITY EDUCATION.

By Michael Foster, University of Cambridge, England. [Address delivered at the Johns Hopkins University, Baltimore, October 11, 1897.]


[President Gilman introducd Prof. Foster in the following words: "I have the pleasure of presenting to this assembly the distinguished physiologist, Dr. Michael Foster, Professor in the University of Cambridge, England, and one of the secretariesof the Royal Society of London. He comes at the invitation of the Medical Faculty of this University, and it is an auspicious opening of the year that brings him here ; auspicious not only by his presence, but by the beautiful weather that has favored us and by the large number of students now enrolled in the medical department.

I can say of him that though his face is not familiar, a very large number of the young men and ladies present feel that they have already taken him by the hand, as his manual of physiology has been in use among us from the beginning of the Johns Hopkins University. You will be glad to be reminded that when biological studies were introduced here it was through the agency of Dr. H. Newell Martin, who had been a pupil of Dr. Foster's, first in London and afterwards in Cambridge. During the past score of years by correspondence we have maintained the most friendly relations, and we rejoice in this favorable opportunity to hear what be may say upon University Education."]

The Johns Hopkins University, which has done me the honor to ask me to say a few words on this occasion, is, although already distinguished, a new and young university. I can remember well its beginning, and as Dr. Gilmau has hinted, I may claim to have taken some small part in its birth. When I moved in 1870 from London to Cambridge, T took with me a bright lad of whose ability and industry I had already taken notice. At Cambridge he became my right hand man, and I had some hopes that I should long have his help; but President Gilman appeared upon the scene, and his influence was so strong that I felt that my own interests were not to be considered, and that I ought to send that favorite across the waters to occupy the first chair of biology in this new university. Although the memories of him whom I need scarcely name, Henry Newell Martin, are tinged with melancholy, still I feel that this university must always look back with pride and affection on the work which he has done in this country, and in this affection and pride I claim a small share for myself.

Your university is a new one. I come from a very old one; one which was founded six hundred years ago, which has lived through all those centuries, and which, though it has some of the charms, has also soine of the evils of antiquity. The traditions of the past weigh heavy upon us. When we attempt to stretch our limbs to meet the new needs of new


times we find some old written law, some well established prejudice, some vested interest preventing our full development. You are a new university; and although I have purposely refrained from refreshing my mind as to the exact status of your regulations and as to how far you may have already entangled yourselves in the toils of enactments, still I will take it for granted that you differ from us in the freedom with which you can move forward towards the needs of the coming times ; and I think perhaps I could not do better at the present moment than to use the opportunity offered me to take my old university as a text and to draw from it and its history some few plain reflections which I hope may be practical and useful with regard to the conduct of universities. Although I understand that I have been especially invited by the medical faculty, I will take leave to treat ouly of general things, since the welfare of the medical faculty is bound up in that of the whole university.

The morphologists tell us we can learn much by studying the embryo, and something perhaps may be learned by looking back at this old University of Cambridge in the days of long ago — in the days when it too was a relatively young university. Things were very different then from what they are now. The dimly

.lighted streets or alleys in which the students lived were an emblem of the whole university. There was little outward show of glory then, there were no beautiful buildings, few books, and each student's duty was, in part, to listen to the lecture, to the reading of something which was written, but whicli he could not see with his own eyes. In spite of all these difficulties there were certain features of the university of that time which I trust I may say have been, with some

, little wavering here and there, maintained since, and which I cannot help thinking have contributed in very large measure to make it what I may venture to call it, a famous and great

_ university. ,;s One of the most striking features of the attitude of both 'students and teachers at that early time was that they recognized in the training of the university a preparation for practical life. There were at that time three main occupations in which learning was of practical use; and in correspondence to those three occupations there were established the three great faculties of the university, the faculty of theology, the faculty of law and the faculty of medicine. And, if one reads what those men of old wrote concerning what they thought ought


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to be done in the university, one is very much impressed by the conviction which they had that the teaching should be an earnest preparation for practical life. If it soon became necessary to establish a fourth faculty, the faculty of arts, that was simply as a faculty preparatory to the others, as one supplying the first steps for and leading up towards the knowledge which should be of use in practical life; and it is worth noting that although they called that faculty the faculty of arts, and although the acquisition of the Latin language was one of the chief studies of that faculty, necessarily so because all the instruction which could be given was given in that tongue, among what they called the arts were the beginnings of the kind of knowledge which we now call science.

Another feature of the university life of those early times was the very strong feeling that the work of the university consisted not in the mere acquisition of knowledge, but in the training of the mind. The amount of knowledge which they had for distribution was very limited ; but they used that small stock of knowledge to the very best of their ability, as the means of awakening the minds of the students and training them for thinking and arriving at conclusions. This is seen even in what they called at that time examinations, though the word then had a very different meaning from what it has now; there were then no written examinations, there was not that demand on paper so characteristic of modern times, and that great necessity of modern civilization, the waste-paper basket, was unknown. The examiners went quietly to work to ascertain in the most sure way whether a student had profited by what he had listened to. Instead of having two examiners for some hundreds of students, they appointed nine to each student; and these went in with him and out with him until they satisfied themselves that he knew something and had gathered something from what bad been told him. And then as a final test they put him on the " stool " and made him debate in public, the test being used in such a way as to bring out his stock of knowledge, and especially his power of using it and of showing that his mind had been trained at the same time that he had gathered in a certain number of facts.

There was another feature of the university which we sometimes find it difficult to realize: the spirit of inquiry was rife among them. At that time the ways of thinking were devious ; but still within the limited circle in which they moved, along the only lines then open to them, the thinkers used their minds in the spirit of free inquiry. When one i-eflects upon the circumstances in which they worked, one cannot help realizing that their long-drawn-out discussions were at bottom an expression of the love of inquiry, and that if they had had the advantages which we enjoy now, that which we call their subtlety would have broken out into discovery and invention.

Lastly, it was a feature of the university at that time that it was willing to take into its bosom any one who showed that he had any promise of benefiting by the instruction there given. It was an open home for all who wished for learning.

These are some of the features of the University of Cambridge in the olden times, and may we not, using them as a text, attempt to draw some conclusions as to what are the proper and essential functions of a university and what ought


to be some of its guiding principles ? As I gaid just now, the knowledge which they possessed was extremely limited, the facts with which they had to deal were very few. What can we say of knowledge at the present time? May we not say, if theirs was too little for them, ours threatens to be too great for us; that we are entering upon an age in which the facts which have to be learned and the various kinds of knowledge which have to be acquired are becoming too many for us ? It is or it may be perfectly true that one of the advantages of learning is that it enables the learner to learn more rapidly ; V)ut is not this true, notwithstanding that the increment of knowledge is increasing far more rapidly than the increment of the power to learn ? Is it not a serious matter for consideration that the things that the university has to teach are rapidly becoming far too numerous for the learner to learn? Is it not true that we cannot do now as they did in those old times, teach the student all that was known ? We are compelled to make a choice, we must teach to the student some things and omit to teach him others. That is a necessity which it seems to me is increasing as the years goon. Nevertheless that position is a cruel one ; for it may be truly said that every kind of knowledge has a vah^e of its own ; each kind of knowledge has for the learner a value which can be given by no other kind, and he who fails to gain any one kind of knowledge is thereby a loser. For building up the student into the full and complete man, the best course would be to take in all the knowledge which can be offered by a university; but as I said just now, a choice must he made, and the consideration of the principles which should guide the decision as to what should be chosen and what should be left demands the most serious attention. Here I think we may venture to follow the example of the old university. Admitting that each kind of knowledge is particularly fitting for a particular calling, that for every jiarticular calling in life there is a knowledge, or there are kinds of knowledge which are suited or fitted for that calling and without which that calling can not be pursued with success, in the necessary choice which must be made between this study and that is it not a wise course to take that which best serves the future calling of the student? I cannot but think that in this choice of which I am speaking, the arguments for what are sometimes called technical education are unanswerable; that one of the principles of most importance in determining the choice of the studies to be taken up by the student lies in the fitness of the study for giving him power in the calling which he proposes to adojjt. We must, however, remember that the knowledge which is thus to be imjiarted to him must be not merely a knowledge of facts, but bring with it the power of thiiiking. If technical education is understood in this way, not as a mere accumulation of facts, not as the mere heaping up of knowledge, but as the training of the mind in some particular kind of knowledge, the dangers, I venture to say, which some fear, will prove unreal, and it will be seen to be a true principle of university education.

There is another aspect in which we may look at university duties. May we not say that the tendency of modern civilization is to smooth down individual differences, and that the whole tendency of the environment of man is to make each


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man increasingly more like his brother? There was a time when one could tell by the dress where a man came from, but this has become les^ and less easy, and it is not in dress alone, but in his very nature that man all over the world becomes more like his fellows. I myself during the short time I have been in this country have felt it more and more difficult to tell what are the differences between an American and an Englishman, and I trust that these differences are equally difficult to you. This may be a favorable aspect, but there is an unfavorable side to this continual influence of things about us. Mr. Francis Galton has shown that there is a great tendency in things to make men more and more alike in stature, and there seems a corresponding tendency to make men all alike in the stature of theii- minds. We seem tending in many ways to a monotonous mediocrity of intellect. This influence is especially strong among young people. I see for myself in the University of Cambridge that when one young man does one thing they all do it ; they go astray like sheep, and they also go straight like sheep. Surely it ought to be a function of the university to counteract this tendency and so to bring the influences of learning upon the young as to develop individual differences. That I take it is one of the most important functions which a university can exercise, but one which is not always kept in view in university enactments. Here I can speak of my own university, and in doing so can lay the blame for the present condition of things on the traditions of the past. I find in my own university discouragement for the development of individual power. Every lad who comes to the University of Cambridge is compelled to pass through the same examination, to know the same things to the same extent, whatever may be the nature of his mind. He must know a little Latin, a little Greek, a little mathematics, a little history and one or two other subjects. Each one who comes, whatever his previous history, must pass through this one gate; the whole university has been pushed through this one common gate. Now I know that this may be defended; it may be said for instance that it is a bad thing not to know Latin. I quite agree with that. I think it a very bad thing not to know Latin, but I also think it a very bad thing for a lad to be thrown into life, it may be to go through life, without any clear idea whatever of the fundamental laws which govern the phenomena of living things. It may be said that it is a bad thing not to know Greek ; I agree with that. Not to know Greek is to my mind worse than not to know Latin, but I think also that it is a bad thing for a lad to go through life ignorant of the fundamental laws of chemical action. If you go along in that line of argument you end by compelling a lad to know everything before he enters the university. If I had my way and could wipe out the traditions of the past I should vary that entrance examination. I should hold on to the old tradition of the university that it was ready to receive everybody who was likely to profit by its instructions. I should make the examination look, not backward as it does now, but forward, and should only insist that the lad must give such proofs of intelligence and industry as to lead to the hojie that the years of university life would not be spent in vain. When the lad has really entered the university (at times he does not do so until he has spent two or even three years at


the place in preparation, and sometimes goes away from the place without having really been admitted), it seems to me there should be a still wider scope for his studies. He has even now, it is true, an opportunity to take a degree in one or other of several branches of learning, but in each case he must follow out a particular schedule which has been laid down and which compels him to walk along a particular path and no other. If he wishes, for example, to study mathematics with philosophy, he would find that he could not do so, for in the examinations mathematicians have nothing to do with philosophy, and philosophy nothing to do with mathematics ; and so in other things. I venture to think that this is not a satisfactory condition of things, and that throughout the who'e academic course there should be a freedom of the young mind to develop in the line in which it was intended to develop. When I urge this upon my friends they all say, " It is very good, but it is impossible, the examination machinery would become so complicated as to break down." But I would ask the question. Are examinations all in all ? were the examinations made for universities, or were universities made for examinations? I myself have no doubt about the answer. I trust that this new university, which can walk with freedom along new lines, will find some way of so arranging studies and examinations that the two will not conflict, and that anybody coming here will find that the particular gifts that have been given to him and which it was intended should be developed will meet their fullest expansion.

Lastly, there was another feature which the old university possessed and which I may also call an essential feature of a university, that is, the spirit of inquiry. No university can prosper as a university that not only does its best to favor special inquiries when these are started within it, but also in the whole course of its teaching develops, or strives to develop the spirit of inquiry. Now here again I fear that examinations — such at all events is my experience — are antagonistic to inquiry; and I would suggest that in arranging examinations one ought always to look ahead to see how far one can possibly order those examinations so as to favor the teaching which teaches in the real and true way, teaching by regarding each bit of learning as in itself an act of inquiry, and so as to favor in the highest degree actual inquiry when it is taken in hand. This of course is antagonistic to one function of examinations, namely, that of putting young men to compete against each other. You cannot so judge inquiries as to put the inquirers in any class list or in any order; the most you can do is to give an inquiry the stamp of approval of the university, a testimony that the inquiry has been carried out in a satisfactory way. It is true that in this way you lose that which is sometimes thought to be of great value, emulation between the scholars ; but if you take away that kind of emulation you substitute for it another one far more strong and effective, that emulation that comes of striving with nature. I take it that the good which is done to a lad in starting him upon an inquiry is infinitely greater than any which can be gained by competition with his fellow students. Here I am glad to say a good word for my own university ; for we have in a very quiet way, and unobserved, secured the adoption of an enactment which allows a lad to enter the


72




university aad obtain his degree and all which follows upon that without entering into a single examination. At the present moment it is possible for one, it is true under exceptional circumstances, to come to the University of Cambridge in England, and if he convinces a competent body of judges that he is a person likely to carry on inquiry in a successful manner he can enter the university as a student, and if he satisfies another body of men after a time that his inquiries have resulted in a real contribution to knowledge he can secure his degree. He can get that without ever having touched a written examination paper, and I am proud that we are able to offer that to the world; for it has happened again and again that a man who had real genius for a par


ticular line of inquiry stumbled over the preliminary studies of which I have spoken, knocked at the door of our university in vain and was sent way. Now such an one would be admitted, and I venture to say that in the long run the university will be the gainer.

These then are some few thoughts concerning universities and their methods. I say I have purposely learned nothing about your enactments, but from what I know of your short jiast I feel confident that this university will in the future be conspicuous for progress. May I hope that it will carry on education along some of the lines which I have indicated to-day, and perhaps some day we in the old country may mend our ways after your pattern.


THE RESULTS OF THE INTRA-TRACHEAL INOCULATION OF THE BACILLUS DIPHTHERm IN

RABBITS.

By Simon Flexner, M. D., Baltimore, and H. B. Anderson, M. D., Toronto. \Proni the Pathological Laboratory of the Johns Hopkins University and Jlospital.]


I.


The interest which was aroused by the discovery of Frosch,' Kolisko and Paltauf," Wright,' and others, that the bacillus diphtherife not uncommonly invades the internal organs in diphtheria, was further stimulated by the publication of the work of Kutscher, which dealt with the relation of the bacillus diphtherias to the pneumonic processes that are associated not infrequently with pharyngeal and laryngeal diphtheria. The studies of the foregoing writers, which will be examined more in detail hereafter, led to the supposition that, contrary to the previously expressed views concerning the aetiology of the pneumonic processes in diphtheria, it was probable that in many cases the diphtheria bacillus might itself be the causative agent. In the winter of 1894 we presented to the Johns Hopkins Hospital Medical Society a preliminary communication on the subject of the effects of the injection of pure cultures of the bacillus dipbtberiae into the tracheae of rabbits. We were then able to say that by this means a definite and wide-spread pneumonic process could be provoked, which led in many instances to the death of the animal. These experiments seemed therefore to be more conclusive than the previous observations upon human beings with reference to the probable action of the diphtheria germ in this respect, for the reason that in the former subsidiary or secondary micro-organisms were definitely excluded from any part in the production of the pathological lesions. Our studies carried us incidentally into a consideration of the fate of the introduced micro-organisms, as it soon appeared that even after considerable numbers of diphtheria bacilli in pure culture had been inserted through the trachea iuto the lung, their recovery from these situations was often attended with much diflBculty and sometimes was impossible.

Although the credit of the demonstration of the invasion of the internal organs by the bacillus diphtheria has usually been given to Frosch, it is an undoubted fact that Loeffler'


had previously encountered these organisms certainly in the lungs and perhaps in the liver, in human beings. In the light of our present knowledge it is interesting to note how LoefHer endeavored to explain away these observations on the supposition that the bacilli had entered these organs post mortem and not during life.

In briefly reviewing the literature we shall confine ourselves to a consideration of those instances in which the organisms have been isolated either alone or together with other bacteria from the lungs, more particularly in association with pneumonic processes.

In the communication in which Frosch' pointed out the common invasion of the internal organs by the specific bacillus in cases of diphtheria he states that the organisms were present in the lungs and elsewhere. AVithout giving any particular details, he adds that as compared with the remaining viscera they were found most often in pneumonic areas, the spleen and the lymphatic glands. Whether they existed there alone or in association with other micro-organisms he does not say. One is led to believe, however, that in a majority of instances at least other micro-organisms were present, inasmuch as he states in conclusion that in almost all of his cases he found a mixed infection with various kinds of bacteria, but generally with streptococci and staphylococci.

Kutscher" investigated the invasion of diphtheria bacilli into the lungs in human beings and their relation to the broncho-pneumonias of diphtheria. For this purpose he studied the lungs of ten children who came to autopsy, and in whom the diagnosis of diphtheria had been made during life. Cultures were made in a part only of the cases ; sections of the organs, however, were studied in all. The cases included examples of pharyngeal and laryngeal diphtheria with extension into the bronchi. The results arrived at by Kutscher indicated that in a small number of instances the


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bacillus diphtherias may be contained alone within the consolidated patches in the lungs, but that there is likely to be an association of bacteria, the chief accompanying forms being the pyogenic streptococci and staphylococci. Diphtheria bacilli were absent from the lung tissue not the seat of hepatization ; not so, however, the streptococci. In some instances the consolidation was entirely microscopic, and in these cases streptococci were found without lesions being pi'esent about them, while, on the other liand, the diphtheria bacilli were discovered only in the broncho-pneumonic foci.

As a result of these studies Kutscher' expressed himself to the effect that the lungs must be considered as the organs most often and most severely implicated in the secondary invasion of the diphtheria organisms. He regards the commonest mode of invasion to be by aspiration, which certainly must be the most usual way, and places next in order of frequency an infection through the lymphatic channels on the ground that bacilli were found in the perivascular lymphatics. Kutscher further pointed out that in not a single instance was he able to demonstrate the presence of these micro-organisms within the blood-vessels themselves. The question whether the bacilli in the internal organs may themselves be the cause of lesions he believes must be answered affirmatively with reference to the lungs. In support of this belief he urges that the bacilli have been found not only in advanced lesions, but often and alone in the earlier ones, and that they occur in bronchi which are little affected, as well as in those filled with a cellular exudate in which the epithelium has been largely destroyed. The probability of the bacilli being secondary invaders after the pulmonary lesions had been brought about in other ways is therefore excluded.

Although in a few cases diptheria bacilli had been demonstrated in the lung by Johnston," Strelitz," Booker" and one of us (Flexner"), the next series of examinations comprising a larger number of cases, and therefore of more conclusive significance, was furnished by Wright, who, in studying fourteen fatal cases of diphtheria, isolated this organism from the lungs in thirteen. For the most part there existed bronchopneumonic areas in which these bacilli were found, although they were associated, as a rule, with the usual pyogenic cocci. In ten of the fourteen autopsies there were distinct lesions of broncho-pneumonia, but the occurrence of the Klebs-Loeffler bacillus in the lung seemed to be independent of the coincidence of these lesions, for, as Wright points out, it was absent in at least one instance of broncho-pneumonia, and present in the tissues in the absence of these lesions. The diphtheria bacillus was associated with the streptococcus in nine cases, in seven of which pneumonia was present.

In a subsequent report by Wright, associated with Stokes, ° an analysis of thirty-one cases of diphtheria is given, in which cultures from the lungs revealed the presence of the KlebsLoeffler bacillus alone or in combination in thirty out of the thirty-one cases examined. Of these thirty-one cases bronchopneumonia was present in nineteen.

Their series of cases also shows that the diphtheria bacillus may be present in the lungs independently of the occurrence of broncho-pneumonia, for in twelve cases in which no pneu


monic condition was demonstrable, cultures from the lungs showed the presence of these micro-organisms.

Belfanti studied a series of 26 cases of broncho-pneumonia associated with diphtheria and found the Klebs-Loeffler bacillus in 21. Of these 21 cases it was present alone in four, and combined with other bacteria seventeen times.

The most recent contribution to this subject has been furnished by Kanthack and Stephens,'- who report that of twentysix fatal cases in which the lungs were examined for their presence, the Klebs-Loeffler bacilli were found in every one with ease and in large numbers. In comparing these results with those obtained from a similar examination of other organs of the body, these authors conclude, and on this point agree with Frosch and with Wright, that the Klebs-Loeffler bacillus escapes most readily into the lungs; indeed they urge that in these organs the bacilli are found not in small numbers, as had been previously considered, but are very numerous. Of the twenty-six cases examined, Kanthack and Stephens describe the lesions of broncho-pneumonia in fifteen, and state that they must take exception to the statement frequently made that the broncho-pneumonia in diphtheria is of pyococcal origin, maintaining that it would rather appear to be a veritable diphtheritic complication. It is worth mentioning that the broncho-pneumonias of diphtheria are according to them most frequently encountered in those cases in which the invasion of the larynx by the membrane had taken place. Of twenty-four laryngeal cases which they describe, bronchopneumonia existed in thirteen.

In interpreting the results of the observations upon the relation of the pyogenic organisms to broncho-pneumonic areas in the lungs with or without the coincidence of the Klebs-Loeffler bacillus, we must take exception to the statement made by Kanthack and Stevens'^ that " staphylococci, pneumococci and streptococci are normal inhabitants of the bronchi, bronchioles and alveoli; and therefore on cultivation must of necessity appear on the agar-agar surfaces." We think a sufficient answer to this statement is found in the frequency with which such cttltures from perfectly normal human lungs at autopsy give negative results. We are far more inclined to regard the pyogenic organisms as not without pathological significance, notwithstanding the fact, as we hope to show, th;it the diphtheria bacillus is quite capable alone of causing definite pneumonic processes.

IL

The results derived from our studies of the intra- tracheal inoculation of fluid cultures and suspensions of the KlebsLoeffler bacillus were unmistakable in their significance. We were able in quite a number of cases to provoke an inflammatory process within the lungs which varied in extent, involving sometimes a small area, even a fragment of the lobe, and at others the gi eater portion of one lung, or considerable parts of both. In the course of these studies attention was directed to some other points, more or less in dispute, and especially to the question of the fate of the introduced micro-organisms and the length of time during which they were demonstrable within the substance of the lungs.

The method pursued in conducting these investigations was


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[No. 85.


quite simple, and after a few preliminary failures uniformly successfnl. It consisted of exj)osing the trachea above the clavicles in half and full-grown rabbits, the precaution having first been taken of carefully removing the hair over the site of operation. The only real difficulty which was encountered was the avoidance of infection of the tissues about the trachea. lu the early experiments this was not always successfully overcome, but later, by introducing the needle through a small pledget of sterilized cotton, placed in contact with the exposed trachea, and withdrawing it through the pad, we were able as a rule to avoid infection of the soft tissues. The wound was sutured and covered with a celloidin dressing.

The amount and the character of the injected material varied with the different cases and are recorded in the individual protocols. The duration of life succeeding inoculation also varied considerably, and the extent of lung involvement seemed to depend more or less upon the j)eriod of incubation. For the study of the pneumonic process in its entirety inoculated animals were allowed to live as long as possible, while for the study of the fate of the introduced micro-organisms, as well as the time required for the development of the jjathological lesions, the animals were killed at intervals varying from one to twelve hours after inoculation.

Our attention was attracted in the early experiments to the frequency with which, in the hepatized lungs, the introduced bacilli were missed in cultures, in cover-slip preparations, and in the tissues, so that it became necessary to search elsewhere for them, or to discover the manner of their destruction in situ.

Exp. 1. Full-grown white rabbit received Feb. 10, 1895, .5 cc. of a bouillon culture of the bacillus diphtheria; reinforced by the addition of five drops of the condensation water of a serum culture two days old. It lived about 65 hours.

Autopsy. Practically no reaction about the local wound ; the lymph glands neither enlarged nor congested. The mucous membrane of the trachea near the larynx showed a few small points of congestion. The trachea and bronchi contained frothy serum. The lungs were voluminous and completely consolidated excepting the edges of the lower lobes, whicli contained air. The pleural surfaces showed points of ecchymosis and had a moist, somewhat glutinous appearance. The consolidated portions presented a peculiar semi-translucent gelatinous appearance, and on section an cedematous fluid in small quantities escaped. The remaining organs showed nothing remarkable.

Bacteriological examination. Trachea ; no diphtheria bacilli found. Pleurfe ; no bacilli found. Lungs; films were examined from various portions, and no distinct bacilli could be found. What may have been pale and perhaps degenerated organisms, two or three in number, were found on one cover-slip. Many pus cells containing amphophilic granules were present.

Cultures on Loeffler's blood serum from the consolidated portion of the lungs, the heart's blood and liver were perfectly negative.

Exp. 2. Full-grown Maltese rabbit received .5 cc. of a 4S-hour old bouillon culture on Feb. 7th. Death in 47 hours. Autopsy immediately after death. Heart still beating slightly, but irregularly. Trachea filled with frothy serum. The lungs, with the exception of the edges of the bases and apices, which contained air, completely consolid.ated. They were voluminous and completely filled the pleural cavities. Beneath the pleura were small h.Tmorrliagic points. Upon section the smooth gelatinous appearance described in the previous animal was observed. The trachea showed slight congestion at tho point of entrance of the needle.


Bacterioscopic examination. In the trachea in the neighborhood of the puncture a few diphtheria bacilli were found, both free and enclosed in epithelial cells. Examination of the pleura was negative. In the lungs what may have been a few extracellular degenerated forms.

Cultures from the lungs and heart's blood negative.

Exp. 3. Half-grown rabbit received .5 cc. of a slightly turbid suspension in condensation water of a blood-serum culture. Died in 27 hours.

Autopsy. The trachea much congested throughout and covered with punctiform luemorrhages, but without visible membrane. The cesophagus also much congested. The local wound somewhat swollen and cedematous. The superior lobes of the right lung were almost completely consolidated, the remaini^er contained air.

Bacterioscopic examination. From the exudate about the trachea a small number of diphtheria bacilli. From the lungs and pleura, negative; from the cesophagus, typical bacilli.

Cultures. Heart's blood and lungs on Loeffler's blood serum negative.

Exp. 4. A white half-grown rabbit received .5 cc. of a bouillon culture reinforced by the addition of five drops of the condensation water of a strum culture two days old. The animal succumbed on the seventh day. There was absolutely no pneumonia ; the lungs appearing somewhat congested, but contained air in all parts.

The cultures were negative. Cause of death not apparent.

Exp. 5. Full-grown rabbit received at 3.15 P. M., June 22nd, .9 cc. of a turbid suspension. Died during the night.

Autopsy. Trachea, no membrane ; somewhat congested.

The lungs much congested ; no definite consolidation.

Bacterioscopic examination. From trachea numerous bacilli, both free and within cells.

Lyings. Upon cover-slips many polymorphonuclear cells, but no bacilli.

The cultures showed Klebs-Loeffler bacilli in the congested portion of the lungs, the bone-marrow (femur) and the heart's blood.

This series of cases shows in the first place that the diphtheria bacillits by itself is capable of provoking a definite and often wide-spread pneumonic process when introduced directly into the lungs of rabbits ; but that in certain cases, notwithstanding the entrance of numerous bacilli into- the lungs, a pneumonic process fails to be provoked. Further, it shows that when the number of bacilli is great the animal may succumb, presumably to the intoxication induced by these organisms, before an outspoken pneumonia has developed, thus illustrating anew the effects of the absorption of the poisonous products from the lung substance. Again, Experiment 5 shows that in addition to the invasion of the body presumably by the toxic products of the diphtheria bacillus, we may have a more or less wide distribution of the organisms themselves, and that they may be found in very distant situations. Finally, this series of experiments proves that after the provocation of the pneumonic process the bacilli may themselves either disappear completely, or be so reduced in numbers as to be iucai)able of demonstration in cover-slips, or that their vitality nuiy be either destroyed or interfered with to such an extent that any attempt at cultivation, even on favorable media, will be followed by negative results.

Exp. 6. A full-grown rabbit received 1.3 cc. of a turbid suspension in bouillon of the bacillus dii)litheria5. The animal was killed by a sharp blow on the back of tlie neck one hour after the inoculation.


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Aulopsi/. The lungs were voluiiiiiious and slightly niottleil. IlMinorrUages were nut discovered beneath the serous membrane.

Bacterioseopie examination. Cover-slips from the lower lobes of the lungs showed, besides a few polymorphonuclear leucocytes containing am])hophilic granules, and some few epithelial cells, bacilli singly as well as in small and in large clumps, chiefly existing free among the cells. Occasionally enclosed within an epithelial cell there was to be found a single bacillus, and more rarely several bacilli. The cells which contained the bacilli stained in the same normal manner as the remaining cells, and the bacilli themselves showed no variation in staining properties as compared with the extracellular forms.

Cultures. From both apices and bases of the lungs a variable number of colonies of the introduced bacilli ; from the pleural membrane a single colony of the same organism. The heart's blood, spleen and bone-marrow gave negative results.

Exp. 7. A black, nearly grown rabbit received 1.3 cc. of a turbid suspension similar to the last ; the animal was chloroformed after the lapse of one hour.

Autopsy. The lower lobes of both lungs were swollen, slightly congested, and the serous membrane covering the lungs showed here and there punctiform ecchymotic spots.

Bacterioseopie examination. The cover-slip preparations from the various parts of the lungs showed essentially the same appearances as those described for the previous experiment, but it seemed as though the cells containing bacilli were perhaps a little more numerous in this case. The polymorphonuclear amphopbiles appearel to be about as numerous as in the preceding experiment, and as in that case the introduced bacilli were never found within these cells. An examination of the bronchial epithelium showed a complete absence of bacilli within the columnar epithelial cells, even when they were quite numerous between them.

Cultures. From the lungs, considerable growth of the introduced bacilli. From the heart's blood, bone-marrow and spleen the cultures remained sterile.

Exp. 8. A nearly full-grown rabbit received on Feb. 2Gth 1 cc. of a turbid suspension of the bacillus dipbtherise. The animal was killed at the end of 3i hours.

Autopsy. Lungs voluminous. In the superior and inferior lobes of both lungs considerable hiemorrhages existed beneath the pleura, which on section could be seen to extend into the lung substance. Admixed with the blood there was much frothy serum ; elsewhere the lung tissue was pale and moderately dry.

Bacterioseopie examination. Fdms prepared from tfie hremorrbagic areas showed large numbers of epithelial cells enclosing diphtheria bacilli. The bacilli were often arranged in the same parallel rows which one observes in the cover-slip preparations from the cultures themselves. The bacilli stained in all respects normally ; rarely there appeal e 1 within the cells specks of chromatin which had the samii staining property as the bacilli and might have been fragments of the latter, but they were hardly more numeious than one occasionally finds in cultures of the same organism. The cells containing these bacilli themselves appeared entirely normal. The bacilli were very rarely found to have invaded the nuclei of the cells. Leucocytes with typically polymorphous nuclei were present in the cover slips, but they were never seen to contain the inoculated bacteria. The free bacilli were seen only exception.ally among the cells ; when found here they were usually single and rarely in clumps.

Cultures. The lungs and spleen gave growths of the bacillus diphtheria!. From the lieart's blood the cultures were sterile.

Exp. 9. Nearly full-grown rabbit received .5 cc. of a faintly turbid suspension of the bacillus diphtheria;. Killed after six hours.

Autopsy. Lungs partly collapsed ; the pleura covered with small hiemorrhages. The lower lobes of the lungs were congested and edematous ; no definite consolidation. Bacterioseopie examination. The films from the superior and mid


dle lubes were negative. From the congested and oedematous li'wer lobes bacilli in small numbers were obtained, occurring singly and in small groups, extracellular and enclosed within epithelial cells. The polymorphonuclear cells, which showed an increase in number as compared with the two previous cases, did not contain the introduced micro-organisms.

Cultures from the lungs and spleen were positive ; from the heart's blood no growth was obtained.

Exp. 10. Full grown rabbit received .75 cc. of suspension of a culture on blood serum two days old. Animal killed at the end of six hours.

Autopsy. The trachea at the seat of inoculation showed some congestion but no false membrane. The bases of the lungs were congested, the pleura covered with minute hiemorrhages.

Bacterioseopie examination, (a) Smears from the mucous membrane of the trachea at the site of inoculation showed diphtheria bacilli in considerable numbers, all extracellular, and among these jiolymorphonuclear cells, (b) From the base of the lungs mononuclear, epithelial and polymorphonuclear cells, the former containing bacilli. Similar micro-organisms, although in smaller number, also existed between the cells.

Cultures. From the lung a large number of colonies. From the s|>leen, bone-marrow, heart's blood and liver, smaller numbers of colonies of the introduced micro-organisms.

Exp. 11. A rabbit received .75 cc. of a turbid suspension of a growth of the bacilli upon blood serum. Killed at the end of twelve hours.

Autopsy. Trachea about the site of inoculation showed much congestion, which extended above and below the point at which the needle had been introduceil, but no false membrane existed. The caudal lobes of the lungs were much congested, and beneath the pleura minute haemorrhages appeared. The spleen appeared enlarged.

Bacterioseopie examination. Smears from the trachea showed numerous polymorphonuclear cells, but no bacilli. From the lungs (bases) bacilli extracellular and polymorphonuclear cells.

Cultures. From the heart's blood, spleen and bone-marrow the introduced bacilli were cultivated. From the tracheal glands and lungs the tubes were negative.

Exp. 12. Was a repetition of the previous experiment and gave similar results, with the exception that the bacilli were cultivated from the congested and oedematous lower lobes of the lungs. It is therefore probable that in the previous case the absence of the bacilli from similar situations is to be regarded as an accidental occurrence.

Exp. 13. Full-grown rabbit received .80 cc. of a suspension of the bacillus diphtberiie. Killed in 18 hours.

Autopsy. The trachea appeared very much congested, but there was an entire absence of false membrane. The caudal lobe of the lung on the right side was dark red in color, but not frankly consolidated, whereas on the left side a definite consolidation in the corresponding lobe had taken place. The spleen was decidedly enlarged and congested.

Bacterioseopie examination. Cover-slips from the trachea show-ed many polymorphonuclear cells, fewer epithelial cells, no bacilli. From the lungs many polymorphonuclear cells and epithelial cells with single nuclei, but no bacilli.

Cultures from the lungs and heart's blood, positive ; from the spleen, liver and bone marrow, negative.

Exp. 14. A large rabbit received 1 cc. of a bouillon culture. Killed after 24 hours by breaking up the medulla.

Autopsy. The middle lobe of the right lung contained a consolidated patch the size of a silver dollar, over which the pleura was congested and contained small hemorrhages. •

Bacterioseopie examination. Films from the consolidated portion of the lung showed many polymorphonuclear leucocytes, some epithelial cells, but no bacilli.


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Cultures from the lung as well as heart's blood, spleen and bonemarrow were negative.

Exp. 15. Full-grown rabbit received .75 cc. of a turbid suspension derived from a blood-serum culture. Killed in 24 hours.

Autopsy. The caudal lobe of the right lung and the lowerpart of the cephalic lobe on the same side were congested and consolidated as well. In addition the caudal lobe of the left lung contained several smaller areas of consolidation. The spleen was much enlarged. The trachea over the site of inoculation and at a distance from it was much congested. There was an entire absence of false membrane.

Bacterioacopic examination. Smears from the consolidated portions of the lung, trachea, spleen, bone-marrow and heart's blood were all negative.

Cultures from the same sources remained entirely sterile.

The object of this group of experiments was two-fold, namely, to determine, if possible, the manner in which the introduced bacilli so completely disappeared, and in the next place to consider the length of time necessary for the development of the pneumonic processes and the nature of the inflammation provoked.

Animals which had received large numbers of the KlebsLoeffler bacilli showed at the end of one hour changes in the lungs, which, however, were not very marked. They consisted simply of an cedema of the tissues, together with more or less mottled congestion. Of greater significance, however, was the fact that an emigration of leucocytes had already taken place, and that some, although few, of the introduced bacilli were enclosed within cells, these being exclusively the epithelial cells of the alveoli. At the end of 3 J hours the pathological process was much more advanced, the first expression apparently resulting from changes in the blood-vessels, to judge from the definite hasmorrhages, often of considerable extent and very numerous, which were discoverable both in the pleura and in the substance of the lung. By this time, although large numbers of the bacilli had been introduced, comparatively few were now free, the overwhelming majority of them being enclosed either within the protoplasm or the nuclei of cells. In this short time the bacilli might be found to have extended their invasion beyond the thoracic organs; and whereas at the end of one hour they were still limited to the substance of the lungs, at the end of 3 J hours they were found in the spleen as well. It should be mentioned here that owing to the small size of the bronchial lymphatic glands, cultures from these were not very satisfactory, and were therefore not regularly made. At the end of G hours the effects of the inoculation were still more noticeable, and the distribution of the microorganisms more extensive, as they were demonstrated by the culture method at the end of this time in the heart's blood, spleen, bone-marrow and liver. The bacilli were still capable of cultivation from these distant organs as well as from the lungs at the end of twelve and eighteen hours, while after the lapse of twenty-four hours, at which time a frank consolidation of the lung substance had taken place, they could not be cultivated either from the lungs or from the remaining organs mentioned. We should like to emphasize that, although the inclusion of the bacteria by cells takes place so rapidly and extensively, in no instance did we succeed in discovering the bacilli within the substance of the polymorphonuclear leucocytes.


The foregoing experiments serve to confirm the observation upon human beings relating to the existence of a jmrely diphtheritic broncho-pneumonia, and lend support to the view that the laryngeal cases are specially prone to the development of such pathological conditions, as they present the most favorable opportunity for the direct aspiration of the infectious agent. That an actual increase of the introduced microorganisms takes place is proven, we think, by the observations made upon human beings which have been given in detail in an earlier part of this paper; in view of which fact the disappearance of the introduced bacteria in cases of experimental inoculation is all the more perplexing. The interpretation of this phenomenon is indeed not at once apparent. On the other hand it is worth considering whether in those cases of human diphtheria in which the bacilli have not been found in the local pathological processes, it may not be also unjustifiable to conclude that the bacilli never were present there, and were not concerned in their causation.

It is certainly interesting to observe that there may take place from the lungs a rapid distribution of the introduced bacilli throughout the body, so that at the end of from four to six hours they may be found widely distributed throughout the organs. It has appeared to us as if the opportunities for such distribution are greater in cases of intra-tracheal inoculation than in the ordinary modes of subcutaneous inoculation, where, as is well known, the bacilli are not found extensively distributed through the viscera. However, there is at least one difference between the observations in the two sets of cases, for in the course of the ordinary subcutaneous inoculation a longer time as a rule elapses between the inoculation and the death of the animal, which may account for the absence of the bacilli in the internal organs. As an illustration of this point we may mention that in animals which were either killed after the lapse of twenty-four hours or died spontaneously later, we failed to obtain the introduced bacilli from these viscera.

The experiments which we have conducted justify us in considering for a moment the question of the action of the lungs as an infection atrium into the body of pathogenic microorganisms, and they would lead us to agree with Hildebrandt," who showed, contrary to the previous belief of Fliigge," that the alveolar epithelium is not a perfect barrier to the invasion of pathogenic bacteria from the interior of the lungs. At the time that the bacilli are already well distributed through the body the alveolar epithelium still appears entirely normal, although containing many bacilli within its substance. The supposition that bacilli are capable of passing from the bodies of the epithelial cells in some way into the general blood current or into the lymphatics, without leaving behind them obvious evidences of injury to these structures, would therefore appear to be justifiable. As to the mechanism of this procedure one can only deal in conjectures, when it is remembered that in this case we are dealing with non-motile organisms which must be transported from place to place by a force not resident within themselves.* The capacity of the alveolar epi


Ultimately, of course, this is the same problem as that dealing with the mode of passage of inert particles, such as soot, India ink


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theliiiui to luke up liviug foreigu matter it: the manner similar to what is observed in dust inhalation had been previously observed by Muskatbliith"' in his experiments upon the effects of the intra-tracheal inoculation of anthrax spores. He observed that in animals which had been killed on an average sixteen hours after inoculation, the greater majority of the bacilli were contained within epithelial cells corresponding with the so-called "staubzellen." Even when the englobing cells were free in the alveoli they gave every indication of having been derived from the pre-existing epithelium of these parts, and indeed were often found to be still in connection with the latter. As in our observations, he found that the leucocytes, the phagocytes par excellenre, had no part in the inclusion of the bacteria. He was neither able to detect evidence of injury to the cells containing the bacteria, nor that the bacteria within them were undergoing disintegration.

It must not be forgotten that after the introduction into the lungs of such numbers of bacteria as were inoculated into these animals a portion at least of them may have been thrown of through the bronchial secretions. In this way not an inconsiderable number may have been finally disposed of, and this possibility is rather strengthened by the observation of Case 3, in which an inflammation of the oesophagus was noted and the Klebs-Loeffler bacilli were found in considerable numbers in this situation. Muskatbliith regarded the reaction on the part of the lungs, with the pouring out of inflammatory products, as favoring the destruction of the anthrax organisms in situ, a conception which could, with more or less justice, be applied to the cases in which at autopsy in the pneumonic areas we failed to obtain the introduced micro-organisms. It is, however, probable in the light of our present knowledge of the mechanisms employed by the animal body to dispose of pathogenic and other micro-organisms, that no inconsiderable action must be attributed to the spleen, liver and bone-marrow.

It appears to be worth while to direct attention to the fact that in not one of our animals was a pseudo-membranous tracheitis observed, although evidences of inflammation were more or less common. This is probably to be explained by the assumption that the injury to the mucous membrane was too slight to afford a favorable opportunity for the development of the organisms in that situation, rather than that the animals did not live, or were not permitted to live, long enough for the membrane to develop.

III.

In order to study the development of the pathological lesions in the lungs, sections of these organs were studied in


and red blood corpuscles, through the alveoli. Arnold in particular has investigated this question and found that these substances are transported to and deposited within the neighboring lymphatic glands. Baumgarten" regards the transportation of bacteria and spores of fungi to be likewise of a purely mechanical nature. Moreover, he found that pathogenic bacteria were capable of being mechanically taken up in the same manner, in the absence of lesions of the alveolar lining; for the intra-tracheal injection of tubercle bacilli, killed by boiling, was followed by their passage in a few hours through the alveolar walls into the intrapulmonary lymph follicles.


the following manner: Beginning with the lungs of the animals killed one hour after inoculation, the succeeding ones were examined in a consecutive series. Sections were prepared from different parts of the organs; in those in which consolidation was apparent the hepatized portions were always included. The staining agents employed consisted of htemotoxylin and eosin, safranin in aqueous solution, and Weigert's fibrin stain. The last sufficed for staining the bacteria, as well as fibrin, when present or when capable of retaining the dye, which was by no means always the case.

The histological lesions in the animals killed after one hour were very inconsiderable and consisted of dilatation of the alveolar capillaries, extravasation of a few red blood corpuscles, the appearance of polymorphonuclear leucocytes in occasional alveoli and in the bronchial walls, more rarely in the lumiua of the bronchi in small numbers, perhaps an increase in the flat epithelial, nucleated cells within the alveoli, and more or less oedema. At the end of three and a half hours, on the other hand, the jiathological condition was well advanced. Small vessels, apparently arteries, contained fibrinous and leucocytic thrombi ; the congestion of the alveolar capillaries and larger interlobular vessels was a striking feature; the blood within the vessels contained an increased number of white elements, and both red and white blood corpuscles had begun to leave the vessels in relatively large numbers. The alveoli contain many cells of an epithelial habitus, and the fact of desquamation of the alveolar epithelium is made directly apparent. There exists at this time a definite purulent bronchitis. Branches of the bronchial tree which are still lined with columnar ciliated epithelium contain many polymorphonuclear leucocytes, and similar cells may be discovered working their way through the walls of the bronchi to reach the lumiua. The lining epithelium of these structures was never found to have suffered severely; no defects existed in this layer. A few cell fragments were seen amid the increasing cellular accumulations.

The animals which were permitted to live six hours showed much more advanced lesions. Up to this time the pathological changes have been limite'd to the interior of the bronchi and alveoli ; but now the stroma of the lungs begins to show changes. As a whole it is thickened, partly owing to oedema and partly to an increase in the cellular constituents. Many of the new cells are polymorphonuclear leucocytes, but among these are many cells with round, solidly staining nuclei which may have been derived from such leucocytes or have had a different origin. Fragments of cells begin to be more common in this situation and karyokinesis begins to be a]iparent. The capillaries, chiefly those in the alveolar walls, show large, somewhat diffusely staining, nucleated protoplasmic masses resembling giant cells. That these masses are the results of the fusion of intravascular white elements seems highly probable. The endothelium of the capillaries and small veins is swollen, but no actual injury was observed. The number of cells within the alveoli is much increased; they still consist of polymorphonuclear and epithelial elements in about equal proportions. Definite mitotic figures begin to be fairly common within the alveolar epithelium, and an occasionally nonnucleated (necrotic?) cell of this kind makes its appearance.


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The bronchi contain much exudate, consisting chiefly of leucocytes with iiTegular nuclei, but mononuclear epithelial cells are also present, and a large amount of detritus derived by fragmentation from cell nuclei. Evidence of cell destruction to a slight extent is to be observed in the walls of the bronchi, and it not infrequently extends into and involves the lymph nodes imbedded in their walls. The lining epithelium shows little or uo injury. As regards the origin of the cells composing the exudate within the bronchi it may be said that the bronchial mucous membrane furnishes but few of the elements. They come almost exclusively from below, from the terminal bronchioles in which the lining epithelium is almost or quite fiat, and from the adjacent atria and air-sacs (Miller)." Specimens twelve hours old show still more clearly that the contents of the larger bronchi are excreted from below, inasmuch as the terminal structures give every evidence of a rapid filling up with cells, while the high epithelium of the former is quite perfect and the bronchial walls but little infiltrated with wandering cells. It is not alone the lumina of the bronchioles, the atria and the air-sacs which give evidences of increased cellular invasion; this is also appai-ent in the stroma as well. The much thickened stroma is overloaded with cells, having as a rule irregular and fragmented nuclei, and showing in addition, here and there, karyokinetic figures, some of which certainly would appear to be within the capillaries. Moreover, the air-cells springing from all these structures, terminal bronchioles, atria and air-sacs, are now more or less completely filled with cells, partly emigrated, partly desquamated from the walls. Fibrin is present in the form of fine fibrils, too fine ajij^arently to retain the Weigert stain, but yet evident upon close inspection. The consolidation of the lungs at this early stage is partial only, and more microscopic than macroscopic in form. Edematous foci and small areas of extravasated blood are intermingled. The pleura is still intact. The succeeding stages, that is, after 2-i, 47 and 65 hours, show appearances similar to those described, with such modifications only as involvement of larger areas and more perfect solidification might be expected to introduce. Adjacent to hepatized foci others of compensatory emphysema or insuiHation exist, and the cellular infiltration of the stroma, always a prominent feature after twelve hours, may involve the emphysematous parts. Ha3morrhages are never entirely absent and may become considerable in the cases of longer duration ; fibrin, never a very prominent feature, increases more or less;* multiplication of cells resembling the offspring of epithelial cells may be so rapid as in some places to be the sole elements within certain alveoli ; the pleura becomes the seat of small leucocytic accumulations upon its surface which are derived from the lung substance, the cells of which may be seen wandering through the endothelial layer, which itself remains intact. Fibrin was never


The lungs of the animal which lived 65 hours (Experiment 1) showed the greatest quantity of fibrin observed. The tissue which had been hardened in Flemming's osmic acid solution and stained in safranin was best adapted for the study of this material. The fl!)rin was found in fine threads and convoluted masses within the alveoli and the intralobular lymphatics. It was perhaps most abundant where the cellular accumulations were least marked.


discovered upon its surface. The extent of destruction of nuclei within the bronchial as well as in the alveolar exudates grows until in many places fragmented nuclei alone compose the consolidating material. In this respect the exudate differs from most of those with which we are familiar in the lungs in acute disease. Even where a whole lobe, or indeed a whole lung, apparently is hepatized, the consolidation is not complete ; the effect is brought about by the imperfect approximation of many foci of lobular consolidation.

The exjjerimental pneumonias following the intra-tracheal inoculation of pure cultures of the bacillus diphtheria; in rabbits are lobular or pseudo-lobar in character ; they are cellular pneumonias for the most part, fibrin playing a relatively inconsiderable role in their production ; they are rapidly developed and originate in the bronchioles, atria and air-sacs; the bronchi are but little affected in the early stages, and even later are hardly more involved than in the acute lobar pneumonias of human beings. The bacillus diphtheriae and its toxic products when introduced directly into the lungs exert their action primarily upon the blood-vessels; very soon, however, the alveoli themselves are deleteriously affected, and within the brief period of six hours the entire framework of the lungs feels the injurious influence. The expression of these effects is seen partly in the exudative and partly in the proliferative changes which ensue. Among the latter the appearance of cell division by mitosis after the lapse of only twelve hours seems worthy of special mention.

The relation of the bacilli to the lung structures is a simple one. Sections stained in Weigert's fibrin stain show, in those cases in which the duration of life of the animal did not exceed twelve hours, many of the characteristic bacilli. They were almost never free, but enclosed in cells, which were either distinctly mononuclear in character or large, flat and scale-like, without demonstrable nuclei, and certainly not of the nature of vascular leucocytes^ That they have come from the alveoli is certain, for similar cells crowded with bacilli may at times be found still attached to the walls. The study of the relation subsisting between the micro-organisms and the lungs shows conclusively that the invasion takes place from the bronchioles, and very soon the bacilli are discovered within cells in the stroma. Whether or not they were contained within definite vessels could not be determined with certainty.*

Within the bronchi the bacteria appear amid the cellular exudate sometimes enclosed within the scale-like cells mentioned, and again, but not certainly, within polymorphonuclear leucocytes. If actually englobed by the latter the process is not a very active one. That the polymorphonuclear leucocytes at times take up the bacilli in cases of human diphtheritic pseudo-membranous bronchitis we have already shown in our studies of the broncho-pneumonia of this disease."

After the lapse of 18 hours the bacilli are found only with difficulty in sections, and in instances of still longer duration


In this connection Miller's observation that lymph-vessels are not found in the structures of the lungs beyond the terminal bronchus is significant. The atria and air-sacs have no lymphatics in their walls."


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not ;it all. We did not discover the bacilli in aniuuils which had lived 24, 47 and 65 hours respectively.

BiP.LIOGKAPHY.

1. Frosch : Die Verlireitung des Diphthcriebacilliis im Korper des Menschen. Zeitschrift fiir Hygiene u. Infectionskrankheiten, XIII, 1893, 49.

2. Kolisko and Paltauf : Znm Wesen des Croups nnd der Diphtheric. Wiener klin. Wocheuschrift, No. 8, 1889.

3. Wright: Studies in the Pathology of Diphtheria. Boston Medical and Surgical Journal, October 4 and 11, 1894.

4. Loeffler : Untersuchungen iiber die Bedeutung der MikroOrgauismen f iir die Entsteliung der Diphtheric beim Menschen, bei der Taube und beim Kalbe. Mittheilungen aus dem Kaiserlichen Gesundheitsamte, II, 1884.

5. Kutscher: Der Nachweis der Diphtheriebacillen in den Lungen mehrerer an Diphtheric verstorbener Kinder durch gefilrbte Schnittpriiparate. Zeitschrift fiir Hygiene u. Infectionskrankheiten, XVIII, 1894, 167.

6. Wright and Stokes: A Keport on the Bacteriological Investigations of Autopsies. Boston Medical and Surgical Journal, March 31 and 38 and April 4, 1895.

7. Belfanti : Snlle Broncopolniito Difteriche — studio batteriologico od anatomo-patologico. Lo Spieri men tale, XLIX, Sezione Biologica, 1895, 278.

8. .Johnston : Notes on the Bacteriological Study of Diphtheria. Montreal Medical Journal, Septembei', 1891.


9. Strelitz : Zur Kenntniss der im ^'erlaufe der Diphtlurien auftretendeu Pneumonien. Arcliiv f. Kinderheilknnde, XIII, 1891.

10. Booker: As to the Aetiology of Primary Pseudo-membranous Inflammation of the Larynx and Trachea, with iiemarks on the Distribution of Diphtheria Bacilli in Organs of the Body distant from the seat of local Infection. Archives of Pediatrics, August, 1893.

11. Flexner: Diphtheria with Broncho-Pneumonia. Bulletin of the Johns Hopkins Hospital, IV, 1893, 33.

13. Kanthack and Stephens : The Escape of Diphtheria Bacilli into the Blood and Tissues. The Journal of Pathology and Bacteriology, IV, 1896, 45.

13. Hildebrandt: Baumgarten's Lehrbuch der pathologischen Mykologie, II, 1890, 455.

14. Fliigge : Die Microorganismen, etc. Leipzig, 1886, p. 605.

15. Muskatbliith: Neue Versnche iiber Infection von den Lungen aus. Centralblatt fiir Bacteriologie und Parasitenkunde, I, 1887, 331.

16. Miller: The Structure of the Lung. Journal of Jlorphology, VIII, No. 1.

17. Baumgarten: Lehrbuch der iiathologischeu Jlykologie, I, 406, Anmerkung 114, 1890.

18. Miller: The Lymphatics of the Lung. Preliminary paper. Auatomische Anzeiger, XII, 1896.

Winter, 1896.


THE BACTERIOLOGY OF PERTUSSIS.=^=

By Henry Koplik, M. D., New York.


Pertussis is a disease which has long been suspected or known to be communicable from individual to individual, and it is not surj^rising to And that various authors have approached the subject of its etiology in divers ways. The sputum seems to have been the principal subject of study, and bacteria and protozoa in the sputum have been selected, each in turn, as etiological factors. I need only mention the names of Deichler, Kurloff, on the one hand, Letzerich, Burger, Affauassjew, Bitter, Cohn and Neumann on the other, to recall to the mind a whole series of studies on the sputum, the one dealing witli protozoan-like bodies in the siJutum, the other with bacterial forms. In my own work, which has spread itself at intervals over several years, and lately culminated in the study of a series of cases of pertussis, I have directed my attention to the bacterial forms esj)ecially found iu the sputum. I will not go into details here of my studies in other directions iu this disease, such as bacterial studies of the blood, for they have led to no results. If we look over the literatute mentioned above we may safely divide the communications on bacterial forms into two distinct sets : those which, like the work of Letzerich and Burger, were carried


Read before the Johns Hopkins Hospital Medical Society, February 21 , 1S98.


out without the aid of modern methods, and in which the instruments used were what we would call primitive ; and those which can be judged to day, inasmuch as the methods employed were modern, such as those of Afanassjew, Szemetzchenko, Cohn and Neumann, and Ritter. Of those mentioned I will consider at length only the work of Burger and Afanassjew. Burger,* by means of a Seitz dry lens, 340 diameters, describes a bacillus or'bacterium which he could easily see and which he calls biscuit form. He saw these in rows and chains and small rods twice as long as they were broad. He mentions distinctly that he found these bacteria in the flocculi of the sputum. It seems at this distance that it would be asking too much to decide just what Burger saw iu the sputum of his cases, more especially as it is now known that both diplococci and bacilli of various varieties and size exist in this sputum. We miss unity in Burger's description. He did not isolate any one form, and from his description may have had several forms in his Held when he studietl the sputum, thinking they were all a single form.

Afanassjew's work appeared in the St. Petersburg Med. Wochen., 1887. Czaplewski and Hensel, who do me the great honor to agree with me in my conclusions, admit that


Berlin, klin. Wochen., 1883.


80




they have not had access to the origiaal work of Afanassjew. In view of this fact I will quote from Afanassjew's original article.

Afanassjew describes the sputum of pertussis as a transparent mucus in which are seen grayish white spots of the size of a pin's head. In the mucus of the sputum are seen bacteria and short, small bacilli, single or in pairs, at times in chains of no great length, arranged in the direction of the mucus of the sputum ; at times in small groups. The length of these bacteria is 0.6 to 2.2 micro-millimeters, and are easily overlooked with low powers, and can only be distinctly seen with higher powers. "For this reason," says Afanassjew, " I doubt whether Burger has seen the bacterium described by me in the sputum, inasmuch as he says that he saw them distinctly with 340 diameters. I have made use only of powers magnifying 700 to 1000, with Zeiss ocular 3 and 4, and immersion y^j with the tube drawn out." Afanassjew describes his bacteria as follows : " In gelatin, after two or three days, we find round or oval colonies, light brown with even borders, also oval colonies with a darker centre. The youngest colonies were almost colorless, but slightly granular, and did not fluidify the gelatin."

He also describes colonies of a thicker shorter bacillus, which in passing I may say may have been a contamination of his cultures. The bacillus described by Afanassjew grows at the temperature of the room, slowly, or more rapidly, at 38° C. or 37° C.

"Agar stick culture gives on the second day on the surface around the puncture a cloudy gray flat growth, transparent, glistening like a drop of fluid. In the following days the surface culture becomes more and more opaque and whitish gray."

"Gelatin stick gives a slower growth, thinner, on the surface flatter, grayish white with irregular edges; later on the edges become whiter and form a nail-head which is dry and rarely reaches to the periphery of the tube. The stick itself is not characteristic."

"Blood serum gives a grayish or whitish growth similar to the agar."

"Potato gives rapid ahtmdant yellowish, and after brownish growth.^'

"In bouillon or hanging droj) we find the bacteria are alive, move very rapidly, inasmuch as they perform bobbing circular movements which soon cease."

" In the bouillon the bacteria grovv in small threads."

I think in this article we may fairly leave out of consideration the work of Cohn and Neumann, and also of Eitter, which are chiefly concerned with the consideration of diplococci not clearly identified, and pass on to the recent work of Czaplewski and Hensel. The work of these authors was made known first through a preliminary communication in the Deutsche Med. Wochen., 1897, No. 37, and in the Centralbl. fiir Bacteriol., Dec. 32, 1897. They had worked upon over 44 cases of pertussis (an epidemic), in 18 of which they isolated what they call a polbacterium or bacillus, reminding one very much as to size of the influenza bacillus, if not smaller. The bacterium is, according to their view, not motile in itself. There was a slight motility in fresh bouillon


cultures, which they were inclined to interpret as a Brown's molecular movement, but no independent movement of their own over the whole field of view. Gram stain did not decolorize fresh cultures, though it did the sputum.

The bacterium grew on Loeflier serum, agar, gelatin (nonfluidifying) bouillon, but not as yet on potato.

Loeflier serum gave an uncharacteristic grayish white growth ; agar a delicate gray growth of transparent confluent colonies. On agar involution forms are described.

On gelatin it does not fluidify the medium, stick is not characteristic, and is made up of delicate whitish yellow granules like streptococci.

In bouillon we have cloudiness after a day and a sediment in the bottom, which on shaking resolves itself into thready slimy masses.

There is no mention in the work of Czaplewski and Hensel of the isolation of their bacillus in pure culture by means of plates and colony inoculation.

My own bacterial work on the sputum of pertussis was first read before the British Medical Association, in the latter part of August, 1897, and published subsequently in the British Medical Journal and the Centralblatt fiir Bakteriologie, 1897, Band XXII, Nos. 8-9.

In this communication I described a series of cases examined during the winter and spring of the same year. There were sixteen cases, and since then I may say I have been examining other cases with identical results.

The sputum was collected during a paroxysm of coughing in sterilized Petri dishes and allowed to stand a short while. The sputum separates in these cases into a glairy colorless mucus, in which are distinctly seen small grayish white particles like the scales of dandruff. These particles were fished out with a platinum needle, and without being subjected to further manipulation, such as washing, were sown in the media employed. In uncomplicated cases the above pellets of sputum are easily recognized, but if bronchitis or pneumonia complicates the case the sputum is more purulent and thick and does not separate as described. I also made use of hydrocele fluid, obliquely solidified at 65° C. to 70° C, in a transparent solid medium in test tubes, as my medium for cultivating this bacterium. I found and still think this medium especially fitted for the cultivation and isolation of the bacterium or bacillus described by me. I think this is due to the fact that hydrocele fluid is a poor medium for most bacterial species and favorable to the one interesting us. I made use of all the other media, but found that it was necessary to use the hydrocele fluid first to get the crude culture en masse, and from this to inoculate other media and make plates. I will not detail individual cases, as this has been done elsewhere, but will desci'ibe the bacillus isolated by me.

7'he Spvtum. If a small grayish white pellet of the sputum of the convulsive stage described above is spread between two cover-glasses stained with Loeffier blue or fuchsin and examined, we see as a constant element a small exceedingly minute bacterium, either singly arranged in the direction of the striae of the sputum or in small colonies ; it may be seen in the epithelial cells or on the epithelial cells, or free, or in the meshes of the sputum. This bacterium or bacillus is so thin and



iACirxrs Peutussis in the Sputum. Fuchsin staiu x 580. Zeiss aiiparatus immersion J,,.



Peuti ssis Bacillus. Puke Cultuue. Loeffler serum x 580 diameters. Zeiss apparatus ' immersion.


ruE .loilNS noPK[.\s Hn


^^m.


April, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


81


small as to be quite easily overlooked even with a -^ immersion, and in zoogloea it looks like a collection of cocci. Close study of the zoogloea reveals the fact of bacillary form. In cases not complicated by bronchitis or pneumonia these minute bacteria or bacilli are the only forms to be seen. As soon, however, as bronchitis or pneumonia sets in, other bacterial forms occur in the sputum and can be seen, and this will partly explain the difficulty of former workers in isolating this bacillus. If a small grayish pellet of the sputum be spread on obliquely solidified hydrocele fluid, or hydrocele fluid f and glucose bouillon i, we obtain after a lapse of 24 to 48 hours in the incubator at 37° C. to 38° C. a mixed bacterial growth of a whitish or transparent gray color. A small part of this is suspended in bouillon according to Loeflier, and then a few platinum loops of the mixture spread on another hydrocele tube. In this way isolated colonies may be obtained, or agar plates may be made in the usual way from the whole growth. In this manner we find that the bacillus grows in pure culture on hydrocele fluid as a delicate grayish white or pearly growth. If sugar bouillon is added to the hydrocele fluid the growth is thicker, not so delicately transparent and more of a creamy color.

On agar we have at first a delicate grayish white growth, which in time becomes thicker and whiter and more opaque. If the agar is white and made with beef extract, the growth is very delicate, grayish and not so white. Colonies in agar are whitish or grayish white by reflected light, of a straw color or deeper olive tint by transmitted light. They are irregularly round or oval.

In gelatin there develops at the room temperature and quite slowly a fine granular stick, whitish, much like that of streptococci. It has a nail-head and does not fluidify the gelatin. Colonies in gelatin have a round or an irregularly round form, whitish yellow by reflected and straw colored or olive colored by transmitted light. They are finely granular. The colonies do not become very large.

In pepton bouillon we have a finely granular appearance after 24 hours and a cloudiness ; after a time we have a sediment in the bottom of the test tube which is made up of small adherent masses. After a week or more the surface of the bouillon becomes covered with a thin sediment membrane which is made up of bacilli.

On Loeffler's diphtheria serum we obtain a whitish growth, reminding one much of the diphtheria growth.

On potato I have not as yet succeeded in obtaining a growth.

On human blood serum which is solidified on the surface of agar, we have a grayish white and abundant growth after forty-eight hours.

It should be here pointed out again that on agar the growth is delicate, grayish, transparent, and sometimes stops growing after a time, never being vigorous if the agar is clear and made of beef extract instead of beef juice. If agar is browner and made with beef juice the growth after a time is seen to be white, almost of an opaque pearly color; after a time, this difference in growth of agar tubes I could well convince myself of when recently working with pure culture obtained by plate colonies. This latter peculiarity will explain why Czaplewski and Hensel talk of a delicate growth on white


agar when mentioning my agar appearances. Cultures and threads which have been allowed to stand in closed tubes for six months are found to be dead and cannot be reinoculated on other media.

The bacterium or bacillus which I have isolated in pure culture and which has the above cultural characteristics, grows anaerobic as well as aerobic.

If stained with LoeflBer blue it appears as an exceedingly minute, delicate, thin, short bacillus form, much thinner than the diphtheria bacillus and not more than i to * its length. It measures 0.8 to 1.7 micro-millimeters in length, and 0.3 to 0.4 micro-millimeters in breadth. When stained with Loeffler blue it has a finely punctate appearance like the diphtheria bacillus, but here the resemblance stops, for it is a much more minute bacillus. In pure culture it is not decolorized by Gram stain. Old cultures on hydrocele and agar show clubshaped forms, the bacillus has a deeply tinged extremity like a club — in other words, involution forms exactly similar to the bacillus diphtheria3. Of course the involution forms are exceedingly delicate and show much smaller than the bacillus diphtherias.

The nameof " pol-bacterium " has been proposed for this bacterium by Czaplewski and Hensel in their article in the Centralblatt fiir Bakteriologie. The pol staining of this bacterium cannot be compared to such distinct pol-stain as that of a chicken-cholera bacillus (Kitt), rabbit septicemia (bacterium bipolar), where the extremities of the bacterium are deeply stained and rounded, and there is a distinct square space in between the poles unstained. The staining of our bacterium is exactly identical with that of the influenza bacillus when stained in pure culture with method blue of Loeflier. The bacterium or bacillus of pertussis stains deeply at the extremities and there is an irregular space or two irregular spaces in the long axis of the bacillus unstained or lightly tinged when stained with methyl blue of Loeffler. Some of the extremities are rather swollen, most of the extremities or poles are round, others are lancet shaped. I have never been able to convince myself by any known methods that this bacillus has spores or flagella.

AfotiUti/. In my first communication I said this bacillus was motile. By this 1 simply meant that in the hanging drop it was seen to have a rapid bobbing circular motion in a very circumscribed area of its own. In some fresh bouillon cultures this very limited motion was active for awhile and then ceased at the room temperature. I think that some would be inclined to deny that this was a movement inherent in itself inasmuch as the bacilli never traversed the microscopic field. I am quite willing to admit that this movement might be classed with cocci movements (Brown's molecular movements).

Animal Experiments. In my first paper I showed how fruitless animal experiments with this bacillus were. It is patho(^euic to mice in large amounts of a J to 3 cc, but in no instance was I able to reproduce symptoms of a disease similar to whooping cough in the lower animals. I think as I did then that accidental inoculation of the human subject could alone enlighten us. It would be going too far to make any such experimental inoculations.


82




From tlie above it will he seen that from the sputum of pertussis cases in the convulsive stage, Gzaplevvski and He.usel and I, independently of each other, have isolated pure for the first time a bacterium which is constant and found inuo other sputum. This bacterium fs especially characterized by a minuteness comparable only to the influenza bacillus (Pfeiffer) or that of septicemia of mice (Koch). In staining the dotted (not granular) appearance spoken of by me and compared to that of the bacillus of diphtheria, can best be brought out by the LoefHer alkaline blue stain. Fuchsin stains more coarsely and more uniform. The swollen end forms, or as I call them the involution forms, can also be brought out by LoelBer blue stain. I wish to point out here also that both in my first paper and in this I worked with pure cultures only (obtained by means of plate colonies). In this perhaps we find a reason why authors who have preceded the communications of myself and Czaplewski and Hensel differ so widely in what they saw. They failed to obtain the bacterium in pure culture. It may be remarked in passing that in my second cases as well as in some of my first cases there could be found among other bacterial forms a bacillus closely resembling the bacterium isolated in this work. This latter is somewhat thicker, grows in longer chains and fluidifies gelatin. I am inclined to think that observers have hitherto been much baffled by this bacillus, which I think with Czaplewski and Hensel is simply accidental. Such must have been the case of Cohn and Neumann.

I have tried to isolate my bacillus or bacterium in the early stages of pertussis before the convulsive paroxysm has ajipeared, and have not succeeded thus far in separating it from the saliva.

What significance can we attribute to the bacterium which is the theme of this paper? I doubt whether this can be solved e.x;cept by direct experiment on the human subject. I


may not be going too far to predict that the bacterium will aid us in understanding the mode of contagion in pertussis. It may be the first definite step in showing that in the sputum of the pertussis sufferer lies the danger of the communication of the affection to others.

Discussion.

Dr. OsLER. — I would ask Dr. Koplik if he has followed a case through from beginning to end and whether there is any difference in the abundance of bacilli during the early and late stages. Some have held that the disease was more infectious in its early stage.

Dr. Koplik. — I would say that I have tried to make a diagnosis of pertussis before the convulsive stage appeared. I could not find the bacillus in the mouth. The bacilli seem to be most abundant in the convulsive stage, but I did not follow up the study to see whether they persisted in the stage of convalescence.

Dr. Welch. — I notice that Dr. Koplik spoke of the staining in his first paper as granular, and Czaplewski supposes that he means polar staining. In Czaplewski's photograph the polar staining is none too definite, and he uses almost altogether carbolic-geutiau-violet, which gives an irregular staining with many bacteria. I would ask if this is a polar staining like that of chicken cholera, or an irregular staining as of the diphtheria bacillus.

Dr. Koplik. — I would classify it as more like the irregular staining in diphtheria. I think that the bacteria are more like the diphtheria organism than a real jjolar bacteria.

Dr. Sternberg. — It seems to me that the photograph does not show an extremely minute organism such as the influenza bacillus for example.


SUPPLEMENTARY REPORT ON THE STERILIZATION OF INSTRUMENTS BY FORMALDEHYDE.

By H. 0. Keik, M. D.


The December number of this Bulletin contained an account of the work performed by Dr. Watson and myself with formaldehyde gas, and we stated then that Meyrowitz of New York was making for us an apparatus especially adapted for the use of this method of sterilization. The accompanying cut represents the sterilizer referred to and which I am now using in my daily work. It is of a size suitable for the ophthalmologist, otologist, laryngologist, or other surgeon who uses comparatively small instruments. Should the general surgeon or the obstetrician desire to adopt the method, a larger sized sterilizer can be readily made and special appliances may be inserted for holding the particular instruments used by him ; as for instance there is figured in the illustration a small tray for carrying such delicate instruments as the cataract knife, etc., so as to prevent their cutting edges from coming into contact with anything.

The sterilizer which I have adopted for myself is 7x13x13 inches, giving an air space of a little more than 1000 cubic inches. The shelves are made of lieavy, wide-meshed wire gauze, the upper one extending entirely across the chamber, while the lower two are only eight inches long, extending from


the right side to an upright standard four inches from the left wall, thus leaving a space four inches wide by eight inches



high which is reserved for the Sobering lamp used in vaporizing the pastilles.


April, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


83


lu the rejiort of our work we called atteutiou to two features in the sterilization of instruments by this method which we thought required further study. The first related to the question of the deposit of paraform on the instruments and the possibility of such a deposit retarding the healing of wounds. The second was the possible effect of the gas upon the cutting edge of the instruments.

I think we are able now to give positive answers to both problems. 'Since receiving my new apparatus I have rejieated all the bacteriological experiments quoted before and with the same results published. I have further exposed instruments to five and six successive sterilizations by the gas, without any washing or cleansing whatever, and at the end of the experiments I was not able by the naked eye to discover any deposit whatever, nor was there any taste of the gas when the instrument was ajiplied to the tongue. A cataract knife so exposed was used in makinsr a corneal section on the rabbit. Healiusf


of the wound took place as usual when a sterile knife is used. Blunt instruments so exposed and then applied to my own conjunctiva produced no irritation.

As to the question regarding the edges of the knives, I tested very cai'efully their sharpness by means of the kid drum, both before and after sterilization, and 1 am not able to discover that the gas affects this in any way. To see whether or not the gas would affect instruments made of other material than steel, I repeatedly exposed the following instruments to the action of the gas: knives with aluminum handles, knives with ivory handles, a hard rubber syringe, soft rubber catheters, a Politzer air bag, and a nickel-plated syringe. None of these objects were in any way affected by the gas.

My conclusions are then that we have in this method a rapid, cheap, easy and sure method of sterilizing instruments without in any way injuring them.


CORRESPOi^DENCE.


DOES WILHITE'S STOKY OF THE NEGRO BOY INCIDENT IN THE DISCOVERY OF ANESTHESIA "LACK PROBABILITY"?

Letter from Dr. Wilhite. To THE Editor: —

My attention has been called to the article published in the August and September issue of this Bulletin from the pen of Dr. Hugh H. Young, Assistant Resident Surgeon Johns Hopkins Hospital, entitled "Long the Discoverer of Ansssthesia."

The writer has in a very interesting manner restated a part of the much discussed history of anaesthesia. I shall then not tax the reader's patience by another recital. Having been an interested spectator as well as a listener at the semi-centennial in Boston, October 16, 1896, of the aUeged first discovery of anaesthesia — at which meeting quite a number of distinguished men of the medical profession, representing different parts of the United States and elsewhere, demonstrated to their entire satisfaction and others that Morton was entitled to the glory aloyie of this discovery — I would have been content to let the matter rest, so far as I am interested, but for the article of Dr. Young, wherein some reflections are cast upon the memory of my deceased father. Dr. P. A. Wilhite, whose statements in New York, 1876, gave rise to the article of Dr. J. Marion Sims, published May, 1877, in the Virginia Medical Monthly. From my youth I have been conversant with the facts as related by my father ; and as he was the life-long friend of Dr. C. W. Long, as well as an enthusiastic supporter of Long's claims to the discovery of anajsthesia, I have been puzzled to understand why twenty years after Dr. Sims' article has appeared, and after Sims, Long and Wilhite have passed beyond the realm of controversy, labored efforts should now be put forth to throw doubt upon Wilhite's statements that first awakened interest in Long's claim, when the only errors


of which Dr. Long himself complained to Wilhite were the mistake made in the date when he and others entered Long's office, and of being present at the first or second operation by Dr. Long, and of saying that the first inhalation of ether in Jefferson was before the same persons. Dr. Young is charitable enough to admit that Long never mentioned this incident as being one of the mistakes in Wilhite's statement. I feel that injustice to the memory of Dr. Wilhite has been done, and that I ought not to permit some of the statements made by Dr. Young on this subject go unnoticed.

In a private letter from Dr. Young I am led to believe that it was not intentional on his part to do injustice in the matter to Dr. Wilhite, and that "his information came largely from papersof Dr. L. B. Grandy, of Atlanta." Since his information comes from Dr. Grandy, whose article was published in the Virginia Medical Monthly, 1893, and since he has courteously invited me to criticise his article and present documentary proof concerning Dr. Wilhite's claims, I will not be regarded a naked trespasser in this fertile field of controversy. Now, let me state at the outset. Dr. Wilhite never claimed to be the 'discoverer of anaesthesia, only so far as being the first one to produce the full ancesthetic effect of sulphuric ether accidentally, and it was only at the earnest solicitations of friends that he placed himself before the medical profession in 1883 to receive such honor as might be due him ; neither did he in any way seek to detract one iota from the honor he believed justly due his old preceptor and friend, Dr. Long. What he claimed then was that on one occasion while a boy at a country frolic in Georgia, he with others caught a negro boy, and while the others held the boy, he (Wilhite) administered to him sulph. ether, rendering him unconscious, etc., so much so that a doctor was sent for to revive the negro boy, and that when studying medicine under Dr. Long he related to him the circumstance. It would seem from recent attacks that Dr. Wilhite's offending consisted mainly in making a statement from "recollection" to Dr. Sims in New York that he was a student under Dr. Long and witnessed the first operations, and further, when a boy about seventeen years old he accidentally etherized a negro boy at a frolic in 1839, when the


84




year, as we shall see, was 1841. lu order to make it ajjpear that the 'story "lacks probability" the date of a letter is shuffled from January 27, 1877, to June 27, 1877, which Dr. Young states is a reply to a letter from Dr. Long, of May 20, 1877, and his daughter is quoted as giving the information that her father " repeatedly told her that he had never heard of it before it appeared in Sims' article." (I shall now take the liberty to refer to his (Dr. Y.) source of information by reference to Dr. Grandy's article, etc.) Dr. Grandy in his article, speaking of Mrs. Taylor's statements, says : " She tells me that the above story was related (italics mine) to Dr. Long by Dr. Wilhite himself in the presence of several of the family, when Wilhite was on a visit to her father's house in the spring (italics mine) of 1877. After hearing it. Dr. Long replied, " Doctor, this is the first time I ever heard of it." Now I submit that Dr. Wilhite's visit to Long, in Athens, was after the publication of Sims' article. Dr. Young says: "The ether controversy was never re-opened and Long's work was unknown to the world until 1877, when J. Marion Sims, hearing of him throtigh accident (italics mine), investigated his claims, was fully convinced of their merit, and vigorously demanded their recognition by the medical profession. His paper appeared in the Virginia Medical Monthly, May, 1877." Then he says again : " This article which obtained for Long the first recognition of any consequence was the outcome of a conversation which Sims had with a Dr. P. A. Wilhite, of Anderson, S. C. (italics mine). He summarizes the statements of Wilhite to Sims, and adds : "Dr. Sims at once communicated toith Dr. Long and soon convitued himself of the truth of his claim, but tin fortunately failed to investigate Wilhite's satetments, but embodied them in full in his article, giving Wilhite the credit of first inlentionallg produci7ig profound ancesthesia with ether " (italics mine). How does Dr. Young know that Dr. Sims never investigated the negro boy story? Does he not state: "Sims sailed for Europe soon after the publication of his article, and Long died in a few mouths, and Wilhite's statements went unchallenged for many years " ? Let us see what Grandy said in 1893. "Sims' article appeared in May, 1877, and Long at once noticed the errors and the absence of promised corrections. He requested Sims to correct the mistakes, but the latter replied that the 'misplacement of a few names and dates would not alter the main facts in the case.' He sailed for Europe in a few days and the matter was dropped." Now as a matter of information and to know when Sims did sail for Europe, I have in my possession a letter from his son which reads as follows :

New York, September 28, 1897. 30 West 58th Street. My Dear Doctor:— On account of nay absence from the city your letter of the 2l8t instant was not received until to-day. In May,

1877, my father was to have sailed for Europe on the Celtic

He and I went to San Francisco in June of that year. He returned here and sailed for Europe some time in July, about the latter part. . . . Believe me, yours sincerely,

(Signed) H. Marion Sims.

Why would Sims have needed to investigate Wilhite's statements further than to write to Long for the facts ? Did not Long send them? See the letter hereinafter quoted. Dr.


Young further states : " The negro boy story lacks probability, as Wilhite did not enter Long's office until 1844, two years after the first operation, as the following letter from Long to Wilhite shows." Now I admit that the letter shows this : Wilhite did not enter Long's office until 1844 and therefore he was not a student in his office in 1842 when the first operations were performed. I challenge Dr. Young to point to one word or sentence in that letter quoted to show that the negro boy story "lacks pi-obability." In order that the -reader may see the point 1 make, I quote the letter as published by Dr. Young:

Athens, Ga., May 20, 1877. Dr. p. a. Wilhite.

Dear Sir: — I received Dr. Sims' article on aniesthesia yesterday and find several mistakes. Dr. Sims states that yourself, Dr. Groves and Drs. J. P. and H. R. J. Long were students of mine and witnessed the operation performed on Venable, 1842. Your recollection failed you at this time, as it was several years, at least two, before either entered my office. You will see that you were mistaken in giving Dr. Sims this information. You also make a mistake in saying that the first inhalation in Jefferson of ether for its exhilarating effects was before the same persons. . . . I wrote to Dr. Sims informing him of the errors and asking him if he considered the mistakes of sufficient importance to be noticed, etc.

(Signed) C.W.Long.

Dr. Young has the candor to say, "In the letter to Wilhite, Long makes no comment upon the negro boy incident." Then why should he say it "lacks probability" from that letter? He, I submit, does injustice by quoting a letter of Dr. Wilhite in that connection to Dr. Long, making it appear that the letter bore date June 27, 1877, and states that it was a reply to Dr. Long's letter of May 20, 1877. I will quote this letter later on in its proper connection, and I am satisfied that he will see its inapplicability to his assertion. Now his proposition is that the negro boy incident "lacks probability." That is the question at issue and he has assumed the affirmative, and the burden of proof rests upon him. I am not called upon to prove a negative. The only thing he has relied upon is the letter quoted and the statements of Dr. Long's daughter, "but his daughter informs me that he repeatedly told her that he never heard of it before it ajipeared in Sims' article." Before impartial judges I submit he has not made out his case and established his proposition. The letter does not do it, for even admitting for the sake of argument that Long never heard of it until he saw it in Sims' article, or never heard of it himself as told to him in the spring of 1877, does not establish its improbability. I might rest the matter here but for the imputation cast upon Dr. P. A. Wilhite's veracity by the proposition, and this I must be permitted to defend. It needs none in South Carolina where he was known, but your Bulletin is not local. It goes among gentlemen who did not know him. It is true that he was a country physician; but in this dawn of the twentieth century the old Pharisaical question, "Can anything good come out of Nazareth?" should be discarded and the Nazarene's command, " Render unto CiBsar the things that are Csesar's," should take its place.

" Honor and fame from no condition rise ; act well your part, there all the honor lies," might have been justly said of Dr. P. A. Wilhite in his limited sphere of action. He spent his life in


April, 1898.]


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the interest of suffering humanity, and when the summons of death came, June 25, 1893, "he wrapped the drapery of his couch about him like one who lies down to peaceful dreams." Neither envy of men nor their sneers will disturb his repose. He eschewed politics and practiced medicine in Anderson, S. C, for nearly forty years upon his merits. The People's Advocate, a newspaper published in the city of Anderson, June 37, 1893, said : " In the death of Dr. P. A. Wilhite, Anderson loses one of her best citizens, liberal and progressive in his nature and upright in character. . . . He was one of our most noted physicians, was esteemed by all classes, and the whole city is in sorrow over his death." . . . The Anderson Intelligencer said: "Dr. P. A. Wilhite, one of the oldest and most skillful and most highly resjjected physicians in this portion of South Carolina, departed this life at his residence this morning. ... In 1878 Dr. Wilhite was appointed a member of the State Board of Health, then created by act of the Legislature of this State, and remained an active and influential member of the Board until his death." .... I might add further extracts from the press, etc.; suflice it to say that neither of these notices was written by relatives, but such is a part of testimony and tribute paid his memory publicly by those with whom he lived and for whom he lived for upwards of forty years. He was born in the State of Georgia about two miles of Danielsville, June 6, 1833 (" Dr. Long in Danielsville"), Dr. Long being about seven years his senior. Dr. Grandy says, " Up to the time of Dr. Long's death the relations between himself (Dr. L.) and Dr. Wilhite appeared to have been very friendly." His daughter had stated that Dr. Wilhite was a visitor to Dr. L. in the spring of 1877. The writer well remembers this visit, as he was an inmate of Dr. Long's house for a long time as a boarder, was then a student in Athens and was frequently in Dr. Long's private place of business, as well as a visitor in the family circle, and he knows of his own personal knowledge that the relations of the two men were friendly and cordial. This was before and after Sims' article appeared, and therefore 1 insist the letter quoted by Dr. Young from Wilhite to Long as of June 37, 1877, is incorrect, for it was not far from about that time when Wilhite visited Long. During this visit I was with my father and Long a great deal of my time and heard them discussing the facts, and to the best of my recollection there was no disagreement as regards the negro boy incident. The letter quoted by Dr. Young from Long to Wilhite shows that Long had then (May 30th) received and read the article, had written to Wilhite about the inaccuracies of dates and persons present, and had never once mentioned the negro boy incident, as Dr. Y. says. The reader will observe the .... (omission) in the letter quoted. Just what was left out I do not know. Until Dr. Grandy's article appeared the statement of Wilhite has not been questioned so far as I know by Long's friends. That Wilhite enjoyed the personal friendship and esteem of both Long and J. Marion Sims is abundantly shown by the visits paid them and their private letters still in our family.

That Wilhite was mistaken as to the true date of etherizing the negro boy, and as to the time he entered Long's office, there is no doubt. He made the statement from memory after


a great number of years in a casual conversation without any memoranda before him. Now let me quote some of the correspondence that bears on this subject :

267 Madison Ave., New York, January 12, 1877. My dear Dr. WmUe:—! wrote to Dr. Crawford W. Long, of Athens, three weeks ago, asking him to give me some notes of himself and special data about his discovery of ether as an anaj.-thetic. He does not reply to my letters. Will you have tlie kindness to write to him and say that I am to prepare a sketch of his life for Johnson's Cyclopedia and would like to have all the facts as soon as possible. Please help me in this matter, and with kind regards to all, believe me, dear Dr. Wilhite,

Most truly yours, (Signed) J. Marion Sims.

Admitting the genuineness of the letters published by Dr. Grandy, Dr. Wilhite wrote upon receipt of this letter as follows :

Anderson, S. C, January IG, 1877. Dr. C. W. Long.

Dear Doctor : — I have just received a letter from Dr. J. Marion Sims of New York, stating that you will not write to him, or at least that he wrote to you about three weeks ago and received no reply. If you don't do so soon it will be too late. He lias been preparing an article for publication, and wants to place you right before the world. You have been apprised,! suppose, of the nature of the article. Why you have been connected with, and will be the leading spirit in the article, tiappened (italics mine) in this way : While I was in New York last summer at one of Dr. Sims' private operations, several prominent physicians being present, I tiappened to remartc that I witnessed the first or second operation ever performed under an ancesttietic. Every one said I was mistaken, and particularly Dr. Sims .... After that I met Sims at his office and gave him such particulars as 1 could recollect of your first operation and also urged yourclaims to the priority. He at once wrote you on the subject and has since become very much interested in the matter. Now, Doctor, it is but justice to you (italics mine), as it is due the world, that you give Dr. Sims such information as he asks for at once, as he is going to all this trouble only to place the proper credit of this great discovery on the man who justly deserves it. 1 honestly hope you will comply with the Doctor's request as soon as possible .... As I have been the means of giving this investigation of thi-i subject its present shape, I am exceedingly anxious that you should give all the information you can, that you may, and justly too, receive the credit of this great discovery. If you will act it will certainly be so. Dr. Sims also wants a short history of your life, which don't fail to give. Hoping to hear from you, I remain,

Y'ours, etc.,

P. A. Wilhite.

I have italicized some of the letter to call attention to the fact that Wilhite was urging Dr. Long to give the facts. The reader will notice that in publishing this letter Dr. G. did not publish it all, as shown by the .... in two places. Dr. G. says to that long letter Dr. Long replied. Here is a copy of his reply never before published and is in my possession :

Athens, Ga., January 22, 1877. Dr. p. a. Wilhite.

Dear Sir : — Your welcome letter of the Itith instant was received a few days ago and I have been too busy to answer it earlier. I regret that my situation was such that I could not write to Dr. Sims earlier. I made a full explanation in a note mailed him before yours was received. This morning in sending off some certificates obtained some years since I find a number lost, yours among


86




the number. Now, Doctor, I wish to obtain yours again as early as possible to send to Dr. Sims.

I see from your letter that you stated to Dr. Sims and other physicians that you witnessed an operation by me under an anaesthetic before any published account of the use of ether to produce this effect.

My recollection is that you entered my office late in 1844, and that early in January, 1845, you were present and witnessed me perform an amputationof a linger of a negro boy belonging to Ralph Bailey, Sr., the boy etherized at the time. I am not positive this was the operation, but as I have the certificates of Mr. Bailey and his son and sons-in-law, who werepresent at this operation, I think this must have been the operation you a!lu<led to. I have mentioned these facts to refresh your memory if you have forgotten names and dates. The correct date of the operation was 8th of January, 1843. If this was the operation alluded to you can from these circumstances give correct report of the operation.

Tou may recollect some other operation ; if so, state the facts in regard to it ... .

Permit me to thank you for the interest you take in estailtshing my claim. If it is established you will have been the mover in it. (Italics in this letter mine.) Yours respectfully,

(Signed) C. W. Long.

Admitting the letter as published by Dr. Graudy, AVilhite replied. I will put this letter iu a parallel column with the letter Dr. Young quotes as beiug written June 27, 1877, in reply to Dr. Long's letter of May 20, 1877.


(Young)

Anderson, S. C, June 27, 1877. Dk. C. W. Long.

Dear Doctor : — Yours of the 22nd instant is at hand, and I have also just received a letter from Dr. J. M. Sims which I will answer today ....


In my statement I did make a mistake in regard to my being present at the first or second operation, which mistake I will correct. But if you still prefer I will send a certificate .... Let me know and I will give you any information or assistance in this great matter. Yours truly, etc.,

(Signed) P. A. Wilhite.


(Grandy)

Anderson, S. C, Jan. 27, 1877. Dr. C. W. Long.

Dear Doctor : — Yours of the 22nd is at hand, and I have also just received a letter from Dr. Sims which I will answer to-day. In regard to the certificates you spoke about it will not be necessary, I think, as Dr. Sims has my statement written out in full. He was particular to get all the points and facts I could recollect.

In ray statement I did 7nake a mistake about my being present at the first or second operation, which mistake Iwill correct (italics mine, L. B. G.).

If you still think proper I will send a certificate. Let me know and I will give you any assistance in this great matter. Yours truly,

P. A. WlLHITE.


I think when Dr. Y. takes the letter of Sims to Wilhite, dated January 12, 1877, Wilhite's letter to Long, dated January 16, 1877, Long's letter in reply to Wilhite's, dated January 22, 1877, and Wilhite's letter to Long, January 27, 1877, in reply to the 22nd letter, he will perceive at a glance that Wilhite could not have written a letter June 37, 1877, iu reply to the letter May 20, 1^77. The internal evidence of the letter and the connection show this.

8inis' article had been published before May 20th, and wliy should Wilhite a month afterwards (June 27, 1877) be writ


ing in reply "yours of the 22d instant" ? Did Long write to Wilhite, June 22, 1877? We have no such letter in the correspondence. Then it would have been a remarkable coincidence for Long to have written January 22nd and also June 22nd, and for Wilhite to have answered January 27th that be had just received a letter from Sims which he would answer that day, and also June 27th in the same words.

After all this correspondence I must be pardoned for again asking the question. How does Dr. Young know that Sims never investigated the Wilhite statements ? I'pon what hypothesis does he rest his proposition that the story of the negro boy " lacks probability " ? The proof is not shown in the published letters. W^hether Wilhite told Long about the negro boy incident or not, was it a fact? Dr. Sims accepted it as a fact on Wilhite's own statement. It was sufficient with him, and it would have been sufficient with his old friend and preceptor Long. Has uot Long requested him to give any additional operation and extended his thanks for his interest, etc.? But these men are all dead and gone. Wilhite (seemingly) being an obscure country physician, it is proposed to brush away in a flippaut manner his statements from the record. I submit to all unprejudiced minds that it is immaterial, as Sims said to Long about certain dates, whether Wilhite was a student in Long's office in 1842 or 1814, so far as the facts of Dr. Long's work is concerned; whether Wilhite was seventeen years old or nineteen years old ; whether it was 1839 or 1841 when he accidentally etherized the negro boy. The sole question is, did he do it the last year mentioned?

Dr. Young says that unfortunately Sims did not investigate Wilhite's statement. Then what did Dr. Sims write to Dr. Long for the facts for ? Why did he write to Wilhite to urge Long to send all the data or facts ? Why did Long ask Wilhite to mention any other additional operation? Suppose Sims had carefully investigated Wilhite's statements independently of his personal confidence he had in his veracity, what would have been the result of the investigation ? Fortunately for the memory of Dr. P. A. Wilhite, the South Carolina Medical Association appointed three of its honored body. Dr. J. R. Bratton, Yorkville, S. C. (died 1897), Dr. B. W. Taylor, Columbia, S. C, and Dr. C. R. Tabor, Fort Motte, S. 0., a committee to investigate the matter. Upon the advice of friends, there still being living wituesses to that incident in no way interested in the matter, Wilhite procured their affidavits, which, with his own statement under oath, he produced before the committee (Trans. S. C. Med. Ass., April, 1883). The original affidavits of his witnesses are now in my possession, and they were not written by Wilhite to fit his case. Fac-simile or photograph copies can be procured if Dr. Y. doubts my statement. Upon this testimony the committee made its report to the S. C. Medical Association, 1883, and published in its proceedings. This is a copy of the affidavits:

I hereby certify that in the year 1841 (exact date I do not remember) I did administer to a negro boy, about twelve years of age, sulphuric ether until he was completely an:esthetized, in which condition he remained for more than an hour. This occurred at the residence of Mr. J. N. Wier, in Clark County, Georgia. It was customary iu those days for the young ladies and gentlemen to


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congregate and have what were called ether frolics. It was on one of these occasions that I administered the ether to the negro boy, who was held by Mr. Robert Wier. I administered the ether on a towel until the boy became fully anaesthetized. When this happened we all became very much alarmed at his condition, he being perfectly insensible, with a slow and stertorousbreathing. Nothing that we did aroused him — slap him, pinch him, roll him over, etc.; so we came to the conclusion that we had killed him. Dr. Sidney Reese, who lived five miles away, was despatched for immediately. The doctor came in about an hour and a half, during which time the boy displayed very little evidence of waking up. After the proper means were applied he was aroused from his state of insensibility.

Personally appeared Dr. P. A. Wilhite before me and makes oath that the statements herein made are correct according to the best of his recollection.

Sworn to and subscribed before me, at my office, Anderson County, S. C, this the 29th day of May, 188.3.

John W. D.^niels, P. A. Wilhite.

Clerk of Court Common Pleas, Anderson County, South Carolina.

This testimony of Dr. P. A. Wilhite is fully corroborated by the affidavit of Samuel B. Wier, which is as follows:

State of Georgia, \

Jackson County. /

I hereby certify that in the year eighteen hundred and forty-one I was present and participated in a social collection of young gentlemen and ladies at John Wier's, at what was called an ether frolic, ami on that occasion I saw a negro boy put to sleep with suli)huric ether, administered by P. A. Wilhite, one of the young men present, now Dr. P. A. Wilhite, of Anderson, S. C. The boy was held by Robert Wier, while Wilhite gave the ether, until the boy became unconscious. The boy remained in that condition for some time, and not waking up, as they thought he should, and breathing very heavily and being perfectly limber, the party became alarmed, believing that Wilhite had killed the boy. A physician was sent for, who arrived in about two hours. Dp to that time the boy had shown but little evidence of waking up.

Dated December Hth, 1882.

(Signed) Samuel B. Wier.

I hereby certify that I was present when the above certificate was signed by Samuel B. Wier. I have known him for twenty-five years and know him to be a gentleman of honor and truthfulness. (Signed) Green R. Duke,

Dept. U. S. Marshal.

State of Georgia, \ Jackson County, j

I, J. L. Williamson, Clerk Superior Court of said county, do hereby certify that S. B. Wier is a citizen of said county and that I know him to be a gentleman of honor and truthfulness. Dated December Uth, 1882.

(Signed) J. L. Williamson,

Clerk S. C.

State of Georgia, I Clark County. J

I, the undersigned, hereby certify that I was present in the year 1811, the exact time not recollected. A collection of young people met at my house for the purpose of having a little fun and an ether frolic, and on that occasion a negro boy was put to sleep with sulphuric ether, administered by P. A. Wilhite, one of the young men present, now Dr. P. A. Wilhite, of Anderson, S. C. The boy was held by one of the young men, and the ether was administered until the boy became perfectly unconscious. Remaining in thatcondition for some time, and showing no signs of waking up, and breathing very heavily, we became alarmed, believing that Wilhite


had killed the boy. A doctor was sent for, he (Dr. Reese) arrived in about two hours, and up to that time the boy had shown but little evidence of coming to consciousness.

Dated December 12, 1882. (Signed) Mrs. L. C. Wieb.

I hereby certify that I was present when the within certificate was signed by Mrs. L. C. Wier. I have known her for fifteen years and she is a lady of high standing and unquestionable veracity.

December 12, 1882. (Signed) Green R. Duke,

Deputy U. S. Marshal.

(The committee of the S. C. Medical Association omitted by oversight this last certificate and omitted giving the full name of Mrs. Wier.)

In conclusion let me say I have tried to avoid saying anything that might appear personally offensive to any of the profession or any one connected therewith. I have claimed the liberty to insert in this statement certain points made by Dr. G., showing the errors of the article of Dr. Young, for each claimed to have access to private papers of Dr. Long.

Dr. Wilhite never by word, deed or act, privately or publicly, sought to claim any honor in this matter for the boyish frolic, etherizing the negro boy in 1841, except what was justly due him; neither do I; and as he, if living, would not seekto pluck one leaf from the laurel of Dr. Long, neither will I seek to rob him or any one else who may have a better claim to the crown. I submit that if human testimony of disinterested witnesses has still any weight or force with gentlemen in the forum of discussion, then no one ought to rise up and make the assertion that Wilhite's statements "lack probability." It was not a figment of his imagination, but a veritable fact. Dr. Long lived over a year after the statement of the negro boy incident as published in Sims' article, and continued in the harness up to his death. If he discredited the statement, he lived in Georgia but a few miles from the place where the incident was stated to have occurred. If it had been a fake, how easy would it have been for him to have gotten the testimony to establish its incredibility had the story been untrue.

With this I must leave the matter where Dr. Sims left it, having faith that an unprejudiced profession as well as the public will in the end render a righteous verdict and see as I do that for his labor of love for Long there is in return now ingratitude. J. 0. Wilhite, M. D.

125 North Main Street, Anderson, S. C, November 1, 1897.

Letter from Dr. Young. To THE Editor:

In the paper of Marion Sims, Wilhite is quoted as saying that previous to the discovery of anfesthesia by Long he was a student in Long's office; that when Long was discussing the possibility of producing anaesthesia with ether, he "encouraged him" by relating how he had unintentionally etherized a negro boy; and when Long, thus persuaded, did administer ether to Venable and operate on him, he, Wilhite, assisted in the operation ; thus modestly taking to himself a large part of the credit of the "great discovery."

The papers in my possession show conclusively that Wilhite did not enter Long's office until two years after Long's discovery; that he was not present at the first operation ; that he


88




was a boy younger by seven years tban Long, and therefore probably not Long's confidant and adviser.

The only remaining statement was the story of etherizing the negro boy, which Wilhite claimed to have done in 1839.

Numerous witnesses testified that the custom of inhaling ether in that part of Georgia began in the winter of 1841 and 1842 and was originated by Long, who had learned of the exhilarating properties of ether at the Medical College in Philadelphia, at least two years later than Wilhite, then a young schoolboy, claimed to have used it.

To say therefore that " the negro boy story lacked probability " seemed to be putting it mildly.

My conviction was further strengthened by finding that L. B. Grandy, first in an article in the Virginia Medical Monthly, October, 1892, and again in the New York Medical Journal, July 20, 1895, had vigorously attacked Wilhite's statements, declaring that they were " fiction, pure and simple— /«fcMS in unofahus in omnibus," and no one, not even his son, bad contradicted Dr. Grandy. Was I not justified therefore in assuming that it was an acknowledged fact that the negro boy story lacked probability? I think so.

Permit me to add that the unimportant inaccuracy of date in my paper, which he attributes to most sinister motives, was due merely to the indistinctness of the manuscript. After debating for a long time I decided that the word was intended for "Jun." and not "Jan.," a mistake, as it now appears, but of no practical import.

Dr. Wilhite's paper is valuable because he brings witnesses to prove that his father really did unintentionally, but nevertheless actually, etherize a boy to complete narcosis, a very interesting point in the history of anaesthesia. But that he had absolutely nothing to do with the discovery of anaesthesia by Long in 1842 must still be considered certain.

Hugh H. Young.


NOTES ON NEW BOOKS.

The American Yeir-Book of Medicine and Surgery. Edited by George M. Gould, M. D. (Philadelphia : W. B. Saunders, 1898.)

The excellence of the editorial work done by Dr Gould is so often exhibited and so well recognized that but few words of praise are needed from us for this work.

Although there has been some change of cullaborators since the last Year-Book appeared, there has been no falling off in the work done, and all the assistants should be congratulated for their help in producing so useful a book and one which requires so much care and labor to make it of value.

As time advances the editing of this Year-Book will become more and more difficult, for there is a large increase yearly in medical articles and journals. This makes a proper selection harder and harder, ami as the personal equation must enter into such selections, they become in a certain degree less and less valuable. No one knows beforehand what apparently insignificant point in some article may prove of significance before the next year is passed, and 80 articles may be omitted from consideration which a year later will prove to have been really important contributions. To remedy tills, we believe lists of articles which have not been touched upon on all important branches should be appended at the end of each chapter. This scheme mfiy not be feasible but if some such sheme is not devised, the value of the Year-Book, whicli is, after all, only


thatof a good reference book, will diminish yearly. Had we Central Ibl, after " in this country there would be less need of a Year-Book, and these " Centrallblatter " have theirdistinct ailvantage in being to a greater or lesser extent limited to special branches of medicine, surgery, etc., so that the practitioner is not obliged to purchase a large Year-Book, only a portion of which interests him, but with his " Centrallblatt" is able from week to week to pursue any special subject in which he may be interested. Why would it not be possible to publish the several sections of the Year-Book separately? We believe they would have a large sale, whereas the price of the Year-Book must keep it out of reach of many practitioners who would be glad to own this work of reference. While the "Centrallblatter " keep us really up to date in the different branches, the Year-Book is always about six months behind ; another factor which lessens its value to the busy and progressive student. He must get the last six months' information elsewhere.

We value the Year-Book and think the remarks of the collaborators of special importance in pointing out both good and bad work, or, better, in showing up errors of judgment. Such remarks should be of real service to younger practitioners who desire to write.

The profession at large should be sincerely grateful to Dr. Gould for the Year-Book, which is issued solely for the benefit of practitioners who are too busy to look up papers in which they may be interested , or too far distant from a good fountain of medical information to know what articles on any medical subject have lately appeared.

Essentials of Bacteriology. By M. V. Bail. ( W. B. Saunders, Philadelphia, Pa., 1897.)

Nothing in technical literature affords more depressing reading than a " compend," and the more widely removed the student from a practical acquaintance with the raw material out of which the subject itself is constructed, so much the more ineffective will be the efforts of any writer to provide him even temporarily with a short cut to knowledge Certain compends may perhaps be defended. In studying anatomy, for instance, the student has probably dissected, though perhaps more or less hurriedly, the whole or at least the greater part of the human body and has familiarized himself with the details, so that he has obtained a mental picture of the various organs and their relations. It is possible, then, that under these circumstances a compend may remind him of many half- forgotten facts, and he may retain this information until the emergency, represented by an examination, is over. But with the scanty opportunities nfforded by most of our medical schools in this country for obtaining any adequate practical acquaintance with bacteriological methods, the need or a<lvantage of a compend is hardly apparent. To any one who has had an opportunity of studying bacteriology in the only way in which it can be learned, namely, by practical work in the laboratory, the scope of the book is altogether too narrow to be of much service. To the student who has had no such opportunities it can have but little meaning, and even a word-for-word knowledge of its contents would hardly enable him to pass a properly conducted examination upon bacteriology.

The author acknowledges his indebtedness to several text-books dealing with the subject both in English and in foreign languages, but among his list we miss the names of some of the most trustworthy authorities. The definitions are terse, but not always free from obscurity or even error.

As a shoit text-book for the beginner, or as an aid in ihe case of the more advanced student to the revival of forgotten knowledge, any compend upon bacteriology must be found wanting.

In view, therefore, of the insuperable difficulties with which he has had lo contend, the author must not be criticized too severely for shortcomings which are necessarily involved in the nature of the subject with which he has h:id to de;il.


April, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


89


PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.


THE JOHNS HOPKINS HOSPITAL REPORTS.

Volume I. 423 pages, 99 plates.

Report in PntholosTT*

The Vessels and Walls of the Dog's Stomach; A Study of the Intestinal Contraction;

Healing of Intestinal Sutures; Reversal of the Intestine; The Contraction of the

Vena Portae and its Influence upon the Circulation. By F. P. Mall, M. D. A Contribution to the Pathology of the Gelatinous Tj-pe of Cerebellar Sclerosis

(Atrophy). By Hexrt J. Berkley, M. D. Reticulated Tissue and its Relation to the Connective Tissue Fibrils. By F. P.

Mall, M. D.

Report in Dermatology. Two Cases of Protozoan (Coccidioidal) Infection of the Skin and other Organs. By

T. C. Gilchrist, M. D., and Emmet Rixford, M. D. A Case of Blastomycetic Dermatitis in Man; Comparisons of the Two Varieties of

Protozoa, and the Blastomyces found in the preceding Caeea, with the so-called

Parasites found in Various Lesions of the Skin, etc. ; Two Cases of MoUuscum

Fibrosuni; The Pathology of a Case of Dermatitis Herpetiformis (Duhring). By

T. C. Gilchrist, M. D.

Report in Pathologry. An Experimental Study of the Thyroid Gland of Dogs, with especial consideration

of Hypertrophy of this Gland. By W. S. Halsted, M. D.


Volume II. 570 pages, with 28 plates and figures.

Report in Medicine.

On Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with

Gallstones. By William Osler, M. D. Some Remarks on Anomalies of the Uvula. By John N. Mackenzie. M. D. On Pyrodin. By H. A. Lafleue, M. D. Cases of Post-febrile Insanity. By William Osler, M. D. Acute Tuberculosis in an Infant of Four Montlis. By Harry Toulhin, M. D. Rare Forms of Cardiac Thrombi. By William Osler, M. D. Notes on Endocarditis in Phthisis. By William Osler, M. D.

Report in Medicine.

Tubercular Peritonitis. By William Osler, M. D.

A Case of Raynaud's Disease. By H. M. Thomab, M. D.

Acute Nephritis in Typhoid Fever. By William Osler, M. D.

Report in Gynecologry.

The Gynecological Operating Room. By Howard A. Kelly, M. D.

The Laparotomies performed from October 16, 1889, to March 3, 1890. By Howard

A. Kelly, M. D., and Hunter Robb, M. D. The Report of the Autopsies in Two Cases Dying in the Gynecological Wards without Operation; Composite Temperature and Pulse Charts of Forty Cases of

Abdominal Section. By Howard A. Kelly, M. D. The Management of the Drainage Tube in Abdominal Section. By Hitnteb Robb,

M. D. The Gonococcus in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Peritoneum;

Ovarian Tumor; General Gynecological Operations from October 15, 1889, to

March 4, 1890. By Howard A. Kelly, M. D. Report of the Urinary Examination of Ninety-one Gj-necological Cases. By Howard

A. Kelly, M. D., and Albert A. Ghrisket, M. D. Ligature of the Trunks of the Uterine and Ovarian Arteries as a Means of CThecking

Hemorrhage from the Uterus, etc. By Howard A. Kelly, M. D. Carcinoma of the CervU Uteri in the Negress. By J. W. Williams, M. D. Elephantiasis of the Clitoris. By Howard A. Kelly, M. D. Myxo-Sarcoma of the Clitoris. By Hukter Robb, M. D. Kolpo-Ureterotomy. Incision of the Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gynecological Operations. By

Howard A. Kelly, M. D.

Report in Snrg-ery, I.

The Treatment of Wounds with Especial Reference to the Value of the Blood Clot in the Management of Dead Spaces. By W. S. Halsted, M. D.

Report in Nenrologry* I.

A Case of Chorea Insaniens. By Henry J. Berkley, M. D. Acute Angio-Neurotic Oedema. By Charles E. Simon, M. D. Haematomyelja. By August Hoch, M. D.

A Case of Cerebro-Spinal Syphilis, with an unusual Lesion in the Spinal Cord. By Hekry M. Thomas, M. D.

Report in Fatbolo^y, I.

Amtfibic Dysentery. By William T. Councilman, M. D., and Henri A. Lafleub, M. D.


Volume III. 766 pages, with 69 plates and figures.

Report in Patholog-y.

Papillomatous Tumors of the Ovary. By J. Whitridge Williams, M. D. Tuoerculosis of the Female Generative Organs. By J. Whitridoe Williams, M. D.

Report in Pntliolog^y.

Multiple Lympho-Sarcomata, with a report of Two Cases. By Simon Fleiner, M. D.

The Cerebellar Cortex of the Dog. By Henry J. Berkley, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman, M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Russell, Ph. D.

Heart Hypertrophy. By Wm. T. Howard, Jr., M. D.

Report in Gynecology.

The Gynecological Operating Room; An External Direct Method of Measuring the Conjugdta Vera; Prolapsus Uteri without Diverticulum and with Anterior Enterocele; Lipoma of the Labium Majus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Source of Error in Gynecological Diag' nosis; Operation for the Suspension of the Retroflexed Uterus. By Howard A Kelly, M. D.

Potassium Permanganate and Oxalic Acid as Germicides against the Pyogenic Cocci, By Mary Sherwood, M. D.

Intestinal Worms as a Complication in Abdominal Surgery. By A. L. Stately, M. D,


Gynecological Operations not involving CcBliotomy. By Howard A. Kelly, M. D. Tabulated by A. L. Stavely, M. D.

The Employment of an Artificial Retroposition of the Uterus in covering Extensive Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdominal Pelvic Operations. By Howard A. Kelly, M. D.

Photography applied to Surgery. By A. S. Murray.

Traumatic Atresia of the Vagina with Haematokolpos and Haematometra. By Howard A. Kelly, M. D.

Urinalysis in Gynecology. By W. W. Russell, M. D.

The Importance of employing Anesthesia in the Diagnosis of Intra-Pelvic Gynecological Conditions. By Hunter Robb. M. D.

Resuscitation in Chloroform Asphyxia. By Howard A. Kelly, M. D.

One Hundred Cases of Ovariotomy performed on Women over Seventy Years of Age. By Howard A. Kelly, M. D., and Mary Sherwood, M. D.

Abdominal Operations performed in the Gynecological Department, from March 5, 1890. to December 17, 1892. By Howard A. Kelly, M. D.

Record of Deaths occurring in the Gynecological Department from June 6, 1890, to May 4, 1892.


Volume IV. 504 pages, 33 charts and illustrations.


Report on Typhoid Fever.


Report in Nenrologry.

Dementia Paralytica in the Negro Race; Studies in the Histology of the Liver; The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supplv of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of "the Submaxillary Gland of ^fll< musculu.<: The Intrinsic Nerves of the ThvToid Gland of the Dog; The Nerve Elements of the Pituitary Gland. By Henry J. Berkley, M. D.

Report in Snrgrery.

The Results of Operations for the Cure of Cancer of the Breast, from June, 1889, to January, 1894. By W. S. Halsted, M. D.

Report in Gynecologry.

'ith a report of twenty-seven cases; Post-Operative Septic Peritonitis:

By T. S. CtTLLEN, M. B.

Report in Pnthologry.

Deciduoma Malignum. By J. Whitridge Williams, M. D.


Volume V. 480 pages, with 32 charts and illustrations.

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  • The Malarial Fevers of Baltimore. By W. S. Thayer, M. D., and J. Hewetson, M. D. A Study of seme Fatal Cases of Malaria. By Lewellys F. Barker, M. B.
  • Stndies in Typhoid Fever. By William Osler, M. D., with additional papers by G. Blumer, M. D., Simon Flexner, M. D., Walter Reed, M. D., and H. C. Parsons. M. D.

Volume VI. 414 pages, with 79 plates and figures.

Report in Xenrology.

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Report in Pathology.

Fatal Puerperal Sepsis due to the Introduction of an Elm Tent. By Thomas S.

CULLEN, M. B.

Pregnancy in a Rudimentary Uterine Horn. Rupture, Death, Probable Migration of

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THE JOHNS HOPKINS MEDICAL SCHOOL. SESSION 1897-1

FACULTY.


DmiEL C. Gn-MAN, LL. D., President.

WmiAM H. Welch, M. D., LL. D., Dean and Professor of Pathology.

iRi Remsen, M. D., Ph. D., LL. D., Professor of Chemistry.

William Osler, M. D., LL. D., F. R. C. P., Professor of the Principles and Practice

of Medicine. Henri M. Hcird, M. D., LL. D,, Professor of Psychiatry. William S. Halsted, M. D., Professor of Surgery. Howard A. Kellt, M. D., Professor of Gynecology and Obstetrics. Franklin P. Mall, M. D., Professor of Anatomy. John J. Abel, M. D., Professor of Pharmacologj'. William H. Howell, Ph. D., M. D., Professor of Physiology.

William K. Brooks, Ph. D., LL. D., Professor of Comparative Anatomy and Zoology. John S. Billings, M. D., LL. D., Lecturer on the History and Literature of Medicine. Alexander C. Abbott, M. D., Lecturer on Hygiene. Charles Wardell Stiles, Ph. D., M. S., Lecturer on Medical Zoology. Robert Fletcher, M. D., M. R. C. S., Lecturer on Forensic Medicine. William D. Booker, M. D., Clinical Professor of Diseases of Children. John N. Mackenzie, M. D., Clinical Professor of Laryngology and Rhinology. Samuel Theobald, M. D., Clinical Professor of Ophthalmology and Otology. Henrt M. I'lioMAS, M. D., Clinical Professor of Diseases of the Nervous System. Simon Fleiner, M. D., Associate Professor of Pathology. J. Whitridge Williams, M. D., Associate Professor of Obstetrics. Lewellys F. Barker, M. B., Associate Professor of Anatomy. William S. Thayer, M. D., Associate Professor of Medicine. John M. T. Finney, M. D., Associate Professor of Surgery.


George P. Debter, Ph. D., Associate in Physiology.

William W. Rdssell, M. D., Associate in Gynecology.

Henry J. Berkley, M. D., Associate in Ncuro-Pathology.

J. Williams Lord, M. D., Associate in Dermatology and Instructor in Anatomy.

T. Caspar Gilchrist, M. R. C. S., Associate in Dermatology.

Robert L. Randolph, M. D., Associate in Ophthalmology and Otology.

Thomas B. Aldrich, Ph. D., Associate in Physiological Chemistry.

THOM.is B. Futcher, M. B., Associate in Medicine.

Joseph C. Bloodgood, M. D., Associate in Surgery.

Thomas S. Cullen, M. B., Associate in Gj-necology.

Ross G. Harrison, Ph. D., Associate in Anatomy.

Fr.\nk R. Smith, M. D., Instructor in Medicine.

George W. Dobbin, M. D., Assistant in Obstetrics.

Walter Jones, Ph. D., Assistant in Physiological Chemistry.

.\DOLPH G. Hoen, M. D., Instructor in Photo-Micrography.

Sydney M. Cone, M. D., Assistant in Surgical Pathology.

Lotris E. Livingood, M. D., Assistant in Pathology.

Henry Barton Jacobs, M. D., Instructor in Medicine.

Charles R. Bardeen, M. D., Assistant in Anatomy.

Stewart Paton, M. D., Assistant in Nervous Diseases.

Norman McL. Harris, M. B., Assistant in Pathology.

Harvey W. CnsniNO. M. D., Assistant in Surgery.

J. M. Lazear, M. D., Assistant in Clinical Microscopy.

J. L. Walz, Ph. G., Assistant in Pharmacy.


GENERAL STATEMENT.

The Medical Department of the Johns Hopkins University was opened for the instruction of students October, 1893. This School of Medicine is an integral and coordinate part of the Johns Hopkins University, and it also derives great advantages from its close affiliation with the Johns Hopkins Hospital.

The required period of study for the degree of Doctor of Medicine is four years. The academic year begins on the first of October and ends the middle of June, with short recesses at Christmas and Easter.

Men and women are admitted upon the same terms.

In the methods of instruction especial emphasis is laid upon practical work in the Laboratories and in the Dispensary and Wards of the Hospital. While the aim of the School is primarily to train practitioners of medicine and surgery, it is recognized that the medical art should rest upon a suitable preliminary education and upon thorough training in the medical sciences. The first two years of the course are devoted mainly to practical work, combined with demonstrations, recitations and, when deemed necessary, lectures, in the Laboratories of Anatomy, Physiology, Physiological Chemistry, Pharmacology and Toxicology, Pathology and Bacteriology. During the last two years the student is given abundant opportunity for the personal study of cases of disease, his time being spent largely in the Hospital Wards and Dispensary and in the Clinical Laboratories. Especially advantageous for thorough clinical training are the arrangements by which the students, divided into groups, engage in practical work in the Dispensary, and throughout the fourth year serve as clinical clerks and sunjical dressers in the wards of the Hospital.

REQUIREMENTS FOR ADMISSION.

As candidates for the degree of Doctor of Medicine the school receives :

1. Those who have satisfactorily completed the Chemical-Biological course which leads to the A. B. degree in this university.

2. Graduates of approved colleges or scientific schools who can furnish evidence: (a) That they have acquaintance with Latin and a good reading knowledge of French and German ; (b) That they have such knowledge of physics, chemistry, and biology as is imparted by the regular minor courses given in these subjects in this university.

The phrase "a minor course," as here employed, means a course that requires a year for its completion. In physics, four class-room exercises and three hours a week in the laboratory are required; in chemistry and biology, four class-room exercises and five hours a week in the laboratory in each subject.

3. Those who give evidence by examination that they possess the general education implied by a degree in arts or in science from an approved college or scientific school, and the knowledge of French, German, Latin, physics, chemistry, and biology above indicated.

Applicants for admission will receive blanks to be filled out relating to their previous courses of study.

They are required to furnish certificates from officers of the colleges or scientific schools where they have studied, as to the courses pursued in physics, chemistry, and biology. If such certificates are satisfactory, no examination in these subjects will be required from those who possess a degree in arts or science from an approved college or scientific school.

Candidates who have not received a degree in arts or in science from an approved college or scientific school, will be required (1) to pass, at the beginning of the session in October, the matriculation examination for admission to the collegiate department of the Johns Hopkins University, (2) then to pass examinations equivalent to those taken by students completing the Chemical-Biological course which leads to the A. B. degree in this University, and (3) to furnish satisfactory certificates that they have had the requisite laboratory training as specified above. It is expected that only in very rare instances will applicants who do not possess a degree in arts or science be able to meet these requirements for admission.

Hearers and special workers, not candidates for a degree, will be received at the discretion of the Faculty.

ADMISSION TO ADVANCED STANDING. Applicants for admission to adv.anced standing must furnish evidence (I) that the foregoing terms of admission as regards proliinluary training have been fulfilled, (2) that courses equivalent in kind and amount to those given here, preceding that year of the course for admission to which application is made, have been satisfactorily completed, and Cli must pass examinations at the beginning of the session in October in all the subjects that have been already pursued by the class to which admission is sought. Certificates of standing elsewhere cannot be accepted in place of these es.iminations.

SPECIAL COURSES FOR GRADUATES IN MEDICINE.

Since the opening of the Johns Hopkins Hospital in 1889, courses of instruction have been offered to graduates in medicine. The attendance upon these courses has steadily increased with each succeeding year and indicates gratifying appreciation of the special advantages here afl'orded. With the completed organization of the Medical School, it was fotmd necessary to give the courses intended especially for physicians at a later period of the academic year than that hitherto selected. It is, however, believed that the period now chosen for this purpose is more convenient for the majority of those desiring to take the courses than the former one. The special courses of instruction for graduates in medicine are now given annually during the months of May and June. During April there is a preliminary course in Normal Histology. These courses are in Pathology, Bacteriology, Clinical Microscopy, General Medicine, Surgery, Gynecology, Dermatology, Diseases of Children, Diseases of the Nervous System, Genito-Urinary Diseases, Laryngology and Rhinology, and Ophthalmology and Otology. The instruction is intended to meet the requirements of practitioners of medicine, and is almost wholly of a practical character. It includes laboratory courses, demonstrations, bedside teaching, and clinical instruction in the wards, dispensary, amphitheatre, and operating rooms of the Hospital. These courses are open to those who have taken a medical degree and who give evidence satisfactory to the several instructors that they are prepared to profit by the opportunities here oflercd. The number of students who can be accommodated in some of the practical courses is necessarily limited. For these the places are assigned according to the date of application.

The Annual Announcement and Catalogue will be sent upon application. Inquiries should be addressed to the

REGISTRAR OF THE JOHNS HOPKINS MEDICAL SCHOOL, BALTIMORE.



Vol. IX.- No. 86

BALTIMORE. MAY, 1898.

Contents

  • Typhoidal Cholecystitis and Cholelithiasis. By Harvey W. Gushing, M.D., 91
  • The Presence of the Bacillus Typhosus in the Gall Bladder Seven YearsafterTyphoid Fever. By G.Brown Miller, M.D., 95
  • The Transplantation of the Rectus Muscle in Certain Cases of Inguinal Hernia in which the Conjoined Tendon is Obliterated. By Jos. C. Bloodgood, M. D., 96
  • Hydraulic Pressure in Genito-Urinary Practice, especially in Contracture of the Bladder. By Hugh H. Young, M.D., -100
  • A Case of Carcinoma Metastases in Bone from a Primary Tumor of the Prostate. By Sydney M. Cone, M. D., - - 114
  • Glossitis in Typhoid Fever, with Report of a Case. By Thomas McCrae, M.B., 118
  • Proceedings of Societies :

Hospital Medical Society, 119

The Bacteriology of Yellow Fever [Dr. Sternberg].

Notes on New Books, 120

Books Received, 122


TYPHOIDAL CHOLECYSTITIS AND CHOLELITHIASIS

REPORT OF A CASE WITHOUT PREVIOUS HISTORY OF TYPHOID FEVER, AND DISCUSSI0N"0F A POSSIBLE AGGLUTINATIVE REACTION IN THE BILE AND ITS RELATION TO STONE FORMATION.


By Harvey \V. Gushing, M. D., Resident Sv.njeon in the Johns Hopkins Hospital.


Suppurative cliolecystitis, since the time of Louis, has been recognized as one of the complicatious of typhoid fever. That it is definitely caused in most cases by infection with the bacillus typhosus was not demonstrated until long after Eberth and GafEky's discovery of that organism and the recognition of it as the aatiological factor in many of the other suppurative sequela3 of enteric fever.

Since the original report by Gilbert and Girode* (1890) of a case of cholecystitis caused by the invasion of the bacillus typhosus, as demonstrated by cultures, a series of most important observations, concerning the relation of typhoid fever and gall-bladder affections, has been made by investigators in various places. The quite constant occurrence of the bacilli in the gall-bladder in cases of experimental inoculation .typhoid in rabbits was first noticed by Blachsteinf (1891) in Professor AVelch's laboratory, and attention was called to the persistence of the organisms in this situation in these animals


Gilbert and Girode, Contribution a I'etude bacteriologique des voies biliaires. Comptes rendus de la Society de Biologie, 1890.

f A. G. Blachstein, Intravenous inoculation of rabbits with the bacillus coli communis and the bacillus typhi abdominalis. Johns Hopkins Hosp. Bulletin, 1891, Vol. II, p. 96.


subsequently by Professor Welch* himself. In one case the observation was made on the 128th day after the inoculation, the bacilli having disappeared from every other organ of the body. This demonstration in 1891 led to the routine examination bacteriologically of the bile in fatal cases of typhoid at this hospital, and Dr. Flexner found in 50 per cent, of the cases a pure culture of typhoid. Clinically these organisms may be present without producing any apparent symptoms. A variety of changes, however, may be set up at any time following their invasion, from simple catarrh with stone formation, to ulceration, perforation or general peritonitis ; a sequence such as is more commonly seen in appendicular disease, the two having many features in common.

Acute suppurative cholecystitis, as recently emphasized by many writers (Mason,t OslerJ and others), is a not uncommon


Wm. H. Welch, Additional note concerning the intravenous Inoculation of the bacillus typhi abdominalis. Johns Hopkins Bulletin, 1801, Vol. II, p. 121.

f A. L. Mason, Gall-bladder infection in typhoid fever. Trans, of Assoc, of Am. Phys., 1897, Vol. XII, p. 23.

nVm. Osier, Hepatic complications of typhoid fever. Trans, of Assoc, of Am. Phys., 1897, Vol. XII, p. 378.


92


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 86.


complication of a late stage of typhoid fever of the usual clinical type. In some of these cases there has been an associated cholelithiasis, but from a study of the reports obtainable it would seem that only a small percentage of cases with this complication during the fe?er were associated with gallstones ; a percentage no greater than could be accounted for by preformed stones.*

There seems, however, to be a distinct group of cases in which acute cholecystitis has appeared, not during the fever, but some mouths after it, and in all of these has there been an associated cholelithiasis. Bernheimf (1889) first called attention to the frequency of gall-stone attacks following typhoid, and DufourtJ (1893) found a history of tyj^hoid, preceding gall-stone attacks by a few months, in 19 cases. A review of the cases of cholecystitis admitted in this Hospital to Prof. Ilalsted's service and subsequently operated on and gall-stones found, shows that 10 out of 31 gave a previous history of typhoid, the interval varying from a few months to twenty years.§ In none, however, but the present case was Eberth's bacillus demonstrated.

Further, in 1890, Professor Welch|| demonstrated the presence of micro-organisms in the centre of gall-stones and suggested that they might have been the starting point for the deposition of the biliary salts. It has been mentioned, how


Prof. Oaler (loc. cit. p. 396) suggests that preformed stones may be an setiological factor in the production of cholecystitis during the fever, as they would render the ducts more receptive of infection. Naunyn (A Treatise on Cholelithiasis, 1896) and Hunter (A Discussion on Cholelithiasis, etc., Montreal Medical Journal, December, 1897) believe in the possibility of a rapid formation of stone following infection. Gilbert et Fournier (Du rule des Microbes dans la genese des Calcules biliaires: Compt. rendus heb. de la Soc. de Biologie, 1896, p. 145) have called attention to the fact that there may be different groups of calculi of various ages, old stones which have sterile centres and recent new formed stones from the nuclei of which positive cultural results may invariably ije obtained. The presence of old stones therefore at times may possibly court the infection whicli leads to the formation of a new group of calculi and associated cholecystitis. Statistics, however, seem to indicate, that of the acute cases, both those operated on during the course of the fever, and those dead of the fever in which acute gall-bladder infection has been found at autopsy, only a small percentage are associated with the presence of calculi. Courvoisier (Casuistisch-statistische Beitriige zur Pathologie und Chirurgie der Gallenwege, Leipzig, 1890) gives in 10 fatal cases of typhoid cholecystitis only two with gall-stones. Hagenmuller (Cholecystitis in Typhoid Fever, These de Paris, 1876) in a oompreliensive study reports 18 cases with death in 16 from fatal peritonitis, of which number there were only two with gall-stones.

f Bernheim, Art. Ictere du Diet. Dechambre, 1889.

t Dufourt, Infection biliaire et lithiase, sc. Eevue de M^d. 1893, p. 274.

§ This long interval would, however, not necessarily rule out an association with the primary infective agent, for in v. Dungern's case (Ueber Cholecy stitis Typhosa, Munch. INIed. Woch. , June 29, '97) fourteen years elapsed between the original attack and the perforative cholecystitis when the bacillus typho.sus was isolated.

II Also Naunyn (" Treatise on Cholelithiasis," New Syd. Soc, 1890, p. 51). Also Hanot (quoted by Dauriac, Gaz. Heb. de Med. et de Chirurg., July 25, 1897). Cf. also Gilbert et Doniinici (La lithiase biliaire est-elle de nature microbienne? Soc. de Biologie, 1894, p. 485).


ever, that calculi are usually not associated with early cases of acute typhoidal cholecystitis despite the great abundance of organisms in the viscus. In the one case, which we have observed in this early stage at operation, the organisms have been free and very motile; in the later cases, however, a distinct clumping of the bacilli in the bile has been noted. Attention was called to these clumps of bacilli by Blachstein, though no importance was attached to them. Richardson* found this condition in a single case and regarded it as a gigantic serumreaction in the gall-bladder. Nichols, working in Professor Welch's laboratory on experimental typhoid in rabbits, has noted the very early appearance of the bacillus in the gallbladder after intravenous iuoculatiou, and the subsequent distinct clumping of the organism in those animals which have later come to autopsy.

These observations naturally lead to the hypothesis that a reaction akin to an agglutinative reaction of the organisms, as Richardson has suggested, may take place in the course of time in the bile, the clumps being the starting point for the deposition of the bilirubin calcium salts and the origin of stone, the symptoms of which occur subsequent to convalescence.

The occurrence of this post-typhoidal cholecystitis, therefore, fuay be readily explained by the above series of observations, summarized as follows : (1) the bacilli during the course of typhoidal infection quite constantly invade the gallbladder; (2) the organisms retain their vitality in this habitat for a long period ; (3) in the course of time the bacilli are almost invariably found to be clumped in the bile, suggesting the occurrence of an intravesical agglutinative reaction ; (4) these clumps presumably represent nuclei for the deposit of biliary salts, as micro-organisms may with regularity be demonstrated in the centres of recently formed stones; (5) gall-stones being present in association with the latent, longlived, infective agents, an inflammatory reaction in the viscus of varying intensity may be provoked at any subsequent period.

The writer has been able to collect but i cases of posttyphoidal cholecystitis associated with stones, in which the bacillus typhosus has been cultivated from the bile at operation. To these, two additional cases are given (cf. Table I).

This sequence apparently may not be limited solely to infection with Eberth's bacillus. In Blachstein s report a similar clumjiing was observed in the bile of rabbits after inoculation with the bacillus coli communis. Dr. Flexner found the bacillus coli communis present in the bile in a small percentage of fatal cases of typhoid in the human, and in a few of the hospital cases of post-typhoidal operation for gall-stones a pure culture of colon has been isolated from the gall-bladder. Gilbert and Fournier,t as a result of their experimental researches, have divided biliary lithiasis into two great pathological groups: lithiasis due to colon, by far the most common, and lithiasis due to typhoid. Mignot


•A case of cholecystitis due to the typhoid bacillus. Boston Medical and Surgical Journal, Dec. 16, 1897.

I Gilbert et Fournier. Lithiase biliaire exp(5rimentale. Compt. rend. Soc. de Biol., Nov. 5, '97, p. 936.


May, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


93


and these writers have reproduced, experimentally, iu gniueapigs and rabbits conditions representing cholelithiasis of these two types. The writer recently operated on one of the cases of this colon groiiiJ two years after a preceding typhoid. The gall-bladder contained a multitude of small faceted stones in the centres of which faintly staining bacilli could be demonstrated on covei'-slip preparations, though cultures from the


centres of the stones were negative. The bile contained a few isolated organisms and many small clumps of bacilli. They possessed the cultural properties of the bacillus coli communis. The patient's blood serum gave an active Widal reaction to typhoid in dilution of 1 to 30. It also gave a slow but distinct clumping reaction with the bacillus which was isolated (cf. Table II).


Table l.^CoUeded cases of post-UjpJioidal Cholecystitis associated tvith Gall Stones wJiich have been operated ujmn and the bacillus

typhosus isolated.



Author.


Sex.


Age.


History.


Operation.


Contents of Gali. Bladder.


I.


Gilbert and Girode,

Comptes Rendus

de la Soc. de Biologie,

1893, p. 95.


F.


45


Gall-bladder symptoms during fever. Subsequent gall-stone attacks.


Operator, Ferrier. Cholecystectomy 5 mos. after fever.


Bac. typhosus, pure. Gall stone. Purulent iluid.


II.


DuI)l•L^ (Chantlmesse's Case), Les infections biliaires. . Paris These, 1891.


F.


45


No attack with fever. Sxibsequent gall-stone colic.


Cholecystenterostomy 8 mos. after fever.


Bac. typhosus, pure. Gall stoue.


III.


V. Dungern,

Miinch. Med. Wocli.,

June 39, '97.


F.


46


No attack with fever. Subsequent cardialgia. Periostitis of lower jaw in 13 yrs. with bac. typh. Acute gall-bladder attack in 14th year. Widal reaction positive.


Operator, Kraske.

Cholecystostomy with evacuation of abscess 14 yrs. after fever.


Bac. typhosus, pure. No stone found, but "probably present." Abscess.


IV.


M. W. Rieliiirdson,

Bost. Med. and Surg. Jour.,

Dec. 16, '97.


F.


50


Recent uncertain history of typhoid. Serum reaction positive.


Operator, M. W. Richardson. Cholecystostomy.


Bac. typhosus, pure. Brownish fluid with bacilli in clumps. Gall stone in cystic duct.


V.


Surg. No. 3835, Jan'y 38, '95.


F.


37


Uncomplicated typhoid 3>.f mos. ago. Gall-stone colic with jaundice three weeks ago. Recent peritonitis.


Operator, Prof. Halsted. Cholecystostomy.


Empyicma of ruptured gallbladder which contained numerous small stones. Bacillus typhosus.


VI.


Writer's Case,

Surg. No. 6339,

Mar. 16, '97.


F.


36


No history of typhoid. Serum reaction positive.


Operator, Prof. Halsted. Cholecystostomy.


Bac. typhosus, pure. Brownish fluid, bacilli in clumps, gall stones.


Several other posHyphoid cases have been reported without bacteriological notes. These are omitted.


Table II. — Si7nilar jwst-tijphoidal cases from the Johns Hojikins Hospital stirgical records mj which the bacillus coli communis has

been isolated.




Date.


Sex.


Age.


History.


Operation.


Contents of Gall Bladder.


I.


Surg. No. 3S05.


1895


M.


30


Gall-bladder symptoms during fever. Frequent attacks of colic since.


Prof. Halsted.

Cholecystostomy 14 mos. after fever.


Mucoid Iluid. Thirty calculi. Bac. coli com. pure.


II.


Surg. No. 44 38 .>;,'.


1895


F.


57


Preceding typhoid, subsequent attack of acute cholecystitis 7 mos. ago.


Bloodgood. Cholecystostomy.


Muco-purulent material. Impacted stones. Bac. coli communis.


III.


Surg. No. 4956.


1895


F.


39


Attack during convalescence.


Bloodgood.

Cholecystostomy 7 mos. after fever.


Purulent fluid. Bac. coli communis. Subsequent discharge of a stone.


IV.


Surg. No. 4411.


1895


F.


34


No symptoms during fever. First attack 18 mos. later. Three subsequent ones.


Bloodgood.

Cholecystostomy 3 yrs. after fever.


Bile-stained fluid. Seven stones. Bac. coli communis.


V.


Surg. No. 7619.


1898


F.


34


"Typhoid-pneumonia" (?) First attack 6 mos. later. Subsequent frequent attacks of gall-stones. Serum reaction positive to typhoid.


Gushing.

Cholecystostomy 3 yrs. after fever.


Bile-stained fluid. Countless small faceted stones. Clumps of rod-shaped bacilli. Bac. coli communis pnre.


Cases, in which bacterJuIoKical notes were incomplete, have been omitted.


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[No. 86.


Most extraordinary, however, is it to find in cholecystitis associated with stones, the presence of Eberth's bacillus when there has been no history of previous typhoid fever, and when the gall-bladder infection seems to be primary, as in the case to be reported.

The widespread occurrence of the bacillus typhosus has but lately been fully recognized, and owing to the definiteness of the serum reaction many cases are clinically recognized as typhoidal infection which have few of the classical symptoms and which at autopsy may be found free from intestinal lesions. Guarnieri* (1892) first described an infection of the biliary passages, liver and spleen with the bacillus typhosus in a case without intestinal lesions. The patient, however, had the clinical symptoms of typhoidal infection. Chiari'sj grouping of the cases of typhoid without intestinal lesions gives no division which would include a case the sole apparent lesion of which is in one organ and which clinically never presented any indications of typhoid.

The history of the case is as follows: J

Mrs. C, a3t. 26 ; entered Professor Halsted's service at the Johns Hopkins Hospital, March 5, 1897, complaining of pain in the right hypochondrium.

The family history was negative.

The personal history was also without particular note. She had had the usual infantile diseases, and with the exception of an attack of pneumonia ten years before entrance she had led a vigorous and active life. She had been subject since childhood to attacks of indigestion and prolonged constipation. She is evidently a careless eater and has had for the past three years occasional attacks of vomiting, usually in the morning after eating too heartily the night before. Her diet has been execrable : coffee, 6 or 8 cups a day ; she is especially fond of pastry, acid things, pickles, salads and the like. Her menstrual history is normal. She has been married five years; has had one still-born and one living child now aged 2 years. There has been absolutely no history of any preceding febrile attack. (Patient and friends were closely questioned about this several times. She lived in the country with, no near neighbors; she knew of no one in the vicinity who had had typhoid or any continuous fever.)

Present Illness. Five days before entrance, after an enormous dinner of beefsteak and gravy, the patient was seized at 11 p. m. with pain in the right hypochondriac region. This continued until the next morning, when after eating breakfast she vomited both her breakfast and the dinner of the preceding day. The quantity she thinks was large — at least 2 quarts. Soon after her pain became very severe and required morphine for its relief, and since then she has suffered from more or less constant pain under the right costal margin. It


Guarnieri, Contributio alia patogenisi delle infezione biliari. Revista generale italiana di clinica medica, 1897. Ref. Baumgarten's Jahresbericht, 1897, p. 234.

fChiari und Krause, Zur Kenntnis des atypischen Typhus abdominalis resp, der reinen "Typhosen Sephthiimie." Zeit. fur Heilkunde, Bd. XVIII, S. 471, Oct. 1897.

X Preliminary mention of this case has been made by Dr. Osier, loc, cit., p. 396.


is not paroxysmal and does not radiate. It is described rather as a soreness than as an actual pain. There has been no vomiting since the first attack; no jaundice has ever been observed. The physician who brought the patient to the hospital states that during the attack she has had some pyrexia, which on the third day reached 102°.

Physical Examination. A large, dark-complexioned woman, well developed and nourished; without jaundice. Pulse regular, 90, of good quality. Temperature 101°. Examination of chest negative. The abdomen was full, slightly tympanitic. There is a distinct rigidity of the right rectus muscle and considerable tenderness in the right hypochondrium. An indistinct tumefaction below the costal margin could be felt on deep palpation. Thei'e was tympany over this area. No increase in hepatic dullness; spleen not palpable.

Subsequent History. On the second day after admission the temperature fell to 99°. Her bowels had been freely moved and she was fairly comfortable. Abdominal tympany had disappeared and the spasm in the right upper quadrant of the abdomen was much less. On the third day the temperature was normal ; there was no rigidity, no tenderness. A hard, movable mass was palpable in the right hypochondrium ; tender only on the deepest pressure. The urine contained no albumen, no bile pigment. The patient was up and felt so well that she was anxious to go home. "From this time she was free from subjective symptoms. A smooth roundish mass of about the size and feeling like a movable kidney, readily obtained bimanually and on deep inspiration easily grasped in the hand, persisted in the right hypochondrium. It was absolutely without tenderness.

On the 16th day Professor Halsted operated. A brief report of the operation is as follows :

Cholecystostomy. Greatly enlarged gall-bladder with recent adhesions and containing gall-stones. Evacuation of contents. Permanent drainage.

A vertical incision was made, 15 cm. long, over the site of the tumor and through the right rectus muscle. The peritoneal cavity was opened, disclosing a distended gall-bladder held by recent adhesions to the liver and omentum. Cultures were taken from these adhesions before separating them. Gall-stones were palpable through the bladder walls and in the cystic duct.

The fundus of the gall-bladder was incised and a small amount of brownish mucoid material, unlike bile, was evacuated with fifteen dark green, smooth faceted gall-stones varying in size from a pea to a large chestnut. Cultures were taken from the interior on making the first incision into the gall-bladder. One of the largest stones was impacted in the cystic duct, from which it was dislocated with considerable difficulty. The deeper ducts were free from stones. A purse string catgut suture was taken about the opening in the fundus, into which a drainage tube surrounded by gauze was inserted. The margin of the opening was then anchored to the neighboring peritoneal edges by fine silk mattress sutures. The rest of the abdominal wound was closed in the usual fashion. Her convalescence was uninterrupted. There was a constant profuse discharge of bile. The drainage was


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omitted on the tenth day and the wound had closed ou the twenty-sixth.

Bacteriological Report. Cultures and cover slips from adhesions about the gall-bladder were negative. Cover-slips from the contents of the gall-bladder show a few rod-shaped organisms with rounded ends.

Eeport on cultures taken from contents of gall-bladder at operation, March 16, '97:

March 17. (A) Cultures taken on agar slants show in 18 hours, twenty or thirty opalescent, separate, whitish colonies. In the water of condensation an abundance of actively motile bacilli. Some very long forms.

March 18. (B) Bouillon inoculation from water of condensation of A gave in two days an abundant cloudy precipitate. No indol reaction obtainable. (C) Gelatine roll from B shows in 24 hours many brownish granular non-liquefying round colonies with a ground glass apjiearance ou surface growth.

March 19. Cultures were taken from a single colony of C and controlled by others from an isolated colony of original agar slant A, as follows: (D) Inoculation on agar shows in 18 hours an abundant opalescent growth of actively motile


bacilli morphologically like typhoid. They decolorize by Gram's method. (E) Sugar agar. No gas production. (F) Potato. An invisible membranous growth. (G) Litmus milk. Slightly acidulated. No coagulation.

March 30. A comparative series of cultures were made from a single colony of the original agar slant A, and as a control an undoubted typhoid bacillus, obtained by Dr. Carter in the pathological laboratory at a recent typhoid autopsy, was used. A variety of media were inoculated from both of these sources with precisely similar results.

April :3, '97. Serum Reactions. The patient's blood serum produces a distinct and rapid agglutinative reaction of the original organism and of the control, both obtained from agar slants four days old.

The blood serum from a case of typhoid fever in the medical wards produces a similar reaction with both organisms. Blood serum obtained from a healthy adult produces no clumping or loss of motility in either case.

Conclusion. A bacillus with the morphological and cultural properties of the typhoid bacillus.

The Widal test is positive both with the serum from the patient and that from a clinically typical typhoid.


THE PRESENCE OF THE BACILLUS TYPHOSUS IN THE GALL BLADDER SEVEN YEARS AFTER

TYPHOID FEVER.

By G. Brown Miller, M. D., Assistant Resident Gynecologist.


The case which I report gave the following history:

Mrs. L. P., white, aged 37 years, was admitted to the public gynecological ward of the Johns Hopkins Hospital, Feb. 1, 1898, complaining of pain in the right hypochondriac region.

Family History. Negative.

Past History. She had croup and whooping, cough as a child, but was otherwise healthy until the present illness.

Her menses appeared at the 16th year and were profuse, painful and regular.

She has been married 14 years; four children; no miscarriages; labors easy; micturition normal; bowels extremely constipated.

Present Illness. In the spring of 1891 she had the first attack of the pain from which she now suffers. This attack began as a severe cramp-like pain beneath the right costal margin. She had some fever but no chills, marked nausea and vomiting (the vomitus consisting of " pure gall "'). This attack lasted 12 hours, and the administration of morphia was necessary in order to give relief from pain. She noticed during this attack an oblong swelling beneath the right costal margin. This tumor, which was tender and sore, gradually diminished in size and within two weeks entirely disappeared. She was much constipated during the attack and her urine was very dark, but cleared up rapidly after it. Another and similar attack followed within a week after recovery from the first.

About one month after this second attack she had an attack of what was called " bilious fever," but which some of her


neighbors thought was "typhoid fever." She had high fever, severe occipital headaches, night sweats and chilly sensations, was extremely nervous and had constipated bowels. She had no pain, no epistaxis ; and no rose spots were remembered. The fever lasted about four weeks, when there was a remission of 4 to 5 weeks, followed by another rise of temperature, which lasted about one month.

. Following this fever she has had up to the date of admission to the hospital attacks of pain similar in character to the first two every three or four weeks. These have varied somewhat as to the severity of the pain, but have been of the same general character. She has now constant pain and tenderness over the gall bladder. She has never been markedly jaundiced.

Examination ofpntieiit. A healthy-looking woman; heart and lungs apparently not diseased; pulse, 90; temperature, 99° F ; abdomen symmetrical. Edge of liver just palpable beneath the costal margin. No tumor nor irregularity was felt, but much tenderness was complained of during deep palpation over the situation of the gall bladder. The right kidney was distinctly felt. Liver dullness one finger-breadth beneath costal margin.

Vaginal examinatiun. Negative.

A diagnosis of "gall stones in the gall bladder and probably in the cystic duct" was made by Dr. Ramsay, resident gynecologist, and an operation was advised.

Operation. She was operated upon, March 19, 1898, by Dr. Kelly, who made the following notes:


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[No. 86.


" Disease. Cholelithiasis, stoues in the cystic duct.

Complications. Extensive adhesions of the colon wallino; off the gall bladder.

Incision in the linea semilunaris, exposing the liver; gall bladder dissected out from adherent colon, exposing a small thick bladder; stones felt low down. Gall bladder incised vertically ; walls very thicli ; one artery cut at upper angle of incision; a small amount of bile and milky fluid escaped; spherical stone 15 cm. in diameter removed with difficulty from the lower part of gall bladder ; below this another stone felt through an opening about 8 mm. in diameter, a thick fibrous septum separating the two stones, which was dilated with the finger, and the second stone was removed with scoop. Below or rather above the gall bladder a hard mass about 3 cm. long and 12 mm. broad was felt running up under liver where it could not be reached except with finger."

The gall bladder was closed, a small gauze drain was inserted just beneath it into the abdominal cavity, and the abdominal incision was partially closed.

Following the operation the patient made a good recovery and was discharged from the hospital, March 34, 1898, apparently well. There was some suppuration along the tract of the drain.

At the time of her discharge she had had no attacks of pain since operation. The wound had entirely healed. Staphylococcus pyogenes aureus was grown from the suppurating drain tract.

Bacteriological Examination of the Contents of the Gall Bladder. Unfortunately cover-glasses of the bile were either not made or were lost after the operation. A smear upon an agar


slant showed after 48 hours a growth of the micro-organism, which proved to be the bacillus typhosus. This gave upon agar a white, semi-transparent growth ; cover-glasses stained with gentian violet showing a micro-organism 2 to 4 times as long as thick, slightly curved with rounded ends and staining rather faintly.

The micro-organism from an 18-hour agar growth was actively motile. Upon potato after a few days a faint, moist appearance only could be seen. Cover-glasses sliowed the same bacillus as upon agar, and some much larger forms were also seen. Irregularities of staining were noticeable. Litmus milk was very slightly acidified but not coagulated. No fermentation took place with glucose-agar. Gelatin was not liquefied, but showed on the surface a thin growth with irregular well marked edges. Widal's reaction was marked, as shown by the following notes made by Dr. Norman B. Gwyu, assistant resident physician :

" An agar smear from patient L. P. agglutinated typically by serum of a typhoid patient. Serum of patient L. P. agglutinates a known typhoid organism rapidly at 1-100 dilution. Reaction is immediate and positive, more like that of an acute attack than of an attack of several years ago."

Summary. The patient had two attacks of pain caused by gall stones in the spring of 1891. These were followed within a month by an attack of what was presumably typhoid fever. The gall bladder became infected by the bacillus typhosus, which caused a chronic inflammation, which continued until the time of operation seven years after the typhoid fever. There was no history of an attack of typhoid fever subsequent to the attack-in 1891.


THE TRANSPLANTATION OF THE RECTUS MUSCLE IN CERTAIN CASES OF INGUINAL HERNIA IN WHICH THE CONJOINED TENDON IS OBLITERATED.

(A PRELIMINARY REPORT.) By Jos. C. Bloodgood, M. D., Associate in Surgery and late Resident Surgeon, The Johns Hopkins Hospital.


The term " obliterated " is used because the extreme condition is more likely to bean acquired one rather than congenital. Undoubtedly the conjoined tendon may be congenitally very narrow or very attenuated. However, the important point to be recognized at the operation is that the conjoined tendon is either obliterated, very narrow, or very attenuated, and that the lower angle of the inguinal canal (Hesselbach's triangle) has lost its strongest support (the conjoined tendon), and that something (the transplanted rectus muscle) must be Substituted for this defect at the operation for hernia.

Thefollowing article will also appear in the Surgical Report No. 3 of the Johns Hopkins Hospital, Fasciculus 3-4, Vol. VII, with the report on the operation for hernia.

A Description of what is meant by the Obliteration

OF the Conjoined Tendon in Cases of

Inguinal Hernia.

On making a careful study of inguinal hernia the writer

has been impressed with the fact that they may be divided


into two groups; the larger group {A) includes those cases in which the conjoined tendon is wide and firm, and the second, a much smaller group {B), includes those cases in which the conjoined tendon is practically completely obliterated.

Grouj) A. In those cases of inguinal hernia in which the tendon is present it is easily discoverable before and demonstrable during the operation. If one inserts the index finger into the external ring, by invaginating the scrotum, the finger meets, after passing the pillars of the ring, a firm wall of tissue, the conjoined tendon, and it is to the outer side of the outer border of this tendon that the finger feels the impulse of the inguinal hernia. At the operation, if one examines the posterior wall of the inguinal canal, this tendon, if present, will be found to extend from the outer border of the rectus muscle to within about 1 cm. of the deep epigastric vessels. In some cases it may be wider, in other cases narrower. This tendon is clearly shown in Quain's Anatomy, 10th edition. Appendix, Fig. 23, p. 52. In Quain's Anatomy it is described as follows (p. 55) : "At the part of the abdominal wall through


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which the direct inguinal hernia finds its way there is recognized on its posterior aspect a triangular interval, the sides of which are formed by the epigastric artery and the margin of the rectus muscle, and the base by Poupart's ligament. It is commonly called the triangle of Hesselbach. The triangle measures about two inches (5 cm.) from above down, and an inch and a half (3.5 cm.) transversely at its base. In this area the abdominal wall consists of, besides the integuments, 1. the aponeurosis of the external oblique muscle, which is perforated toward the lower and inner corner of the space by the external abdominal ring; 2. the inner portion of the cremaster muscle covering the spermatic cord at the lower and outer part of the space, and above this, the lower fibres of the internal oblique and transversalis muscles passing to their insertion by the covjoined tendon, which, as a rule, extends over the inner twothirds of the lower part of the triangle ; 3. transversalis fascia; 4. subperitoneal tissue, and 5. peritoneum.

The conjoined tendon varies greatly in its development. I u many cases it is very slight and scarcely to be distinguished, while in others its deeper portion, derived from the transversalis muscle, covers the whole breadth of the triangle, reaching outwards along the deep femoral arch as far as the internal abdominal ring."

The observations by the writer on the variations in the width of the conjoined tendon and its complete obliteration in some cases were made p

without the knowledge

of the statement just quoted in Quain's Anatomy, and he was very glad to find a confirmation of his observations. The writer is not familiar with any other surgeon or anatomist who has dwelt upon the importance of the obliteration of the conjoined tendon as the chief cause of recurrence in these cases of hernia.

In cases of hernia in which the conjoined tendon is wide and firm the rupture takes place between the outer border of the tendon and internal oblique muscle. It may be either of the direct or indirect variety. It then extends down along the inguinal canal and protrudes from the external ring.



In these cases the problem is a simple one; it is only necessary to suture the tissues down to or just beyond the outer border of the tendon. There is no tendency to recur in the lower angle of the wound just above the pubes and to the outer side of the outer border of the rectus, because at this position the protrusion of the peritoneum is prevented by the conjoined tendon. If one does not transplant the cord a hernia may take place along the cord, protruding between the outer border of the conjoined tendon and sutured tissues. If one transplants the cord (as in Halsted's or Bassini's operation) the probability of a recurrence at this position (the lower angle), at least as far as our cases are concerned, is practically nil.

The probability of a recurrence if the cord is transplanted (as in the Halsted or Bassini operation) is very much less than in the older operations in which the cord was not transplanted. Theoretically (in my opinion) the position of the cord in Halsted's operation is better than the position of the cord in Bassini's operation, as the cord is made to protrude through the thickest part of the abdominal wall (aponeurosis of the external oblique and divided internal oblique muscle); practically the results after Halsted's operation in which the wounds have healed per primam are better than in any list of cases yet published, although only very slightly better than after Bassini's operation (143 cases — 3 very small recurrences at the position of the cord).

Grovp B. In cases in which the conjoined tendon is obliterated, if one inserts the index finger (invaginating the scrotum), after passing through the external ling, the finger does not meet any obstruction, but can be introduced without difficulty into the abdominal cavity for some distance; in this position, to the medial side the finger feels the sheath of the rectus muscle; by curving the finger downwards and backwards the posterior surface of the symphysis pubis can be easily palpated. The opening into the abdominal cavity extends from the outer border of the rectus and from the arch of the pubes, upwards and outwards to the internal oblique muscle. Before operation the number of fingers which can be intro


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JOHNS HOPKINS HOSPITAL BULLETIN.


[Xo. 86.


duced is limited by the size of the external abdominal ring. In some cases it is but one finger, in others two or more fingers. At the operation, however, after the division of the aponeurosis of the external oblique from the position of the external ring upwards, one can usually introduce the entire hand into the abdommal cavity ; in these cases the conjoined tendon is either thin and relaxed or completely obliterated, and the posterior wall of the inguinal canal from the outer border of the rectus upwards and outwards to the internal oblique muscle, and downwards and outwards to Poupart's and Gimbernat's ligament, is formed only by the thin and easily stretched transversalis fascia and areolar tissue.

The following figures, taken from the "Second Report on Hernia" which the writer is about to publish, demonstrate theimportanceof the obliteration of the conjoined tendon as a factor (perhaps the chief factor) in the recurrence of the hernia. As stated before, the larger group includes those cases of hernia in which the conjoined tendon is wide and firm. In this group (A) there have been 211 cases with 7 rec u r r e n c e s . In 6 cases (about 3 per cent.) the recurrence has taken place at the position of the transplanted cord, to the outer border of the conjoined tendon; all of these recurrences occurred i within one year, and

each one is a very small affair. In one case (4 per cent.) the recurrence took place 5 years after operation, in the lower angle of the wound. After a severe illness associated with a constant cough, in this case the conjoined tendon gave way.

In the smaller group (J5) in which the conjoined tendon was obliterated there are 10 cases, with 5 recurrences (50 per cent.) ; each i-ecurrence took place in the lower angle of the wound within a few months or a year, and the recurrent hernia is larger in each case than those in group A. In two cases the rupture descended into the scrotum.



Suppuration in both groups A and B has also been associated with the recurrence of the hernia.

In the larger group (A) the following figures show the relation of suppuration to recurrence, but also support the conclusion in regard to the conjoined tendon.

Wounds which Healed Per Primam.

(1) Halsted's typical operation, 143 cases, 3 recurrences.

Each recurrent hernia small and situated at the position of

the transplanted cord.

(2) Cases in which the cord has been excised, 43 cases, 1 recurrence. In this ( use the recurrence lias taken place through a split in the aponeurosis of the external oblique, to the outer side of the conjoined tendon.

Wounds which Suppurated. 1 1) Halsted's typical operation, 20 cases, 3 recurrences. 1 n two cases the reriirrent hernia is situated at the position of the transplanted rord, in one at the lower angle of the wound, described before.

(2) Cases in which the cord has been excised, 5 cases, no recurrences.

In the 10 cases included in the smaller uroup (i>) there have iiLL'u 3 recurrences among 7 cases in which the wound healed per primam, and 2 recurrences in the 3 cases in which the wound suppurated; in these 2 cases the recurrent hernia descended into the scrotum, and they represent the only complete recurrences in the entire series of 231 cases.

Impressed by the large proportion of recurrences in the few rases (3 recurrences in 7 cases) in which the conjoined tendon was obliterated, and with a hope of solving the additional problem presented by the obliteration of this tendon, the writer has devised, and in 8 cases performed a plastic operation on the rectus muscle, bringing this muscle down and suturing it with the other available tissues to Poupart's ligament and to


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the aponeurosis of the external oblique from the arch of the pubes up to the position of the transplanted cord. The procedure is a very simple oue, and the inclusion of the transplanted rectus in this portion of the wound must add strength. In the past we have learned the proper introduction and utilization of muscular tissue in laparotomy wounds. Every surgeon is familiar with the numerous hernias after laparotomies in which the incision has been made in the linea alba, in which cases only the fascia was sutured. In -i of our own operations for umbilical hernia in which only fascia had been sutured there have been 3 recurrences ; in those cases in which the rectus muscle had been exposed and sutured there have been no recurrences. After a careful observation of all the laparotomies performed by us in this hospital for a period of over eight years we find that there has been but one hernia in a laparotomy wound, which has healed per primam throughout, and in which muscle as well as fascia has been approximated. So impressed have we been with the importance of including muscle in the suture after laparotomy wounds that it is our rule in medium laparotomy to cut through the inner border of the rectus muscle rather than through the linea alba, and through the outer border of the rectus rather than through the semilunaris; and Prof. Halsted in his original conception of his ojieration for inguinal hernia divided the internal oblique muscle with this object in view. He states in his original communication, "I make and close the wound in operations for hernia on the same principle as in any other laparotomy wound." The writer F therefore claims no originality whatever in the use of the muscle to strengthen the hernial wound, but simply the original idea of transplanting the rectus to strengthen the wound in certain cases of hernia. The procedure is a very simple one; the method of ojoeration with this exception is the same as that followed in the typical Halsted operation. Before inserting the deep sutures the sheath of the rectus muscle is exposed; this is easily done by retracting upwards and inwards the aponeurosis of the external oblique and internal oblique muscles. The sheath of the rectus is divided in the direction of the muscle bundles from its insertion in the symphysis pubis upwards for a distance of 5 cm. After the division of the sheath the outer border of the



belly of the muscle bulges out; it is caught with two or three sutures of heavy black silk which are used as retractors to draw the muscle outwards and downwards. The operation at this stage is shown in Fig. 2. The deep sutures of silver wire are then inserted in exactly the same manner as described in Halsted's operation, with the addition that the four sutures below the transplanted cord include the sheath of the rectus and the muscle (Fig. 4); when these sutures are tied the rectus muscle is approximated to Poupart's ligament and the aponeurosis of the external oblique, from a position just below the transplanted cord down to the symphysis pubis, in addition to the divided and transplanted internal oblique muscle. Fig. 4 and Fig. 5 clearly demonstrate that the transplanted rectus strengthens the lower portion of the wound, which has been weakened by the obliteration of the conjoined tendon, better than any other available tissue could do.

The writer had this idea in mind for over a year, but not until April, 1897, did a case present itself in which the conjoined tendon was obliterated and in which he considered it necessary to transplant the rectus.

These drawings were made by Mr. Max Brodel from careful dissection on the cadaver and from operations.

explanatiok of the

Plates. Fig. 1. Halsted's operation, second stage. The aponeurosis of the external oblique has been divided, exposing the inguinal canal and j the internal oblique muscle. The dotted lines on the _^-, ! muscle represent the direc' i tion and extent of its divi J sion.

Fig. 2. The sac has been

excised and the peritoneal

cavity closed. The internal oblique muscle has been divided

and the rectus exposed and transplanted ; at this stage the

wound is ready for the insertion of the deep sutures.

Fig. 3. Halsted's operation, deep sutures inserted. This drawing demonstrates that there has been no attempt to completely close the external ring, and even if this should be done, there is no available muscle to approximate, unless the rectus is transplanted. If the conjoined tendon is wide and firm it is not necessary to completely close the external ring. Recurrence is prevented in the lower angle (Hesselbach's triangle) by this tendon.

Fig. 4. The transplanted rectus muscle included by the


J


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JOHNS HOPKINS HOSPITAL BULLETIN.


[Xo. 86.


deep sutures. In this drawing the cord has been excised in order to represent the operation more clearly. This drawing clearly demonstrates that the rectus muscle fills the lower angle of the wound, the part included by the lower two sutures. It also shows that the rectus strengthens the entire wound up to the position of the transplanted cord.


Fig. 5. Diagram of the position of the transplanted rectus muscle demonstrates the slight change in the direction of its fibres.

KoTE.— April, 1898. During the last few months Prof. Halsted in one case and Dr. Gushing in three cases have transplanted the rectus muscle.



~ ttctc/iment ot fiectu to i=y/r? . pu i> .


Diugram of the position of the transplanted rectus muscle, demonstratins t slight change in the direction of its fibres.


HYDRAULIC PRESSURE IN rxEXITO-URINARY PRACTICE, ESPECIALLY IN COXTRACTURE OF THE

BLADDER.


By Hugh H. Young, M.I)., Instructor in Genito- Urinary Surgery, Johns Ilojikins Unirersity.


Since the opening of the Johns llojikins Hospital in 1889 it has been the custom to treat cystitis by intravesical irrigations of various solutions. The irrigations have been performed without the use of a catheter, hydraulic pressure alone being used to force the irrigating fluid back into the bladder, which when full is emptied by the simple act of micturition.


This method was a direct sequence to Dr. Halsted's method of treating gonorrhoea by copious irrigations of antiseptic solutions which he promulgated in New York in 1883. AVhile irrigating the urethra he found that some of the fluid would be forced back into the bladder if the irrigating bag were held suflicientlv hiah.


Mat, 1898.1


JOHNS HOPKINS HOSPITAL BULLETIN.


101


The iicorn nozzle (Fig. 1) which he had devised for urethral irrigation was used, but held crowded into the meatus until the fluid was forced into the bladder by hydraulic pressure.

According to this method many cases of cystitis have been treated at the Johns Hopkins Hospital with remarkably satisfactory results.

While treating a number of these cases I found Dr. Halsted's acorn urethral nozzle unsatisfactory for intravesical irrigations, because it is so blunt that it cannot be wedged into the meatus tight enough to prevent the escape of fluid around it. To obviate this I had a nozzle* made with conical point of much more gradual slope, which can be tightly wedged into the meatus without hurting the patient. This has proved very satisfactory (Fig. 2). By the use of tins nozzle we have never found a case in which the bladder could not be irrigated without a catheter.

I have lately found that somewhat similar nozzles have been devised by Janet and Valentine.



Fig. 1. — IlalsU'd's Acorn Urethral Nozzl


Fig. 2. — Nozzle for Intravesical Irrigations


Case I. During the. summer of 1896 a patient was admitted to the hosjiital suffering with chronic pyonephrosis and cystitis. He was very weak and emaciated, and his urine, which was loaded with i)us and mucus, was voided every half-hour in small amounts. An examination of his bladder showed that it was greatly contracted, holding only 40 cc. (about an ounce). The mucous membrane was rough, corrugated, very tender and bled easily.

After bladder irrigations were begun it occurred to me that benefit might be obtained by dilating his bladder by hydraulic jiressure, thus lessening the disagreeable frequency of urination.

At first only 40 cc. could be forced into the bladder, but its capacity soon began to increase, and at the end of ten days his bladder held 150 cc. (5 oz.), and urination was not nearly so frequent. His cystitis was also improved.


Made by Whitall, Tatum &. Co., Pbila.


Unfortunately I was prevented from continuing the treatment longer, and though the results were very promising the outcome was still uncertain. The next case, however, surpassed my most sanguine expectations. I will report it at length.

Case II. — Severe chronic cystitis, 30 years' duration. Contracture of bladder, constant dribbling urine for three years. Capacity of bladder 30 cc. Dilatation to 290 cc. by hydraulic pressure. Return of continence of urine.

I. H., set. 65. American. Occupation, huckster. Admitted Dec. 17, 1896, on account of continual dribbling of urine.

Family History. Negative.

Previous History. He denies syphilis and gonorrhoea.

Present Trouble. Thirty years ago he injured his perineum in a fall, following which he says he had extravasation of urine, required frequent catheterization and was very sick for several months. At the end of seven months perineal section was performed in New York (probably for stricture of urethra following traumatism). After that he passed sounds on himself about twice weekly for twenty years. Cystitis, which was continuously present, became greatly aggravated six years ago, frequency of micturition increased greatly, and for the past three years there has been a constant dribbling of urine.

Status PriBsens. The urine dribbles continually, patient wearing cloths between thighs to absorb it. The odor is very offensive even ten feet away. Patient suffers severe pain in bladder and urethra and is perfectly miserable. He is unable to work and is shunned by his friends.

Examination. He is a thin, emaciated old man, with clothing wet from urine with a very foul ammoniacal odor, which appears to dribble continually.

A searcher passes into bladder readily, but reveals several irregularities in the urethra.

Bladder very small, not admitting the rotation of searcher. When fully distended with fluid it holds only 30 cc. ( 5 i), any further distension causing pain. Prostate not enlarged. No stone or intravesical growth made out. Mucous membrane of bladder rough. Searcher caused no hemorrhage. Kidneys not palpable.

Analysis of Urine. Heavy gray sediment amounting to onethird of specimen. Reaction intensely alkaline. Much stringy mucus. Albumen in large amount. No sugar. Microscopically mucus and pus cells, triple phosphates. One week after admission daily forced dilatation of bladder begun, using a solution of bichloride of mercury, 1 to 150,000.

The tabulation on page 102 shows the improvement made.

Remarks. — In this case cystitis had been present for 30 years. Continued inflammation had probably destroyed the mucous membrane, caused the muscle to be replaced by fibrous tissue, througli the cicatricial contraction of which the capacity of the bladder was steadily reduced until it Ijnally held hardly one ounce and had entirely lost its power of expelling urine. As a result the urine had dribbled constantly for three years before he entered the hospital.

Under forced dilatation the capacity of bladder rapidly increased from 30 to 290 cc. (gi to gx), but the contractile power did not fully return, probably owing to the fibrous replacement of the bladder muscle. There was a constant residual of 60 to 100 cc. and as a result micturition was frequent.

Whether the tonicity would have returned in time we are unable to say, as we have never seen the patient since. Improvement, however, was very great.


102


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 86.


Date.


Day of Treatment.


Capacity of Bladder.

Largest amount

held on forced

distension.


Interval. Longest time between two

urinations.


Remarks.— Case II.


Dec. 17

" 2G ....

" 30

Jan. 6

" 11

" 16

" 23

" 24

Feb. 20 ....

" 27

March . . . .


1 4 11 16

21

38


Cu. Cm. 30

40 90 200 340

24.5 2.55

215

290 280


Hr.

1

1

3


Min. Dribbling

30 30


Severe chronic cystitis 30 years. Urine ammoniacal, loaded with mucus.

Clothes saturated with urine. Dilatation begun. Irrigation of bicliloride followed by boric twice daily.

Trine clearer, reaction less alkaline.

Reaction acid. Great improvement in general health.

Has ceased to dribble, but bladder is unable to expel ali of urine, 60 cc.

residual, seems to have very little contractile power. At times voids 160 cc. naturally. Urine acid, pus slight.

He feels very badly. Some pyrexia. Refuses dilatation treatment. Treatment resumed. Urine has become alkaline again and is voided at frequent intervals. Great increase in pus.

Bladder seems to have no muscular power. After catheterization he is able to retain urine for 3 or 4 hours, but then he only voids a small amount, and after that voids every half-hour or so, leaving a residual of about 100. Patient is devoid of will and energy, does not try to do better. Is greatly improved in general health. Dribbling has ceased and cystitis much improved. Discharged.


Case III. — Vhronic cystitis 10 years. Contracture of bladder, holding only 40 cc. Micturition every 30 minutes. Under forced dilatation capacity increased to 160 cc, and interval to 4 hours.

Surg. No. 6573. J. T. Age 41. American. Farmer. Admitted May 26, '97.

Complaint. Frequent and painful micturition.

Family History. Negative.

Past History. Denies gonorrhoea and syphilis.

Present Trouble. Ten years ago began to have frequent and

having gonorrhcea. Had no instruments passed into urethra. Had been in good health previously.

Urination continuing frequent and painful, with occasional tinges of blood, patient consulted a physician at the end of a month, who passed an instrument to detect a calculus, but none was found.

Following examination he had chills and fever, lasting two or three days, accompanied by marked aggravation of bladder trouble.

At the end of two years patient suffered severe pain in bladder, and his urine contained a great deal of blood, and dribbles continually.

To relieve distress of patient a perineal section was done in Philadelphia. This operation was followed by marked improve

ment of symptoms. Perineal fistula continued for two years, and patient suffered very little till ten months ago when he again began to pass blood. Urination soon became very frequent and painful, and since then his bladder symptoms have steadily grown worse.

Status Pro'sens. Patient now voids urine every fifteen minutes, though at times half an hour may intervene. He suffers a constant pain located in lower abdomen, worse at end of urination, and then extending into penis. Urine often contains blood, free and clotted, and most at end of micturition. Stream frequently stops suddenly, accompanied by pain running to end of penis. Has never passed gravel.

In anterior part of anus is a fissure which he has had for several years.

Analysis of Urine. June 5th, Smoky, blood-stained deposit of mucus. Alkaline in reaction. Microscopically pus cells, red blood corpuscles and squamous epithelium.

On June 3rd treatment was begun. Bladder distended four times daily with Thompson's fluid.

In six days its capacity was doubled (60 cc), and .in two weeks trebled. Accompanying this, the interval between urinations increased from fifty minutes to one hour and thirty-five minutes. A great change bad taken place in bis general condition ; the con

Date.


Day of Treatment.


Bladdeu Capacitv.

Largest amount

held on forced

distension.


Ukine.

Largest amount

voided at one

time.


Interval. Longest time between two

urinations.


Remarks. — Case III.


June 3

11 8

" 11

" IS

" 2S

July 14 ... " 23 ... " 29 ...

Sept. 23....


1

5

8

ir,

25


Cu. Cm. 40

GO

85

105 130

100 135 ICO


Cu. Cm.

30

40 70

80 110

SO 100 130


11 r.

1 1

3 4


Min. 30

15 40

30


Constant severe paiu iu bladder, causing him to stoop. Urine loaded with pus, mucus and blood. Reaction alkaline.

General health improved. Pain now absent. Can now walk

erect. Urine much clearer. Has gained 8i<2 pounds in weight. Patient discharged ; to continue treatment at home. Patient

lost ground for a time, but soon improved rapidly.

He writes that he feels like a new man, passes no blood or mucus, is free from paiu and has no trouble conducting treatmeut at home.

Irrigations have been discontinued, contrary to orders, for more than a month. He writes that he still holds his urine three or four hours at a time ; has no pain and is very well.


May, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


103


stant pain in bladder, intensified by urination, which was present on entrance, had practically disappeareii, the urine had become acid, and the amount of pus diminished markedly. He had gained 8i lbs. in weight.

At the end of three weeks his bladder held 130 cc, he voided naturally 110 cc, and the ioterval between acts of micturition was two hours and thirty minutes.

The tabulation on the previous page shows graphically the improvement. (See also chart of cases appended).

Remarks. — In this case the bladder was exquisitely tendeiand would stand very little dilatation, the increase in capacity was therefore slower. I have not heard from him for a month, but I believe the capacity will be fully restored.

Case IV. — Chronic cysliiis 5 years. Contracture of bladder, capacity 60 cc. Micturition every 45 minutes. Pott's disease. Intestinal tuberculosis. Under forced dilatation size of bladder increased to 195 cc. and interval to 3 hours 30 minutes. Marked amelioration of cystitis.

Surg. No. 0580. G. L., single. Age 28. American. Laborer. Admitted May 30th, '97.

Complaint. Frequent and painful micturition.

Family History. Measles, pneumonia (?). Deniesliiesand gonorrhoea. Pott's disease 16 years ago, following injury, has never given rise to abscess, gives no pain now, seems to have undergone resolution.

Present Illness. Indefinite history of cystitis for five years or more. Denies gonorrhcea, but acknowledges having bad sounds passed two years previously. Cystitis characterized by burning pain running down to end of penis, intermittent appearance of


blood in urine, free and clotted, increased frequency of micturition, now every thirty to forty minutes. During past year has passed sounds on himself every week, no antiseptic precautions.

Patient has suffered from intermittent attacks of severe abdominal pain, every week or so, for a long time, associated with a continued diarrhffia, mucus and occasional streaks oi blood.

Examination. Well nourished man, with a marked stoop from kyphosis in middle dorsal region.

Chest and abdomen negative. Cystic swelling attached to each epididymis.

Rectal Examination. Prostate enlarged, irregular, with slight no<lular roughnesses. Very tender on pressure.

Bladder. Instrument introduced easily. No urethral stricture. Introduction causes considerable pain in region of prostate. Bladder contracted. On forced distension holds only 60 cc. ( § ij). No stone present. No intravesical growth made out. With finger in rectum and instrument in bladder, prostate feels nodular and extremely tender.

Instrument causes slight hemorrhage.

Tuberculin injected, small l)ut definite reaction following. It is probable that tuberculosis of intestine and prostate is present, along with latent vertebral tuberculosis.

Urinary Analysis, March 30th. Smoky, shreds of mucus, small blood clot, heavy white precipitate. Acid, sp.gr. 1020. Albumen, trace. No sugar. Microscopically red blood corpuscles, leucocytes and epithelial cells in abundance. No casts.

There was manifestly little hope of curing his bladder trouble, but the relief afforded by forced dilatation for only three weeks was wonderful, as shown in diagram.


Date.


Day of Treatment.


Bladder Capacitv.

Largest amount

held on forced

distension.


Urine.

Largest amount

voided at one

time.


Interval. Longest time between two

urinations.


Remarks. — Case IV.


May 30

June 5

" 8

" 10

" 18

" 23

" 27


1

13 18


Cu. Cm.

80 110 130 160 180 196


Cu. Cm. 00

60

90 130 160 180


Hr.

1

3 3 3


Min. 4.5

10

5 35

.55 30


Admitted. Suffers with severe pain in bladder. Urine acid,

with pus and blood. Systematic dilatation begun.

Almost free from pain. Feels greatly improved.

During the latter part of three weeks conti.nued diarrhoea, with pain in anus and prostate. Urine free from blood ; muci less pus. Cystitis considerably improved.


Case \.—t bladder, hold Urine alkalir blonder dilat increased to 4

Mr. G. B.

Complaint. minutes, wit

Family Hi

Past Histor

First and epididymitis months. F in bladder, quency, etc.

Vesical d temporary r

Cystitis so mucus. Pal numerous p local irrigati


evere chronic ng 20 cc. ( 3 V e, with much d to 370 cc. ( -5 hours.

Age 40. Ca Frequency h pain, bloo itory. Negat y. Usual di only attack

and poster Dur months pain on mi

sturbance h smissions. on became n in bladder hysicians an ons through


cystitis for \^ years. Or a ) on entrance. Micturitioi mucus and pus. Under 1 3 xii), and interval betweet

ladian. Drummer. Adn r of micturition, every i and mucus, ive.

seases of childhood, of gonorrhcea fourteen y€ lor urethritis. Discharg later began to have a cturition in end of pen

as continued since that

pery severe, urine foul, often very severe. Has d hospitals, with intern catheter, with only temp


dually contractin I every 15 minute lydraulic pressui acts of urinatio

litted May 4, '9 ten or fiftee

ars ago. Doub e lasted severs sense of fullnes 8, increased fr(

time, with onl

much blood an been treated b al remedies an arary relief.


9 s. •e

n

I. n

e

il

s

y

d

y

d



Following indiscretion in drinking, etc., every few months patient has had acute exacerbations of disease, accompanied by chills, high fever, vomiting, pain and frequent micturition.

The interval between acts of urination has steadily become shorter, and for the past two years patient has voided urine every ten or fifteen minutes. In order to attend to business he has found it necessary to wear a rubber urinal, which has produced a severe balanitis.

Status Prmsens. Increased frequency of micturition, every 10-15 minutes night and day.

Pain. Site in perineum, continual, scalding or burning.

Urine. Always slightly bloodstained, ammoniacal odor, considerable mucus.

Capacity of bladder, rarely passes over 1 ss.

General health fair, but rendered unhappy and miserable by bladder trouble. Unable to attend to business.

Physical Examination. A fairly well nourished man. Facies worried. Chest and abdomen negative. Kidneys not palpable. Eight testicle atrophied, an irregular nodule in epididymis.

Rectal Examination. No enlargement of prostate. Vesiculse seminales palpable. No abnormality. No has fond. No stone


104


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 86.


palpable bimanually, tenderness marked in region of neck of bladder. Cicatrix in perineum from old perineal section.

Bladder. Urine chart shows that about 20 cc. ( 3 v) is largest amount passed, with an interval of 15 minutes between acts of urination. When bladder is filled with fluid by hydraulic pressure without catheter, 22 co. is the largest amount which bladder can hold without severe pain.

Urinalysis. Light yellow, cloudy, large clot of mucus. Strongly alkaline. Microscopically pus cells in great numbers, triple phosphates, numerous red blood corpuscles.

Treatment, May 6th. Systematic dilatation of bladder by hydraulic pressure begun ; with nozzle held tight in meatus, an elevation of four feet easily forces irrigating fluid into bladder.

Patient instructed to allow fluid to distend bladder as much as can be borne without great pain, then to withdraw nozzle and force the fluid out by urination. This is repeated until lOOO cc. is used. This is to be done every four hours by patient, with assibtance of orderly. Thompson's fluid used for irrigation.

The chart shows the progress of dilatation.


April 23, 1898. Patient returns for examination. He has irrigated bladder with moderate regularity once or twice daily up to present time. Solution of boracic acid used. Xo attempt to dilate bladder. He says he has been in fine health, and but for the presence of pus in urine would feel perfectly well. He urinates every four to six hours ; control of bladder, good. Last night did not void for six hours.

Examination. General health good. 200 cc. of urine voided at one time. Urine alkaline, cloudy with pus. Many cocci and bacilli like proteus present.

On forcible distension bladder holds .325 cc. Slight recontraction of urethral stricture at site of previous operation.

Patient voids urine with ease.

It is now one year since the dilatation treatment was begun, and there is no tendency to a recurrence of contracture.

Remarks. — The improvement iu this case was remarkable and is graphically shown on the chart which accompanies.


Date.


Day of Treatment.


Capacitt of Bladder.

Largest amount

held on forced

dilatation.


UlUNE.

Largest amount

voided at one

time.


Interval. Average time between two

urinations.


Remarks. — Cask V

May 3

" 6

" 15

" 21

" 39

Juue 10

" 30

" 39

July 15

" 31

" 29

Aug. 9

Sept. 30


1

9

15

34 36 46 55


Cu. em. 33

23 94 115

130 170 190 250

335 375

340 370 365


Cn. Cm. 20

20 40 70

105 120 1.55 190

150 190

260 260

280


Hr.

1

3 4

3

5 6

4


Miu. 15

25 45

10 10

35

35 30

30

30


Severe pain in bladder and penis. Urine filled with blood, mucus and pus and strongly ammoniacal. Wears a rubber urinal. Has voided urine every fifteen minutes for two years.

Dilatation begun — every four hours. Thompson's fluid.

Injected with tuberculin. No reaction.

Improvement has been rapid. Pain has entirely gone. Appetite is ravenous. One irrigation of silver nitrate given daily (1 to 400). Urine greatly improved.

Vritie acid. Very little sediment. No blood.

Urine acid.

Feels like a new man. Can now walk about town four hours without desiring to urinate ; is entirely free from pain. Urine is almost clear, acid in reaction. Discharged to continue dilation at home.

Home treatment. Lost some ground while traveling.

Conducts his own treatment, using one nitrate of silver irrigation and three Thompson fluid irrigations daily.

He is now practically well.

Still some pus in urine, but patient feels perfectly well.


Case VL—

rate. Capaa dilated in on minutes. Or

G. C, whi

Complaint.

History. C ning cystitis, turition. Hj twenty times

Urine. Pa in large amoi at bottom. 1 passed is IOC stone, bladde tender. Noi holds 140 cc. taken four ti

Table on ps

Is there i


Chronic eysti ty of bladder e month fro eat general im e, set. 32. E

Frequent a ronorrhoea IC

Frequent 1 IS lost fifteei intwenty-fo e, heavy gra mt. No sugi Jrination ev

cc, genera r wall rougl esidual urin

Forced im nes daily by ige 105 show

Ge I ureteral r


ti» 7 months. Contractur 140 cc. Micturition evei n 140 to 500, with inter provement. ngineer.

nd painful micturition, months ago. Three mo tematuria. Increasing f 1 pounds in six months ir hours, burning pain at f sediment, slightly acid, ir. Microscopically pus jry hour, on the average lly less. Examination v, , corrugated, prostate n i. Bladder distended un gations of Thompson's fl patient. 3 progress of case. Also

NERAL Remarks. efluxf AVhen this me


5 of bladder mode y hour. Bladde ual of 4 hours 5

nths later begin requency of mic He now void snd of urination 1012. Albumei cells, mucus clo , largest amoun ith searcher, n< ot enlarged, no til quite painful uid begun, to b(

chart.

thod was firs


r


8

1 t t

t t



might not be forced up the ureter, when the bladder became forcibly distended. If such were the case pus and dangerous micro-organisms would be carried along, and ascending intlammation and pyonephrosis would certainly result.

The valve-like arrangement of the orifice of the ureter produced by its oblique course for H inches in the bladder wall would seem to be a special provision of nature to prevent the backward flow^ of finids from the bladder into the ureters.

In order to determine whether fluid, under considerable hydraulic pressure, would be forced into the ureters I experimented on a cadaver. After the intestines were removed the ureters were dissected out and cut across within a few inches of the bladder. A very strong solution of methylene blue was prepared and forced into the bladder through the urethra from an elevation of fourteen feet.

The bladder rapidly distended, but no fluid ran out of the cut ureters, although the distension was kept up until 1700 cc. (nearly two quarts) were forced in, and the walls became so


adopted the question arose whether some of the irrigating fluid thin that the blue solution shone through, and the threaten


May, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


105


ing aspect of the huge bladder caused most of the bystauders to leave the I'oom.

Wheu the bladder was incised the mucous membrane was found deejjly stained blue, but the stain did not extend -^ of an inch into the ureteral orifices.

In another cadaver, with large sacculated bladder and double hydro-ureters, I found it impossible to force fluid from bladder into ureters.

To further test the matter I made the following observation upon a dog, April 4th :

A small male dog received 1 gr. morphia hypodermically. Very deep colored solution of gentian violet prepared. By hydraulic pressure of 11 feet (above dog) the fluid was forced into the bladder without a catheter until the greatly distended bladder could be seen through abdomen.


Abdomen then cleaned, dog etherized, laparotomy performed. Bladder greatly dilated, and dark purple in color from fluid within, intestines pushed aside, ureter located. It contained perfectly clear urine and not a particle of the violet stain. Kidney exposed, no stain present. Although ureter was watched for some time, no vermicular movement was noticed until fluid was evacuated from bladder, when it was distinctly to be seen. Bladder had remained distended for fully 10 minutes. On another dog under ether we exposed the ureter after laparotomy, and watched it carefully while various amounts of fluid were forced into bladder. There was never any passing of the fluid into the ureter. No reverse peristalsis was made out.

These observations seem to show conclusively that fluid cannot be forced up the ureters from the bladder in the dog




CAPACITY OF Bladder.


Urine.


Interval.



Date.


Day of


Largest amount


Largest amount


Average time


Remarks. Case VI.



Treatment.


held on forced


voided at one


between two





dilatation.


time.


urinations.





Cu. Cm.


Cu. Cm.


Hr.


Min.



Sept. 4




100


1



Burning pain in bladder. Urine faintly acid, very cloudy, heavy sediment of pus and mucus.


" 6


1


140


100


1


5


Forced dilatation begun. Thompson's fluid four times daily.


" 11


5


230


160


1


30


Much relieved-.


" 15


9


380


200


2




" 21


15


340


260


3



Free from pain.


" 2.5


19


390


320


3



Urine acid. Pus less, but still considerable.


" 28


22


400


380


3


30



Oct. 3


27


500


440


4


50



" 4


28


500


460


4


50


Patient discharged. Is free from any bladder symptoms. Holds urine often for 6 hours during night. Has gained 10 lbs. in weight. Feels like a new man. Urine acid, almost clear, very little pus.


In this case forced dilatation had been used daily in dispensary for a week or so before entrance, and I wish to thank Dr. Gaither for the interest he has shown in the method. Partial dilatation had been accomplished. Cystitis was of 7 months' duration, so there was probably less fibrous tissue present, and dilatation was therefore more rapid than in other eases. Improvement, however, was rapid and marked ; relief afforded great ; result, cystitis practically cured.

January 10. Capacity 500 cc, interval 5 hours. Feels perfectly well. Does not urinate at all at night. Can hold urine for 10 hours if necessary. Left hospital November 15th. Took irrigations 4 a day up to December 1st. During December twice daily. Since December 28th once daily. Thompson's fluid.


and in man, and they have been borne out by clinical evidence, for in none of the cases has there been any evidence of ascending infection, although the bladders contained many virulent organisms, some streptococci.*


While this article was in the hands of the printer our attention was called to the work of Lewin and Goldschmidt in regard to reflux from the bladder into the ureter, and their findings are of such importance that I will add them here.

These authors (Virch. Arch. vol. 134, 189.3, p. 33), after anfesthetizing rabbits, performed laparotomy and injected fluid into the bladder under pressure. The ureters were then exposed and cut to see if the fluid had entered them. In nearly'all cases they found that a small amount of fluid slowly injected would enter the ureter of the rabbit.

Their conclusions are as follows :

" The backward movement of the contents of the bladder into the ureter and pelvis can be produced as well by injection as by artificial retention.

"This result always took place in bladders which were still capable of contraction and not strongly distended. The result con


sisted essentially in an over-distension of the ureters, or, on the other hand, an excitation to increased activity expressed in peristaltic or anti-peristaltic waves.

" When the bladder is omr-distended it is impossible to open the ureteral mouths with the injected fluid."

Courtade and Guyon repeated these experiments on rabbits and also on dogs. Their work is discussed at length by Guyon in his Lecons cliniques sur les maladies des voies urinaires. In rabbits the reflux into the ureters occurred in 20 out of 32 times, but in dogs only 5 out of 25 times — or strictly 5 out of 38 trials. Guyon says in substance : " In the rabbit as in the dog, entrance into the ureters is only forced when the walls of the bladder are put in a state of resistance from the beginning of the injection. In both animals, every time that the bladder remained flaccid and was passively distended the ureter was not invaded, no matter how much fluid nor how much pressure was used.

" It is established that early tension of the bladder-wall produced by injection of a small quantity of liquid is the condition when the reflux can be observed. No other condition can accomplish it.

"In the five positive experiments the reflux showed itself after tlie first injection, but never after the second. Once put on its guard, the vesical muscle does not allow itself to be surprised again.


106


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 86.


Hydraulic Urethral Dilatation. — I have had au opportunity to observe the eifect of hydraulic pressure on a urethral stricture in two cases. I may say that it is very easy to


When the contractions of the bladder are total and active, rather than favoring the entrance of the vesical contentB into the ureter, it opposes it.

"The mechanism depends on the fact that there is a band of muscle-fibres surrounding the ureter and wall of the bladder which act as a sphincter, and if these are cut without disturbing the relations of tlie ureteral mouth at all, the reflux can then occur as regularly in the dog as in the rabbit.

" However, we can scarcely fear the refluxin man, provided the intraparietal part of the ureter lias not been changed anatomically." But then, in the face of that statement, on the same page Gnyon says :

" This possibility of reflux is a new objection to the employment of irrigations in cystitis, and is also an indication not to allow painful bladders to strive against their contents.

"With a pathologically accentuated sensibility the bladder is put in tension by very small quantities of liquid.

"The abstention from lavage, the retained catheter, and perineal and suprapubic drainage receive new justification, and physiology again asserts the preponderating role of the tension of the bladder."

Guyon says the reflux is brought about by a sudden early pa.ssive contraction of the bladder, occurring when very little fluid has entered the bladder ; and again, if the contraction brought about by the injection of the fluid is active and total, i. e. involves the whole bladder, the reflux cannot occur.

The only conclusion therefore is that this precocious contraction must be a partial one in which the muscular fibres which surround the ureters in the bladder-wall have not taken part. The ureters are probably asleep with their mouths open, according to Guyon, and "once awalsened the bladder cannot be again surprised."

When we consider that Guyon only succeeded in obtaining the reflux 5 times in 38 cases, and that then it was often only on one side; that the narcosis might have been responsible for the "drowsy condition" of the bladder-muscle and ureteral sphincters; that it occurred every time in the thin bladders of rabbits, only 5 times in 38 in the thicker bladders of dogs, and that the human bladder is considerably thicker than that of dogs ; thatin the numerous cases of cystitis which have been treated by irrigations we have never seen any symptoms of renal pain or infection, we are led to believe that the aforesaid experiments are inconclusive, and that the ureteral reflux does not occur in man, or even in dogs, except under peculiar and exceptional circumstances. We even wonder how Guyon and Courtade could distinguish a " passive " partial contraction of the bladder which did not involve the ureteral sphincters from an "active total contraction." The operation of dividing the sphincter of the ureter, situated as it is behind the bladder, without weakening the bladder-muscle or injuring the mucous membrane of the ureter, is probably the most delicate operation ever performed.

We can justify our practice of forced dilatation by the assertion of Lewin and Goldschmidt that when the bladder of the rabbit, even, is over-distended, it is impossible for fluids to get into the ureters. According to all these investigators, then, a small amount of fluid injected slowly may bring about ureteral reflux with fatal kidney infection, while a large amount rapidly forced in cannot enter the ureter. Accepting these assumptions, then our method of flushing bladders with copious irrigations is much less dangerous than Guyon's favorite instillations of small amounts.

When we consider, then, the great uncertainty of the existence of a ureteral reflux in man, and the very satisfactory results we have had with forced dilatation in cases of contracture of the bladder, we are constrained to think that their use is not contraindicated.


force fluid into the bladder through strictures of very small calibre.

In one case — a man convalescing from an operation for cranial abscess — the stricture of fifteen years' duration would not admit the passage of the finest bougie. Urination was extremely difficult, so much so that patient was obliged to squat on the floor and to strain so severely that a hemorrhoidal mass as large as the fist would be forced out.

His bladder was easily irrigated with an elevation of about ten feet, and after this had been done several times daily for two weeks he could void his urine while lying on his back in bed without an extrusion of the piles. The stream of urine became considerably larger.

Another case of moderately tight stricture showed decided evidence of dilatation after a week's treatment. I do not mean to advise this in preference to urethrotomy, but in cases of stricture complicated by severe cystitis, where operation is often followed by absorjjtion of septic materials, chill, fever, and occasionally fatal pysemia, preparatory lavage of the bladder in this manner is certainly indicated.

When a patient is discharged after dilatation of a stricture the daily use of this method would probably tend to prevent the recurrence of a stricture, and be of benefit to any bladder infection which might coexist.

After perineal section, where it is desirable, on account of cystitis, to continue bladder irrigations, I have found it very easy to force the fluid into the bladder by simply closing the perineal wound with the fingers, or if the ojieniug is small, by the pressure of a sponge covered with rubber protective.

In cases of enlarged prostate, fluid may be easily forced into the bladder without a catheter, but the same trouble is encountered in evacuating it as with the urine. After suprapubic operation, however, it is a very valuable procedure and the most thorough method of cleaning the bladder and combating infection. By closing the suprapubic sinus with a plug or the finger the bladder may be dilated, thus curing or averting one of the most undesirable effects of suprapubic drainage, viz. contracture of the bladder.

Vesical Calculus. In several cases of stone in which the bladder was small we have employed forced dilatation with very gratifying results. In a case now in the wards, who on admission had a severe acid cystitis with a staphylococcus pyogenes albus infection and a bladder which when fully distended held only about 140 cc, we were able in a week to increase the capacity to 400 cc. This was followed by a marked improvement in the cystitis and greatly decreased frequency of micturition. The bladder was then easily reached by suprapubic operation, and the bladder infection so much bettered that it was thought advisable to suture the bladder after removal of the calculus. We consider such preliminary treatment very valuable where infection or contracture is present.

Atony of the Bladder. The possibility of benefiting an atonic bladder by alternate distension and evacuation, a form of massage, so to speak, for the weakened muscle, is shown in the following case (VII).

An old man, paralytic, constantly requiring catheterization from paralysis of bladder, after a time began to regain use of


May, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


107


limbs, but the power of expelling urine did uot return, probably from atrophy and lessened tonicity of the bladder muscle.

Systematic forcible distension of bladder with iluid was begun and given twice daily. At first it seemed that the catheter would be required to withdraw fluid, but its use was deferred, and after a few minutes, to our satisfaction, the fluid was expelled. After a few weeks of treatment the tonicity of the bladder was practically restored and the patieQt required no further catheterization. The following case also shows the marked benefit obtained.

Case VIII. — Syphilis of cord, paraplegia, paralysis of bladder, catheterization, cystitis. Cure of paraplegia under iodides, but contracture of bladder with incontinence persisting. Capacity of bladder 65 CO. Urination every 20 minutes. Under forced dilatation capacity increased to 500 cc. and interval to 4 hours. Almost complete restoration of muscular power of bladder.

R. 0., age 4G. Cigarmaker. Admitted Sept. 17, 1897.

Complaint. Frequent micturition, every fifteen minutes.

Past History. Gonorrhoea twice, but no bladder trouble with it. Syphilis 15 years ago. Positive history of secondaries and tertiaries. Took K. I. very irregularly for three years, after which cutaneous lesions disappeared. In 1891 pains and sores returned, and again he took treatment irregularly.

In 1895 had a stroke of paralysis. Girdle sensation around body at level of navel, left leg completely paralyzed, right only partially. Retention of urine, incontinence of fseces. After being catheterized for 2 months began to h ave incontinence of urine. Urine became very


foul. Patient took heavy doses of K. I. and in two months power of limbs began to improve, and in 4 months he could walk fairly well. Bladder trouble did not improve, but urine continued to be voided involuntarily in small amounts, and patient has worn a rubber urinal to catch urine.

Status Prmsens. Voids urine every 10-15 minutes. No pain or dysuria. Wears urinal by day. Catbeterizes himself three times at night, as by so doing he does not void so frequently. After catheterization can hold urine for half an hour.

Rectum. Has fairly good control of bowel, except when faeces are very liquid.

Examination. Knee jerks increased activity, muscular power of left leg weaker than right. Prepuce, glans and skin of penis excoriated from use of urinal. Meatus small. Searcher passed easily into bladder. No stricture. No prostatic enlargement. Record shows that 40 cc. is largest amount of urine voided, and generally 20 cc. Bladder small, capacity 40 cc, walls rough, manipulation of searcher causes hemorrhage. Urine withdrawn acid and very purulent.

When forcibly distended until painful bladder holds 65 cc; on second trial 70 cc. forced in; Distension causes hemorrhage. Two days later 120 cc. could be forced in with considerable pressure. The bladder in this case is more easily dilatable than others. Bladder is forcibly distended with fluid four times daily without catheter by hydraulic pressure. K. I., which patient has been taking regularly before entrance, is continued.

Note. — Following this treatment the improvement of bladder was marked, capacity and interval rapidly increased, and with it the patient regained more and more control over micturition.

The following table shows the rapidity of improvement :


Day of Treatment.


Capacity of Bladder.

Largest amount

held on forced

distension.


Urine.

Largest amount

voided at one

time.


Interval.

Average time

between

urinations.


Remarks. — Case VIII.


Sept. 18.


130 200 370 330 340 435


40 100 100 100 140 175


Paralysis 2 years ago. Retention of urine. Catheterization. Cystitis. Incontinence of urine. Gradually increasing contracture of bladder. Urine now voided involuntarily every twenty minutes. Forcible irrigations begun, four times daily. Thompson's fluid.

Much improved.

Power of voluntary control returning.

Voids urine more frequently at night than during the day.

Condition markedly improved. Can now hold urine often for three hours and void at pleasure. Has given up use of urinal. No more dribbling. Has not fully regained expulsive power of bladder. Has 130 cc. residual, but muscular tonus is improving daily. Patient became insubordinate and was discharged.


Feb. 3, 1898. Patient returns to genito-urinary dispensary asking to be treated. Has not been under treatment since he left hospital (several months ago). Bladder has retained its size, patient voids urine at will, no dribbling, but still has a moderate residual. Still uses catheter from habit. Urine acid, pus moderate in amount. Prostate not enlarged.

Feb. 26. Condition as in last note. Irrigation bag prescribed to irrigate bladder without catheter three times a day with boric acid solution. Instructed to discontinue catheter habit.

Feb. 28. Has discontinued catheter and finds that he can hold his urine 4 hours during day. Bladder holds about 500 cc.

Mar. 29. Patient has irrigated bladder with boric solution twice daily. Bladder holds 580 cc. During day urine is voided every 3^ hours in amounts varying from 70 to 130 cc. After voiding a residual of 100 cc. is present. Expulsive power of bladder still


defective. Still walks with a limp, rectal control not perfect, still taking iodides.

Remarks. — Tlie results obtained in this unpromising case are very satisfactory and show the improvement of muscular tonus and continence obtainable by the exercise of the muscle. The gain in capacity of bladder was also marked.

Technique of Irrigating the Bladder withotd Catheter. Articles Necessary. — An ordinary fountain syringe with tube about eight feet long, a conical nozzle which will fit tightly into the meatus but not injure the urethral mucous membrane, and a pole or other apparatus by which the irrigating bac may be elevated or lowered as desired. (A nail in the wall will answer the purpose.)


108


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 86.


The patient should lie on his back on a bed or couch which is covered by an oilcloth, with a basin between his legs. The operator stands on the right side, takes the penis between thumb and finger of his left hand, the sterile nozzle in his right. The foreskin is retracted, and with the bag elevated three or four feet, the fluid is allowed to play upon glans penis and meatus. The urethra is alternately distended with fluid and emptied to clean the anterior urethra, and the nozzle is then crowded tightly into the meatus, the bag raised to an eleviition of about seven feet, the penis being held just back of the corona so as not to compress the urethra, as shown in Fig. 4. Valentine's complicated nozzle and stopcock are unnecessary.

The urethra will soon become ballooned out and for a time the fluid will be seen to stop flowing through the nozzle, but very soon the sphincters will give way and a " purling " sensation be conveyed to the hand by the fluid flowing into the bladder. After the sphincters are overcome very little pressure is required to force fluid into the bladder, and it is best to lower to a height of four and a half or five feet, as too much pressure may produce spasm of the bladder and prevent dilatation.

As the fluid flows gently into bladder the patient will soon experience a sense of fulness and tiien of gradually increasing pain.

In cases of contracture where systematic dilatation is to be adopted, the distension must be continued until pain is very considerable and the patient tells you he cannot " stand any more." The tube is then squeezed to cut off the flow, the nozzle withdrawn, and the fluid, which is ejected with considerable force, caught in a half -litre glass or other receptacle.

The operation is repeated until the quart of fluid has been used.

The procedure is so simple that patients soon learn to conduct their own treatment. They always become intensely interested in the progress of the dilatation and vie with each other as to the amount of fluid and urine held.*

Solutions Used. — Very bland fluids are the most satisfactory in most cases. Best of all is Thompson's fluid, which is composed of borax, glycerine, sodium chloride and water. It is the most soothing preparation for any inflamed mucous membrane that we know of. Boric acid in 2 per cent, solution is excellent.

A very good plan is to use occasionally a stronger antiseptic fluid, such as silver nitrate gr. J to gi, or bichloride of mercury 1 to 150,000 solution, up to 1 to 50,000.

When four or five irrigations are given daily it is well to use one of these once daily, followed by a weaker solution.

Silver nitrate is especially effective where an ulcerative condition of the mucous membrane exists.


Up to a few months ago there was scarcely anything on the possibility of irrigating the bladder without catheter in American literature, but since the popularization of the so-called Janet method of treating gonorrbcea, it has been very widely employed. Janet deserves credit for the energetic way in which hehaslauded the virtues of copious irrigations of dilute antiseptics, but the only originality is in the substitution of permanganate for bichloride in Dr. Halsted's method.


Very little internal treatment is of value. Boric acid or salol

in gr. v-x doses may be' given if the urine is alkaline, and citrate of potassium when hyperacidity causes much burning.

The reaction of the urine in cystitis depends almost entirely on the character of bacterium present, and it is irrational to attempt to change its reaction by internal drugs.

As shown in these cases, the urine becomes acid as the fjladder inflammation begins to subside.

Contracture of the Bladder. JIoiv ]wodured. — As in inflammation elsewhere, there is at first a proliferation and infiltration of round cells, which as time goes on become more and more spindle-shaped and finally form fibrous tissue. Ulcerative areas in the mucous membrane also lead to the production of scar tissue, with its inherent tendency to contract. The inflamed mucous membrane, irritated fjy the presence of urine,, expels it frequently; the bladder is therefore never fully distended and offers no resistance to the contraction of the scar tissue, and contracture results. In this process the blood supply of mucosa is greatly interfered with, and the mucous membrane is thrown into folds and pockets which retain the purulent exudate, thus adding to the inflammation.

The effect of forced dilatation with fluids is probably as follows:

Irritating secretions are washed away.

The individual bundles of fibrous tissue are separated or loosened, allowing increased vascularity.

Folds and pockets of mucous membrane are smoothed out. Ulcers are stretched and cracked, allowing new blood-vessels to grow out, in precisely the same way that leg ulcers are cured by scariflcation. The bladder muscle is exercised and the tone is improved. The mixcous membrane cleaned, stretched, and with increased vascularity, is given a chance to throw ofl: the inflammation.

In a normal empty bladder the epithelium is several layers thick, but when fully distended is said to be only one layer thick. Dilatation of an inflamed bladder therefore gives the antiseptic fluids a better chance to reach the disease.

Conclusions.

Cases II, V, VI, and VIII may be taken as examples of what can be accomplished toward dilating a contracted bladder and restoring the normal frequency and power of urination. The improvement in case V is really wonderful.

A review of these cases shows :

That it is possible to restore the capacity of a bladder contracted by chronic inflammation of the worst character, by systematic distension by hydraulic pressure.

That such dilatation has a most beneficial effect on the vesical inflammation and muscular tonicity.

That the number of urinations daily may thus be greatly diminished.

That no ill effects are produced by considerable hydraulic pressure, and there is no danger of infecting the kidney.

One of the most striking features of the treatment is the rapidity with which patients improve. Pain present for years may disappear in a few days, pus and mucus diminish markedly, and strongly ammouiacal urine become acid in a short time.


May, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


109



EQUIPMENT FOR IRRIfJATIOX.S AT TIIK (4ENIT0-URINART DISPENSARY OF THE JOHNS HOPKINS HOSPITAL.

1. Bottles containing stock solutions of Bichloride of Mercury, Silver Nitrate, Boric Acid and Thompson's Fluid. 3. Copper reservoir of sterile water kept at proper temperature by a Bunsen burner.

3. Printed formula' for making up various irrigations.

4. Irrigators suspended from pulleys, 13 feet above the tloor, the right hand for anterior urethral and the left hand for intravesical irrigations .5. Halsted's table for Geuito-Urinary work.



METIIon OF HOLDINfi PENIS AND NOZZLE FOR BLADDER IRRIGATIONS.

The tube passes between thumb and fori-liny-cr so the flow cnn be regulated at will. The nozzle is held firmly with the other lingers.


110


JOHNS HOPKINS HOSPITAL BULLETIN.


[\o. 86.


And yet a late text-book on geni to-urinary diseases says as follows :

" The theory that the capacity of an inflamed bladder can be increased by dilatation is contrary to physiology and anatomy. To attempt by forced injections to relieve frequent micturition cannot be too strongly condemned."

Discussion.

Dr. CuLLEN. — I have been much gratified with Dr. Young's method, and it is certainly destined to be of great service not only in the male but also in the treatment of cystitis in women. Last summer we had quite a number of cases showing varying degrees of vesical inflammation, and I had the opportunity of testing the efficacy of the treatment as outlined by Dr. Young. In all, with the exception of one case, much improvement followed, and subsequent examination proved that this patient was suffering from tuberculosis of the bladder, as demonstrated by sections of the bladder wall. One marked case is especially worthy of mention.

A patient (Gynecological No. 5351) was admitted to the Johns Hopkins Hospital on June 25th, 1897, complaining of frequent and painful micturition. Eight years ago she gave indefinite signs of renal colic, and the urine contained blood for two months, since which time the urine has been bloodtinged on an average every three months for 3 or 4 days, and during the'greater part of the eight years micturition has been frequent and painful.

On admission the patient micturates very frequently, at times every few minutes, and has to rise eight or more times during the night, often so frequently that she no sooner gets to sleep than the desire to micturate wakes her up. The pain is most severe after the bladder is empty, and she feels as if the viscus contains a stone.

Examination wonder ether, June 26th. The urethra easily admits a No. 11 cystoscope. The base and the anterior surface of the bladder are red, injected and covered by whitish yellow patches which on removal are found to be composed of mucus and calcareous particles. On examining more closely these areas are found to be covered with ulcerations, and the calcareous particles occupy the centres of the excavations. The lateral bladder walls are normal, and bimanual palpation fails to reveal any calculus.

The patient was treated by irrigations with HCl, to dissolve the calcareous pai-ticles, and the hydrochloric acid was removed by washing out with boracic acid solution, and after the bladder was emptied, by the application of 10 per cent, ichthyol.

Jujie 29/!/*. Patient being in knee-chest position, the bladder was irrigated with 1-1000 HCl, followed by boracic acid solution and then 10 per cent, ichthyol, to ensure the widespread application of which Clark's vesical balloon was introduced. The distension caused by the rubber balloon gave great pain.

June SOth. Topical application of ichthyol to the bladder after irrigation with HCl and boracic acid solution was made.

July 2nd. Irrigation with HCl and boracic acid was repeated. The treatment is very painful, but the patient says that she ah'eady feels improvement. Frequent irrigations were


employed, and on July 10th the following note was made: "All the calcareous particles have disappeared, and the mucosa, while still red and injected, has materially improved. The solution of HCl was now discontinued, and the bladder was washed out three times a week with the boracic solution, and then 10 per cent, ichthyol applied with or without the balloon."

July 16th. The posterior and anterior surfaces of the bladder are much imjiroved, but on examination of the base just within the inner orifice of the urethra several white calcareous patches are seen. With the patient in the kneechest posture the HCl had evidently not come in contact with those areas. After several irrigations with the patient in the dorsal position these disajipeared.

July 'dlst. The bladder has not been treated for eight days and a marked improvement is seen. The areas of ulceration at the trigonum are still covered by pus, which can, however, be easily removed by the applicator.

As the bladder mucosa did not assume its normal ajipearauce as rapidly as we had hoped, dilatation of the bladder was commenced, with forced irrigations of boracic acid. The following amounts were injected each day :


ugust Ith,


160 cc.


A


ugu


t 13th,


250 cc


5th,


170



"


I4th,


260


" 6th,


180



"


15th,


270


7th,


190



"


18th,


180


8th,


200



« 


20th,


200


9th,


210



((


21st,


210


10th,


220



a


22ud,


200


11th,


230



a


23rd,


250


12th,


240






It will be seen that the dilatation was progressive up to the 15th, and then after a cessation of three days the bladder did not contain as much, but that in a very short time the maximum amount was again nearly reached. In this patient the amelioration of the symptoms was most marked. Micturition became less and less frequent, and the urine could be held from two to four hours. The pain likewise ceased, and she rose once or twice only at night.

On leaving the hospital on September Sth the patient felt comparatively well and had practically no trouble with the urine. I received a letter from her three months afterward and learned that she was doing her home-work and was feeling well. (See charts of cases appended).


THE JOHNS HOPKINS HOSPITAL BULLETIN.

The Hospital Bulletin contains announcements of courses of lectures, programmes of clinical and pathological study, details of hospital and dispensary practice, abstracts of papers read and other proceedings of the Medical Society of the Hospital, reports of lectures, and other matters of general interest in connection with the work of the Hospital. It is issued monthly.

Volume IX is now in progress.

The subscription price is $1.00 ppr year.

( omplete set (Vols. I-VIII), bound in cloth, for $13.00.


Mat, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


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112


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Mat, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


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114


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 86.


A CASE OF CARCINOMA METASTASES IN BONE FROM A PRIMARY TUMOR OF THE PROSTATE.

By Stdney M. Cone, M. D., Assistant in Surgical Pathology, The Johns HojjMns University.


Von Eecklinghausen' writes of osteoplastic changes in bone accompanying metastases from primary carcinoma of the prostate. He compares the changes with fibrous ostitis and osteomalacia of bone, and makes many valuable additions to our knowledge of the gross and mici'oscopic structure of bone in disease. He records five cases of his own and refers to one case of cai'cinoma of the prostate with subsequent metastases in the vertebrae — that of Sir Henry Thompson.^ This case is reported in full in the Transactions of the Pathological Society of London, in 1854, Vol. V, p. 204, with a pathological report by J. Hutchinson. Saase' has recently reported a similar case and gives a comprehensive view of the work of Von Eecklinghausen in this report.

The case I am going to report does not differ in any essentials from those previously reported, but is interesting as confirming several very important points in the pathology of bone, and discrediting the existence of primary carcinoma of the osseous system.

The patient, W. B. M., aged 75, white, was admitted to Dr. Halsted's wards in the Johns Hopkins Hospital, in September, 1895, suffering with cystitis, and was discharged October 10th, improved. He returned December 26, 1896, complaining of a painful swelling over his right tibia : he also had symptoms of cystitis with incontinence of urine. Notes made at this time by Dr. Young refer to the great enlargement of the prostate and probable existence of a tumor. Careful examination excluded the existence of tumor of any other organs. On January 5, 1897, Dr. Halsted amputated the leg and the patient made an uninterrupted recovery, returning to his home in February.

The gross appearance of the tumor of the tibia suggested to the operator carcinoma. Sections were made at once after boiling and immediate decalcification in concentrated hydrochloric acid. The appearance of these sections suggested endothelioma. Even the later results of microscopic examination showed the pictures illustrating Marckwald's* article on " Jlultiple intravascular endotheliomas in the whole bony skeleton."

Not being sure of a primary carcinoma existing in the prostate, and disbelieving the existence of primary carcinoma in bone, Marckwald's explanation seemed to be a good one. He refers, however, to the ease with which his endothelioma might he mistaken for carcinoma. Von Recklinghausen likewise mentions how readily one might mistake one of his cases for endothelioma.

When seen at his home in July the patient was very much emaciated, having lost about 30 pounds in weight. He complained of pain in his back, chest and right hip. His urinary symptoms had improved under treatment. The patient died September 12, 1897.

Autopsy. A man of large frame, very much emaciated. The stump of the right leg is covered by a pad of dense scar tissue, otherwise the leg is normal. There are no external marks to indicate tumor formation, except a few dark moles over his back and abdomen (these existed foryears, according to the history). Onfirm palpation a nodule is felt at the right iliac crest within the pelvis. Another spindle-shaped mass can be felt over the second rib on the right side.

Examination of the abdominal viscera reveals no abnormalities except in the pelvis.where the prostate is found very much enlarged and adherent posteriorly to surrounding structures ; elsewhere it is sharply circumscribed. The prostate measures 6x5x5 cm. The


lateral lobes are symmetrically enlarged and measure 3 cm. in diameter. The middle lobe measures 3x1.5 cm. and seems continuous with surrounding structures.

Section of the lateral lobes shows a firm surface variable in appearance. There are bulging, gray, translucent areas and yellow, soft, expressible dots between the firmer, opaque stroma which makes up the greater mass of the gland. The middle lobe presents quite a different picture. It varies in different parts. The greater portion is soft, with a varying cut surface — yellow, soft, pus-like material being enclosed by a thin, opaque, fibrous stroma. The greater portion of this soft pulpy tissue is posterior, away from the urethra, and infiltrates the surrounding structures. The tissues about the middle lobe cannot be differentiated from one another, and no distinct pelvic lymphatic glands are to be seen, all being matted in a firm fibrous mass. The glands along the vertebrse are firm but do not show metastases. The prostatic and hemorrhoidal veins are plugged with phleboliths. The seminal vesicles are enclosed in a dense fibrous tissue.

The bones which show greatest evidence of disease are the second, third and fourth lumbar vertebra;, the second rib and the ilium. The vertebrie bulge laterally and anteriorly and can be easily penetrated by a knife blade. The rib presents a symmetrical spindle-shaped enlargement, bulging for the most part into the pleural cavity. It is covered by periosteum and pleura. The pleurae are adherent at this point. The bone is rough beneath the periosteum and can be easily penetrated. It measures at its greatest diameter 4 cm.

Section through the rib shows a stalactitic growth of bone into the pleural cavity, the plates appearing smooth and asbestos-like. The remaining bone is granular and presents no symmetry in its arrangement. Between the plates of bone is seen a soft white material in dots and fixed in a smooth, shining lining wall. There are cysts between the plates of bone just beneath the periosteum and in the granular bone. The lining wall of these cysts shows a thin, shining, smooth surface 1 to 2 mm. in thickness. About these cysts the bone in th e granular areas is denser than elsewhere. The appearance of the granular bone varies in color from a reddish to a dark brown and it contains lighter white dots. The bone is very friable. The stalactitic growths seem to be directly continuous with the granular central bone and push the periosteum ahead. There is no evidence of periosteal new-bone formation in the ribs.

The node on the ilium projects 1.5 cm. and has a diameter of 2 cm. It is covered by thickened periosteum. There is a central white, softer, fibrous mass surrounded by granular bone like that in the rib. The rim of the nodule is made up of plates of bone, asbestos-like in appearance ; these seem to grow from the periosteum. In this bone is seen the white tissue described in the rib.

The vertebrse show none of the flat plates of bone, but present the same granular new growth of bone seen in the rib and the ilium. There is no spongy bone with branching cancelli in any of the new growths of bone described.

An enlarged gland alongside the trachea is for the most part firm and darkly pigmented. It contains a well-circumscribed area, white in color (this proved to be carcinoma). There is a cystic dilatation at one end of the gland filled with a dark reddish fluid (this is microscopically a cyst lined by epithelial cells such as were found in the bone and prostate). One of the abdominal lymph glands attached to the vertebra is firm, whitish-gray in color and homogeneous on section.

Description of the Tmnor in the Tibia. — Six cm. from the internal malleolus and on the.anterior aspect of the tibia, lying under the


May, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


115


periosteum, is a bulging tumor measuring 4 cm. in diameter. The shaftof the bone beneath the bulging mass is eroded, and the tumor seems continuous with a mass filling the medullary cavity. This medullary mass is an irregular mixture of bony spicules, hemorrhagic soft tissue, dark brown, soft, friable tissue with a sprinkling of gray, pin-head-sized areas throughout. This tissue fades inlo a more homogeneous, gelatinous, gray substance with intervening cancelli of bone, as it approaches the periosteum. The cortex is destroyed and the new growth spreads itself beneath the thickened periosteum, between itandthe dense cortical bone, aboveand below the place where it has found its way out. This bone is irregularly eroded where the tumor growth appears. Perpendicular to the shaft and situated between the light soft masses are bone lamellse, formed from the periosteum and intimately associated with it. Sections of this tissue fixed in boiling water and decalcified at once in concentrated muriatic acid, show epithelial cells forming a mosaic between the cancelli of new bone which are directly continuous with bands of connective tissue of the periosteum.

The microscopical examination of the prostate gland shows a great hyperplasia of the muscular elements in the lateral lobes and a proliferation of the glandular element. Some of the gland tubules are filled with loose masses of epithelial cells and alveoli of cells. Others are lined by one and two layers of cuboidal cells with a deeply stained round nucleus at the base. There is a clear refractive space or several retractile globules next the lumen. In the middle lobe all of the spaces are filled with cells in various stages of degeneration. Very few normal tubules are to be seen. Some few spaces are paved as if by a mosaic. There are few real tubules — it resembles more a mesh work of fibrous structure in which the tissue has condensed about large polygonal fenestras, most of which are full of cells, loose and in tubular arrangement. These spaces are uniform in size, being about the size of an air vesicle of the lung ; they are bounded by a condensation of the fibrous and muscular tissue of the prostate. Some of the spaces communicate with one another and give the appearance of a breaking-down of tissue by masses of cells which seem to invade the tissues at these parts.

In describing the microscopic appearance of the tumor as it appears in the prostate, bones and bronchial lymph gland, there are so many points in common that one description will suffice. Two appearances are presented by the tumor — first, a tubular adenomatous growth, cystic in places ; second, a conglomerate mass of cells which have lost theirarrangement in tubules. This latter gives the impression of round cell infiltration or lymphoid nodules — the cells having lost their cylindrical or cuboidal shape and the nuclei staining quite deeply and appearing homogeneous. At the outskirts of these masses there may be seen the type of cell lining the alveoli and cysts. The tubular form of the tumor is best demonstrated in the bones and the bronchial lymph gland, but can also be seen in the blood-vessels of the prostatic plexus and in the primary tumor. There is very little stroma between the tubules; the lumina are seldom seen patulous, for the cells project into them, cylindrical in shape, meeting one another in the middle line. The nuclei are situated at the base of the cells and are perfectly round, deeply staining and homogeneous in character. It is this situation of the nuclei which aids one in distinguishing the lumen from the delicate stroma which may be wanting. The character of the cells is that of the cell lining the prostate gland tubules, only they vary in shape as already stated. Another characteristic is the vacuolization and division of the clear zone situated toward the lumen into small clear spherical globules. These are sometimes so uniform in size as to give the appearance of "shadows" of red blood corpuscles filling dilated alveoli. It maybe stated here that some of the alveoli are seen filled with red blood cells, causing a close resemblance to endothelioma.

As to the individual sections it maybe stated that the bladder wall shows evidence of chronic inflammation, its walls being infil


trated with round cells and showing connective tissue increase; there is no carcinoma in its walls. In the tissue posterior to the prostate is a tumor filling the blood-vessels and invading the structures surrounding them. The lymph glands show connective tissue growth, but no tumor in them. One of the largest vessels filled with the cells shows a peripheral mass of cells in tubular arrangement lining the vessel wall ; toward the central lumen and surrounding a blood clot are numerous cells, massed in such numbers as to give the appearance of round cell infiltration. In none of these sections are polymorphonuclears present. A gland attached to the vertebra shows a marked proliferation of its endothelium and formation of fibrous tissue along the lymph spaces ; there is no evidence of metastases here. The gland next the bifurcation of the trachea shows a branching network of tubules, lined by cuboidal and cylindrical cells, through a blood clot. Blood pigment is situated in the dense connective tissue about tlie gland. A cyst has formed at one end of the gland and is lined by cylindrical epithelium one layer deep ; it resembles the cysts in the bones.

For histological study the new-formed bone about the cysts in the rib is most interesting. The lining is of cylindrical cells on a thin fibrous tissue in which are scattered little areas of cells arranged in alveoli. The alveoli are more or less dilated in various stages of cyst formation. This same appearance is presented among the cancelli of new bone branching about the outer wall of the cyst. In fact, wherever there are new bone cancelli one sees tumor formation. The cells in these tubules come in contact with the bone — in places grooving the same. Commonly there is a fibrous tissue intervening between tubules and bone cancelli, and osteoclasts fill the grooves in the bone. The spaces between the cancelli, when not containing epithelial masses, are filled with a vascular connective tissue. The nodule in the ilium, besides showing the appearances of a tumor in the bone just described, presents a cartilaginous nodule in the midst of denser new bone formation. Even the dense bone contains tumor cells. In the cysts of tliis section is seen a homogeneous substance deeply stained with eosin and resembling colloid. The usual contents of the dilated tubules are granular with des-quamated cells.

The section of the vertebra presents dense new bone, poorly staining granular bone and free trabeculse in the midst of tubules of epithelial cells. Microscopic examination of the bone removed at the first operation shows a new growth of bone from the periosteum ; in the medulla there is evidence of necrosis of the old trabecular of the tibia, fragments lying free in the midst of the tumor and refusing to stain. Tubules of epithelial cells lie between the periosteal new-formed trabeculse.

Some of the observations of Von Recklinghausen which we were able to note in our case are of great interest. lie mentions the order in which carcinoma metastases occur in bonea as: vertebrse, femora and pelvis, ribs and sternum, humerus, flat bones of the skull, fibula, tibia, radius and ulna. Many interesting observations are made in the different cases described by him which make it seem valuable to mention his individual cases.

Case 1. The first case was in a man aged 75, who entered the hospital because of a large hard tumor of the right forehead ; it projected 15 mm. from the bone, and was not adherent to the skin.

The operation consisted in shelling out the tumor, which was easily done, even though it extended to the dura mater. The tissue of the tumor was reddish-white, and was typically alveolar, being made up of hollow tubules and cysts lined by cubical or low cylindrical epithelium.

"A marked vascular connective tissue with alveoli of the


116


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 86.


size and form found in the thyroid gland led to the diagnosis carcinoma and to suggest the primary lesion in the thyroid, like in a case described by Gohnheim." The ribs and bones of the skull at their points of thickening were no more easily injured than other boues, yet on the interior of them were found white prominences which proved to be carcinoma. At the trigone of the bladder was seen a flat elevation, made up of separate white pea-sized elevations covered by mucous membrane. The prostate was three times its normal size and surrounded by a bean-shaped connective tissue mass filled with carcinoma nodules.

New bone cancelli of finished or unfinished bone were found not only in the osteophytes outside the bone but also within the medullary spaces of the diploii and spougiosa. Some of these were old decalcified bone, others were new formed. (His methods for determining these points are contained in the same article.) The microscope shows the spicules in the frontal bone tumor to be a new formation and not old decalcified bone. There was great spindle-cell hyiierplasia in the spaces of the new bone. Sharply bound cell-nests were held iu real alveoli of the poorly fibrous and feebly cellular marrow tissue.

"The new bone formed plates about scattered carcinoma areas, not only as an evidence of reactive irritation at its border, like chains of outposts (guards) formed by the old tissue in the manner of an inflammatory proliferation against an invading enemy, but also as an integral part of the bone tumor even though it was a carcinoma."

In spite of the great ossification and absence of degeneration it was a case of multiple bone carcinoma arising from the prostate as the primary seat of the tumor. The reason for this was that all the tumors contained the type of epithelial cell found in the prostate, and especially because the lymph gland metastases followed the route which the " materia peccans " took from the prostate. It was carried by the blood to the bones alone. There would have been no examination of the other bones had it not been for the peculiarity of the tumor in the frontal bone.

Case 3. A man aged 77 years.

There were small nodules at the neck of the bladder. The prostate was hard. The lymph glands in the lumbar region were hard and contained a milky sap. Those about the jugular vein acted likewise. A cheesy gland was found at the base of the tongue. A string of lymph glands was on the left side of the prostate. A milky juice (carcinomatous) was expressed from the left lobe of the prostate, otherwise there was no degeneration or discoloration. Microscopically it resembled the first case. It was generalized in bone, but not iu the soft parts. " On palpating the smooth surface of the tumors in bone one got the sensation of rubbing a file covered by a cloth." Most of the tumors were covered by periosteum. A strong needle pierced the tumor but could not penetrate the surrounding bone. The impression was made that the tumor sprung from the medulla and became secondarily subperiosteal. The axial portions of the spongy bones were the parts mostly involved. The external tumors preferred the rough places on the bones, i. e. " where largest vessels came to the surface." One could have thought


of osteoma were it not for the microscopic examination. In all spaces, even in the densest bone, were strings and alveoli of cells iu mosaic arrangement as in Case 1.

In connection with this case the following points were noted: There were not two distinct diseases growing side by side, but the carcinoma caused the secondary hyperplastic ostitis by the active congestion awakened by its presence. Bone formatiou was evidenced by these facts :

1. Nuclei of spongy bone with the beginning tumor formation were present; 2. sclerosis and eburnation of the axial spongiosa existed; 3. the ribs and vertebra showed thickening within the affected areas ; 4. the cancelli took up new arrangements, forming stars and appearing as radii in the callus; 5. the osteophytic growths like those seen in spina ventosa.

Case 3. A man, aged 73. Primary carcinoma in the prostate, secondary to the glands along the vertebral column, lungs and bones.

There were white areas in both lobes of the prostate and infiltration of the walls of the seminal vesicles. The areas iu the bones appeared white and yellowish-white, and owing to the ill-defined boundaries gave the impression of an " infiltrating growth." Osteosclerosis and osteoporosis went hand in hand. Besides the femora, humeri, iliac bones and vertebra?, the spine of the scapula was also involved. The microscopic appearances were the same as iu the other cases. In the lymph glands it was not easy to show alveolar and tubular arrangement of the cells on account of the poor connective tissue framework ; one might have diagnosed sarcoma from these sections. " The lung metastases were due to reti"ograde transport from the bronchial glands."

Case 4. A man, aged 76. Carcinoma of the prostate with metastases to the pelvis, vertebras, ribs and femora, and doubtful carcinoma of the abdominal lymph glands. The prostate tumor measured 55x30 mm. and resembled a venous angioma.

Case 5. A man, aged 74. Carcinoma of the prostate with regionary metastases to the ureter, bladder and glands; miliary carcinoma of the serous membranes ; osteoplastic carcinosis. There was considerable infiltration of the tissues of the pelvis. The prostate was atrophic, measuring 35x20 mm., was hard and white and smooth on section. The glands in the axilla were involved.

Case 6. A skeleton preserved iu the museum and described by Lobstein. The conclusion is drawn that it was a case of carcinomatous ostitis probably arising from a primary tumor in the prostate. The conclusion was made from the appearance and location of the osteophytes and endosteal bone formation, together with certain points made by Lobstein from the fresh specimen.

Some of the points peculiar to bone carcinomas obtained from the above cases were summarized under four heads :

1. These were infiltrating in character and because of this resembled inflammatory changes. Because of the diffuse growth the term carcinomatous ostitis was justified.

3. The new boue formation was prominent, the destructive character of the tumor was in the background.

3. The exostoses were seen at the exit of the vessels, while in osteomalacia the ligaments and muscle attachments were preferred.


Mat, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


117


4. The begiuuiug of the carcinoma was within the bone and broke through from the medulla.

Comparing the changes in this series of cases with those in metastases following carcinoma of the breast, the author mentioned that the contour of the metastases in the latter is usually sharp, but when they become infiltrating, osteoplastic changes occur. Prostatic carcinoma will probably be found to be the cause of general bone carcinosis as often in man as is the mammary carcinoma its origin in women.

It is hard to make out carcinoma in the prostate with the naked eye; the tissue does not degenerate much.

Sir Henry Thompson's case was a man aged 60. The prostate gland was involved in a growth about the size of an orange; some of the adjacent glands were also infiltrated. There were " encephaloid " growths along the lower dorsal vertebrje.

Hutchinson's report on the case is quite full. He refers to the soft creamy material infiltrating the prostatic tissue. A lymph gland on the posterior surface of the bladder presented on section the same creamy material which showed microscopically the same appearance as that from the prostate. In the spinal canal attached to the lamina of a lumbar vertebra was a mass the size of a filbert enclosed in a dense fibrous envelope. This tumor presented the same appearance as the lymph gland except that "it was less succulent." The involvement of the bones seems to differ from the cases described by Von Kecklinghausen in not being infiltrating in character. Saase before giving his case discusses the origin of carcinoma in bone ; he quotes V^ou Recklinghausen's work at some length. The case reported was a man aged 61 years. The diagnosis was not made during his life. The prostate was twice its normal size; pressure expressed a grayish white sap from its cut surface. One of the lymph glands of the pelvis showed metastases ; these were located in the hilus, none were in the cortex. The vertebrae cut with ease; the femora were sclerosed in part and were spongy and friable in the lower half. The microscope showed between cancelli of bone cylindrical cells pressed together. No stroma was visible, it being substituted by cancelli and plates of new bone. He differs with Von Recklinghausen,' who thinks the origin of the bone tumors to be only from the marrow. The route of the metastases suggested a vascular origin of the tumor, i. e. that it was an endothelioma or that the primary tumor was sarcoma.

Von Recklinghausen points out the fact that the tumors of the prostate very readily get into the blood-vessels and spread in this way. Cohuheim' made similar observations on tumors of the thyroid ( Virch. Arch., No. 08), and two years later (1878) Winiwarter made the statement, " the breaking of carcinomas directly into the veins is more common in thyroid carcinomas than any others. Very often a general infection occurs without intermediate lymph gland involvement. It reminds one more of a general development of sarcoma." Middledorpf," in writing of the bone metastases from thyroid carcinomas, refers to Von Eiselsberg's work and corroborates Cohuheim's view that the tumor grows directly into the veins of the thyroid.

• Those who believe in endothelioma in bone have no difficulty in explaining the fact that the bones are involved with


out a necessary involvement of the lymph glands. Some go so far as to oppose the diagnosis of carcinoma in cases set down as such long ago by such men as Von Recklinghausen. Ruuge's' case, reported in Virch. Arch., No. 66, is a notable example of this fact. It involved the atlas and axis of the spinal column and was diagnosed by Von Recklinghausen as carcinoma. Driessen" (Ziegler's Beitrage, Vol. XII, 1893) calls this an endothelioma. He gives a fair expose of both sides of the subject and reports a number of adenomatous-looking growths of the bones which are endothelial in origin.

The case reported by MarckwakV as multii^le endothelioma in many of the bones shows numerous points of resemblance to the carcinomas described. The nodules are soft, brown, splierical and seem to originate in the medullary canal and ])ierce the bone, pushing the periosteum ahead. New bone cancelli are formed in the outgrowths. There is also a dense new bone formation in the medulla and periosteum. There are regular rows of cells, rich in protoplasm and with a large round nucleus. There is little stroma and the whole suggests carcinoma. Red blood corpuscles fill spaces between the epithelium, and these spaces widen greatly in places. Some of the cells are cylindrical and show a broad protoplasmic border next to the lumen. There is no degeneration to be seen. The greatest involvement is in the vertebrae, sternum, ribs and pelvic bones; the skull is also involved. Marchand" reports a case of cylindroma of the antrum of Highmore. In this case the lymph glands too were involved. The tumor resembled " the so-called bone carcinomas."

Against the endothelioma idea may be stated the fact that frequently small non-suspected primary foci of carcinoma have been found where least suspected. See for instance Cohuheim's case of goitre giving metastases, and Von Recklinghausen's remarks on the small size of the tumors of the prostate which can give metastases. Geissler' cites a case of carcinoma of the scapula excised for a primary bone sarcoma, whereas the autojisy revealed a carcinoma of the bladder, the primary growth.

If one were to depend on the shape of the cell and character of its nucleus in differentiating an endothelial growth from one of epithelial origin it is easily conceivable that he could readily err. Hansemann" states that the endothelium in ordinary proliferation looks like epithelium. It becomes cubical and cylindrical and may not have intercellular substance. He can well understand the difficulty Volkmann might have in convincing those not disposed to believe his views about endothelioma, yet he agrees with him. One need only see the diagrams of the capillaries of the uterus of the bat pictured in Bohm and Davidoff's histology to see how confusing this distinction between endothelium and epithelium may become. Orth in his Pathologisch-Anatomisclie Diagnostik states that by increase in size a hyaline swelling of the endothelium of the greatly multiplied vessels may thei-e appear gland-like canals. These appear in sections as if cut in various positions, causing it to resemble gland very closely.

The literature on the subject of endothelioma is too extensive to bring into the bounds of this paper. The work on the tumors of the parotid promises the best field for clearing up this subject.


118


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 86.


This case and those referred to lead us to make the following conclusions:

1. Tumors like carcinoma in bone, without an evident primary focus, must lead one to suspect prostate or thyroid.

2. Endothelioma and carcinoma are not readily distinguished from one another.

3. Statical and traumatic influences are potent in locating the metastases.

4. The new hone formation and location of the metastases are significant of carcinoma of the prostate.

5. The metastases occur by the veins.

6. The organs are rarely the seat of metastases.

7. The pelvic lymph glands may not be involved.

8. Very small nodules of carcinoma may give rise to extensive metastases.

9. There is an extensive new bone formation (osteoplastic carcinosis).

It is due to the kindness of Dr. Branham that we were enabled to get an autopsy and thus prove the origin of the disease. I wish to thank Dr. Liviugood for performing the autopsy at the patient's home.

Bibliography.

1. Von Eeckliughausen : Festschrift zu Rudolf Virchow, 1891.

2. Thompson : Transactions of the Path. Soc. Lond., Vol.V, p. 204.

3. Saase: Arch, fiir klin. Chir., No. 48, p. 593.


4. Marckwald: Virch. Arch., No. 141.

5. Runge: Virch. Arch., No. 06.

6. Driessen: Ziegler's Beitriige, Vol. XII, 1893.

7. Geissler: Arch, fiir klin. Chir., Vol. XLV, p. 704.

8. Cohnheim: Virch. Arch., Vol. 68.

9. Hansemaun: Die mik. Diag. der bosartigen Geschwiilste. Berlin, 1897.

10. Middledorpf : Arch, fiir klin. Chir., Vol. XLVIII, p. 501, 1894.

11. Marchand: Ziegler's Beitriige, Vol. XIII.

Description of the Diagrams.

I. Periosteal new bone with thickened periosteum and tumor.

a, thickened periosteum.

h, carcinoma in the periosteum.

c, new formed bone caucelli of periosteal origin.

d, carcinoma between new formed bone cancelli.

e, degenerated carcinomatous area. /, a blood-vessel.

II. From the medullary cavity of bone.

«, red blood corpuscles filling a dilated alveolus. h, new formed bone.

c, tumor showing cuboidal and cylindrical cells and cystic dilatation of alveoli.

d, degenerated centre of a carcinomatous area.

e, fibrous tissue between the bone caucelli.


GLOSSITIS IN TYPHOID FEVER, WITH REPORT OF A CASE.

By Thomas McCrae, M. B., Assistant Resident Physician, The Johns Hopkins Hospital.


ITie cases of the occurrence of this complication iu typhoid fever reported iu the literature appear to be very few, the condition itself being a comparatively rare one. In over 700 cases of typhoid fever treated in the Johns Hopkins Hospital this is the first time that this condition has been found. In the case to be reported it is of especial interest, iu that it occurred during convalescence from the original attack and ushered in a relapse.

There are numerous references by the older writers to the association of glossitis with the eruptive fevers. Thus, Kerr, writing on glossitis in a Cyclopedia of Practical Medicine published in London in 1833, speaks of "tumefied states of the tongue which occur in typhoid and various fevers attended with an atonic condition of the system." There are numerous references to glossitis coming on during the course of or in convalescence from acute febrile diseases. Clark in his work on the tongue says, "Indeed, slight attacks of intercurrent glossitis are not infrequent in the course of erujitive fevers." But neither he nor Butlin in his " Diseases of the Tongue " refers to any instance in which it occurred with typhoid fever. No reference to the association of the two was to be found in any of the text-books of medicine. Hoffmann in his book on the pathological conditions in typhoid fever does not speak of


it. Sorel' in his statistics of 871 cases does not report its occurrence, nor Freundlich in a statistical report of cases in Freiburg. Eenou' and (lallety-Bosviel,' in special articles on the tongue and mouth iu typhoid fever, do not mention glossitis. The reports of Berg,' Jenner' and Studer," embracing the reports of the examinations of 1984 cases, do not speak of it. Ilolscher," in the statistics of 2000 cases, speaks of "purulent infiltration " of the tongue iu three cases, while Dopfer' in 927 cases found the same condition in two cases.

Nichols' has reported a case of " septic infection in typhoid fever" in which two days before death swelling of the right half of the tongue was noted. The case came to autopsy and the tongue was found red, swollen and glazed in its right half. On section it showed haemorrhages and small abscesses. Cultures yielded streptococci, staphylococci und the colon bacillus. This may perhaps be the same condition as Ilolscher aud Dopfer have spoken of as "purulent infiltration" of the tongue.

The case reported is from Dr. Osier's clinic iu the Johns Hopkins Hospital :

W'. U., aged 27, white, dredger. Admitted on November 27, 1897, with a mild attack of typhoid fever. The previous history was unimportant. The attack was quite characteris


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tic — fever, rose spots, enlarged spleen and the Widal reaction all being present. The temperature fell to normal on the IGth day and he made an uninterrupted recovery. He was discharged on December 31, 1897, on the 37th day of his disease, and after 22 days of normal temperature. He seemed perfectly well on discharge.

On January 3, 1898, the fourth day after leaving the hospital, he was re-admitted, comjilaining of pain in the throat with soreness and swelling of the tongue. He gave a history of having felt well until January 2ud, when he had a chill, soon followed by pain in the head and throat. Swelling of the tongue and behind the jaw accompanied by pain on swallowing also came on. There was no history of the taking of mercury or the application of any irritant. His condition rapidly grew worse until his admission.

On admission — temperature 104.2°, pulse 100, face flushed, the neck full and swollen at the angles of the jaws. The mouth presented a striking picture. The tongue was much swollen, protruding between the teeth and preventing the closing of the mouth. There was a profuse constant flow of saliva. The tongue was red, inflamed, symmetrically enlarged, markedly tender and somewhat indurated as far back as could be felt. No spot of softening could be found. The throat could not be seen. Swallowing was difficult. Cultures were taken from the left half of the tongue by Dr. Gwyn. Bleeding followed the punctures. On the following day the swelling was less and the left half was rather smaller than the right, due probably to the bleeding following the punctures. Two days later there was less swelling, less pain and the mouth could be closed. Three days later the tongue was practically normal.

The temperature, which on admission was 101.2°, fell to


normal on the day after admission and then rose gradually each day until it reached 101° on January 7tb. With this he had a typical relapse, with continued fever, rose spots and enlarged spleen. This lasted for about two weeks and was mild throughout. The temperature fell to normal on the 16th day of the relapse and he was discharged well on January 26th. The cultures from the tongue were negative.

In this case after 31 days of normal temperature the glossitis seemed to be the first symptom of the relapse. The relapse itself was mild save for the severe onset, and as soon as the swelling subsided the patient had no further trouble in swallowing or distress of any kind. The diminution of the swelling in the left half of the tongue after the blood removed in taking the cultures supports the value of the treatment advised in severe cases, namely, free incisions into the substance of the tongue.

References.

1. Sorel : Bull, et mem. soc. med. d'hOp. de Paris, 1889, 3. s., 224-246.

2. Eenou : Bull. Soc. denied, d' Angers, 1875-76, n. s. 89-90, pp. 103-109.

3. Gallety-Bosviel: Oontrib. a I'etude des alterations de la bouche dans la fievre typhoTde. Paris, 1889, No. 233.

4. Berg: Deut. Archiv f. klin. Med., Bd. LIV, Heft 2 and 3, 1895, p. 161.

5. Jenner: Edin. Month. Jour.of Med., 1850, Vol. X, p. 311. G. Studer: Deut. Archiv f. klin. Med., Bd. XLIX, Heft 2

and 3.

7. Holscher: Miinch. Med. Wochen., 1891, pp. 44 and 62.

8. Dopfer: Miinch. Med. Wochen., 1888, p. 621.

9. Nichols : Montreal Medical Journal, 1896, p. 104.


PROCEEDINGS OF SOCIETIES,


THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Meeting of February 21, 1898.

The meeting was called to order by the President, Dr. Barker.

The Bacteriology of Yellow Fever. — Dr. Gko. M. Sternberg, of Wasliington. [Dr. Sternberg gave an interesting review of his bacteriological studies in yellow fever and illustrated his remarks by many excellent lantern slides. As the address was unwritten we regret that it cannot be reproduced. — Editor.]

Discussion.

Dr. Welch. — Dr. Sternberg has presented to us in a most interesting way the history and present status of the bacteriology of yellow fever. Incidentally he spoke of his observation that organs taken fresh from the body and at once wrapped in cloths soaked with sublimate solution frequently show within forty-eight hours development of bacteria in their interior. This is in accordance with our experience. Several years ago Dr. C 0. Miller in my laboratory removed


with antiseptic precautions from recently killed animals the liver, spleen, kidneys and other organs and threw them entire into solutions of sublimate as strong as 1 to 500. Often bacteria developed in the interior of these organs, especially often in the liver.

Dr. Sternberg's bacteriological studies of yellow fever are generally recognized as most trustworthy. He successfully disjiroved the claims of the numerous alleged discoverers of the specific organism of this disease. Dr. Sternberg's attitude of caution as to the acceptance of Sanarelli's bacillus icteroides as the causative agent of yellow fever seems to me entirely warranted in the present state of the evidence. It may be demonstrated that this bacillus is the cause of the disease, but the matter is still open to debate. Weak jioints in the evidence thus far are the small number of cases of yellow fever examined by Sanarelliand the failure to demonstrate his bacillus in nearly half of his cases. His explanation of this failure does not seem to me entirely satisfactory. The results of inoculation of animals by this bacillus are regarded by Sanarelli as a main support of his conclusions, but suggestive and striking as these results are they do not suffice to warrant the statement that yellow fever has been produced exjierimentally by


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inoculation of Sanarelli's bacillus. The remarkable necroses of the liver, of wbich Dr. Sternberg lias shown photographs, may be caused by inoculation with many kinds of bacteria as well as by various toxins.

Probably the strongest argument at present in support of Sanarelli's bacillus as the cause of yellow fever is its agglutination by the blood of yellow fever patients, but here also further observations are needed.

Dr. Booker. — ^The interesting review Dr. Sternberg has given us of his work on yellow fever is a pleasant reminder to me of the time we worked together, in the pathological laboratory of this institution, upon our respective investigations on yellow fever and the summer diarrhceas of infants. Some of the illustrations Dr. Sternberg has exhibited to-night are familiar objects in my work, and it is interesting to note the points of resemblance of some of the toxic lesions and the bacteria found in the two diseases. His picture of the kidney might well be used to represent the condition of this organ in fatal cases of summer diarrha3a. Degeneration of tubular epithelium occurred in nearly all of my cases, and hyaline tube casts were found in the tubules in many cases. The form of degeneration he has represented for the liver in yellow fever I have not seen, but other kinds of degeneration of the liver are often found in fatal cases of summer diarrhoja. We frequently made comparison of the bacteria isolated from our cases, and among other bacteria which showed resemblance was a strongly pathogenic bacillus isolated by Dr. Sternberg from yellow fever patients in Decatur, and, at first, thought to be of considerable importance, which proved to be identical with bacillus a of my series. It is a liquefying bacillus, and causes diarrhcea convulsions, and death when injected subcutaneously in rabbits. When the identity of the two organisms was established Dr. Sternberg abandoned its study, and soon afterwards became interested in bacillus x, which he has just described to us, and which did not resemble any of the bacteria found in my cases.

Although Dr. Sternberg removed from the laboratory before the study of this organism was completed, I remember that he was greatly impressed with its importance, and considered it, even then, to be highly promising.

The rosette colony which he described as a rare growth for the colon bacillus isolated from his yellow fever cases was frequently seen in the cultures of the colon bacillus isolated from the feces of infants affected with summer diarrhoea, especially when the cultures were made in old gelatine.


NOTES ON NEW BOOKS.


Diseases of the Stomach. By John C. Hemmetke, M. B., M. D., Ph. D. (P. Blakialon, Sons & Co., Philadelphia, 1897.)

This large volume of 788 pages is prefaced by an introductory chapter in which Prof. Da Costa is quoted as having said that "books attract books, and, as a rule, any new work in any particular class has a striking familiar resemblance to those already published." The author, in justification of the publication of this work, remarks that "if this new contribution to the pathology and treatment of organic diseases of the stomach does not conform to Da Costa's generalization, it is not because of any premeditated


plan to make it different from other works on the same subject, but because a number of entirely new methods of diagnosis have entered into it, and because an attempt has been made to do justice to the work of American clinicians in this department." Attention is drawn to the extensive contributions made to our knowledge of the normal and diseased stomach and its functions by the clinicians, surgeons, pathologists, anatomists and physiologists of America.

The work of the pultlishers has been well executed, the paper and printing being excellent, while the figures and plates, which are quite numerous, have been well reproduced.

The subject-matter is divided into three parts, all of which are more or less closely related. In each division the various subjects are dealt with in detail.

Part I, which is subdivided into nineteen chapters, deals with the " Anatomy and Physiology of the Digestive Organs — Methods and Technics of Diagnosis." In the chapter on the " Histology of the Stomach " extensive quotations are made from the valuable contributions of Mall and of Bensley on this subject, and two beautiful colored plates devised by Mall on the block system for showing the vascular and lymphatic supply of the various coats of the stomach are reproduced.

The originality of the author is more amply illustrated in this than in any other part of the work. Among others, reference may be made to his method of intubating the duodenum to obtain the intestinal contents ; to his device for determining the capacity of the stomach by the use of a dilatable intragastric rubber bag having the general form of the stomach, the capacity being indicated by the amount of air required to distend the bag sufficiently to just fill the stomach ; and finally to his method of testing the activity and character of gastric peristalsis (also by the use of an intragastric dilatable rubber bag), in which the peristaltic waves are recorded on a kymograph. Whereas these methods may, with further use, yield valuable information, they cannot be expected to come into general use and must necessarily be largely confined to ward and laboratory use.

The chapters on the chemistry of the gastric juice are concise and to the point. Whereas German text-books on diseases of the stomach usually give a greater variety of methods, here only those that have been found of most practical value are described.

In this section we find some inconsistencies in spelling, which cannot altogether be attributed to typographical errors. Thus, on page 6G and in one or two other places we find "von Mehring" instead of " von Mering," which is the usual spelling where this author's name is quoted. Another inconsistency is the manner of spelling the plural of apparatus ; in some places "apparati" and in others "apparatuses" are found.

Part II, comprising nine chapters, is devoted to the " Therapy and Materia Medica of Stomach Diseases." The principles of the dietetic treatment of gastric diseases are dealt with at considerable length. A valuable chapter is devoted to the diet kitchen, and to the preparation of various articles of diet, which cannot help but be of great value to the practitioner in the dietetic treatment of gastric diseases. The therapeutic uses of electricity, mineral waters and various medicinal substances are discussed. Chapters are devoted to the various surgical operations used for the relief of the organic diseases of the stomach, and to the urine and blood in gastric affections.

Part III, subdivided into thirteen chapters, comprises a little more than one-half of the volume. It includes a very thorough consideration of the etiology, symptomatology, pathology and treatment of the various diseases to which the stomach is subject. The different forms of gastritis are described at considerable length.

The chapters on gastric ulcer, malignant growths, gnstroptosis and dilatations, and gastric neuroses are deserving of special mention. In considering the diagnosis of carcinoma ventriculi considerable stress is laid on the diagnostic value of the presence of the Oppler-Boas bacillus in the stomach contents.


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In some chapters the work is less systematic than is desirable. On page 530 the author proceeds to give a resume of the diagnostic factors in carcinoma ventriculi. He divides the tumors under three headings as regards their position, viz. (1) Carcinoma of the cardia ; (2) Carcinoma of the body of stomach, i. e. the curvatures and the fundus and walls ; (3) Of the pylorus. The first two divisions are discussed at length, but one looks in vain for a separate discussion of the last division, the most important, and finds to his disappointment that it has been included under division 2.

Altogether the volume is a very creditable American production. We think that it might, with advantage, have been curtailed at certain points, and certain unnecessary repetitions might have been avoided.

The author shows that he has kept abreast with the current medical literature. The bibliography on all the subjects is very extensive, thus increasing the value of the volume as a book of reference.

Constipation inAdultsand Children. By H. Illoway, M. D. {The Macmillan Company, New York, 1897.)

This work is divided into two parts ; the first consisting of 400 pages dealing with the causes and treatment of constipation in adults ; the second with the same conditions in infants. Under the heading treatment, most attention is given to massage and Swedish movements, illustrated by numerous cheap cuts. The work has many pictures, but most of them are poorly reproduced and do not add essentially to its value. Much space is taken up with long histories of cases of constipation, quoted from other authors, which had better have been omitted or at least abbreviated.

The tendency throughout the work is to magnify the importance of constipation, which, after all is said, is notadiseasebutasymptom.

The author evidently has a "bee in his bonnet" and does not weigh fairly the diiference between cause and effect. He seems to us to be continually putting the cart before the horse and thus injuring his plea. The book should be condensed to be really valuable. It is a mistake and a work of supererogation to devote so much attention to a symptom. One might with equal fairness write a book on headache or stomach-ache.

We do not intend to discuss the author's views, but diflEer essentially with him on many points. We cannot agree in thinking that appendicitis is frequently a result of constipation, or that torpidity of the liver results from it ; after both conditions exist a vicious circle may be set up, but we believe constipation in both these instances rather the result than the cause. As to its effects on the nature and consistency of the chyme there is only doubt, nothing is actually known on this point. The author does not believe that auto-intoxication is the result of constipation, except when the latter is associated with a certain degree of diarrhoea. The question of auto-intoxication is a most obscure one as yet, but we think many of the symptoms so often associated with chronic constipation are the results of this condition and the patient may be said to suffer from autointoxication.

The book will prove helpful to many if they are willing to wade through it, although there is nothing new in it; but constipation is frequently a difficult condition to manage satisfactorily, and the detail of treatment herein described will be appreciated by those who have been troubled by these trying cases.

The Bulletin of the Ohio Hospital for Epileptics. (Puhliahed by the Hospital, Oallipolis, Ohio, January, 189S.)

The first number of this bulletin contains a report of more than ordinary interest and suggestiveness by Ohlmacher, the director of the pathological laboratory. Although divided into two parts it is practically but one paper ; the first half givingthe clinical histories ami pathological findings of six cases of epilepsy which came to autopsy, and the second half being "Upon the resemblance of


the foregoing cases of epilepsy to certain diseases associated with ' thymic hyperplasia."

These six cases all occurred in adults, and all but one suffered from grand mal ; " in Case VI," as the author says, " the unsatisfactory evidences of the existence of epilepsy seem to be verified by the results of the autopsy." In three cases the thymus was found persistent and enlarged, in two others remnants of this gland were found, and in one only that body known as "fatty thymus," which shows no traces microscopically of a true thymus gland. In but one instance did death apparently occur suddenly. To quote again : " While the presence of a persistent or enlarged thymus gland in three of these cases must naturally be regarded as an important matter, itshould be distinctly noted that the presence of the thymus gland makes but a portion of a series of anatomical findings relating to a peculiar hyperplastic condition of the lymphatic structures in the body." In four of the cases other glands such as tonsils, bronchial and mesenteric were found enlarged, in another there was carcinoma, and in that case where only the "fatty thymus" was found no enlargement of lymph glands could be demonstrated.

The importance of this paper rests on the very careful microscopical work done by the pathologist, and the attention he has drawn to the concurrent existence of epilepsy and persistent thymus. In his introduction to the second paper he says : " A study of the literature bearing upon the persistence and enlargement of the thymus gland in human adults, which was suggested by the discovery of a persistent or enlarged thymus in three out of five cases of genuine epilepsy, results in centering attention upon at least two morbid states, one of which has long been suspected to have a clinical aSinity with epilepsy. In these two conditions a third disease may be added on account of the possibility of its morbid anatomical analogy with what we have found in our cases. These three conditions are: 1. Thymic asthma; 2. Sudden death in adults with persistent thymus; and 3. Exophthalmic goitre."

Whatever deductions we may feel inclined to draw from the result of this study of Ohlmacher's, we are grateful for the appearance of such a thorough piece of work and one which is a most valuable contribution to the literature on these conditions. We are still in profound darkness as to the purport of the thymus gland in the human system, or of the whole system of lymph glands, and also as to the causes of epilepsy and exophthalmic goitre. We know that the thymus usually is quite atrophied at the end of the second year of life, but that it does frequently persist and remain active, and that many cases of sudden death have occurred in adults where the only pathological (?) findings were an enlarged, active thymus, with hyperplasia of other lymph glands. The action of its secretion is not yet understood, but it is not hard to believe it possible that in adults its hyper-secretion, or hyposecretion, or perhaps some modified secretion, may give rise to epilepsy. If such a syndrome of toxic symptoms is caused by modifications of the thyroid gland secretion as wesee in exophthalmic goitre, why is it not easy to conceive of epilepsy and even sudden death occurring from changes in the secretion of the thymus? It is more difficult to explain the co-existent lymphatic hyperplasia, but enlargement of the lymph glands is frequently found as a result of toxic influences, and the constant secretion of the thymus gland in adults might readily lead to hyperplasia of the smaller lymph glands. However, it is not worth while to enter into vague speculation as to these conditions. We desire merely to draw attention to this most admirable contribution to our knowledge of the thymus, which has appeared at a most opportune time, when much more attention than formerly is devoted to the study of all the glands, and especially to the large ductless ones of the human system. There are pathologists at other epileptic and insane asylums who have abundant opportunity to investigate these points, and we hope it will not be long before we have further illumina


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tion on these obscure diseases. There are three first-rate illustrations in this article.

The ho.spital board of governors is to be much congratulated on having obtained the services of such an excellent pathologist as Ohlmacher, and the future bulletins of this institution will be awaited with much interest. The remaining papers in this bulletin are of lesser import, but as a first number from a but little known institution we have only words of praise for it and believe that it deserves most hearty recognition from all interested in the science of medicine.

A Text-Book of the Diseases of Women. By Henry J. GAEniouES, A. M., M. D., Professor of Gynecology and Obstetrics in the New York School of Clinical Medicine. Containing three hundred and thirty-five engravings and colored plates. 728 pp. Second edition. {Philadelphia : W. B. Sminders, 1897.)

This neatly bound and well-printed book contains a large amount of information upon diseases of women. The writer has treated the subject in a systematic manner, and his style is clear and for the most part concise. The illustrations are, as a rule, old ones, and mostof the photographs among the new ones are indistinct and show little. The book was written to meet the demands of the medical student and the general practitioner of medicine. One feature of the book which will be of particular value to the medical student is the large number of methods for the surgical treatment of the different gynecological diseases. To meet the demands of the general practitioners of medicine, general treatment is dwelt upon at some length. The chapter upon Anatomy is full, while the paragraphs upon Pathology leave much to be desired. Taken as a whole the work is one of the most complete which we have seen printed in English and will, no doubt, have a large number of readers. G. B. M.

Elements of Latin. For Students of Medicine and Pharmacy. By George D. Ckothers, A. M., M. D., Teacher of Latin and Greek in the St. Joseph (Mo.) High School, and Hiram H. Bice, A. M., Instructor in Latin and Greek in the Boys' High School of New York City, xii-242 pp. (The F. A. Davis Co., Publishers, Philadelphia, New York City, and Chicago, III.)

This is an excellent little book for those who wish to know enough of Latin to write or to read prescriptions and to understand anatomical terms. The method employed is simple and sensible, the vocabularies are carefully selected and the arrangement of the book is good. The "Notes" seem rather far-fetched and are of doubtful utility. They are cumbered with extracts from the U. S. Dispensatory which seem to have little connection with the study of Latin and are of little utility to the student of medicine.


BOOKS RECEIVED.


The American Tear-Book of Medicine and Surgery. Collected and arranged with critical editorial comments. By S. W. Abbott, M. D.,«(! al. Under the general editorial charge of George M. Gould, M. D. 1898. 4to. 1077 pages. W. B. Saunders, Philadelphia.

Orthopedic Surgery. By James E. Moore, M. D. 1898. 8vo. 354 pages. AV. B. Saunders, Philadelphia.

Therapy of the Clinics of the Royal and Imperial Hospital of Vienna, Austria. Translated and revised with notes from the last two compilations of Earnest Landesmann, M. D. By John H. Metzerott, M. D. 1897. 12mo. 765 pages. Fergus Printing Co., Chicago.

The Diseases of Infancy and Childhood. By L. Emmett Holt, A. M., M. D. 1898. 8vo. 1117 pages. D. Appleton & Co., New York.


Prize Essays on Leprosy. Thompson. Cantlie. 1897. 8vo. 413 pages. The New Sydenham Society.

A Guide to the Clinical Examination of the Blood for Diagnostic Purposes. By Richard C. Cabot, M. D. 1897. Svo. 405 pages. William Wood & Co., New York.

The Medical Annual and Practitioner's Index. 1898. Sixteenth year. 12mo. 847 pages. John Wright & Co., Stone Bridge, Bristol.

Transactions of the College of Physicians of Philadelphia. Third series. Vol.19. 1897. 8vo. 256 pages. Printed for the College, Phila.

Diseases of the Stomach. In three parts. By John C. Hemmeter, M. B., M.D., Ph.D. 1897. Svo. 788 pages. P. Blakiston, Son& Co., Phila.

Atlas of Methods of Clinical Investigation, with an Epitome of Clinical Diagnosis and of Special Pathology and Treatment of Internal Diseases. By Dr. Christfried Jakob. Authorized translation from the German. Edited by A. A. Eshner, M. D. 1898. 12mo. 259 pages. W. B. Saunders, Phila.

The Surgical Complicationsand Sequels of Typhoid Fever. By William W. Keen, M.D., LL. D. Based upon tables of 1700 cases. Compiled by the author and by Thompson S. Westcott, M. D. With a chapter on the Ocular Complications of Typhoid Fever. By G.

E. de Schweinitz, A. M., M. D. And as an appendix the Toner Lecture, No. V. 1898. Syo. 386 pages. W. B. Saunders, Phila.

A Compendium of Insanity. By John B. Chapin. 1898. 12mo. 234 pages. W. B. Saunders, Phila.

Doctor and Patient : Hints to Both. By Dr. Robert Gersuny. Translated by A. S. Levetus. With a preface by D. J. Leech, M. D.,

F. R.C. P., etc. 1898. 12mo. 79 pages. John Wright & Co., Bristol.

Annual and Analytical Cyclopccdia of Practical Medicine. By Charles E. de M. Sajous, M. D., and one hundred associate editors, assisted by corresponding editors, collaborators and correspondents. Vol. I. 1898. 4to. 601 pages. The F. A. Davis Co., Publishers. Philadelphia, New York, Chicago.

A Modern Pathological and Therapeutical Study of Rheumatism, Oout, Rheumatoid Arthritis and Allied Affections. By Edmund L. Gros, M.D., of the Faculty of Paris. {Translated from the French.) 1897. 16mo. 47 pages.

The Anatomy and Functions of the Muscles of the Hand and of the Extensor Tendons of the Thinnb. By J. Francis Walsh, M. D. Essay awarded the "Boylston" prize for 1897, Department of Anatomy and Physiology, by the Boylston Medical Committee. Boston, Mass. 1897. 8vo. 51 pages. Charles H. Walsh, Philadelphia.

An American Text-Book of Oenito-Urinary Diseases, Sy2>hilis and Diseases of the Skin. Edited by L. Bolton Bangs, M. D., and W. A. Hardaway, A. M., M. D. 1898. 4to. 1229 pages. W. B. Saunders, Philadelphia.

Medical and Surgical Reports of the Boston City Hospital. Ninth Series. Edited by C. F.Folsom, M. D., AV.T. Councilmaii, M. D., and Herbert L. Burrell, M. D. 1898. Svo. 276 pages. Published by the Trustees, Boston.

DESCRIPTION OF THE JOHNS HOPKINS HOSPITAL.

By John S. Billinos, M. D., LL. D.

Containing 56 large quarto plates, phototypes, and lithographs, with views, plans and detail drawings of all buildings, and their interior arrangements — also woodcuts of apparatus and lixtures ; also 116 pages of letter-press describing the plans followed in the construction, and giving full details of heating-apparatus, ventilation, sewerage and plumbing. Price, bound in cloth, $7.50.


May, 1898.J


JOHNS HOPKINS HOSPITAL BULLETIN.


123


PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.


THE JOHNS HOPKINS HOSPITAL REPORTS. Volume I. 423 pages, 99 plates.

Report in Pathologry.

The Vessels and Walls o( the Dog's Stomach; A Study of the Intestinal Contraction: Healing of Intestinal Sutures; Reversal of the Intestine; The Contraction of the Vena Portae and its Influence upon the Circulation. By F. P. &fALL, M. D.

A Contribution to the Pathology of the Gelatinous Type of Cerebellar Sclerosis (Atrophy). By Henry J. Berkley, M. D.

Reticulated Tissue and its Relation to the Connective Tissue Fibrils, By F, P, Mall, M. D.

Report in Dermatolof^y.

Two Cases of Protozoan (Coccidioidal) Infection of the Skin and other Organs. By T. C. Gilchrist, M. D., and Emmet Rixford. M. D.

A Case of Blastomycetic Dermatitis in Man; Comparisons of the Two Varieties of Protozoa, and the Blastomyces found in the preceding Cases, with the so-called Parasites found in Various Lesions of the Sliin, etc. ; Two Cases of Molluscum Fibrosum; The Pathology of a Case of Dermatitis Herpetiformis (Duhring). By T. 0. Gilchrist, M. D.

Report in Patlioloery.

An Experimental Study of the Thyroid Gland of Dogs, with especial consideration of Hypertrophy of this Gland. By W. S. Halsted, M. D.


Volume II. 570 pages, with 28 plates and figures.

Report in Meiliclne.

Od Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with

Gallstones. By William Osler, M. D. Some Remarks on Anomalies of the Uvula. By John N. Mackenzie, M. D. On Pyrodin. By H. A. Lafleck, M. D. Cases of Post-febrile Insanity. By William Oeler, M. D. Acute Tuberculosis in an Infant of Four Months. By Harry Todlmin, M. D. Rare Forms of Cardiac Thrombi. By William Osler, M. D. Notes on Endocarditis in Phthisis. By William Osler, M. D.

Report in Medicine.

Tubercular Peritonitis. By William Osler, M. D.

A Case of Raynaud's Disease. By H. M. Thomas, M. D.

Acute Nephritis in Typhoid Fever. By William Osler, M. D.

Report in Gynecologry. The Gynecological Operating Room. By Howard A. Kelly, M. D. The Laparotomies performed from October 16, 1889, to March 3, 1890. By Howard

A. Kelly, M. D., and Hunter Robb, M. D. The Report of the Autopsies in Two Cases Dying in the Gynecological Wards without Operation; Composite Temperature and Pulse Charts of Forty Cases of

Abdominal Section. By Howard A. Kelly, M. D. The Management of the Drainage Tube in Abdominal Section. By Hunter Robq,

M. D. The Gonococcus in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Peritoneum;

Ovarian Tumor; General Gynecological Operations from October 15, 1889, to

March 4, 1890. By Howard A. Kelly, M. D. Report of the Urinary Examination of Ninety-one Gynecological Cases. By Howard

A. Kelly, M. D., and Albert A. Ghriskey, M. D. Ligature of the Trunks of the Uterine and Ovarian Arteries as a Means of Checking

Hemorrhage from the Uterus, etc. By Howard A. Kelly, M. D. Carcinoma of the Cervix Uteri in the Negress. By J. W. Williams, M. D. Elephantiasis of the Clitoris. By Howard A. Kelly, M. D. Myxo-Sarcoma of the Clitoris. By Hunter Robb, M. D. Kolpo-Ureterotomy. Incision of the Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gynecological Operations. By

Howard A. Kelly, M. D.

Report in Snrgery, I.

The Treatment of Wounds with Especial Reference to the Value of the Blood Clot in the Management of Dead Spaces. By W. S. Halsted, M. D.

Report in Neurologry* I.

A Case of Chorea Insaniens. By Henry J. Berkley, M. D. Acute Angio-Neurotic Oedema. By Charles E. Simon, M. D. Haematomyelia. By August Hoch, M. D.

A Case of Cerebro-Spinal Syphilis, with an unusual Lesion in the Spinal Cord. By Henry M. Thomas, M. D.

Report in Patliologry, I.

Amoebic Dysentery. By William T. Cooncilman, M. D., and Hinri A. Latleub, M. D.


Volume III. 766 pages, -with 69 plates and figures.

Report in Pattiologry.

Papillomatous Tumors of the Ovary. By J. Whitridoe Williams, M. D. Tuberculosis of the Female Generative Organs. By J. Whitridoe Williams, M. D.

Report in Patlioloey.

Multiple Lympho-Sarcomata, with a report of Two Cases. By Simon Flexner, M. D.

The Cerebellar Cortex of the Dog. By Henry J. Berkley, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman, M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Russell, Ph. D.

Heart Hypertrophy. By Wm. T. Howard, Jr., M. D.

Report in Gynecology.

The Gynecological Operating Room; An External Direct Method of Measuring the Conjugdta Vera; Prolapsus Uteri without Diverticulum and with Anterior Enterocele; Lipoma of the Labium Majus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Source of Error in Gynecological Diagnosis; Operation for the Suspension of the Retroflexed Uterus. By UoWABD A Kelly, M. D.

Potassium Permanganate and Oxalic Acid as Germicides against the Pyogenic Cocci. By Mart Sherwood. M. D,

Intestinal Worms as a (jompUcatioo in Abdominal Surgery. By A. L. Stavily, M. D.


Gynecological Operations not involving Cceliotomy. By Howard A. Kelly, M. D. Tabulated by A. L. Stavely, M. D.

The Employment of an Artificial Retroposition of the Uterus in covering Extensive Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdominal Pelvic Operations. By Howard A. Kelly, M. D.

Photography applied to Surgery. By A. S. SIcrray.

Traumatic Atresia of the Vagina with Ifematokolpos and Haematometra. By Howard A. Kelly, M. D.

Urinalysis in Gynecology. By W. W. Russell, M. D.

The Importance of employing Anesthesia in the Diagnosis of Intra-Pelvic Gynecological Conditions. By Hunter Robb, M. D.

Resuscitation in Chloroform Asphyxia. By Howard A. Kelly, M. D.

One Hundred Cases of Ovariotomy performed on Women over Seventy Years of Age. By Howard A. Kelly, M. D., and Mary Sherwood, M. D.

Abdominal Operations performed in the Gynecological Department, from March 5, 1890, to December 17, 1892. By Howard A. Kelly, M. D.

Record of Deaths occurring in the Gynecological Department from June 6, 1890, to May 4, 1S92.


Volume IV. 504 pages, 33 charts and illustrations.


Report on Typlioid Fever.


Report in Nenrolosry.

Dementia Paralytica in the Negro Race; Studies in the Histology of the Liver; The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of the Subma.\illary Gland of Miis mitsculus; The Intrinsic Nerves of the Thvroid Gland of the Dog; The Nerve Elements of the Pituitary Gland. By Henry J. Berkley,

Report in Surgery.

The Results of Operations for the Cure of Cancer of the Breast, from June, 1889, to January, 1894. By W. S. Halsted, M. D.

Report in Gynecology.

Hydrosalpinx, with a report of twenty-seven cases; Post-Operative Septic Peritonitis; Tuberculosis of the Endometrium. By T. S. Cullen, M. B.

Report in Pathology.

Deciduoma Malignum. By J. Whitridoe Williams, M. D.


Volume V. 480 pages, with 32 charts and illustrations.

CONTENTS

  • The Malarial Fevers of Baltimore. By W. S. Thayer, M. D., and J. Hewetson, M. D. A Study of seme Fatal Cases of Malaria. By Lewellys F. Barker, M. B.

Stndles in Typhoid Fever.

By William Osler, M. D., with additional papers by G. Blumer, M. D., Simon Flexner, M. D., Walter Reed, M. D., and H. C. Parsons, M. D.


Volume VI. 414 pages, with 79 plates and figures.

Report in Nenrology.

Studies on the Lesions produced by the Action of Certain Poisons on the Cortical Nerve Cell (Studies Nob. I to V). By Henry J. Berkley, M. D.

Introductory.— Recent Literature on the Pathology of Diseases of the Brain by the Chromate of Silver Methods; Part I.— Alcohol Poisoning.— Experimental Lesions produced by Chronic Alcoholic Poisoning (Ethvl Alcohol). 2. Experimental Lesions produced by Acute Alcoholic Poisoning (Ethyl Alcohol) ; Part II.— Serum Poisoning. — Experimental Lesions induced by the Action of the Dog's Serum on the Cortical Nerve Cell; Part III.— Ricin Poisoning.— Experimental lesions induced by Acute Ricin Poisoning. 2. Experimental Lesions induced by Chronic Ricin Poisoning; Part IV.— Hydrophobic Toxaemia.— Lesions of the Cortical Nerve Cell produced by the Toxine of Experimental Rabies; Part V.— Pathological Alterations in the Nuclei and Nucleoli of Nerve Cells from the Effects of Alcohol and Ricin Intoxication; Nerve Fibre Terminal Apparatus; Asthenic Bulbar Paralysis. By Henry J. Berkley, M. D.

Report in Patliology.

Fatal Puerperal Sepsis due to the Introduction of an Elm Tent. By Thomas S.

Cullen, M. B. Pregnancy in a Rudimentary Uterine Horn. Rupture, Death, Probable Migration of

Ovum and Spermatozoa. By Thomas S. Cullen, M. B., and G. L. Wilkins, M. D. Adeno-Myoma Uteri Diffusum Benignum. By Thomas S. Cullen, M. B. A Bacteriological and Anatomical Study of the Summer Diarrhoeas of Infants. By

William D. Booker, M. D. The Pathology of Toxalbumin Intoxications. By Simon Flexner, M. D. T7ie pricp of n Di-t hound in cloth [Tols. T-TI] of the Hospital Jtrports in

$30.00. roll. I, II and III are not sold separately. The price of

Vols, ir, r and ri is $5.00 each.


Monographs.

The following papers are reprinted from Vols. I, IV, V and VI of the Keports. for those who desire to purchase in this form : STUDIES IN DERMATOLOGY. By T. C. Gilchrist, M. D., and Emmet Rixpord,

M. D. 1 volume of 164 pages and 41 full-page plates. Price, bound in paper,

$3.00. THE MALARIAL FEVERS OF BALTIMORE. By W. S. Thayer, M. D., and J.

Hewetson. M. D. And A STUDY OF SOME FATAL CASES OF MALARIA.

By Lewei.lyb F. Barker, M. B. 1 volume of 280 pages. Price, in paper, $2.75. STUDIES IN TYPHOID FEVER. By William Osler, M. D., and others. Extracted

from Vols. IV and V of the Johns Hopkins Hospital Reports. 1 volume of 481

pages. Price, bound in paper, $3.00. THE PATHOLOGY OF TOXALRTTMIN INTOXICATIONS. Bv .=lnion Flexner, M. D.

volume of 1.10 pages with I full-page llthogniphs. i rice, bound in paper, J'i.OO. Subscriptions for the above publications may be sent to

The Johns Hofkins Press, Baivumou, Ho.


124


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 86.


THE JOHNS HOPKINS MEDICAL SCHOOL. SESSION 1897-1


FACULTY.


Dahiel O. Oilman, LL. D., President.

William H. Welch, M. D., LL. D., Dean and Professor of Pathology.

Ira Remsen, M. D., Ph. D., LL. D., Professor of Chemistry.

WiLLiAU OsLER, M. D., LL. D., F. R. C. P., Professor of the Principles and Practice

of Medicine. Henry M. Hdrd, M. D., LL. D., Professor of Psychiatry. WiLLiAU S. Halsted, M. D., Professor of Surgery. Howard A. Kelly, M. D., Professor of Gynecology and Obstetrics. Franklin P. Mall, M. D., Professor of Anatomy. John J. Abel, M. D., Professor of Pharmacology. William H. Howell, Ph. D., M. D., Professor of Physiology.

William K. Brooks, Ph. D., LL. D., Professor of Comparative Anatomy and Zoology. John S. Billings, M. D., LL. D., Lecturer on the History and Literature of Medicine. Alexander C. Abbott, M. D., Lecturer on Hygiene. Charles Wardell Stiles, Ph. D., M. S., Lecturer on Medical Zoology. Robert Fletchlr, M. D., M. R. C. S., Eng., Lecturer on Forensic Medicine. William D. Booker, M. D., Clinical Professor of Diseases of Children. John N. Mackenzie, M. D., Clinical Professor of Laryngology and Rhinology. Samuel Theobald, M. D., Clinical Professor of Ophthalmology and Otology. Henrt M. I'homas, M. D., Clinical Professor of Diseases of the Nervous System. Simon Flexner, M. D., Associate Professor of Pathology. J. Whitridge Williams, M. D., Associate Professor of Obstetrics. Lewellys F. Barker, M. B., Associate Professor of Anatomy. William S. Thayer, M. D., Associate Professor of Medicine. John M. T. Finney, M. D., Associate Professor of Surgery.


Georob p. Dreter, Ph. 0., Associate in Physiology.

William W. Russell, M. D., Associate in Gynecology,

Henry J. Berkley, M. D., Associate in Neuro- Pathology.

.1. Williams Lord, M. D., Associate in Dermatology and Instructor in Anatomy.

T. Caspar Gilchrist, M. R. C. S., Associate in Dermatology.

Robert L. Randolph, M. D., Associate in Ophthalmology and Otology.

Thomas B. Aldrich, Ph. D., Associate in Physiological Chemistry.

Thomas B. Futcher, M. B., Associate in Medicine.

Joseph C. Bloodgood, M. D., Associate in Surgery.

Thomas S, Cullen, M. B., Associate in Gynecology.

Ross G. Harrison, Ph. D., Associate in Anatomy.

Frank R. Smith, M. D., Instructor in Medicine.

George W. Dobbin, M. D., Assistant in Obstetrics.

Walter Jones, Ph. D., Assistant in Physiological Chemistry.

Adolph G. Hoen, M. D., Instructor in Photo-Micrography.

Sydney M. Cone, M. D., Assistant in Surgical Pathology.

Louis E. LiviNGOOD, M. D., Assistant in Pathology.

Henry Barton Jacobs, M. D,, Instructor in Medicine.

Charles R. Bardeen, M. D., Assistant in Anatomy.

Stewart Paton. M. D., Assistant in Nervous Diseases.

Norman McL. Harris, M. B., Assistant in Pathology.

Harvey W. Ccshing, M. D., Assistant in Surgery.

J. M. Lazear, M. D., Assistant in Clinical Microscopy.

J. L. Walz, Ph. O., Assistant in Pharmacy.


GENERAL STATEMENT.

The Medical Department of the Johns Hopkins University was opened for the instruction of students October, 1893. This School of Medicine is an integral and coordinate part of the Johns Hopkins University, and it also derives great advantages from its close affiliation with the Johns Hopkins Hospital.

The required period of study for the degree of Doctor of Medicine is four years. The academic year begins on the first of October and ends the middle of June, with short recesses at Christmas and Easter.

Men and women are admitted upon the same terms.

In the methods of instruction especial emphasis is laid upon practical work in the Laboratories and in the Dispensary and Wards of the Hospital. While the aim of the School is primarily to train practitioners of medicine and surgery, it is recognized that the medical art should rest upon a suitable preliminary education and upon thorough training in the medical sciences. The first two years of the course are devoted mainly to practical work, combined with demonstrations, recitations and, when deemed necessary, lectures, in 'the Laboratories of Anatomy, Physiology, Physiological Chemistry, Pharmacology and Toxicology, Pathology and Bacteriology. During the last two years the student is given "abundant opportunity for the personal study of cases of disease, his time being spent largely in the Hospital Wards and Dispensary and in the Clinical Laboratories. Especially advantageous for thorough clinical training are the arrangements by which the students, divided into groups, engage in practical work in the Dispensary, and throughout the fourth year serve as clinical clerks and surgical dressers in the wards of the Hospital.

REQUIREMENTS FOR ADMISSION.

As candidates for the degree of Doctor of Medicine the school feceives :

1. Those who have satisfactorily completed the Chemical-Biological course which leads to the A. B. degree in this university.

3. Graduates of approved colleges or scientific schools who can furnish evidence ; (a)'That they have acquaintance with Latin and a good reading knowledge of French and German ; (6) That they have such knowledge of physics, chemistry, and biology as is imparted by the regular minor courses given in these subjects in this university.

The phrase "a minor course," as here employed, means a course that requires a year for its completion. In physics, four class-room exercises and three hours a week in the laboratory are required; in chemistry and biology, four class-room exercises and five hours a week in the laboratory in each subject.

S. Those who give evidence by examination that they possess the general education implied by a degree in arts or in science from an approved college or scientific school, and the knowledge of French, German, Latin, physics, chemistry, and biology above indicated.

Applicants for admission will receive blanks to be filled out relating to their previous courses of study.

They are required to furnish certificates from officers of the colleges or scientific schools where they have studied, as to the courses pursued in physics, chemistry, and biology. If such certificates are satisfactory, no examination in these subjects will be required from those who possess a degree in arts or science from an approved college or scientific school.

Candidates who have not received a degree in arts or in science from an approved college or scientific school, will be required (1) to pass, at the beginning of the session in October, the matriculation examination for admission to the collegiate department of the Johns Hopkins University, (2) then to pass examinations equivalent to those taken by students completing the Chemical-Biological course which leads to the A. B. degree in this University, and (3) to furnish satisfactory certificates that they have had tlie requisite laboratory training as specified above. It is expected that only in very rare instances will applicants who do not possess a degree in arts or science be able to meet these requirements for admission.

Hearers and special workers, not candidates for a degree, will be received at the discretion of the Faculty.

ADMISSION TO ADVANCED STANDING. Applicants t<iradmlssirm to advanced standlug must furnish evidence (1) that tho foregoing terms of admission as regards prelliniuary training have been tulfllled, (2) that courses equivalent in lilud and amount to those given here, preceding that year of the course for admission to which application is made, have been satlstactorliy completed, and (3i must pass examinations at the beginning of the session In October In all the subjects that have been already pursued by the class to which admission is sought. Certifloates of standlug elsewhere caunot be accepted in jilace of these examinations.

SPECIAL COURSES FOR GRADUATES IN MEDICINE.

Since the opening of the Johns Hopkins Hospital in 1889, courses of instruction have been offered to graduates in medicine. The attendance upon these courses has steadily increased with each succeeding year and indicates gratifying appreciation of the special advantages here afforded. With the completed organization of the Medical School, it was found necessary to give the courses intended especially for physicians at a later period of the academic year than that hitherto selected. It is, however, believed that the period now chosen for this purpose is more convenient for the majority of those desiring to take the courses than the former one. The special courses of instruction for graduates in medicine are now given annually during the months of May and June. During April there is a preliminary course in Normal Histology. These courses are in Pathology, Bacteriology, Clinical Microscopy, General Medicine, Surgery, Gynecology, Dermatology, Diseases of Children, Diseases of the Nervous System, Genito-Ui-inary Diseases, Laryngology and Rhinology, and Ophthalmology and Otology. The instruction is intended to meet the requirements of practitioners of medicine, and is almost wholly of a practical character, it includes laboratory courses, demonstrations, bedside teaching, and clinical instruction in the wards, dispensary, amphitheatre, and operating rooms of the Hospital. These courses are open to those who have taken a medical degree and who give evidence satisfactory to the several instructors tliat they are prepared to profit by the opportunities here ofi'ered. The number of students who can be accommodated in some of the practical courses is necessarily limited. For these the places are assigued according to the date of application.

The Annual Announcement and Catalogue will be sent upon application. Inquiries should be addressed to the

REGISTRAR OF THE JOHNS HOPKINS MEDICAL SCHOOL, BALTIMORE.


The Johns Hopkins Hospital Bulletins are issued montMy. They are printed by THE FRIEDENWALD CO., Baltimore. Single copies may be promred from Messrs. CUSHINO & CO. and the BALTIMORE NEWS COMPANY, Baltimore. Subscriptions, $1.00 a year, maybe addressed to the publisliers, THE JOHNS HOPKINS PRESS, BALTIMORE ; single copies will be sent by mail for fifteen cents each.


BULLETIN


OF


THE JOHNS HOPKINS HOSPITAL.


Vol. IX.- No. 87.]


BALTIMORE, JUNE, 1898.




coisTTDEJisrars.


PAGE.

A Microscopical Study of the Spinal Cord in Two Cases of Pott's Disease. By William G. Spiller, M.D., ----- 125

Note on the Osteoid Tissue found in the Tubercular Exudate in the Thoracic Region of the Cord. [Dr. Flexner], - -133

A Case of Osteitis Deformans. By AVm. T. Watson, M. D., - 133

The Rise of the Theory of Electrolytic Dissociation, and a few of its Applications in Chemistry, Physics, and Biology. By Harry C. Jones, Ph. D.,

Localized Scleroses of the Aorta of Probable Syphilitic Origin. Clinical Report and Necropsy in two Cases. By Clement A. Penrose, M. D., .--.- -...


136


140


Further Remarks on Adeno-Myoma of the Round Ligament. By Thomas S. CuLLBN, M.B., - - - •- 142

Proceedings of Societies :

Hospital Medical Society, - . - - 144

Regeneration of the Dorsal Root of the Second Cervical Nerve within the Spinal Cord [Messrs. Baer, Dawson and Marshall] ; — Hydraulic Pressure in Genito-Urinary Practice [Dr. H. H. Young] ; — Forty-six Intubated Cases of Diphtheria treated with Antitoxine [W. T. Watson, M. D.].

Notes on New Books, _.___- 147

Books Received, ---------- 148


A MICROSCOPICAL STUDY OF THE SPINAL CORD IN TWO CASES OF POTT'S DISEASE.*

By William G. Spillee, M. D., Professor of Diseases of the Nervous Si/s^em in the PhiladelpMa Polyclinic; Associ(de in the William Pepper Laboratory of Clinical Medicine, Univerdty of Pennsylvania.

[From the William Pepper Labofatory of Clinical Medicine.]


We have learned much about spinal caries since Percival Pottf wrote his work on this disease so many years ago, but we have not exhausted the subject, and it is still one of much interest.

The two cases which I have the honor to present for your consideration represent two forms of the affection, an early and a late; one in which the cord has not been comjjressed by displaced vertebraj, and one — and rather a rare variety — in which the cord has been almost severed as the result of such displacement in connection with an extradural tuberculous


The cause of the compression is only mentioned in thirtynine of the fifty-two cases of paralysis from spondylitis which Schmaus collected from the literature;! in thirty-three of these a caseous pachymeningitis was noted; in six the com


Read by invitation before the Johns Hopkins Hospital, January 17th, 1898.

fPott, Remarks on that kind of palsy of the lower limbs which is frequently found to accompany a curvature of the spine, etc. The Chirurgical Works of Percival Pott, F. R. S., Vol. III.

t Die Compression-Myelitis bei Caries der Wirbelsiiule. Wiesbaden, 1890. J. F. Bergmann. Quoted by Kraske.


pression was caused by dislocation of the vertebra^ and in five of these six the odontoid process of the axis was dislocated. Therefore only in one of thirty-nine cases the compression was due to kyphotic displacement. Kraske* adds to this number and shows that only in one case out of fifty-two was the compression of the cord due to deviation of the vertebn« alone (omitting the five cases above mentioned). He tells us that only in about two per cent, of the cases the paralysis from spondylitis is caused by kyphosis alone; in all the rest it is due to compression from a peripuchymeningitic exudate.

The case B. H. is, therefore, one of considerable interest, for the compression was chiefly due to displaced vertebrae, though there was also a peripachymeningitis.

The first case — for which I am indebted to Dr. Willard and Dr. Lloyd — was in a boy of about twelve years of age. Dr. Lloyd, who frequently saw the patient during his lifetime, told me that the boy had complained of great pain in the region of a cervico-thoracic kyphosis. He was not paralyzed. Before death dyspncea became intense, and Dr. Lloyd believed


Kraske, Archiv fiir klin. Chirurgie, Vol. XLI.


126


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 87.


that death was due to paralysis of the respiratory muscles. This was possibly the result of intense round cell infiltration of the cord in the mid-cervical region where the phrenic nerve has its origin.

The report of the necropsy is as follows: The hody was that of a much emaciated boy. Kyphosis was present without scoliosis, and the prominence was at the fifth, sixth, seventh cervical and first thoracic vertebra;, and was greatest at the junction of the seventh cervical with the first thoracic. Much pus was found within the cervical portion of the vertebral canal, external to the dura. The dura was adherent by its anterior surface to the bodies of the seventh cervical and first thoracic vertebra, and a cheesy, fibrous mass was observed on its ventral and external surface. The bodies of the lower cervical and first thoracic vertebra; were carious and yielded to slight pressure from a blunt instmment. No tuberculous lesions were found elsewhere.

The spinal cord was not compressed and secondary degeneration was not noted. The chief interest of this case lies in the fact that it shows the earlier stages of Pott's disease — whereas the following case shows the late— and presents a very intense round cell infiltration of the meninges and cord, without specific signs of a tuberculous process interior to the dura. Such signs are, however, very abundant in the mass external to the dura. The dura has acted to some degree as a barrier, but it also shows some round cell infiltration. Along the periphery of the lateral columns in the upper thoracic region spaces are found from which the nerve fibres have disappeared, and in some sections a few swollen axis cylinders are seen. There is very distinct perivascular infiltration of round cells within the cord ; this is well marked at the mid-cervical region and involves the vessels of all parts of the transverse area, and is noticed also within the anterior horns. The perivascular infiltration is especially noticeable at this level, about the vessels of the anterior fissure and posterior septum. In the posterior columns of the mid-cervical region necrotic areas are seen, which stain faintly with Weigert's hajmatoxyliu solution and show a diminution in the number of nerve fibres. When the carmine and Delafield's hematoxylin are used, moderate round cell infiltration, some proliferation of neuroglia, and some slight swelling of the axis cylinders are noticed in these areas. This necrosis is probably dependent on the vascular condition. No other necrotic areas have been noticed within the cord. The motor cells of the mid-cervical region do not appear greatly altered, but unfortunately the method of Nissl could not be used. In the first and second cervical segments the infiltration is much less in intensity, but it is very distinct in the lumbar region, where the vessels are also much dilated.

The anterior roots in the upper thoracic region are greatly degenerated, but the posterior have partially escaped. The motor cells in this portion of the cord are distinctly altered. The Marchi stain does not reveal degenerated fibres.

In the mass external to the dura many giant cells, large collections of round and epithelioid cells, and caseous areas are found.

The second case, for which I am indebted to Dr. Willard, is as follows: The child, B. H., came of a tuberculous family and suffered from bronchitis every winter. The evidences of


Pott's disease first appeared when the patient was three years of age. She complained of pain in the back, and kyphosis was soon afterward noticed. About four months after the first evidences of the disease were detected the child was found to be liable to fall without sufficient cause. A year later the tendons of both heels were operated on, a fact which shows that the disease progressed rapidly. At eight years of age prominence of the first, second and third thoracic vertebra?, atrophy of the legs with paralysis, contracture of the hamstring tendons, and large sores over the hip-joints were noticed. The child died when eight years old; the process, therefore, lasted five years. It is stated that she had had no power of motion in the legs and no control of the bladder, although rectal disturbance had not been noted.

When the vertebral column was examined at the necropsy the body of the seventh cervical vertebra was found almost at a right angle with that of the first thoracic. The latter was carious and yielded to slight pressure from a blunt instrument. Permission was not obtained to remove any of the bony part of the spinal column, and more careful examination of the vertebrse could not be made. The cord was very small in the region corresponding to the prominence made by the first thoracic with the seventh cervical vertebra, and had evidently very little space for growth. The unusual degree of compression was possibly the result of the development of the Pott's disease at the early age of three years. Segments an inch above or below the seat of compression were much larger. The compressed portion was soft and was removed with difficulty. A cheesy fibrous mass was found adherent to the external and right side of the dura, extending downward about an inch, and upward about half an inch from the compressed region, and together with the displaced vertebrae had caused the signs of compression. The dura was not adherent to the cord, and no evidence of internal meningitis was present.

Dr. Sailer examined the thoracic and abdominal viscera and found areas of pneumonic infiltration in the stage of red hepatization in the middle lobe of the right lung and in the lower part of the upper lobe of the left.

After the spinal cord had been hardened it was examined microscopically. In the region of greatest compression, at the cervico-thoracic junction of the vertebrse, the cord contains very few medullated fibres, and even those present are most irregularly arranged. It is impossible to make any distinction between gray and white matter. The vessels within the cord are sclerosed. Numerous nuclei, both round and elongated, are found in all parts of the sections, and some of a these probably represent a round cell infiltration. No nerve ^ cells are observed. The pia is much thickened and contains altered blood pigment. Both anterior and posterior roots external to the cord are in a fairly good state of preservation. The vessels within the cord stand out prominently from the surrounding tissue as faintly stained pink patches when the carmine is used, and as pale yellow ones with Weigert's hamiatoxylin. The central canal is closed at this portion of the cord.

Sections two to three root segments above the area of greatest compression show the central canal quite widely open. There is little round cell inliltration. The columns of Goll,


JCJNE, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


127


with the esceptiou of a few fibres along their jieriphery, are greatly degeuenited. These few normal fibres have probably escaped destruction at the area of compression. A few scattered normal fibres are found also in other parts of these columns. Kormal fibres from the posterior commissure are distinctly seen passing into the degenerated columns of Goll. Burdach's columns also are not free from degeneration. The direct cerebellar tracts and columns of Gowers are much degenerated, but just below the motor decussation many medullated fibres may be seen within the former; it would seem, therefore, that these tracts are partly formed by nerve fibres whose cells are situated above the lower cervical region, or that — and this is more probable — fibres of the crossed pyramidal tracts are more intimately mingled with those of the direct cerebellar tracts at this level. Very distinct ascending degeneration of the lateral columns in the area of the crossed pyramidal tracts is noted, and this extends through several root segments and gradually disappears above the mid-cervical region. The direct pyramidal tracts show an ascending degeneration of less intensity.

Below the compressed area the horns of the cord gradually assume their normal form, and medullatecl fibres first appear nearest the gray matter and gradually increase in extent toward the periphery. The crossed pyramidal, Gowers', and the direct cerebellar tracts are greatly degenerated, and the direct pyramidal is also involved. Very few medullated fibres are found in the area of the lateral motor tracts below and near the region of compression, and though the number of these increases as lower levels of the cord are examined, they are never as abundant as one might expect. There are, therefore, associative fibres within the crossed pyramidal tracts, but their number is limited.

In the lateral columns the degeneration extends considerably in advance of that marked out as the area of the lateral motor columns by secondary degeneration from cerebral lesions. Degeneration of the peripheral part of the anterior columns near the anterior fissure may be ti'aced well into the mid-lumbar region.

The central canal is enlarged both above and below the cervico-thoracic junction, and in the lumbar region is surrounded by so much gliar tissue that it almost resembles the condition frequently seen in syringomyelia. Very distinct degeneration is seen in the posterior columns below the area of compression, not limited to Schultze's comma zones, and involving most of the transverse area of the posterior columns, except at their periphery, where the long neurones from the lumbo-sacral cord are found. This degeneration may be traced fully three and a half to four centimetres below the compressed portion of the cord.

The cells of the anterior horns in the lumbar cord appear to be normal both in shape and number, but Clarke's columns are entirely deprived of cells throughout their extent in the thoracic region, and in the upper part of the lumbar cord, where they contain normally very many cells, they present the usual form but are without cells. The fibres within these columns from the posterior roots are normal in number. Careful seai-ch may possibly reveal here and there an atrophied cell in these columns.


This is evidently a case in which compression has played the chief role, but there is some round cell infiltration about the vessels of the pia and certain of those of the cord as far as the lower thoracic region.

The Marchi stain reveals degenerated fibres scattered all over the transverse area of the cord below the compression, but these are most numerous in the anterior columns.

The ascending degeneration in the pyramidal tracts, both crossed and direct, observed in the case B. H., is worthy of mention. In the crossed pyramidal tract this is more distinct than in the direct, and extends through several cervical segments. This retrograde degeneration has formed the subject of study in a number of cases, and in 1896, in the American Journal of the Medical Sciences, Dercum and Spiller gave the literature on the subject so far as they were able to obtain it. It has been explained by some writers, and especially by Sottas, as an upward degeneration in motor fibres which, of course, conduct impulses downward ; by others it has been thought to be an involvement of associative fibres — of fibres which arise within the spinal cinerea, pass out into the lateral column and terminate within the cinerea at higher levels. In favor of the first view is the fact that it is found usually in processes of long duration, for I am unaware that it has been described as occurring in any acute process, which we should expect would be the case if it is merely a cellulifugal degeneration. Then again, when the remaining part of the lateral column and the crossed pyramidal tract are degenerated the process often does not extend so far upward in the former as in the latter. Thus Hoche* mentions degeneration of fibres in the lateral column, not belonging to any known system, extending through three segments above the focal lesion, and of the crossed pyramidal tract extending through seven segments. It is not easy to explain this on the assumption that longer associative fibres are found in the crossed pyramidal tract than in the remaining part of the lateral column. " The law of the excentric position of the long tracts in the spinal cord " (Flatau, Zeitschrift f. klin. Med., Vol. XXXIII, Nos. 1 and 2), which simply means that the long fibres take a peripheral and posterior location, might possibly be used as an argument. Eggerf explains the retrograde degeneration of the crossed pyramidal tracts, observed in his case, by the theory that it represented short fibres, and that sclerosis occurred when these fibres were degenerated, and that this in turn caused degeneration of the long pyramidal fibres. I have several times observed this retrograde degeneration of the motor tracts and am convinced that it is more common than is usually supposed. In my case B. H. the normal fibres in the crossed pyramidal tract below and near the focal lesion are not numerous. Below the transverse lesion these ascending associative fibres, having their origin in the sjiinal cinerea, should not be affected, and they should be in normal number, if retrograde degeneration is to be discarded. If we grant that retrograde degeneration may occur in associative fibres, we should be at a loss to explain why the pyramidal fibres are not subject to the same laws, and we must


Hoche, Archiv fiir Psychiatrie, Vol. XXVIII, 189G. f Egger, Archiv fiir Psychiatrie, Vol. XXVII.


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grant the possibility of this form of degeneration in order to exphiin the degeneration of the direct cerebellar tracts below the transverse lesion in this case.

lu the direct pyramidal tracts the degeneration possibly is confined to Marie's* sulco-marginal zones, but does not extend very far upward. 1 know of no way in which the question as to whether it involves associative fibres here, or fibres of the direct motor tracts, may be settled. These areas may degenerate upward for a long distance. Iloche (1. c), for instance, has traced this degeneration from a lesion in the mid-thoracic region into the motor decussation, and Dercum and Sjiiller (/. c.) traced it from the upjier thoracic region to the same point.

The degeneration of Gowers' tract below the lesion, which is observed in the case B. H., has been found also in other cases, and it seems to be generally held that this tract contains fibres which conduct impulses in both directions. Hoche (/. 6".) in a case with a lesion of the mid-thoracic region found this bundle degenerated below the lesion as far as the lower lumbar cord. This is where many neuropathologists believe the bundle arises, — at a lower level than the direct cerebellar tract. Daxenbergert and others speak of descending degeneration of Gowers' tract.

The fact that fibres of the antero-lateral column not belonging to any known system degenerate only a few segments either above or below a transverse lesion of the cord has been observed in many cases. This may be well seen in the case B. H. The restoration of fibres in the antero-lateral column begins always nearest the cinerea, for these in this portion are short associative fibres, and the Grenzschicht of Flechsig is never degenerated through any great extent of the spinal cord. This is in conformity with "the law of the excentric position of the long tracts in the spinal cord." (Flatau, I. c.)

As a rule the comma zonesof the posterior columns can only be traced a short distance by Weigert's stain, two, three or four segments, but when the Marchi method has been employed they have been followed much further. In the case B. H. they are not sharply separated from the degenerated fibres in the rest of the posterior columns, though the area occupied by them is possibly slightly paler by Weigert's stain. This generalized degeneration of the posterior columns seems to me well worthy of note, for it can be followed four centimetres below the focal lesion, through several segments, in portions of the cord in which the gray matter is apparently normal. It seems to be more extensive than that we are accustomed to speak of as the traumatic zone, for according to Schiefferdecker the traumatic degeneration extends above or below a focal lesion only about J to 1 cm. (quoted by Worotynski, Neurologisches Centralblatt, No. 23, 1897). I am inclined to regard this descending degeneration in the posterior columns as retrograde, if we have the right to use such a term for a process which is more one of atrophy than degeneration. It may be that the development of the compression at the early age of


Marie, Lerons sur les maladies de la moelle. Paris, 1892. fDaxenberger, De itsche Zeitschrift fiir Nervenheilkunde, Vol


IV.


three years explains this condition, for we have been taught that the pyramidal fibres are not fully developed until the fourth year of extra-utei'ine life. We know that the fibres of the posterior columns receive their medullary sheaths quite early, but it is possible that at the third year of extra-uterine life— if we can believe that the compression of the cord in the case B. H. was already well developed at that period — these fibres are less resistant than they are later.

Similar diffuse descending degeneration in the posterior columns below the area of compression has been noticed in a case of Pott's disease by Fiirstner. In his case the compression was at the level of the ninth thoracic vertebra. He describes the lesion as follows : " There is a degeneration in the posterior columns which is not very intense, but which may be traced into the lumbar region, and occupies almost the entire width of the posterior columns, with the exception of the peripheral })ortion of these columns and of the well known band of fibres which has its course parallel to the posterior horns." This degeneration of the posterior columns Fiirstner* regarded as wider than that we not infrequently see in Schultze's comma zones.

Cellulipetal degeneration of sensory fibres has been considered a rare occurrence, and indeed I have seen the statement (Nageottef) that retrograde intramedullary degeneration of posterior root fibres has never been observed. It would be difficult to explain the descending degeneration of the posterior columns as an involvement of the associative fibres, for V. LenhossekJ tells us that positively there are only a few cells in the posterior horns which send their axis cylinders into the posterior columns.

The descending degeneration of the direct cerebellar tracts has not been frequently mentioned, and the completeness of it in the case B. H. is possibly due to the early age of the patient at the time the destruction began. Striimpell,§ Daxenberger,|| and BischofTTf have spoken of it, and Bischoff thinks it is possible that the destruction of the direct cerebellar tract in his case may have had a connection with the descending cerebellar fibres described by Biedl.** In his case the cells of Clarke's column were normal. Thomas,ftin lesions experimentally produced on the cerebellum in the dog, found atrophy of these cells. In Daxenberger's (I. c.) case also these cells were not normal in number and size, nor were they normal in Striimpell's {I. c.) case. I have, therefore, searched carefully for cells in Clarke's column in the case B. H. and have been unable to find them, even in the lumbo-thoracic segments, where normally they are most abundant. A very few atrophied cells may be found by diligent search. The fibres within Clarke's columns are normal in appearance, as we should expect them to be, inasmuch as most of them come


Fiirstner, Archiv fiir Psycliiatrie, Vol. XXVII. f Nageotte, Revue Neurologique, 1 895.

I v. Lenhosst'k, Der feinere Bau des Nervensystems. Second edition, p. 355. »

§Striimpell, Archiv fiir Psychiatric, Vol. X.

I Daxenberger, Deutsche Zeitschrift f. Nervenheilkunde, Vol. IV.

1[ Bischoff, Wiener klin. Wochenschrift, No. 37, lS9fi.

Biedl, Neurologisches Centralbl., 1895, p. 434. ft Thomas, Le Cervelet. G. Steiuheil, Paris, 1897.


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from the jjosterior roots. This retrograde degeneration of sensory fibres — for we hiive every reason to believe that the direct cerebellar tract is sensory — extending even to the origin of the fibres within the cells of Clarke's colnmn, is of considerable importance and has rarely been described. It is probably due to the fact that the destruction began when the jiatient was very young, for such complete cellular atrophy is far more common in the young, as many experimental lesions have shown. It is also possible that the cells of Clarke's column were altered by the "reaction at distance" before the fibres of the direct cerebellar tracts were entirely degenerated.

In the case B. H. the area of degeneration, representing the fibres of the crossed pyramidal tract, in its downward course passes toward the periphery of the cord, and in the lumbothoracic region occupies the external and posterior part of the lateral column. Normal fibres are found in the crossed pyramidal tract below the area of compression, but they are not nearly as numerous as I have been led to expect from similar lesions of this tract reported in the literature, though in my case B. H. the normal fibres within this tract are more numerous at low than at high levels of the thoracic cord. It has been frequently stated that degeneration of the crossed pyramidal tract, resulting from a cerebral lesion, is less extensive than that following a spinal lesion. It may be that fibres of cerebellar origin — Van Gehuchten's* cortico-ponto-cerebellospinal tract — are added to the cortico-spinal tract, or that a system of fibres forming the anterior part of the crossed pyramidal tract arises in the thalamus, as v. Bechterewf has concluded from the investigations of Boyce and Sakowitsch and from a study of the greater area of the lateral motor tract as represented during its myelination, compared with the area as represented by degeneration from cerebral lesions.

It is unquestionably true that the degenerated area of the crossed motor tract in the case B. II. is greater than that we find after cerebral lesions, but this is also partly due to the fact that many associative fibres are destroyed. It is probable that some associative fibres are contained within the lateral motor tract, but I cannot believe, from the case B. H., that fibres which arise below the lower cervical segments and pass downward are very numerous within this tract.

There is no atro23hy of the motor cells of the anterior horns in the lumbar region, although we should expect to find it in this case, if in any, on account of the early age at which the transverse lesion occurred. I have never been able to observe this atrophy of the cell body of the peripheral neurone resulting from a lesion of the central neurone, and confess that I have always been most skeptical regarding statements concerning its existence. Recently, however, SchafferJ has published some noteworthy observations of tertiary degeneration. It may be mentioned that Egger {I. c.) says that in his case the cells were less numerous in one anterior horn in the lumbar region. I am not questioning Egger's statement, but from repeated observation we know how likely one is to be misled


in an investigation of this kind, for often in normal cords the cells in the two anterior horns are not equally numerous, and we have no standard of what constitutes a normal number of cells.

Bruns* found the crossed pyramidal tracts, esjiecially the right, wonderfully well preserved below and near a transverse lesion, though they were not entirely normal ; and the explanation he suggests is that the degeneration began in the peripheral end of these tracts and had not extended to the traumatic area within the space of about four months. In my case B. H., which had lasted five years, this difference in the degree of degeneration in the distal and more proximal portions of the pyramidal tracts is not observable.

The degeneration in the antero-lateral columns in Bruns' case was believed by the author to represent the fibres of the direct pyramidal tract, descending fibres of Glowers' column, fibres of the systeme descendant du zone sulco-marginale (Marie) or faisceau marginal (Lowenthal), fibres of the faisceau intermediaire du cordon lateral (Lowenthal), and the descending cerebellar tract of Marchi. The latter has never been demonstrated in man (Thomas). These areas are degenerated in the case B. H., and they have been found altered by Westphal, Schnltze, Tooth, Schmauss, Daxenberger (quoted by Bruns) and others in cases observed by them.

Bechterewt has recently shown that there is still another system in the inner portion of the anterior column of the cord, and that this system arises in the anterior part of the corpora quadrigemina. He gives no name to this or to his system anterior to the crossed pyramidal tract, and we may, perhaps, speak of them as the quadrigemiuo-spinal and the thalamo-spinal tracts.

Dr. Young states that the patellar reflex in the case B. II. was diminished. So much has been written on the loss of the reflexes in total transverse lesions situated high in the cord that I may simply refer to the excellent papers by Bastian,! Bruns,§ Egger,|| Hoche,][ Habel** and others. Bruns' case was the first in which the reflexes were lost, and the entire spinal cord, the roots of the Cauda equina, and a number of nerves and muscles of the lower extremities were examined microscopically. The changes in the nerves and muscles were not of great importance and could not be used to explain the absence of the patellar reflex and the flaccidity of the paralysis.

The posterior roots in Bruns' (I. c.) case in the area of total traumatic degeneration were remarkably well preserved, but the anterior were totally degenerated. He gives no satisfactory explanation for this. In the first case reported in this


Van Gehuchten, Journal de Neurologieet d'Hypnologie, 1897. t V. Bechterew, Neurologisclies Centralblatt, No. 23, 1897. JSchaffer, Jlonatsschrift fiir Psychiatrieund Neurologie, Vol.11, No. 1.


Bruns, Archiv fiir Psychiatrie, Vol. XXV, 1893. f Bechterew, Neurolog. Centralbl. No. 23, 1897.

IBastian, A Dictionary of Medicine, edited by Richard Quain, M. D., F. R. S., p. 1481. Medico-Chirurgical Transactions, published by the Royal Medical and Chirurgical Society of London, Vol. 73, p. 151.

§ Bruns, Archiv fiir Psychiatrie, XXV.

II Egger, Archiv fiir Psychiatrie, XXVII.

II Hoche, Archiv fiir Psychiatrie, XXVIII.

Habel, Archiv fiir Psychiatrie, XXIX.


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paper the postorior roots were less affected. This is probably due to the fact that the anterior roots were most exposed to pressure and the invasion of the tuberculous process, and shielded to some degree the posterior roots placed behind them.

Bischoff (7. c ) concluded from his examination of a case of Pott's disease that the root fibres which enter below the second thoracic segment do not form all of Goll's columns, inasmuch as the ventral and lateral portions of these columns in the cervical region are formed by fibres from higher segments and IJrobably not by those from the thoracic region.

If this view of Bischoff, viz. that the ventral and lateral parts of Goll's column are formed by fibres of the cervical roots, is correct, we are not surprised that these are the portions which the cervical fibres occupy. We know that the higher the degeneration of the posterior roots extends, the greater is the degeneration of the ventral and lateral portions of the postero-median columns in the cervical region. Reference may be made to the two cases pictured in the author's digest on the pathology of tabes,* or to many other cases, in illustration of this point. But there is considerable evidence to show that above the sixth thoracic roots the column of Goll in man is fully formed. In Pfeiffer'st case in which the first and second thoracic roots, in Nageotte'sJ case in which certain fibres of the second and third posterior thoracic roots, in Marguli6s'§ case in which the right sixth posterior thoracic root, and in Dejerine and Thomas'|| case in which the eighth cervical and first thoracic roots were affected, the columns of Goll in the cervical region were not degenerated. Bischoff employed the method of Marchi, and his results were possibly more accurate than those of the above-mentioned cases in which the hisematoxylin of Weigert was used.

The case B. H. bears on this subject. The transverse lesion is situated in the lower cervical and upjier thoracic cord, and at the mid-cervical region the columns of Goll are degenerated as far as the posterior commissure and spread out against the commissure in the well known flask-like form. The columns of Burdach also show distinct degeneration, but just below the motor decussation (first to second cervical segments) the degeneration is almost entirely confined to the columns of Goll, and only along their lateral borders is a slight degeneration of the columns of Burdach. At this level the columns of Goll do not extend to the posterior commissure. The columns of Goll, as they are represented by the degenerated area in the sections from the case B. H., do not receive cervical fibres except from the lowest cervical roots, if they receive them from these.

In a paper read at the last meeting of the American Medical Association IT[ attempted to show that there is considerable evidence for the theory that tuberculosis of the cord and its


Spiller, International Med. Map. 1897. •fPfeiffer, Deutsche Zeitschrift fiir Nervenheilkunde, Vol. I.

X Nageotte, Revue Neurologique, 1895.

gMargulies, Neurologisches Centralblatt, 1896, p. 347.

II Dejerine and Thomas, Comptes rendiis de la Societe de Biologie, 1896, p. 679.

II Spiller, The Journal of the American Medical Association, April 9, 1S98.


membranes may appear in the form of simple meningomyelitis, without the presence of giant cells, miliary tubercles, or even detectable bacilli, especially if Miiller's fluid has been used for hardening. I was led to this conclusion after the examination of a case of meningomyelitis, apparently due neither to syphilis nor tuberculosis, as far as specific lesions were concerned, in a person who had died from generalized tuberculosis.

When the idea that spinal tuberculosis might appear as simple meningomyelitis first presented itself to my mind I was not aware of the attention which this subject had received, and was therefore somewhat surprised by the results of my examination of the literature. I found that a number of writers hold that both syphilis and tuberculosis may appear as simple meningomyelitis. Oppenheim, for instance, says: "We observe in syphilitic and tuberculous persons a form of myelitis which neither clinically nor anatomically can be considered specific, and yet it must stand in some relation to the infectious process."*

In the examination of these two cases of Pott's disease I have not noticed any lesions interior to the dura which might be called specific. It hardly seems probable that any one would hesitate to call these two cases tuberculous, unless the question of the rare manifestation of syphilis in this form might arise. The caries of the vertebras, the external pachymeningiti?, the giant cells, the necrosis of tissue within the tubercles, the epithelioid cells, render the diagnosis of a tuberculous process very probable. Within the dura, especially in the first case, the meninges are infiltrated with round cells, some of the vessels show a distinct endarteritis, round cell infiltration may be found about certain vessels within the cord, and in the first case several foci of degeneration may be noticed in the posterior columns at a considerable distance above the point of compression. A nuclear stain shows that these foci are the seat of a slight round cell infiltration. Within the dura, therefore, at least in one of these two cases of tuberculous spondylitis, only the signs of an ordinary meningomyelitis are present, even at some little distance from the seat of compression. Indeed in this first case the compression was so slight that it did not produce ascending or descending degeneration. The action of bacterial products on the cord need cause no surprise. We have had numerous experiments on this subject, and in this country Welchf and FlexnerJ have done much to enlighten us.

It is' not clearly proven that the tuberculous process, external to the dura in my first case, has been the cause of the meningomyelitis, but it seems probable. If now a simple meningoijiyelitis may be produced by a process probably tuberculous external to the dura, what is there objectionable in the theory that it may also be produced by a tuberculous process external to the vertebrse ?

Boettiger§ has attempted to show that the tuberculous and


Oppenheim, Lehrbuch der Nervenkrankheiten, p. 224. I Welch and Flexner, The Johns Hopkins Hospital Bulletin, II, 107, 1891 ; III, 17, 1892. ) Flexner, The Johns Hopkins Hospital Reports, VI, 1897. § Boettiger, Archiv fiir Psychiatrie, Vol. XXVI, 1894,


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the syj^bilitic meuingomyelitis are the same in their histological appearances, and Raymond says that " the syphilitic meningomyelitis at its commencement has nothing specific but its cause ; it has nothing specific so far as relates to the appearances under the microscope."* It therefore follows from this and other papers that the tuberculous meningomyelitis has nothing specific histologically at its commencement except the bacillus.

Virchowt teaches, if I understand him rightly, that in contusion and similar conditions with extravasation of blood, chemical products are formed which act as irritants with or without the presence of bacteria, and he compares these products with those formed by the micro-organisms. If this is true it may have some relation to the meningomyelitis in my first case.

I have been much interested in trying to find the nature of this round cell proliferation observed in these and other cases of meuingomyelitis, and its final destiny. Raymond {1. f.) speaks in very positive terms, and Virchow (I. c.) in his paper on inflammation says that even yet the expression "small cell infiltration" is commonly used. I have been frequently struck by the expression "leucocytic infiltration," and have sought to find some authority for its use. It seems to be the opinion of some writers that unless we find multinuclear cells or cells with multilobular nuclei we have no right to speak of "leucocytic infiltration," and that we should regard the cells containing little protoplasm and large single and round nuclei as proliferations of connective tissue or its analogon, the neuroglia. But surely there are such cells as these within the blood.

Raymond (J. c), in speaking more especially of syphilis, tells us that these round cells may undergo a retrograde change and disappear, or that they may form larger or smaller masses and undergo a gummatous change, or that they may form connective tissue and give rise to sclerosis.

StriimpellJ takes a very decided stand in regard to the presence of meuingomyelitis in Pott's disease. He says that all the changes in the spinal cord in spinal caries are only the necessary consequences of purely mechanical pressure. "At all events," he continues, " as we must state after numerous examinations made by us, in opposition to the prevailing view, no one has the slightest right to explain the paralysis occurring from sjjondylitis as the result of secondary myelitis." If preparations are made from the spinal cord, there are, according to Striimpell, no vascular changes to be found, no hypersemia, no accumulations of cells about the vessels, and only occasionally small traumatic haemorrhages. Frequently thei'e are foci of degenerating nerve fibres, groups of swollen axis cylinders with partial or complete loss of their medullary sheaths, and in places spaces from which the nerve fibres have disappeared. In later stages there is proliferation of the neuroglia.

We can hardly be in doubt from this as to what Striimpell considers evidences of inflammation, for our views on this subject do not always harmonize.

Striimpell finds a supporter in Kraske {I. c), who also says


•Raymond, Le(;on sur les maladies du Bysteme nerveux, deuxieme serie, p. 491.

f Virchow, Virchow's Archiv, Band 149, Folge XIV, Band IX, 1897.

t Striimpell, Lehrbuch der spec. Path. u. Ther,, Vol. III.


that the paralysis cannot be attributed to secondary inflammatory changes in the cord, and that this is equally true of the rare cases in which the cord is involved in the tuberculous inflammation, for this involvement occurs after the paralysis and toward the end of life. He acknowledges that the views regarding the relation of the paralysis to the tuberculous inflammation are still contradictory to one another.

Dinkier* reports a case in which two lesions were present in the spinal cord, one at the second and third thoracic segments, and one at the sixth, seventh and eighth thoracic segments. The lower lesion was evidently the older and showed proliferation of the glia, round cell infiltration, distension of vessels, etc. The upper lesion Dinkier regarded as the result of a dural tuberculosis, and he states that it was a typical compression lesion such as was described by Schmaus. Dinkier mentions, however, that at this upper level he noticed round cell infiltration in the pia and arachnoid. It seems to me, therefore, that both these lesions must be regarded as iuflalnmatory. Dinkier states that tuberculosis of the lungs and vertebrae of ten causes mixed infection, and bethinks the lower lesion was possibly a metastatic process which had its origin in the pulmonai-y tuberculosis. It is difficult to see why the lower lesion should not be regarded as tuberculous, but be that as it may, it is evident that meningomyelitis may be caused either directly or indirectly by the tubercle bacillus, and even before paralysis appears, as in my first case.

Furstnerl observed intense round cell infiltration of the membranes and cord in a case of Pott's disease. He had operated on his patient, but there is no reason to think the cord was infected at the time of operation. It would not be difficult to quote other cases of Pott's disease in which meningomyelitis was observed.

In one of my cases there are large accumulations of round cells within the cord about the vessels, vascular dilatation and some swollen axis cylinders. These are distinct signs of inflammation, and indeed it seems to me after reading Virchow's recent address in Moscow that we should regard the swelling of the axis cylinders as a sign of parenchymatous inflammation. If we do so, we shall have difficulty in separating degeneration of nerve tissue from inflammation. These are Virchow's words : " I chose the name of parenchymatous inflammation for that process which, in the first place, produces swelling of the specific portions."

It is not easy, according to Bruns,J to determine the truly inflammatory nature of myelitis, and anatomically it is possible with certainty only in the very rare cases in which the producers of the inflammation (Eutziindungserregern) have been shown to be present in the cord. By this I suppose he means the bacteria. All other histological findings which are regarded as chai'acteristic of inflammation are found in cases of tumor and compression, cases which cannot truly be regarded as inflammatory. They are present also in thrombotic softening.


Dinkier, Deutsche Zeitschrift fiir Nervenheilkiinde, Vol. XI, Nos. 3 and 4. f Furstner, Archiv fur Psychiatric, XXVII. |Bruns, Allgemeine Zeitschrift liirPsychiatrie, Vol. LIII, p. 614.


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In contradiction to the statements of Striimpell, Noble Smith* informs us that the nerve symptoms in spinal caries are much more frequently the result of the inflammatory process extending to the cord or nerves than they are of pressure. This, however, does not seem tobe the generally accepted view. I cannot follow Smith when he says that recovery occurring after symptoms of paralysis may indicate regeneration of pyramidal fibres. While regeneration frequently occurs in the peripheral nerves, and theoretically there is no reason why it should not occur within the cord, as a matter of fact the evidence of the latter is not satisfactory, as Leyden and Goldschcider state.

I shall merely touch upon the subject of operation in Pott's disease, as it hardly comes within the scope of this paper. Paralysis so frequently exists without degeneration of fibres that we can hardly be too cautious in suggesting surgical interference, at least by any of the older methods. It is not uncommon to find that the paralysis disappears even when it has existed for some time. It seems to be in these cases merely the expression of a functional change. Oppenheimt reports a case in which the paralysis disappeared after a duration of five or six years. Recently Calot's method has received great attention, although one writer states that its principle is as old as Hippocrates. This statement, however, can hardly detract from the honor due Calot. The time has been too short to judge fully of the eiHcacy of the method. The chief fear seems to be that the forcible reduction may arouse a quiescent process. In the first of my two cases there is a possibility that it might have increased the meningomyelitis, and in the second case it could have done little or no good, but in this case Calot would not have advised it.

Occasionally we hear of cases in which the method has not been sue 3ssful and the patient has died of tuberculous meningitis after a few months. We cannot forget the hopes that were at one time raised by the suggestions of operation on the spinal vertebraj in Pott's disease, but the papers of Kraske {I. c), F".stnerJ and ])inkler§ are not encouraging, and Willard,|| at a meeting of the New York Neurological Society, voiced the general opinion of those present when he spoke of the disappointment which has followed surgical interference in these cases by the older methods.

Discussion. Dr. Barker. — There are many points in Dr. Spiller's report in common with a case which has recently been studied in the anatomical laboratory by J. Rosenheim. The latter has cut sections from many segments of the spinal cord of a case of Pott's disease, and although the results of the study have not yet been published, they are soon to appear. The pressurelesion in Mr. Rosenheim's case was situated between the 8th cervical and the 4th thoracic nerves, some three segmeats of the spinal cord being extensively involved. Above the lesion


Smith, Spinal Caries, second edition. tOppenheim, Berliner klin. Wochenschrift, No. 47, 1896. X Furstner, Archiv fiir Psychiatrie, XXVII.

§ Dinkier, Deutsche Zeitschrift fiir Nervenheilkunde, Vol. XI, Nos. 3 and 4. 1 WillarJ, Journal of Nervous and Mental Disease, April, 1897.


there was marked degeneration of Gowers' tract and of the direct cerebellar tract as well as of the dorsal funiculi. Below the lesions there were the typical degenerations in the pyramidal tracts.

Dr. Spiller has been able to trace a degeneration in the comma tract for a distance of 4 cm. below the lesion ; in Mr. Rosenheim's case it was possible to follow it through some three segments. We know now from the studies of Hoche, Mann and others that this tract is really a long tract extending throughout the whole thoracic region of the spinal cord. I did not understand from Dr. Spiller's paper whether or not he had found degenerations in the oval field of Flechsig in the lower portion of the cord. Mr. Rosenheim has been able to demonstrate degeneration in this area in his case, and there can be but little doubt from his findings and those in similar cases by Hoche that in some way or another certain fibres from the upper part of the cord are continuous with the oval field of Flechsig. It seems probable from Hoche's studies and from the researches of Bruce and Muir that there are two distinct descending endogenous tracts in the dorsal funiculi, one more ventrally placed corresponding to the " comma " tract and the "cornu-commissural fibres" of Marie; the other more dorsally placed and corresponding to somewhat scattered fibres in the upj^er portions of the cord, iu the lower portions to more compact bundles, the septo-marginal tract of Bruce and Muir, the oval field of Flechsig, and further down the triangle median of Gombault and Philippe. In order to bring these endogenous fibres of the dorsal funiculi into accord with corresponding fibres in the ventral and lateral funiculi I would suggest that we speak of the two ti-acts together under the name of the fasciculus dorsalis jn-oprius, distinguishing & jmts ventralis from a. pars dorsalis.

I am glad that Dr. Spiller has referred to the views of von Bechterew and others regarding descending fibres in the region of the pyramidal tracts, which probably have their origin in centres below the pallium. There is much evidence in favor of the view that very numerous nerve fibres come down from the region of the inter-brain and the mid-brain to the medulla and to the spinal cord, fibres which throw the lower motor neurones under the influence of higher centres. Without such fibres it would be difficult to explain many of the facts of comparative anatomy and of ontogeny. The studies of Dr. Melius show the importance of the substantia nigra as a waystation between the pallium and lower centres.

The changes referred to iu the nucleus dorsalis of Clarke are of especial interest, and Dr. Spiller has brought further confirmation of the view now universally held that the fibres of the direct cerebellar tract represent the medullated axones of the cells in the nucleus dorsalis. Thus far no one, unless it be Laura, has actually demonstrated the connection of Clarke's nucleus with the fibres of the fasciculus cerebello spinalis. The embryological studies of Flechsig, however, and the results of experimental degeneration as investigated by Mott, taken together with evidence which has been afforded by the study of changes in the nucleus secondary to lesions of the tract (as in cerebrosijjnal meningitis), make it almost certain that the axones of the tract and the cells of the nucleus both represent constituent portions of the same set of neurones.



Fig. 1.

Section just below tlie pyramidal decussation. The columns of Goll are entirely degenerated, with the exception of a few fibres along their periphery, and do not extend to the posterior commissure. The columns of Burdach are slightly degenerated adjoining the columns of Goll. Normal fibres are found in the area of the direct cerebellar tracts (tin).



Fig. o.

Section from the region of greatest compression, at the cervico-thoracic junction of the spinal column. The normal arrangement of the white and trray matter is entirely altered, and only a few normal fibres are present witliin the cord.




Fig. S.

Section from the niid-ccrvical region. The direct cerebellar tracts (pp) and columns of Gowers are greatly degenerated. The crossed and direct pyramidal tracts are also much degenerated. The columns of Goll extend to the posterior commissure. The columns of Burdach are not entirely free from degeneration.




Fig. 4.

Section from the lower part of the compressed area. The anterior horns uu are indistinctly marked out by normal fibres in the adjoining columns. The greater portion of the section is entirely dcircnerated.



1 m »3 J,



Fig. 5.

Section 3}^ em. below Fig. 3. The antero-lateral columns, includini^ the direct cerebellar and Gowers' tracts (lyy) and the periphery of the anterior columns, are greatly degenerated. The ventral portion of the posterior columns is also distinctly degenerated.



^ Section from the mid-cervical region in Case I, showing intense cellular infiltration in the posterior septum (»;) near the posterior commissure. U Right and left columns of Goll.



Fig. 6.

Section fiom the mid-lumbar retrion. The direct (//•) and crossed pyramidal tracts are degenerated.

Figures 1 to 6 inclusive are from Case II.




.7--'^5H'




Osteoid masses contained within the tuberculous e.\udate in the tlioracic region (Case I). The majority of them are present in the outer zone of the exudate near the bony canal and only slightly removed from the intervertebral discs which show irregularities and are becoming clarified.


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Dr. Flexner. — Dr. Spillers pajier is an embarrassment of riches. There are two or three points only which the limited time will permit me to refer to. The first concerns the relation of degeneration in the nerve-raets and peripheral spinal nerves to changes in the motor cells of the anterior horns. I was surprised at the slight changes observed in the cells notwithstanding the extensive degenerations of the nerves. It is, of course, unnecessary to remind Dr. Spiller, or this audience, of the experimental and other work of Von Gudden, Friedlander, Grigoriew and Nissl, which has shown that the nerve cells suffer severely following injury to and removal of the peripheral nerves.

Dr. Spiller's remarks on this topic have raised the question of what characters stamp an inflammation as specific, that is, in this instance, as tuberculous. We have come to recognize in the micro-organisms of the specific diseases a capacity to produce definite histological structures which can be at once recognized as due to that cause — so, for example, the miliary tubercle — and at the same time, to give rise to other changes of a simple and non-specific inflammatory type. The thickening of the framework in the lung in tuberculosis is one example of such an action, and many other fibroid and degenerative processes in the body have the same origin. An intermediate sort of lesion is found in the diffuse tuberculous tissue in which even giant cells may be wanting and bloodvessels present, and whose specific characters are given through the presence of tubercle bacilli and the degenerations which it tends to undergo. The crucial test, of course, is the finding of the tubercle bacillus, and in many chronic conditions this is a laborious undertaking.

It is interesting to have Dr. Spiller bring up again the Virchow conception of parenchymatous inflammation. Since the days of Cohnheim, jjathologists have demanded something more than a mere degenerative lesion before stamping the process "inflammation," and they have attemjjted, although it must be confessed not always with success, to mark off more sharply simple degenerative from actual inflammatory changes.

Dr. Spiller. — It is well known, as Dr. Flexner states, that the cells of the anterior horns of the spinal cord are affected by degenerative changes in the anterior roots. It is much to be regretted that the spinal cord in my first case was hardened in Miiller's fluid and that the application of the Nissl stain was impossible. In the thoracic region the motor cells were


distinctly altered. Could the Nissl stain have been employed, the cells of the mid-cervical region might also have been found degenerated. I have not intended to deny the existence of cellular lesions in the latter portion of the cord visible by Nissl's method, but I place very little value on studies of cells stained by carmine alone, unless the changes are of an intense degree.

I have been unable to stain the tubercle bacillus in this tissue hardened in Miiller's fluid, but Dr. Abbott and Dr. Flexner tell me that they know the bacillus has been found under similar conditions. As Dr. Flexner puts it, "it is a labor of love."

It is impossible to assert that the myelitis in my first case has been caused by the tubercle bacillus, though I have found no other cause. It is, however, a very important fact that myelitis of considerable intensity, withpolynuclear and mononuclear cellular infiltration, may occur in Pott's disease, and it is possible that some of the symptoms of this disease may at times be due to the myelitis and not entirely to the compression.

I should like to emphasize the statement that the degeneration of the posterior columns in my second case was not confined to Schultze's comma zones, but was much more extensive. This diffuse form of descending degeneration in the posterior columns of the cord has rarely been reported, and is entirely diflferent from the degeneration frequently observed in Schultze's comma zones, inasmuch as it is not systemic.

Note ou the osteoid tissue found iu the tubercular exudate iu the thoracic region of the cord. — Dr. Flexner. There is contained amid the typical tuberculous exudate, outside the dura, scattered masses of osteoid tissue. These are of irregular form and shape. They consist of a ground substance which is homogeneous or faintly granular or fibrillated, and contain irregular nuclei resembling, in part, bone corpuscles. For the most part the masses are non-calcified. But now and then calcification can be seen to be going on, and in such cases the masses take a blue hajmatoxylin stain. The majority of the flakes are in the outer zone of the exudatenearest the bony canal; and the cartilage of the intervertebral discs (0 shows slight irregularity, and in places is undergoing calcification. It is therefore not improbable that serial sections might have shown the osteoid masses to have originated from the intervertebral cartilages.


A CASE OF OSTEITIS DEFORMANS.


By Wm. T. Watson, M. IX, of Baltimore.


In 1876 Sir .James Paget reported to the Medical and Chirurgical Society of London, five cases of a previously undescribed disease to which he gave the name " Osteitis Deformans." He described one case in great detail and gave reports of both microscopical and chemical examinations of the bone.


Read before the Johns Hopkins Hospital Jledical Society, February 7, 1898.


Although a good many cases have since been reported, about sixty in all, nothing very material has been added to the description of the disease as first given by Paget. He gave as the chief characteristics of the disease the following :

It begins in middle age, or later ; is very slow in progress ; may continue for many years without influence on the general health, and may give no other troubles than those which are due to the changes of shape, size and direction of the diseased bone. Even


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when the skull is hugely thickened and all its bones exceedingly altered in structure the mind remains unaffected.

The disease affects most frequently the long bones of the lower extremities and the skull, and is usually symmetrical. The bones enlarge and soften, and those bearing weight yield and become unnaturally curved and misshapen. The spine, whether by yielding to the weight of the overgrown skull, or by change in its own structures, may sink and seem to shorten, with greatly increased dorsal and lumbar curves ; the pelvis may become wide ; the necks of the femora may become nearly horizontal, but the limbs, however misshapen, remain strong and fit to support tlie trunk.

In its earlier periods, and sometimes through all its course, the disease is attended with pains in the affected bones, pains widely various in severity and variously described as rheumatic, gouty or neuralgic, not especially nocturnal or periodical. It is not attended with fever. No characteristic conditions of urine or feces have been found in it. It is not associated with syphilis or any other known constitutional disease, unless it be cancer.

The bones examined after death show the consequences of an inflammation affecting, in the skull the whole thickness, in the long bones chiefly the compact structure of their walls, and not only the walls of their shafts, but, in a very characteristic manner, those of their articular surfaces.

In 1890, fourteen years later, after Paget bad seen 33 cases of the disease, he made the following statement :

1. The preponderance of males among the patients affected with this disease is confirmed.

2. The most frequent ages at which the disease was flrstobserved were between 40 and 50.

3. The frequency of cancer or sarcoma occurring in those affected with osteitis is confirmed. Of eight cases traced to the end, five died with cancer or sarcoma. This fact, confirmed as I believe it is by the observations of others, is decisive as to an intimate relation between osteitis and the formation of malignant tumors. I do not venture to guess what that relation is.

4. It may be only by chance coincidence, but it seems worth mentioning that in 23 cases, 4, after long continuance of the osteitis, became blind — 1 with choroiditis, 3 with retinal ha;morrhages.

5. I have tried in vain to trace any inherited tendencies to the disease. Many have had gouty ancestors, but I do not think more than any other equal number of persons in the same rank in life.

6. The most frequent seats of the osteitis are the tibise, femora, clavicles, spine, and vault of the skull. The posterior and regularly median curvature of the spine is always well marked, the pelvis often broad. I have never seen any evidence of the disease in the bones of the face, hands or feet. In this respect the contrast with the acromegaly of Marie has seemed complete.

The morbid anatomy, as given by Paget, is as follows :

Periosteum not visibly changed. The outer surface of the walls of the bones irregularly and finely nodular, as with external deposits or outgrowths of bone, deeply grooved with channels for the periosteal blood-vessels, finely but visibly perforated in every part for the transmission of the enlarged small blood-vessels. Everything seemed to indicate a greatly increased quantity of blood in the vessels of the bone.

The medullary structures appeared to the naked eye as little changed as the periosteum. . . . The medullary spaces were not encroached upon.

The compact substance of the bones was in every part increased in thickness. ... In the greater part of the walls of the shafts of the bones the whole construction of the bone was altered into a hard, porous or finely reticulate substance like very fine coral. In some places there were small, ill-defined patches of pale, dense and hard bone, looking as solid as a brick.

lu the compact covering of the articular ends of the long bones


. . . the increase of thickness was due to encroachment on the cancellous texture, as if by filling its spaces with compact porous new-formed bone.

The microscopical appearance as given by Mr. Butlin is as follows:

The number of Haversian systems and canals in any given section would seem to be much diminished. The space between the Haversian canals was occupied by ordinary bone substance, containing numerous lacunae and canaliculi. The Haversian canals were enormously widened, many of them were confluent, and thus the appearance of a number of communicating medullary spaces was obtained ; an appearance that was rendered still more striking by the presence in the canals of a large quantity of ill-developed tissue in addition to the blood-vessels.

The contents of the Haversian canals were seen to consist generally of a homogeneous or granular basis, containing cells of round or oval form, about the size and having much the appearance of leucocytes. Larger nucleated cells were also present, and fibres or fibro-cells sometimes in considerable quantity. Myeloid cells were occasionally observed, but they were not plentiful. Fat also existed in many of the larger spaces, especially in the skull. The vessels were unusually small compared with the channels in which they ran ; indeed, they did not seem to be larger than those of normal bones.

The walls of some of the canals were lined by a single layer of osteoblasts — a condition precisely similar to that observed in a normal ossification of the bone in membrane.

The presence of new bone was most evident in the periosteum of the tibia, external to the ordinary compact layer of the shaft. This external layer was of course but thin, and was much softer and less developed than the cortex of the bone from which it sprung. It evidently was not nearly sufficient to account for the great increase in the diameter of the tibia. There was no similar recent formation of bone on the outskirts of the medullary canal.

The number of lamellse surrounding the Haversian canals was no larger than in normal bone, whilst tne arrangement of the intervening space was most complex and totally different from that of healthy bone. Lacunse and canaliculi throughout the sections did not strikingly differ from those of ordinary bone.

As to the nature of the disease, Paget, Butliu, Clutton, Eve, Silcock and others believe it to be a chronic inflammation of bone, but Goodhart, Lunn and others do not deem that its inflammatory nature has been proven.

Lunn, who reported 4 cases in 1885, while admitting that chronic inflammation might have some share in the process, thought that it would not altogether account for the changes found after death. His conclusions were that osteitis deformans consists of —

1. A constitutional disease, producing atrophy and absorption of a large part of the osseous system.

2. Consequent weakening of the bones so that they yield when exposed to strain.

3. Compensatory strengthening by the growth of what may be looked upon as a variety of callous.

4. The occasional formation of definite tumors.

5. A fatal cachexia.

Commenting upon these views, Silcock, in 1885, said : It is difficult to imagine how a process can primarily be one of atrophy and absorption when the first recognizable sign of the disease is the thickening and enlargement of the bone. Nor can the superadded bone in this case be regarded in the light of "compensatory strengthening " of the curves, or of a buttress-like forma


Fici. 1. Skiagraph ol' left Uunu juint. Tibia sieatly eiiiargx'd. Fibula aiipaiontly iioi'mal.



Side view, sljowiug bowing of liaeli ami lower extremities.



Fid. :,.

Head view, sliowing enlariremeiit of cranium, the face bones remaining normal.



Slviasrraph of left tibia, showing marked anterior curvature, and srreat thickening. Dark and light areas probably eorrcspcind to areas of condensation and rarefaction.


June, 1898.


JOHNS HOPKINS HOSPITAL BULLETIN.


135


tion, since the mass of it is deposited on tlie convexity of tlie curve and not in tlie concavity. As^ain, the external thickening of the bones of tlie cranium is wholly inexplicable on the theory enunciated. As held by Paget and Butlin, the essential features of the osseous lesions of the disease are indistinguishable from, if not highly characteristic of, inflammation.

Concerning the etiology of osteitis deformans absolutely nothing is known.

It is more frequently seen in England than elsewhere, and is more common in London than in other parts of England. This fact led Johnathan Hutchinson to conclude that the malady was probably connected with gout, but this view has not been accepted by others.

Diagnosis: The diseases with which it might possibly be confounded are rickets and osteomalacia. In rickets the bones are too short and not too long, too small, not too large; and their curvatures are not like those of osteitis.

In osteomalacia the walls of the bones become exceedingly thin, and when they yield it is not with regular curving, but with angular bending or breaking.

The course of the disease is very chronic. When death ensues it is from some coincident disease which has been aggravated by the condition of the bones only in so far as they may have diminished the range of breathing and the general muscular activity.

Sis cases of this disease have been reported in America, the first by McPhedran in Toronto in 1885, the second by Gibney in New York in 1890, the third by Mackensie in Toronto in 1891, the fourth and fifth cases by Taylor in New York, 1892, and the sixth by Herwisch in Philadelphia in 1896.

The present case is then the seventh to be reported in America and is more typical than any of the others.

I had hoped to be able to bring the case before you to-night, but have been disappointed. I have, however, some photographs which will in some measure make up for his absence.

R., aged 63. Family history unusually good. His father was a French Canadian, born near Montreal, who "never had a day's sickness," and died of congestion of the brain at the age of 79. His father's brother, at the age of 100, was killed while walking on a railroad track. His mother was born in New Jersey and died on her 90th birthday of old age. He has two brothers living at the ages of 73 and 75. No relative ever died of cancer.

Personal histori/. He was never in bed a day from any illness. A slight attack of measles in childhood and a carbuncle ten years ago were his only ailments. He has always led a very active life. He conducted a successful business from 1860 until 1886, and did not then retire on account of physical or mental disability. Every year since he was a boy he has indulged in fishing, duck shooting, sailing and outdoor sports. Up to the age of 43 he was strong and active, " as straight as an arrow," and five feet eleven and three quarter inches in height.

The present malady began about 35 years ago, when the skin over the anterior portion of the upper half of the left leg became inflamed, the inflammation gradually spreading to the ankle. Later on an inflammation appeared on the correspond


ing portion of the right leg. This lasted four or five months and then subsided, leaving behind some large pigmented areas.

About twenty years ago he began to have pains in the bones and calves of his legs. The calf muscle would be drawn into bunches. These pains have persisted more or less ever since, usually worse at night. At the onset of these pains he noticed for the first time that his legs were bending and his height was diminishing. This bending of the legs has steadily advanced and is still progressing.

About fifteen years ago the increased size of his head began to attract attention. This increase, the patient is confident, began 35 years ago, when at the age of 37 he had to increase the size of his hat from a No. 7 to a 7 J. At intervals of four to five years he has had to take a hat a size larger, until now he wears a No. 8. This indicates a total change in circumference of 3y^y inches. There has been no evident increase in the size of the head for three or four years past. He has never had pain or discomfort of any kind in his head.

Ten years ago his back commenced to bow and the shape of his chest to change, becoming flatter in front. These changes are still progressing. His height was formerly five feet eleven and three quarter inches. In July, 1897, it was five feet three inches. At the present time it is five feet two and one-half inches. Total loss in height nine and one quarter inches. This loss of height, due to bowing of the back and lower extremities, is rapidly progressing.

The general health of the patient has continued very good. While his gait is awkward it is steady, and his only complaint is of the pains in his legs and thighs, which are not so annoying as formerly. His intellect is unimpaired.

In the fall of 1896 he went on a hunting trip. When attempting to take aim he found to his surprise that he could not see with his right eye.

Present: condition. In July, 1897, I took R. to Dr. Osier, who made the diagnosis and dictated the following note:

" Head fairly symmetrical, looks large ; the most marked prominences are just over the temporal muscle at the squamoparietal junction. Above this there is a distinct groove like flattening, and then a marked prominence on either side of the parietal suture. The j^osterior parts of the parietal bone and the occipital bone are uniform and symmetrical.

No apparent enlarging of the bones of the face; no enlargino- of the jaws or of the zygoma ; in fact the face looks small in proportion to the size of the head. Teeth are bad ; nearly all gone. No enlargement of maxillary process.

Body: No enlargement of cervical vertebra. A most remarkable bowing of the dorsal spine. The lordosis is of the most extreme grade. There is no special prominence of any of the vertebra;. The ribs do not appear to be enlarged. The chest, from the front, is singularly box-shaped, a perfectly quadrilateral thorax. There is a little scoliosis, the curve being towards the left.

No enlargement of the clavicle or shoulder-blades. No enlaro-ement of the bones of the arm or of the hand. No clubbing of the fingers. Dupuytren's contraction in both hands.

The pelvis is not enlarged, crests of the ilia feel normal.

Legs are remarkably bowed. With the heels together, from


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[No. 87.


the inner side of one knee-pan to the other is 23 cm. From the crest of one tibia to the other is 26 cm. The thigh bones do not seem enlarged. The tibiae present the most remarkable deformity. They are both extremely curved anteriorly, enormonsly enlarged ; a condition of diffuse hyperostosis. The left leg is larger than the right. Measurement of the most prominent part of the calf: left, 37 cm.; right, 35.5 cm. The bones are smooth and uniform, except on the anterior margin, where both are a little rough. The fibulfe feel a little enlarged at the upper end, but do not seem to be involved to the same extent. On the anterior surface of both legs and over the outer maleoli there are old pigmented changes in the skin, which is rough and hard. Both inner condyles of the femur look enlarged. Measurements over the knee joint: right, 39.5 cm. ; left, 38 cm. Height five feet three inches."

Dr. Reik has recently examined his eyes and reports as follows :

Mr. R. has a high grade of myopia, with large posterior staphyloma and extensive choroidial changes in each eye. In the right eye there is in addition a central lens opacity and consequently vision is practically nil. Vision in the left eye is ^f with a — 12 Ds.; with a —8 Ds. he can read Jaeger No. 1.

Discussion. Dr. Cone. — It is interesting in the bibliography of this case to bring in the work of V'on Recklinghausen. He mentions cases of osteitis deformans in which there was a development of fibroma and of sarcoma, and mentions also that cysts frequently form in these cases, and he describes them very fully. The walls are fibrous, contain a spongy network of bone, and


outside of this is fatty marrow. He mentions that the seat of these changes is the spots where the bone is under most statical pressure. As to the inflammatory origin of the disease, there is one case cited by Gruber in which, following erysipelas, there was this hyperostosis and a condition resembling elephantiasis.

Dr. Watson. — In reply to Dr. Osier I would say that in Paget's experience the cranial bones were frequently aifected. In four of the six American cases there was enlargement of the head. In Mackensie's case, aside from some spinal curvature, a very much enlarged cranium was the sole lesion. In Herwisch's case, in addition to an enlarged cranium there was some thickening and curving of the femora and left tibia and some thickening of the crests of the ilia. In the case of Dr. Gibney the head was increased in size and the legs very much bowed.

In one of Dr. Taylor's eases there was a very large head, considerable bowing of the spine, some enlargement of the pelvis and enlargement and bowing of the right femur. In his second case there was no head enlargement, the sole lesions consisting of enlargement and bowing of the right femur and some lateral spinal curvature. In McPhedrau's case the only bones involved were the right tibia and femur.

The case reported to-night corresponds more closely to Paget's description than any of the American cases, although one of Dr. Taylor's cases is almost as typical.

The statement made by Paget that there is a preponderance of males among the patients affected with this disease seems to be contradicted by later statistics, for of 43 cases analyzed by Thieberge in 1890, 21 were men and 22 were women.


THE RISE OF THE THEORY OF ELECTROLYTIC DISSOCIATION, AND A FEW OF ITS APPLICATIONS IN CHEMISTRY, PHYSICS, AND BIOLOGY.*

By Harry C. Jones, Ph. D., Instructor in Physical Chemistry, Johns Hopkins University.


It is doubtless unusual for this Society to be confronted with a subject which is apparently so widely removed from medicine as that of physical chemistry. But since certain comparatively recent developments have made it probable that the latter is destined to exert some influence upon the former, I have been kindly asked by your President to discuss that side of physical chemistry which has already been brought in touch with certain biological problems. I shall therefore give a very brief account of the origin and development of the theory of electrolytic dissociation, which is one of the keystones to the whole science of physical chemistry.

The botanist, Pfeffei', carried out a quantitative investigation of the osmotic pressure which solutions of both non-electrolytes and electrolytes exert against the pure solvent. His work is so well known that a mere reference to it is nearly sufficient. The artificial membranes which he devised, by depositing some finely divided precipitate, such as copper ferro


Read before the Johns Hopkins Hospital MeJical Society, March 7, 1898.


cyanide, in the walls of fine-grained jiorcelain, were seraipermeable, i. e. they allowed the solvent to pass through them, but prevented the dissolved substance from doing so. With such membranes he was enabled, for the first time, to make a careful quantitative study of the amount of osmotic pressure which different substances exert.

The results of Pfeffer were examined by Van't Hoff, who pointed out that they led to the following interesting and important generalizations :

I. The osmotic pressure of solutions of non-electrolytes is proportional to the concentration.

II. The temperature coefficient of osmotic pressure is very nearly yi-j of the osmotic pressure, for every degree Centigrade.

III. The osmotic pressure of a solution is exactly equal to the gas pressure which the dissolved substance would exert, if it were present as a gas, in a space equal to that occupied by the solution. A molecule exerts the same osmotic pressure as it would exert gas pressure under the same conditions of temperature.


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These three laws of osmotic pressure will be recognized, at once, to be strictly analogous to the three laws of gases — that of Boyle, that of Gay-Lussac, and. that of Avogadro.

Van't Hoff further pointed out that the electrolytes — strong acids, and bases, and the salts — present exceptions, and exercise a greater osmotic pressure, for equivalent concentration, than the non-electrolytes.

The explanation of this difEerence was offered by Arrhenius. He studied the depression of the freezing-point of water produced by both electrolytes and non-electrolytes, and found that the former was always greater than the latter. He took into account, also, the property of solutions of electrolytes to conduct the current, and pointed out a quantitative relation between the conductivity of such solutions and the depression of the freezing-point of the solvent produced by the dissolved electrolyte. He showed, thus, that solutions of those substances which give abnormally large osmotic pressure, give abnormally great depression of the freezing-point of the solvent, and conduct the current.

It had already been shown by Raoult, that the depression of the freezing-point of a solvent by any dissolved substance, depended upon the relation between the number of parts of the dissolved substance and of the solvent. It seemed, then, that in the case of electrolytes there were more parts of the electrolyte present than could be accounted for on the assumption that the substance was present in the solution in the simplest molecular condition. To account for such facts as these, Arrhenius proposed the theory which has become so well known as the theory of electrolytic dissociation. When an electrolyte is dissolved in a solvent like water, the molecules break down, not into atoms, but into ions, which are atoms, or groups of atoms, charged with electricity. The amount of such dissociation is dependent upon the concentration of the solution. The more dilute the solution, the greater the dissociation of the molecules into ions, and at about one one-thousandth normal, the dissociation of all the strong acids, and bases, and most of the salts, is complete. This means that there are no molecules of the electrolyte present, but only the ions into which the molecules have dissociated.

This suggestion, it must be said, is not entirely new with Arrhenius, it is closely related to certain views held by Grotthuss, Williamson and Clausius. But the broad application of the theory to these newly discovered facts, together with quantitative methods for measuring the amount of the dissociation in a given case, we owe to Arrhenius.

Given the theory, the all-important question remains, is it true ? The time at my disposal will not permit me to discuss many of the lines of evidence which bear upon the theory of electrolytic dissociation. It is so far-reaching in its significance, so fundamental in its bearing, that any physical or chemical property of solutions can reasonably be summoned to furnish evidence as to its validity. I will refer very briefly to a few points which bear directly upon the theory in hand. If dilute aqueous solutions of electrolytes contain only ions, and no molecules, then it is clear that all the properties of such solutions must be the properties of ions, and notof molecules, since there are no molecules present. But since a


molecule always dissociates into at least two ions — a cation, which is charged positively, and an anion, which is charged negatively — the properties of completely dissociated solutions must be a function of two constants, the one depending upon the cation and the other upon the anion. If we study the physical properties of such solutions, such as their specific gravity, power to refract light, power to rotate the plane of polarization of light, color, etc., we find that they are the sum of a constant for the cation and a constant for the anion.

If we turn to the property of completely dissociated solutions to conduct the current, we find here again the same additive condition. The conductivity of these solutions is the sum of two constants, which is the well known law of Kohlrausch, usually expressed as the law of the independent migration velocities of the ions.

A quantitative test of the theory may be made by a study of the osmotic pressure of solutions of electrolytes. It will be remembered that the generalizations of Van't Hoff were reached through a study of Pfeffer's measurements of the absolute osmotic pressure exerted by non-electrolytes. Pfeffer found also that electrolytes exert a greater osmotic pressure than non-electrolytes. De Vries, using the plasmolytic, or living cell method, which gives only relative osmotic pressures, found, also, that electrolytes exert a greater osmotic pressure than non-electrolytes. This excess in the osmotic pressure of non-electrolytes is, in terms of the theory, due to a dissociation of the molecules into ions. De Vries showed that solutions of undissociated substances, containing the same number of molecules in a given volume, exerted the same osmotic pressure. Such solutions were terms isohydric. The same applies to solutions of electrolytes, with this difference, that at moderate dilutions we have to deal with the sum of the molecules and the ions present. De Vries was able by his method to determine the concentrations of solutions of electrolytes which are isohydric with one another. When these concentrations were represented in molecular quantities their reciprocal values were termed isotonic coefficients.

The dissociation of electrolytes can be calculated from the measurements of the osmotic pressure of solutions made by De Vries, and also from the measurements of the conductivity of the same solutions, and these two sets of values should agree with one another, if the theory of electrolytic dissociation is true. Below are given the amounts of the dissociation of a few substances, calculated for a given dilution, from osmotic pressure and from conductivity :


Substance.


Dissociation

from

Osmotic Pressure.


Dissociation

from

Conductivit}'


KNO3 NaNOa


69^ 69


80^ 73


KCl


(i9


84


NaCl


71


• 82


(COOK)^

K,SO,


61 60


66 67


( 'onsidering the large error involved in the osmotic pressure method, the agreement is probably within the error of experiment.


138


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 87.


It was early found that the power of electrolytes to lower the vapor-tension, or to lower the freeziug-poiut of the solvent in which they are dissolved, is greater than that of non-electrolytes. Either of these properties of solutions of electrolytes can be used to measure their dissociation. Since the method of measuring the freezing-points of solvents and solutions has been worked out far more accurately than the method of determining their boiling-points, the former is to be preferred as a method for measuring dissociation. I will give some results of the dissociation of electrolytes as calculated from my own measurements of the freezing-point depression of solvents, produced by them, and compare these with the dissociation of the same dilutions of the same electrolytes as calculated from Kohlrausch's conductivity work.


Substance.


Concentration.

Gram-molecular

normal.


Dissociation

from Conductivity.


Dissociation from

Freeziug-point

Lowering:.


NaCl


n.ooi


9S.0%


98.4^


"


11.111


93. 5


90.7


"


0.1


84.1


83.5


KCl


O.Odl


98.0


101.0


"


0.01


94.2


90.7


"


0.1


86.0


83.4


H.,SO,


0.003


89.8


86.0


"


0.00.5


85.4


83.8


"


0.0.5


62.3


60.7


HCl


0.002


100.0


98.4


"


0.01


98.9


95.8


"


0.1


93.9


88.6


HNO3


0.003


100.0


98.4



0.01


98.5


96.8



0.1


93.5


87.8


KOH


0.002


100.0


98.4


"


0.01


99.2


93.7


"


0.1


92.8


83.1


These are but a few results taken from a large number, involving all classes of electrolytes — acids, bases, and salts. The agreement is so striking that comment is superfluous.

Another line of evidence is to be sought in the study of mixtures of salt solutions. In terms of our theory, a dilute solution of potassium chloride contains only potassium ions and chlorine ions, and, similarly, a dilute solution of sodium bromide contains only sodium ions and bromine ions. These facts would be e.xpressed thus :

KC1 = K-|-C1

NaBr = Na-|-Br

A mixture of these solutions would contain, then, potassium, sodium, chlorine, and bromine ions; and all the properties of this mixture would be a function of the properties of these four ions, there being no molecules present. If, on the other hand, we started with potassium bromide and sodium chloride, and mix their dilute solutions, we would have exactly the same ions present, and the properties of the second mixture should be, for the same concentration, exactly the same as the first, and such is the case.

But if we should mix solutions of substances which are undissociated, such as methyl chloride and ethyl bromide, we ought to obtain a mixture with properties which arc different from a mixture of methyl bromide and ethyl chlo


ride, because we have here to deal only with molecules, which would be different in the two cases. And here again the facts agree perfectly with the theory. A mixture of methyl chloride and ethyl bromide has properties which are different from a mixture of methyl bromide and ethyl chloride.

Would that time permitted to take up an adequate number of the many lines of evidence which point to the theory of electrolytic dissociation in solution in water, and, to a less extent in many other solvents, but it does not.

I believe that when all the evidence at hand is taken into account, it points so conclusively to the general truth of the theory of electrolytic dissociation that we can accept it with the same degree of confidence as we do the law of Avogadro or many of the so-called laws of nature. And it may be said that the theory is now generally accepted by those who have impartially examined the evidence which is available.

If the theory be true, the question which next arises is, what is its scientific value? Has it been helpful in correlating facts which have hitherto appeared to be unconnected ? If so, its value is apparent. Or does it suggest, or point out new lines of experimental investigation ? If it does, its value is unquestioned. If it should assist in both of these directions, so much the greater is its worth. I can take up only a few examples. Take the well known reaction of the neutralization of acids and bases. In terms of the theory of electrolytic dissociation, a dilute aqueous solution of a strongly dissociated electrolyte contains no molecules, only ions. A solution of a base contains the hydroxyl anion, and a cation whose nature depends upon the base used. A solution of an acid contains the hydrogen cation, and an anion whose nature depends upon the acid chosen. Similarly, a solution of a salt is but a solution of anions and cations. To take as a concrete example, hydrochloric acid and sodium hydroxide, the reaction would be represented thus :

CI + H + oil + Na = 01 + Na -I- H.O, or in general :

A-|-H + OH + C = A-f6-|-H=0.

The anion of the acid and the cation of the base remain unchanged in the process of neutralization, which consists only in the formation of water. If this is true, then the process of neutralization of a given acid by a given base, is the same as the neutralization of any other acid by any other base.

This can be tested directly by experiment. The heat liberated in the neutralization of an equivalent of a completely dissociated acid by an equivalent of a completely dissociated Ijuse, being always the heat of formation of the same amount of water from the ions H and OH, must be a constant, independent of the nature of the acid or of the nature of the base. The following results show that this is true:



HCl. H Br.


Ht.


HNOj.


CHjCOOH.


HCOOH.


XaOTI


13.7 C


al.


13.7 Cal.


13.3 Cal.


13.4 Cal


KOH


13.7



13.8


13.3


13.4


.5Ca(0Il).j


14.0



13.9


13.4


13.5


.,Bii(Oll),


13. S



13.9


13.4


13.5


.\t<r(OII)„


14.1



13.9


13.3


13.5


June, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


139


The agreement between the heats of neutralization is striking, in consideration of the necessary errors involved in thermo-chemical measurements.

The theory of electrolytic dissociation thus brings together all the processes of neutralization of acids by bases, and refers them to a common cause, the union of the hydrogen and hydroxyl ions to form water.

It may be stated that it has been shown by no less than a half-dozen sejiarate pieces of work, that hydrogen and hydroxyl ions cannot exist in the presence of one another, in any appreciable quantity, uncombined; or, in a word, water is un dissociated.

Another example may be taken from chemistry.

If the properties of solutions of electrolytes are properties of the ions, then what relation exists between the chemical activity of solutions and their dissociation ? The dissociation of substances must be determined, .and also their power to effect chemical reaction, and the results of these two measurements must tlien be compared. A few of the many results available will suffice to bring out the relation. In column I are given the dissociations of acids referred to hydrochloric acid as 100; in II, the velocities with which they effect the catalysis of methyl acetate; in III, the velocities with which they invert cane sugar.


HCl


ion


100


100


n,so,


65.1


73.


73.3


HCOOH


1.68


1.31


1..53


CIT.COOH


0.43


0.34


0.40


CII^CICOOII


4.90


4.30


4. 84


CIICUCOOH


25.3


33.0


37.1


CC13COOH


63.3


68.3


75.4


(COOII)^


19.7


17.0


18.0


CII,(COOII),


3.1


3.87


3.08


c,H.(COon),


0.58


0.50


0.55


The agreement is as satisfactory as the conditions would allow us to expect.

The strength of acids is thus directly proportional to their dissociation.

We then naturally look for a common cause of that property which we describe as (wid,iii compounds such as those

given in the last table, and this is easily found. All of these

+ compounds dissociate into a hydrogen cation (H) and an

anion, whose nature depends upon the compound in question,

varying with every acid. Wherever we have hydrogen ions

we have the acid property, and the strength of any acid

depends only upon the number of hydrogen ions present.

The same applies to hydroxyl bases, where their strength depends upon the number of hydroxyl anions (OH) present.

The direct quantitative relation between chemical activity and dissociation has now been so frequently established that we often use dissociation to measure chemical activity, and also chemical activity to measure the amount of dissociation.

And this raises the question as to whether chemical activity is due solely to ions. Are molecules incapable of reacting


with one another ? It would be going too far, in the light of our present knowledge, to maintain this. There are substances known which apparently do not conduct at all (are completely undissociated), and yet react chemically. There are cases known of dry solids, which we suppose contain only molecules, reacting with one another. We have well characterized chemical compounds formed by the union of two parts of apparently the same general electrical character: thus phosphorus and chlorine, chlorine and bromine, chlorine and iodine, etc. Yet chemical reactions in which acids and bases are involved are now known to be reactions involving only ions, molecules as such not coming into play. And indeed the number of reactions which are known to be purely ionic, is very great, including the majority of the cases with which we have to deal in chemistry.

The application of the theory of electrolytic dissociation is by no means limited to chemical phenomena. It touches with equal success, certain sides of physics. With its aid we are now able to calculate the electromotive force of many forms of primary cells, knowing the concentration of the solutions of electrolytes used around the electrodes. We have also, for the first time, been able to locate the seat of ijotential in such cells, which has been an unsettled question every since the discovery of the battery by Galvani and Volta, at the close of the last century.

The theory of electrolytic dissociation was not applied to biological problems as early as to chemical and physical. This is probably due to the greater complexity of those phenomena in which life is involved. But a beginning has already been made in this direction. Kahlenberg and True have shown that the toxic action of a number of acids on a certain plant, is due to the hydrogen ions of the acids, and similarly the toxic action of a number of bases can be ascribed to the hydroxyl ion of the base.

Loeb has found that the power of a frog's muscle to absorb water in the presence of acids, is dependent upon the number of hydrogen ions present, — upon the dissociation of the acid.

The pharmacologists have actively employed the theory of electrolytic dissociation in the solution of a number of problems. In this connection the work of Dreser is especially to be mentioned, and the theory has also been extended to problems in disinfection, by Paul and Kronig.

The applications of the theory of electrolytic dissociation above considered, are but a very few, taken from a large number where its significance has been already recognized. While it has suggested much new experimental work in several branches of chemistry, and in the study of the electromotive force of elements, yet, it seems to me, that perhaps its greatest service thus far to science has been in correlating facts, pointing out relations hitherto unobserved, and thus leading us from unclassified to at least partly classified knowledge. This has resulted, in a number of cases, in wide-reaching generalizations. We are thus led one step nearer to the solution of the question, not simply how do substances behave in the presence of one another, but why do the phenomena observed take place ?

Chemical Labobatorv, .Ioii.ns Hopkins Umv.


140


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 87.


LOCALIZED SCLEROSES OF THE AORTA OF PROBABLE SYPHILITIC ORIGIN.

AND NECROPSY IN TWO CASES.


CLINICAL REPORT


By Clement A. Penrose, M. D., House Medical Officer, The Johns Hopkins Hospital.


At the request of Dr. Osier 1 presented (February 7, 1898) to the Medical Society the clinical i-epoit and necropsy in a case of circumscribed or nodular arterio-sclerosis of probable syphilitic origin and located quite definitely in two portions of the aorta. Since then we have been fortunate enough to obtain the notes in a second case, that died recently in the hospital, and showed also a well localized sclerosis of the aorta of a circumscribed or nodular type,' less advanced and with an even more positive etiology of syphilis.

Case I. J. K., age 36, married, white, an American, a barber by trade, was admitted Tuesday, Jan. 4, 1898, to ward F of the Johns Hopkins Hospital.

Famihi History. As a child had measles, mumps, whooping cough, and pneumonia. At 19 thought he had syphilis; remembered a primary sore, but could give no definite history of secondary symptoms or treatment. One year later an attack of gonorrhQ3a. Malarial fever at 24, and at 29 acute rheumatism, with a second attack one year ago. When a young man was a sailor, worked hard, and was not infrequently drunk.

Present Illness. Was well and strong until Nov. 1897, when symptoms of nou-compensatiou of the heart, shortness of breath, palpitation, oedema, etc., set in acutely, and increased in severity up to the time of admission.

Phi/sical Examination. A well-nourished, strongly built man, with symptoms of marked aortic and mitral insufficiency and the corresponding physical signs. Of especial interest is a roughened first heart sound in the second right interspace, pronounced dysjinoea relative to other symptoms, absence of any hardening of the radials, for the most part a normal or subnormal temperature, with comparatively slow rate of pulse and respiration (average 90 and 25 per minute), and lastly, a poor reaction to treatment.

The patient improved somewhat, left the hospital 12 days after admission to arrange some private matters, was away one week and returned in about the same condition as on first entry. He gradually sank, and died Jan. 24, 1898, with Cheyne-Stokes respiration for one hour, and slight convulsive movements for a few minutes before death.

Autopsy. The following conditions were found: a slight insufficiency of the aortic valves as indicated by the water test ; an absence of vegetations on any of the valves, which were normal, except for a slight thickening and shortening of one of the aortic segments, and considerable hypertrophy with some dilatation of the heart confined chiefly to the left ventricle. The heart muscle on section showed exquisite fatty degeneration, with here and there fibrous areas.

Of special interest was a circumscribed or nodular form of sclerosis, localized in two portions of the aorta, one patch of which involved the ascending and transvere sections of the arch and gave rise to an aneurismal dilatation about the size of one's fist (12 cm. long by 17 wide) extending posteriorly and to the right, containing no blood clots. The walls of '


the aorta in this region presented a rough, uneven surface; no atheromatous or calcareous degeneration was visible.

The descending portion of the arch and thoracic aorta were practically free from sclerosis until a point was reached a short distance above where it pierces the diaphragm. Here a second patch of sclerosis was found extending down about 8 cm. to the cffiliac axis, showing diffuse thickening with nodular elevations especially well marked about the openings of the intercostal arteries.

Microscopical examination showed considerable round cell infiltration and degeneration of the media, interrupting here and there the course of its muscle fibres, with marked irregular thickening of the intima. In i^laces there was some round cell infiltration of the adventitia also. Dr. Flexner in one section found a rather suspicious nodule of epithelioid cells in the media, suggesting a gummatous formation.

Case II. J. R., age 35, single, colored, a laborer, admitted Feb. 2, 1898, to Ward M.

Family History. Negative.

Personal History. None of the diseases of childhood. At 35 had rheumatism, and has had one or two attacks since. Gonorrhcea at 27. He denied syphilis, but showed on corona of penis a well defined, elevated scar about 1.5 cm. in diameter, which seemed fairly recent. He drank moderately. Was not a hard worker.

Present illness began four months ago with shortness of breath, palpitation and cfidema, which have been growing steadily worse.

P/iysical Examination. Strong, well-nourished man, presenting symptoms of aortic and mitral insufficiency with corresponding signs. Dr. Osier, in a note made Feb. 26th, called attention to the wiry character of the systolic murmur in the mitral area, the development of a Flint murmur just outside the nipple, and to the moderate grade of sclerosis of the arteries.

The patient slowly sank, and died quietly, March 3, 1898. His average pulse rate was 104, his respiratory 24, and his temperature 99.5° F.

Autopsy. The heart was much enlarged, both ventricles hypertrophied and dilated. The aortic valve was insufficient to the water test and showed on examination a diffuse thickening with shrinking of the anterior and posterior coronary segments, the intercoronary segment being fairly normal.

The aorta just above the lesion in the valve was the seat of an irregular patch of atheroma, 3 by 4 cm. in diameter, which extended into the sinus of Valsalva of both the anterior and posterior segments and from there out on the valve. The aorta appeared slightly dilated at the portion of the arch where the sclerosis was situated. The anterior and posterior coronary arteries showed yellow patches of atheroma along their course, but no evidences of calcification or occlusion. The aorta


June, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


141


generally was free from atheroma excepting a few yellow patches scattered here and there over the iiitima.

Microscopical exnminntion of the patch of sclerosis showed marked round cell infiltration of the media, which in places appeared to be quite broken up, the muscle fibres being separated by an oedematous cellular tissue. The adventitia was also considerably infiltrated with small round cells, but the vasa-vasorum showed, however, little change. Nowhere were any definite gummatous nodules found, although a number of sections were examined.

In addition specimens of the chancre scar were examined which showed marked thickening of the epithelium, with an elevation above the surrounding coronal tissue and much subepithelial granulation tissue formation, but no especial vascular changes.

On consulting some of the authorities as to the significance of these localized arterio-scleroses one is impressed with their unsatisfactory classification from a clinical point of view.

Accepting Dr. Councilman's division of arterio-scleroses into the nodular or circumscribed, the diffuse and senile forms, we scarcely know where to place those cases in which both nodular and diffuse scleroses coexist, or cases in which the lesions are definitely localized, at least macroscopically. In addition many writers seem to confuse the term nodular or circumscribed with localized, the former applying more properly to the small nodular elevations or compensatory thickenings in the vessel wall than to the sclerosis as a whole.

It was necessary therefore to look up the subject of localized sclerosis under each one of its etiological factors in the various works at hand, and chiefly under the heading of syphilis, thinking it to be the most probable agent in the two cases under consideration. Forms of localized inflammations and degenerations in arteries arising from local influences such as injuries, burns, skin diseases, tuberculosis and leprosy, fade so gradually into those general arterial conditions arising from general influences such as gout, rheumatism, hard-work and alcohol, that, midway, we find a group of cases very hard to classify.

Syphilis demonstrates remarkably in its different stages this transition from the local chavgef in the arteries in the region of a primary chancre and in various secondary phenomena, uj) to the later general arterio-scleroses of the tertiary period; while intermediate are cases similar to the two reported, where the conditions causing the sclerosis seem general but which present a more or less localized manifestation.

Thoma says we must discriminate between the effects of the luetic virus and disturbances in nutrition caused by lues, when considering arterio scleroses.

George Thibierge says: "The sclerosis of syphilis is less diffuse than that due to other causes, is more localized, shows often a marked proliferating endarteritis and periarteritis, and is occasionally associated with the formation of gummata containing epithelioid cells and giant cells#"

Ziegler says : "Nodular scleroses have a greater tendency to be localized," and later he shows that syphilitic sclero&is tends to be nodular.


Neumann says: " Syphilitic arteritis tends to be nodular."

Chiari described a typical endarteritis obliterans in a child 5 months old, dead from congenital syphilis, and suggests this as an etiological factor in obscure cases of arterio-sclerosis.

Oettinger cites cases of localized arterio-scleroses following acute infective diseases, but occurring in cases under 20 years of age, and quotes Parrot, Andral and Crisp.

Many of the authors, Nasse, Cornil, Huchard and others, show that in tuberculosis we have well localized arterioscleroses in arteries of the lung and brain.

Ileubner says: "Luetic sclerosis begins as a subendothelial growth and later invades the adventitia."

Baumgarten and Laucereaux say: "It starts first in the lymph vessels of the adventitia and later attacks the intima."

Arthur Ernest Sansom says the great pain in certain cases of syphilitic arterio-sclerosis is due to the especial involvement of the adventitia, which has a more abundant nerve supply. He quotes Huchard, who said 35 out of 150 cases of angina pectoris gave a luetic history. He shows that the most pronounced cases of aneurism of the aorta among young persons or among those in the prime of life, were due to syphilis, and that prostitutes for this reason are affected with aneurism of the aorta much more frequently than other classes of women. He quotes Karl Malmsten of Stockholm, who said 80 per cent, of his cases of aneurism were luetic, and Aitken, who said 50 per cent, of soldiers thus afflicted gave a syphilitic history, 5 per cent, a gouty and 5 per cent, a rheumatic.

Welch says that the nodular forms of arterio-sclerosis or endarteritis deformans are limited to the aorta and larger arteries.

Osier thinks that the points of origin of the large branches of the aorta are more prone to undergo sclerotic changes and hence form aneurisms.

Huchard in a very satisfactory manner, in his elaborate article on arterio-sclerosis, sums up his conclusions regarding the effects of syphilis on the arterial system as follows :

Local scleroses are only a beginning of a general condition, as is shown by the microscope, and he quotes Duplaix, who says "General sclerosis is always found by those who look for it." The chief characteristics of syphilitic sclerosis are:

(1) It is nodular and not diffuse.

(2) It has a tendency to invade portions only of a vesselwall.

(3) Its onset is usually chronic, but it may be acute. (1) The points of attack in order of frequency are:

1. Cerebral arteries.

2. Aorta — especially ascending portion of arch.

3. Arteries of heart.

4. Arteries of pericardium.

(5) It has a tendency to obliterate vessels. (G) It has a tendency to form aneurisms. (7) In analogy with tuberculosis it has a tendency to obliterate arteries, to form aneurisms, and to become localized.

Literature.

Iknibner: Die luetische Erkrank. d. Hirnarterian. Leipzig, 1874.

Ehrlich : Arteritis syphilitica. Zeitschr. f. klin. Med. 1879.


142


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 87.


Huber: Syi^h'ilitische Gefilsserk rank hung. Virch. Arch., 79 Bd., 1880."

Baumgiirten : Syphilis der Hinigefiisse. Virch. Arch., 86 Bd. 1881.

Chiari: Arteritis syphilitica. Wien. med. Woch. 1881.

Lancereaii X : Traite d'anal. Pathol. II. Paris, 1881.

V. Langeiibeck : Arteritis syphilitica. Arch. f. klin. Chir. XXVI.

Duplaix: L'etude de la sclerose. These inangnrale. Paris, 1883.

Councilmau : Trans, of Assoc, of American Physicians, Vol. VI, 1891.


George Thibierge: Traite de Medecine, Vol. II, 1892.

Stanziale: Syphilis of the Cerebral Arteries, Annal. de Neurol. 1893.

Oettinger: Traite de Medecine, Vol. V, 1893.

Iluchard: Traite clinique des malades dii coeur et des vaisseaux, 1893.

AVelch : Personal Notes of, 1891.

Osier: Practice of Medicine, 1895.

Zeigler: Lehrbuch der allgemeiuen Pathologic, 189G.

Thoma: Text-book of Pathology, 1896.

Neumann: Nothnagel Speciale Pathologic, 1897.


FURTHER REMARKS ON ADENOMVOMA OF THE ROUND LIGAMENT.

By Thomas S. Opllen, M. B. (Tor.), Associate in Gynecology, Johns Hopkins University.


In the May-June number of the Bulletin, 1890, 1 reported a case of adeno-myoma of the round ligament, the first on record. Since that time three cases bearing ou the same subject have occurred, and our own case has revealed some very instructive etiological factors.

Pfannenstiel* reports the case of an unmarried woman, 39 years of age, who had long been suffering from dysmenorrhcea, and who came under observation on account of a tumor in the right inguinal region which had made its appearance about six months previously. On examining the patient a nodule was also found in the vagina ; this Pfannenstiel supposed was the primary tumor, and inferred that the nodule in the inguinal region was a metastasis. The uterus and its right appendages, together with the nodules in the inguinal region and vagina, were removed. The vaginal nodule on section presented the picture of a myoma, but scattered throughout it were yellowish-brown dots of pigment, and it contained fine depressions and cysts. On histological examination the tissue was found penetrated in all directions by glands, and in their cavities were pigment granules, and in one place a pseudo-glomernlus was found. The nodule from the inguinal region was scarcely the size of a walnut. It was situated a short distance within the external ring and presented the same picture as the vaginal nodule. In short, Pfannenstiel says there was a simultaneous appearance of adeno-myoma at two different points in the genital tract. He identifies his case with the same grouj) as the one reported by us.

V. Herflif examined two vaginal myomata removed by Fehling during a hysterectomy for prolapsus uteri. One of these contained numerous delicate glands, some of which were branched and slightly dilated, others formed small cysts. These glands lay as little islands in the musculature. The gland epithelium was either cuboidal or low cylindrical. At no point could a comb like arrangement of the glands or the pseudo-glomeruli of v. Eecklinghausen be demonstrated.


Ueber die Adenomyome des Genitalstranges. Verhandlungen der Deutschen Gesellschaft flir Gyn., 1897.

t Ueber Cystotnyome und Adenomyome der Scheide. Verhandlungen der Deutschen Gesellsch. f. Gyn., 1897.


Blumer's* case, 47 years of age, had first noticed the growth 23 years before coming under observation. At that time it formed two distinct nodules, each about 6 mm. in diameter, in the right groin. These gradually coalesced and the combined tumor grew slowly until six months ago, since which time it rapidly increased in size, being at the operation as large as a hen's egg. The growth had never been painful, even at the menstrual period. Dr. Van der Veer, who removed the tumor, believed that it originated in the inguinal canal.

The tumor was firm in consistence, greyish-white in color, and contained pin-point hemorrhages; in most points it resembled an ordinary uterine myoma. Histological examination showed that the tumor was composed mainly of nonstriped muscle fibres, and in one section gland elements were found. These appeared round or oval, but occasionally as dichotomously branched spaces. The gland epithelium was cylindrical and contained oval, darkly staining nuclei ; in some places cilia could be seen. The glands were in direct contact with the muscle, there being no stroma intervening, and Blumer was unable to fiud any structures resembling pseudoglomeruli or to make out any sign of pigmentation.

Our patient (Gyn. No. 5286) was readmitted to the gynecological ward. May 25, 1897. Shortly after the previous operation she noticed a swelling in the opposite or left inguinal region immediately above the pubes. This has gradually increased in size and is quite painful. The menstrual period has not been regular, occurring at intervals of from three to five weeks. The last menstruation commenced May ISth and ceased May 23d. On May 26th I removed the nodule with little difficulty and found that it was directly continuous with the left round ligament.

Pathological report. Gyn. Path. No. 174:1. The specimen consists of an irregular mass approximately 3 cm. in its various diameters. It comj)rises a firm central portion 1.5 cm. in diameter, which is surrounded on all sides by adipose


A Case of Adeno-myoma of the Round Ligament. American Journal of Obstetrics, 1898, XXXVII, p. 37.


Juke, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


143


tissue. Traversing the central portion are Eumerous delicate fibres, and at several points are brown or yellow homogeneous areas. Several pin-point cavities are demonstrable. At one point is a semicircular slit 2 mm. long, and in the immediate vicinity an irregular cavity averaging 3 mm. in diameter. The walls of this cavity are rather uneven and are slightly granular.

Histologkal examinatioji. The adipose tissue in the outlying portions is comparatively normal, but as one approaches the firm nodule the blood-vessels increase in number and size, young capillaries are found wandering in between the fat cells, and there is considerable connective tissue increase, the fat cells becoming gradually separated from one another. At the margin of the firm nodule the tissue is composed almost exclusively of connective tissue. Here and there this connective tissue encircles round or oval clumps of cells having oval, fairly deeply staining nuclei, and scattered between these are a few small round cells and occasionally polymorphonuclear leucocytes. Such areas are very striking on account of their richness in nuclei, in contrast to the surrounding tissue which is poor in cell elements. The cellular areas resemble closely the stroma of the uterine mucosa. On passing toward the centre of the nodule similar areas are found containing one or more glands lying in their centre or at the periphery. These glands, according to the angle at which they are cut, are round, elongate or slightly branching. Their epithelium is cylindrical, apparently ciliated, and their nuclei are oval and situated some distance from the base of the cell. In short these glands cannot be distinguished from uterine glands. The majority of the gland cavities are completely filled with blood and desquamated epithelial cells. The stroma of the central portion of the nodule is composed almost entirely of non-striped muscle fibres, and here the glands are more abundant and present a more complicated picture. The glands are branching, form narrow channels and little bays, and in places can be traced in their continuity for at least 4 mm. On one side of the gland there is usually considerable stroma separating the epithelium from the underlying muscle. At such points the epithelium is cylindrical, but on the opposite side where the cells rest directly on the muscle it is frequently flattened. There are a few areas corresponding to von Recklinghausen's pseudo-glomeruli ; some of these contain glands, others do not.

Origin. Even from such a small number of cases we are able to gather valuable information as to the distribution of these tumors. In v. Herff's case the nodule was limited to the vagina, Blumer's to one inguinal region, while Pfannenstiel's contained two nodules, one in the inguinal region and a second in the vagina, and in our case nodules were found in both inguinal regions. This apparently varied distribution seems nevertheless to follow definite channels, viz. the round ligament on one or both sides, and it will be little wonder if in later publications reports of adeno-myomata near the uterine end of the round ligament will be recorded.

I'fannenstiel and v. HerfE meution nothing as to any definite relation between menstruation and the nodule, but Blumer states that menstruation in no way affected the nodule in his case. When publishing our case I drew attention to the


excessive pain in the nodule at the menstrual period, suggesting some definite sympathetic relation between the uterus and the nodule in the round ligament.

Two sources of origin for these tumors have been suggested, viz., from a displacement of a portion of the Wolffian body or from a jjart of Miiller's duct. v. Eecklinghansen has very kindly examined sections from the nodule removed from the right round ligament in our case and thinks that it is undoubtedly of Wolffian origin, v. Eecklinghansen,* after seeing Pfannenstiel's and v. Herff's specimens, says that these also are of AVolffian origin. When publishing our case I made the following remark : "While admitting the probability of the glands in our case being due to remains of the Wolffian body, we cannot, from their striking resemblance to those of the uterine mucosa, and from the fact that their stroma resembles that of the mucosa, refrain from suggesting the possibility that they may be due to an abnormal embryonic deposit of a portion of Miiller's duct." In this connection the relation of the last menstrual period to the presence of blood in the glands is interesting. Menstruation commenced May 18th, ceasing May the 33rd, or just three days before operation, and on making sections the glands were found filled with well preserved blood. In adeno-myomata of the uterus and also of the round ligament, blood or blood pigment is met with in the gland cavities in the gland epithelium or in the underlying stroma. If these glands be derived from a portion of Miiller's duct we would naturally expect them to fulfil, at least in part, the functions of the normal uterine mucosa, viz., furnish their quota of blood at the menstrual jjeriod. Under the existing conditions, however, this blood cannot escape and will be gradually taken up by desquamated cells lying in the gland cavity, by the epithelium or by the stroma cells. In our case the blood was not perfectly fresh, but the corpuscle outlines were still intact. This is what might be expected, assuming that the hemorrhage had occurred at the menstrual period. I am still more inclined to favor the Miillerian origin than heretofore.

Prognosis. Our case was of eight years' duration, and on histological examination gave no signs of malignancy, showing that the growth was benign in character. Blumer's case is even more convincing, as it had been followed for 23 years, the growth in that time not becoming larger than a hen's egg, and on microscopic examination also showing its harmless character.


THE JOHNS HOPKINS HOSPITAL BULLETIN.

The Hospital Bulletin contains announcements of courses of lectures, programmes of clinical and pathological study, details of hospital and dispensary practice, abstracts of papers read and other proceedings of the Medical Society of the Hospital, reports of lectures, and other matters of general interest in connection with the work of the Hospital. It is issued monthly.

Volume IX is now in progress.

The subscription price is $1.00 per year.

Complete set (Vols. I-VIII), bound in cloth, for $13.00.


' Personal communication.


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PROCEEDINGS OF SOCIETIES.


THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Meeting of February 31, 1898 {continued).

Regeneration of the Dorsal Root of the Second Cervical Nerve within the Spinal Cord.

Messrs. Baer, Dawson and Marshall. — The present work was undertaken in order to determine whether it is possible to obtain regeneration of the nerve fibres within the spinal cord, and these studies were confined to the regeneration of the dorsal-root fibres after their continuity had been destroyed between the spinal ganglion and the cord.

The second cervical nerve of the dog was selected for the experiments, because the spinal ganglion of this nerve lies outside the intervertebral foramen. The dorsal root can, therefore, be operated upon much more readily and with less danger of injuring the cord than would be the case if it were necessary to open into the vertebral canal. There were, also, reasons connected with the histological work which made it advisable to select the second cervical nerve.

The two roots of this nerve pass together to the ganglion 2 mm. beyond the foramen, the trunk then subdividing to supply muscular and cutaneous branches to the neck and base of skull. The occipitalis magnus, with which we are chiefly concerned, courses through the neck muscles and beneath the skin, to end in the integument behind the ear. The second cervical is connected with the sympathetic, not by a mixed ramus communicans, but by a gray ramus alone.

The present article deals only with the physiological results ; the histological studies will be completed at a later day. Our method of investigation included two operations. At the first, the roots of the second cervical were tightly ligated, so as to destroy the continuity of the dorsal-root fibres and cause them to degenerate throughout their extent in the cord. The animals were kept alive long enough to allow regeneration to follow the degeneration.

At the second operation the nerve was tested for return of function of the dorsal root. Such a return would be indicated by reflex variations in respiration, blood pressure and pulse rate, which might follow stimulation of the nerve in question.

As control experiments, kymographic tracings were obtained from two normal dogs, showing the reflex changes due to stimulating the second cervical nerve.

At the first operation the occipitalis magnus was followed through the muscles and exposed as far as the cord. The roots were freed from surrounding tissue, a ligature was passed around them and tied tightly, great care being taken to avoid exerting traction upon the cord. The ligature was then cut away, leaving a constriction plainly visible at the point of ligation ; the two parts of the nerve being united only by a tube of translucent connective tissue — the epineurium — while the continuity of the enclosed fibres was destroyed. In every case the wound healed per primam.


The interval between the first and second operations was about 90 days, the two longest intervals being 109 and 151 days.

At the test for regeneration a canula was inserted into the carotid artery and connected with a mercury manometer which was made to record upon a kymograph. Similarly the trachea was connected with a tambour which was arranged to give a kymographic record. A time recorder and a stimulating or short-circuiting key also recorded upon the kymograph, so that the tracings were made to give four simultaneous records, that of circulation, respiration, time, and duration of stimulation.

Scar tissue rendered dissection more difficult than previously, but the nerve was exposed as at the first operation and stimulations were applied at various points along the occipitalis magnus, upon the ganglion and upon the roots. Stimulations were of two kinds, faradic and mechanical. The current was never of greater strength than sufficient to cause slight pain when the electrodes were touched to the tongue, and for the most part a weaker current was used. Mechanical stimulation consisted in crushing the nerve with forceps or a ligatui'e.

The results obtained upon the several dogs may be summarized as follows :

In the two normal dogs, used as controls, every stimulation of the second cervical nerve was followed by marked increase in the frequency of pulse and respiration, increased amplitude of respiration and a rise of blood pressure; these being the usual reflex effects of stimulating a sensory nerve.

In dog I, every stimulation caused increased amplitude of respiration, rise of blood pressure, and usually, but not always, a quickening of pulse and respiration.

In dog II, stimulation of the ganglion and roots caused an increase in the amplitude and rate of respiration and a rise of blood pressure. The pulse rate showed practically no reflex change. i

In dog III, faradic stimulation at the ganglion and mechanical stimulation of the occipitalis magnus caused a rise of blood pressure, with an increase in the rate and amplitude of respiration. The pulse rate was affected variably and to only a slight degree.

Dog IV responded less to stimulation than any dog of the series. Eespiration was unaffected throughout. The pulse rate and blood pressure showed reflex variations for the first three stimulations of the occipitalis magnus, after which there was no sensory reflex present.

Dog V" gave positive but diminished changes after stimulation in respiration, blood pressure and pulse rate.

Dog VI responded very slightly, but gave both respiratory and cardio-vascular reflex changes.

In the case of dog VII very positive reflex changes were obtained. Blood pressure was greatly affected, while the respiratoi-y reflex was tremendous.

From a study of the above experiments it appears that a more or less complete return of function oecui'red in every


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case, although the reflex effects were very slight in dogs IV ami VI. Such an apparent return of function might he produced in several ways.

1. By failure to destroy the continuity of all the dorsal-root fibres at the first operation. The following facts contradict this assumption. After obtaining the usual effects from stimulating the second cervical nerve of a normal dog, the roots were ligated in the usual manner. Subsequent stimulation produced uo effect. Again, after giving the routine stimulations to dog III, with positive results, the roots were again ligated. Subsequent stimulation was without effect, and microscopical examination showed a complete break in the continuity of the fibres at the point of ligation.

2. The apparent return of function might be due to anastomosis with neighboring nerves. But the above-mentioned controls on dog III and a normal dog show that although the finer ramifications of the second cervical anastomose with neighboring nerves, it is not possible for impulses to pass from a branch of the second cervical to the cord through these connections.

Again, escape of current to the cord might be assumed to account for the ajiparent return of function, but that this was not the case is shown by the positive results of mechanical stimulation of the nerve. Moreover, in every case the nerve was dissected out and retracted from the surrounding tissues before the electrodes were ajiplied, and in some cases jjositive results were obtained from stimulation with weak currents ai^plied at the extreme periphery of the occipitalis magnus about 6 cm. from the ganglion. In the case of the ganglion, where retraction was impossible, many of the stimulations, especially with strong currents, were accompanied by control stimulations of the surrounding tissues, and always with negative results.

We are left, then, with but one explanation of this return of function, which is, that the reflex effects were produced by impulses passing through the dorsal root of the nerve stimulated, that is to say, through the dorsal root of the second cervical nerve.

Such a return of function could occur in only one of two ways. Either the root may be regenerated from fibres having their trophic centers within the cord, or else the regeneration may proceed from trophic centers outside the cord. From a study of the literature it is a Jiistifiable conclusion that all the fibres of the dorsal root of the second cervical nerve in the dog spring from centers outside the cord. Therefore, any return of function of the injured dorsal root is proof of regeneration of the injured fibres both in the root and within the cord itself.

As we have seen, there was return of function in every animal experimented upon, though the degree of restoration varied in the different cases.

Owing to the limited number of our experiments we have been unable to determine how complete regeneration may be, and how it is influenced by varying conditions.

After the first few days the animals did not appear to suffer inconvenience from the first operation, nor was there any evidence of trophic disturbance over the area supplied by the injured nerve.


The completeness of functional return appeared to depend very little upon the length of the interval between the first and the second operations. The most complete return of function occurred in dogs I and VII, with an interval between the operations of 90 days and 109 days respectively. The lowest degree of regeneration was seen in dogs IV and VI, with intervals of gO and 151 days respectively.

We could not determine how the power of regeneration is affected by the age of the animal selected for experimentation. Of the only two adult dogs ojjerated upon, one (dog I) gave marked reflexes, the other (dog IV) gave only slight evidence of regeneration.

There is, however, one condition, namely, scar tissue around the nerve, which exerts an unfavorable influence upon regeneration. This action has been frequently discussed by other observers, and we consider that the successful regeneration of the dorsal-root fibres in these cases has been due, in gi-eat measure, to the fact that the new growth of the fibres was not interfered with by the presence of excessive scar tissue; the operation employed reducing to a minimum the cicatricial tissue at the growing point of the nerve. In only one case, dog VI, was the spinal ganglion affected by scar tissue. Here the ganglion was distorted and bound down by adhesions, and, correspondingly, the sensory reflexes were very slight in this case.

From the experiments described above we feel justified in concluding that, after severance of the fibres of the dorsal root of the spinal cord, between the ganglion and the. cord, regeneration of the fibi'es into the cord will take place under suitable conditions, so that normal reflexes upon the respiratory, cardiac and vaso-motor centers may be obtained.

Finally, we wish to thank Dr. Howell for his many valuable suggestions and the interest which he has taken in our work.

Discussion.

Dr. Barker. — This study, if confirmed, and it seems likely that it will be confirmed, includes results of importance not only for the physiologist and anatomist but also for the clinician. It leads us to hope that regeneration within the central nervous system may occur much more extensively than has hitherto been thought possible. It is true that most investigators believe at present that destruction of cells within the central nervous system means a permanent loss, since the opinion is general that there can be no regeneration of ganglion cells once destroyed. There have been two researches, however, recently, one by Vitzou and another by Tedeschi, on regeneration of nerve cells in the cortex of monkeys after extirpation. The results of these experiments, though worthy of note and control, by no means justify the extravagant enthusiasm which has been manifested by certain lay journals. The problem in the research reported to-night, however, is somewhat different, inasmuch as the regeneration of nerve fibres alone is postulated, not the regeneration of total neurones.

In connexion with this study of Messrs. Baer, Dawson and Marshall we shall await with interest the results of the histological examination. It is necessary that the return of fibres within the dorsal root and within the cord itself shall be


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histologically demonstrated, although from the physiological experiments reported there can be but little doubt that this proof will be easy to bring forward.

Mr. Marshall. — With Dr. Barker, we look forward with great interest to the histological findings iu the cases just reported, but we are, nevertheless, of the opinion that the physiological evidence is weightier and of more positive value than the histological.

When the experiments were undertaken, I may say, it was our intention to complete both the physiological and histological sections before making public our results. But the former method yielded results which were so unequivocal that we felt justified in publishing the physiological work alone, in the belief that the histological studies could be only confirmatory.

Hydraulic Pressure iu Genito-Urinary Practice.— Dr. H. H.

Young. [See May Bulletin, p. 100.]

Dr. KusSELL. — At the request of Dr. Kelly I will briefly report the following case of cystitis treated iu his private hospital by Dr. Young's method. The case, although not one of contracted bladder, shows the value of this method iu the treatment of cases of chronic cystitis where the ordinary irrigation and drainage have failed. Mrs. L. F. D., age 32, five years ago, after an instrumental labor, had a severe attack of acnte cystitis, and since then there has been almost constant bladder trouble. She cannot hold her urine longer than two hours, day or night, and usually the interval is much less. Urination is nearly always attended by severe pain, and occasionally she loses control over the bladder. Three years ago she had Emmet's button-hole operation, which gave relief during the eight months the bladder was drained, but as soon as the fistula was closed the old trouble returned. Pus has been present in variable quantity during this time, and occasionally blood. Once there was quite a free hemorrhage from the bladder. Her husband has been washing out the bladder through a catheter, which has given temporary relief.

February 25, 1898. — An examination revealed a complete tear through the perineum and an acutely retroflexed uterus. The bladder on the posterior surface was deeply reddened, but no vessels were seen. In the left lower quadrant was a deposit of white lymph and mucus intimately adherent to the surface beneath it. The vault of the bladder was mottled with red injected areas, and absolutely no vessels could be seen. The affection was most severe at the base of the bladder, which was covered with extensive greyish deposits, the largest area being on the left side at the junction of the wall and base, covering an area about 3x3 cm. The left ureteral orifice appeared as a little point in the midst of a white area. These greyish areas had irregular margins covering shallow ulcers of the mucous membrane. The only trace of sound mucosa was about the internal orifice of the urethra.

The bladder was then thoroughly curetted by a sharp curette, and about 2 oz. of a twenty per cent, solution of silver nitrate was injected, followed immediately by a pint of normal salt solution.

Two days later Dr. Young's method was employed, the irrigation being given every two hours. After two weeks the


improvement was so marked that the number of irrigations was dropped to intervals of four hours.

March 16th. — On account of some return of jiain the patient was again examined under ether. The change in the local condition was astonishing; in every direction the mucous membrane had returned to normal, except at the left and base of bladder. This area has the same appearance as previously described and bleeds easily on touch. These points were again curetted and an application of silver nitrate made. The intervals between the irrigations were then reduced to six hours.

March 2'drd. — A continuous steady improvement has been noted since the Young method was adopted. The patient now goes four to six hours frequently without voiding urine and sometimes sleeps all night. Several times during the past ten days the patient has been able to hold 500 cc. of solution during irrigation. The urine, which upon admission was loaded with pus and mucus and was always strongly alkaline, is now at times slightly acid and has only a small sediment.

Forty-six Intubated Cases of Diplitlieria treated witli Anti toxiue.— W. T. Watson, M. D.

Of the 46 cases reported, 37 recovered and died, giving a mortality of 19.5 per cent.

The recovered cases were of all grades of severity, from the cases in which the constitutional symptoms were slight and the children lively and playful as soon as the laryngeal stenosis was relieved, to those in which there was such profound prostration that for days life was desjmired of. In some cases the tube was coughed up in two or three days and did not have to be replaced; in others it had to remain iu for two weeks, and iu one instance for 22 days. In the earlier cases the tube was allowed to remain in place for a week, unless coughed up or taken out to be cleaned. In the later cases, according to the practice of O'Dwyer, the tube was removed in four days and reinserted if necessary.

In some cases the nourishment was entirely liiiuid ; iu others, particularly the later cases, the children were given anything they would take, liquid or solid, of a wholesome character.

Only in one case, where for two days the patient was unable to swallow, was nasal feeding found necessary.

The amount of antitoxine in the earlier cases was almost invariably 1000 units ; in the later cases the initial dose was usually 1000 units for a child under two years and 2000 units for children of two and over. It was usually given just after intubation.

The diagnosis was confirmed by culture, by membrane in the pharynx or which came up from the larynx during or after intubation, or by the presence of diphtheria in other members of the family.

Particular attention was paid to a study of the nine fatal cases. In at least four of them death was due to neglect, the children being in a practically moribund condition when intubation was performed and antitoxine administered. In one case, an infant of 11 months, the tube became blocked with a, tough piece of membrane and the baby immediately suffocated. One died of broncho-jmeumonia four days after the tube had been removed and the laryngeal symjjtoms had disappeared.


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The other three cases received antitoxine and were intubated reasonably early, but died with symptoms of Inug complication.

The death-rate from laryngeal diphtheria before the advent of intubation was almost 100 per cent. After the introduction of intubation it fell to about 75 per cent. At present with the antitoxine treatment some cases do not require operation, but in the operated cases the death-rate has fallen to about 27 per cent.

This death-rate is far too high and will be much reduced in the future when physicians are more impressed with the importance of the early use of antitoxine and early operation to relieve stenosis.

Intubation should be performed upon the first advent of dyspncea. In some cases where the dyspnoea is slight the amount of mucus which will escape from its imprisonment below the glottis, during and after intubation, is often surprising. If this mucus is allowed to accumulate for many hours it is possible that it might be the means of conveying infection to the lungs and setting up a broncho-pneumonia.

Discussion.

Dr. Plexner. — The last point made by Dr. Watson, that of the release of the bronchial mucus and its expectoration, impresses me as very important. We know now, thanks to the studies of Wright and Kanthack and Stephens, that the secondary pneumonias of diphtheria are caused in the majority of instances by the Klebs-LoefHer bacillus, and are notpyococcal in origin as was formerly believed. Dr. Anderson and myself have also been able to show that intratracheal inoculation of pure cultures of the b.icilius diphtheriae in rabbits provokes a pneumonic process. The bronchial and tracheal mucus contains the diphtheria organisms, and often in large numbers, so that its aspiration into the lung substance is to be prevented as far as possible, in the hope of averting the lobular pneumonias which so often are the immediate cause of death.

Dr. Watson. — In determining to intubate every case where the first signs of dyspnoea appear I am led to do so because no harm can result from it. It is painless, bloodless, and can do nothing but good.

I think, too, that intubation should be done by the general practitioner. He sees these cases first, and sometimes the parents have already delayed the matter too long, and in some cases by the time the physician has arranged to secure the services of a specialist, the child is dead, or at least it is too late for it to recover. I recently had a case where the child died a few minutes after intubation just from exhaustion ; it had been struggling for breath for 24 hours. I have been called to three cases within the last year and a half where the children were dead before I arrived, and I know that others in this city have had similar experiences. When the general practitioner becomes qualified to intubate the death-rate of laryngeal diphtheria will be greatly lowered.

HOSPITAL PLANS.

Five essays relating to the coustruetlon, orgaaizallonand raanageraeut of Hospluls. contributed by their authors tor the use of The Johns Hopkins Hospital.

These essays were written by Dus. John S. Billings, o( the n. S. Army, Norton FoLsoM of Boston, Joseph Jones of New Orleans. Caspak Moruis of PhUadelphia, and STEPHEN Smith of New York. They were originally published In 1876. One volume, bound in cloth, price $5.00.


NOTES ON NEW BOOKS.

Die Anaemic. I. Abthfilung. Normale un(] |iathologische Histologie des Blutes. Von Geh. Jled.-R. Prof. Dr. P. Khrlich und Dr. A. Lazarus. 8vo. Wieti : Alfred Holder, ]898. [Extract from Specielle Pathologic und Therapie. Herausgegeben von Hofrath Prof. Dr. Herman Nothnagbl. Bd. viii, I. Theil, 1. Heft.]

Tlie contributions of Professor Ehrlich and his pupils to the study of the blood have been of such great importance that this work has been looked forward to with considerable interest, both by physiologists and practitioners ; and neither will be disappointed in tlieir anticipation.

The present volume deals only with the general normal and pathological histology of the blood. The consideration of the pathology of the blood in special diseases will be dealt with in a second fasciculus. In an introduction the clinical methods of lilood examination are considered. In discussing the methods of estimation of hMmoglobin the authors justly speak of the value of the very simple clinical test, consisting in allowing a drop of blood to flow upon a piece of white cloth or filter paper, a method which if more used would prevent many a careless diagnosis of "anaemia."

They next take up the morphology of the blood, recommending especially the study of dried and stained specimens. The methods of preparing and examining dried cover-glass specimens are thoroughly set forth, and several valuable formulae are given for the preparation of different staining solutions ; that for t)ie preparation of the triacid stain is of particular value as a distinct improvement over the previously recommended methods.

The section upon the normal and pathological histology of the blood begins with the consideration of the red blood corpuscles The well known idea of Ehrlich as to the manner of origin of poikilocytosis (schistocytosis) and its conservative significance is reiterated. The question of the manner of origin and significance of the different varieties of nucleated red corpuscles is then discussed in a most interesting manner. The authors maintain that the disappearance of the nucleus takes place in the normoblasts by extrusion, in the megaloblasts by fragmentation and absorption. These latter elements they have found only in pernicious and inbothriocepbalus anaemia. The megaloblastic degeneration of the bone marrow is believed to be due to chemical influences of unknown origin.

The section upon the colorless corpuscles is, as might have been expected, one of great interest and importance.

The function of the spleen with regard to blood formation is considered at length. The conclusions reached from the work of Kurlov and others— that the spleen is of little importance as a producer of colorless corpuscles — that if cells be produced in the spleen, these are non-granular elements— that its function in this respect is more similar to that of the glands than to that of the bone-marrow — that "the spleen has not the least relation to ordinary leucocytosis," seem to be abundantly justified.

The fact that the glands are the seat of origin of the lymphocytes is clearly brought forth, and great emphasis is laid on the fact that no sufficient proof has yet been advanced that these cells have any genetic relation to the ordinary polymorphonuclear leucocytes. They form, according to the authors, a totally distinct and separate class of elements. This conclusion is in sharp contradistinction to that of the school of Uskov, who have assumed that the cellular elements of the blood have a distinct genetic relation to one another, the lymphocytes representing the youngest forms, the polymorphonuclear neutrophiles the fully developed or "old" elements, an attractive but hardly justifiable view.

It is interesting to note that the authors deny positively the power of lymphocytes ever to emigrate from the blood-vessels.

The bone marrow is shown to be the point of origin of those blood cells possessing specific granulations, neutrophilic, eosinophilic and basophilic (Mastzellen). The possible origin of the eosinophiles from fixed tissue cells is doubted. Beside being the


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point of origin of the majority of the leucocytes in the blood, the bone marrow is regarded as a storehouse for the polymorphonuclear neutrophiles, from which, by chemotactic inriueiices, they may be called forth in great numbers. ' Leucoeytosis is a pure function of the hone marrow." In the section on the " Demonairation and significance of the granules" the original view of Ehrlich that these elements represent specific metabolic products of the cell is maintained. The granules of the cellular elements of the blood are believed to be truly specific; but one variety of granule ever appears in a single cell. The common idea that eosinophilic and basophilic granules may occur in the same cell is believed by Ehrlich to be due to misinterpretation of a staining reaction which may occur in young imperfectly developed eosinophilic cells, where some of the granules may fur some time show a more or less well marked basophilic tendency. This color reaction is, however, always distinct from the sharp metachromatic stain taken by the true Mastzellen granulations. There is, the authors believe, some evidence that under circumstances the substance of the granules may become dissolved and escape from the cell. In conclusiun they say: "In general the granuUsof the wandering cells are capable of being given off into the neighborhood. This elimination is possibly one of the important functions of the polynuclear leucocyte."

Leucoeytosis is divided into an active and a passive form according to whether the cells increased in the circulation are incapable of individual movement and appear in answer to chemotactic irritants, or whether they are elements without locomobility which are washed passively into the circulation by mechanical influences. The type of the active form is represented by the ordinary polymorphonuclear leucoeytosis ; of the passive, by conditions of lymphKmia.

The active leucocytoses are separated into : " (a). Polynuclear leucocytoses :

(1) Polynuclear neutrophilic leucoeytosis.

(2) Polynuclear eosinophilic leucoeytosis.

(b). Mixed leucocytoses in which granular mononuclear elements take part: ' Myelaemia.'"

The leucoeytosis of the death agony is believed to be due solely to circulatory changes ; the slowing of the current is followed by an accumulation of the leucocytes alor^g the walls of the vessels. The polynuclear neutrophilic leucoeytosis is considered, as has been said before, to be purely a function of the bone marrow, dependent upon chemotactic substances calling forth the neutrophilic cells from their storehouse. The authors also believe that in most instances the substances jiositively chemotactic for the neutrophilic cellsact in a negative manner toward the eosinophiles ; hence the small number of the latter cells in ordinary leutocytoses. All active leucocytoses are not, however, of chemotactic origin. In some forms an increased activity of the bone marrow or an extensive change of fatty into red marrow may be the exciting cause.

The various conditions under which the polynuclear eosinophilic leucoeytosis occara are next considered. The authors are strongly of the opinion that the eosinophilic leucoeytosis depends also upon chemotactic causes, other, however, than those calling forth the polynuclear leucoeytosis. They do not believe in the local origin of eosinophilic cells elsewhere than in the bone marrow, nor do they agree with those who believe that the eosinophilic granules may arise from a direct transformation of the neutrophilic elements, a view which, it is but fair to say, has considerable in its favor, especially the remarkable observations of Brown in trichinosis. They believe that these chemotactic substances, while in some cases— for instance, in helminthiasis— foreign to the organism, are, for the most part, the products of some tissue destruction in the body itself. Attention is drawn to the remarka'de relation between the presence of Charcot's crystals and the increase in eosinophilic cells

The section upon leukmmia is extremely interesting. With jus


tice, apparently, the authors insist that, from an haematological standpoint, there exist but two forms of leukjemia :

"(I). Leukemic processes associated with an hyperplasia of lymphoid tistue : ' Lymphatic leukiemia.'

"(2). Leukasmic processes associated with hyperplasiaof myeloid tissue: ' Myelogenous leukiemia.'"

Lymphatic leuktemia is divided into an acute and a chronic form. The increase in the number of lymphocytes is believed to be due to a passive washing out into the blood, not to an active emigration due to chemotactic influences.

Myelogenous leuka?mia is discussed at length and an admirable description of the elements is given. " The microscopical picture of myelogenous leukaemia, apart from the almost invariable extensive increase in the colorless corpuscles, is conspicuous for its extremely variable and changeable character. This results from the association of various anomalies, namely:

A. Beside the polynuclear cells and their forerunners, the mononuclear granular leucocytes circulate in the blood.

B. All three types of the granulated cells, neutrophiles, eosinophiUs and mast-cellf, take part in the increase in the colorless corpuscles.

C. Atypical cell-forms appear ; for instance, dwarf forms of different varieties of colorless corpuscles, and, moreover, mitotic figures.

D. The blood always contains nucleated red blood corpuscles, often in considerable numbers."

Attention is called to the constancy of the absolute increase in the number of eosinophilic cells in leukaemia, one of Ehrlich's original observations which every competent observer has been able to confirm.

Emphasis is also laid on the constant increase in the number of mast-cells in this disease. This is a point which, so far as we are aware, has been little emphasized and yet one of considerable importance. The authors justly remark that the mast-cells may be recognized as well in specimens stained with the triacid mixture as with the characteristic stains for basophilic granules, inasmuch as they are here represented by polynuclear non-granulated elements. We believe that in many instances il is possible to actually distinguish the non-stained granules in such specimens.

The nature of myelogenous leukaemia is discussed in an interesting manner, and the conclusion is reached that the "origin of the leuksemic blood picture is to be explained by the assumption that, under the influence of the specific leukaemic poison, not only the ripe polynuclear elements but also their mononuclear eosinophilic as well as neutrophilic forerunners, wander into the blood ; that, therefore, myelogenic leukaemia is in all probability to be classed among the active leucocytoses."

The diminution of the leucocytes observed experimentally preceding leucocytoses, and believed by Loewit and others to be due to an actual destructive process {leucolysis), is thought to depend rather upon a negative chemotaxis. Attention is, however, called to the true leucopenia which may exist in some grave anaemias, dependent apparently upon a lack of activity of the bone marrow.

The authors speak guardedly with regard to the nature of the blood platelets as well as of the hcemokonion of Mueller.

The volume is a clear and direct statement of the views of the foremost living authority upon changes in the blood ; it is an extremely valuable addition to medical literature. It is to be hoped that the second part will be soon forthcoming. W. S. T.


BOOKS RECEIVKl).


Operative Gynecology . By Howard A. Kelly, A. B., M. D. Vol. I. 1S9S. 4to. 5ti3 pages. D. Appleton &Co., New York.

Manual of Operative Surgery. By H. J. Waring, M.S., M. B., B.Sc. (Lonil.;, F.R.C. S. 1S9S. T2mo. 661 pages. Young J. Pentland, Edinburgh, and The Macmillan t'o., N. Y.









Note.— This plate is intended to accompany Dr. Cone's article in the May number. To face p. IIS.


June, 1898.J


JOHNS HOPKINS HOSPITAL BULLETIN.


149


PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.


THE JOHNS HOPKINS HOSPITAL REPORTS. Volume I. 423 pages, 99 plates.

Jleport in PntUologry*

The Vessels aod Walls of the Dog's Stomach; A Study of the Intestinal Contraction;

Healing of Intestinal Sutures; Reversal of the Intestine; The Contraction of the

Vena Portae and its Influence upon the Circulation. By F. P. Mall, M. D. A Contribution to the Pathology of the Gelatinous Type of Cerebellar Sclerosis

(Atrophy). By Henry J. Behrley, M. D. Reticulated Tissue and its Relation to the Connective Tissue Fibrils. By F. P.

Mall, M. D.

Report in Dermatology. Two Cases of Protozoan (Coccidioidal) Infection of the Skin and other Organs. By

T. C. Gilchrist, M. D., and Emmet Rixford, M. D. A Case of Blastomycetic Dermatitis in Man; (Comparisons of the Two Varieties of

Protozoa, and the Blastomyces found in the preceding Cases, with the so-called

Parasites found in Various Lesions of the Skin, etc.; Two Cases of Molluscum

Fibrosum; The Pathology of a Case of Dermatitis Herpetiformis (Duhring). By

T. C. Gilchrist, M. D.

Report in Pntholog^y. An Experimental Study of the Thyroid Gland of Dogs, with especial consideration

of Hypertrophy of this Gland. By W. S. Halsted. M. D.


Volume II. 570 pages, with 28 plates and figures.

Report in 3Ie«lielne.

On Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with

Gallstones. By William Osler, M. D. Some Remarks on Anomalies of the Uvula. By John N. Mackenzie, M. D. On Pyrodin. By H. A. Lafledr, M. D. Cases of Post-febrile Insanity. By William Oslkr, M. D. Acute Tuberculosis in an Infant of Four Months. By Harry Toulmin, M. D. Rare Forms of Cardiac Thrombi. By William Osler. M. D. Notes on Endocarditis in Phthisis. By William Osler, M. D.

Report in ]^ledicine.

Tubercular Peritonitis. By William Osler, M. D. A Case of Raynaud's Disease. By H. M. Thomas, M. D. •

Acute Nephritis in Typhoid Fever, By William Osler, M. D. Report in Gynecology.

The Gynecological Operating Room. By Howard A. Kelly, M. D.

The Laparotomies performed from October 16, 1889, to March 3, 1890. By Howard

A. Kelly, M. D., and Hunter Robb, M. D. The Report of the Autopsies in Two Cases Dying in the Gynecological Wards without Operation; Composite Temperature and Pulse Charts of Forty Cases of

Abdominal Section. By Howard A. Kelly, M. D. The Management of the Drainage Tube in Abdominal Section. By Hdnter Robb,

M. D. The Gonococcus in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Peritoneum;

Ovarian Tumor; General Gynecological Operations from October 15, 1889, to

March 4, 1890. By Howard A. Kelly, M. D. Report of the Urinaiy Examination of Ninety-one Gynecological Cases. By Howabd

A. Kellt, M. D., and Albert A. Ghrisket, M. D. Ligature of the Trunks of the Uterine and Ovarian Arteries as a Means of Checking

Hemorrhage from the Uterus, etc. By Howard A. Kelly, M. D. Carcinoma of the Cervix Uteri in the Negress. By J. W. Williams, M. D. Elephantiasis of the Clitoris. By Howard A. Kelly, M. D. Myxo-Sarcoma of the Clitoris. By Hunter Robb, M. D. Kolpo-Ureterotomy. Incision of the Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gynecological Operations. By

Howard A. Kelly, M. D.

Report in Surgery, I,

The Treatment of Wounds with Especial Reference to the Value of the Blood Clot in the Management of Dead Spaces. By W. S. Halsted, M. D.

Report in Neurology, I.

A Case of Chorea Insaniens. By Henry J. Berkley, M. D. Acute Angio-N«urotic Oedema. By Charles E. Simon, M. D. Haematomyelia. By August Hoch, M, D.

A Case of Cerebro-Spinal Syphilis, with an unusual Lesion in the Spinal Cord. By Henry M. Thomas, M. D.

Report in Pathology, I.

Amoebic Dysentery. By Williau T. Councilman, M. D., and Henri A. Lapleur, M. D.


Volume III. 766 pages, with 69 plates and figures.

Report in Patboloey.

Pi.pillomatoii8 Tumors of the Ovary. By J. Whitridqe Williams, M. D. Tuberculosis of the Female Generative Organs. By J. Whitbidoe Williams, M. D.

Report in Pathology.

Multiple L} mpho-Sarconiata, with a report of Two Cases. By Simon Flexner, M. D.

The Cerebellar Cortex of the Dog. By Henry J. Berkley, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman, M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Russell, Ph. D.

Heart Hypertrophy. By Wm. T. Howard, Jr., M. D.

Report in Gynecology.

The Gynecological Operating Room; An External Direct Method of Measuring the Conjugdta Vera; Prolapsus Uteri without Diverticulum and with Anterior Enterocele; Lipoma of the Labium Majus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Source of Error in Gynecological Diagnosis; Operation for the Suspension of the Retroflexed Uterus. By Howard A. Kelly. M. D.

Potassium Permanganate and Oxalic Acid as Germicides against the Pyogenic Cocci. By Mary Sherwood, M. D.

Intestinal Worms as a Complication in Abdominal Surgery. By A. L. STArxLT, M. D.


Gynecological Oporations not involving Celiotomy. By Howard A. Kelly, M. -D. Tabulated by A. L. Stavelt, M. D.

The Employment of an Artificial Retroposition of the Uterus in covering Extensive Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdominal Pelvic Operations. By Howard A. Kelly, M. D.

Photography applied to Surgery. By A. S. Mcrray.

Traumatic Atresia of the Vagina with Haematokolpos and Hxmatometra. By Howard A. Kelly, M. D.

Urinalysis in Gynecology. By W. W. Russell, M. D.

The Importance of employing Anesthesia in the Diagnosis of Intra-Pelvic Gynecological Conditions. By Hunter Robb, M. D.

Resuscitation in Chloroform Asphyxia. By Howard A. Kelly, M. D.

One Hundred Cases of Ovariotomy performed on Women over Seventy Years of Age. By Howard A. Kelly, M. D., and Mary Sherwood. M. D.

Abdominal Operations performed in the Gvnecological Department, from March 5, 1890, to December 17, 1892. By Howard A. Kelly, M. D.

Record of Deaths occurring in the Gynecological Department from June 6, 1890, to May 4, 1892.


Volume IV. 504 pages, 33 charts and illustrations.

Report on Typlioid Fever.

D., and J.

Report in Nenrology.

Dementia Paralytica in the Negro Race; Studies in the Histology of the Liver; The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supplv of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of the Submaxillary Gland of M^i^ musculus; The Intrinsic Nerves of the Thvroid Gland of the Dog; The Nerve Elements of the Pituitary Gland. By Henry J. Berklet, M. D.

Report in Snrgery.

The Results of Operations for the Cure of Cancer of the Breast, from June, 1889, to January, 1894. By W. S. Halsted, M. D.

Report in Gynecology.

Hydrosalpinx, with a report of twenty-seven cases; Post-Operative Septic Peritonitts; Tuberculosis of the Endometrium. By T. S. Cullen, M. B.

Iteport in Pathology.

Deciduoma Malignum. By J. Whitridqe AVilliams, M. D.


Volume V. 480 pages, with 32 charts and illustrations,

CONTENTS

  • The Malarial Fevers of Baltimore. By W. S. Thayer, M. D., and J, Hewetson, M. D.
  • A Study of seme Fatal Cases of Malaria. By Lewellts F. Barker, M. B.
  • Studies in Typhoid Fever. By William Osler, M. D., with additional papers by G. Blumer, M. D., Simon Flexner, M. D., Walter Reed. M. D., and H. C. Parsons, M. D.


Volume VL 414 pages, with 79 plates and figures.

Report in Neurology.

Studies on the Lesions produced by the Action of Certain Poisons on the Cortical Nerve Cell (Studies Nos. I to V). By Henry J. Berkley, M. D.

Introductory.— Recent Literature on the Pathology of Diseases of the Brain by the Chromate of Silver Methods; Part I.— Alcohol Poisoning.— Experimental Lesions produced by Chronic Alcoholic Poisoning (Ethyl Alcohol). 2. Experimental Lesions produced by Acute Alcoholic Poisoning (Ethyl Alcohol); Part H.— Serum Poisoning. — Experimental Lesions induced by the Action of the Dog's Serum on the Cortical Nerve Cell; Part HI.— Ricin Poisoning.— Experimental Lesions induced by Acute Ricin Poisoning. 2. Experimental Lesions induced by Chronic Ricin Poisoning; Part IV.— Hydrophobic To.xaemia.— Lesions of the Cortical Nerve Cell produced by the Toxine of Experimental Rabies; Part V.— Pathological Alterations in the Nuclei and Nucleoli of Nerve Cells from the Effects of Alcohol and Ricin Intoxication; Nerve Fibre Terminal Apparatus; Asthenic Bulbar Paralysis. By Henry J. Berkley, M. D.

Report in Pathology,

Fatal Puerperal Sepsis due to the Introduction of an Elm Tent. By Tuomas S. Cullen, M. B.

Pregnancy in a Rudimentary Uterine Horn. Rupture, Death, Probable Migration of 0\aim and Spermatozoa. By Thomas S. Cullen, M. B., and O. L. Wilkins, M. D.

Adeno-Myoma Uteri Diffusum Benignum. By Thomas S. Citllen. M. B.

A Bacteriological and Anatomical Study of the Summer Diarrhoeas of Infants. By William D. Booker. M. D.

The Pathology of Toxalbumin Intoxications. By Simon Fleinbr, M. D.

TAP price of a srt Uouml iti eh,t1, [Vols. I-VI] of thr Hospital Jtrports is $30.00. Vol.s. J, II ami III are not sold sepavateltj. The j'tice o/ Vols. IV, V and Vl is $3.00 each.


Monographs.

The following papers arc reprinted from Vols. I, IV, V and VI of the Reports, for those who desire to purchase in this form: STUDIES IN DERMATOLOGY, By T. C. Gilchrist, M. D., and Emmet Rixford,

M. D. 1 volume of 164 pages and 41 full-page plates. Price, bound in paper,

$3.00. THE MALARIAL FEVERS OF BALTIMORE. By W. S. Thayer, M. D., and J.

Hewetson, M. D. And A STUDY OF SOME FATAL CASES OF MALARIA.

By Lewellys F. Barker, M. B. 1 volume of 280 pages. Price, in paper, $2.75. STUDIES IN TYPHOID FEVER. By William Osler. M. D., and others. Extracted

from Vols. IV and V of the .Johns Hopkins Hospital Reports. 1 volume of 481

pages. Price, bound in paper, $3.00. THE PATHOLOGY OK TOXALBUMIN INTOXICATIONS, }^y Simon Flexner, M. 1>.


THE JOHNS HOPKINS MEDICAL SCHOOL. SESSION 1897-1898.

FACULTY.


Daniel C. Oilman^ LL, D., President.

WiLLiAU H. Welch, M. D., LL. D., Dean and Professor of Pathology.

Ira Remsen, M. D., Ph. D., LL. D., Professor of Chemistry.

William Osler, M. D., LL. D., F. R. C. P., Professor of the Principles and Practice

of Medicine. HENRr M. HoRD, M. D., LL. D., Professor of Psychiatry. William S. Halsted, M. D., Professor of Surgery. Howard A. Kelly, M. D., Professor of Gynecology and Obstetrica. Franklin P. Mall, M. D., Professor of Anatomy. John J. Abel, M. D., Professor of Pharmacology. William H. Howell, Ph. D., M. D., Professor of Physiology.

William K. Brooks, Ph. D., LL. D., Professor of Comparative Anatomy and Zoology. John S. Billings, M. D., LL. D., Lecturer on the History and Literature of Medicine. Alexander C. Abbott, M. D., Lecturer on Hygiene. Charles Wardell Stiles, Ph. D., M. S., Lecturer on Medical Zoology. Robert Fletcher, M. D., M. R. C. S., Eng., Lecturer on Forensic Medicine. William D. Cooker, M. D., Clinical Professor of Diseases of Children. John N. MACFtENZiE, M. D., Clinical Professor of Laryngology and Rhinology. Samuel Theobald, M. D., Clinical Professor of Ophthalmology and Otology. Henrt M. Thomas, M. D., Clinical Professor of Diseases of the Nervous System. Simon Flexner, M. D., Associate Professor of Pathology. J. Whitridqe Williams, M. D., Associate Professor of Obstetrics. Lewelltb F. Barker, M. B., Associate Professor of Anatomy. William S. Thayer, M. D., Associate Professor of Medicine. John M. T. Finney, M. D., Associate Professor of Surgery.


Georqb P. Dreyeb, Ph, D., Associate in PhyBiology.

William W. Russell, M. D., Associate in Gynecology.

Henry J. Berkley, M. D., Associate in Neuro-Pathology,

J. Williams Lord, M. D., Associate in Dermatology and Instructor in Anatomy.

T. Caspar Gilchrist, M. R. C. S., Associate in Dermatology.

Robert L. Randolph, M. D., Associate in Ophthalmology and Otology.

Thomas B. Aldrich, Ph. D., Associate in Physiological Chemistry.

Thomas B. Futcher, M. B., Associate in Medicine.

Joseph C. Bloodgood, M. D., Associate in Surgery.

Thomas S. Cullen, M. B., Associate in Gynecology.

Ross G. Harrison, Ph. D., Associate in Anatomy.

Frank R. Smith. M. D., Instructor in Medicine.

Georgi! W. Dobbin, M. D., Assistant in Obstetrics.

Walter Jo.ves, Ph. D., Assistant in Physiological Chemistry.

Adolph G. Hoen, M. D.. Instructor in Photo-Micrography.

Sydney M. Cone, M. D., Assistant in Surgical Pathology.

Louis E. Livingood, M. D., Assistant in Pathology.

Henry Barton Jacobs, M. D., Instructor in Medicine.

Charles R. Bardeen, M. D., Assistant in Anatomy.

Stewart Paton, M. D., Assistant in Nervous Diseases.

Norman McL. Harris, M. B., A^istant in Pathology.

Harv^ey W. Cushino, M. D., Assistant in Surgery,

J. M. Lazear, M. D., Assistant in Clinical Microscopy.

J. L. Wal2, Ph. G., Assistant in Pharmacy.


GENERAL STATEMENT.

The Medical Department of the Johns Hopkins University was opent-d for the instruction of students October, 1803. This School of Medicine is an integral and coordinate part of the Johns Hopliins University, and it also derives great advantages from its close affiliation with the Johns Hopkins Hospital.

The required period of study for the degree of Doctor of Medicine is four years. The academic year begins on the first of October and ends the middle of June, with short recesses at Christmas and Easter.

Men and women are admitted upon the same terms.

In the methods of instruction especial emphasis is laid upon practical work in the Laboratories and in the Dispensary and Wards of the Hospital. While the aim of the School is primarily to train practitioners of medicine and surgery, it is recognized that the medical art should rest upon a suitable preliminary education and upon thorough training in the medical sciences. The first two years of the course are devoted mainly to practical work, combined with demonstrations, recitations and, when deemed necessary, lectures, in the Laboratories of Anatomy, Physiology, Physiological Chemistry, Pharmacology and Toxicology, Pathology and Bacteriology. During the last two years the student is given abundant opportunity for the personal study of cases of disease, his time being spent largely in the Hospital Wards and Dispensary and in the Clinical Laboratories. Especially advantageous for thorough clinical training are the arrangements by which the students, divided into groups, engage in practical work in the Dispensary, and throughout the fourth year serve as clinical clerks and surgical dressers in the wards of the Hospital.

REQUIREMENTS FOR ADMISSION.

As candidates for the degree of Doctor of Medicine the school receives :

1. Those who have satisfactorily completed the Chemical-Biological course which leads to the A. B. degree in this university.

2. Graduates of approved colleges or scientific schools who can furnish evidence : (a) That they have acquaintance with Latin and a good reading knowledge of French and German ; (6) That they have such knowledge of physics, chemistry, and biology as is imparted by the regular minor courses given in these subjects in this university.

The phrase "a minor course," as here employed, means a course that requires a year for Its completion. In physios, four class-room exercises and three hours a week in the laboratory are required; in chemistry and biology, four class-room exercises and five hours a week in the laboratory in each subject.

3. Those who give evidence by examination that they possess the general education implied by a degree in arts or in science from an approved college or scientific school, and the knowledge of French, German, Latin, physics, chemistry, and biology above indicated.

Applicants for admission will receive blanks to be filled out relating to their previous courses of study.

They are required to furnish certificates from officers of the colleges or scientific schools where they have studied, as to the courses pursued in physics, chemistry, and biology. If such certificates are satisfactory, no examination in these subjects will be required from those who possess a degree in arts or science from an approved college or scientific school.

Candidates who have not received a degree in arts or in science from an approved college or scientific school, will be required (1) to pass, at the beginning of the session in October, the matriculation examination for admission to the collegiate department of the Johns Hopkins University, (2) then to pass examinations equivalent to those taken by students completing the Chemical-Biological course which leads to the A. B. degree in this University, and (3) to furnish satisfactory certificates that they have had the requisite laboratory training as specified above. It is expected that only in very rare instances will applicants who do not possess a degree in arts or science be able to meet these requirements for admission.

Hearers and special workers, not candidates for a degree, will be received at the discretion of the Faculty.

ADMISSION TO ADVANCED STANDING.

Applicants for admission to advanced »tan(3lug must furnish evidence (1) that the foregoing terms of admission as regards prellmiuary training have been tulfllled, (2) that ciiurses equivalent In kind and amount to those given here, preceding that year of the course for admission to which application is made, have been satisfactorily completed, and (ai must pass examinations at the beginning of the session in Octobor in all the subjects that have been already pursued by the class to which admission Is sought. CertlBcates of standing elsewhere cannot be accepted in place of these examinations.

SPECIAL COURSES FOR GRADUATES IN MEDICINE.

Since the opening of the Johns Hopkins Hospital in 1880, courses of instruction have been ottered to graduates in medicine. The attendance upon these courses has steadily increased with each succeeding year and indicates gratifying appreciation of the special advantages here aB'orded. With the completed organization of the Medical School, it was found necessary to give the courses intended especially for physicians at a later period of the academic year than that hitherto selected. It is, however, believed that the period now chosen for this purpose is more convenient for the majority of those desiring to take the courses than the former one. The special courses of instruction for graduates in medicine are now given annually during the months of May and June. During April there is a preliminary course in Normal Histology. These courses are in Pathology, Bacteriology, Clinical Microscopy, General Medicine, Surgery, Gynecology, Dermatology, Diseases of Children, Diseases of the Nervous System, Genito-Urinary Diseases, Laryngology and Rhinology, and Ophthalmology and Otology. The instruction is intended to meet the requirements of practitioners of medicine, and is almost wholly of a practical character. It includes laboratory courses, demonstrations, bedside teaching, and clinical instruction in the wards, dispensary, amphitheatre, and operating rooms of the Hospital. These courses arc open to those who have taken a medical degree and who give evidence satisfactory to the several instructors that they are prepared to profit by the opportunities here offered. The number of students who can be accommodated in some of the practical courses is necessarily limited. For these the places are assigned according to the date of application.

The Annual Announcement and Catalogue will be sent upon application. Inquiries should be addressed to the

REGISTRAR OF THE JOHNS HOPKINS MEDICAL SCHOOL, BALTIMORE.


Vol. IX.- No. 88.


BALTIMORE. JULY, 1898.


Contents

  • Remarks at the Presentation of the Candidates for the Degree of Doctor of Medicine at the Commencement of the Johns Hopkins University, June 14, 189S. By Wm. H. Welch, M. D., ------ 151
  • Conclusions from Clinical and Bacteriological Experiments with Holocain. By Robert L. Randolph, M. D., - - - -154
  • Observations on the Epithelium of the Urinary Bladder in ]Man. By Percy M. Dawson, M. D. . . - - 155
  • A Case of Sarcoma of the CEsophagus. By L. E. Livingood, M. D., - 159
  • Papilloma of the Fallopian Tube. By J. G. Clark, M. D., - - 163 The Histo-Pathology of Herpes Iris. With Report of Two Cases. By Lucius Crocker Pardee, M. D., 165
  • Notes on New Books, 171

Books Received, 172


REMARKS AT THE PRESENTATION OF THE CANDIDATES FOR THE DEGREE OF DOCTOR OF MEDICINE AT THE COMMENCEMENT OF THE JOHNS HOPKINS UNIVERSITY, JUNE 14, 1898

By William H. Welch, M. D., Dean of the Medical Faculty.


Mr. President, Gentlemen of the Board of Trustees, Ladies and Gentlemen :

As this is only the second class to receive the degree of Doctor of Medicine from this University, it will not be inappropriate, before presenting the candidates for the degree, to say a few words concerning the development and aims of the recently organized Medical Department of the University.

Through the munificent gift of Miss Mary Elizabeth Garrett, added to a smaller but generous contribution from other public-spirited women, and supplementing the available resources of the University and Hospital, the Trustees of the University were enabled to open the Medical Department for the instruction of men and women on the second of October, 1893. At two previous commencement exercises the opportunity has been afforded me to present in some detail the plan of organization and the purposes of the new Medical School, and it is not necessary to repeat what was then said.

We began live years ago with only the first year of the course organized, with a teaching staff of fifteen, and with an entering class of students numbering eighteen. A year from last October the organization of the entire four years' course was completed, and last .Tune we graduated our first class of fifteen students. During the academic year now closing 167 students have been enrolled as candidates for the degree of Doctor of Medicine, 26 in the fourth year, 3-1 in the third,


41 in the second, and 63 in the first. All of these are college graduates, and before admission spent a year or more in the study of chemistry, physics and biology. In addition, 69 physicians have been in attendance upon special courses or have engaged in research, making a total attendance of 236. The teaching staff numbers 53, of whom 21 are professors, clinical professors or associate professors. The steady growth of the Medical Department with each succeeding year has, therefore, been most gratifying and has laid to rest the fears, which some at first entertained, that our high standard of admission, necessitating not only a degree in arts or science, but also a good practical training in physics, chemistry and biology, with a reading knowledge of French and German, and acquaintance with Latin, would restrict unduly the number of students.

Not less significant is the national character of this Medical School as shown by the distribution of the students among the several States. 30 are credited to Maryland, but of these a number have made this their home only since entrance into the School. Of the remainder, 32 come from New England, 22 from the Middle States, 27 from the Southern, 38 from the Middle West or Central States, 13 from the West (11 being from Calfornia), and 5 from Canada, Hawaii and India.

47 colleges are represented, the Johns Hopkins University by 31 students, Yale by 29, Harvard and the University of


152


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 88.


Wisconsin by 9 each, Wellesley and Smith by 7 each, the Leland Stanford Jr. University and the University of California by 6 each, and Princeton, Williams, Amherst, Vassar, Cornell, the University of Chicago dud other colleges by smaller numbers.

But more significant than the growth of the School in numbers or the wide area from which our students are drawn are the contributions to the advancement of medical education in this country which we may fairly claim to have made. The mere addition of a new medical school to an already overburdened list can hardly be regarded as a meritorious act. We have realized from the start that unless we had something to contribute to the promotion of medical education and knowledge, there was no reason for our existence. No one familiar with the conditions of medical education in this country could fail to see that the opportunity existed to do for medical education what this University has accomplished for university education in this country. With the inspiration of such an example and with these high ideals before us, what better place could be found for such a work than in this University and in the city of Baltimore ? It would occupy too much time on this occasion to enter into details upon this subject, but concerning two or three of the more distinctive features of this medical school I shall ask permission to say a few words.

We have raised the requirement as to the training preliminary to the study of medicine to a point not only beyond that of any other medical school in this country, which in view of the former low demands in this respect might not signify much, but to one equal to, if not in advance of, that of any foreign university. This high standard of admission, instead of proving a weakness, has been one of the main sources of our strength. It has secured for us students whose average fitness for the study and practice of medicine is unquestionably greater than has been hitherto attained in our medical schools, and it has brought to us not a few of unusual capacity and promise. Students are attracted to an institution where their associations are wholly with liberally educated classmates, and the resulting tone and morale of the School are elevated, in welcome contrast to the traditional conception of the social and moral atmosphere of a medical school. It is evident that far better methods of teaching and better results can be secured with highly trained students than with those without adequate jH-eparation.

While we designate our required period of medical study as four years, it is in reality from five to six years, for we relegate to the period of preliminary collegiate training the study of general chemistry, physics and biology, which are included in the medical curriculum of many schools, especially in Europe. The study of these sciences, which is justly considered to be an essential part of a thorough medical education, can be pursued to greater advantage in a college or university than in a medical school, and the arrangement which we have adopted adjusts itself readily to the existing conditions in our best colleges and universities.

Coming to us with this exceptional training, our students have a right to expect exceptional advantages for the study of the profession which they have chosen, and, so far as our


resources permit, we have endeavored not to disappoint them in this respect. The aim of the School is primarily to train practitioners well grounded in the fundamental medical sciences and in practical medicine and surgery and their branches. We have broken completely with the old idea that reading books and listening to lectures is an adequate training for those who are to assume the responsible duties of practitioners of medicine. Anatomy, physiology, physiological chemistry, pathology, bacteriology, pliarmacology and toxicology are taught during the first two years by practical work in the laboratory, and in the last two years disease is studied in the dispensary and at the bedside, not merely as it is described in books.

At the beginning we had only one laboratory building; in 1894 we were provided with a second commodious building, the Women's Fund Memorial building, intended for the various anatomical sciences; in 1890, through a generous gift to the Hospital, we were enabled to construct the Clinical Laboratory, and in the coming autumn a still larger building, now in process of erection, will be ready for the laboratories of physiology, physiological chemistry and pharmacology. We shall then be well equipped with the needed laboratories, which constitute the workshops of our students during the first two yeai's of the course.

From these laboratories the students pass at the beginning of the third year directly to the Dispensary and the wards of the Hospital, where our arrangements to enable them to become practically familiar with the symptoms, the diagnosis and the treatment of disease constitute perhaps our most original and valuable contribution to the methods of teaching practical medicine. The generous cooperation of the Trustees of the Johns Hopkins Hospital, in accordance with the wishes of its founder, in rendering available for the instruction of students the resources of this great institution, has placed it in our power to make the years devoted to the training in the practical branches of medicine and surgery peculiarly attractive and efficient. They also provide for a large number of our graduates, as well as to others, opportunities to serve as interns in the Hospital.

The advantages of thus coming throughout the entire course into direct j^ersonal contact with the objects of study are not merely that the students thereby acquire a more useful and living knowledge of them, but that they become familiar with scientific methods and acquire something of the scientific spirit of investigation and of approaching medical problems. They should thus be enabled by their subsequent observations and experience to carry on an education, only begun at the medical school, and which should continue throughout their professional lives.

To obtain the best results of practical training of the kind mentioned it is of importance that the student should be brought into contact with those who are not merely teachers but also investigators. In the selection of heads of departments the Trustees of the University and of the Hospital have kept in view that a great medical school should not only teach medicine but also advance the medical scier.ce and art. We feel that we may take just pride in the number and value of the published contributions to medical knowledge by nieni


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btTS of the staff of the School and llosjiital, ami, iiuleetl, it is a sign of great promise that several of our students have already conducted noteworthy investigations, leading in some instances to important discoveries.

In a school with such standards for preliminary training and with such opportunities and methods of study, it is selfevident that the standard of attainment should also be kept high, so that the bestowal of its diploma may be a real distinction to such as attain it. In this respect the Faculty have felt a serious sense of responsibility, directed solely by the desire that no one shall be promoted to the doctorate of medicine in this University who does not measure up to the high standards which have here been set.

I have endeavored to point out in a few words the lines along which this Medical School in the short period of its existence has developed and certain of its salient characteristics. We feel that we have here an unrivaled opportunity for the development of a great medical school, devoted to higher education and the advancement of medicine. The time is one of marvellous activity and progress in medicine, with new paths and new vistas constantly opening for exploration. We cannot occupy the vast field so fully as we desire. We need ampler resources to take full advantage of our opportunities. I know of no direction in which pecuniary investments for education will yield larger returns in advancement of knowledge and promotion of the welfare of mankind than in the endowment of higher medical education.

Medical departments of universities in this country have usually been such in name only and at best have been looked upon as step-children, out of harmony with true, university life and ideals. A medical department which brings to the University only liberally educated men and women, provides a four years' course of study conducted with the best methods, cherishes "the scientific spirit and contributes to the advancement of knowledge, is surely a worthy member of a university, however high its ideals. The medical department which has here been founded has been cordially received by this University as equal and coordinate with its philosophical department. This intimate union of Medical School and University is of mutual benefit, and in this close association we find constant encouragement and incentive to attain the best. We have been guided throughout by the unceasing care and wise direction of the President of this University, and we believe that the enlightened and generous policy of the Trustees of the University and the Hospital has brought to fulfillment the wishes of the founder of this University and of the Hospital concerning the Medical School for which he provided.

Members of the Graduating Class :

In behalf of my colleagues and for myself I congratulate you upon the satisfactory completion of a prolonged period of liberal and professional study in preparation for your chosen career.

You, with the class which preceded you, came to us when you could not see plainly the end from the beginning, trusting in assurances held out to you for the future. You have participated in the establishment of this Medical School. This


circumstance imparts peculiar interest and intimacy to your relations with us.

It is during this formative period that the impress of students' ideals and conduct upon the inner life of a university is most distinctly felt and that traditions are formed which may powerfully influence the future health and vigor of the institution. That your influence upon this inner life has been for good, we feel assured. During all these four years we have been stimulated by your diligence, enthusiasm, ability and desire for knowledge, and we appreciate your hearty cooperation with our efforts. We, your teachers, have acquired more than a teacher's interest in you. Intimate acquaintance has led to genuine friendship, and we do not doubt that we shall have occasion to feel a personal pride in your future good work. Yon go forth with the best wishes and high expectations of all of us.

You have acquired some knowledge of the fundamental principles of medical science, some practical familiarity with the nature and treatment of disease and injury, the ability to iTse the instruments of your profession, and, above all, I trust, correct methods of work and a trained scientific spirit of investigation. Of the entire contents of the science and art of medicine you have, however, learned relatively only a small part, but you are now in position to increase your knowledge through your own individual efforts and through experience to acquire wisdom.

Such a training as you have received should enable you to derive satisfaction of a high order in the pursuit of your profession, a satisfaction not to be obtained from its practice merely as a ti'ade and means of subsistence. The scientific physician of to-day finds intellectual pleasures, as never before, in the study of the science and the practice of the art of medicine, and this scientific interest is dignified and enhanced by the power, ever increasing, of doing good to others through the relief of pain and suffering. To the ranks of this noble and useful profession we now welcome you.

Mr. President :

In the name of the Medical Faculty I have the honor to present to you twenty-two candidates whom we recommend for promotion to the degree of Doctor of Medicine in this University. All, after receiving a liberal education indicated by a degree in arts or science and fulfilling all of our requirements for admission, have spent four years in the study of medicine and have satisfactorily completed the course in this University.

List of Students Receiving the Degree of Doctor of Medicine.

William Stevenson Baku. A. B., Jolins Hoplvins University, 1S94. Baltimore.

William Jephtha Calvekt. A. B., University of Kentuclvy, 18U:J; Graduate Stndent, Kentucliy State College, 1893-94. Lexington, Ky.

Patkick .Joseph Cassidy. A. B., Yale University, 1894. Norwich, Conn.

.liiiiN Williams Coe, ,Tu. Ph. B., Yale University, 1893. JleriJen, Conn.

Percy Millauh Dawson. A. B., .lohns Hopkins University, 1894. Montreal, Canada.


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Ahthuk Wells Eltinq. A. B., Yale University, 1S04. Upper Red Hook, N. T.

William Weber Fokd. A. B., Adelbert College, 1893. Norwalk, O.

Thomas Wood Hastings. A. B., Johns Hopkins University, 1894. Morristown, N. J.

Alfred Birch HERitinc. A. B., Williams Collese, 1S94. Amsterdam, N. T.

James Hall Mason Knox, Jr. A. B., Yule University, 1892, and Ph. n., 1894. New Haven, Conn.

Millard Lanofeld. A. B., Johns Hopkins University, 189.S. Baltimore.

Gertrode Light. S. B., University of Wisconsin, 1894. Milwaukee, Wis.

James Daniel Madison. S. B., University of Wisconsin, 1894. Mazomauie, Wis.

Harry Taylor Marshall. A. B., Johns Hopkins University, 1894, Baltimore.


Roger Griswolu Perkins. A. B., Union College, 189:3, and Harvard University, 1894. Schenectady, N. Y.

Katuerine Porter. A. B., Bryn Mawr College, 1894. Baltimore.

Joseph Hersey Pratt. Ph. B., Yale University, 1894. North Middleboro, Mass.

Georgiana Sands. A. B., Vassar College, 189.3; Graduate Student, Barnard College (N. Y.), 1893-94. Port Chester, N. Y.

BEN.TAMIN Robinson Schenck. A. B., Williams College, 1894. Syracuse, N. Y.

Walter Ralph Steiner. A. B., Yale University, 1892, and A. M., 189.5; Graduate Student, Johns Hopkins University, 1802-94. Baltimore.

Emma Elizabeth Walker. A. B., Smith College, 1887. Parkersburg, W. Va.

Andrew Henderson Whitridge. S. 15., Harvard University, 1894. Baltimore.


CONCLUSIONS FROM CLINICAL AND BACTERIOLOGICAL EXPERIMENTS WITH HOLOCAIN.

By Robert L. Kandolph, M. D.


I have been using holocaiu for some months and have recorded here fifty-four cases where I employed it in the eye clinic of the Johns Hopkins Hospital. Seventeen of these cases were foreign bodies in the cornea, and the average time employed to produce anesthesia was a little less than two minutes. In three cases iridectomy was performed, and in eight cases cataract extraction. Here I made the same number of instillations as I do when employing cocain, that is, three in fifteen minutes, and all that can be said is that I noticed no difference in the anesthesia from that produced by cocain, and the same may be said of eight tenotomies. The other cases were where the holocain was employed after the aj)plication of irritating substances as copper sulphate, nitrate of silver, and after the passing of probes, in operations for tarsal cysts and pterygia. With the exception of the tarsal cysts the anesthesia was produced in a little more than two minutes.*

Most of those who have reported ou the subject of holocain have alluded to its germicidal properties. I have looked through the literature and, with the exception of some very meagre experiments made by Heinz showing that the yeast bacteria are retarded in their growth by contact with holocain, have found no record of experiments proving that a solution of holocain is germicidal.

The following exjjeriments were made to throw some light upon this aspect of the question.

I. To determine the effect of a 1 per cent, solution of holocain upon the micrococcus epidermidis albus (Welch). For this purpose thirty wooden toothpicks were sterilized by boiling for ten minutes. They were then immersed for five minutes in a suspension of the organisms in sterilized water, afterwards taken out and dropped into a 1 per cent, solution of holocain. Here they were allowed to remain fifteen minutes. They were then taken out with long sterilized


For an exliaustive account of the clinical aspect of holocain see the various reports of Henry Wiirdemann, M. D., Milwaukee.


forceps and plunged each into a tube containing nutrient agar. After being in the thermostat twenty-four hours they were inspected and in every tube there was a luxuriant growth. Control tubes showed that the pieces of wood were sterile before immersion in the suspension of organisms. The growth in half of the tubes was examined and the micrococcus epidermidis albus was found in every instance. Fifteen experiments made with the staphylococcus pyogenes aureus resulted in the same manner. In another series glass rods were employed instead of pieces of wood. The rods were sterilized by holding them in the flame. They were then dropped into a suspension of the aureus in sterilized water and allowed to remain there five minutes. When taken out, instead of putting them directly into the holocaiu solution as was done in the first and second series, they were put into a sterile tube and allowed to dry thoroughly, and then immersed fifteen minutes in a 1 per cent, solution of holocain, after which each rod was plunged into a tube of nutrient agar. The result was the same as in the first and second series.

II. To determine whether a ] per cent, solution of holocain has an inhibitory effect upon these same organisms.

Five grains of holocain were dissolved by boiling in 8 cc. of water, and to this were added 3-t cc. of fluid agar. The resulting mixture was practically a 1 per cent, solution of holocain. Twenty tubes of " slant agar " were prepared in this way, and ten "smear cultures" made of the staphylococcus pyogenes aureus, and ten of the micrococcus epidermidis albus. These tubes wei'e inspected every day for three days, but there was never any evidence of a growth. This experiment was repeated a number of times by others in the laboratory as a control measure, and in every instance with the same result. Neither the staphylococcus pyogenes aureus nor the micrococcus eiiidermidis albus would grow in a medium containing holocain in the proportion mentioned. It should be said that these organisms will grow in nutrient agar containing holocain ill the proportion of J of 1 per cent.

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holocaiu had an inhibitory effect upon the organisms would seem to indicate that some of the organisms on the glass rods and pieces of wood in the first, second and third series were killed. To determine this question the following experiments were made. A thick suspension of the staphylococcus pyogenes albus was made in a physiological salt solution. Five loops of this suspension were transferred to a tube containing 8 cc. of a 1 per cent, solution of holocaiu, and five loops were transferred to a tube containing the same quantity of salt solution ; this latter measure as a control. After allowing the organisms which had been transferred to the holocain solution to renuiiu there five minutes, two loops of the latter solution were carried into fluid agar and plate cultures made. This was repeated after ten, fifteen, twenty and thirty-five minutes, and finally after twenty-four hours. In the first plate (after five minutes) there were fifteen colonies; in the second jilate (after ten minutes) there were about the same number; in the third plate (after fifteen minutes) there were five colonies; after twenty minutes three colonies; after thirty-five minutes two colonies and a big impurity, and finally after twenty-four hours the plate was sterile. This series was repeated and with practically the same result. There was a gradual diminution in the number of the colonies the longer the organisms were allowed to remain in the holocain, and after twenty-four hours it was seen that the holocain no longer contained living organisms. Plate cultures made after twenty-four hours from the salt solution showed numerous colonies.*

Conclusions : Holocain, in so far as its anesthetic properties are concerned, seemed in these fifty-four cases to have been sufficiently effective. In those cases where a test was made of the rapidity of its action, as for instance in foreign bodies in the cornea, pterygia, and after the application of irritating


substances, the quickness with which ^liesthesia was produced was striking. Whether the anesthesia produced after two minutes is sufficiently profound to guarantee a painless iridectomy or a satisfactory cataract extraction I did not determine, but in those cases where operations of this character were performed, and where the holocain was instilled just as we do eocain, no difference was observed in the anesthesia from that produced by the latter.

The drying of the cornea and desiccation of its epithelium and the dilatation of the pupil, the absence of which phenomena has been noted by others, have been confirmed by my own observations. The absence of these two properties should recommend it for office use for the removal of foreign bodies, as it is well known that after the employment of cocaiu in such cases, blurred vision and slight photophobia are often present for hours.

A 1 per cent, solution of holocain has not only an inhibitory effect upon the pus organisms, but these organisms are killed when exposed to a solution of this strength for a certain length of time. No attempt was made to determine the point of time at which these organisms lose their vitality on exposure to holocain, but it may be safely said that this point is somewhere within twenty-four hours. Furthermore, exposure to a 1 per cent, solution of holocain for periods of five, ten, fifteen, twenty, twenty-five and thirty-five minutes showed in every instance a gradually diminishing number of colonies in the plates, so that it is plain, in spite of the luxuriant growth around the glass rods and pieces 'of wood, many of the organisms were killed.

It may be said in conclusion, then, that a solution of holocain of the strength employed in 02)hthalmic practice possesses distinct germicidal properties, a fact which it is evident enhances the value of this product.


OBSERVATIONS ON THE EPITHELIUM OF THE URINARY BLADDER IN MAN.

By Percy M. Dawson, M. D.


The following report deals, first, with the clinical history of a patient treated for urethritis in the genito-urinary dispensary of the Johns Hopkins Hospital; secondly, with the microscopical study of specimens of bladder epithelium obtained from this patient during the course of treatment.

CLINICAL HISTORY.

F. S., male, aet. 33, single, huckster, native of Baltimore. The patient presented himself at the dispensary on January 6, 1898, complaining of swelling of the left testicle. He gave


It is evident that the amount of holocain brought over in the loops was not sufficient to alter the properties of the agar to the extent of inhibiting tlie growth of organisms. In order to produce this effect more than ^ of 1 per cent, holocain should be present in a given quantity of agar. Harilly more than two or three drops in all of holocain were brought over in the loops, so the reason, then, that the organisms did not grow was because they were killed before they were transferred to the plates.


a history of an attack of gonorrhoea one year ago, and of a second attack which began about December 18, 1897. Of this last attack the period of incubation was nine days. There was considerable ardor urinre, but only a slight discharge. No other local symptoms and no constitutional symptoms were present. By December 38, 1897, the discharge had become too scanty to be observed by the j)atient. On January 3, 1898, he noticed a swelling of the left testicle and also tenderness on pressure.

On examination (January 0, 1898), the contents of the left scrotal sac measured 3.5 x 4 x 7 cm., the swelling being chiefly in the globus minor, which was extremely tender on pressure. The skin of the scrotum was red, slightly cedematous, but not adherent. The left cord was slightly enlarged and somewhat tender. Eight testicle and cord normal; inguinal glands palpable on both sides, but not enlarged.

The urethral discharge was thick, slightly yellowish and very scanty. It contained a few pus cells and a few cocci


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and short thick bacilli which did not decolorize by the Gram method.

The urine was of a pale amber color and slighly acid. In the flrst glass of the two-glass test the urine was uniformly cloudy, but on standing a small quantity of light, white, flocculent sediment was deposited, leaving only a few mucous shreds in the supernatant fluid. This sediment was found to contain a considerable number of pus cells and a very few epithelial cells. The contents of tlie second glass were similar except that the sediment was very scanty and contained no pus.

The treatment adopted was the vigorous use of the rai(iieliii cautery over the atfected epididymis, as recommended by Halsted, and for the urethritis intravesical injections of a solution of potassium permanganate, 1 : 6000. An order was given for an irrigation apparatus and for permanganate tablets, and the patient was directed to force the solution into his bladder three or four times daily.

On January 10, 1898, the patient returned. The urethral discharge had ceased. The urine showed a diminution in the amount of sediment and in the number of pus cells which it contained.

On January 11, 1898, the patient began to retain the irrigation fluid in his bladder, sometimes for as long as one or two hours, thinking that this might hasten his recovery. This maucEuvre was persisted in for two days (January 11, 12), in spite of the fact that the patient experienced a dull heavy pain in the region of the sacrum while holding the irrigation fluid. This pain always disappeared immediately on micturition.

On January 13, 1898, the patient came complaining of these pains in his back and of a sensation of itching on the glans penis. The affected testicle, though still considerably swollen, was much less painful. The meatus looked a little reddened, but there was no discliarge. The patient had not emptied his bladder since his last injection at 8 a. m. and it was then 10.30 a. m. The urine when voided was of a peculiar smoky brownish color and contained a number of small brownish flakes which soon settled to the bottom. There was also a considerable sediment composed of such flakes. In the supernatant urine floated about twenty large membranous flakes, of extreme thinness and of a dark brownish color. Several of these flakes were as large as the little finger-nail, one measuring 8x12 mm. T'hey hung quivering just beneath the surface of the liquid for some hours before finally settling to the bottom.

On microscopical examination, these bits of membrane were found to consist of a single layer of polyhedral cells, forming a perfect mosaic and entirely intact. The sediment was coml)osed of cell detritus and a great number of epithelial cells, single or in groups, some well preserved, others more or less decomposed or necrotic. No pus was observed and no blood.

The contents of the two glasses were similar, except that the first contained a larger quantity of sediment.

The patient was directed to continue the use of the permanganate solutions, but not to retain them in the bladder.

All this was at 10.30 a. m. At 1 p. m. the patient irrigated himself, but on expelling the fluid observed nothing unusual. At 4.30 p. m. he made the same observation. At 8.30 p. m. he came to the hospital and voided there perfectly normal urine.


in which neither pus cell nor epithelial cell could be demonstrated even after centrifugalization.

Subsequently the patient returned to the dispensary several times. His last visit was on January 31. He assured us that he felt perfectly well. He had been away from home since January 17 and had irrigated himself only four times during the past two weeks.

The left globus minor was slightly larger than the right (which may have been normal) and was not at all tender. There was no discharge. The urine was amber, slightly cloudy, with one or two shreds in each glass. On standing, a small amount of sediment was deposited in the first glass, which on examiiuition was found not to contain pus cells.

MICKOSCOPICAL EXAMINATION.

The specimens obtained from the patient, F. S., consist entirely of surface epithelium. They were fixed and hardened, some in sublimate, others in absolute alcohol, and were stained with saflFranin or by the iron-hajmatoxylin method.

The larger cells are irregular and polygonal in form ; the smaller ones are often hexagonal. Their outlines are very clear. Along the margins of many of the cells is a row of short teeth-like processes which seem to bind together the adjacent cells. They resemble the intercellular protoplasmic bridges described by some authors, but from our preparations their exact nature cannot be determined.

The granular protoplasm usually fills the entire cell, but sometimes, especially in the larger cells, there is a clear nongranular zone in the periphery. In the cells in which the finer structure can be made out, the cell body appears to be composed of countless minute vacuoles, between which the protoplasm is uniformly granular. In some cases the whole cell body appears homogeneous, but usually this vacuolated structure can be observed.

The nucleus is round or oval, sharply outlined, and situated at or near the centre of the cell. The chromatin is difl'nsed throughout the nucleus, and also concentrated into several dark irregular masses about five to fifteen in number. With careful focusing connecting bauds between these masses may sometimes be found, resembling somewhat a nuclear figure composed of several moniliform chromosomes knotted and coiled together.

In many instances vacuolated nuclei were found. There is rarely more than one vacuole in a nucleus. They are usually central, and the chromatic masses are displaced and lie upon the surface of the vacuole.

In the protoplasm of many of the cells vacuoles can be seen, some quite small, some so large that the nucleus is crowded to the periphery, the whole cell being swollen and jiresentiug the signet-ring appearance so characteristic of fat cells. Between these extremes all sizes of vacuoles and all degrees of nuclear displacement occur.

The most striking phenomenon observed in the study of these cells is the budding of the nuclei. In some cases the buds occur as knobs upon the surface of the mother nucleus; in others they are attached to the mother nucleus by a pedicle containing a chromatic material which may be either short and liroad or may a]ipear as a fine uniting band. Or agiiin, the bud may be free in the cell protoplasm, and in such cases it is only


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their small size which suggests tlieir origin. The larger buds contain one or more masses of chromatin ; the smaller ones usually do not. The varieties of these budding forms are almost innumerable. There may be one to four buds each varying independently of the others in size and in the manner of their attachment, so that examples of all stages of this process occur in abundance.

In addition to the cells with budding nuclei there are many multinucleated cells, and the rarity with which one linds the nuclei dividing into equal daughter nuclei, and the fact that between the nucleus witli a little broken-otf bud and the binucleated cell every gradation exists, strongly suggests that the multinucleated cells are derived from tlie mononucleated by a process of budding.

There is a class of cells of which examples are frequently found. They differ from those above described in being larger, with one or two larger and paler nuclei which are sometimes irregularly fragmented. These may be cells which have become swollen and degenerated either before the budding process had begun or perhaps just after the first division of the mother nucleus.

Not only do cells with two nuclei occur, but we also find them with three, four, up to huge giant cells with fifteen nuclei. As a rule the nuclei of these giant cells stain more feebly than do those' of the mononuclear cells. The protoplasm is somewhat more granular, the clear zone bordering tlie periphery is often very marked, and the surrounding cells often appear to bulge into them. The protoplasm is often vacuolated, and in some, one or more of the nuclei are found budding.

To give some idea of the frequency of the budding and of the multinucleated forms, a differential cell count was made. In an area which under the low power did not appear particularly promising there were in 1000 cells — 70 cells with 1 bud, 15 " '• 2 buds, 5 « " 3 " 3 " « 4 "

93 cells with budding nuclei. Also -to cells with 3 nuclei,

3 " " 3 "

43 multinucleated cells. And in another area where the giant cells were abundant there were in two adjacent fields of the ^ oil immersion —

5 cells with 3 nuclei, 3 '• "3 " 3 " "4 •' 1 " "6 "

Literature.

The literature on the structure of the bladder mucosa appears to be very scanty. Our text-books on histology are almost silent on the subject, and it w-as only in an article by Dogiel that a detailed description has been found.

In 1890, A. 8. Dogiel, professor of histology in tlie University of Tomsk, published in the Arch. f. Micro. Anatomic an article entitled ' Zur Frage iiber das Epithel der Harnblase."


In his study of the epithelium Dogiel employed paraffin sections and macerated preparations of the bladders of the house mouse, white mouse, rat, hamster, cat, dog, and man.

He describes the epithelium as being composed of four layers: the first consisting of squamous cells; the second of cuboidal, columnar, and pyriform cells; a third layer similar to the second; and the fourth layer of round or fusiform cells filling up the interstices between the cells of the third layer.

The cells of the first layer resemble thick plates. They are irregular, polygonal, and sometimes divided into two parts by a central constriction.

The protoplasm of the cell usually consists of two more or less distinct parts — an upper and a lower. The upper is onethird the whole thickness of the cell, homogeneous or only slightly granular, and stains red with picrocarmine. The lower part is very granular and stains yellow with picro-carniine. The granular appearance is due to a network of rather thick fibres, between which is a clear interfibrillar substance.

On tlie under surface of the cell one finds rather deep depressions. They are from three to ten in number, depending upon the size of the cell. Into these depressions fit the upper ends of the cells of the second layer. From the bottom of each of these depressions several canals of various calibres arise and run towards the upper surface of the cell, passing almost comjiletely through the granular layer. These canals have usually an oblique direction and end blindly. They are continuous with the cup-shaped depressions on the under surface of the cells. They contain protoplasmic prolongations arising from the underlying cells, which, together with protoplasmic threads hanging down from the cells of the superficial layer, intimately unite the cells of the two layers. These canals and protoplasmic threads are conspicuous in the mouse and rat, but are poorly developed in other animals.

On the superior surface of these cells one often finds one or more nodular, polypoid or sausage-shaped projections composed of a granular material. These granules may be regarded as being of a mucous character, for they bear a close morphological resemblance to mucous granules and stain intensely with hffiuiatoxylin. Hence the whole surface of the bladder may be regarded as a spread-out mucous gland.

In the granular part of each epithelial cell lies the large vesicular nucleus, round or oval in shape, and surrounded by a rather thick membrane with a double contour. In some cases vacuoles occur in the nuclei.

The nuclear network is composed of threads of varying thickness running from the center to the periphery. In each nucleus occur two to fifteen round, oval, or rod-shaped granules, one usually being larger than the rest. They stain much more deeply than the rest of the nucleus and sometimes appear to have a bright border.

Of these nuclei there are present in each cell one to twelve or more. The multinucleated cells are quite abundant in the small rodents, while in the cat, dog and man this is not the case. The nuclei may be in one or more groups, or scattered, or in pairs and biscuit-shaped. In size these nuclei vary greatly. There may be a number of equal nuclei, or one nucleus may have a number of smaller nuclei clustered about it, forming a sort of colony.


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One often meets with nuclei which are constricted by a circuhir furrow, sometimes of such a depth that the two parts of the nucleus are united by only a slender band. In many cases there are two or more sncli furrows. The parts into which the nucleus is thus divided vary greatly in their relative sizes, and hence the variation in the size of the nuclei of the multinucleated cells.

Throughout this division the nuclear membrane remains perfectly distinct and there is no observable change in the chromatin. Hence we have to do Avith a process of amitotic division, or rather of budding.

As to whether or not the division of the nucleus is followed by a division of the cell body, Dogiel is unable to decide, but merely remarks that the occurrence of constricted cells favors the view that such division does occur.

The remaining layers of the mucosa concern us but little. Their cells increase by a process of mitosis and not by budding. In the rodents the cells of the second layer are brought into intimate relation with those of the first layer by means of the protoplasmic processes above mentioned.

Conclusions.

It will be observed that the description of the cells obtained from the urine of the dispensary patient agrees in part with the description given by Dogiel. There are, however, some noteworthy differences.

In these specimens no stellate arrangement of the chromatin is present, nor any pale ring surrounding the masses of chromatin, nor is there any tendency for one mass of chromatin to exceed the rest in size. There is no cupping of the under surfiice of the cells, nor any sausage- shaped projections from the upper surface.

Dogiel makes no mention of the "bridges" between the cells of the superficial layer, while on the other hand our specimens do not show the canals and threads which Dogiel describes as being so well developed in the small rodents but so poorly developed in the larger manimalia. In our specimens, the absence of these connecting threads and the existence of the cell bridges may explain the occurrence of the large Hakes of mucosa, the connections between the individual cells of the superficial being so much stronger than the connections between this layer and t!ie one below" it.

That there is any protoplasmic network of rather thick fibers, such as Dogiel describes, these specimens afford no evidence at all. Whenever any finer structure can be made out, the cell body is seen to be composed of vacuoles with a uniformly granular protoplasm between them.

Of the occurrence of the giant cells, Dogiel says that they are common in the small rodents but rare in man. In these specimens of human bladder, however, there is quite a different state of things, as the result of the dift'erential cell count shows.

What is the significance of this formation of giant cells ? Is it a simple process of proliferation, as Dogiel thought, or is it a process, so to speak, of slow and orderly fragmentation? The specimens have furnished not the slightest evidence that this is a true cell division and not merely a nuclear division, for in no instance have cells been found having a central constriction of the protoplasm such as Dogiel has described. It is not


probable that the weak solution of potassium permanganate produced any particular change in the cells. The giant cells contain large vacuoles much more often than do the mononuclear cells, their nuclei usually stain more feebly and are more often seen to be fragmenting irregularly. All these observations, namely (1) the absence of cell division, (3) the deficient nuclear staining, (3) vacuolization, (4) karyorhexis, point to the fact that we have to do with a process of degeneration.

In conclusion I wish to thank Dr. Young for the permission to report the case, and for the interest he has shown in the study of the specimens.

Fig. 1. — a. Nucleus with two buds.

b. Large pale nucleus with bud.

c. Nucleus with vacuole.

d. Nucleus dividing.

e. Cell with two nuclei

/. " " three " (near center of field). g. " " four " h. " " five " I. " '• ten " /. " " vacuole.

k. Giant cell with vacuole displacing nuclei. I. " " " degenerated nuclei and vacuolated protoplasm.

Fig. 3. — Shows single cells with "teeth-like margins," and more or less distinct vacuolization of the protoplasm.

(t, 1), c. Cells with one, two and three nuclei resjiectively.

(/. Cell with nucleus in process of division.

e. Cell with three nuclei, of which one has a large and a small bud.

Discussion.

Dr. Bauker. — We are to be congratulated upon having this case so thoroughly worked up. It is curious that the epithelium is shed in such large sheets. It looks as though the cement substance connecting the superficial layer with the parts below is more susceptible to attack by the permanganate solution than that between the individual cells of the superficial layer. I have had the opportunity of studying these specimens with Sir. Dawson and have been much interested in many of the pictures he has obtained. The number of giant cells present is surprising. It is important to determine whether or not as many as he finds are normally jn-esent, that is to say whether or not the permanganate solution has actually caused an increase in the number of these cells. There is some evidence that these giant cells of the bladder wall may play a part in pathological processes. The late Dr. Brown once showed me a section from a carcinoma of the bladder in which there were large numbers of such multinucleated epithelial giant cells.

It would be easy to continue the study by animal experiment, and I would suggest if it should turn out that water alone is incapable of causing the changes described in the bladder, that an attempt be made to determine just what constituent of the permanganate solution it is that is active, the cation, the anion, or the non-dissociated molecule. It would seem probable a priori that the anion is the constituent concerned.


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Dr. Thayer. — I saw some of the siiecimens and I would like to call attention to the great similarity of some of the pigment of the nuclei to that of some of the blood corpuscles in grave diseases. In the hlood there can be very little doubt that it is a karyolitic process.

Dr. OsLER. — It would be very interesting to have Jlr. Dawson study the epithelium of the bladder in a series of post-mor


tem cases. I think he would probably iind a very large number of these giant cells with many nuclei.

Mr. Dawson.— Dogiel used two methods, that of cutting sections and that of maceration in various fluids. He does not mention having obtained by the latter method any large flakes of mucosa, but he does describe the single cells obtained in this


A CASE OF SARCOMA OF THE (ESOPHAGUS.*

By L. E. Livingooi), M. D., Associate in Pathology, Johns Hopkins University.


Through the courtesy of Dr. Frank IJ. Smith I have to present this evening a specimen obtained at autopsy from a patient who died of sarcoma of the (esophagus.

On July G, 1897, H. S., a German by birth, cal)inetmaker, ast. 55, was admitted to the Johns Hopkins Hospital complaining of difficulty in swallowing and " rheumatic pains," especially in the shoulder.

From careful notes taken by Dr. ilcCrae I have made the following abstract :

" Family history negative. He has been an active, healthy man ; denies venereal infection; takes beer moderately, a glass of whiskey regularly in the morning ; his work is done indoors. He has lived in Baltimore 15 years; has had rheumatic pain at times during past two years.

"About April 1, 1897, he began to complain of pain in the throat in the neighborhood of the sternal notch. The onset was gradual, and at first the pain was not constant, the patient attributing it to having caught cold. The pain was increased by swallowing, and there developed difficulty in swallowing solids, especially bread. The pain on swallowing seemed to begin at the sternal notch and to extend to the stomach. It persisted only for a few moments. The pain in the neck, however, was constant and was sometimes severe enough to keep him awake. Sometimes on swallowing the pain would run up to both ears, not infrequently bringing tears to his eyes.

"The appetite has been fairly good. No regurgitation of food, no vomiting, no cough, no expectoration, no shortness of breath ; bowels regular. He has lost 30 pounds in the last 3 months, but does not think he has lost any strength. No increase of pain on deep breathing, no interference with respiration. Patient was able to keep at his woi'k until July 3rd, nearly 3 months after the symptoms were first noted."

"On admission. Fairly well nourished. No emaciation. Color fair. Puffiness under the eyes. Sclerotics somewhat injected. Pupils equal. Tongue coated, edges I'ed and indented. Gums and mucous membrane of mouth of a fair color. No mass to be felt in the neck. No tracheal tugging. No marked pulsation. Thorax: large and muscular. No pulsation seen or felt. Expansion poor. Pespiration largely abdominal. On percussion the note seems clear ; possibly


Read before the Johns Hopkins Hospital Medical Society, May 16, 1898.


there is slight relative dullness behind on the right side in the interscapular region. Breath sounds clear. Heart sounds appear clear, second sounds strong. Pulse strong, synchronous and of equal volume in radials and femorals. Well marked dermatographia. No general glandular enlargement. Soft tube passed into stomach easily, no obstruction." It may be noted that before entering the hospital patient was seen in the dispensary and an attempt to pass a stomach tube was made. Just before entering the stomach it seemed to meet with an obstruction; patient became very much distressed; the tube was withdrawn and a little blood was seen upon the end.

On July 12th the following note was made:

"Stomach tube meets with no obstruction where patient complains of pain, but when passed 44 cm. from the lips there is some resistance to passage of tube. Pressure on tube causes pain. Small amount of bloody material was removed on the point of the tube, but on microscopic examination was found to consist of red blood cells, pus and squamous epithelial cells. No fragments of tissue found.

"The blood examination showed hajmoglobin 88 per cent., red cells 5,040,000, whites 7500. Urine practically normal (3 exms.). On one occasion a faint trace of albumin was found and one hyaline cast. No diazo reaction. No sugar. Specific gravity 1018. The temperature ranged between normal and 101° F. Patient was discharged on July 17th, improved, especially in regard to the rheumatic pains."

From this time on he was seen occasionally at his own home by Dr. Smith. His condition varied a good deal. At times he felt a little stronger and seemed to gain slightly in weight. At other times he complained of great pain and was unable to swallow anything but the smallest quantity of li([uids. With the latter he ofteu had great difficulty. For several days at a time he could hardly take any nourishment and complained of a severe cough and pain. On more than one occasion after severe coughing he brought up fragments containing mucus and what looked like necrotic tissue and blood. One specimen of tiiis was examined under the microscope, but it was too much decomposed to give any clue as to the nature of the disease. However, the existence of a new growth (probably carcinoma) was strongly suspected. For several days after coughing up this material, patient's condition was materially improved. He could take liquids easily, and even partially solid food could be swallowed. About four days before his death he was suddenly seized with intense


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pain over the lumbar region and between the shoulders. The abdomen was much distended and was tympanitic. It was not, however, very painful and the distension disappeared in the course of a day or so. After this the patient sank almost into a state of collapse, but occasionally revived and said that he felt much better. lie finally died on the 20th of November, 1897, at 4 P. M.

Autopsy at 9.30 P. M., 5 J hours after death. Body of strongly built man. Very much emaciated. Skin of sallow hue. Body still warm. Small amount of deep yellow fat. Abdominal cavity shows nothing abnormal.

Thorax. — Lungs voluminous. Left pleural cavity free from adhesions. Eight pleural cavity obliterated over lower lobe posteriorly by recent adhesions which can be readily broken up. Left lung shows congestion in posterior portions. Right lung: Anterior and upper portion pale and slightly emphysematous. Upper lobes somewhat puckered and at one point bound by fibrous adhesions to ribs. A few fine adhesions between the middle, upper and lower lobes. On freeing the lower lobe the lung tissue about the root and posteriorly is torn, and a foul-smellitig necrotic material escapes, the last part of which is more fluid and smells sour. The lower lobe is large, firm and congested. The serous surface from which the adhesions spring is roughened and ha^morrhagic. About the place where the lung has been torn on removal the tissue is much discolored, soft and necrotic. On cutting the lung loose from its root a cavity communicating with the oesophagus is opened up, from which more sour-smelling turbid fluid pours. The lung in this portion is soft and discolored, and in it there is a gangrenous cavity which could contain several ounces of fluid. The lobe (lower) around this gangrenous area is irregularly consolidated, the consolidation affecting the posterior inferior two-thirds of the lobe. On section the surface in this area is deep red, slightly elevated, dry or granular. The lung is completely airless. The bronchi in this portion of the lung are congested and contain a purulent discolored material. The middle lobe is normal. The upper lobe contains an encapsulated calcareous nodule.

The pericardial cavity normal. The heart is of moderate size. The wall is rather soft and pale. Surface of section is dry. Endocardium normal. Slight atheroma of aorta just above valve. The spleen weighs 250 grams. Condition described as that of acute spleen tumor. Kidneys are large, each weighs about 220 grams. They were in condition of cloudy swelling with congestion of glomerular capillaries. Liver large; condition of cloudy swelling. No evidence of tumor metastases. Other abdominal organs were normal.

Descriplion of Ihunor. — About 4 cm. below the bifurcation of the trachea the lumen of the cesophagus is obstructed by a new growth, made up of a main body with several smaller polyp-like masses extending down from it. The main mass presents a thick circular ridge arising abrujitly from the mucous membrane of the oesophagus and almost completely encircling a crater-like central portion. It measures about 6 cm. from the upper to the lower edge. It does not entirely surround the lumen of the oesophagus, but leaves a strip of mucous membrane about 2 cm. wide running vertically between its lateral adjacent edges. This thickest part of the


mass representing the upper portion of the ridge projects about 1..5 cm. into the lumen, and overhangs the mucous membrane. Its edge is quite regular, sharply defined from the mucous membrane, although the latter is reflected for a short distance upon it. The surface is smooth, rounded, nodular, yellow-white in color; its inner surface, representing the wall of the depressed center, becomes more and more discolored and necrotic. The crater in the center is partially filled with foul-smelling purulent material and shreds of necrotic tumor tissue. The floor is discolored, necrotic, soft and friable, and in the lowest part is continuous, through a short fistulous opening several cm. in diameter, with a gangrenous cavity in the right lung. From the lower end the new growth is seen invading the mucous membrane without much elevation, at first uncovered by epithelium, later projecting beneath the epithelium as a very slightly elevated spur.

This main mass of the new growth extends to within 4.5 cm. of the cardiac orifice of the stomach. Growing down from it for a distance of 1.5 cm. and projecting still further is an elevated irregularly formed polyp-like mass, about the size of the last two phalanges of the little finger, from which i

a second polyp projects into the lumen. This mass also I

arises abruptly and regularly from the mucous membrane which is reflected for a short distance over it. Its surface is smooth, white or slightly discolored. The smaller projecting j

polyp has become necrotic and is quite readily friable. The I

line of continuity between the two main masses is plainly '

evident. There is a small nodule the size of a small bean in the muscularis of the cesoj^hagus, about 4 cm. above the main tumor mass, apparently quite distinct from it, although the wall of the cesophagus between them is thickened. This nodule is only visible on section of the wall.

These tumor masses are uniformly firm, elastic, and not friable except in those places in which necrosis has occurred. The surface and edges are smooth, with no appearance of vegetation or excrescences. The surface of section of the periphery of the tumor, when the oisophagus is cut open, shows a shining, uniform, white or slightly pink, moist

appearance. It is made up of delicate circling strands of ^

tissue. The mass is subdivided into small nodules by strands of more vascular tissue, extending upwards here and there from the muscularis. No juice can be squeezed from the cut surface. Its surface is somewhat discolored towards the central portion, which is friable, discolored and necrotic, and which penetrates deeply into the wall, and at one point entirely through it. The inner muscular layer of the esophagus seems to be involved in the new growth, and small areas of new growth appear in the outer muscular coat.

At the upper limit of the growth the muscular wall, mucosa and submucosa, become rapidly normal, showing that the tumor is not infiltrating the wall, as a carcinoma would naturally do.

In the lower polyp the new growth seems to rest upon the inner muscular coat and to be continuous with it. The surrounding tissues are more congested than normal portions, and more congested than the tumor tissue.

'IMie (t'sophagus is slightly distended above the mass. Its mucous membrane is congested and discolored, having a


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green-gray appearance for several cm. above and below it. The external fibrous coat is greatly thickened. Its outer surface is roughened. Corresponding to the central part of the tumor, several pea-sized nodules, which on section are seen to be practically continuous with the tumor tissue, project from the surface. One of these, which is yellow and opaque, is readily broken into and appears to form the floor of a necrotic crypt. To the right of this point the right lung is closely adherent to the Q?3ophagus. Its substance here is gangrenous, of a green-black color, soft and friable. The adjacent portions of the lung are deeply congested. At the point of perforation the lung substance has disintegrated, and there has been formed an irregular gangrenous cavity filled with putrid material. The main bronchi, which run to and through this portiou of the lung, contain a blood-stained gangrenous material. Their walls are deeply congested, but are intact. The bronchial lymph glands are diffusely pigmented, enlarged and congested, but careful study shows that they are not infiltrated. A small lymph gland is found lying in the outer wall of oesophagus which is apparently normal.

Bacle^-iohgical Examination.— Qosqv-s\\\is from lung (consolidated area) showed: (1) a number of typical capsulated forms of a lancet-shaped diplococcus ; (2) long slender bacilli with pointed ends ; (.3) a shorter form of thin bacillus, staining irregularly. The diplococcus forms were subsequently isolated in jiure culture and identified as diplococcus lanceolatus. The bacilli failed to grow under aerobic conditions. Cultures taken from the spleen and liver were negative.

Microscopic Examinalioii. — Sections cut from a number of points in the tumor show it to be rather uniform in its structure, mails up of a tissue rich in cells, often arranged in whorls, but not with distinct alveolar appearance. The deeper portions of the tumor are the most cellular, the superficial portions gradually become necrotic and the cells are separated by wider intervals, giving the appearance of oedema.

The cells are of spindle shape, varying in size, usually rather large, surrounded by more or less intercellular substance. The nuclei of the cells are of two distinct types, both elongated and vesicular. One type is small, more deeply staining and irregular ; the other is large, pale, sometimes greatly swollen. This latter type of nucleus is usually closely intermingled with the smaller type throughout the tissue. At one place, however, these nuclei seem to lie concentrically placed about a small space and are hemmed in by a zone of cells of smaller type. These larger cells resemble the endothelium lining the tissue spaces and vessels; the smaller represent the fibroblasts of young connective tissue.

The tissue is vascular. The fully formed blood-vessels of the mucosa and submucosa have persisted and lie in deeper parts of the tissue. In tlie younger parts the blood-vessels consist of a single layer of endothelium, often without even the appearance of a basement membrane separating them from the tissue elements.

For the most part the tumor lies on the muscularis, having infiltrated the submucous an<l mucous coats, and projects as a group of polyp-like nodules into the lumen of the asophagus. At the lower margin the transition from normal tissue of submucosa to the cellular tissue of the tumor is quite abrupt. Here the new tissue seems to spring from the muscularis or submucosa. It lies directly on the muscular layer, while strands of muscle tissue project upwards into it.

About the middle of the tumor the now tissue cells have infiltrated in masses and strands the muscularis, and extend down even into the thickened fibrous tissue layer. At a point near the per


foration the layers of the oesophagus are seen to be infiltrated, but owing to the great thickening. of the fibrous sheath the new growth does not completely penetrate the ro.sophagus at any point.

Just above the tumor the normal tissues of the cesophagns are very much indurated. There is marked proliferation of small round cells, which are arranged in groups running longitudinally in the mucosa under the epithelium and along the blood-vessels.

A line of union between the main mass and small nodule lying in submucosa above cannot be traced ; the small mass seems to have had a separate origin. For a short distance at the periphery the epithelium of the mucosa covers the surface of the new growth, but it soon becomes desquamated.

The surface of the mass is almost everywhere necrotic. Approaching the surface the nuclei stain more and more feebly and the tissue about them becomes (Edematous. There is swelling and fragmentation of nuclei. At the edge the nuclei fail to take the stain. Usually there is no polymorphonuclear cell infiltration on the surface.

At some points beginning necrosis is indicated by more marked changes in cells. The nuclei become greatly swollen and contain deeply staining globules of their chromatic elements ; this enlargement and hyperchromatosis is a common appearance. Sometimes a cell will contain 2 to 3 large swollen vesicular nuclei, about which there will be a distinct zone of protoplasm staining deeply in eosin. In the lower part the tumor shows most extensive degeneration and is infiltrated with polymorphonuclear leucocytes. The surface is covered with bacteria.

The wall of the perforating sinus extending through the outer nail of the (esophagus is not lined loith sarcoma tissue, but with necrotic, fully formed fibrous tissue, very vascular, congested and infiltrated with leucocytes, red blood corpuscles and bacteria. This fact indicates clearly that the tumor did not come from the outside nor did it completely penetrate the a-sophagus. The penetration was due to destructive action of bacteria which found lodgment in the crypts formed by breaking off of necrotic masses.

Sections stained with polychrome methylene blue show a number of "mastzellen" scattered through the tissues, and occasionally where the tissue is especially cellular, a few "plasma cells" of Unna grouped about blood-vessels. They can have little to do with tumor formation. It appears most probable that the tumor took its origin from the submucosa, growing in form of a polyp, and that all the connective tissue elements of the part entered into its formation. The tissues were fixed in formalin, hardened in alcohol, and stained with hsematoxylin and eosin, picric acid, fuchsin, and polychrome methylene-blue.

Although the tumor appears of rather benign type of sarcoma, the presence everywhere of karyokinetic figures in cells indicates, aside from the clinical history, that its growth was rapid. These evidences of proliferation were not more marked at the points of contact with the normal tissues than near the necrotic surface, and usually there was appearance of but little reaction on the part of tissues adjacent to either tumor tissue. From this one may assume that the direction of growth was not so much into the surrounding tissues as into the lumen of the gullet. There was no evidence of proliferation of muscle nuclei, and nothing which indicated vascular origin for the tumor except the occasional concentric arrangement of the larger endothelial-like cells.

The literature on sarcoma of the <:csoj)hagus, strictly speaking, is very meagre, although text-books on special pathology mentien its occurrence. Virchow mentions it in a oroiip with others. Sarcoma of the pharynx, on the other hand, is not uncommon. It is not improbable that this apparent rarity is due to a lack of careful histological study


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of tumors arising in this part, where carcinoma is of such frequent origin as to throw one off his guard. Clinically and even on macroscopic examination these two can appear in the same guise. Under certain conditions it maybe mistaken for a fibrous polyp.

In the first thousand autopsy I'ecords of the Johns Hopkins Hospital primary carcinoma of the cesophagus occurs 11 times, whereas this is the first primary sarcoma noted arising in that part.

In 1877 S. H. Chapman reported a ease, which may be included here, of sarcoma of the inferior constrictor of the pharynx and inlet of the cesophagus. The patient was a woman, aged 45. No family history of new growth. No distinct evidence of trauma. Had symptoms of increasing dysphagia during one winter. Died of exhaustion.

Wall of cesophagus was thickened like an inverted cone. On right side of ffisophagus, in midst of densest tissue, a cavity communicated from lumen of oesophagus with body of a tumor lying apparently outside, closely adherent to oesophagus and an enlarged gland. The structure of tumor is described as "alveolar." To the right and in front of the carotid artery was another larger gland measuring 1x2 inches of alveolar structure, enclosed in dense wall and containing some sero-purulent fluid. Cells of the tumor were mostly spindle cells and large oval granular cells which had formerly occupied the alveoli made by interlacing fibrous tissue strands. The new tissue involved, in some places, mucosa, submucosa and muscularis, *and consisted almost entirely of spindle cells, although an earlier stage, of round cells, was observable. No involvement of pharyngeal glands; no secondary deposits anywhere. Chapman believed that the tumor began in the cellular tissue in the inlet and spread upwards and downwards in the wall of the oesophagus.

In the Transactions of the Pathological Society of London three cases are to be found. The first reported by Targett, which the author states is the very first to be reported to that venerable society, occurred in a man of 70. The patient had suffered for three months with much pain between the shoulders and with difficulty in deglutition. He had physical signs of lobular pneumonia in both lungs. The tumor mass, which was attached to the outer wall of the gullet, measured iJxSJxli inches. Its upper border was just opposite to the bifurcation of the trachea and extended downwards nearly to the cardia. The oesophagus was dilated at the site of the growth, which here was moulded in the form of a tube. The tumor sprang from the submucosa. The muscular coat was free from infiltration except at one spot. The mucous membrane could be traced for a short distance over the upper and lower ends, but on the free surface it had been destroyed by ulceration and sloughing of the tumor itself. The tumor looked white, was uniformly succulent and resembled an "encephaloid cancer." Histological examination showed "small round spindle and tailed cells, some of the latter being very large and containing four nuclei." The spindle cells were arranged as bands and ran in all directions. Some parts resembled myxomatous tissue ; no secondary growths.

Shaw recorded a case occurring in a woman of 38. She


had suffered from dysphagia for several months, was unable to take her food and became rapidly emaciated. The growth consisted of an ulcer with well defined raised edges encircling the cesophagus. In front it extended up to within one inch of the cricoid cartilage and measured vertically three inches. For the most part the ulcer had merely destroyed the mucous membrane, but in front it involved all the coats and had perforated the trachea a short distance above the bifurcation. Some neighboring lymph glands had been enlarged by the deposit. Microscopically the esophagus was found infiltrated by a sarcomatous growth consisting of round and oval cells. Secondary deposits were found in the lungs and kidneys. The committee chosen to examine the specimen reported that " The cells are too large for a lympho-sarcoma, nor has the stroma the typical disi)Osition seen in that form of tumor."

Eolleston's case occurred in a man aged 54, who for seven months had suffered from difficulty in swallowing. Two months before he died there developed a painless tumor in the left hypochondrium. Cause of death, lobular pneumonia.

The cesophagus for the lower three inches was narrowed and thickened owing to the presence of a firm growth which completely encircled the lumen. The mucous membrane bad ulcerated over the greater portion of the surface of the growth. The growth was adherent to the pericardium, but had not penetrated it. It was fii mly united to the right lung. In the upper part of the structure there was a fistulous passage through the growth leading into a gangrenous cavity in the lower lobe of the right lung. The lower lobe was solid, gray in color and cedematous. Several of the glands on the root of the lung were swollen and infiltrated. The whole naked-eye appearance was that of an epithelioma of the cesophagus. Microscopically, the narrow part of the resophagus was found infiltrated with a growth composed of mediumsized round cells. Towards the edges the growth was seen to begin in the submucosa and to pass underneath the mucosa and outwards into the muscular coat, which was extensively but irregularly infiltrated with nodules of new growth. No alveolar arrangement was noted, except when tumor was invading muscle tissue. There was a fluctuating tumor, very vascular, the size of a man's fist, growing from and displacing the lower ribs on the left side. In the right iliac and in the middle fossa of the skull, and on the first and sixth ribs, and in the lymph glands, vascular soft tumor masses were found, the cells of which resembled those present in the tumor of the oesophagus. Kolleston considers that the growth must have been primary in the cesophagus, judging from its position and its density.

Oppenheimer's tumor seems to have reached the cesophagus by direct invasion from the outside. From his description one is led to believe that he was dealing with an aneurism of the oesophageal artery with an organizing lamellated clot.

From a study of the few reported cases it appears that clinically there is uo essential difference between these growths and carcinoma occurring in the cesophagus, and a diagnosis must depend upon those features which indicate the presence of the latter. Age and sex will not distinguish them ; they are both incident to more advanced life. The ages correspond veiy closely to those given by Orth for carcinonui : 40 to 70


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years. They occur more frequently in males. The advance, however, of the sarcomata is always rapid, and duration of illness after first appearance of symptoms does not extend over nine months. The factors of causation which are invoked for carcinoma and sarcoma generally, are hidden in these cases.

The symptoms of progressively increasing dysphagia, associated with painful deglutition, exhaustion and cachexia, are common to both.

The partial relief of dysphagia after the disch.arge of a necrotic mass was noted in one of these cases. Microscopic examination of such a mass might reveal the exact nature of the growth.

The occurrence of wide-spread metastases is apparently as infrequent as is carcinoma, and the localization of these metastases is not more definite.

The more frequent immediate causes of death from sarcomata, too, are exhaustion, with terminal lobular pneumonia or perforation, occurring in one case into the trachea, and in two cases into the lung followed by gangrene of the organ.

With the few cases at command and the abridged descriptions one cannot make more than a provisional statement as to the types of sarcoma most frequent in the oesophagus, their point of origin and their position.

Presumably three of the tumors are of the same type, spindle cell sarcomata, in Shaw's, Targett's and our own ; although Shaw's approaches the round cell type.

All of these are without any alveolar structure and seem to have S25rung from the submucosa. Kolleston's case appears to be a large round cell sarcoma without any appearance of


alveolation. The origin of his tumor is not clear. Chapman's tumor is difficult to understand ; it is alveolated and appears to have sprung from the tissues outside of the esophagus and to have penetrated its walls. A natural conclusion would be that it arose in a lymph gland, although he describes the cells occupying the alveoli as large, oval and granular.

The tumors may occur at any point in the length of the oesophagus, more frequently they appear iii the upper part. They may infiltrate all the coats and project into the lumen of the oesophagus. Necrosis of the superficial parts due to contact with the food masses occurs, and extensive sloughing and ulceration with perforation follow.

Kolleston's and Shaw's cases show wide-spread metastases. The liver has always escaped.

Bibliography.

Chapman, H. : American Journal of Medical Sciences, 1877, LXXIV, p. 433.

Kolleston, H. D.: Trans. Path. Soc. Loudon, 1892-93, XLIV, pp. 65-67.

Targett, J. H. : Trans. Path. Soc. London, 1889, XL, p. 76.

Shaw, L. : Trans. Path. Soc. London, 1891, XLII, p. 90.

Oppenheimer, L. S. : Louisville Medical News, 1879, VII, p. 74.

Korner: Ueber die nicht carcinomatosen Geschwi'ilste des (Esophagus. Inaug. Diss., Berlin, 1884.

Virchow : Die krankhaften Geschwiilste, II, III.


PAPILLOMA OF THE FALLOPIAN TUBE.


By J. G. Clark, M. D. {From the Pathological-Anatomical Laboratory of Professor Chiari in Prag.]


Up to the present time only six cases of simple, non-malignant ])apilloma of the Fallopian tube have been reported, abstracts of the histories of which, accompanied by a very excellent n'siime of the salient points of the subject, have lately been made by Sanger and Harth (Die Krankheiten derEileiter; Martin, 1895). Of these cases three have been reported by Albau Doran, two by Bland Sutton and one by Doleris.

Doran, who first called attention to tlie subject, inclined to the theory that these growths are not so much tumors as a simple hyperplastic process jiroduced by chronic infianimation.

On account of the rarity of these cases the following wellmarked example, which Prof. Chiari has kindly placed at my disposal for stndy, appears worthy of report.

HISTORY OF THE CASE.

Museum specimen No. 4769. A cystic tumor removed by Prof. F>ayer, from a woman aged 60, June 11, 1892.

The following clinical notes were obtained by Prof. Bayer from Dr. Slansky, the attending physician.

The patient had never miscarried or given birth to a full


term child, and until one year ago had been healthy. At that time she discovered a tumor in the abdomen, which, according to her statement, completely disappeared after a thermal cure, but later again appeared. During the first months of the year 1892 she was confined to bed on three occasions, first for three weeks, then for eight days, and again for three weeks, with attacks of peritonitis. After her recovery she consulted her physician with regard to the abdominal tumor.

Her general condition, as noted at that time by Dr. Slansky, was as follows: A rather weakly built, emaciated woman, of good facial color; heart and lungs normal; tongue slightly coated. The hypogastrium presents the vaulted appearance of a woman six mouths pregnant. The tumor which gives this appearance to the abdomen is globular, elastic, fluctuating, and in its upper part, towards the groin, is somewhat movable. Tlie cervix is movable, the uterus is deviated to the right, and although the fundus cannot be palpated, it appears to be small and adlierent to the tumor, which lies to the right. By digital examination a point in Douglas' cul-de-sac a considerable distance above the cystic tumor may be reached.


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[Xo. 88.


Prom this examination Dr. Slansky diagnosticated an ovarian cyst of the right side and advised its extirpation.

Owing to violent retching by the incompletely narcotized patient, during the preliminary cleansing of the abdomen the cyst was rnptured, and at once became soft and flat, and on physical examination free fln id could be demonstrated in the sides. Upon opening the abdomen, the contents of the cyst, a viscid, clear, honey-yellow fluid, were discharged and the top of the cyst prolapsed through the incision. With this part as a tractor, the entire tumor, which now appeared to be about the size of a child's head, was drawn out upon the abdomen and was found to be connected with the right mesometron by a small band-like pedicle about four fingers in length.

The ovary was situated below this pedicle and appeared perfectly normal. The central part of the pedicle consisted of the uterine half of the right Fallopian tube, which passed over into the tumor, where it became lost. In view of these points the diagnosis of an ovarian cyst was abandoned, and the thought of a parovarian cyst came niucb more prominently into mind. The pedicle was ligated in several sections and cut through transversely, after which the stump was cauterized, and separate ligatures were applied to all of the larger vessels. The contents of the cyst remaining in the abdomen after extirpation of the tumor were evacuated as completely as possible by rolling the patient over on her side The convalescence was uninterrupted and the patient was discharged well.

MACROSCOPICAL DESCRIPTION.

Cystic tumor half the size of a man's head (12 x 13 cm.), presenting at one spot an amputated surface 4 cm. square, at one point of which is a very short pedicle having the appearance of the enlarged uterine end of the Fallopian tube. Close to the point of amputation is an irregularly torn opening, through which the fluid contents of the cyst have escaped.

The exterior of the tumor is smooth, and in the superficial parts of the wall there are a few large dilated blood-vessels, wandering in irregular tortuous channels, while in the deeper parts an occasional necrotic area is noted.

The internal surface is almost completely covered with a thick papillary growth, consisting of multiple fungus-like excrescences, which, in some areas, are massed together in thick dense clumps, presenting a typical cauliflower appearance. The branches of these excrescences vary in size from delicate fimbriaj to large fusiform projections which contain small cysts. At one place, not far from the point of amputation, are circular folds, some of which reach the height of i cm., only covered with delicate velvet-like and small knobbed excrescences. The arrangement and general appearance of these folds at once remind one of those in the normal Fallopian tube. Bordering this area is a palm-sized surface devoid of papillary excrescences.

Upon spreading the excrescences apart, they are found in some parts of the cyst to spring from folds resembling those just described. Here and there these folds have become adherent and pressed back against the cyst wall, forming locculated spaces, some of which also contain papillary growths.


MICROSCOPICAL DESCRIPTION.

Sections through the circular folds show a greatly attenuated cyst wall measuring only 0.05 to 0.1 cm. in thickness. Layers of tissue are seen in the following order, counting from the outside towards the cyst cavity: peritoneum, circular muscle fillers, thin stratum of connective tissue, longitudinal muscle fibers followed by a denser layer of connective tissue, npon which one layer of columnar epithelium arranged in regular order rests. Except in the bay-like projections between the folds, the epithelium is non-ciliated, and even in these spaces the ciliated cells are only rarely found.

Numerous large dilated blood-vessels occupy the connective tissue layer beneath the epithelium. The folds of the Fallopian tube, as such, are no longer present, but are represented by sessile and pedunculated papillary growths.

The low sessile projections are composed of dense connective tissue, like that seen in chronic inflammation of the tube, whose cells extend at right angles from the underlying circular fibers, forming warty prominences clad with one layer of columnar ei)ithelium which gradually shades oft' into the low columnar and cuboidal variety as the domes of the projections are reached. Besides the sessile excrescences there are a few long, slender processes to which are attached daughter offshoots. The main stem in all instances contains large dilated blood-vessels. The connective tissue forming the stroma of these papillas shows a marked variation in its structure in different areas. At the bases of the papilL-e the cells are closely crowded together and contain deeply-staining spindle-shaped nuclei. This appearance is maintained until the apices or domes of the growths are approached, when the cells gradually become hyaliue, and in turn shade off into a pure mucoid degeneration.

Sections from the thicker portions of the cyst wall (0.5 cm. thick) show unstriated muscle fibers scattered very sparsely among the connective tissue fibers which make wp the chief part of the section. The internal surface of the cyst wall is covered with innumerable, vigorous growing papillomata, whose main stems extend far out into the lumen of the cyst, forming the most complicated, coral-like systems. The ofl'shoots have, in many instances, coalesced, forming spaces which contain small papillary growths.

In some instances the main stems have become adherent to each other, enclosing much larger gland-like spaces. The mucoid degeneration noted above is even more marked here, and in the large fusiform ends of some of the branches the entire stroma has undergone this transformation, giving the cystic appearance noted in the macroscopical description. Hemorrhage has occurred into some of these spaces containing the mucous tissue, leaving a granular debris which stains a bright yellow by Van (iieson's method.

The ends undergoing degeneration are covered by one layer of shrunken cuboidal epithelium, which rests upon a thin layer of hyaline connective tissue. Besides the cystic spaces formed by the fusion of the ])ai)illomata, others are found occupying a deeper portion of the cyst wall, lined by cuboidal epithelium and surrounded by a dense connective tissue stroma like those seen in " sacto-salphinx pseudo-follicularis." (J/rrW/x.)

In one of these spaces a small papillouui is seen in jirocess of formation. The single layer of cuboidal epithelium lining the


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cavity forms an uninterrupted line, except at one point, wliere it assumes a columnar shape and becomes heaped upon a delicate connective tissue papilla projecting from the main stroma.

Concluding Note.

In a general survey of the sections taken from various parts of the cyst wall tiie muscular tissue appears to be much less abundant and the connective tissue greatly increased over that seen in the normal ttibe. The papillomatous growtlis throughout have a non-malignant appearance, the epithelium being in general one-layered and at no place tends to invade the underlying tissue.

According to Siinger and Barth the differential diagnosis in these cases is rendered diflQcult on account of the tendency of all new growths of the Fallopian tube to assume a papillary appearance; in this case, however, its non-malignant character is so evident that its recognition is comparatively easy.

The early stages of primary carcinoma, before the epithelial cells have deeply penetrated tlie underlying tissue, or have formed metastatic foci in adjacent parts of the tube, may closely simulate the non-malignant papillary growths, especially wliere the latter possess the low wart-like form first described by Kokitansky and Henuig.

On account of the marked tendency as pointed out by Williams which papillomata of the ovary show to undergo cancerous degeneration, these growths of the tube must also be


looked upon witli suspicion, for even if they do not become malignant they may give rise to transplantation growths to the peritoneum, which may so seriously impair the function of this organ as to cause death.

From the foregoing history it appears that the patient suffered with repeated -attacks of pelvic inllammation, and the liistological examination of the tube shows a condition similar to that seen in chronic inflammation of the tube, plus the papillomatous growths, which sustains throughout the theory advanced by Alban Uoran, that iiapillomata of the tube are but the after-results of inflammatory changes. While some of the smaller growths, especially the sessile ones seen on the remaining folds of the tube, appear as simple hyperplastic processes, as suggested by Doran, the majority are essentially new growths, in which there is a great increase in the connective tissue associated with proliferation of the epithelium.

Bland Sutton has recorded a case similar to the foregoing one, which he classifies as an adenoma, holding to Henuig's original theory that the spaces between the folds of the tube are glands, and therefore new growths which affect them are of the glandular type.

Sanger and Barth ([uite properly reject Sutton's classification, substituting for it the term papillmna lubcp, cyslicnm s. resiculosum. As our case presents, besides the papillomatc us growths, the cystic spaces, it can properly be classified under this title.


THE HISTO-PATHOLOGY OF HERPES IRIS. WITH REPORT OF TWO CASES.


By Lucius Crocker Pardee, M. D.

(From the Dermatological Department of the Johns Hopkins Hospital Dispensary and the Pathological Laboratory of the Johns Hopkins University

and Hospital.)


Although herpes iris as a clinical entity has been recognized since the early part of the century,* and notwithstanding the fact that considerable clinical knowledge has been added by dermatologists during the last few years, comparatively little attention has been directed to its histo-pathology. Even such an extensive writer as Unna has given but a very unsatisfactory description of its pathology, and the usual account which one finds in looking through the literature of tlie subject may be practically summed up as follows: Oedema, vascular dilatation and "round cell infiltration" (whatever that may mean). In the following case, in connection with which the opportunity of a very complete investigation from clinical, pathological and bacteriological standpoints was offered, many interesting features presented themselves, which seem worthy of some attention and may possibly lead to a clue as to its etiology.

On December 4, 1807, there appeared in the Disi)ensary of the .Johns Hopkins Hospital a case presenting vesiculo bullous lesions on the skin, concerning which the following history was obtained. The patient was a girl eigiit years of age, fairly well developed, slight but not thin, with dark hair and com


Bateman and Willan (1810).


plexion. She seemed bright and intelligent, and was in fact somewhat precocious. Her antecedents did not reveal anything of interest.

Family History. Her father, mother and brotlier are all living and in good health.

Hislory. Personally, beyond one attack of measles which occurred two years ago, and habitual constipation, the patient had always been in good health up to the present time. She had, however, always been, as her mother expressed it, "a nervous cliild." Her present trouble began two weeks before applying for treatment. At that time she was vaccinated and now has the remains of a fairly typical vesicle on her arm. Directly after the vaccination she began to complain of flushes of heat and chilly sensations, the latter being of a transitory nature. These symptoms were ascribed to the vaccination and no particular attention was paid to them.

In a few days there appeared on the extensor surface of the right forearm "a blister" which was about the size of a split pel when first noticed. This was soon followed by others of like character in the same region, and also upon the left forearm and wrist, together with isolated lesions scattered over the trunk and lower extremities. She was taken to tjie family physician, who pronounced the case as one of "poisoning"


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[No. 88.


(meaning Rhus toxicodendron), which is quite common in and about Baltimore. A j^atent mixture of sarsaparilla compound was ordered,* but no local treatment, other than bicarbonate of soda baths, was given.

Present Condition. The patient upon examination presented an eruption, consisting of vesicles and bullffi varying in size from one to five millimeters in diameter, mostly discrete (thongli some showed signs of confluence), and arising from apparently normal skin. They were tensely filled with a clear colorless fluid, and the lesions which had existed for a day or two possessed a slight erythematous halo, and their contents had become opaque. These lesions occurred principally upon tlie extensor surfaces of the forearms (Figs. 1, 11, HI), the right being the more affected, though scattered vesicles were found upon other regions, as follows: one small discrete vesicle was to be seen upon the tip of the right ear, a group of similar ones just beneath the chin, and a few discrete lesions on the buttocks. Upon the dorsum of the right foot were also a number of vesicles less developed than those of the regions mentioned. The mucous membranes were free of any eruption, with the exception of a small herpetiform group upon the inner surface of the vulva. The majority of the lesions were discrete and showed but little tendency to group. One bulla iipon the right forearm (probably the first to appear) was sunken at the center, its roof having become adherent to the base, and the peripheral portion, still being tense and filled with opaque fluid, presented the appearance of having been formed by the confluence of smaller lesions which had surrounded a central bulla. No marked subjective symptoms were complained of other than the malaise already mentioned, which still persisted, and a slight feeling of tenseness and itching of the cutaneous lesions, which was most troublesome at night. The itciiing, however, must have been very slight, as neither excoriations nor rujitured bullaj were observed.

At this stage of the eruption erythema bullosum was principally thought of on account of the distribution, but the character of the lesions seemed to point to the pemphigus group, and liquor potassii arsenitis was ordered as an aid to diagnosis. At the same time two vesicles, each of about two millimeters in diameter, situated on the forearm, were excised and dropped into 95 per cent, alcohol for microscopical examination. The patient returned three days later feeling much worse and showing a much more extensive eruption. New vesicular lesions of tlie character already mentioned had appeared on all the regions previously affected, and the older ones had increased somewhat in size.

Tlie forearms, wrists and backs of the hands and feet were most markedly aflected. Upon the back of the right hand was seen a bulla about one-half cm. in diameter surrounded by small (3 mm.) vesicles which had formed. a complete circle, the whole patch being situated upon an erythematous base. (See photograph. Fig. I.) Some of the older lesions upon the arms also presented ring-like formations (Fig. II), and the case was now definitely diagnosed as erythema exudativum multi


The potassium iodid, which such mixtures usually contain, may have aggravated the eruption ; this feature has been noted by many authors, though some report to the contrary.


forme, of the bullous variety (herpes iris). Appropriate treatment was ordered and special directions given as regards the diet.

During the next few days no improvement occurred other than the drying up of some of the lesions, which had first appeared and were now desquamating, leaving reddened plaques. New vesicles and buUm still continued to make their appearance, the duration of each individual lesion being about a week or ten days. No primary lesions other than vesicles and builffi were noticed. At the end of the first week the patient became confined to her bed, because of the vesicular lesions, which had formed continuous patches on both feet, making walking quite painful.

The temperature at this time was almost constantly above normal (103° being the highest point noted) and slight chills were complained of. The bowels were extremely constipated and the appetite completely lost. The tongue became heavily coated and the breath very foul. During the next few weeks the emaciation became somewhat marked, although the physical examination of the various organs did not reveal anything abnormal. At the end of the second and beginning of the third week the disease was at its height, the patient suffering great discomfort and complaining somewhat of the itching, which seemed to have increased in severity, especially in the lesions on the feet. Pains in the great toe joints were now complained of, the left one being the more aflected. This symptom was not constant, as the pain seemed to vary in intensity at different times and was usually worse at night. The lesions now (three weeks after their first appearance) presented all stages of development and resorption and were pretty generally distributed over the entire body.

The regions most affected at this stage were not only the forearms and backs of the hands and legs and dorsal surface of the feet, but the back, thighs, buttocks and perineum also were attacked. Upon the back a large patch 20 cm. in diameter had formed, and the lesions upon the buttocks, perineum and inner surfaces of the thighs were continuous. The neck also was completely encircled by a band of lesions, which extended jiartly into the hair behind and included both ears.

Smaller, dark venous red colored patches, the ragged edges of whicii reminded one of the edge of a desquamating syphilitic lesion, and in whose center new vesicles could be seen appearing beneath the thin newly formed epidermis, were situated upon the knees and calves, and about the ankle in the region covered by the shoe. The parts least aflected, via. the upper part of the face, tlie anterior surface of the thorax, the abdomen, the upper arms, anterior surface of the thiglis, and the ]ialms and soles, all showed scattered lesions with large areas of normal skin between them. Even the scalp did not escape entirely, as crusts (probably the remains of aborted vesicles) were noticed in this region, but no true vesicles.

Although comparatively few lesicms existed upon the mucous membranes, yet the inner surface of the lips, including the red border, presented fairly numerous aborted vesicles and vesicular detritus; but with these exceptions and one small vesicle upon the hard palate which soon disapjieared, no eruption was seen.

During the next three weeks the condition varied, sometimes


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showing considerable iinpvovenient and at others a slight relapse. No return of a temperature above 100° was observed after the time already mentioned. The pains in the joints gradually decreased, both in frequency and severity, and the older lesions began to dry up and desquamate, leaving brownish pigmentations. New vesicles still continued to appear, however, although their niimber and size were less, and they were mostly discrete and of a shorter duration.

About this time (sis weeks after the outbreak) an enlargement of the lymph glands of the right femoral region was noticed. They formed a somewhat tender and doughy mass which measured 3 cm. broad by 6 cm. long. No other glandular enlargements were found. After being eight weeks under treatment the general health of the patient became much improved, in spite of the fiict that the parents had insisted on keeping the child at home, where the attentions were of the poorest and the surroundings most squalid. The appetite also returned, and she seemed to be gaining in weight and strength.

Although all the larger patches had now disappeared, leaving pigmented areas, yet there were still quite a number of lesions to be seen, especially upon the backs of the hands and wrists.

Upon the left ankle there was now formed the only lesion other than vesicles or bullic observed during the entire course, and it also presented the typical iris-like formation. It was composed of four concentric, slightly raised erythematous rings snrrouuding a darker central spot, and possessed the typical iridescent appearance which characterizes the disease. After twelve weeks had elapsed since the beginning of the attack the child was able to be up and about again ; she seemed comparatively well, but came occasionally to the clinic. The hands were still troublesome, and isolated lesions occasionally appeared upon the trunk and extremities, and the attack, therefore, could not yet be said to be at an end. This condition of the skin persisted until about March 30, 1898, when a severe relapse occurred. The photograph shown in Fig. Ill, was then taken. During this relapse the lesions were almost entirely confined to the forearms and hands. Itching was absent, and among the lesions were many typical of herpes iris. Upon the right arm was to be seen a bulla half surrounded by three semicircular lines of vesicles. A like arrangement occurred upon the left wrist. Kemains of other circular patches are also shown in the photograph.

The blood count during this relapse gave the following results regarding the leucocytes:

Polynuclear 70 per cent.

Mononuclear (small), 18 " (large), 5 "

Transitional 3 "

Eosinophile 8 "

The treatment was symi)tomatic throughout, and being along well recognized lines laid down by so many dermatologists, need not to be gone into in iletail.

During the attack the blood was examined several times, both fresh and in dried and stained specimens.

Erlich's triple stain and eosin and aqueous methyl blue were chiefly used.


Beyond a slight increase of the white-blood corpuscles, observed in the specimens which were taken during the first week, nothing abnormal was noted.

A number of eosinophiles were present in all the preparations, but their relative proportion was, however, not markedly increased. No plasmodia inalariaj were found, although their ju'esence was diligently sought for.

The contents of the vesicles were examined fresh and stained in situ and after having been mounted, but all gave results which did not differ from the findings in the cutaneous sections which will be described later.

Numerous cultures from the vesicles were made upon slant agar, but no positive results were obtained, with the exception of one tube which showed a growth of the staphylococcus pyogenes albus, probably derived from the surface of the skin.

It may be mentioned here that while dressing the patient, her mother in pressing upon a tense bulla ruptured it suddenly, discharging its contents directly into her eye, from which no results followed.

During the second week of this relapse the patient was admitted into the Johns Hopkins Hospital. During the acute stage the treatment consisted of mild laxatives, strict attention to diet and the application of a mild ointment. Three weeks after the acute stage has passed into a chronic condition Fowler's solution, 3 mins. three times a day was given, and when it was found to be beneficial it was gradually increased to 1 mins. No further relapses occurred but the patieut began to improve remarkably in health and all the lesions disappeared. The ])atient was discharged quite cured four and a half mouths after the first lesion appeared.

PATHOLOGICAL HISTOLOGY.

The portions of skin taken for examination were from the flexor surface of the forearm, and each represented a vesicle about two millimeters in diameter. They were discrete and arose from apparently normal skin. They" were hardened in alcohol and stained with haematoxylin and eosin, Loetfleur's blue, Unna's polychrome methylene blue, aniline gentian violet, and by Weigert's method.

The epidermis (Fig. IV) as a whole was practically very little affected, except mechanically. The stratum corneum (i) (as one would naturally expect to find it in this region) was of a loose rather than of a compact nature. The stratum lucidum was visible only in places, and was nowhere well defined. The stratum granulosum (c) was well marked. It consisted of from one to two layers of cells and was practically unaltered.

The rete mucosum (f/) showed a slight dilatation of its interepithelial spaces and a consequent increase in depth. This increase, however, was only to be seen at the edges of the vesicle, as over the vesicle itself it was somewhat flattened by the pressure from beneath of the vesicular contents acting against the resistance of the horny layer. The cells of the rete showed no change beyond slight so-called vacuolation, such as is to be observed in many cutaneous afl'ections, as well as in the normal skin. No mitoses were observed above the germinal layers. Here and there, in the inter-epithelial spaces, lymphoid cells and jiolynuclear leucocytes were found, and near the vesicle a suuill amount of nuclear detritus. (Fig. IV.)


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[No. 88.


The corium (Fig. IV, e ) in the affected area showed acute inflanimatory changes, limited to its upper half. These consisted of a localized cedenia, marked dilatation of the superficial network of blood-vessels, large numbers of polynuclear leucocytes and a great increase in the number of lymphoid cells. Tiiese cells were massed in and about the blood-vessels (/), and also scattered about in the connective tissue, making their WA"^ toward the epidermis. The papillary body, and more especially the j)apillw themselves, were most markedly involved, being the seat of acute cedematous inllammation. The serum appears to have exuded so rapiuly that instead of producing a marked ceJema of the epidermis, the latter was raised mechanically.

On examining the earliest stage of this pathological condition, which could easily be observed at the periphery of the minute vesicle, one could see how the lesion commenced. In one papilla (Fig. V) the upper third was replaced by serous exudation, as shown by the presence of line granules and a network of fibrin, among which a number of polynuclear lexicocytes were present. These could be seen at all stages of disintegration, from the disappearance of their protoplasm to the breaking up and separation of their nuclei. (Fig. VI.)

The next stage of the process showed the entire papilla filled with coagulated serum, fibrin, and large masses of broken-down nuclei, with only comparatively few polynuclear leucocytes, and the nuclei of a few detached connective tissue cells.

The papillas in other places were completely destroyed, or flattened out so as to be unrecognizable, their place being taken by a mass of nuclear detritus suspended in a network of fibrin and the remains of the connective tissue. (Fig. VI.)

The vesicle was formed, therefore, by the simultaneous involvement of several neighboring papillaj; the roof being represented by the compressed, but otherwise unaltered epidermis, with the twisted and distorted iuterpapillary processes dependent from it and extending into the vesicle proper, while the corium with its compressed and swollen papilhc formed the floor.

The contents of the vesicle consisted of a finely granular substance (coagulated serum), strands of fibrin, mononuclear and polynuclear leucocytes, occasional detached epithelial cells, much nuclear detritus and a few eosinophiles.

The lymph vessels were slightly dilated in the vicinity of the vesicle, but the hair follicles, sebaceous glands and sweat coils and ducts were unaffected.

The lower half of the corium showed a slight redema, but was otherwise normal, as was also the subcutaneous tissue. No micro-organisms were found in sections stained for that purpose.

DIAGKOSIS.

In connection with the diagnosis of this case the chief points to be considered were, (1) its acute onset, (3) the vesicular and bullous character of the lesions, which were frequently to be seen arranged in patches consisting of a central bulla surrounded by one or more concentric rings of vesicles, as is well depicted in Fig. I, and (3) the symmetrical distribution, which was chiefly upon the forearms and hands, the lower part of the legs and dorsal surface of the feet,


appearing first in these regions and persisting there after having disappeared from the other portions of the body.

The marked itching of the lesions on the feet at the height of the attack caused one to think of dermatitis herpetiformis or of pemphigus pruriginosus. According to Duhring, however, the itching in the former disease "is out of all proportion to the eruiition," while in the case which has been described it was only when the patient was nearly covered with lesions that this symptom was at all troublesome, and even then it was limited to a portion of the eruption only.

Another point of difference was the purity of the lesional tyjie as already mentioned, in contrast to dermatitis herpetiformis, which even when of the vesicular variety is extremely apt to show a mixture of primary lesions (i. e. wheals, vesicles, pustules, etc.) with the vesicular form predominating, while in the present case no lesions other than vesicles and bulla3 were noted, with the single exception of a typical patch of iris-like erythematous rings, which teuded to strengthen rather than disprove the diagnosis.

From a microscopical standpoint the pictures were about as similar as the clinical, but likewise presented decided differences. Several slides* from a typical case of dermatitis herpetiformis were carefully gone over, the points of difference from the present case being chiefly the enormous number of eosinophiles present in dermatitis herpetiformis and the entire absence of nuclear fragmentation, in contrast to the small number of eosinophiles and the large mass of nuclear fragments present in the sections from the case described.

The blood examinations not showing an increase of the eosinophiles, did not correspond to the reports of Leredde, Perrin and Fordyce, who found an increase of these cells present in the blood of patients with dermatitis herpetiformis.

The diagnosis of pemphigus pruriginosus (a typical case is now under observation at the Johns Hopkins Hospital Dispensary, from which material was obtained for comparison) may be thrown out for similar reasons, as the clinical pictures are seemingly enough different to warrant this. The fact that in pemphigus of this variety there is no tendency to special arrangement of the lesions, and no especial seats of predilection manifested by the eruption, would render such a diagnosis in this case improbable.

Case II. — In connection with the above case may be mentioned another which appeared a few weeks later. It occurred in a man twenty-six years old, a Kussian by birth, and with no regular occupation at the time. His past history was negative, and no reliable data of his family were obtainable.

Three days before applying for treatment he noticed that his hands felt puffy and stiff, and upon compressing the palms he noticed a " blotchy " eruption which had escaped his attention before, being hidden by the natural redness of the skin. Soon after, spots began to appear on the backs of his hands and wrists, and a few also on the feet, which caused enough apprehension to bring him to the Dispensary for treatment.

Upon examination there w'as found present a slight erup


These specimens were from a case already published by Gilchrist (Johns Hopkins Hospital Reports, Vol. I).


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tiou, limited to the forearms and hauds and backs of tlie feet, which consisted of macalo-paj)ules, ronndish in shape, varying from two to three cm. in diameter, and of a dark purplish red color.

Some of these were slightly elevated at the edges, giving them the appearance of having depressed centers. The lesions were discrete and few in number. Upon the palms the above mentioned blotches were to be seen when the skin was compressed so as to cause partial blanching, but were not perceptible otherwise.

Two of the lesions on the forearm showed a tendency to vesiculation, the vesicle appearing as an addition to the maculo-papule. No constitutional symptoms were present, nor were there subjective symptoms of any kind.

Three sections of skin were excised for examination. One represented the macular stage, the lesion selected not being raised above the level of the skin, of a pinkish red color and showing no central depression. The second was a papulovesicular formation, the vesicle being aboiit two millimeters in diameter, and situated upon a raised erythematous base which extended about one millimeter beyond it.

At the same time cultures were taken from the other vesicles, which resulted in the growth of staphylococci (pyogenes albus and aureus). The patient was put upon diuretics and laxatives, and all symptoms disapf)eared in ten days.

The preparations from the excised lesions presented histologically an almost identical picture with those of the first mentioned case, with the following exceptions : The lymph channels of the epidermis were considerably dilated, causing a spreading apart of the epidermal cells, especially of the basal layers, and their consequent detachment upon the fornuition of the vesicle. This dilatation caused an apparent widening of the entire epidermis, so that over the vesicle it was broader than normal, instead of being compressed.

The destruction of the polynuclear leucocytes, so marked in the first case, was only very slightly present.

The leucocytes were massed at the tips of the papilla?, but appeared in much greater proportion to the amount of serum, the latter having escaped into the epidermis. Otherwise, the findings of the two cases as before mentioned were practically identical in character and correspond in almost every particular with sections prepared from a series of typical cases of erythema exudativum multiforme kindly lent by Dr. Gilchrist for examination and comparison.

Among the various theories of inflammation those formulated by Metchnikolf (although opposed by many eminent pathologists) seem to explain some of the phenomena observed in this case.

According to this author, any foreign substance, upon gaining entrance to the tissues, will (provided it is cajjable of causing an irritation) exert an attractive power (positive chemotaxis) over the leucocytes.

When the invading body is of a powerful nature as compared with the resisting I'ower of the leucocytes, certain of the latter perish in the attempt to nullify its effects, and are either absorbed by other phagocytes and carried away, or escape as detritus in purulent formations. Whether the substance causing the irritation gains entrance to the tissues


from within or without, and whether it is physical, chemical or biological, the result is the same, provided it has or produces other substances which have positive chemotactic properties.

Leloir and Gilchrist have demonstrated in numerous cases of true urticaria that excised urticarial wheals present the picture of an acute inflammation.

Gilchrist has further noticed in factitious wheals, excised from several cases of chronic urticaria (many sections of which were carefully examined) fifteen minutes after irritating the apparently normal skin, that together with the general emigration of leucocytes there occurred a limited destruction of the same, their nuclei appearing as fragments throughout the affected area, this fact suggesting the idea that possibly the mechanical irritation had set free some poison strong enough to attract the leucocytes and to destroy a certain number of them.

Leloir has demonstrated the fact that the lesions of erythema exudativum multiforme show from the beginning the successive steps of an exudative inflammation.

If the cutaneous manifestations of this disease are examined at the earliest stage (at which point many cases cease to develop and the lesions disappear), even at this period a slight migration of the white blood corpuscles may be observed; and as one investigates lesions of a more advanced condition, signs of a more profound disturbance of an inflammatory character are discovered. In herpes iris, representing as it does the most advanced type of erythema exudativum multiforme, the inflammatory process has reached nearly the highest grade shown in primary lesions, the step from the vesicle to the pustule being a slight one.

The observation in Case I of the very rapid breaking down of the polynuclear leucocytes, occurring even as soon as they made their appearance in the papilla? outside of the vessel walls, has not, as far as could be learned, been before reported in connection with this disease, and has suggested the idea that possibly the rapid death was due to a toxine set free from the capillaries of the papilla?, which represent a point of least resistance in the vascular system.

Such a toxine would act as the chemotactic agent, which, in this case, had probably proved jiowerful enough to cause the death and destruction of the emigrated cells.

What this toxine (if present) is, or how it obtains entrance to the blood stream, is a question which can only be discussed problematically.

The origin of such a toxine might, however, occur in the intestinal canal, and, acting on a nervous system already less resistant than normal, produce the phenomena above described.

The opinion given by some authors, that a toxine causing such a reaction could be formed by some specific microorganism unrecognizable by present methods of investigation, which gains entrance to the cutaneous tissues through the blood stream, has neither been proved nor disproved as yet.

This hypothesis may seem to combat the term angioneurosis, and to a certain extent it does, unless the understanding expressed by v. Duhring is accepted. This author says that the term angio-neurosis must be taken "not in an etiological sense . . . but rather as the jihysiological method bv


170


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[Xo. 88.


which the lesions are developed. Schwimmer's definition, that "one designates as vasomotor and angioneurotic affections all those caused by pathological changes in the innervation of the blood-vessels," is quoted by v. Duhring, who then says, "There is scarcely an hyperemia, arterial or venous, transient or of long duration, and no inflammation acute or chronic, be what kind it may, tliat according to this definition one may not designate an angio-neurosis."

Some difference of opinion is to be found in the reports given by the various autliors who have written an account of their observation of the histological changes to be seen in herpes iris, especially as regards the formation of the vesicle. Unna, after saying that "the histological examination of the simple erythema multiforme gives almost the same result as that of the vesicular and iris forms," and that " in the latter cases the epidermis changes are more pronounced," and "so far as concerns the changes in the cutis we have . . . altogether four different symptoms: dilatation of the vessels, cell proliferation around the vessel walls, emigration, and cedema of the cutis," goes on to say in reference to the formation of the vesicle, " Where there is actual vesicular development on the border of the eruption we find a marked widening of all the lymph spaces of the epithelium, and in certain spots dilatation into a subcorneal vesicle containing pure lymph. In many eruptions this extends with undermining of *the horny layer and neighboring vesicles to a large nionolocular blister, under which the prickle layer is simply compressed without undergoing in any sense degenerative changes."

Elliot (Morrow's System of Genito-Urinary and Skin Diseases) says that " vesicles and bulls are formed by the penetration of the exudation through the intercellular spaces of the rete, and the lifting up of the stratum corneum and portions of the stratum lucidiim and granulosum to constitute the outer wall."

Crocker is also of the opinion that the vesicle is formed by the serum " forcing its way between the rete cells."

In contradistinction to these views is that of Gilchrist (Duhring's Cutaneous Medicine), who holds that the vesicle is formed beneath the epidermis. It seems not improbable that in cases of the milder form, where the process of vesicular formation is slow and is preceded by the macular or papular forms of erythema, the view of Elliot and Crocker may be correct. AVith such cases the process observed in Case II might easily be made to conform, with the supposition of a more gradual infiltration of serum. In cases of a more severe tyi)e, however, the accumulation of fiuid appears to be so rapid that no time is given for the dilatation of the inter-epithelial spaces, and the epithelium is lifted as a whole from the cedematous 2iaf)illary body, and becomes more or less compressed by the intra-vesicular pressure acting against the resistance of the horny layer.

" Subcorneal vesicles" with the contents of "pure serum," such as Uuna describes, were not observed.

The other features in the cases here reported agree in the main witli those of other observers. The following exceptions, however, appear. Unna found many mitoses in the perithelia of the blood-vessels and of the epidermal cells. Neither of these locations showed marked proliferation of their respective cells


in sections from any of the cases examined, and the point to which special attention has been directed, /. e. the fragmentation of the polynuclear leucocytes even immediately after leaving the vessels, does not appear to have been mentioned by any previous observer, and yet it is a fact on which some stress should be laid.

The findings in these two cases are well supported by those of Gilclirist (numerous sections from his six typical cases of the various stages of erythema exudativiim multiforme were carefully investigated, the specimens being kindly lent by him for comparison) and it seems probable that the description here given is the correct one as regards the severe type of the exudative erythemata as shown in herpes iris.


The cases here reported represent, in Case I, a severe type of erythema exudativum multiforme bullosum, or herpes iris, which had a protracted course and developed considerable constitutional disturbance.

Case II was of the mild form, the whole attack being limited to two weeks, and only a few of the lesions showing a tendency to vesicular formation.

The distribution and character of the lesions in both cases were typical.

The histopathology may be summarized as an acute exudative inflammation of the upper half of the corium, with dilatation of the superficial network of blood-vessels and lymphatics (the latter being slight), accompanied by a considerable emigration of polynuclear leucocytes, which in Case I became almost immediately disintegrated after leaving the capillaries of the papillas. The latter, as the process extended, became practically filled with niiclear detritus, and by the confluence of neighboring papillaj similarly affected the vesicle was formed. This phenomenon of nuclear fragmentation does not apjiear to have been noted by any previous observer.

In Case II, which presented the same general microscopical features, the breaking up of the polynuclear leucocytes was much less marked.

In both cases the vesicle was formed by the lifting of the entire epidermis from the pajiillary body, the former becoming compressed over the vesicle in Case I, and in Case II appearing swollen and edematous, and showing more or less dilatation of tiie inter-epithelial spaces and detachment of the cells of the basal layers of the epithelium. The contents of the vesicles were always the same, and consisted of coagulated serum, polynuclear and mononuclear leucocytes, occasional detached epithelial cells, strands of fibrin, and in Case 1 much nuclear detritus.

No infarcts of blood-vessels and no hemorrhages were noted.

The sweat apparatus, hair follicles and sebaceous glands were unaffected.

In closing I wish to express my obligations to Dr. T. Caspar Gilchrist of the Johns Hopkins Hospital for his invaluable aid and suggestions in the pre]iaration of this paper.

BiBLlOURAPHY.

Textbooks : Duhring (Cutaneous Medicine), Crocker, 5Iorrow (System of Genito-Urinary and Skiu Diseases), Hyde





Mm- **i



9^i:i^







JaLT, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


171


(Tweutietli Century Practice), Unua (Histopathology of Diseases of the Skin, 189G); Bateman and Willan (1810).

I. Besuier: Aunales de Der. et de Hyph., 1890, p. 1.

3. Bulkiey: Jonr. of Gut. and G. U. Dis., 1589, Vol. VII, p. 146.

3. Finger : Wiener med. Presse, 1892, p. 1539.

4. Fox : Jour, of Cut. and G. U. Dis., 1888, Vol. VI, p. 146.

5. Fox: .Jour, of Cut. and G. U. Dis., 1890, Vol. VIIT, p. 31.

6. Gilchrist : .Johns Hopkins Hospital Keports, Vol. I.

7. Hallopeau : Annales de Der. et de Syph., 1896, Vol. VII, p. 375.

8. Heubner: Deutsh. Arch, fiir klin. Med., 1883, Vol. XXXI, p. 297.

9. Kaposi: Wiener med. Woch., 1878, No. 30.

10. Knox: Jour. Cut. and G. U. Dis., 1897, Vol. XV, p. 127.

II. Kiihn: Berliner klin. Woch., 1880, p. 49.

12. Leloir: Bull, de la Soc. Anat., 1884, p. 294.

13. Leloir: Charito Aunalen, Bd. Ill, 1878, pp. 308 and 653.

14. Lewin : Berliner klin. Woch., 1876, p. 331.

15. Lewin : Chariti:' Annalen, Bd. Ill, 1878, p. 632.

16. Lewin : Bull, de la Soc. Anat.,1884, Avril.

17. Lewin : ProgrOs Medical, 1884.

18. Lukasiewicz : Wiener klin. Woch., 1896, Vol. IX, p. 23.

19. Metchuikoff: Comp. Path, of Inflammation.

20. Neumann : Wiener med. Presse, 1883, p. 338.

21. Pick : Wiener med. Presse, 1893, p. 1236.

22. Pick: Wiener med. Presse, 1883, p. 408.

33. Schoetz : Berliner klin. Woch., 1889, p. 612.

24. Villemain: Bull, de I'Acad. de Med., 1886.

25. Vou Duhriug: Arch, fiir Der. und Syph., 1896, Vol. XXXV, p. 311.

36. Wermann: Derm. Zeitsch., 1896, Vol. Ill, p. 52.

Photographs of Case of (I) Herpes Iris.

Fig. I was taken 24 hours after the appearance upon the back of the riii;ht hand, of the first lesion characteristic of herpes iris. The central bulla, with a circle of vesicles surrounding it, is well shown. Various sized, tense, discrete Tcsicles and bulla', as well as numerous crusts, are scattered over the forearms.

Fig. II represents the antero-external surface of the forearms.

Fig. Ill shows a relapse 14 weeks after the first attack. The characteristic features of herpes iris are again well developed. In several places four half circles of vesicles have made their appearance.

Sections fuo.m Case I.

Fig. IV represents one of the minute vesicles from the forearm. It shows an acute inflammation of the upper half of the coriurn (<). The epidermis (f) is practically normal, save a slight increase in depth {(/) at the edge of the vesicle, and a narrowing over it (c. c). The vesicular formation (c) was wholly subepidermal, and its contents were serum, fibrin, mononuclear and polynuclear leucocytes, and much nuclear detritus. (P) indicates two papilhr, showing the earliest stage of the process, and (F) one somewhat later. [IT) Horny layer of the epidermis, ( O) granular and (J/) prickle layer, ( S) sweat ducts, ( A') dilated blood-vessels surrounded by emigrated cells.

Fio. V represents a magnified papilla, with only the two adjoining rows of epidermis (c). The earliest stage of the process is sliown by the microscopic vesicle (v) which has displaced the upper third of the


papilla, and eontaius serum, fibrin, one polynuclear leucocyte ( /'|, and frugnieuted nuclei (A'). ( C) connective tissue.

Fig. VI shows a later stage than Fig. V. The entire papilla is here displaced by serum, fibrin, a few polynuclear lencoeytes, and a mass of nuclear detritus. Lettering the same as Fig. V.


NOTES ON NEW BOOKS.

The Metlical Annual an<l Practitioner's Index. 189S. Sixteenth

year. {Bristol: John Wright & Co.)

This volume of the ]\Iedical Annual not only will compare favorably with its predecessors, but in some respects it easily exceeds them. The leading articles continue to be supplied by some of the best known writers in the English language and physicians whose interests and field of work especially fit them to present the contributions associated with their names. In a volume containing so much of interest to the busy physician who wishes to be placed en rapport with the latest authoritative utterances on medical topics, one can but select a few examples to consider in a brief-review. A. Mitra, of Kashmir, supplies the article on bubonic pl.igue. The results of the recent bacteriological and epidemological studies of the outbreaks in China and India are used freely. Attention is called to the contagiousness of the disease, which, it appears, had been rather underestimated. Although the treatment occupies a large part of the article, its richness is embarrassing and depressing rather than inspiring of hope. Thus far no specific remedy has been discovered, and the preventive inoculations of Haffkine and the serum treatment of Borel and Calmette are to be regarded still as subjudiee. The operation for obliteration of the deformity in Pott's disease, introduced by Calot of Berck-sur-mer, is discussed by Messrs. Jones and Tubby. These writers give an account of the treatment of 56 cases, two of which resulted fatally — "one under circumstances very unsatisfactory," the other from epilepsy five weeks after operation. The tabulated account of these 56 cases will be read with much interest by surgeons. The curves found best suited to treat by this method are (a) those occurring in the young; (b) those in which the disease is active ; and (c) those in which the angle of deformity is changing ; (d) in those cases where paralysis is present, and as an alternative to laminectomy, which in their experience has often failed to relieve the pressure point. Theauthors, despite their relatively limited experience which does not permit them to predict unqualified success in this new departure, would yet point out that "the diseased spinal column is no longer too sacred to be touched."

Mr. Shattock has contributed a chapter on the bacteria pathogenic in the human subject, the value of which isgreatly enhanced because of the excellent illustrations which accompany it. When this contribution is completed, which it is promised will be achieved in the succeeding volume, the whole will comprise an atlas of pathogenic bacteria very useful to physicians, surgeons and specialists. The drawings are true to nature, and are printed in the colors in which the stained bacteria are usually seen under the microscope. It is a pleasure to recommend this handy volume to the medical profession. S. F.

Jakob: Atlas of Methods of Clinical Investigation, with an Efiitome

of Clinical Diagnosis, etc. Edited by Augustus A. Esuner, M. D.

Authorized translation from the German. {Philadelphia : W. B.

Saunders, 1898.)

A properly executed atlas on clinical diagnosis is to be commended very warmly. Undoubtedly this is the age in medical teaching and practice in which intuition, the so-called "Aerztliches Gefiihl," counts for least. Instead of tradition and authority we have substituted observation and experiment anil the practitioner who follows in the inarch of clinical methods resoits to the stethoscope and perhaps the fluoroscope, counts and studies the


172


1)1 ooil, estimates the jjercentage of lucmoijlobin, difTerentiates tlie several kinds of leucocytes, collects the serum for the Widal test, looks carefully at the urinary sediment, neglects not the diazoreaction, gives test-breakfasts and analyzes the stomach contents, stains the sputa for bacteria, makes bacteriological cultures from the blood, and at last perchance follows the patient into the dead-house and post-mortem chamber. The small and handy volume under consideration is designed to be an aid to these and many other operations, by supplying as far as i)Ossible lifelike reproductions of the various appearances observed in liealtb and disease in the blood, urine, stomach and intestinal contents, viscera, etc. The plates in the volume cover the normal histology of the red and white blood corpuscles, the special changes in the blood in leuksemia, pernicious anaemia, leucocytosis, malaria, relapsing fever, anthrax, etc. The blood spectra are given and blood crystals represented. The microscopic appearances of the buccal and nasal secretion in gingival deposit, thrush, diphtheria, etc., and reproductions of unstained and stained (asthma, etc.) sputa in health, cardiac disease, actinomycosis of the lung, etc., are given. Next follow plates representative of the microscopy of the contents of the stomach and intestines, the most important color reactions of the gastric juice, urinary sediments, crystalline and organized, the most important color-reactions of the urine, the commoner pyogenic micro-organisms, etc. Part II is devoted to normal projection of the viscera and percutory topography. The diseases of the lungs, heart and abdominal organs are represented in outline. The concluding part of the volume treats of the various steps embraced in the physical examination, and discusses briefly the special pathology and therapy of the more important diseases.

This very convenient volume can be recommended unhesitatingly to the practising physician no less than to the student in clinical microscopy and physical diagnosis. S. F.

The Elements of Clinical Diagnosis. By Professor G. Klemperee, First American from the seventh German edition. Translated by N. E. Bkill, M. D., and S. M. Bkicknee, M. D., of New York. (The ifacmitlan Company, 18"8.)

This work appears to be the result of an attempt to state as much regarding clinical diagnosis in as small space as possilile. As a result clearness is apt to be sacrificed to brevity, and accur.ate description to siiace. There are many excellent points in the book, but one needs a previous knowledge to appreciate them. A student using it for atextbook frequently would be apt to be led into error, especially through many statements made without necessary qualification. Parts of the book are put clearly and well. Many of the illustrations would have been better left out; they leave much to be desired.


BOOKS RECEIVKD.


Proceedings of the Dedication of Hie Hunt Memorial Building by the Hartford Medical Society, February 1, 1808. 8vo, 48 pp.

The Methodist Episcopal Hospital Reports, Vol. I, 1887-1897. Edited by L. S. Pilcher, M. D., and G. R. Butler, M. D. 1898. 4to, 55,3 pp. Published by the Hospital, New York.

Transactions of the American Pediatric Society. Ninth Session held in Washington, D. C, May 4tb, 5tb and 6th, 1897. Edited by F. M. Crandall, M. D. Vol. IX, 1897. 8vo, 218 pp. Reprinted from the Archives of Pediatrics.

Sixteenth Annual Report of the Provincial Board of Health of Ontario. Being for the year 1897. Printed by order of the Legislative Assembly. 8vo, 133 + clxxxv pp. Warwick Bros. & Rutter, Toronto.


Report relating to the Rc.gistriilion <f Births. Marriages and Deaths in the Province of Ontario for the Year ending 'i\st December, 1896. Printed by order of the Legislative Assembly of Ontario, 1898. 8vo, 37 + ccxii pp. Warwick Bros. & Rutter, Toronto.

Yellow Fever. Clinical Notes by Just Touatre, M. D. (Paris). Translated from the French by Charles Chassaignac, M. D. 1898. 12nio, 20G pp. New Orleans Medical and Surgical Journal, Ltd., New Orleans. Medical and Surgical Report of the Presbyterian Hospital in the City of New York. Edited by Andrew J. jNIcCosh and Walter B. James. Vol. Ill, January, 1898. 8vo, 414 pp. Trow Directory Printing and Bookbinding Co., New York.

Transactions of the Obstetrical Society of London. Vol. XL. 1898. Part 1, Jan. and Feb. Edited by John Phillips, M. A., M. D., and Percy Boulton, M. D. 8vo. Ill pages. Published by the Society, London.

Twentieth Century Practice. An International Encyclopaedia of Modern Medical Science by Leading Authorities of Europe and America. Edited by Thomas L. Sledman, M. D. In twenty volumes. Vol. XIV. Infectious Diseases. 1S98. 8vo. 602 pages. Wm. Wood & Co., New York.

Public Health Reports. (Formerly, Abstract of Sanitary Reports.) Issued by the Supervising Surgeon-General, Marine-Hospital Service. Under the National (Juarantine Act of April 29, 1878, and the Act Granting Additional Quarantine Powers and Imposing Additional Duties upon the Marino-Hospital Service, approved Feb. 15, 1893. Vol XII. Nos. 1-53. 1897. 8vo. 1441 pages. 1898. Government Printing Office, Washington.

LOUIS euge:n^e livingood, m. d.


A T A MEETING HELD AT XOON ON THE EKillTII OF .IL'LY, ^-^ IN THE OFFICE OF THE SUPERINTENDENT OF THE JOHNS HOPKINS HOSPITAL, PRESIDED OVER BY PROF. W. H. WELCH, THE FOLLOWING RESOLUTIONS WERE ADOPTED:

WnEiiEAS, on the Fourth of July the steamsliip La Bonrguiiiie sank at sea with more than .500 passengers ; and

Whekeas, among those lost was onr beloved colleague, Louis Eugene Livingood ;

Be it ItesoUed, That we, the Medical Faculty of the Johns Hopkhis University and the staff of the Johns Hopkins Hospital, who for live years have been his associates and friends, do express to his family our deepest and most heartfelt sympathy in their cruel bereavement.

He has left a record of unusual purity of character, of singleness of inirpose, of devotion to duty, of work well done, which wiH remain a treasured memory to all who knew him.

-t«(/. Be it Further licxohvd, That a copy of these resolutions be transmitted to his family and published in the Baltimore News and in the Bulletin of the .Tolius Hopldns HospitaL

GEORGE W. DOBBIN, LEWELLYS F. BARKER, WILLIAM SYDNEY THAYER,

Committee.

DESCRIPTION OF THE JOHNS HOPKINS HOSPITAL.

Ry .Tohn S. nir.i.iNOS, M. D , LI,. O.

Containing 56 large quarto plates, jihototypes, and lithographs, with views, plans and detail drawings of all buildings, and their interior arrangements— also woodcuts of apparatus and fixtures; also 1 16 i>ages of letter-press describing the plans followed in tlie construction, and giving full details of heating ai)paratuB, ventilation, sewerage and plumbing. Price, bound in cloth, $7.50.


July, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


173


PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.


THE JOHNS HOPKINS HOSPITAL REPORTS.


Volume I. 423 pages, 99 plates.


Report in Patliologry.

The Vessels and Walls of the Dog's Stomach; A Study of the Intestinal Contraction;

Healing of Intestinal Sutures; Reversal of the Intestine; The Contraction of the

Vena Portae and its Influence upon the Circulation. By F. P. Mall, M. D. A Contribution to the Pathology of the Gelatinous Type of Cerebellar Sclerosis

(Atrophy). By Henry J. Berkley, M. D. Reticulated Tissue and its Relation to the Connective Tissue Fibrils. By F. P.

Mall, M. D.

Report in Derniatolog'T. Two Cases of Protozoan (Coccidioidal) Infection of the Skin and other Organs. By

T. C. Gilchrist, M. D., and Emmet Riiford, M. D. A Case of Blastomycetic Dermatitis in Man; Comparisons of the Two Varieties of

Protozoa, and the Blastomyces found in the preceding Cases, with the so-called

Parasites found in Various Lesions of the Skin, etc.; Two Cases of MoUuscum

Fibrosum; The Pathology of a Case of Dermatitis Herpetiformis (Duhring). By

T. C. Gilchrist, M. D.

Report In Patliology. Ad Experimental Study of the Thyroid Gland of Dogs, with especial consideration

of Hypertrophy of this Gland. By W. S. Halsted, U. D.


Volume IL 570 pages, with 28 plates and figures.

Report in Medicine.

On Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with

Gallstones. By William Osler, M. D. Some Remarks on Anomalies of the Uvula. By John N. Mackbnzie, M. D. On Pyrodiu. By H. A. Lafleur. M. D. Cases of Post-febrile Insanity. By William Osler, M. D. Acute Tuberculosis in an Infant of Four Months. By Harry Toulmin, M. D. Rare Forms of Cardiac Thrombi. By William Osler, M. D. Notes on Endocarditis in Phthisis. By William Osler, M. D.

Report in Medicine.

Tubercular Peritonitis. By Williau Osler, M. D.

A Case of Raynaud's Disease. By H. M. Thomas, M. D.

Acute Nephritis in Typhoid Fever. By William Osler, M. D.

Report in Gynecoloery The Gynecological Operating Room. By Howard A. Kellt, M. D.

The Laparotomies performed from October 16, 1889, to March 3, 1890. By Howard

A. Kellt. M. D., and Hunter Robb, M. D. The Report o? the Autopsies in Two Cases Dying in the Gynecological Wards without Operation; Composite Temperature and Pulse Charts of Forty Cases of

Abdominal Section. By Howard A. Kellt, M. D. The Management of the Drainage Tube in Abdominal Section. By Hunter Robb,

M. D. The Gonococcus in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Peritoneum;

Ovarian Tumor; General Gynecological Operations from October 15, 1889, to

March 4, 1890. By Howard A. Kellt, M. D. Report of the Urinary Examination of Ninety-one Gynecological Cases. By HowaKD

A. Kelly, M. D., and Albert A. Ghrisket, M. D. Ligature of the Trunks of the Uterine and Ovarian Arteries as a Means of Checking

Hemorrhage from the Uterus, etc. By Howard A. Kellt, M. D. Carcinoma of the Cervix Uteri in the Negress. By J. W. Williams, M. D. Elephantiasis of the Clitoris. By Howard A. Kelly, M, D. Myio-Sarcoma of the Clitoris. By Hunter Robb, M. D. Kolpo-Ureterotomy. Incision of the Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gynecological Operations. By

Howard A. Kelly, M. D.

Report in Snrgery, I.

The Treatment of Wounds with Especial Reference to the Value of the Blood Clot in the Management of Dead Spaces. By W. S. Halsted, M. D.

Report in Nenrolog'y, I.

A Case of Chorea Insaniens. By Henry J. Berkley, M. D. Acute Angio-Neurotic Oedema. By Charles E. Simon, M. D. Haematomyelia. By August Hoch, M. D.

A Case of Cerebro-Spinal Syphilis, with an unusual Lesion in the Spinal Cord. By Henry M. Thomas, M. D.

Report in Patholog'y, I.

Aniffibic Dysentery. By Williau T. Councilman, M. D., and Henri A. La/leub, M. D.


Volume III. 766 pages, with 69 plates and figures.

Report in Patbologry.

Papillomatous Tumors of the Ovary. By J. Whitridoe Williams, M. D. Tuberculosis of the Female Generative Organs. By J. Whitridoe Williams, M. D.

Report in Putholoery.

Multiple Lympho-Sarcomata, with a report of Two Cases. By SiuoN Flexxer, M. D.

The Cerebellar Cortex of the Dog. By Henry J. Berkley, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman, M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Rubsell, Ph. D.

Heart Hypertrophy. By Wm. T. Howard, Jr., M. D.

Report in Gynecology*

The Gynecological Operating Room; An External Direct Method of Measuring the Conjugata Vera; Prolapsus Uteri without Diverticulum and with Anterior Enteroceie; Lipoma of the Labium Majus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Source of Error in Gynecological Diagnosis; Operation for the Suspension of the Retroflexed Uterus. By Howard A. Kelly, M. D.

Potassium Permanganate and Oxalic Acid as Germicides against the Pyogenic Cocci. By Mart Sherwood. M. D.

Intestinal Worms as a Complication in Abdominsl Surgery. By A. L. Stav«lt, M, D.


Gynecological Operations not Involving Cceliotomy. By Howard A. Kelly* M. D. Tabulated by A. L. Stavely, M. D.

The Employment of an Artificial Retroposition of the Uterus in covering Extensive Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdominal Pelvic Operations. By Howard A. Kelly, M. D.

Photography applied to Surgery. By A. S. Murray.

Traumatic Atresia of the Vagina with Hsmatokolpos and Hsmatometra. By Howard A. Kelly, M. D.

Urinalysis in Gynecology. By W. W. Russell, M. D.

The Importance of employing Anassthesia in the Diagnosis of Intra-Pelvic Gynecological Conditions. By Hunter Robb, M. D.

Resuscitation in Chloroform Asphy.\ia. By Howard A. Kelly, M. D.

One Hundred Cases of Ovariotomy performed on Women over Seventy Years of Age. By Howard A. Kelly, M. D., and Mary Sherwood, M. D.

Abduiiiinal Operations performed in the Gynecological Department, from March 5, 1890, to December 17. 1892. By Howard A. Kelly, M. D.

Record of Deaths occurring in the Gynecological Department from June 6, 1890, to May 4, 1892.


Volume IV. 504 pages, 33 charts and illustrations.

Report on Typhoid Fever.

By William Osler, M. D., with additional papers by W. S. Thayer, M. D., and J. Hewetson, M. D.

Report in Nenrologry*

Dementia Paralytica in the Negro Race; Studies in the Histology of the Liver; The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of the Submaxillary Gland of il/"^- viuso/lu:^; The Intrinsic Nerves of the Thyroid Gland of tlie Dog; The Nerve Elements of the Pituitary Gland. By IIenry J. Berkley, M. D.

Report in Surgery.

The Results of Operations for the Cure of Cancer of the Breast, from June, 1889, to January, 1894. By W. S. Halsted, M. D.

Report in Gynecologry.

Hydrosalpin.T, with a report of twenty-seven cases; Post-Operative Septic Peritonitis;

Tuberculosis of the Endometrium. By T. S. Cdllen, M. B.

Report in Pntliolog-y.

Deciduoma Malignum. By J. Whitridoe AVilliams, M. D.


Volume V. 480 pages, with 32 charts and illustrations.

CONTENTS

  • The Malarial Fevers of Baltimore. By W. S. Thayer, M. D., and J. Hewetson, M. D. A Study of seme Fatal Cases of Malaria. By Lewellts F. Barker, M. B.
  • Studies in Typhoid Fever. By William Osler, M. D., with additional papers by G. Blumer, M. D., Simon Flexner, M. D., Walter Reed, M. D., and H. C. Parsons, M. D.

Volume VI. 414 pages,, with 79 plates and figures.

  • Report in Nenroloer Studies on the Lesions produced by the Action of Certain Poisons on the Cortical Nerve Cell (Studies Nus. I to V). By Henry J. Berkley, M. D.
    • Introductory. — Recent Literature on the Pathology of Diseases of the Brain by the Chromate of Silver Methods;
    • Part I.— Alcohol Poisoning. — Experimental Lesions produced by Chronic Alcoholic Poisoning (Ethyl Alcohol). 2. Experimental Lesions produced by Acute Alcoholic Poisoning (Ethyl Alcohol);
    • Part II.^^L-rum Poisoning.— E.xperimental Lesions induced by the Action of the Dog's Serum on the Cortical Nerve Cell;
    • Part III.— Ricin Poisoning.— Experimental Lesions induced by Acute Ricin Poisoning. 2. Experimental Lesions induced by CJhronic Ricin Poisoning;
    • Part IV.— Hydrophobic Toxaemia.— Lesions of the Cortical Nerve Cell produced by the Toxine of Experimental Rabies;
    • Part V.— Pathological Alterations in the Nuclei and Nucleoli of Nerve Cells from the Effects of Alcohol and Ricin Intoxication; Nerve Fibre Terminal Apparatus; Asthenic Bulbar Paralysis. By Henry J. Berkley, M. D.

Report in Pathologry.

Fatal Puerperal Sepsis due to the Introduction of an Elm Tent. By Thomas S.

Cl-llen, M. B. Pregnancy in a Rudimentary Uterine Horn. Rupture, Death, Probable Migration of

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  • Adeno-Myoma Uteri Diffusum Benignum. By Thomas S. Cullen, M. B. X Bacteriological and Anatomical Study of the Summer Diarrhoeas of Infants. By William D. Booker, M. D.
  • The Pathology of Toxalburain Intoxications. By Simon Flexnvr, M. D.



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No. 88.


THE JOHNS HOPKINS MEDICAL SCHOOL. SESSION 1897-1898.

FACULTY.


Dakiel C. Giluan, LL. D., President.

WiLLiAU H. Welch, M. D., hL. D., Dean and Professor of Pathologj.

Ira Reusen, M. D., Ph. D., LL. D., Professor of Chemistry.

WiLLiAU OsLER, M. D., LL. D., F, R. C. P.. Professor of the Principles and Practice

of Medicine. Henry M. Hurd, M. D., LL. D., Professor of Psychiatry. William S. Halsted, M. D., Professor of Surgery. Howard A. Kelly, M. D., Professor of Gynecology and Obstetrics. Franklin P. Mall, M. D., Professor of Anatomy. John J. Abel, M. D., Professor of Pharmacology. William H. Howell, Ph. D., M. D., Professor of Physiologry.

William K. Brooks, Ph. D., LL. D., Professor of Comparative Anatomy and Zoology. John S. Billings, M. D., LL. D., Lecturer on the History and Literature of Medicine. Alexander C. Abbott, M. D., Lecturer on Hygiene. Charles Wardell Stiles, Ph. D., M. S., Lecturer on Medical Zoology. Robert Fletcher, M. D., M. R. C. S., Eng., Lecturer on Forensic Medicine. William D. Cooker, M. D., Clinical Professor of Diseases of Children. John N. MACfiENZiE, M. D., Clinical Professor of Laryngology and Rhinology. Samuel Theobald, M. D., Clinical Professor of Ophthalmology and Otology. Hekrt M. Thomas, M. D., Clinical Professor of Diseases of the Nervous System. Simon Fleiner, M. D., Associate Professor of Pathology. J, Whitridoe Williams, M. D., Associate Professor of Obstetrics. Lewellvb F. Barker, M. B., Associate Professor of Anatomy. William S. Thayer, M. D., Associate Professor of Medicine. John M. T. Finney, M. D., Associate Professor of Surgery.


George P. Dreybe, Ph. D., Associate in Phyeiology.

William W. Russell, M. D., Associate in Gynecology.

Henry J. Berkley, M. D., Associate in Neuro- Pathology.

J. Williams Lord, M. D., Associate in Dermatology and Instructor in Anatomy.

T. Caspar Gilchrist, M. R. C. S., Associate in Dermatology.

Robert L. Randolph, M. D., Associate in Ophthalmology and Otology.

Thomas B. Aldrich, Ph. D., Associate in Physiological Chemistry.

Thomas B. Futcher, M. B., Associate in Medicine.

Joseph O. Bloodqood, M. D., Associate in Surgery.

Thomas S. Ccllen, M. B., Associate in Gynecology.

Robs G. Harrison, Ph. D., Associate in Anatomy,

Frank R. Smith, M. D., Instructor in Medicine.

George W. Dodbin, M. D., Assistant in Obstetrics.

Walter Jones, Ph. D., Assistant in Physiological Chemistry.

Adolph G. Hoen, M. D., Instructor in Photo-Micrography.

Sydney M. Cone, M. D., Assistant in Surgical Pathology.

Lons E. LiviNGOOD, M. D., Assistant in Pathology.

Henry Barton Jacobs, M. D., Instructor in Medicine.

Charles R. Bardeen, M. D., Assistant in Anatomy.

Stewart Paton. M. D., Assistant in Nervous Diseasefl.

NoKMAN McL. Harris, M. B., Assistant in Pathology.

Harvey W. Cushing, M. D., Assistant in Surgery.

J. M. Lazear, M. D., Assistant in Clinical Microscopy.

J. L. Walz, Ph. G., Asflifltant Id Pharmacy.


GENERAL STATEMENT.

The Medical Department of the Johns Hopkins University was openeii for the instruction of students October, 1893. This School of Medicine is an integral and coordinate part of the Johns Hopkins University, and it also derives great advantages from its close affiliation with ihe Johns Hopkins Hospital.

The required period of study for the degree of Doctor of Medicine is tour years. The academic year begins on the first of October and ends the middle of June, with short recesses at Christmas and Easter.

Men and women are admitted upon the same terms.

In the methods of instruction especial emphasis is laid upon practical work in the Laboratories and in the Dispensary and Wards of the Hospital. While the aim of the School is primarily to train practitioners of medicine and surgery, it is recognized that the medical art should rest upon a suitable preliminary education and upon thorough training in the medical sciences. The first two years of the course are devoted mainly to practical work, combined with demonstrations, recitations and, when deemed necessary, lectures, in the Laboratories of Anatomy, Physiology, Physiological Chemistry, Pharmacology and Toxicology, Pathology and Bacteriology. During the last two years the student is given abundant opportunity for the personal study of cases of disease, his time being spent largely in the Hospital Wards and Dispensary and iu the Clinical Laboratories. Especially advantageous for thorough clinical training are the arrangements by which the students, divided into groups, engage in practical work in the Dispensary, and throughout the fourth year serve as clinical clerks and surgical dressers iu the wards of the Hospital.

REQUIREMENTS FOR ADMISSION.

As candidates for the degree of Doctor of Jlediciue the school receivrs :

1. Those who have satisfactorily completed the Chemical-Biological course which leads to the A. B. degree in this university.

3. Graduates of approved colleges or scientific schools who can furnish evidence : (a) That they have acquaintance with Latin and a good reading knowledge of French and German ; (6) That they have such knowledge of physics, chemistry, and biology as is imparted by the regular minor courses given in these subjects iu this university.

The phrase "a minor course," as here employed, meains a course that requires a year for its completion. In physics, four class-room exercises and three hours a week in the laboratory are required; in chemistry and biology, four class-room exercises and five hours a week in the laboratory in each subject.

3. Those who give evidence by examination that they possess the general education implied by a degree in arts or iu science from an approved college or scientitic school, and the knowledge of French, German, Latin, physics, chemistry, and biology above indicated.

Applicants for admission will receive blanks to be filled out relating to their previous courses of study.

They are required to furnish certificates from officers of the colleges or scientific schools where they have studied, as to the courses pursued in physics, chemistry, and biology. If such certificates are satisfactory, no examination in these subjects will be required from those who possess a degree in arts or science from an approved college or scientific school.

Candidates who have not received a degree in arts or in science from an approved college or scientific school, will be required (1) to pass, at the beginning of the session in October, the matriculation examination for admission to the collegiate department of the Johns Hopkins University, (3) then to pass examinations equivalent to those taken by students completing the Chemical-Biological course which leads to the A. B. degree in this University, and (o) to furnish satisfactory certificates that they have had the requisite laboratory training as specified above. It is expected that only iu very rare instances will applicants who do not possess a degree in arts or science be able to meet these requirements for admission.

Hearers and special workers, not candidates for a degree, will be received at the discretion of the Faculty.

ADMISSION TO ADVANCED STANDING. Applicauta for admission to advanced staudiug must furuish evidence II) that the foregoiug terms of admission as regards prolimluary training have been fulflllerl, (•2) that cuurses eqiiivaleut in kind aud aiuoimt to those given here, preceding that year of tlie course for aduilssiou to whicli appiication is nmde. have been sallsfaclorily compieted, and (3) must pass examiuatious at the begiuulng of the ses.sion in October in all the subjects that have been aiready pursued by the class to which admission is sought. CerliQcates of standing elsewhere cannot be accepted iu place of these examinations.

SPECIAL COURSES FOR GRADUATES IN MEDICINE.

Since the opening of the Johns Hopkins Hospital in 1889, courses ol instruction have been ofl'crcd to graduates in medicine. The attendance upon these courses has steadily increased with each succeeding year and indicates gratifying appreciation of the special advantages here afforded. With the completed organization of the Medical School, it was found necessary to give the courses intended especially for physicians at a later period of the academic year than that hitherto selected. It is, however, believed that the period now chosen for this purpose is more convenient for the majority of those desiring to take the cotirses than the former one. The special courses of instruction for graduates in medicine are now given annually during the months of May and June. During April there is a preliminary course iu Normal Histology. These courses are in Pathology, Bacteriology, Clinical Microscopy, General Medicine, Surgery, Gynecology, Dermatology, Diseases of Children, Diseases of the Nervous System, Genito-Urinary Diseases, Laryngology and Rhinology, and Ophthalmology and Otology. The instruction is intended to meet the requirements of practitioners of medicine, and is almost wholly of a practical character. It includes laboratory courses, demonstrations, bedside teaching, and clinical instruction in the wards, dispensary, amphitheatre, and operating rooms of the Hospital. These courses are Open to those who have taken a medical degree and who give evidence satisfactory to the several instructors that they are prepared to profit by the opportunities here offered. The number of students who can be accommodated in some of the practical courses is necessarily limited. For these the places are assigned according to the date of application.

The Annual Announcement and Catalogue will be sent upon application. Inquiries should be addressed to the

REGISTRAR OF THE JOHNS HOPKINS MEDICAL SCHOOL, BALTIMORE.


The JohriH Uopkins ITospiial Bulletins are issued monthly. They are printed by THE FRIEDENWALD CO., Baltimore. Single copies may be procured from Messrs. GUSHING & CO. and the BALTIMORE NEWS COMPANY, Baltimore. Subscriptions, $1.00 o year, maybe addressed to the publishers, THE JOHNS HOPKINS PliESS, BALTIMORE ; simjle copies will be sent by mail for fifteen cents each.



Vol. IX.- No. 89.


BALTIMORE, AUGUST, 1898.

Contents

  • A Tragedy of the Great Plague of Milan in 1630. By Rubert Fletcuer, M. D., J75
  • Sir John Charles Bucknill, M. D., F. R. C. P., F. R. S. By A. R. Uequhart, M. D., - 180
  • Medical Fees in Ancient Greece and Rome. By Charles Carroll Bosibaugh, A. M., M. D., 183
  • Endothelioma of the Cervix Uteri. By Elizabeth Hurdon, M.D., 186
  • On the Specific Gravity of the Urine during Anassthesia and after Salt-Solution Enemata. By Thomas R. Brown, M. D., 190
  • Correspondence : Hydraulic Pressure in Bladder Contracture. By Ferd. C. Valentine, M. D.,
  • Proceedings of Societies :

The Hospital Medical Society, ---------- Cocaine Ansesthesia in the Treatment of Certain Cases of Hernia and in Operations for Thyroid Tumors [Dr. Cusiiing] ;— a Word of Warning as to the Indiscriminate Use of Cocaine in the Treatment of Diseases of the Eye [Dr. Theobald] ; — On the Pathology of Fragmentatio Myocardii and Myocarditis Fibrosa [Mr. MacCallcm].

Notes on New Books, -.


A TRAGEDY OF THE GREAT PLAGUE OF MILAN IN 1630

By Robert Fletcher, M. D.


In early Bible history there are records of the utter destruction of temples or even cities, the removal of every stone which marked their existence, and the sowing of the ground with suit, so that it might ever after be sterile. Of the efficacy of the latter part of the proceeding, some doubts might be entertained. In more modern times the residence of some notorious criminal has, in like manner, been destroyed and removed with the solemn declaration by the State that the ground upon which it had stood should be held as accursed, and that no building should ever be erected upon it. There are two noteworthy instances in which, in addition, a stone column with an inscription describing the crime and its punishment was erected upon the site of the dwelling of the criminal. The first in order of date is still in existence in Genoa. A certain Julius Cajsar Vacchero, known as the "richest merchant of Genoa," entered into a conspiracy in 1628 to destroy the republican government of Genoa and to deliver the State to the Duke of Savoy. He was beheaded with many of his fellow conspirators, his wife and children were banished, and by a decree of the Senate his palace was razed to the ground, every stone removed, and a pillar with an inscription devoting him to "eternal infamy" was erected


on its site. A naval officer * who visited the spot a few years ago described to me the desolate appearance of this vast space of ground overgrown with brambles and weeds, with the weather-beaten stone pillar in its centre. In reply to his enquiries, no one could tell him anything of the story connected with the place, only that the ground was "accursed," and the pillar was " colonna d'infiwna."

The other column was erected in ]\lilan, in 1G30, and the tragedy it commemorated is the subject of the present sketch.

Traditions of the terrible pestilence known as the Black Death, which ravaged Europe in 1348, and which, according to estimates made from such sources as were accessible, swept away one-third of the inhabitants of the known world, were still rife in Milan when the great plague of 1630 broke out in that city. A writer has left a vivid description of the conditions brought about by the former visitation. He says:


♦Captain Greer, now Rear Admiral Greer, U.S.N. (Retired). He copied the inscription, which corresponds exactly with that given in the account of Vacchero's conspiracy in the Archivio storico d' Italia, an important collection of public documents published by the Italian Government, and amounting to nearly a hundred volumes.


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JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 89.


" Wild places were sought for shelter ; some went into ships and anchored themselves afar off on the waters. But the angel that was pouring the vial had a foot on the sea as well as on the dry land. No place was so wild that the plague did not visit — none so secret that the quick-sighted pestilence did not discover — none could fly that it did not overtake.

"For a time all commerce was in coffins and shrouds, but even that ended. IShrift there was none; churches and chapels were open, but neither priests nor penitents entered — all went to the charnel-house. The sexton and the physician were cast into the same deep and wide grave; the testator, and his heirs and executors were hurled from the same cart into the same hole together. Fire became extinguished, as if its element had expired, and the seams of the sailorless ships yawned to the sun. Though doors were open and coffers unwatched, there was no theft; all offenses ceased, and no cry but the universal woe of the pestilence was heard among men."

There is nothing more cruel than fear, and no fear more debasing than that which is engendered by the presence or approach of a pestilence. We have not been without some experience of this in our own day, but when we add to this ignominious cowardice, the gross ignorance and superstition which existed at the period of which I am about to speak, we can understand, partly at least, how such a story became possible.

Manzoni, the famous Italian writer, the author of the best romance of the century in his language, " I promessi sposi,"' "The Betrothed," has told the story of this Milanese column in a small work published in 1840, iStoria della Colonna infame. It has not been translated into English, though there is a French version of it.

The column in question was erected in 1630, and was blown down during a storm, in 1788. The inscription upon it was in Latin, which, in its construction, very closely resembles some portions of the inscription on the Genoese pillar. The literal translation of it is this :

" Here, where this plot of ground extends, formerly stood the shop of the barber Giangiacomo Mora, who had conspired with Guglielmo Piazza, Commissary of the Public Health, and with others, while a frightful plague exercised its ravages, by means of deadly ointments spread on all sides, to hurl many citizens to a cruel death. For this, the Senate, having declared them both to be enemies of their country, decreed that, jjlaced on an elevated car, their flesh should be torn with red-hot pincers, their right hands be cut off, and their bones be broken ; that they should be extended on the wheel, and at the end of six hours be put to death, and burnt. Then, and that there might remain no trace of these guilty men, their possessions should be sold at public sale, their ashes thrown into the river, and to perpetuate the memory of their deed the Senate wills that the house in which the crime was projected shall be razed to the ground, shall never be rebuilt, and that in its place a column shall be erected which shall be called Infamous. Keep afar off, then, afar off, good citizens, lest this accursed ground should pollute yon with its infamy. August, 1630."

This barbarous sentence was executed in all its details, and for a hundred and fifty years, this pillar, intended to blast the memory of two really innocent persons, stood as the proof of


the ignorance and credulity of their judges. In 1777, a certain Count Pietro Verri, Counsellor of State in the service of the Empress Maria Theresa, wrote a work, which, however, did not see the light until 1804, twenty-seven years later, entitled (translated) " Remarks upon torture, with special relation to the effects of the baleful ointments to which was attributed the plague which devastated Milan in the year 1630." Count Verri had carefully perused all the records of the trial of Piazza and Mora, and while pointing out the injustice done these wretched men, he decried in good set phrase the legalized use of torture. It is not surprising that he delayed the publication of his treatise. As late as 1768 the Empress Maria Theresa had authorized the publication of a codification of the laws relating to the use of torture by the courts. The judicial application of torture, or "the question," as it was termed by a delicate eujihemism, comes down from the Roman code of laws. Count Verri quotes from the writings of many jurists as to the rights of the accused, and the power of the judges, in cases where it was necessary to extract the truth. The late Dr. Welling, of Washington, delivered an address on the law of torture, giving the codification of Guazzini, a famous Italian jurisconsult, which was published in 1612. There is a wonderful resemblance in the provisions of all these laws as described by Guazzini, Verri, and the later codification of Maria Theresa. Great discretion was given to the judges, but they were forbidden to apiply the torture in any case more then three times. If the accused, appropriately named I'afflitto, the sufferer, bore these three administrations without confessing, then he was to be held guiltless as by Divine decision. In the "Ancient customs of Brittany," a very curious compilation made in 1330 and 1340, the same limitation was made, and if the accused bore it all without yielding, then he was to be, in the language of the compiler, " Safe and free, because it was evident that God exhibited miracles for him."

Another provision of the law regulating the application of torture, which was violated in the case in question, was that which forbids its use for the discovery of the corpus delicti, which must appear aliunde — from other sources — but only for the purpose of discovering the author and accomplices of the crime. Here there was certainly neither dead body nor injured person.

The preparation of the accused for the torture was ceremonious. It was a general belief of the times that an amulet or compact with the evil one which would enable him to endure the crudest suffering, and thus evade the desired confession, might be concealed in his clothes, hair, or even in his stomach or bowels. His clothing was therefore changed, every particle of hair was shaved off, and a purgative was given him, so that he might be effectually deprived of all diabolic aid. Piazza was thus prepared every time that he was tortured.* The belief in this protective power was of ancient date. A distinguished Italian magistrate,t in a work on criminal law published in 1533, states that an accused man revealed the


" Abraso prius dicto Gulielmo, at vestibus Curire induto, propinata etiam potione ea purgante." (Processo [etc.], p. 41.) t Hippolytus de Marsiliis. Practica criminalis [etc.], fob, Venetiis, 1532, fol. 12.


AaGUST, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


177


secret of his ability to resist torture and refrain from cries or disclosures. He confessed that one of his relatives had prepared for him a cake of wheat flour, to which was added the mixed milk of a mother and daughter. Every day he was to swallow some crumbs of this cake, and as long as it lasted it insured his insensibility to torment. On the other hand, there were certain liquids and greases which, when rubbed into the body of an accused person, counteracted all his protective charms, and, says Marsiliis, with cynical exultation, "when that was done one could hear the joints crack and the bones sing." M. Le Blanc* says that these counter-charms were known in England in the 12th century, in Italy in the 14th century, and in China to quite recent days.f

The original account of the proceedings which led to the tragic end of Piazza and ]Mora is that of the Canon Ripamonti. He was born in 1577, and was historiographer of Milan. He published the first ten volumes of the Ecclesiastical History of Milan, in 1617, and by request of the Decurions wrote an account of the plague which devasted the city in 1630. This latter is a quarto book of 410 pages, written in Latin, and published at Milan in 1641. The title-page is a copper-plate engraving, curiously emblematic. There is a gigantic skeleton filling the entii'e page; his hands hold weapons, armor, and books of devotion ; his bony feet protrude from under a carpet on which lies a man, the victim of the plague. In front of the skeleton is an altar with a crucifix, to which a woman, seated, with the usual naked boy attending her, points with a sword.

Two hundred years later, in 1841, this work was translated into Italian by Francesco Cusani, who has added many valuable notes in an appendix.

In 1839 the full official account of the trials of the "Anoiuters " was published in Milan.J It is in Italian, but all that relates to the ajiplication of the torture is discreetly veiled in the less familiar Latin, which, however, the modern editor has translated into Italian.

From these sources the facts have been obtained, now to be briefly presented.

Early in the morning of the 21st of June, 1630, during the prevalence of the plague in Milan, a woman of the lower classes saw from her window a man going down the street who was writing on a paper. He wiped his fingers on the wall of a house, probably to get rid of ink-stains, but with the readiness of ignorance and fear, she was sure that he was smearing deadly ointments to promote the spread of the pestilence. A crowd of excited women invaded the Council-chamber, and the Senate was informed of the occurrence. Orders were immediately given to trace out and arrest the guilty man.

It must seem strange to us that the rulers of a great city, even at that time, could have been so ignorant as to believe


Le Blanc, ( Edmond ). Del'ancient croyance a des moyens secrets de defier la torture. Paris, 1892, p. 14. t Bodin states that magic words conferring immunity under torture were sometimes written on the scalp of sorcerers, where it was concealed by the hair. ( De la demonomanie des sorcieres, 1587.)

t Processo originate degli Untori nella peste del 1630. Milan, 1839. 8°.


that such means could be productive of the pestilence, or that any man or men could desire to destroy their fellow-citizens, and risk their own lives besides. But extraordinary occurrences demanded extraordinary causes to account for them. The plague was attributed to hail, to the poisoning of the fountains by the Jews — to deadly ointments so placed that passers-by would touch them. It became dangerous for any one to touch walls or buildings. Ripamonti relates that three French travelers admiring the fagade of a building, one of them touched the marble, and was immediately set upon by the mob and dragged half dead to the prison. An old man, 80 years of age, about to sit down on a bench in the church of San Antonio, wiped off the dust with his cloak. A woman cried out that he was anointing the benches, and even there, in the house of God, the worshippers beat and kicked the life out of the unfortunate man. Such was the spirit of the time.

The earliest notice, perhaps, of this belief in "Anointers" is to be found in the works of Guy de Chauliac, who was physician to Pope Clement VI and was living in Avignon, in 1348, when the Black Death ravaged that city. He says: " It was believed that the Jews had poisoned the world, for which reason they were slain. In other places they drove away beggars after cutting off their ears * * * and if it was found that any one had powders or ointments, he was compelled to swallow them, to show they were not poisons.*

Ambroise Pare, in his Livre de la peste, throws further light on the matter. In his Advice to Magistrates, during the visitation of the pestilence, he concludes the chapter thus :

" What shall I add ? They must keep an eye on certain thieves, murderers, poisoners, worse than inhuman, who grease and smear the walls and doors of rich houses with matter from buboes and carbuncles, and other excretions of the jjlaguestricken, so as to infect the houses and thus be enabled to break into them, pillage and strip them, and even strangle the poor sick people in their beds ; which was done at Lyons in the year 1565. God! what punishment such fellows deserve ; but this I leave to the discretion of the Magistrates who have charge of such duties."|

The scrivener, with the ink-horn at his belt, was discovered, and proved to be a certain Guglielmo Piazza, a commissioner of health, a petty officer employed to report cases of the disease. He stoutly denied all knowledge of the crime charged to him, and maintained his resolution through two applications of torture, although the second one was the "question extraordinary," in which atrocious complications were added to the ordinary proceeding. But in his cell, broken down with the effects of the torments he had twice experienced, and dreading their renewal, which he knew would come, the unhappy man yielded to the insidious suggestions of those around him. He confessed his guilt, and declared that he obtained the death-dealing ointment from the barber Giangiacomo Mora. The latter was immediately arrested, but was likewise vehement in his declarations of innocence, avowing that he had never seen or known Piazza. The latter was made of sterner stuff than the barber, who yielded at the first application of


Cyrurgica, 1499, fol. 19.


tCEuvres, 1575, fob, p. 662.


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JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 89.


the torture, and confessed everything they suggested to him. From that time on these two wretched men vied with each other in manufacturing falsehoods. They implicated even a Count Padilla, the son of the Commandant of the Castle. He was arrested, but having powerful friends, his trial did not take place until long after the execution of Piazza and Mora. It was from the documentary evidence on his trial that Count Verri obtained the full details of the iniquitous treatment of the two victims who had perished. Count Padilla was ultimately acquitted.

Mora, the barber, had a wife and five children ; the eldest, a young man, assisting him in his business. The latter was arrested with his father, and the entire contents of the shop were seized and carried to the court. As was usual in those days, the barber dabbled in medicine, and he declared, no doubt with truth, that the various pans and vessels contained remedies for or preservatives from the pest. The sale of these specifics was very extensive. A man who was hanged for robbery during the height of the pestilence confessed, with the rope around his neck, that he had prepared an ointment as a charm against the Anointers. Cusani, in his notes, gives the formula of what became known as Unguento dell' Impiccato, " The ointment of the hanged man." It may take its place with the " Vinegar of the four thieves," which had its origin during the plague of Marseilles. Its composition was supposed to be: Wax, 3 ounces ; Olive oil, 2 ounces; Oil ivy, Oil stone. Leaves of Anethum, or dill, Lai^rel berries, Sage and Rosemary, of each J ounce. A little vinegar was added.

It is interesting to observe that these remedies, or preventatives, were composed almost entirely of aromatics, some of which furnish the accepted germicides of our own day. The apertures of the body were to be especially guarded by application of these waters or tinctures. Ambroise Pare recommends that a surgeon called to attend patients with the plague should first be purged and bled. Next he should have two issues made, one at the insertion of the deltoid of the right arm, and another about three fingers' breadth below the left knee. He considerately adds that these need not be made if the surgeon already has any running sore. "For truly," he declares, " we know from experience, that they who have such open sores, have not been subject to the plague, and have taken no harm, though they were every day among cases of it." *

Pare also gives a formula of a " Preservative water," with which the surgeon was to wash his whole body " very frequently," and he adds, " it is a good thing to wash the mouth with it, and draw a little of it up the nose, and put a few drops into the ear."

This preservative consisted of a mixture of rose water, elderflower water, and wine, in which were boiled, by slow heat, the roots of inula, angelica, gentian, bistort and zedoary ; also the leaves of sage, rosemary, wormwood and rue; juniper and ivy berries with lemon peel, and the mystic theriac and mithridate were finally added.

As a proof of the danger of contact with the bodies of infected persons, Pare relates in his vivid style how he himself


Op. eit., 663.


nearly fell a victim to a sudden deadly syncope, the result of the overpowering efBuvia which arose from the buboes and carbuncles of a plague-patient, as he uncovered him. Upon regaining consciousness he sneezed violently ten or twelve times, so that his nose bled, and he attributes his escape to " virtue of the expulsive power of his brain, seeing that all his other faculties were dead for the time." *

The barber's acquaintance with Piazza seems to have been limited to occasional visits of the latter to his shop for the usual service of his trade, and they both stated that Mora bad undertaken to prepare a pot of his "preservative" for his customer. On this slight foundation was built a superstructure of conspiracy for wholesale murder, by the never-failing power of torture. Once, in his agony, the wretched barber cried to his judges that if they would tell him what they wanted him to say, he would say it! He confessed everything that was insidiously suggested, such as that he had mixed foam from the mouths of those dead of the plague with his ointment, and then declared that Piazza, whose business took him among the dead bodies, had supplied him with the material.

In the account of the trial there is frequent allusion to the " purging the infamy " of the accused. A Roman law, given by Justinian,! provides that gladiators, slaves, and infamous persons like them, when called as witnesses, should be first put to the torture, so as to insure their telling the truth. In like manner, in the Italian laws regulating the legal application of torture, the accused person was declared to be "infamous," and his implication of others in his crime was not to be accepted as proof, unless he maintained his charge while subjected to torture. If he then reiterated his declaration he was said to have " purged his infamy," and his evidence was admitted. Piazza, as he involved others in his accusations, was, on each fresh occasion, tortured to " purge his infamy," and thus make his charges applicable. The degree of suffering inflicted upon him seems to have been much lighter than on other occasions. He had been promised immunity from his sentence by the Auditor of the Court if he made full confession, another instance of the treachery of these oflBcials, for the Governor only could exercise such power.

More than once. Piazza and Mora recanted, and declared that their confessions were false, and uttered only in fear of further torments. A threat of another application of the question, and, above all, the hope that if no longer recalcitrant they might expect some mitigation of the horrible punishmen which had been decreed as their fate, soon reduced them to submission. They were in the hands of men who were destitute of pity. The plague was raging, and the populace, fierce and ignorant, demanded their victims. The Commandant of the Castle, the father of Count Padilla who had been accused of complicity in the alleged crime, demanded of the Court that the execution of the sentence on Piazza and Jlora should be delayed in order that they might be confronted with his son and their accusations be met. The judge refused to accede to his request on the ground that " the people were clamorous."


Oj}. cii., p. ()H4. t Digest, lib. XX, tit. V, dc testibus, 1, 21.


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AVhen the condemned men found that their examinations were at an end, and that, despite the promise of impunity, they were to be submitted to the full execution of their terrible sentence, they retracted in their confessions to the priest all the charges they had made against other persons, declaring that they were made under the agonies of torture, or in the apprehension of further suffering.

In the collection of medical portraits and engravings in the library of the Surgeon-General's office, at Washington, is an elaborate j^rint, representing in all its details the execution of Piazza and Mora.

The engraving, which is from a copper-plate, is about sixteen inches square. It was published in Rome by the authority of the Nuncio of the Roman College. The engraver was Horatio Colombo. There is no date, but it is probable that it was brought out close upon the event it commemorates.*

The title on the top is (translated), "The sentence pronounced on those who had poisoned many persons in Milan in the year 1630. This is followed by the names of the Magnificos who sat in judgment, and the particulars of the punishment decreed. Each scene in the picture has its letter, which is referred to in an explanatory legend below. The entire disregard of the unities of time and place which characterized such productions is well displayed in this curious engraving. On the right is the shop of the barber Mora, and in front of it the " Column of Infamy " is already erected. A large platform car, drawn by two oxen, exhibits the victims, executioners, and priests. A brazier of live charcoal contains the pincers with which the flesh was to be torn. The barber's right hand is on the block, and a chopper held over the wrist is about to be struck down by a wooden mallet held aloft by the executioner. Further on is seen a large platform, on which the two victims are having their limbs broken by an iron bar, preparatory to their exposure on the wheel for six hours. The wheels are also displayed, one of them already on a pole, with the men bound upon it.

Still further on are the fires consuming the bodies, and, last scene of all, on the extreme left is a fussy little stream foaming under bridges, which is supposed to be a river, and into it a man is throwing the ashes of the two malefactors.

Comment upon this tragic occurrence is needless. It tells its own story and bears its own moral.

A few words may be added as to the mortality of this pestilence and the measures adopted by the authorities to encounter it. Like all statistics of those early times, the estimates are variable, but there are letters from the Sanita to the Governor, which state the then daily mortality at 500. It is probable that the total number of deaths was about 150,000.

The tribunal of the Sanita, a body something like a modern board of health, seem to have acted with sense and energy, though impeded by the obstinacy and ignorance of the Senate, the Council of Decurious and the Magistrates. To declare that the plague had appeared in Milan was to drive the people off, and to frighten trade away. The two physicians of the


• In the Processo originale degl' Untori, Milan, 1839, there is at the end a folding plate, which is a poor copy of this engraving. The editor speaks of the original as " una atampa di quel tempo."


Sanita, Taddino and Settala, scarcely dared to appear in the streets, and the latter, who was 80 years old, nearly lost his life from the angry mob. Later, when the existence of the pestilence had to be admitted, some strange precautions were adopted. An immense procession was to proceed through the city in honor of San Carlo and to implore his aid, and the authorities ordered the doors of all sequestered houses to be nailed up lest the distempered inmates should try to join the procession. There were 500 such houses, according to the Cavalier Somiglia, who also wrote an account of this fearful time.



Fig. s.

An immense hospital was constructed to accommodate 2,000 persons, though at one time, in the height of the disease, the number of its patients had increased to 16,000. The pits dug for the dead became filled, and bodies in all stages of putrefaction were lying in houses and in the streets. In despair, the Sanita applied to two priests who had been efficient in their aid. They promised that in four days all the corpses should be removed. They went into the country, and summoning the people in the name of religion, they succeeded in having three immense pits dug. The vionatti of the Sanita were employed to bring out the dead, and in the stipulated time the good fathers had fulfilled their pledge. The persons in the employ of the Sanita for removing corpses were of three grades. The monatti carried the bodies out of the houses and carted them to the pits. The apparUori, or summoners (the name is still preserved in the English Ecclesiastical Courts as


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apparitors) went before with a bell notifying the people to bring out their dead. The covimissari were in control of the other two. It will be remembered that the unfortunate Piazza was a commissario.

Among the precautious taken by physicians for their own protection, while visiting plague-stricken patients, was the adoption of a particular dress. Pare recommends that the material should be camlet, serge, satin, taffeta, or morocco, but not cloth, frieze, or fur, lest these latter should harbor the poison, and death should be thus conveyed to the healthy. Manget, in his Traite de la peste (Geneve, 1721, 2 vols.), has a frontispiece to the first volume representing the dress of a doctor during the jilague at Marseilles. From his description it seems that the mantle, breeches, shirt, boots, gloves, and hat, were all of morocco leather. The beak attached to the mask was filled with aromatics, the air passing over them in resjiiration. Figure 2 is a reproduction of this plate from Manget's work. In a recent number of Janus (Amsterdam, 1897, 15. 297), M. Keber gives an interesting account of an engraving in his possession, the work of the artist Jolin Melchior Fuesslin, which also represents a doctor at Marseilles during the plague, and is, he thinks, of about the same date as the


work of Manget. His engraving is herewith reproduced as Fig. 3. The legend underneath may be translated :

" Sketch of a Cordovau-leather-clad doctor of Marseilles, having also a nose-case filled with smoking material to keep off the plague. With the wand he is to feel the pulse."

In Manget's sketch the Skklein becomes a veritable stick, but the information conveyed by it would probably be quite as useful in the one case as in the other. The appearance of this leather-clad doctor, with his nez fumant, could scarcely have been reassuring to the plague-stricken wretch.

Since this address was written I have received the March number of the Bristol Medico-Ghirurgical Journal, which contains a notice of the Manget and Reber sketches by Dr. L. M. Griffiths, the accomplished assistant editor. He reproduces the plates from the Janus blocks, and mentions that an amulet of arsenic was worn on the chest in time of plague, as a prophylactic, in the city of Bristol, as well as elsewhere. He quotes Kemp's treatise, 1665, thereanent. Ambroise Pare had, however, recommended this device a hundred years before. It was to be worn over the heart, in order that " the heart might become accustomed to poison, and so be the less injured when other poisons sought it."


SIR JOHN CHARLES BUCKNILL, M.D, F.R.C.P., F.R.S.*

By a. R. Urquhart, M. D., Perth, Scotland.


A notable personality has been lost to the medical profession by the death of Sir John Bucknill. During his long career of activity he worthily occupied a prominent position in the specialty of psychological medicine, giving forth no uncertain sound, and commanding respectful attention even from those who were most strenuously opposed to his utterances. He was a man of high ideals, fruitful in resources, indomitable in execution of what he conceived to be right. A masterful man, dealing shrewd blows, and unconscious of defeat.

Sir John Charles Bucknill was born at Market Bosworth, in Leicestershire, on the 25th December, 1817. His father, Mr. John Bucknill, practiced in that town as a surgeon. His younger brother, Alfred, who died at an early age, served in a regiment of the East India Company. He had two sisters, and a half-sister (by his father's second wife), who still survives.

Dr. Bucknill was educated at the grammar school of his native town, and at Rugby, uuder the great Dr. Arnold. In 1835 he entered University College, London; and, five years latei", took the degree of Bachelor of Medicine, at London University. His career as a student was distinguished, and he served as house-surgeon under Listen, at University College Hospital, where Sir John Eric Erichsen and Sir Richard Quain were among his contemporaries.

After resigning that appointment. Dr. Bucknill began the practice of his profession in Chelsea, where he remained for


Presented to the Johns Hopkins Hospital Medical Society, June 5, 1898.


four years. He married, in 1842, Mary Anne, the only child of Mr. Thomas Townsend, of Hill-Morton Manor, Warwickshire. By her he had three sons — Colonel Bucknill, late of the Royal Engineers; Mr. T. T. Bucknill, Q. C, M. P. for the Epsom Divison of Mid-Surrey; and Charles, now dead. Mrs. Bucknill died 1889.

His health having broken down. Dr. Bucknill was advised to live in a warmer climate; and this, no doubt, determined his application for the post of medical superintendent of the Devon County Asylum. He was appointed in 1844, and held office for eighteen years. The Devon County Asylum was designed on a system of radiating blocks, and expressed the latest improvements in construction at that time. Its first superintendent entered on his duties with characteristic energy and conspicuous ability, and soon organized it in accordance with his own ideas. The Committee of Management and the Commissioners in Lunacy were not slow to recognize that tlie institution had been jilaced in the front rank of hospitals for the insane. Dr. Bucknill was as active in the scientific duties of his office as he was in the administration of domestic details; while immersed in the study of medico-legal questions, and assiduous in journalistic work, at the same time he found leisure to occupy himself with the organization of the volunteers.

His literary work began in 1851, with a pamphlet on the Classification and Treatment of Criminal Lunatics. This was followed in 1852 by another on the Law and Theory of Insanity. Dr. Bucknill's first important book was published in 1854 — " Unsoundness of Mind in Relation to Criminal Acts," being the first Sugdeu Prize Essay. It appeared again iu a second


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edition iu 1857. These studies showed the beut of Dr. Bucknill's miud, and to the last he maintained his interest in them, publishing papers on cognate subjects down to ISSl. In the Sugden Prize Essay he clearly stated that " responsibility depends upon power, not upon knowledge, still less upon feeling. A man is responsible to do that which he can do, not that which he feels or knows it right to do." In process of time, this position is slowly but surely being assumed by the legal profession, and the difficulties which then embarrassed the administration of justice are now less formidable in practice.

The first number of the Journal of Mental Science appeared in 1853, under the title of The Asylum Journal. Dr. Damerow, of Halle, had suggested a periodical on similar lines, in 1844, in which year The American Journal of Insanity was brought out. He found an active supporter iu Dr. Bucknill. The association of medical officers of Asylums and Hospitals for the Insane, at a meeting held in Oxford, iu 1852, unanimously resolved to establish their journal, and to confide the editorial labors and responsibilities to Dr. Bucknill, who continued to edit it until 1862, when he was compelled to resign office ou his appointment as Lord Chancellor's visitor. Reference to the early volumes will show how he labored to make the journal worthy of its high aims, and what success followed ou his devotion to its interests. Year by year, each volume has been prefaced by his eloquent and stirring words, which still incite us "to pursue that knowledge which is to be obtained in the practical departments of science."

His literary abilities and sound judgment were .soon recognized, and he became a frequent contributor to the British and Foreign Medico-Chirurgical Review, which was then at its zenith. He had the highest opinion of the value of that Review, and counted it an honor to be a contributor. His article on the Pathology of Insanity, in 1855, was the germ of his greatest work, iu which he was associated with the late Dr. Hack Tuke. The " Manual of Psychological Medicine, " published iu 1858, at once became a standard authority, and ran through four editions, the last appearing in 1879. Dr. Bucknill's share of this volume comprised the eminently practical sections relating to Diagnosis, Pathology and Treatment. His ripened experience and careful observations betrayed no trace of fatigue, his delineations of disease showed the hand of a master.

In the more immediate duties of his office the same originality of thought and the same determination to advance were obvious. In 1859, the Commissioners in Lunacy reported in favorable terms of his treatment of patients in cottages beyond the immediate precincts of the asylum. The evolution of this method of care has proved successful beyond all question. From the modest cottages at Exminster to the full development of such institutions as Alt Scherbitz, or Toledo, is a far cry ; but the tone is triumphant. I do not know if Dr. Bucknill anticipated such far-reaching issues when he laid his modest plans of home-like surroundings for the insane, but I do know that the issues of his plan for National Defense greatly surpassed the imaginings of his fertile brain. When he invited four gentlemen to dinner on the evening of the 27tb January, 1852, for the purpose of considering the possibility of raising a corps of Rifle Volunteers in South Devon, he so ap


pealed to men that their new-found interest caused them to enter on the project with heart and soul. The Earl Fortescue, then Lord Lieutenant of the county, received their communication favorably; the Government, through him, accepted their services; and from that small beginning arose the present volunteer force of the country, with a roll of 224,525 efficient men.

While still at Exminster, Dr. Bucknill proceeded to take the degree of M. D., Loudon, and became a Fellow of University College in 1852. Seven years later he was admitted a Fellow of the Royal College of Physicians, where he subsequently served as Censor ( 1879-81 ) and as Lumleian Lecturer (1877).

In 1859 and 1860 he published works of more general interest — " The Psychology of Shakespeare," and "The Medical Knowledge of Shakespeare." These were well received, and a second edition of the latter, under the title of the " Mad Folk of Shakespeare," was produced in 1867.

On Dr. Bucknill's appointment as Lord Chancellor's visitor, ill 1862, he came to London and resided in the corner house of Cleveland Square, formerly occupied by Lord Playfair. After a time he moved to Wingate street; and, later, to Hill-Morton Manor, where he turned his attention to farming, and served the county as a member of the committee of the Warwickshire Asylum, to which his first assistant. Dr. Parsey, had been appointed medical superintendent.

In 1876, Dr. Bucknill resigned bis office under the Lord Chancellor, and began practice as a consulting physician in mental diseases. At the Leeds meeting of the British Medical Association, in the following year, he delivered a presidential address before the section of psychology, entitled The Priest and the Physician. It was a powerful oration, and at once recalled attention to one who had been but little before the world during his period of official seclusion. The wide knowledge of men and affairs which Dr. Bucknill had garnered was given forth with no unsparing hand. He delivered a warning message to his colleagues, in advising the mental physician to breathe the pure air of a rational life, for his own sake, and for the sake of his patients ; and inculcated the the greater need of understanding incoherence and delusion, and sympathizing with morbid feeling. He uttered the prophetic caution that we should walk with prudence and circumspection in the well-trod paths of medical reticence, forbearance and wisdom. Turning to those clergymen who had, at that time, achieved notoriety in connection with the book entitled The Priest in Absolution, he disposed once for all of the attempt to establish an identity between sin and disease. From the assertion that the physician is a naturalist, the priest a supernaturalist, and that no sophistry can bridge the abyss between them. Dr. Bucknill developed arguments in support of his position. This renascence of Heinroth's theory of the common origin of insanity and sin was strangled in his powerful grasp.

About this time, Dr. Bucknill published two little books, which were received with much hostile criticism. He had travelled in the United States in 1875, and his account of "Asylums for the Insane iu America" was issued in the following year. The echoes of that controversy have not yet died


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away, and I have no wish to re-awaken them now. Dr. Bucknill was a strong man. He held strong opinions and expressed them forcibly. His adherence to the principles and practice of Conolly was most tenacions. Although, in the preparation of the Manual of Psychological Medicine, points of difference had arisen between him and his collaborator, Dr. Hack Tuke, these were not obviously stated. The vexed question of mechanical restraint was one of these. As is now well known, the latter never adopted the extreme opinions Dr. Bucknill entertained. No doubt, Conolly set an impress on the minds of those brought into contact with him, and fired their zeal in no common measure. I have heard Dr. Bucknill say that every asylum physician should read every word Conolly published, and in truth, reforms of magnitude are not to be carried through without that overwhelming sense of necessity which rouses public interest and sweeps resistance aside. The time for a drastic remedy had come. I believe, too, at this late date, when the reorganized, reconstructed asylums of America have attained a level of eflBciency unsurpassed in any other country, and much evil has been atoned by ameliorated conditions, that the specialty can well afford to admit that Dr. Bucknill's caustic pen was not employed in vain.

As to the other brochure on "Habitual Drunkenness," there will be more difference of opinion. The advance of Socialistic legislation is consequent on the alteration of the political equation. The treatment of habitual drunkards, whether by way of "reformation " or by way of "cure," is in an unsatisfactory state. Proceeding on the dogma that drunkenness is not per se a crime, we are on the eve of receiving some enactment dealing with those who mingle inebriety with offenses against the law. It does not appear to us, who see so much of the devastation wrought by this vice, that the moiety of legislation in progress is sufficient; but it may be accepted as an instalment. At the same time, we who occupy no extreme position must admit that Dr. Bucknill's shrewd common sense did much to clear the atmosphere.

His strictures upon private asylums, and suggestions for radical alterations in the care of the insane, were published in 1880, as a reprint of articles which had appeared in the British Medical Journal. It was in this direction that Dr. Bucknill diverged most widely from his colleagues. The book is entitled " The Care of the Insane and their Legal Control," and presents opinions and arguments most forcibly expressed. In brief. Dr. Bucknill advocated the abolition of the Commissioners in Lunacy, and would have relegated their duties to the Local Government Board in the case of paupers, and to the Loi'd Chancellor's office in the case of those possessed of property. This was generally received as an impossible policy, and failed for want of general support. His attack on private asylums, however, has been followed by most untoward results. His demand that the insane should not be " confined as a profitable private business" would at a stroke abolish private treatment. In fact, he did not or would not recognize that every kind of arrangement should be available, and that under eflBcient supervision the fittest should survive. The state of matters in England, at present, is far from satisfactory, the amended law of lunacy having resulted in grave and increasing evils. The discussion of these would be out of place


on this occasion, but any presentment of Dr. Bucknill which would omit reference to his honest opinions and strenuous advocacy of them after a long life of observation and debate, would be partial and misleading.

In April, 1878, the first number of "Brain" appeared. With Dr. Bucknill, Sir James Crichton-Browne, Dr. Ferrier and Dr. Hughlings-Jackson were associated as editors. It was felt that there was room for a journal devoted to neurology, and the brilliant success with which " Brain " began and has continued showed that Dr. Bucknill had rightly judged the necessities of the medical profession in this direction. He continued to share in the direction of this journal for nine years, until it was firmly established as the organ of the Neurological Society.

Later communications to the current periodicals may be mentioned : In 1881, an article on Lord Chief Justine Cockburn ; in 1882, a pajjer on the ResponsihiUfy of Guiteau ; in 1884, a lecture on the Relation of Madness to Crime.

Dr. Bucknill had many honors showered upon him. He was a member of the Athenreum and Garrick Clubs, a Fellow of the Koyal Society, a Justice of Peace for the County of Warwick, and a Governor of Bethlem Hospital. But the crowning mark of distinction of his long and active life was the Knighthood bestowed upon him in 1894. He was then entertained at Exeter by a distinguished company, who met to do him honor, and there to unveil a memorial of the inauguration of the Volunteer Force, which is decorated with a medallion bust of Sir John Bucknill, and bears an appropriate inscription. The Duke of Cambridge, so long the head of the army, in the course of an admirable speech presented him with a scroll commemorative of the occasion, and spoke in high terms of his services.

Sir John Bucknill was a keen sportsman, fond of all outdoor sports, as became one who was possessed of a commanding presence and a robust frame. He was also interested in music and the graphic arts. In early life, he allied himself with Palmerston in politics, but gradually changed to a moderate conservative.

Sir John Bucknill died at Bournemouth, where he spent the last years of his life, on 20th July, 1897, and was buried at Clifton, or Dunsmore, near Rugby. The cause of death was disease of the kidneys and bladder, leading to septic absorption. A photogravure from the Exeter Memorial published in the Journal of Medical Science is here reproduced ; and Sir John Bucknill's biography is now in preparation by his eldest son.

Bibliography.

1857. An Inquiry into the Classification and Treatment of Criminal Lunatics. Pamphlet.

1853. The Law and Theory of Insanity. Pamphlet.

1854. Unsoundness of Mind in Relation to Criminal Acts. (The first Sugden Prize Essay.) 12mo. 2nd ed., 1857.

1855. Medical Evidence and Testimony in Cases of Insanity. Pamphlet.

1855. Pathology of Insanity. ( Rep. B. and F. Med. Chir. Rev.)

1858. A Manual of Psychological Medicine. (With Dr. Hack Tuke.) 4th ed., 1879.


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1859. Psychology of Shakespeare.

1860. The Medical Knowledge of Shakespeare.

1867. The Mad Folk of Shakespeare. ( 2nd ed. of the Psychology of Shakespeare.)

1874. The Law of Murder in iis Medical Aspects.

1876. Psychological Medicine in America. ( M. T. and G.) " Notes on Asylums for the Insane in America.

1877. The Law of Insanity. ( Lunileiau Lectures.) The Priest and the Physician. ( B. M. J.)


1878. Habitual Drunkenness and Insane Drunkards.

1880. On the Care of the Insane and their Legal Control.

1881. The late Lord Chief Justice of England. (Cockburn.) re Lunacy. Pamphlet.

1882. The Responsibility of Guiteau. Pamphlet.

1884. The Abolition of Private Asylums. (XIX Century.)

" The Relation of Madness to Crime. ( Lecture at

London Institute.)


MEDICAL FEES IN ANCIENT GREECE AND ROME.

By Charles Carroll Bombaugh, A. M., M. D., Baltimore, Md.


Those who examine with curious interest the 199 surgical instruments found in 1819 in the Via Cousularis in Pompeii, and preserved in the National Museum at Naples, or their counterparts recovered from excavations in Rome and collected by Professor Scalzi, will remember that that interest centres in their remote antiquity and in their actual use more than eighteen centuries ago. At the same time the attentive observer cannot forget that they were not originals or prototypes, for the archeologists tell us that twenty centuries before Pompeii was buried by the shower of ashes from Vesuvius, the ancient Egyptians covered the ceilings and walls of the temples at Tentyra, Karnac and Luxor with basso relievos representing surgical operations and the instruments employed, many of which are analogous to the instruments in use at the present day.

Horace says in one of his Odes that there were brave men living before Agamemnon, the Grecian commander. We may quite as confidently say that there were good physicians before Hippocrates. And so, the father of medicine, transcendent as he was, originative, constructive as he was, belonged, let us remember, to the family of the Asclepiadae, the hereditary physicians of Greece, and therefore enjoyed special educational advantages in preparation for his immortal work. Granting that he brought order and law and symmetry out of chaos, the materials must have been ready at hand, for we are assured that observations and descriptions of symptoms were already numerous, and were marked by much acuteness. Granting that we owe to him the conception of the oath which he transmitted to posterity, that the strikingportraiture of the true physician which he drew for all time was the outcome of his own creative power, there must have been sources of inspiration behind and beyond. Granting the authorship of his treatise on fractures and luxations, the genuineness of which is conceded, there were expert bone-setters on the stage of action long before his day. The master spirits that sway the multitude do not leap into the arena full panoplied as Minerva sprang from the brain of Jove.

Whether the story of Esculapius comes from the Greek mythology, or whether it is of Oriental origin, it helps the


Read before tlie Historical Cliibof the Johns Hopkins Hospital, May 9, 1898.


historian to establish the existence of medical men as a separate class among the earliest communities. Such traditions show that as far back as legendary history goes there existed men who made disease and the healing art a special study, and derived their means of subsistence from the practice of their craft.

Let us turn for a moment from history to mythology, from narrative to fable, though perhaps one is as purely legendary as the other. According to the best authorities, the siege of Troy took place about twelve hundred years before the Christian era. Four hundred years later, i. e. eight hundred years B. C, Homer wrote the Iliad. One of the first points we note in Homer's account is that medicine in Greece was not subordinated to religion and made a function of the priesthood, as it was in Egypt and in Asiatic countries where the offices of the priest and the physician were combined in the same person. If ever exercised in Greece by religions impostors, it must have been secularized at a very early period. Whatever may have been the familiarity of the cultivated Greeks with domestic remedies and vulnerary herbs, a more advanced knowledge of medical and surgical treatment appears to have been an accomplishment of the heroes of the Iliad. Pope, in his Essay on the character of Homer, says that " the state of war in which Greece lived required a knowledge of the healing of wounds, and this might make him breed his princes, Achilles, Patroclus, Podalirius and JIachaon, to the science. What Homer thus attributes to others he himself knew, and he has given us reason to believe not slightly, for if we consider his insight into the structure of the human body, it is so nice that he has been judged by some to have "wounded his heroes with too much science."

Dr. Payne of London, in his History of Medicine, says that "the Homeric heroes themselves are represented as having considerable skill in surgery, and as able to attend to ordinary wounds and injuries, but there is also a professional class represented by Machaon and Podalirius, the two sons of Asclepius, who are treated with great respect. It would appear, too, from the Ethiopis of Archinus (quoted by Welcker and Haeser) that the duties of those two were not precisely the same. Machaon's task was more especially to heal injuries, while Podalirius had received from his father the gift of


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recognizing what was not visible to the eye. In other words, a rough indication of the separation of medicine and surgery."

Assuming that these medical officers were real characters, or, at least, that they were types or representatives of a professional class, it would be a matter of interest to learn what remuneration they received for their services during the ten years' siege of Troy. Let us hope, for the honor of the profession, that they were better paid than was Bernal, the physician of Christopher Columbus on his first voyage. For his seven months' detail for such duty Bernal received a sum equivalent to $37 of our money; that is to say, about seventeen cents a day. What Marco, the surgeon of the expedition, received, we are not told.

Hippocrates was in his prime about four hundred years B. C. Contemporaneous with the father of medicine was another Greek, Herodotus, who was called the " father of history." Herodotus traveled extensively in Asia, Africa and Southern Europe, and in his intercourse with the learned men of the day acquired a large fund of curious information. He refers briefly in his first book, Clio, to the rude beginnings of the medical art among the Assyrians, the Babylonians and the Persians, and the manner in which, in the absence of professional teachers, the facts of experience were accumulated and transmitted. He says: "Such as are diseased among them they carry into some public square; they have no professors of medicine, but the passengers in general interrogate the sick person concerning his malady; that if any person has either been afflicted with a similar disease himself, or seen its operation upon another, he may communicate the process by which his own recovery was effected, or by which, in any other instance, he knew the disease to be removed. No one may jiass by the afflicted person in silence, or without inquiry into the nature of the complaint." A cynic might say that this sort of history repeats itself in our day in the gratuitous advice and the infallible formularies that are thrust ujjon the helpless invalid by officious busy-bodies.

In his second book, Euterpe (84), he points out the germs or rudimentary forms of specialism in medical practice, the limitation to certain specified diseases, or to the diseases of a simple organ or class. He says: "The art of medicine in Egypt is thus exercised: One physician is confined to the study and management of one disease; there are, of course, a great number who practice this art; some attend to disorders of the eyes ; others to those of the head ; some take care of the teeth ; others are conversant with all diseases of the bowels ; whilst many attend to the cure of maladies which are less conspicuous."

Not until we come to his third book, Thalia, does Herodotus give us a glimpse of the question of compensation, recompense, requital, fee, honorarium, rjuid pro quo. We are told that the governor of Sardis, a Persian named Oroetes, in a fit of maddening jealousy, conceived the atrocious design of encompassing the death of Polycrates of Samos. He sent a messenger to Polycrates to request a visit from him on some plausible pretext, and the latter, unsuspicious of harm, set sail with a retinue befitting his rank, including Democedes of Crotoua, who was reputed to be the most skillful practitioner


of his time. When opportunity offered, Polycrates was assassinated, but afterward, on learning the facts, King Darius, of Persia, ordered the execution of Oroetes. Soon after this occurrence Darius, in leaping from his horse, twisted his foot with so much violence as to occasion sprain and luxation of the ankle joint.

Herodotus says: "Having at his court some Egyptians, supposed to be the skillful of the medical profession, he trusted to their assistance. They, however, increased the evil by twisting and otherwise violently handling the parts affected; from the extreme pain which he endured the king passed seven days and as many nights without sleep. In this situation on the eighth day, some one ventured to recommend Democedes of Crotona, having heard of his reputation at Sardis. Darius immediately sent for him; he w"as discovered among the slaves of Oroetes, where he had been allowed to remain in neglect, and was brought to the king just as he was found, in chains and in rags. He at once applied such strong fomentations and soothing remedies as were used in the treatment of similar cases in Greece, and by these means Darius, who had despaired of ever recovering the entire use of his foot, was not only enabled to sleep, but in a short time was completely restored. In acknowledgment of his cure Darius presented him with two pairs of fetters of gold.

This is the first medical fee of which I find any distinct or specific record in profane history. As to its significance, or to its fitness as a mark of gratitude, we may leave both to inference or to conjecture. If a condition of enforced servitude was to continue, golden fetters would have been quite as irksome as shackles of a baser metal. Thereupon Democedes ventured to ask the king whether, in return for restoring him to health, he wished to double his calamity. This reference to two pairs or sets of fetters pleased the king so much that he sent him to the apartments of the women for his reward. The eunuchs who conducted him informed the women that this was the man who had restored the king to life. Accordingly, they took a jar of gold, filled it with gold coin, and presented it to him. But royal munificence went beyond this mark of regard. A sumptuous house was provided for Democedes at Susa; he was entertained at the king's own table; he was held in the highest estimation, and he was supplied with all that heart could wish except the restriction of not being able to return to Greece. In the course of time it happened that Atossa, daughter of Cyrus and wife of Darius, had a troublesome ulcer on her breast, for which she consulted Democedes. He told her that he was able to cure it, but exacted of her an oath that in return she should serve him in whatever he might require, which, he assured her, would not involve any dishonor. Atossa was cured by his skill, and, observant of her promise and of his instructions, she persuaded Darius, on some artful pretext, to undertake a military excursion to Greece, and to direct Democedes to accompany the expedition both as medical adviser and pilot. Darius directed him to take with him all of his valuables as presents for his father and his brethren, assuring him of gifts of greater value on his return. But the wily physician profited l)y the voyage to make his escape. To him, as to many another exile, there was no place like home. Moreover, he


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bad been sufficiently remunerated at home to take off the sharp edge of the Persian temptation.

We are told that in his day, in Greece, the usual fee paid to physicians for incidental visits was very small ; in fact, not more than two groats, sixteen cents, or about one-thirtieth of the customary fee in England in our time, one guinea. But remember that it was usual at that remote period for municijialities to hire physicians by the year, and pay them out of the public funds for attendance upon the citizens. When Deniocedes lived in ^Egina his services were engaged at the rate of one talent per annum, about $2000, as near as we can estimate with our limited knowledge of relative values. At Athens his salary from the city treasury was one hundred minae, about $2400. When he afterward fixed his residence at Samos, Polycrates allowed him a pension which, according to the Attic standard of values, amounted to about $2400. But of all special acknowledgments or expressions of gratitude, one reported by Pliny takes the lead. He tells us that Cleombrotus received one hundred talents for the care and recovei'y of King Antiochus. If the Attic talent of the standard of Alexander is meant, this would amount to £24,375 ; if the standard of the coins of the Ptolemies, it would amount to £39,375, over $156,000, a sum that seems incredible, and which remains unmatched among the bounties of royalty at the present day.

Every Greek city had not only one or more public medical men in the municipal service, whose duty it was to visit the sick in the city and suburbs, but there was also a large dispensary, iatrium, where the practitioner, aided by his pupils, held consultations, performed operations and distributed the needful medicines. Beds were reserved for patients who could not be removed, or for very serious cases. The rich being able to be cared for at home, those who needed the aid of the public dispensary were the poor. Yet in the state of society at that period, the isolated poor, those without patron and "without brothers," as the phrase went, meaning those who were not members of a society having a mutual benefit fund, were not numerous. But what poor there were, we are assured by histoi'ians, were faithfully attended to in accordance with the precept of Hippocrates. Inscriptions show that it was an obligation that was gracefully and generously fulfilled. One of these, found at Cos, is an honorary decree regarding a physician who daring an epidemic had particularly distinguished himself by his devotion. Another inscription is a decree granting a crown of gold to Metrodorus, who, for twenty years a public physician, has saved many citizens, and now lives in poverty, having refused from them any fees.

Passing on to the Eoman Empire, we note that, as Montaigne says in his Essays, " no Roman till Pliny's time had ever vouchsafed to practice physic; that office was only jierformed by Greeks." It should be added, however, that it was largely in the hands of the slaves of wealthy Roman masters. In the early days of the republic, when the Romans were absorbed in their wars of conquest, medical assistance could only be obtained from persons of servile rank, a fact which held the profession for a long time in disrepute. Nearly two centuries before the establishment of the empire a Greek doctor named Archagathos came and settled in Rome. As


Duruy tells us, at first he was welcomed there and received the citizenship. He induced the Senate to apply the public money to the purchase of a house for him where he could treat surgical cases, his practice being limited to the treatment of fractures and dislocations, to amputations, and the dressing of wounds, ulcers and abscesses, internal maladies being left to quacks. For a time he was the fashion, and did a lucrative business, but his methods were so barbarous tliat he was eventually stigmatized with the epithet Carnifex (butcher). The elder Cato, who was noted for the acerbity of his temper, came out with a broadside against Greek doctors, winding up his denunciation by saying : " They make us pay dearly for obtaining our confidence, and poison us the more easily." Yet Cato himself made some pretension to medical knowledge, and wrote a book on domestic medicine. It was only a jumble of old women's remedies, however, and of such recipes as village sorcerers of later days might recommend.

As we approach the period of the establishment of the empire, or about the commencement of the Christian era, we find that the practice of medicine was still in the hands of the Greek physicians, but as Greece was then under the protectorate of Rome, they were treated with distinguished consideration. Pliny says " the medical art did not harmonize with Eoman gravity," whatever that means. In order to attract the Greek physicians to Rome, Osesar gave them the jus Quiritium, and afterward Augustus exempted them from taxation. They were allowed certain special privileges, which the physicians of our day who are by courtesy exempted from jury duty can appreciate. With these concessions, and the attraction of liberal fees from the luxuriously inclined Romans, they flocked from all parts of Greece, but those who were not Athenians, we are told, were obliged to borrow their idiom as well as their recipes from the big-wigs of Athens in order to obtain patronage. They spoke at Rome the language of Athens, just as the French doctors at Paris, in Molicre's time, spoke the Latin language. As educated men, their society was welcomed by the rulers and statesmen of Rome. Artorius, for instance, was called the friend of Augustus ; Asclapo was the f rietid of Cicero ; Asclepiades was the friend of Crassus, the orator, and so on.

In the course of time Roman citizens became i^ractitioners. Of the education necessary to qualify them for their duties we have no account; we only know that it was under the superintendence of the arcliiatri. This was a favored or superior class, the first physician bearing the title being Andromachus, the medical adviser of Nero. During the reign of Nero the archiatri were divided into two classes, the physicians of the different quarters of the city, archiatri jJopulares, and the physicians of the palace, archiatri palatini. The former were assigned to the relief of the poor, and each city was provided with five, seven or ten, according to its size. Rome had fourteen, besides one for the vestal virgins and one for the gymnasia. The latter, the saticti palatii, were men of elevated social position, and of high rank, not only in the exercise of their profession, but as counsellor of the government. Both were paid salaries, and were allowed special immunities and exemjitions. Later on, in the time of Hadrian and the Autonines, such concessions were made still more


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liberal, and the chief archiater ranked as a vicegerent. While the populares were obliged to attend their poor patients gratis, they were allowed to receive fees from the rich. They were not appointed by the municipal authorities, but were elected by the people, and while their office was less honorable than that of the palatini, it was more lucrative. In the time of Vespasian they had a retiring pension.

Tyitli regard to the amount of their income, the students of Eoman antiquities have not been able to furnish satisfactory data. We learn from Pliny that at the beginning of the imperial reign such eminent physicians as Albutius, Arruntius, Calpetanus, Cassius and Kubrius made 350,000 sesterces per annum, which is equivalent to £1950, or $9750. We also learn from Pliny that Quintus Stertinius, the favorite of the Emperor Claudius, was content with the honor of serving the the Emperor at the rate of 500,000 sesterces ($19,500) per annum, though his fame was such that he might have made 600,000 sesterces, or $23,500 in private practice. He and his brother, who received the same annual income from Claudius, left between them at their death, notwithstanding large sums they had spent in beautifying the city of Naples, the sum of 30,000,000 of sesterces, equal to $1,170,000.

Among the outward and visible manifestations of gratitude for restoration to health is one ^hich is preserved to this day. Antonius Musa, the physician of Augustus, according to some accounts, effected a radical cure of an obstinate cutaneous affection. Other accounts state that he was instrumental in saving the life of the Emperor. Whatever the precise fact, Augustus had a statue made of Musa, which he placed among his family group of bronze and marble memorials as one of the highest honors he could bestow. To-day, in the Vatican, it retains its place among the clustered family of the Cwsars, but though it is the impersonation or counterfeit presentment of Antonius Musa, it was adopted centuries ago, and is still accepted as the emblem or symbol of Esculapius. In later days, when the Byzantine and Western sections of the empire were alienated, and when Justinian, who called himself defender of the faith, was emperor at Constantinople, there were two Eastern brothers who practiced 'medicine in Cilicia, named Damian and Cosmas — names that were afterward enrolled in the list of Christian martyrs. They were nicknamed Anargyri, literally, "without money," because they refused recompense for professional services. Whatever was forced upon them, in spite of their reluctance, they turned over to the church, and when they were fortunate enough to cure Justinian of a perilous disease, and he insisted upon a


generous reward, they stipulated that he should build churches, which he did on a large scale, and with an enormous outlay of money, in gratitude for his recovery.

In reviewing medical progress under the empire we note frequent foreshadowings of the methods and usages of later times. There were specialists in considerable variety ; there were female doctors (unlike Athens, where females were forbidden by law to practice) ; there were public dispensaries for the treatment of the poor ; there were quacks not only among the lower orders of ignorance and presumption, but among men of high degree ; there were doctors for the aristocratic set who made fat fees by humoring the caprice and the selfcoddling of the valetudinarian, or by ministering to the distempered fancy of the malade imaginaire. Doctors signed their prescriptions, and of the seals or stamps which they used there are still in existence 150. There were also apothecaries, who gave advice behind the backs of medical practitioners as ours do, but they charged for their advice as well as their medicines. Then, as now, the instructor of classes of medical students received pay for tuition. This payment was called " minerval," but the term was eventually made more comprehensive, and included the fees paid by patients for attendance. We are warranted in the inference that in the case of some rich patients, the minerval was disproportionately large when measured by the insufficiency of the service rendered ; it certainly gave free scope to ilartial for his epigrammatic satire. Finally, there were periods in which overcrowding of the i-anks remind us of the forcible remark of Addison in the Spectator : " I am troubled when I reflect how the profession of physic is overburdened with practitioners, and filled with multitudes of ingenious gentlemen who starve one another."

Medicine in its embryonic or rudimentary state eighteen or twenty centuries ago, and medicine in its present state of advancement and achievement, are as wide apart as the Poles. Yet running through the ages they present certain features in common, and not the least of these is the standing acknowledgment of the homely old maxim of St. Paul, " the laborer is worthy of his hire." But while mercenaries of the Paracelsus stripe, or gold-loving doctors of physic, like Chaucer's in the Canterbury Tales, have always abounded, yet from time immemorial to the present hour, foremost and uppermost is the spirit of self-sacrifice, of self-renunciation, that is ever ready to lighten the burden of sorrow, to lift the heavy and the weary weight of suffering, and to listen respousively to what Wordsworth calls •' the still, sad music of huniauity."


ENDOTHELIOMA OF THE CERYIX UTERI.

By Elizabeth Hurdon, M. D., Assistant in Gynecology, Johns Hopkins University.


The following case of endothelioma is of interest chiefly on account of the rarity of this variety of tumor in the cervix. While, according to Pick's investigations, a large percentage of all endothelial tumors are found in the female generative organs, they are for the most part situated in the ovary, and so far as I can discover bu t three cases have been described as


occurring in the uterus, two of which belonged to the cervix, and we add a third. The first case was reported by Amaun. Jr., in his work on neoplasms of the cervix. The patient was a multipara 31 years old. The tumor consisted of a connective-tissue stroma in which were numerous anastomosing cells, strands and masses which contained central lumina. They were


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composed of large epithelial-like cells, and in the lamina were nnmerous leucocytes embedded in fibrin, but no red blood corpuscles were seen. Neither the epithelium lining the cervical canal, nor the gland epithelium showed any proliferation, and by means of serial sections the writer conclusively proved the absence of any relation between the cells of the neoplasm and the cervical epithelium. Amann considered the tumor to be a true endothelioma originating from the endothelium of the lymph vessels in the deeper portion of the cervical mucosa.

A similar tumor also originating in the endothelium of the lymph vessels has been described by Braetz. The patient was a nullipara 18 years old. Attached to the posterior cervical lip was a papillary tumor which macroscopically could not be differentiated from a carcinoma. This tumor also consisted of a somewhat scanty connective-tissue stroma in which were cell strands of various forms containing central lamina. At some points round cells embedded in fibrin were found in the lumina, but more sparingly than in Amann's case. The cervical glands were unaltered and the cylindrical epithelium intact and showed no proliferation.

Ziegler has recently adopted a new classification for the sarcomata which have an alveolar or organized structure. The term endothelioma is practically limited to the tumors which originate from the endothelial lining of the lymph spaces or vessels, and the tumors arising from blood vessels are designated angio-sarcomata, but he states that of the latter group those which come from the endothelium of the vessels may also be called eudotheliomata.

It is possible, moreover, that many of the perivascular angio-sarcomata are lymphatic eudotheliomata, as it is easily conceivable that the network or loops of lymph channels which surround the blood vessel may be the site of origin of such a growth. In the restricted sense, however, the term endothelioma is still applicable to the new growths of the cervix described by Amann and Braetz, and also to our case, as they all are apparently of lymphatic origin. The remaining case of endothelioma of the uterus described by Pick as occurring in the body is not so clearly of the same nature.

History of the case. Mrs. S. was admitted to Prof. Kelly's private sanatorium, November, 1896.

For about nine years the patient had suffered from attacks of severe pain in the side, radiating down into the bladder, which were supposed to be renal colic. There was no suspicion of pelvic disease uutil three weeks before admission, when a slight hemorrhage occurred for the first time since the menopause ten years before. On examination the cervix was found to be hard and choked by a Hat mass 3x3 cm., which at first sight looked like a polyp and was discolored and showed white patches on its surface. (The mass which was attached to both the anterior and posterior lips was excised, being too dense to yield to the sharp curette. Surprisingly little bleeding followed, but when the mass was dissected out to the vaginal vault the disease appeared to extend farther.) The uterine body was small, the cervical end being larger than the body. The ovaries appeared normal. The left broad ligament was free. The right side was held by a firm


band. No nodules, however, were felt in the broad ligament. The uterus was freely movable.

Operation. After catheterizing the left ureter (the right catheter could not be inserted) abdominal hysterectomy was performed, special care being taken to enucleate the right broad ligament out to the pelvic wall and down to its floor. The most dangerous part of the enucleation was anteriorly, where the vesical peritoneum was pinned to the uterus by adhesions apparently dependent upon the extension of the growth to the base of the bladder. The bladder, however, was dissected free without injury. The uterus was removed with the uf)per part of the vagina, including extensive tissue at the base of the broad ligaments.

The patient died on" the 15th day, apparently of sepsis. Unfortunately, no autopsy could be obtained.

It will be observed how slight the local manifestations were, compared with the advancement of the growth, which had extended beyond possibility of complete removal before the attention was directed to the pelvic organs. This rajjiditv of growth was also observed in the cases reported by Amann and Braetz. As autopsies were obtained in none of the cases, the tendency to metastasize cannot be determined.

Pathologiral rejwrf. Gyn.-Path. Nos. 1405 and 1443. Dec. 14, 1896.

The specimen consists of the uterus with its appendages. The uterus is 8x5x3 cm. and is smooth and glistening. The cervical portion is enlarged, measuring 4.5x3.5 cm. in diameter, and is markedly indurated. The external os is represented by a crater-like excavation 3.5x3 cm. in diameter, and 3 cm. in depth. The anterior lip lias been eaten away and the posterior is thickened laterally, being 3 to 3 cm. in thickness. The floor of the excavation is corrugated and roughened, but there is no evidence of softening nor of friability. The mucous membrane of the upper part of the cervical canal is apparently unaltered, but the walls of the entire cervix and also of the lower segment of the body, particularly on the left side and posteriorly, are thickened and indurated, and on section present a dense fibrillated structure. The uterine cavity has a smooth mucous membrane. • On the posterior wall, however, there is a small polypoid thickening, and springing from the centre of the anterior wall is a pedunculated flattened mushroomlike polyp 3 cm. in diameter. The appendages present nothing of interest.

Histological examination. The lower portion of the cervix is covered with stratified squamous epithelium, but on advancing inward toward the apex of the excavation, which macroscopically presented an eroded appearance, the surface is necrotic. Above the necrotic area the cervical canal is lined with normal cylindrical epithelium. The cervical glands are in a few places dilated, but on the whole are practically normal. Penetrating all portions of the cervix extending to the mucous membrane internally, involving the lower portion of the body, and laterally reaching the parametrial cellular tissue are myriads of tubules (Fig. I). These may be dilated to form large alveoli and show some branching, but as a rule they appear as narrow channels, round or oval spaces, or as strands of cells two or three layers thick. Many of the small spaces, and more especially the larger ones, are lined by one layer


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of spindle-shaped cells, which resemble normal endothelium, and which in some places are so flat as to be scarcely recognizable. Others of the small spaces, and also some of the



Fig. I. Is a cbaracteristio field, and shows the large and small round or irregular spaces lined by one or more layers of cells. Note the intimate relationship between the cells lining the cavities and the surrounding stroma; in uo place do these cells tend to become separated from the wall. The stroma is composed of spindle-shaped cells.

large ones, are lined with one uniform layer of cuboidal cells, having oval, well-stained nuclei. In many places the cells have proliferated and the spaces are lined by two, three or



Fig. II. Shows the individual cell elements clearly; a represents a cavity lined by one layer of cells, which tend to become spindle-shaped ; i and c are more advanced; the cells are several layers in thickness, and are gradually narrowing the lumen. At d a space has become completely tilled, no cavity remaining, and c portrays a similar mass of cells on longitudinal section. At / the space is at one point lined by two layers of cells, a little further on by three layers; g is a good example of a dilated space, partially filled with granular material. Note in all these areas, especially / and ;/, the intimate relation between the stroma and the cells lining the spaces, also that there is no desquamation of cells. The stroma is, in places, abundantly infiltrated with small round cells.

more layers of cells, or again the cavity is completely obliterated and solid cylinders or nests of cells are formed (Fig. II).


Where several layers of cells are present they are usually larger and more spherical or cuboidal, but in general present more or less of their elongated form. Often a tubule is seen lined on one side with two or more layers of large roundish or oval cells, while on the opposite side is a single layer of flat, scarcely visible cells. In such instances the swollen cells are sometimes covered over with a layer of flat cells similar to those lining the opposite wall, thus suggesting a proliferation of the periendothelial cells. Again, a space lined with several layers of large cuboidal or oval cells merges directly into a narrow channel lined with one layer of endothelial-like cells and with difficulty distinguished from the small lymph or blood vessels near by. Surrounding many of the tubules is a narrow zone of hyaline giving the appearance of a sclerotic vessel wall. A notable feature of this tumor is the absence of any tendency on the part of the tumor cells to retract from the surrounding connective tissue, indicating the organic relation of the one to the other. This intimate connection is emphasized in many places by the imperceptible transition of the tumor cells into the connective tissue cells of the stroma. On the other hand, the epithelium of the glands and on the surface of the mucosa exhibits the usual tendency to separate from the underlying tissue. The surface epithelium is quite normal to the margin of the necrotic area, then gradually disappears, and although the mucosa is everywhere invaded by the new growth tubules or cell strands penetrating between the glands in close proximity to them and even encroaching upon the gland cavity, there is no metamorphosis of the epithelial cells into the cells of the tumor. It must be mentioned, however, that at one or two points where the growth reaches the surface there is at first sight an apparent relation between the epithelium and tumorcells, but on careful inspection it is seen that, although the epithelial cells are altered, they are of a quite different type from the cells of the neoplasm. The cell nuclei are large, vesicular, with finely granular or homogeneous character. The protoplasm is somewhat scanty, and it is generally impossible to differentiate the protoplasm of one cell from another. Where the cells are in several layers the nuclei are usually swollen and more faintly stained, scattered between these pale nuclei, however, are others which take an intense diffuse stain. Mitotic figures, both symmetrical and asymmetrical, and showing the various stages of division, are fairly abundant.

The majority of the tubules are empty, some, however, contain desquamated cells, a few small round cells, fragmented nuclei and shadows of cells. Sections from the tissue excised for diagnosis before the radical operation was performed, show fresh blood in many of the spaces, probably due to manipulation, as blood is not found in the tubules in sections from the organ which was removed entire. Careful search fails to reveal clumps of lymphoid cells in tubules, such as Braetz and Aniann have described; serial sections, however, were not examined. Nevertheless, it is probable that this tumor has developed from the endothelium of the lymph spaces, a view supported by the general arrangement of the tubules which most frequently show a definite relation to the larger blood vessels. This is most characteristically shown in the deeper portions of the uterine walls, and in the parametrium, where the early


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stages of the growth may be studied. The tissue is penetrated here and there by slender cords of cells, which usually contain central lumina, and present numerous ampullar spaces. Occasionally, larger solid cylinders of cells are seen. These cell strands are, for the most part, in the immediate vicinity of the blood vessels, sometimes apparently surrounding the vessel wall, again running parallel with it. Here and there wavy strands, consisting of one or two rows of spindle cells, suggest a transformation of connective issue rather than a tubular formation. At three or four points interesting pictures are seen, as represented in Fig. III. This is, apparently, a cioss section of a nerve, which shows nests of tumor cells, evidently developing in lymph channels of the nerve sheath.



Fig. III. b is probably a cross section of a nerve, but a definite statement cannot be made, as further sections could not be obtained for special staining.

a and a are masses of tumor cells evidently in the lymph channels of the nerve sheath. A few tumor cells are also found at the point indicated by c.

The stroma of the tissue is abundant, is exceedingly dense, and consists, to a great extent, of normal cervical tissue. In the deeper portions there is considerable smooth muscle, and a moderate small round-celled infiltration. Blood vessels are fairly numerous and show marked obliterative endarteritis and arterio-sclerosis. The uterine mucosa is practically unaltered, and the polypi noted above consist of the normal elements of the uterine mucosa. The tubes and ovaries present the usual senile appearance.

This growth presents many characteristics differing from a carcinoma. It was ptcnliarly dense, even in the superficial portions, while in carcinomata the surface is easily curetted away. The only excresence consisted of a large Hat polyp-like mass, with a regular outline, and there were none of the friable papillary outgrowths usually seen in carcinoma.

On histological examination, although there are points of similarity, yet the differences are marked. In the first place, the cervical glands, even in the older portions of the growth, appear normal, while in adeno-carcinoma they usually show


cell proliferation and metamorphosis. Secondly, there are no tuft-like ingrowths of the cells, such as are so often seen in carcinoma. Thirdly, many of the spaces, both large and small, are lined with one layer of spindle cells. In adeno-carcinoma it is exceptional to find the epithelium spindle-shaped, and then only where the gland is distended and the epithelium has been flattened by pressure. The tubules in this case offer no evidence of pressure. The cells in general have their long axis running parallel with the circumference, and it is only rarely that cylindrical cells are found. Fourthly, the cells lining the tubules show no tendency to retract fi'om their walls, but, on the contrary, there is an intimate relation between the tumor cells and the surrounding connective tissue, and where retraction of tissue has occurred, a few stroma cells accompany the cells lining the alveoli. In the case described by Braetz there was a sharp demarcation between the tumor cells and the stroma. Fifthly, although the tubules frequently anastomose, the tendency toward branching is not marked.

An arrangement especially emphasized by Braetz is in jilaces observed in our case, that is that the tubules, particularly in the early stages of the growth, pursue a more or less parallel course.

Many of the tubules are surrounded by zones of hyaline, a condition which I have not noticed in adeno-carcinoma of the cervix.

Finally, the growth is widely distributed in the deeper tissues of the organ, the mucosa lining the upper j)ortion of the cervical canal and the uterine cavity being practically free from extension of the growth, while the entire cervical walls and the lower third of the muscular coats of the body are everywhere invaded, and the parametrium is also involved. The extension is always apparently by direct continuity, and not by metastasis.

We are, therefore, dealing with a new growth, characterized by the formation of tubules and cell strands which follow the course of the blood vessels. The cells of the growth, moreover, show a definite relation to the surrounding stroma cells, while the epithelial elements of the tissue are practically normal.

In conclusion I wish to express my hearty thanks to Dr. Kelly for allowing me to report this unusual case.

Bibliography. Braetz : Inaug. Diss.

Amann : Ueber Neubild. der cervicalport. des Uterus, 1893. Amann : Archiv f. Gyn., Bd. 46. Pick : Archiv f. Gyn , Bd. 46 und 49. Lubarsch : Ergeb. der allg. Path, und path. Anat., 1897. Ziegler: Lehrbuch der allg. und spec. path. Anat., 1898.


DESCRIPTION OF THE JOHNS HOPKINS HOSPITAL.

By John S. Billings, M. D., LL. D.

Containinfi 56 large quarto plates, phototypes, and lithographs, with viewB, plans and detail drawings of all buildings, and their interior arrangements — also woodcuts of apparatus and fixtures ; also 116 pages of letter-press describing the plans followed in the construction, and giving full details of heating apparatus, ventilation, sewerage and plumbing. Price, bound in cloth, |7.50.


190


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 89.


ON THE SPECIFIC GRAVITY OF THE URINE DURING ANAESTHESIA AND AFTER SALTSOLUTION ENEMATA.

By Thomas R. Brown, M. D., The Johns Hopkins Hospital.


Although it is known that under certain conditions a decrease in the specific gravity of the urine is seen, as notably in conditions of hysteria and neurasthenia, yet it is difficult to obtain definite information regarding the amount of this diminution; and to determine the exact decrease under certain conditions has been the object of this investigation, which was undertaken at the suggestion of Dr. Howard A. Kelly.

I. — During Ether An^esthetization. (See Chart I.)

The first series of experiments, twenty-five in number, were carried on in the Gynecological Operating Room of the Johns Hopkins Hospital, and were designed to study the effect of ether anaesthesia upon the urinary specific gravity. The instrument used was the ordinary urinometer, tested and found to be accurate before the commencement of the experiments. In these cases from thirty to fifty minutes usually elapsed from the beginning of the administration of the narcotic to the catheterization of the urethra and the emptying of the bladder just before the commencement of the operation. As the patients had not been catheterizated immediately preceding the anesthetization, there was presumably present in the bladder a certain quantity of urine. In most cases, however, this was very small, as either catheterization or natural voiding had taken place recently, and the urine was not in sufficient quantity to affect very materially the result.

In certain cases, however (cases VI, IX, XVIII, XXI, XXIII), the amount of urine present in the bladder was so great — as evidenced by the fact that by catheterization thirty minutes later, from two to five hundred cubic centimeters were obtained — that the comparatively small quantity secreted during anaesthesia had but little effect upon the specific gravity, and we had for examination urine differing but slightly from the normal urine of the patient, the specific gravity of which was decreased but slightly below the average of that especial case, and the color of which differed but slightly from that of normal urine.

In the remaining twenty cases, on the other hand, the quantity obtained was small, varying between thirty and one hundred cubic centimeters, probably a large part of which was secreted during the administration of the ether. In these cases the urine appeared quite differently ; the color varied from a pale straw to that of water barely tinged, and the examination of the specific gravity showed that there was a marked decrease, from 1.0177 (the average of the average specific gravities of the urines of the twenty cases taken on several occasions previous and subsequent to the operation) to 1.066, the average specific gravity of the urines after the administration of ether.

In one of the cases the specific gravity of the just catheterized specimen of urine, i. e. at the body temperature, was .999, though on being allowed to stand until it acquired the temperature of the room, at which all the specific gravities were determined, it rose to 1.002. It will thus be seen that one of the effects of ether narcosis is a marked diminution in the


urinary specific gravity, and that this is not a typical hydruria can be concluded from the fact that the quantity of urine secreted was not large, being no more than one would expect within the thirty to fifty minutes occupied in the administration of the narcotic.

From this it can be surmised that the effect of the ether upon the kidneys is to diminish markedly the secretion of the solid constituents, while the elimination of water is, in a certain number of cases at least, not so markedly affected. It is of interest, however, to note that in some cases the quantity obtainable was very small — less than ten cubic centimeters, and in these cases, evidently, water-elimination as well as solid constituent-excretion has been very much decreased. It was impossible in this investigation to draw any conclusions regarding the role played by the nervous element, as the decrease in the specific gravity was quite as marked in those who took the ether with a stoical calm as in especially neurotic patients.

II. — After Normal Salt-Solution Enemata. (iS'ee Chart II.)

The second series of experiments — ten in number — were designed to determine the effect of enemata of normal salt solution upon the specific gravity of the urine.

The method employed was as follows: the patient, immediately after voiding urine, was given five hundred cubic centimeters of normal salt solution through a rectal tube passed as far up as possible. In all bucone of the cases this quantity was easily retained and caused the patient no discomfort. The patient was not allowed to drink water or any other fluid during the next four hours, and during this period the urine passed was carefully collected. In some cases urine was voided but once, in other cases twice during the four hours, but in them all between two hundred and fifty and four hundred cubic centimeters were voided, i. e. between one-half and four-fifths of the quantity given by rectum. The specific gravity fell markedly in all cases, the average fall being .008, from 1.016, the average specific gravity of the urines of the ten cases (each taken several times previously) to 1.008, the average of the specific gravities of the urines voided within four hours from the time the enemata were given. The color of the urine in these cases was exceedingly pale. These cases are in all probability true cases of hydruria, where the diminution in specific gravity is due not to a decreased excretion of solid constituents, but to a marked increase in the elimination of water. While the first series of experiments are of more interest from a scientific standpoint, the second series, showing as they do such rapid elimination of water with decreased specific gravity, suggest the possibility of giving rectal enemata of normal salt solution or water, to increase the How of urine, and thereby jirobably to stimulate diuresis in someafTections of the kidney, and as a method of internal irrigation, as it were, in some cases of cystitis.


August, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


191


Showing the Effect of Anesthetization upon the Specific

GliAVITY of the UKINE.


Ciiae


Average sp. gr.


Sp. gr. after aui£slhesla.


HEMAKK3.


I


1.015


l.OOfi



II


1. 030


1.005



III


1.01.5


1.004



IV


1.03-J


1.007



V


1.013


1.010



VI


1.031


1.015


Very large amount of cUirk-uolorcd urine iu bladder.


VII


1.010


1.003



VIII


1.01.5


1.007



IX


1.036


1.018


Large quantity of deeply pigmented urine in bladder.


X


1,035


1.009



XI


1.033


1.003



XII


1.032


1.003



XIII


1.030


1.005



XIV


1.030


1.010



XV


1.013


1.008



XVI


1.008


1.011



XVII


1.038


1.018



XVIII


1.018


1.017


Large amount of dark-colored urine in bladder.


XIX


1.013


1.005



XX


1.018


1.005



XXI


1.033


1.031


Large amount of dark-colored urine in bladder.


XXII


1.023


1.006



XXIII


1.033


1.020


Large amount of dark-colored urine in bladder.


XXIV


1.013


1.003



XXV


1.013


1.010



Average of av.

Bp. grs. i)f the

25 oases.


Average ot Ih Bp. gr. after

aD£Bstheala o the 23 cases.




1.01852


1.00932



Average of average ap.grs.

ot all cases except VI, IX,

XVIII, XXI, XXIII.


Average of

sp. gr after

aueDsihesla u

of all cases

except VI. IX

XVin, XXI,

XXIII,




1.0177


1,00665





CHART II.


SnowiKG THE Effect op Salt-Solution Enemata upon the Specific Gravity of the Ukine.


Case.

I

II

III

IV

V

VI

VII

VIII

IX

X


sp, gr, 1.015 1.031 1.015 1.012 1.014 1.019 1.014 1.018 1,014 1.020

Average ot

average

sp. grs, of the

10 cases.


Sp. gr. ot 1st specimen

voided after enema. 1,005 1,012 1.007 1.008 1:008 1,010 1,006 1,008 1,005 1.013


Sp, gr. of 2nd

specimen voided after

1.009 1.010


1,006 1.005 1.013

1.008 1.007 1,012


Average sp. gr. Average sp, gr,

of the 1st voided of 2nd voided

specimens specimens

of the 10 cases, ot the 10 cases.


Sp, gr, of urine

voided under 4

hrs. after enema

was given.

1.007

1.011

1.007

1.007

1.006

LOll

1.006

1.008

1.006

1.012

Average sp. gr, of urine voided within 4 hrs, after giving ot enema in the 10 cases. 1,0081


CORRESPONDENCE.


HYUllAULIC PEESSUKE IN BLADDER CONTRACTURE.

To the Edilor : — It is but voicing the sentiment of the profession, I am confident, to say that all engaged in genito-urinary work are under obligations to Dr. Hugh H. Young for his exquisite study of hydraulic pressure in contracture of the bladder. (Johns Hopkins Hospital Bulletin, May, 1898.) The value of " vesical gymnastics " to overcome this distressing trouble is emphasized by Dr. Young's article in your May issue, whose perusal I, as I think all teachers of genitourinary diseases should, heartily recommend to my students.

There are, however, a few details in the article to which I must take exception.

The author employs a nozzle "somewhat similar to those devised by Janet and Valentine." The illustration shows that the nozzle is that of Janet, with two bulbs instead of one. For easy removal from the rubber tube and replacement, I have done away with the bulbs entirely ; otherwise Dr. Young's nozzle is exactly like my sharp nozzle, which serves all purposes in the majority of cases. But there are men whose meatus is too large or too small for the sharp nozzle ; for those the dome-shaped or flat-topped nozzle is required.

The author says (page 108): "Valentine's complicated nozzle and stopcock are unnecessary." It would seem from the illustration upon page 109 that a much more complicated apparatus is necessary.

I assume that the author has been imposed ujiou by some unscrupulous manufacturer, who palmed off an alleged "Valentine Irrigator" for the simple device whose description appears in the Medical Record for April 16th, 1898, and which I had the honor of first demonstrating at the Hospital Necker (Paris) on September 15th, 1897. The principal advantages of this apparatus are :

1. That it requires no change of elevation for irrigating the anterior urethra, the posterior urethra and the bladder ;

2. The variations in hydraulic pressure are easily procured by a slight motion of the operator's thumb ;

3. Nearly every patient can be irrigated while sitting on a chair; most can urinate without rising, while Dr. Young's apparatus required that the patients are irrigated while lying down. This entails getting from the table and clambering up again for a second or third irrigation;

4. Greater cleanliness, for the simple metal shield which is part of the stop-cock catches the fluid that spurts from the urethra and diverts it into the basin held by the patient. Neither the penis, scrotum or nates of the patient, nor the operator's fingers, save the third and fourth of his left hand, are even moistened by an irrigation.

Still, I must agree with the author that no apparatus beyond a rubber tube is necessary for urethral or intravesical irrigations, provided the ojierator has the skill which experience gives, to wash the urethra and fill the bladder without even the aid of a nozzle. Yet for convenience and cleanliness, as well as for economy, the majority of the profession use the irrigator I devised.


192


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 89.


I am iirepiiring .i new article on urethral and intravesical irrigations, in which I sliall endeavor to more fully set fortli the ideas suggested above. Very trnly yours,

Fer)). 0. Valentine, 242 West 43rd Street, New York.

[In reply to Dr. Valentine, I will simply state that although I had the nozzle in question made several years ago, long before I saw the subsequent publications of himself and Janet, I lay no special claim to it, considering it simply a modilication of Dr. Ilalsted's nozzle, which was brought out by him twelve years ago.


We frequently irrigate the bladder without placing the patient on the operating tables, which are pictured iu the Bulletin, and no apparatus could be simpler than a glass percolator suspended on a pulley, which we use and which costs exactly 75 cents for the whole outfit.

The tank of sterile warm water is a "complication " which we deem very important where asepsis is to be practiced. The fact that cystitis has more than once been inaugurated by careless technique in giving bladder irrigations Avith weak antiseptics during gonorrhoea is sufficient justification for the greatest care. Hugh H. Young.]


PROCEEDINGS OF SOCIETIES,


THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.


Cocaine Aiiicstlicsia in the Treatment of Certain Cases of Hernia and in Operations for Thyroid Tumors. — Dr.

Harvey W. Gushing.

The following cases illustrate the great benefit which the use of cocaine affords the operator in dealing with certain conditions when the administration of a general anesthetic is contraindicated.

Operative interference is oftentimes considered inadvisable in cases of hernia occurring in old people who may be suffering from chronic bronchitis, or in whom pronounced cardiovascular changes render the administration of ether dangerous.

Case I. Tliis patient is 67 years of age. He has had a large right inguinal hernia for 10 years, wliich was not controlled by a truss and wliich of late has frequently become incarcerated. He is suffering from chronic broncliitis and emphysema, which possibly had been responsible for the recent increase in size of the hernia and the attacks of incarceration. His radial arteries, as you may see, are tortuous and calcified, and there is a systolic murmur at the apex transmitted to the axilla. Two weeks ago to-day the liernia was operated on by the usual Halsted method, but under local anaesthesia. The patient suffered little pain and was sent back to the ward to have his dinner. This is the first dressing. The wound under the silver foil has healed, leaving only a fine linear cicatrix.

Had it not been possible to make use of a local anaesthetic in this case an operation would hardly have been deemed advisable. It is a great relief to the operator to be free from the responsibilities connected not only with the administration of a general anaesthetic to an aged person, but also with the recovery therefrom. In all of these cases a preliminary hypodermic of morphia has been given. The skin at the proposed site of incision has been infiltrated with a weak Schleich's solution. Practically no further cocainization was necessary, which was fortunate, as the infiltration method is hardly applicable to the deeper structures. The patient suffered little pain, and then only during the ligation of vessels, when the internal oblique muscle was divided and when the deep silver mattress sutures were drawn up and tightened. The sac seems to have no sensory nerves worth considering, and it is well


recognized that handling a non-inflamed bowel is free from subjective sensation on the part of the patient.

There is another condition of hernia in which the administration of a general anaesthetic is attended with risk. Patients with strangulated hernia are often in such a state of shock that one dreads the effect of etherization, especially when, as is not uncommon in these conditions, vomiting is a prominent feature. The speaker had an unfortunate experience a few months ago with such a case. The patient, an old blind syphilitic with a strangulation of twenty-four hours' duration, died under ether shortly after reaching the operating table. The autopsy revealed a gumma occupying each occipital lobe and advanced arterio-sclerosis. A cocaine operation would doubtless have been free from danger. Furthermore, in these cases it is almost impossible to foretell the condition of the strangulated bowel. The experience at this hospital seems to have been that in cases where resection and intestinal suture is found to be necessary, an immediate anastomosis is attended with a very high mortality. The cases which have recovered are largely those in which an immediate fecal fistula has been established. The fistula may be closed some weeks later, when the patient's condition will enable him to stand an operation for intestinal suture better than when suffering from the shock of complete strangulation. Undet cocaine ausesthesia it is a simple matter to open the sac and divide the constriction, and if the strangulated bowel is no longer viable the establishment of a fistula is a simple procedure. If the condition of the bowel allows of reduction, it is possible at times to complete the operation for radical cure at the time. If the patient's condition prohibits this, the external wound may be closed and a subsequent careful herniotomy performed under general anesthesia.

Case II. This patient is 6.3 years of age. He liad a large liernia for 30 years, which under a sudden muscular effort passed liis truss and could not be reduced. lie entered tlie l)OSi:ital 34 hours later, distended, vomiting and in considerable shock. Obstipation was complete. There was a large tender tumor the size of two fists occupying tlie left groin and scrotum. Tlie patient was given stimulants and morphia, and under cocaine ana-sthesia the contents of the sac were liberated, proved viable and reduced. The sac was very thick, adherent, and was excised with some (iifficutty. The surrounding tissues were so indurated that little attempt was


August, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


193


maile to ilo more than roughly close the wound. There was iriimediate relief to all symptoms. He returned three weeks ago to have his hernia on the opposite side operated on, and at that time a more perfect plastic was made at the original site wliere there was evidently some wealmess of the wall.

Case III. This colored man entered the hospital ten days ago with a six-hour strangulation. He was in great pain, vomiting and hiccoughing, with a tender pyriform tumor, the size of a fist, in the left groin. He was given morphia, and under cocaine the sac was opened, the constriction divided and a large daik loop of bowel proved viable and reduced. The patient's racial characteristics would not allow of further proceJure, and as his condition was good, under primary chloroform anfesthesia the usual operation for radical cure was completed. This is his first dressing.

I was recently called upon to operate alone iu the country for a strangulated femoral hernia of three days' duration in a rather feeble woman. The cocaine anaesthesia was most satisfactory, not only for operative purposes, but because the patient could be left alone without waiting for an ether recovery and feeding could be immediately begun.

There is another operation which is often attended with great risk, due to a general aiiajsthetization. That is thyroidectomy. Patients with enlarged thyroids proverbially take ether badly. The resultant cyanosis makes the operative field a bloody one, and a clean dissection is difficult. Furthermore, as Kocher pointed out in his original paper (Ueber Kropfe.xtirpation und ihre Folgen, Archiv f. klin. Chir., Bd. XXIX, 1883), the tracheas of these patients are often distorted and flattened, so that manipulations of the tumor may completely obstruct respiration by flattening out the already narrow passage. A case was lost at this hospital a year ago from this very cause. A large goitre, when almost enucleated, was lifted partially from its bed, when respiration immediately ceased and all attempts to relieve the pressure and resuscitate the patient were unavailing. A few months ago the speaker had an unpleasant experience while operating upon an Irish setter for the removal of a large hemorrhagic cyst of the thyroid such as Bradley has lately described (.Journal of Experimental Medicine, Vol. I, 1896). The animal took ether very badly, the operative field was very bloody, and respiration several times was seriously impeded. On removing the tumor the trachea was found very greatly flattened and pushed far from the median line.

Case IV. This man is 44 years of age. He has had a tumor of the thyroid tor ten years, which lately had begun to embarrass his respiration so that he was unable to work. The left half of the thyroid with the tumor was removed a month ago. Shortly before the operation a quarter of a grain of morphia was given. The skin alone was anesthetized, and the lobe of the thyroid was enucleated in the layer of reticular tissue just outsiileof that occupied by the large veins to the gland, so that comparatively few and only the large branches at some distance from the gland had to be ligated. The operation was practically bloodless. The large veins, many the size of a pencil, were divided between ligatures. The tying of these ligatures was the only thing which caused the patient pain. Manipulation of the tumor would frequently emliarrass his respiration, but he would always give warning of this dyspnrea so that the method of attack could be changed. His chief complaint was of a smothered feeling, so that he had to be constantly fanned and given water to drink. The advantage of a dry and bloodless field was demonstrated at the end of the operation, when the recurrent laryngeal nerve was seen


arching up through the last bit of tissue which held the tumor. Had the tissue been blood-stained it would doubtless have been divided. The trachea was quite flattened out and could be readily occluded by slight pressure between the fingers. His recovery was uneventful.

X Word of Warning as to the ludiscriininate Use of Cocaine in the Treatment of Diseases of the Eye.— Dr.

Theobald.

I shall not present a paper, but merely make some observations, which seem to me not untimely, in regard to the iudiscriminate use of cocaine in the treatment of diseases of the eye. It has come to be quite common for the general practitioner to use cocaine in eye inflammations, the inducement being that it diminishes the pain temporarily and so causes a measure of relief. The conditions in which it is used are various. I have met with many instances in which it was prescribed in simple catarrhal conjunctivitis. There seems to be no indication for its employment under such circumstances, and it is capable of doing much more harm than good, as I shall show by the history of several cases.

Because of its pronounced disturbing effect upon the nutrition of the cornea, cocaine is not a remedy to be used carelessly in eye diseases. It acts, as you know, through the sympathetic nerves, or chiefly in that way, and besides anajsthetizing the eye, it dries the cornea to a remarkable degree. Some authorities say this drying is due to the fact that, as the sensibility of the cornea is annulled, winking does not take place as usual, and so the cornea is not moistened by the action of the lids; but I am sure that this is not the correct explanation. For I have observed that, although the eye be kept closed during the application of cocaine (a precaution which is now usually taken), the cornea will sometimes become quite dry and lose its lustre very soon after the speculum is introduced. This never occurred in the days before we used cocaine, so I think there can be no doubt that the drying does not depend upon the mere lack of winking the lids, but is due to a marked disturbance of the corneal nutrition. Probably the contraction of the vessels of the conjunctiva, and possibly some more direct action of the cocaine upon the lymph spaces of the cornea, disturbs its normal supply of fluids. The result is that the cornea not only becomes dry, but the epithelium becomes loosened, so that it is easily rubbed off, sometimes by the friction of the lids, or from the slightest touch of the instruments being used. Any agent that has so marked an eft'ect as this upon the nourishment of the cornea certainly seems not to be a safe one to use, unless there is a clear indication for its employment.

The field of usefulness for cocaine, apart from its anfesthetic action, is extremely lin)ited. I scarcely think, indeed, there is any occasion to prescribe it as a remedy in eye diseases, though it may be used sometimes to increase the action of other drugs ; for instance, atropia, or homatropia, will dilate the pupil more quickly and powerfully if combined with cocaine. Even here 1 prefer to keep the solutions separate, and to instill the cocaine first and then the atropia. It is also useful as preliminary to the application of astringents or caustics, like the sulphate of copper or nitrate of silver, as it greatly lessens the discomfort, but this is only another phase of its anaesthetic action.


194


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 89.


I have picked out one or two rather striking examples of what may happen from its use in some of the conditions I have alluded to.

Case 1. Mr. H. had an acute catarrhal conjunctivitis. A 4 per cent, solution of cocaine had been prescribed for him, to be used every hour. After each instillation there had been a period of comfort, though the discomfort was not great previously; but after he had used the cocaine in this manner for some days he came to me with the central part of the cornea steamy and the epithelium considerably roughened. The nerve endings were thus exposed, and as soon as the temporary effect of each apj)lication of the cocaine had worn off he felt a great deal of pain and experienced much photophobia. It was simply a case of catarrhal conjunctivitis, and this unusual condition of the cornea was solely the result of the use of cocaine.

Ordinarily one would prescribe for such a conjunctivitis a weak solution of sulphate of zinc and boracic acid, but here we had to use atropia until the irritation of the cornea had ceased and tlien give boracic acid. After two or three days of such treatment I heard from him that the eye was rapidly improving.

Case 2. This case occurred only a few weeks ago. A school teacher had a catarrhal conjunctivitis which had lasted about four weeks. She had been using a solution of cocaine in rose water. The eyes were quite irritable and a conjunctivitis that should have gotten well in a very short time was getting worse, and might have persisted indefinitely under this treatment. I prescribed a lotion of opium to be applied over the lids, and a solution of sulphate of zinc and boracic acid to be dropped into the eyes, and iu a few days she was well.

Case 3. A few days since I had another case, an acute inflammatory glaucoma, where the chief reliance had been placed on the use of cocaine. Temporary relief had been gained, but of course it had no remedial effect whatever, and its use was unfortunate because the physician was placing reliance upon something that had no effect other than to lessen the pain for a time.

I have thought it worth while to report these typical cases, because I am sure that it is getting to be a very common thing for the general practitioner to prescribe cocaine indiscriminately in eye diseases, and, as I feel that its field of usefulness is so limited, a word of warning upon this point seemed to me not amiss.

On the Pathology of Fragmeutatio Myocardil and Myocarditis Fibrosa.* — John Bruce MacCallum. The normal adult heart muscle consists of rliomboidal branching cells whose protoplasm is made up of fibril bundles separated by sarcoplasm. The fibril bundles possess a narrow striation called Krause's membrane, and a broader one known as Briicke's line. The sarcoplasm is divided into compartments or discs, whose horizontal boundaries are continuous with the narrow striations on the fibril bundles. These compartments have been called sarcoplasmic discs. Tlie proto


Synopsis of a paper read before the Johns Hopkins Hospital Medical vSociety, to be published in full in the Journal of Experimental Medicine.


plasm of the cell then consists of a definite network made up of the fibril bundles and the membranes bounding the sarcoplasmic discs. • The earliest stage in the development of the cell shows an irregular network in the protoplasm. This tends to become more regular, giving rise to disc-like meshes. Some of these break up into smaller ones, and in the angles between them there is an accumulation or a differentiation of the substance of the network, giving rise to longitudinally disposed masses which become the fibril bundles. The discs left are the sarcoplasmic discs. This formation of fibril bundles takes place first at the periphery of the cell, so that the bundles last formed are those nearest the centre of the cell. It is thus probable that the network spoken of in the adult fibre is derived directly from the primitive network of the embryonic cell.

In the extended condition the structure of the fibre is somewhat different from that described. The cells are narrow; the Krause's membranes are further apart ; the fibril bundles themselves are closer together; and the Briicke's lines are much more consjiicuous tlian in the contracted muscle. These and some additional minor diflerences make it easy to recognize an extended fibre.

Fragmentatio Mi/ocardii. In all severe cases of fragmentation there is an uneven extension and contraction of the fibres. Two adjacent cells may be in the states of extension and contraction respectively. Often on following a contracted fibre down to the cement line, one finds the cell on the other side of the cement line extended. This condition is often jiresentalso in the same cell, that is, one part of a cell may be extended, while another part is contracted. The breaks which accompany this condition may take place in the body of the cell or iu the cement line. In tiie cell body the lesion is more severe in extended than in contracted muscle.

In addition to these simple breaks tliere is a definite degenerative process which leads to the disintegration of the part affected, and a consequent fragmentation of the fibre. The initial stage in this process is an extreme extension of the fibre. Following this there are irregularities produced iu the rows of striations, and changes in the relation of the sarcoplasm to the fibril bundles. This irregularity increases until no definite arrangement of the fibril bundles can be made out. The fragments of the fibril bundles then gradually disappear. There is finally a complete disintegration of the part and a breaking of the fibre. For this process I propose the name sarcolytic degeneration.

Tlie exact relation between this degeneration and the simple fragmentation is not clear. They occur together and are obviously closely related. The simple breaks do not difler from those produced mechanically. The degenerative fragmentation, however, seems to be a gradual process. It was found in practically all the cases examined, and was the most conspicuous lesion in each instance. Such a wide process of disintegration must throw much of the muscle out of function, and the extra work must be done by the remaining normal muscle. It is conceivable that this unusual strain might cause iu the otherwise normal muscle such simjile breaks as those described. If this be true the main lesion in fragmentation is the sarcolytic degeneration, while the simple breaks in the various


August, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


195


locations are the mechanical results of the unusual strain thrown on the muscle which remains undegenerated.

Myocarditis Fibrosa. In fibrous myocarditis the disappearance of muscle takes place by atrophy and degeneration of the cells. This degeneration is brought about by a definite process, which may be described m brief as follows : There is at first a marked increase in the undifferentiated sarcoplasm in the centre of the cell, accompanied by a disappearance of the fibril bundles there. This disappearance of fibril bundles increases until there is left only a single row around the periphery of the cell. These are gradually lost, and only the sarcoplasmic discs remain. The cell at the same time becomes small and somewhat spindle-shaped, and finally disintegrates entirely.

This process is interesting in connection with the histogenesis of the cell. The fibril bundles are formed first at the periphery of the cell, and develop towards the centre, so that those which are formed last are nearest the centre of the cell. As described above, however, it is these centrally placed fibril bundles which are the first to disappear. The degeneration proceeds from the centre out (centrifugally), while the development has occurred from the periphery in (centripetally). The earliest stage in the development is a sjiindle-shaped cell with simjjle sarcoplasmic discs, while the latest stage in the degeneration could be described in the same words. The process of degeneration is thus approximately a reversal of the process of development. The first structures formed are the last to degenerate, and the last to develop are the first to disappear.


NOTES ON NEW BOOKS.

Alias of Legal Medicine. By De. E. von Hofmanx, Professor of Legal Medicine at Vienna. Authorized Translation. Edited by Frederick Peterson, M. D., and Ai.oysius Kelly, i\L D. ( IK B. Saunders, Philadelphia, 1S98.)

The first impression obtained in glancing over the highly colored lithograpljs of suicides and murders is tliat one has entered the "chamber of horrors," at Madame Tussaud's. A deeper insight shows more clearly the real value of the work from a scientific and medico-legal standpoint.

The first section, comprising malformations of the external organs of generation may be passed without comment, as similar pictures are to be found in a number of text-books on special departments of medicine.

Next in order follow the plates of various hymens, virginal and deflorated, the appearance of the os uteri, normal and pathological, uteri in the earliest stages of pregnancy, the lesions following instrumental and other forms of abortion, pictures of the degree of ossification of the epiphyses of the bones of full term and immature foetuses, and the lungs of new-born infants. A very large and interesting section is devoted to illustrations of injuries of the skull bones, the hole fractures, so frequently met, claiming especial attention. Injuries of the lungs, brain and intestines are depicted in colored plates.

Injuries to the body inflicted in suicidal or murderous attempts, punctured wounds of the stomach, intestine and skull by different instruments, together with plates of. gunshot wounds, occupy a considerable space.

Colored illustrations of suicides by hanging, burning, and other lethal means, the appearance of the body after several days' suspension by the neck, and the distribution of the hypostases and the appearance of the skin after long immersion in water, are all reproduced.

The best section of the book, as well as the one having the best plates, is devoted to the pathological conditions of the organs fol


lowing intentional or accidental ingestion of the irritant poisons, concentrated and dilute acids, corrosive sublimate, caustic potash, potassium cyanide, arsenic and phosphorus. The gross pathological appearances of the stomach, liver, intestines and kidneys are faithfully depicted in natural colors, and this section is one of the most useful of the work.

The illustrations throughout the book are rather unequal in merit, and a number could have been omitted without detriment. The description of the plates and figures is freer from the idioms of the original language, than is ordinarily found in translations, and marks the careful supervision of the editors. H. J.

Report on Bubonic Plague : Being a report based upon observations on 939 cases of Bubonic Plagup, treated at the Municipal Hospital for Infectious Diseases, at Arthur Road, Bombav, from September 24, ]896. to February L'8, 1897. By Khan Bahahur N. H. Choksv. Extra Assistant Health Officer, Bombay Municipality. {Reprint : Bombay , ISi'dl .)

Choksy's observations give us a clear and comprehensive idea of the nature of the fearful scourge that visited western India in 1896-7, and recurred with even greater violence in 1897-8.

Apart from the difficulties of properly caring for the patients brought to the hospital, the staff had to contend against the prevalent superstition in the minds of the patients' friends, who circulated rumors to the effect that patients were killed, their hearts removed and sent to the Queen in order to appease lier wrath at the disfigurement of her statue in the city. A raid was finally made on the hospital by 1000 mill hands, who desired vengeance for the alleged killing. Several of the staff and patients were injured by stones thrown, and the mob was dispersed only after police interference. The death rate in the 939 cases observed was 73.26 per cent., or, excluding those who were brought in a moribund condition, 60.34 per cent. Mr. Choksy notes that the death rate was lower among the meat-eating patients than among the vegetarians. The clinical report is the most interesting and is very complete. Three types of the disease were found to be the most prevalent : (a) Pestis Simplex, (b) Pestis Septica (in which the blood is affected with the plague bacillus), (c) Pestis Pulmonalis, in which the lungs are primarily affected. This was at once the most insidious as well as the most infectious and the most fatal form of the plague. In Aoyoma's report of the Hongkong Plague (see J. H. Hospital Bulletin, Sept., 1896) but one case of pneumonia, as a complication, was recorded, while in Bombay it was of frequent occurrence, the most distressing symptom being dyspno;a, due to cedema of the lungs. In further contrast to the report of Aoyoma, Mr. Choksy's observations indicate that not more than 5 per cent, of the patients showed evidence of infection through breach of surface, in spite of the fact that most of the patients were accustomed to going barefooted and had many cracks in the soles of their feet. Pus from incised buboes, the sputum, and inspiration, are noted as methods of infection.

Almost every patient showed the iypicaX fades pestica, a peculiar look of fright or sadness, which, togetlier with the hesitating speech usually observed in plague patients, formed an important means of diagnosis.

55 (48 per cent.) of tlie buboes were in the femoral or femoroinguinal regions, and in connection with theseglandular swellings, lymphangitis was frequently observed. In the Hongkong epidemic, Aoyoma reports that this was a rare complication.

Choksy declares that " in no other disease is the disproportion in the normal ratio between pulse, temperature, and respiration so divergent." For instance, with a temperature of 105° the extremities miglit be icy cold, the pulse very quick, and so weak that it was often scarcely perceptible. Aoyoma, on the other hand, noted that plague patients usually showed a pulse of good volume. Serum therapy does not seem to have been very effective. Yersin's curative serum Choksy regards as having been a failure, and Dr. HafEkin's as only partially successful. Dr. Lustig's serum, however, gave good results in the few cases where it was tried, although the routine treatment of the hospital was always continued.

Fifty-four autopsies are reported, each case showing bfemorrhages in every conceivable and inconceivable part of the body.

A complete set of typical temperature, pulse and respiration charts is appended to the report.


196 JOHNS HOPKINS HOSPITAL BULLETIN. [No. 89.

THE JOHNS HOPKINS MEDICAL SCHOOL. SESSION 1898-1899.

FACULTY.

Daniel C. Oilman, LL. D., President. William W. Russrll, M. D., Associate in Gynecology.

William H. Welch, iM. D., LL. D , Dean and Piofcssor of Pathology. Hfnky J. Beeklhv, M D., Associate in Neuropathology.

Ira Remsen, M. D., Ph. D , LL. D., Professor of Chemistry. J. Williams Lord, M. D., Clinical Professor of Dermatology and Instructor in Analomv.

William Osler, M. D., LL. D., F. R. C. P., Professor of the Principles and Practice of T.Caspar (.ilchkist, M. R C. S., Clinical Professor of Dermatology

Medicine. Rorekt L. Randolph, M. D., Associate in Ophihalmology and OtolcEV.

Hfnkv M. Hl'RD, U. U., LL. D., Professor of Psychialry. Thomas B. Futcher, M. B., Associate in Medicine.

William S. Halsteii. M. D., Professor of Surgery. Jcshph C. Blooiigooi>, M. D., Associate in Surgery.

Howard A. Kbllv, M. D., Professor of Gynecology and Obstetrics. Thomas S Chllen, M. B., Associate in Gynecology.

Franklin F. Mall, M D., Professor of Anatomy. Ross G. Harrison, Ph. D., Associate in Anatomy.

John J. Abel, ^L U., Professor of Pharmacology. Rn.D Hunt, Ph. D., M. D., Associate in Pharmacology.

William H. Howell, Ph. D., M. D., Professor of Physiology. • Frank R. Smith, M. D., Instructor in Medicine.

WiLLiAvi K. Brocks, Ph. D., LL D., Professor of Comparative Anatomy and Zoology. (;eorgk W. Dobbin, M. D., Assistant in Obstetrics.

John S. Billings, M. D., LL D., Lecturer on the History and Literature of Medicine. Waltrr Jones, Ph. D., Assistant in Physiological Chemistry and Toxicology.

Alexander C. Abboti, M. D., Lecrurer on Hygiene. SvDNEV M. Cone, M. D.. Assistant in Surgical Pathology.

Charles Wardbll S i iles. Ph. D,, M. S.. Lecturer on Medical Zoology. Harvev W. Cushing, M. D., Assistant in Surgery.

RoiiERT Fletcher, M D , M. R. C. S., Eng., Lecturer on Forensic Medicine. Hrnrv IIarton Jacobs, M. D., Instructor in Medicine.

William D. Booker, M. D., Clinical Profes-or of Diseases of Children. Hugh H. Y..ung, M. D,, Instructor in Genito-Urinary Diseases.

Iohn N, Mackfnzie, M. D., Clinical frofessor of Laryngology and Rhinology. Charles R. Bardeen, M D., Assistant in Anatomy.

Samuel Theobald, M. D., Clinical Professor of Ophthalmology and Otology. Stewart Paton, M. D., Assistant in Nervous Diseases.

HsNRV M. Thomas, M. D., Clincal Professor of Diseases of the Nervous System. Norman McL. Harris, M. B., Assistant in Bacteriology.

Simon FLEXNfR, M. D., Associate Proscssor of Pathology. Aibert C. Crawford, M. D., Assistant in Pharmacology.

J. Whitridce Williams, M. D., Associate Professor of Obstetrics. J. W. Lazear, M. D., Assistant in Clinical Microscopy.

Lewellvs F. Barker, M. B , Associate Professor of Anatomy. Henry O. Reik, M. D., Assistant in Ophthalmology and Otology.

William S. Thayer, M. D., Associate Professor of Medicine. Elizabeth Hukdon, M. D., Assistant in Gynecology.

John M. T. Finnbv. M. D., Associate Professor of Surgery. Walter S. Davis, M. D., Assistant in Clinical Microscopy.

George P. Drbvek, Ph. D., Associate in Physiology. ]. L. Walz, Ph. G., Assistant in Pharmacy.

GENERAL STATEMENT.

The Medical Department of the Johns Hopkins University was opened for the instruction of students October, 1893. This School of Medicine is an integral and coordinate part of the Johns Hopkins University, and it also derives great advantages from its close affiliation with the Johns Hopkins Hospital.

The required period of study for the degree of Doctor of Medicine is four years. The academic year begins on the first of October and ends the middle of June, with short recesses at Christmas and Easter.

Men and women are admitted upon the same terms.

In the methods of instruction especial emphasis is laid upon practical work in the Laboratories and in the Dispensary and Wards of the Hospital. While the aim of the School is primarily to train practitioners of medicine and surgery, it is recognized that the medical art should rest upon a suitable preliminary education and upon thorough training in the medical sciences. The first two years of the course are devoted mainly to practical work, combined with demonstrations, recitations and, when deemed necessary, lectures, in the Laboratories of Anatomy, Physiology, Physiological Chemistry, Pharmacology and Toxicology, Pathology and Bacteriology. During the last two years the student is given abundant opportunity for the personal study of cases of disease, his time being spent largely in the Hospital Wards and Dispensary and in the Clinical Laboratories. Especially advantageous for thorough clinical training are the arrangements by which the students, divided into groups, engage in practical work in the Dispensary, and throughout the fourth year serve as clinical clerks and surgical dressers in the wards of the Hospital.

REQUIREMENTS FOR ADMISSION.

As candidates for the degree of Doctor of Medicine the school receives :

1. Those who have satisfactorily completed the Chemical-Biological course which leads to the A. B. degree in this university.

2. Graduates of approved colleges or scientific schools who can furnish evidence : (a) That they have acquaintance with Latin and a good reading knowledge of French and German ; (6) That they have such knowledge of physics, chemistry, and biology as is imparted by the regular minor courses given in these subjects in this university.

The phrase "a minor course," as here employed, means a course that requires a year for its completion. In physics, four class-room exercises and three hours a week in the laboratory are required; in chemistry and biology, four class-room exercises and five hours a week in the laboratory in each subject.

3. Those who give evidence by examination that they possess the general education implied by a degree in arts or in science from an approved college or scientific school, and the knowledge of French, German, Latin, physics, chemistry, and biology above indicated.

Applicants for admission will receive blanks to be filled out relating to their previous courses of study.

They are required to furnish certificates from officers of the colleges or scientific schools where they have studied, as to the courses pursued in physics, chemistry, and biology. If such certificates are satisfactory, no examination in these subjects will be required from those who possess a degree in arts or science from an approved college or scientific school.

Candidates who have not received a degree in arts or in science from an approved college or scientific school, will be required (1) to pass, at the beginning of the session in October, the matriculation examination for admission to the collegiate department of file Johns Hopkins University, (2) then to pass examinations equivalent to those taken by students completing the Chemical-Biological course which leads to the A. B.' degree in this University, and (3) to furnish satisfactory certificates that they have had the requisite laboratory training as specified above. It is expected that only in very rare instances will applicants who do not possess a degree in arts or science be able to meet these requirements for admission.

Hearers and special workers, not candidates for a degree, will be received at the discretion of the Faculty.

ADMISSION TO' ADVANCED STANDING. Applicants for admission to advanced standing must furnish evidence (1) that the foregoiug terms of admission as regards preliminary training have been tulfllled, (2) that courses equivalent In kind and amount to those given here, preceding that year of the course for admission to which application is made, have been satisfactorily completed, and (3i must pass examinations at the beginning of the session in October in all the subjects that have been already pursued by the class to which admlssiou is sought. Certificates of standing elsewhere cannot be accepted In place of these examluations.

SPECIAL COURSES FOR GRADUATES IN MEDICINE.

Since the opening of the Johns Hopkins Hospital in 1880, courses of iustrnction have been otTered to graduates in medicine. The attendance upon these cotirses lias steadily increased with each succeeding year and indicates gratifying appreciation of the special advantages here afforded. With the completed organization of the Medical School, it was found necessary to give the courses intended especially for physicians at a later period of the academic year than that hitherto selected. It is, however, believed that the period now chosen for this purpose is more convenient for the majority of those desiring to take the courses than the former one. The special courses of instruction for graduates in medicine are now given annually during the months of May and June. During April there is a preliminary course in Normal Histology. These courses are in Pathology, Bacteriology, Clinical Microscopy, general Medicine, Surgery, Gynecology, Dermatology, Diseases of Children, Diseases of the Nervous System, Genito-Urinary Diseases, Laryngology and Rhinology, and Ophthalmology and Otology. The instruction is intended to meet the requirements of practitioners of medicine, and is almost wholly of a practical character. It includes laboratory courses, demonstrations, bedside teaching, and clinical instruction in the wards, dispensary, amphitheatre, and operating rooms of the Hospital. These courses are open to those who have taken a medical degree and who give evidence satisfactory to the several instructors that they are prepared to profit by the opportunities here offered. The number of students who can be accommodated in some of the practical courses is necessarily limited. For these the places are assigned according to the date of application.

The Annual Announcement and Catalogue will be sent upon application. Inquiries should be addressed to the

REGISTRAR OF THE JOHNS HOPKINS MEDICAL SCHOOL, BALTIMORE.

The Johns Hopkins Hospital Bulletins are issued montJily. They are printed by THE FRIEDENWALD CO., Baltimore. Single copies may be procured from Messrs. CUSHINQ & CO. and the BALTIMORE NEWS COMPANY, Baltimore. Subscriptions, $1.00 a year, may bt addressed to the publishers, THE JOHNS HOPKINS PUESS, BALTIMORE; single copies will be sent by rnail for fifteen cents each.


BULLETIN


OF


THE JOHNS HOPKINS HOSPITAL.


Vol. IX.- No. 90-91.]


BALTIMORE. SEPTEMBER-OCTOBER, 1898.


[Price, 30 Cents.


Contents

  • Development of the Human Intestine and its Position in the Adult. By Franklin P. Mall, 197
  • On the Histoaenesis of the Striated Muscle Fibre, and the Growth of the Human Sartorius Muscle. By John Bruce MacCallum 208
  • Further Observations on the Chemical Nature of the Active Principle of the Suprarenal Capsule. By John J. Abrl, M.D. 215
  • The Lobule of the Spleen. By Franklin P. Mall, 218
  • The Development of the Bile-Capillaries as Revealed by Golgi's Method. By William F. Hendrickson, 220
  • A Study of the Musculature of the Entire Extra-Hepatic Biliary System, including that of the Duodenal Portion of the Common Bile-duct and of the Sphincter. By William F. HENDRICKiSON, 221
  • Development of the Internal Mammary and Deep Epigastric Arteries in Man. By Franklin P. Mall, 232
  • Two Instances in which the Musculus Sternalis Existed. — One Associated with other Anomalies. By Henry A. Christian, 235
  • On the Pathological Changes in the Spinal Cord in a Case of Pott's Disease. By Sylvan Rosenheim, 240
  • The Treatment of Otomycosis by the InsufHation of Boracic Acid and Oxide of Zinc. By Samuel Theobald, M. D., - 251
  • Books Received, 252


DEVELOPMENT OF THE HUMAN INTESTINE AND ITS POSITION IN THE ADULT

Mall FP. Development of the human intestine and its position in the adult. (1898) Johns Hopkins Hospital Bulletin 9: 197-208.


By Franklin P. Mall, Professor of Anatomy, Johns Hopkins University.


Our knowledge of the early development of the human intestine is very complete, and at first thought it seems impossible to contribute anything new to it ; yet, when we consider the topographical anatomy of the adult intestine, we are struck by the fact that there is dispute regarding the position of its various parts, and nothing is known about the development of its convolutions.

The aim in this study has been to follow the successive stages of the development of the human intestine, loop by loop, from the simplest form in the embryo to the adult. As a result, it has been found that the various loops of the adult intestine, as well as their position, are already marked in embryos of five weeks, and that the position of the convolutions in the adult is as definite as the convolutions of the brain.

The present study is closely associated with one recently published upon the development of the human coelom, and the embryos here described were also published in part at that time.f In that paper the shifting of the viscera was emphasized in connection with the development of the coelom, while in this paper only the convolutions of the intestine are considered.


•This paper has appeared in German in the Festschrift fur Professor Wilhelm His zum 22. October, 1897, Archiv fur Anatomie, Supplement-Band, 1897.

f Mall, Journal of Morphology, vols. 12 and 14.


The set of specimens in my possession is fairly complete, as all the important stages are represented. It is self-evident that a subject like this can be studied only by resorting to models, as a simple comparison of sections gives no opportunity to study the loops. A number of important stages were selected aud modeled according to the method of Born. A list of these embryos is given in the accompanying table : Table op Embryos Modeled. Lengtb in mm.


No.


V. B.


N. B.


of Model.



From Whom Obtained.


XII


3.1


1.0


100.


Dr.


Ellis, Elkton, Md.


II


3.


7.


67.


Dr.


C. O. Miller, Baltimore.


IX


17.


14.


.50.


Dr.


Eyclesheimer, Chicago.


X


34.


30.


3.5.


Dr.


W. S. Miller, Madisou, Wis.


VI


34.



3.5.


Dr.


C. O. Miller, Baltimore.


XLV


3S.


10.


35.


Dr.


Douglas, Nashville, Tenn.


XXXIV


80.


60.


10.


Dr.


Ellis, Elkton, Md.


XLVIIl


130.


110.


10.


Dr.


Wilson, Worcester, Mass.


These models were then compared with one another, in order to follow the growth of the loops from stage to stage, using as guides the outline of the intestines in the sections and the blood-vessels, as well as the dissections of other embryos and those of the adult.

The loops which appeared to be homologous in the various models were next painted with the successive colors of the spectrum, beginning with the duodenum, and ending with the


198


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 90-91.


csecum. In this way, loops whose position were at first obscure, were finally found to have meaning. It is noteworthy that the successive stages in the development fit into one another accurately, showing that the first loops in the embryo are destined to form certain loops in the adult, and that this primary folding is in no way a haphazard process.

EARLY FORMATION OF THE ALIMENTARY CANAL.

The observations, upon the human embryo, of the first formation of the alimentary canal from the entoderm have now been extended to the very earliest stages.* In Graf Spec's embryo v. H. the entoderm lines the wh ^le of the umbilical vesicle, and is in no way incorporated within the body of the future embryo. In fact, its plane is curved away from the entoderm, and is just the reverse of its direction in a later


The next older stage is found in Graf Spec's embryo Gle, in which there is shown the beginning of the fore-gut. These two stages, given by Graf Spee, are the important ones to make our knowledge of the develojiment of the alimentary canal complete, and from them we can easily follow thi'ough the successive stages until the adult form is reached.

After Graf Spee's embryo Gle, we have next to observe the constriction of the umbilical vesicle from the entoderm. The beginning of this constriction is already well marked in Kollmann'sf embryo Bulle, my embyro No. XII, J and His's§ embryos SR and Lg. Unfortunately, we have no data regarding the extent of the alimentary canal in Kollmanu's embryo Bulle, nor His's embryo SR. My embryo XII, however, is of about the same stage as the other two, and it has been cut into sections which are about perfect. The history of this embryo, as well as its coelom, have been described by me recently, so I need not repeat them at this time.

EMBRYO No. XII. (2.1 mm. LONG).

The Figures 1 and 2, on Plate I, give the external form of the embryo, as well as the extent of the alimentary canal, which was taken from a reconstruction. The entoderm is already divided into fore-gut, mid-gut, and hind-gut. The fore-gut marks the pharynx, from which there are four diverticula on the dorsal side ( Br', Br"), one on the ventral side (T), and two near the mouth ( M and S ). These diverticula mark the first two branchial pouches, thyroid gland, mouth and Seessel's pocket respectively. At the junction of the pharynx and the umbilical vesicle there is a large diverticulum of the entoderm into the septum transversum, L, the beginning of the liver.

The hind-gut is a sharply defined cavity lodged in the tail of the embryo, communicating on the one hand with the allantois. All, and on the other with the neural tube by means of the neurenteric canal, N. C.

The attachment of the umbilical vesicle to the body indi


Graf Spee, His's Archiv, 1889 and 1896. tKollmann, His's Archiv, 1889 and 1891. t Mall, Journal of Morphology, vol. 12, 1897, p. 417. 'i His, Anatomie mensch. Embryonen, 1885.


cates the extent of the mid-gut from which the future intestine is to arise. The coelom is already beginning to be incorporated into the body to form the body cavity, and in the region of the liver and the omphalo-mesenteric vein the peritoneal cavities of the two sides of the embryo communicate freely, showing that at this early stage there is no complete ventral mesentery as has been described. This communication, marked 0, gradually approaches the communication above the allantois, 0', and ultimately cuts off the umbilical vesicle altogether. A stage just before the umbilical vesicle



Fig. a. — Reconstruction of Embryo No. II. Enlarged 17 times. V and X, fifth and tenth cranial nerves; 1, 2, 3 and 4, cast of the branchial pocliets ; 1 and 8, first and eighth cervical nerves ; 12, twelfth dorsal nerve; A, auricle; V, ventricle; L, lung; S, stomach; P, pancreas; WD, Wolffian duct; K, kidney; M, mesentery; ST, septum transversum; O, openings which communicate with the peritoneal cavity on the opposite side.

is completely separated from the embryo is represented in Fig. A, taken from embryo No. II.* By comparing Figs. 1 and A it will readily be seen that the spaces marked and 0' in the two embryos are the same.

The intestinal canal of embryo II is given in Fig. 3. The drawing was made from the right side and gives the irregularity of the tube more accurately than my previous figures have done. The part between the liver duct and the cjecum, of course, marks the extent of the small intestine, and the part behind this, the large intestine. At this early stage, therefore, the cajcum is distinctly outlined. Attached to the small intestine there is this marked umbilical stem, but the vesicle no longer communicates with the intestinal canal. From the


Mall, Jour, of Morph., vol. 6; and vol. 12, p. 429.


f


September-October, 1898.1


JOHNS HOPKINS HOSPITAL BULLETIN.


199


umbilical stem there haugs down an extensive papilliform process which, from its appearance in section as well as its presence in younger embryos, shows that it is nothing more than an island of vessels and villi from the umbilical vesicle. These seem always to be incorporated within the body at this point and degenerate later on.

Thus far it is very easy to follow the formation of the intestine, when the embryos already described by His are also taken into consideration. My embryos, Nos. XII and II, are from the end of the second and fourth weeks respectively, so it takes about two weeks for the intestine to become outlined after the entoderm is incorporated within the body of the embryo. The intermediate stages have all been described by His in his great monograph. In his Atlas the external form of embryos intermediate to XII and II is given, and in the text the alimentary canal of embryos Lg, BB, Lr and R is again pictured in woodcuts. They all show the gradual constriction of the stem of the umbilical vesicle to form the intestinal tube between it and the liver.

As the umbilical vesicle is being separated from the intestine, all of the viscera are moving from the anterior end of the embryo towards its tail. This is also the case with the diaphragm and the origin of the cceliac axis and the superior mesenteric arteries from the aorta.* A comparison of figures A and 1 shows that the whole stem of the umbilical vesicle in embryo XII must have moved toward the tail through the space of at least ten body segments to have gained the position it holds in embryo II.

At the same time that the intestine is bending towards the ventral median line the loop is also beginning to turn upon itself, so that the aboral end moves towards the left side, and the oral end to the right of the body. This process is already beginning in embryo II, Fig. 3, but rapidly becomes more marked, as is beautifully shown by the His embryos and their models made by Ziegler. By this process the loop is separated into right and left halves, the left half to form the large intestine, and the right half, the small intestine. In a short time, however, as the loof) grows longer and longer, not all of the left half is occupied by the large intestine, as the cascum is now no longer in the middle of the loop.

EXTENSION OF THE LOOP INTO THE CORD.

As the loop of intestine enlarges it extends immediately into the umbilical cord, as was first shown by Meckelf for the human embryo. To what extent this is common to the mammals is not known, but my experience is that it is frequently found in other mammals, and from the examination of many pigs' embryos I can state that in them a portion of the intestine always extends into the cord.

Figures 4, 5 and B are from embryo IX, a specimen about five weeks old. The intestine extends into the cord as a single loop, with the plane of its mesentery horizontal to the long axis of the body. In general its arrangement is much like that


of His's embryos Si, Sch*, KOf and 11M|. It is noticed in the figures that the large intestine lies altogether within the sagittal plane of the body, a position it retains until the intestine is returned to the peritoneal cavity proper. The right half of the loop has a number of small bends in it, which are of great importance in the further development of the intestine. I have marked them with the numbers 1, 2, 3, 4, 5 and 6 in order to follow them with greater ease in the drawings of older embryos.



•Mali, Jour, of Morph., vol. 12, pp. 441 and 442. t Meckel, Meckel's Archiv, 1817.


Fio. B. Reconstruction of Embryo No. IX. Eulars^ed 20 'times.

ST, septum transversum; L, liver; S, stomach; C, caecum; W, Wolffian body; K, kidney; 1 to 13, dorsal f^anglia; O, omphalo-meseuteric artery; SC, suprarenal capsule; X, communication between pleural and peritoneal cavities.

In the middle of the mesentery of the loop and in the median line lie the omphalo-mesenteric vein and artery. At the point where these vessels cross the intestine. Fig. 4, u, we have a landmark which is of use in comparing the intestine of this embryo with that of older embryos. The point of communication between the umbilical vesicle and the intestine also represents the position of the persistent Meckel's diverti


His, A. m. E., Ill, p. 19. fHis, Abhandl. d. sach. Gesch., XIV, Taf. II, Fig. 3.

JHis, ibid.XV, p. 677.


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JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 90-91.


culum. If the adult intestine is about six meters long, and if the distance from the cjecum and Meckel's diverticulum is about one meter, then the length of the intestine between the omphalo-mesenteric vessels and the caecum is about one-sixth of the whole intestine. In both embryos IX and X, as well as in His's embryos Si and Sch, the extreme bend of the intestine (Fig. 4, u) marks one-sixth the distance from the crecum to the duodenum.

The blood-vessels to this whole loop within the umbilical cord arise from the omphalo-mesenteric or the future superior mesenteric artery. AVhen this is compared with the arterial supply in the adult intestine it is again found to correspond. In this early stage the omphalo-mesenteric artery supplies the same portions of the intestine that the superior mesenteric artery does in the adult. Not only by the form of the large intestine, but also by its blood supply can we divide it into two portions, that jwrtion which is at right angles to the body, supplied by the superior mesenteric artery, and that parallel with the body and supplied by the inferior mesenteric artery.

The relation of the intestine and liver to the body of the embryo is given in Fig. B.



Fig. C. — Reconstruction of Embryo No. X. Enlarged 8 times. 1 to 13, dorsal ganglia; SC, suprarenal capsule; W, Wolfflan body; K, kidney; L, liver; S, stomach; C, ciecum.


BEGINNING OF THE CONVOLUTIONS. A stage somewhat older than the one just described is given in Figures 6, 7 and C. In comparing Figures B and C it is seen that the liver has descended decidedly ; it has moved


away from the head to the extent of at least three segments. While in embryo IX the septum trausversum is opposite the eighth dorsal nerve, and the lower edge of the liver opposite the first lumbar nerve, in embryo X the septum is opposite the eleventh dorsal, and the lower edge of the liver opposite the second sacral nerve. In other words, the septum has descended three segments and the lower edge of the liver six segments. Not only has the liver descended through its absolute growth, but the whole organ has descended ajso. This movement has had a marked effect upon the form of the large intestine, and the direction of the intestine in general, as the figures will readily show.

While this movement is taking place the convolutions are also becoming more and more distinct. Every loop as outlined in embryo IX is more marked in embryo X. In general, the twisting has become more pronounced as the caecum is approached. The loops 1, 2 and 3 are only slightly more bent in X than in IX, while the loops 4, 5 and 6 have become much more sharply defined. In general, the length of the loops has doubled itself while the diameter of the intestine increased but one-third.


.w\


Pjo d. — Reconstruction of Embryo No. VI. Enlarged 8 times. S, stomach; SC, suprarenal capsule; C, ca'cum ; K, kidney; W, Wolffian body.

The next embryo (VI) I have modeled is only slightly larger than No. X. I give the same views for this embryo as I gave for Nos. IX and X. Fig. D compared with Fig. C gives the general relation of the intestine to the body. The large intestine has not changed its position much ; it has


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elongated, but has uot increased its diameter. There is now added to the cisecum a marked vermiform appendix. The stomach has descended more than before, the great omentum forming a sac and extending well over the large intestine.

A comparisou of Figs. 6 and 7 with Figs. 8 and 9 shows the growth of the small intestine. The duodenum is still bulged at its stomach end and only the lower portion of it is as small as the rest of the intestine. This enlarged duodenum is so decided that, at first sight, one might think it belongs to the stomach, but since the liver and pancreatic ducts open into it in all the specimens, there is no doubt but that it belongs to the intestine. Of course there is the possibility of these ducts shifting, but this seems to me very improbable.

The second portion of the intestine, 2, is now curved towards the dorsal side of the embryo, and, as in embryo X, this is also the case with its mesenteric attachment. We are all familiar with this portion of the intestine in section, as it has this hooked mesentery showing that the intestine has bent backward. The next portion, 3, is bent upon itself to such an extent that it rolls around on the dorsal side of the omphalomesenteric artery, to project to the left side of the clump, as shown in Fig. 8. It also has the hooked mesentery in section, as the mesentery is very much bent upon itself.

It has been customary for embryologists in discussing sections of the intestine with me to call this portion of the intestine the duodenum, on account of its position, as well as for its very characteristic mesentery. At first I was strongly inclined towards this view, but more mature consideration of models convinced me that both the loops 3 and 3 are finally transferred to the left side of the body to form the upper part of the jejunum.

The fourth portion of the intestine. Fig. 8, 4, has its beginning in the earlier embry.j on the left side of the mesentery as shown in Fig. 6. It is readily seen by the comparison of the two figures that the loop 4, in Fig. 8, is only an exaggeration of the same in Fig. 6. While this loop begins on the left side it ends on the right. In all the figures the extreme bend of the loop 4 is marked a, and a comparison of the figures will readily show that this is always the homologous loop.

Following the loop 4 there is the loop 5, which is altogether on the right side in embryo X, Fig. 6, and about equally distributed on both sides in embryo VI. In both Figs. 6 and 8 the end of the loop 5, b, approaches the loop 3, and this relation is also present in Fig. 10. In the figures this point is marked b, and the similarity of this loop in them is very apparent. Loops b and 3 are just touching in Fig. 6, while in Fig. 8, through the elaboration of loop 4 and its gliding to the right side of the mesentery, the loop 5 has been brought nearly in contact with loop 3. At any rate the relations of loops 5 and 6 to the umbilical vein in both figures show that the numbering of the two loops is not far amiss.

The loop b in Figs. 4, 6, 8 and 10 holds the same relation to the ca3cum and umbilical vessels in all four embryos. This point seems to be the fixed point for the loop on the right side of the mesentery as the point marked a is for the left. Between b and the ctecum the intestine is thinner and the loops are smaller than in the upper part of the intestine. |


For this reason as well as for the fact that there is no sharp landmark other than the umbilical vessels between loop b and the cascum, I have classed this whole region as one group and marked it with the single number 6.

The convolutions in embryo XLV, Figs. 10 and 11, are only an exaggeration of those of embryo VI. The loops 1, 2 and 3 are much the same as before. The loop 1 is again defined by the extent of the head of the pancreas. The loops 2 and 3 together are now S-shaped instead of a simple curve as in embryo VI. My interpretation of this is that the loop 3 is held in place by the opening of the umbilical cord, as at this point the intestine leaves the body, while the loop 2 is beginning to rotate to the left side of the body with the rest of the intestine. The loop 4 on the right side has enlarged, however, and has pushed its way in between the loops 3 and 5. On the left side the loop 4 has made for itself another twist, so it now appears as several loops. The loop 5 is much as it was before, only it has increased its length somewhat. It is easy to see the loop 6 of embryo VI converted into that of embryo XLV by imagining x in Fig. 9 to be drawn over to the opposite side to form x in Fig. 10. In so doing x' and x" remain back to form the loops marked the same in Fig. 11. In addition to this the loop y in Fig. 9 has become bent over to the left side to form y in Fig. 11.

All these twists and curves in the small intestines of the four embryos just descril)ed can be followed fairly well in the figures, and the reader may think that there is considerable imagination required to do this. Any one, however, who may study the models in which the corresponding loops have been marked as in the figures will not doubt regarding the accuracy of this description. It is a most remarkable fact that four specimens should correspond as well as they do here. Were the whole affair more or less haphazard no comparisou whatever could have been made.

ROTATION OF THE SMALL INTESTINE.

A comparison of embryos II, IX, X, VI, His's Pr and KO, shows that the change in position of the intestine and its future twisting is due to the descent of the abdominal viscera, accompanied by the relatively rapid growth of the small intestine. The following table gives the measurements of the intestines in these embryos as well as the level of the stomach

ind the caecum. The measurements of the intestine of embryos Pr* and KOf have been taken from the illustrations given by His and are only approximations. The position of the stomach here given is its lowest measurements including the omental bag.

Table giving tue Position and Length of the Small Intestine.

Length of Intestine.


Number of Embryo- Position of Stomach.

II 1 Dorsal


3 Lumbar 5 Lumbar 1 Sacral


Position of Csecum. Small. Large.

(• Dorsal 1.7 mm. 1.5 mm.

10 " 3. 1.5

13 '< 4. ;i

5 Lumbar 9. 3.7

3 Sacral I'J. 7.

1 Sacral ' 34. 8.

52. 8.


His, Atlas, Theil III, Taf. 1, Fig. 4. fHis, Abhandl. d. K. S. Ges. d. Wiss., U


Bel. XIV, No. 7.


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[Nos. 90-91


A study of this table by comparing it with the illustrations shows that the intestine is gradually elongating and at the same time being pushed towards the pelvis by the large liver and other organs descending upon it. In No. II the intestinal canal is still a comparatively straight tube, but in Pr and KO it is already well bent, is much larger than in No. TI and is pushed into the cord. In No. IX it is located in the cord. From No. II to No. IX the small intestine has increased its length five times and the large intestine over two times, and the space which they should occupy within the body has remained the same. Under these conditions the intestine must escape if it has a chance, and the coelomic space within this cord naturally receives it. This movement of the intestine is due to mechanical causes and, were the ccelom of the cord not there to receive it, the intestine no doubt would make room for itself within the body. I do not think that the umbilical ducts had anything to do with it any more than to keep the opening in the cord open, for, before the intestine begins to enter the cord, its connection with the duct is severed.

After the intestine has entered the cord. No. IX, Fig. B, the small intestine grows rapidly, as the table and Figs. C and D show. Embryos IX, X and VI are all about the same size, but no doubt VI is considerably older than IX ; the organs are all firmer and more developed, and the small intestine has increased its length considerably more than the large intestine. The organs have all been pressed down to the pelvis as far as they will go, as Fig. D. shows. In so doing the large intestine makes a sharp bend in the neighborhood of the fourth lumbar segment, in all of the embryos given in the above table. This bend, therefore, may be looked upon as a fixed point toward which the viscera descend, but beyond which they do not go. Of course after the intestine is in the cord the loops may descend lower, but within the body this is a very fixed point.

After the intestine is within the cord its further elongation and its mesenteric attachment causes it to be thrown into coils, as shown in the plates. The large intestine lies, however, in the sagittal plane of the body, partly within the body and partly within the cord. It does not grow as rapidly as the small intestine ; and, as the small intestine is folded into coils, the whole begins to rotate around an axis which is identical with that of the large intestine. By this process the small intestine is gradually turned from the right to the left side of the body, and in so doing is rolled under the superior mesenteric artery. This takes place while the large intestine has an antero-posterior direction and before there is any transverse colon. This latter is the result of a kinking which is to follow, and is in no way formed by a shoving of the large intestine over the small, as given in the Hertwig diagrams.

RETURN OF THE INTESTINE TO THE PERITONEAL CAVITY.

Although it is comparatively easy to understand how the intestine leaves the peritoneal cavity to enter the cord, it is extremely difficult to see how and why it returns. When the intestine enters the cord the communication of coelom with the body cavity is very free and the intestine is small, but when


the intestine returns to the body cavity the intestine is large, while the opening is small. Fig. D.

In embryo No. II, and in younger embryos, the belly stalk is very large and contains within it no muscles nor permanent blood-vessels of the abdominal walls of the future individual. It is not until the muscles wander, carrying with them their nerves and to a certain extent their blood-vessels, that the belly wall is finally completed.* In embryo No. VI, for instance, the rectus abdominis is about half-way around from the dorsal to the ventral median line, thus leaving a large area between the two recti, which is little more than a membrane. It seems that, until the abdominal walls are fairly completed, the intestine remains within the cord, and, at the last moment before the two recti come together in the middle line, the intestine returns to the peritoneal cavity.

In very young pigs' embryos, when the mammary ridge is still over the muscle plates, I have found that the segmental arteries form an anastomosis with one another throughout the extent of this ridge. This artery goes through a series of muscles which have just been split off from the muscle plates. As the embryos grow, the mammary ridge wanders towards the ventral median linef and carries with it this anastomosis of segmental arteries and the portion of muscle plates which are destined to form respectively the internal mammary, deep epigastric arteries and the rectus abdominis muscles. The nerve connections of the various segments of the rectus are formed as the muscle is splitting off from the muscle plates, and in this way the origin of the different parts of the rectus is indicated, as already shown by Nussbaum. What I have here described for the pig can also be verified for the human embryo, and this will make it plain how the lateral body walls are formed from the belly stalk.

But the closing off also takes place from above downwards. In an early stage, while the septum transversum is still in the neck, the umbilical vesicle also extends upwards. The heart is first closed off by the beginning of the membrana reuniens, and the ventral wall is completed by the amnion moving over the embryo from left to right.J Then the umbilical vesicle is pinched off from above downwards, corresponding with the descent of the liver and other viscera. In embryo II the stalk extends from opposite the third dorsal vertebra to opposite the second sacral, while in embryo IX it extends from opposite the second lumbar segment to opposite the fourth sacral. In other words, the oral end of the stalk has receded eleven segments, and its aboral end two segments ; or the whole stalk is moving away from the head, and its attachment to the body is rapidly becoming smaller and smaller. Later the growth of the abdominal walls is greater between the cord and the pelvis, as shown by the sections made by Merke].§

At one time I thought of the possibility of the expansion of the coelom of the cord and its incorporation with the abdominal cavity, and this was also carefully investigated. Were this


See also Nussbaum, Verhandl. d. anat. Ges., 1894, '95 and '96. to. Schultze, Anat. Anz., Bd. 7 ; and Verhandl. d. phys. med. Ges. Wurzburg, Bd. 26. t Mall, Journal of Morphology, vol. XII. i Merkel, Abhandl. d. k. Ges. d. Wiss. in Gottiugen, Bd. 40.


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JOHNS HOPKINS HOSPITAL BULLETIN.


203


the case it would be necessary to find stages in which the rectus abdominis had wandered up into the stalk to incorporate it and to enclose the intestine within it. No such stage has ever been found, while on the contrary the recti nearly close the communication between the stalk and peritoneal cavities, before the intestine slides back into the body.

The return of the intestine into the body must take place very rapidly, for I have never seen a specimen in which it is in the process of returning. Embryos 40 mm. long either have the intestine in the cord or in the peritoneal cavity, and, if it is in the latter, the communication between the cord and peritoneal cavity is open and surrounded by a thin membrane, showing that it also is being closed. This membrane now closes the whole opening, and later the recti muscles wander into it to complete the abdominal walls.

Since I was unable to find the desired stage in the human embryo, I examined a number of pigs' embryos, hoping in this way to find stages in which the intestine is returning to the peritoneal cavity.

In a pig's embryo 12 mm. long a single loop of intestine extends into the extra-embryonic cojlom, beyond the cord and on the right side of the body. It is still in communication with the umbilical vesicle, which, in turn, is attached to the ventral body wall over the heart. As the loops of the intestine increase in number in older embryos, they make room for themselves below the liver and in front of the Wolffian body, for, unlike the human embryo, there is considerable space in this region. In general the greater number of loops remain within the body cavity of the embryo, and the loops within the cord are not numerous. The increase of loops within the body cavity and their rotation seem to draw upon the loops within the cord, so that when the embryo has reached 35 mm. in length, the loops have all returned to the body cavity.

No doubt, in the human embryo some similar mechanism is present in the return of the loops to the peritoneal cavity, but, as the critical stage has not yet presented itself, this question must be left open for future observation.

POSITION OF LOOPS AFTER THE INTESTINE HAS RETURNED TO THE PERITONEAL CAVITY.

Although it is extremely difficult to understand how the intestine returns to the peritoneal cavity, it is not difficult to recognize the various loops after their return. Unfortunately I have not been able to study carefully a good stage between embryos XLV and XXXIV, as the various specimens of this stage at my disposal were not perfect, or if so, the series of sections were broken. It was not until a number of good specimens had been spoiled for this present purpose that I found that, by removing the ventral abdominal walls, good series could be obtained. If this is not done, the intestine is very liable to be imbedded poorly, and as a result the sections are not perfect. Dissected specimens, on the other hand, cannot be relied upon, for, when once handled, it is impossible to replace the intestines to their original position with certainty, unless they have been modeled as soon as the abdominal walls were removed. Of course dissection is an extremely good method of control, but for a comparison of the loops I think that no method will improve the model. Then it was found


that all the loops represented in No. XLV are again recognizable in XXXIV, and on this account it is believed that an intermediate stage is unnecessary, unless that stage is one in which the intestine is in process of returning from the cord to the peritoneal cavity.

A comparison of Figs. 10 and 13 shows that the loops of XLV are again represented in XXXIV. The marked change is that the mesentery of the large intestine has increased greatly. The loops of the upper part of the intestine have rolled completely to the left of the superior mesenteric artery, and the loops which were formerly within the cord have now been transferred in Mo to the right side of the body. While this has been taking place the stomach has been enlarging also, and by the tilting of the intestine the pyloric portion of the stomach, d, has come nearer the cscum, about to the point marked d' in Fig. 10.

This shifting of the loops, half to the right and half to the left side, as well as the sliding down of the stomach towards the Cfficum, has finally locked the duodenum (loop 1) around the root of the mesentery, as shown in Figs. 13 and 13. As the loops come out on the left side. Fig. 13, we have the beginning of the second group of loops (3) of the intestine. The deeper layer of these loops, not shown in the figures, is a single curve lying immediately in front of the mesocolon. The loops 3 together can easily be imagined as arising from the same as in Fig. 10 by a simple bending of the portion on the dorsal side of the large intestine towards the ventral median line. The loop 3 which lay formerly on the right side of the body is now altogether on the left side. In the illustration, with the exception of its ending in loop 4, it cannot be recognized as the loop 3 of Figs. 10 and 11. In the models, however, the loop 3 forms a distinct cluster situated between the loops 2 and 4, and therefore, by exclusion, it must represent the loop 3 of embryo XLV.

The similarity of the loop 4 in embryos XLV and XXXIV is very striking. Its beginning, the arrangement of convolutions and their position are much the same in both embryos, if the change in position of the intestine in the older embryo is taken into consideration. The next cluster I have marked 5, and the remaining portion 6. The loops 6 are again smaller, and their diameter is less than those of the upper part of the intestine.

In this embryo we can see pretty well the adult form of the intestine, only that the mesentery is transverse to the body rather than diagonally downward toward the right side. In this embryo we also see the relation of the intestine to the mesentery better than in the adult. At this time the mesentery is relatively simple, as but few secondary adhesions have taken place. Unraveling this stage into the one represented by embryo XLV, we can fully understand the relation of the mesentery to the abdominal viscera. These two stages represent beautifully the arrangement of the intestine in the dog and monkey respectively.

The following table gives the length of the various loops of intestine in the embryos described. The measurement was taken along the distal border of the intestine and therefore is considerably longer than along the mesenteric border. But this is a border easily measured, and the length of the hard


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[Nos. 90-91.


ened iutestiue is considerably less than where it is taken out fresh and stretched. The table shows that the lower end of the intestine grows more rapidly than the upper end until the intestine is returned to the peritoneal cavity, when the upper end of the intestine grows more rapidly. ^


Length


IN Millimeters of


THE DIFFERENT Pt


KTIONS


OP THE


Intes


T


NE IN


THE DIFFERENT EmBRTOS


STUDIED.






Small Intestine.




Large


Total Length.


No. of Enil>ryo.


1


S


3


4


5


6


Intee- Small tine. Iniestine. I


wliole itestine.


II






_


_



J. 5


1.7


3.3


IX


1.6


1.3


1.3


1.3


1.4


3.4


3.7


9.1


13.8


X


2.


3.6


3.6


3.6


3.4


.5.8


7.


19.


26.


VI


1.8


3.9


3.8


7.4


7.3


10.8


8.


33.9


41.9


XLV


3.6


3.3


.5.6


13.3


9.3


17.3


8.


53.


60.


XXXIV


11.


39.


50.


89.


07.


110.


50.


366.


416.


XLVIII


33.


62.


70.


1.50.


95.


175.


86.


474.


560.


Infant '


_







570.


3100.



Adults









5373.



•After Weinberg






'After Sernoff



It is not difficult to follow the development of the intestine from embryo XXXIV to the adult, by simple dissection ; but, in order to be more certain of the relation of the deeper layers of the intestine of an older embryo, I had the intestine of a four months' foetus modeled. In this, however, the mesentery was not included, as the loops only were desired. The intestine was removed from the body in toto, and carefully imbedded in paraffin, after which it was cut into sections 100 /a thick. These were drawn upon wax plates, at a scale of ten, thus making each plate one millimeter thick. The intestine outlines were then cut out, and the remaining frame-work of wax plates was carefully piled, and the cavities cast with plaster of Paris. After the plaster had set, the wax was melted in hot water, leaving the plaster cast of the intestines enlarged ten times.

Figs. 14 and 15 are drawings of this model, and they show about what would be expected in a stage more advanced than embryo XXXIV. The large intestine has become more extensive, the transverse colon having become bent forward, and the descending colon having a very marked S in it before it passes over to the rectum. The intestines, as a whole, are shifted more to the left side of the body, so that the colon encircles the intestine rather than simply marks its border. The lower part of the small intestine is filled with a great quantity of meconium at this stage, showing that vermicular action must take place at this early time, as all this substance has been propelled downward to the cfficum. This same condition I have noticed in other embryos of the same stage.

The loops have shifted somewhat over one another, but one could not unwittingly separate the model so that it would not fall into its respective groups. This separation is given in Fig. 15.

It is evident that the loops are now shifting and adjusting themselves to the space they have to occupy. The loops 2 and 3 are still recognizable, while the loop 4 has been pushed back of them and extends over about as great an area as loop 6. The loop 5 lies about in the middle line, is more to the left than in the younger specimens, and is destined, ultimately, to


lie in the left iliac fossa. The loop 6 will descend into the pelvis when the pelvis becomes large enough to hold it, making room for the green, which is shifted to the right side and to the umbilical region. All this will be accomplished with the descent of the caecum to form the ascending colon, thus bringing about the re-arrangement of the position of the loops by a rotation of the lower end of the intestine toward the pelvis.

POSITION OF THE INTESTINE AFTER BIRTH AND IN THE ADULT.

It is relatively easy to follow the intestines in an older fcetus or in a new-born child after they have been hardened in formalin or other substances which keep the intestines sufficiently in place while they are being handled. I have examined the intestines by this method in a number of new-born children, and have found them much the same as in fcetus XXXIV and XLVIII. The intestine passes over and back along its mesenteric attachment from left to right, while in foetus XXXIV and XLVIII, the direction of the mesentery of the intestine is at right angles to the axis of the body, in the new-born this attachment is from the left hypochondriac region diagonally downward towards the right iliac fossa, with a curve somewhat towards the right fossa. This makes its course a curved line, which is also curved spirally around the body. While above it is left and deep, below it is right and superficial. The intestine now is attached along this line, crossing and recrossing it, over and back again from duodenum to csecum. In so doing, the convolutions above lie to the left of the mesentery, and are piled upon one another, making the planes of their circles at right angles to the body, while below and to the right they lie in front of the mesentery, and the planes of the convolutions are jjerpendicular to the body.

For the adult I have examined the intestines of about 50 cadavers, in which 41 were not diseased nor adherent in any way. Of them, one-half were negroes. The intestines were all coagulated in position, the cadaver being on its back, with about 1.5 to 2 kilos of pure carbolic acid. It was injected in 33 per cent, solution to preserve the subjects for dissection. After the abdominal cavity was opened the position of the intestines was either sketched or photographed and then the intestines removed, loop by loop, making a tracing of their course at the same time. In this way the general course of the intestine was followed. In removing the loops it was found that in nearly all specimens they came out as distinct groups, as for instance the group on the right side of the body was usually one loop crossing the middle line but twice; once to communicate with the loops above, and once with those below. To follow the intestine in this way the method was amply sufficient, but free-hand modeling or corrosion gives a much more satisfactory result. The models of three specimens which I have made in this way have proved to be of great value in gaining a clear idea of the position of the intestines. A large number of diagrams, sketches, photographs, and models were compared with one another till I was finally able to convert them into a common scheme, by which I have been in the habit of demonstrating the course of the intestines to students, and then immediately verifying


September-October, 1898.]


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it on the cadaver. In doing this, it is necessary to be prepaied for the variations, and these again can be classified.

WORK OP HENKE, SERNOFF AND WEINBERG.

It was generally believed that the intestines within the abdominal cavity had no definite position until a few years ago, when Ilenke* demonstrated that this was not the case. A glance at the various standard test-books on anatomy shows that there is a tendency among them to locate the main groups of the small intestine in fairly definite portions of the abdominal cavity. Gegenbaurt gives an illustration copied from Luschka in which the jejunum and ileum are located respectively in the upper and lower portions of the abdomen. In the text he expressly states that the jejunum is located in the upper portion of the abdominal cavity and extends down to the left iliac fossa. The ileum, however, is located in the lower portion of the abdominal cavity and in the pelvis, and extends over to the right iliac fossa. HoffmannJ gives an excellent illustration of the coils of the small intestine, locating the jejunum mainly in the umbilical and left iliac regions, with the ileum within the pelvis and lower abdominal regions. Similar descriptions are given by Testnt§ and by Q,uain,|| with the exception that they are more cautious about locating definite loops. Quain states, "the jejunum lies above and to the left side of the ileum, but the coils are so irregular that the position of any individual loop offers but little clue to the part of the intestine it belongs," while Testut states that tlie position of the intestine changes, due to the muscular contraction, and so on.

The first decided step in advance to locate the position of the intestine was made by Henke when he studied carefully the spaces in which the intestine may lie. He found that the abdominal cavity may be divided into four compartments, the greater of which lies within the concavity of the diaphragm and is filled with the organs which are more or less firmly fixed with ligaments. The other three compartments are separated from one another by the ridge formed by the two psoas muscles and by the vertebral column. This makes a right and left compartment and a lower compartment which extends into the pelvis. Into these three compartments the intestine must accommodate itself, and Ilenke thinks it has a fairly definite position. He is cautious enough, however, to state that under certain conditions the loops may shift from one space to another, but what the regularity of the position is, or what the rule of the shifting, is difficult to determine from Henke's paper. His illustrations, however, are very good, but, according to my experience, do not represent the normal type of the intestine. Of course, we could not expect them to do so, for the number of cadavers he studied carefully appears to have been but three.

Henke's method of study was to make sketches of loops of intestine and then to remove them, sketching again the loop


•Henke, His's Archiv, 1891.

tGegenbaur, Anatomie, 1890, Bd. 2, S. .59.

^ Hoffmann-Rauber, Anatomie, 188G, Bd. 1, S. 557.

<> Testut, Anatomie, 1894, t. 3, p. 505.

II Quain, Anatomy, 189«, vol. 3, pt. 4, p. 103.


below. By combining the drawings he finally outlined the course of the intestine from the duodenum to the ca3cum. Of course, he examined a great number of intestines in fresh cadavers, but it is difficult to trace the course of the intestine in them, as the slightest disturbance will make one's result uncertain. While, therefore, he gives very little certainty regarding the course of the intestine, he states definitely that the course of the loops on the left side is horizontal to the body, while on the right side it is perpendicular.

A few years later Sernoff* studied a few cadavers more carefully and with more accurate methods than Henke, but did not verify Henke's result. Sernoff injected the cadaver with a large quantity of chromic acid, and in this way the intestine and mesentery were hardened in position. Then, alter opening the abdominal cavity, a cast was made of the intestine, and finally the surface loops were stained with fuchsiu. In this way the surface loops were marked after disturbing the intestine for purpose of exploration and measurement. Next the intestine was removed, showing the form and position of the mesentery which was left within the body. I'he method throughout is accurate, but the number of specimens is not numerous enough for any generalization of the position of the loops. Only two records of intestines in normal position are given, and although Sernoff believes that these are diametrically opposed to each other in position, I think it is not difficult to see that there is a great similarity in them. The fact that a higher loop may be on the right of a lower one in one case and the reverse in another does not necessarily overthrow a general scheme. Also, it is not of much significance regarding the general course of the intestine that in specimens 2 and 3 (he does not picture No. 2) the direction of the convolution is not horizontal above and to the left and perpendicular below and to the right.

Recently Weinberg! has studied a number of specimens in new-born infants very carefully. He gives good illustrations and descriptions of ten specimens which were studied with the method employed by Sernoff. In general, Weinberg's specimens are all after the same plan, showing that the intestine goes over and back, antero-posteriorly, beginning at the upper left side and ending in the lower right side. In seven specimens out of the ten the large upj)er segment of the jejunum lay in the left upper part of the abdominal cavity. In three specimens, only a short portion of the jejunum lay in the left hypochondriac fossa and the rest came up in contact with the ventral abdominal wall. The direction of the loop ill this region was mainly transverse to the body, and, in general, the extent of them was about two-fifths of the length of the small intestine. Following these loops there is a group of irregular convolutions which lie in the left iliac fossa, and include the middle fifth of the intestine. Then the intestine crosses the left psoas muscle, and the remaining two-tifihs of the small intestine lie between this and the right psoas, as well as ou the right side of the abdominal cavity. The direction of the convolutions of this portion is mainly perpendicular. The extent of the intestine which comes in contact


Sernoff, Internat. Monatsch. f. Anat. u. Phys., 1894. t Weinberg, Internat. Monatsch. f. Anat. u. Phys., 1896.


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[Nos. 90-91.


with the anterior abdominal wall is about one-third of its whole length, which corresponds with the measurements given by Sernoff for the adult.

In general, Weinberg's results confirm Henke's and give for my purpose the important intermediate stage between the foetus and the adult. I have also examined the intestine of a number of new-born babies after they had been hardened in situ in formalin or in carbolic acid and can confirm the work of Weinberg.

In describing the direction of the loops of the intestine in the various portions of the abdominal cavity it is not well to state the direction of the external loop to the body cavity, for this loop may be only the connecting link between two more important loops above and below. The main loops must be isolated whether they are superficial or deep, and the plane of the circle which they describe makes the general direction of the loop. If the intestine makes a continuous spiral, then the direction of any one of the loops is about parallel with the circles the loops describe ; but if the spiral reverses itself, then the connecting loop is at right angles with the plane of the circles. If this is not considered, it may be that the suj)erficial loops are perpendicular, while the main loops are transverse to the body axis.

POSITION OF THE INTESTINE IN FORTY-ONE CADAVERS.

The cadavers had all been carried in the sujiine position for at least two kilometers over the rough cobblestones of Baltimore before they were delivered at the laboratory, and this shaking may account for the regularity of the arrangement of the intestine. They were then injected with about 1.5 to 2 kilograms of carbolic acid crystals in the form of a 33 per cent, solution into the femoral artery. This coagulates completely the abdominal and thoracic viscera. After that the bodies were frozen and some of them were not studied until two years later, while most of them were opened at about the end of a year. The older bodies are preferable, as the surplus water has evaporated and the tissues are fairly dry and somewhat hard.

In all of these specimens the general direction of the intestine was diagonally across the abdomen from the left hypochondriac space towards the right iliac fossa, usually diverging once or sometimes twice towards the right side of the abdomen and always towards its end, into the cavity of the pelvis.

The general form and position of the mesentery is well shown in Fig. 17, as well as in Figs. 5 and 8 by Sernoff. These figures show the large curves made by the mesentery to attach itself to the loops, first on one side of the root of the mesentery and then on the other. I have tried to follow rather the greater groups of couvolutions, for it is hopeless to attempt to number every individual loop. .

In 31 of the specimens the arrangement of the loops was after the same plan ; therefore I shall consider this the normal, and the arrangements of the intestine in the other specimens as variations of this plan. In these specimens the jeji;num first arranged itself into two distinct groups of loops situated well up in the left hypochondriac region. Each group made more than a complete circle, and both of them


came in contact with the anterior abdominal walls. They are marked 2 and 3 respectively in Fig. 16, the loop 2 being the one which communicates with the duodenum. After this the intestine passes through the umbilical region to the right side of the body. This loop is marked 4 in the figure. Then the intestine recrosses the median line to make a few convolutions in the left iliac fossa (5), after which it fills the pelvis and lower abdominal cavities between the psoas muscles (6). The course of the intestine which has been pictured in Fig. 16 is given in Fig. 18.

When now this arrangement of the intestine is compared with that of foetuses XXXIV and XLVIII, as well as with Weinberg's specimens, it is fairly easy to see the gradual transformation of XXXIV into the adult type. Fig. 12 still shows the intestine about equally distributed on both sides of the body, with the caecum still very high. In Fig. 14 there is already a marked descent of the cfficum towards the future pelvis. In comparing these two figures it is to be observed that Fig. 12 is a ventral view and Fig. 14 a view from above. The outlines of the stomachs in the two figures will show from what point the models have been drawn.

When we pass from these two specimens to the figures of Weinberg, we see a similarity between them and most of his figures, but in a number of them the intestines have begun to shift more and more. In general there is a tendency for the irregular lines of mesentery to bend towards the left iliac fossa, for, with the descent of the csecum, the whole mesentery is rotating towards the left side. Weinberg's Fig. 18 shows this well. Hand in hand with this movement one or more loops move towards the right side of the body, as his Figures 11 and 19 show. As yet there is no marked pelvic cavity to take the lower end of the ileum, and as soon as the pelvis is large enough to hold it, we can easily imagine the intestine pictured by Weinberg in Figs. 5, 9, 11, 16, 17, 18 and 19 to be converted into my Fig. E by a simple descent of the ileum into the pelvic cavity. The other few specimens may be considered as variations.

In a shifting of this sort it is probable that the middle loops of the intestine would be transferred to the right side, while the upper half would remain on the left side, and the lower half in the pelvis and lower abdominal regions. According to Sernoff's three measurements, on an average 41 per cent, of the length of the intestine is on the left side, 41 per cent, in the pelvic cavity and about 18 per cent, on the right side. In embryos IX, X, VI and XLV the loops 2, 3 and 4 together are shorter than the loops 5 and 6, while in XXXIV and XLVIII, these first three groups are somewhat greater in length than the lower two. In the younger embryos it was the ileum which grows more rapidly, while in the older embryos the jejunum is beginning to overtake the ileum. So from these measurements, as well as from the indication in Figs. 12 and 14, it is the loop 4 which is destined to cross the middle line and to take its position on the right side of the body.

Heuke showed that it is not difficult to separate the intestine into two great groups, the dividing line of which is the left psoas muscle. This, usually, is also the limit between the loops 4 aud 5, as shown in Fig. 16. The diagrammatic



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Fig. E shows this still better between loops 4 and 5. When the loops 5 are within the pelvis this separation made by the psoas is still more marked. Also in those specimens iu which the position of the intestine is as iu Fig. E, the loop 4 can be lifted towards the left side, making a beantiful demonstration of the attachment of this loop. A glance at Fig. 17, as well as at Sernoff's Figs. 5 and 8, will easily explain why this should be so.

/



Fig. E. — Scheme of the intestine. The arrows indicate the Tariations. The variations a and bb were most frequent ; the variation e least frequent.


VARIATIONrf IN THE POSITION OF THE INTESTINE.

One of the most common variations I have found is one in which there were no intestines on the right side of the peritoneal cavity. The loop 4 had been transferred to the left side of the body, as indicated in Fig. E by the arrow a. Otherwise the intestine had its usual position. It is this loop which is so easily isolated and, probably on this account, it is readily displaced by an enlarged caecum or ascending colon. It may possibly be that this loop can be shaken to the left side, and this could easily be tested by experiment. In one of these specimens the sigmoid flexure of the colon filled the right side of the abdominal cavity.

The second variation, as w^ell as the first, occurred six times. It is marked by the arrows bb in Fig. E. The loop 4 was again displaced to the left side, and the loops 2 and 3 were displaced to the right side. In other words, the very upper part of the jejunum formed the loop on the right side of the body.

The third variation occurred five times. In these specimens the intestine had its normal position, with the exception that an additional loop arose out of the pelvis and filled a portion of the right side of the body, as indicated by the arrow c. Sernoff's specimen, pictured in Figs. 3, 4 and 5, is to be included with this group.

The next variation occurred two times. It is indicated by


the arrows d in Fig. E. The large loop 4 was again drawn to the left side, and the space it formerly occupied was filled by two loops, one from the upper part of the jejunum, and the other from the lower part of the ileum.

The last variation occurred once. It is marked by the arrows e. The loop 4 was displaced and its place taken by a large loop which arose from the ileum within the pelvis. Henke's specimen B seems to belong to this group, if I can judge by his illustrations.

MARKED VARIATIONS.

The variations given above all fit within the common scheme and can easily be explained. In all of my specimens I found but one extreme variation, and in this the intestine crossed the middle line at the beginning of the jejunum and then filled the right fossa. From here it descended immediately into the pelvis and filled it and the lower abdominal cavity completely. Then it left the pelvic cavity and filled the left fossa, extending up to the beginning of the duodenum. When it hud reached this point it took a fairly direct course along the descending colon over the floor of the pelvis, and passed directly to the cascum. Henke* has also described a variation practically identical with this. WeiubergI has also described one similar to this, only that the jejunum descends immediately to the pelvis and then gradually rises to the left side, and finally over to the right side. What kind of a mechanism can bring about this extreme variation is not possible to state.

It could be asiBerted that these few instances of marked variations indicate the normal, but in my specimens it is one in forty-two; in Weinberg's, one in ten; and in Henke's specimens it is not stated how many cadavers were examined carefully.

SHIFTING OF THE INTESTINE.

Henke has stated that the loops of the intestine may shift from one of the abdominal fossas to the other, and, no doubt, this is true. We are familiar with the fact that a distension of any of the pelvic viscera pushes all of the loops of intestine out of the pelvis,J and emptying it again allows the loop to descend to the floor of the pelvis. So likewise a distension of the colon or a certain number of loops of small intestines will displace a certain member of loops from their natural position. Since, however, the intestine was located after one plan in 41 cadavers, I do not think it probable that ordinary shaking will displace any number of loops. Pure mechanical disturbances, as by returning the intestines after operation, will also be overcome by the intestines shifting about to their normal position, guided by the attachment of the mesentery, its length and the space within the abdomen. To give this last question a thorough test I made a number of experiments upon dogs. In these animals the intestine is closely rolled up in a very regular fashion below the stomach, and the whole is carefully tucked in by the very large omentum. Upon opening an animal, one is struck with the neatness and accuracy of the


»Henke, His's Archiv, 1891, p. 101, Taf. IV, Fig. 12. \ Weinberg, Internat. Monatsch. f . Anat. u. Phys., 1896. I Among others, Garson, His's Archiv, 1878.


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adjustment of the omentum, and it is easily disturbed by handling. When, however, the intestine and omentum are withdrawn through an abdominal wound, they are disturbed to such an extent that it is impossible to return them to the abdominal cavity as they were found, with the omentum covering them. After the intestines have been pushed into the abdominal cavity in a haphazard way and the animal sewed up, using all antiseptic precautions, the loops as well as the omentum readjust themselves as they were before, provided no marked inflammation takes place. So in the dog, the intestine and omentum seek their normal position after they have been disturbed.

PLATE I.

Fia. 1. — Profile view of Embryo No. XII. Enlarged 38 times. The body wall over the heart has been cut out. Am, amnion ; UV, umbilical vesicle; OV, optic vesicle ; AV., auditory vesicle; Oa, third occipital muscle plate ; Cb, eigthth cervical muscle plate ; H, heart; P, pericardial cavity ; VOM, omphalo-mesenteric vein ; MR, membrana reuniens ; D, D', openings which connect the peritoneal cavities of the two sides with each other.

Fig. 2. — Same as Fig. 1, but half of the model has been removed to show the extent of the ectoderm and entoderm. Br', Br", first and second branchial pouches; M, mouth ; S, Seessel's pocket ; T, thyroid ; L, liver ; NC, neurenteric canal.

Fig. 3. — Intestine of Embryo II, viewed from the right side. Enlarged 34 times. C, caecum; M, mesentery ; y, remnant of yolk sac.

Figs. 4 and 5. — Intestine and liver of Embryo IX. Enlarged 25 times. C, ciecum ; OMA, omphalo-mesenteric artery ; HV, hepatic vein ; UV, umbilical vein ; PV, portal vein ; FW, foramen of Winslow ; GB, gall bladder.


PLATE II.

Figs. 6 and 7. — Intestine and liver of Embryo X. Enlarged 12i times. U, position of umbilical vessels ; C, caecum ; FW, foramen of Winslow.

Figs. 8 and 9.— Intestine and liver of Embryo VI. Enlarged 12i times.

PLATE III.

Figs. 10 and 11. — Intestine and stomach of Embryo No. XLV. Enlarged 16 times.

Figs. 12 and 13.— Intestine of Embryo No. XXXIV. Enlarged 4 times. Viewed from the ventral side. In Fig. 13 certain loops have been lifted off to show the deeper loops.

PLATE IV.

Figs. 14 and 15.— Intestine of Embryo No. XLVIII. Enlarged 2* times. The view is from the ventral and cephalic side of the model. The mesentery was not included in the model. Fig. 15 is a dissected model to show the deeper loops. The lower part of the intestine is enormously distended with cell debris, etc., showing that vermicular action is present at this early stage.

Fig. 16. — Usual position of the intestine in the abdominal cavity. Although this is an actual specimen, it represents the condition in twenty-one out of forty-one cadavers. The numbers in the figure mark the parts which are homologous with the loops correspondingly numbered in the other figures.

PLATE V.

Fig. 17. — Usual position of the mesentery.

Fig. 18.— Course of the intestine. This figure is taken from a model made from the same cadaver from which Figs. 16 and 17 were drawn.


ON THE HISTOGENESIS OF THE STRIATED MUSCLE FIBRE, AND THE GROWTH OF THE HUMAN SARTORIUS MUSCLE

Template:Ref-MacCallum1898

By John Bruce MacCallum.

[From the Anatomical Laboratory of the Johns Hopkins University, Baltimore.)


In a previous paper* I described the structure and histogenesis of the heart muscle cell of mammals. The process of development, as demonstrated in embryo pigs, was found to be quite definite, and in order to complete this work I have studied the heart muscle of a series of lower vertebrates, taking representatives from the various large classes. The definite stages in the histogenesis of the muscle cell, confirmed by its comparative histology, made it seem possible to determine the method of growth of a muscle as a whole ; that is, to learn by what means a small embryonic muscle gradually becomes large, as in the adult. Such a study of the heart seemed to present many difficulties which that of a simpler system of muscles would not. I therefore turned to the striated muscle of other parts of the body, the so-called voluntary muscles, and with this problem in view I studied the histogenesis of the striated


J. B. MacCallum, On the Histology and Histogenesis of the Heart Muscle Cell. Anatomischer Anzeiger, Jena, Bd. xiii. No. 23, 1897, S. 609-620.


muscle fibre of the thigh in embryo pigs. In these a process was demonstrated which proved to be essentially the same as that found in heart muscle, with differences made necessary by the difference between the respective adult tissues. Knowing, then, the course of growth of the individual muscle cells, I have endeavored to determine the relation of this to the growth of the muscle as a whole. In order to begin with the simplest problem, I have chosen the sartorius muscle, as it seemed to show less complexity of structure than many other muscles. Two sides of this problem presented themselves. On the one hand it was necessary to determine how far the growth in size of tiie muscle as a whole was caused by increase in the number of fibres, and how far it was due to a mere growth in size of the individual cells. On the other hand it was necessary to make out the relation between the various stages in the histogenesis of the muscle cell and these two methods of growth. These problems I have endeavored to solve by the study of a series of human embryos, using the sartorius as the


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type of a simple muscle. For the sake of clearness I will give the results of this work under three headings, as follows:

I. Synopsis of the work already done on the histogenesis of the heart muscle cell, supplemented by a study of its comparative histology.

II. The histogenesis of the voluntary striated muscle cell.

III. The growth of the sartorius muscle and its relation to the histogenesis.

I.— HISTOGENESIS AND COMPARATIVE HISTOLOGY OF HEART MUSCLE.

As described iu the article referred to above, the adult human heart muscle is made up of rhomboidal branching cells whose processes come together end to end. The protoplasm of each cell consists of a number of darkly staining columns, running longitudinally, which are separated by unstained substance. The columns are commonly called fibril bundles, and the unstained substance is the sarcoplasm. With special methods of staining, particularly by Kolossow's osmic acid method, a definite relation can be made out between these two parts of the cell. The fibril bundles present regular striatious in the form of darkly staining lines. Narrow striations, the so-called Krause's membranes, alternate with broader bands which are known in voluntary muscle as Briicke's lines. The Krause's membranes, however, do not belong to the fibril bundles alone. They can be seen also extending across the sarcoplasm, as shown in Fig. 1. The sarcoplasm is thus divided into compartments which are limited horizontally by membranes continuous with the narrow striations on the fibril bundles. In cross section (Fig. 2) the muscle fibre is seen to be made up of dark masses, the cross-sections of fibril bundles, separated by sarcoplasm which is divided into definite circular or polygonal areas. The compartments of the sarcoplasm, then, are disc shaped, and I have proposed for them the name sarcoplasmic discs. As described, they are bounded by membranes which are continuous with the fibril bundles at definite points, namely, at the narrow striations or Krause's membranes. It will then be seen that there is a definite network in the cell made up of the fibril bundles and the membranes bounding the sarcoplasmic discs.



Fiii. 1. — Longitudinal section of Adult Human Heart Muscle. -ff, Krause's membrane; .S', sarcoplasmic disc ; F, fibril bundle.




Fir.. 2. — Cross-section of Adult Human Heart Muscle. C, central sarcoplasm; F, fibril bundle; S, sarcoplasmic disc.


The stages in the embryo leading up to this adult structure e.\'pluin the relation of the fibril bundles to the sarcoplasm.


The earliest stage iu the development shows an irregular network in the cell protoplasm with no fibril bundles. This network tends to become more and more regular until the meshes are of the form of large discs. Some of these break up into smaller ones, and in the nodal points of the network there is an accumulation or differentiation of its substance, giving rise to longitudinally disposed masses. These become what in the adult are known as fibril bundles, and the discs left are the sarcoplasmic discs. This formation of fibril bundles takes place first at the periphery of the cell, so that those which are the latest to appear are nearest the centre of the cell. It is apparent, then, that the continuous network spoken of in the adult fibre, made up of the fibril bundles and the membranes bounding the sarcoplasmic discs, is developed directly by a process of differentiation from the primitive protoplasmic network of the embryonic cell. The gradual acquirement of a special function has so altered this network that a complicated structure is formed out of an extremely simple one.

The study of the heart muscle of lower animals gives an interesting repetition of some of the stages of this process. Although the structures met with iu the comparative histology of the organ do not make up an uninterrupted sequence as in its histogenesis, yet there is a sufficient resemblance to confirm the results obtained in embryonic tissues. Hearts from animals representing the various large groups of vertebrates were studied. Of the fishes several species were obtained, among which were the larval lamprey (Ammoccetes), the adult lamprey, and several kinds of Teleosts. The Amphibians were represented by the frog and the toad, while of the reptiles the snake and turtle were used. Several species of birds were studied, such as the English sparrow, the crow, aud the common fowl.

In the heart of Ammoccetes the muscle cells are small and spindle shaped. In some of them no fibril bundles can be seen, but most of the cells show a single row of very narrow fibril bundles at the periphery. The rest of the cell is made up of sarcoplasmic discs. In the lamjjrey the structure is similar, while in the higher fishes, such as the pickerel, the cells are considerably larger and the fibril bundles are more conspicuous. In longitudinal sections the individual fibril bundles are quite similar to those in adult mammalian muscle. The same striations are present, and the same relation of these to the sarcoplasm exists. In the frog and toad the structure of the heart muscle differs only slightly from that described in fishes. The cells are larger, aud the fibril bundles are closer together, tending to form large irregular columns. The nucleus is in the centre of the cell, and the fibril bundles are only at the periphery. The heart muscle of the Keptilia, as shown in the turtle and snake, is made up of cells which are not markedly different from those of the Amphibian heart. The fibril bundles at the periphery of the cell are large and conspicuous, and in many cells there are smaller ones more centrally placed. In the birds, however, there is a very decided advance on the structures described so far. The cells are very large, almost as great as the adult mammalian fibre. In cross-section they resemble the structure described iu mammals. The nucleus is in the centre aud the rest of the




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cell is almost filled with fibril bundles. These are in the form of flat bands around the periphery, as in mammalian muscle, and are separated by sarcoplasmic discs. There is a very great difference between these cells and those found in the hearts of Fishes, Amphibians and Eeptiles. As regards the structure of the heart muscle, then, the classes of Vertebrates are divided into two groups, one comprising the Fishes, Amphibians and Eeptiles, and the other the Birds and Mammals. It will be noticed that these groups are the cold-blooded and warm-blooded animals respectively ; and it is possible that in addition to the control of the temperature by the central nervous system, there is a relation between the heat regulation and the degree of development of the circulatory system. The mammalian embryo in utero resembles the cold-blooded animals in the fact that its temperature is the same as that of its surroundings. They are under similar conditions in this respect, and the structure of the heart muscle is almost identical. Although the transition from the structure of the heart muscle of low^er to that of higher animals is not perfectly gradual, yet the comparative histology corresponds roughly with the histogenesis of the cell. The Fishes, Amphibians and Reptiles, which in other respects are clearly lower than the Mammals and Birds, possess also au embryonic type of heart muscle. The heart of an adult fish, for example, is made up of cells which are almost identical with an early stage in the development of the mammalian fibre. While the comparative anatomy and the embryology of many organs run parallel to one another, it is interesting to note that this same relation holds good even in the internal structure of a single cell, and that the most minute details of the cell structure in the adult heart muscle of the lower animals are identical with those in embi'yonic mammalian tissue.

II.— HISTOGENESIS OF THE VOLUNTARY STRIATED MUSCLE FIBRE.

In order to determine the course of development of the voluntary striated muscle cell I have used a series of human embryos and one of embryo pigs. Of the former I used the sartorius muscle in each case, and in the latter the muscles in the front of the thigh. The human series consisted of embryos of the following lengths in millimeters from vertex to breech: 10, 30, 75, 102, 130, 170 and 200. The series of pig embryos was made up of specimens of the following lengths in millimeters: 25, 34, 45, 57, 64, 70, 75, 100, 125 and 150. The sartorius of an embryo rabbit 35 mm. in length was also studied.

The embryos, which were obtained iu a fresh condition, were treated according to Kolossow's osmic acid method,* and the sections afterwards stained iu safranin. Those which were already hardened in formalin, alcohol, or Miiller's fluid, were cut iu paraffin, and the sections treated by a method somewhat similar to Kolossow's. They were immersed in 2 per cent, osmic acid for three or four minutes, and then transferred to Kolossow's reducing fluid and left until the


precipitation wa« complete. They were then stained in safranin to differentiate the nucleus. Sections stained in this way show the protoplasmic structure with great clearness.

In an embryo pig 25 mm. long the voluntary muscle has quite an undifferentiated character. The sartorius in a crosssection of the leg cannot be recognized with certainty. There are merely small groups of spindle shaped cells with a loose connective tissue between. In the muscle cells there are no fibril bundles, and the protoplasm is very scanty as compared with that in the adult cell. If in a cross-section the cell has its nucleus cut through, the protoplasm is hardly visible. It is seen only as a narrow rim around the centrally placed nucleus. The cross-section of a cell above or below the nucleus shows a definite network which divides the cell into small circles. These correspond with the structures spoken of as sarcoplasmic discs. This is shown in Fig. 3.




Ws]'



S>/;


'^im.A


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'^IG. 3. — Cross-section of Volui. 7 Muscle from the Thigh of an Embryo Pig, 25 mm. loug. .1, cell showing the nucleus; B, cell showing sarcoplasmic discs.


Fig. 4. — Cross-section of Voluntary Muscle from the Thigh of an Embryo Pig, 45 mm. long, showing fibril bundles at the periphery of the cells.


•A. K0I088OW. Ueber eine neue Methode der Bearbeitung der Gewebe mit Osmiumsiiure. Ztschr. f. wissensch. Mikr., Brnschwg., Bd. ix, 1892-3, S. 38-43.


The muscle of an embryo pig 34 mm. in length is somewhat farther advanced in development. The bundles of cells making up the individual muscles are quite distinct and separate. The cells themselves show a centrally placed nucleus, and protoplasm which is very slightly differentiated. In some places fibril bundles can be made out at the periphery of the cell, but these are not very distinct.

In an embryo pig 45 mm. in length the muscle cells contain definite fibril bundles. These are present in a single row around the periphery of the cell, as shown in Fig. 4. The nucleus is still situated in the centre of the cell. The protoplasm near the nucleus contains no fibril bundles, and is divided into sarcoplasmic discs as described before. In longitudinal sections the fibril bundles are seen to be definitely related to the sarcoplasm in the way described above. The horizontal boundaries of the sarcoplasmic discs are membranes continuous with the fibril bundles at the narrow striations.

Very similar cells are found in the muscle of an embryo 57 mm. long. The fibril bundles, however, are somewhat more conspicuous. In embryos 64 mm. and 70 mm. in length the muscle cells contain, iu addition to the peripheral row of fibril bundles, scattered fibril bundles nearer the nucleus. In many cells nuclei are seen, both at the periphery and in the centre.


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In the muscle cells of an embryo pig 75 mm. long, the peripheral and central nuclei are seen very clearly. These diiier somewhat in appearance. The peripherally placed nucleus stains deeply and uniformly, and has a solid appearance. The central nucleus, however, is large and vesicular. It possesses a definite nuclear membrane, and the chromatin network is delicate and distinct, as shown in Pig. 5. In some places the outline of this nucleus grows irregular. What finally becomes of it it is difficult to say. The nuclei in adult muscle cells are all peripherally placed, and have an af)pearance resembling the peripheral nucleus described here.



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Fig. 5. — Cross-section of Voluntary Muscle from the Tliigh of an Embryo Pig, 75 mm. in leugtli. A, central vesicular nucleus; B, peripheral solid nucleus.

In a pig 100 mm. long the appearance of the muscle cells is not essentially different. The fibril bundles are more numerous and somewhat closer together. The muscle cells of an embryo 150 mm. in length, however, are entirely filled with fibril bundles. The sarcoplasm is not abundant. In some of the cells the central nucleus cannot be made out, while in others it is still present.

In adult muscle the nuclei are all at the periphery of the cell. In longitudinal sections the fibre consists of fibril bundles separated by a very small amount of sarcoplasm. The fibril bundles possess alternating narrow and broad striations. In many cases the narrow striation (Krause's membrane) can be seen extending across the sarcoplasm, dividing it into compartments. This is approximately the same structure as that which has been described in heart muscle. In the latter, however, the sarcoplasm between the fibril bundles is so abundant that the narrow striations form disc-shaped compartments, or sarcoplasmic discs. In voluntary muscle the sarcoplasm is very scanty, and the discs are so encroached upon by the growth of the fibril bundles that they are hardly recognizable. As in heart muscle, the lines dividing the sarcoplasm are continuous with the fibril bundles at the narrow striations.

The course of the development, as shown in the series of human embryos, is made up of stages which are very similar to those described in the embryo pig. In human embryos 10 mm. and 30 mm. in length the muscle cells contain no fibril bundles. In embryos 75 mm. and 102 mm. long there is a single row of fibril bundles around the periphery of the


muscle cell. The nucleus is of a vesicular character and is situated in the centre of the cell. In an embryo 130 mm. long the muscle cells contain a vesicular central nucleus and one or more solid deeply staining peripheral ones. There are fibril bundles in the central part of the cell as well as at the outside. The muscle of an embryo 170 mm. in length is made up of cells which are very similar to those of an embryo pig 150 mm. long. The cells are filled entirely with fibril bundles, and the centrally placed nucleus is not often present. In older embryos, in the new-born, and in the adult subjects, the nuclei of the muscle cells are all at the periphery.

The course of development, then, seems to be quite definite. Beginning with a cell which contains only a protoplasmic network, the extremely complex voluntary muscle fibre is gradually formed. The first step is an accumulation of the network at definite places around the periphery of the cell, giving rise to fibril bundles. This accumulation takes place in the angles of the network, so that the meshes remain as discs between the fibril bundles. The membranes, bounding these discs horizontally, are continuous with the narrow striations on the fibril bundles. The formation of fibril bundles goes on until they occupy a large part of the cell. The sarcoplasm in this way becomes gradually replaced, and in the adult cell it is very inconspicuous. At the same time the nuclei undergo changes. The cell which at first contains only a centrally placed nucleus acquires other nuclei which are situated at the periphery. It is possible that the latter are derived from the centrally placed nucleus which is finally lost.

It seems that the same hypothesis is applicable here as was suggested for the development of heart muscle. It simplifies the conception of the structure of striated muscle very greatly to consider the fibril bundles and the membranes bounding the compartments in the sarcoplasm, as derived from the primitive network found in the muscle cells of very young embryos.

These results show that the same process of growth takes place in all kinds of striated muscle cells. The adult structure of voluntary muscle is, however, somewhat different from that of heart muscle, and as a consequence the later stages in the development are different. One of the most noticeable differences is the position of the nucleus. Why it should remain in the centre of the cell in heart muscle, and in the voluntary muscle cell be situated at the periphery, is difficult to determine. Until more is known concerning the relation between the function of the cell protoplasm and that of the nucleus, this can only be the subject of hypothesis.

Since the beginning of the differentiation is the same in both heart muscle and voluntary muscle, the development of the power of contraction must run a somewhat similar course. If this be so, it is conceivable that contractions in definite directions begin when the irregular network of the primitive cell becomes made up of regular membranes at right angles to one another. When there is need of more perfect and stronger contractions, it is probable that the power for this is brought about by a strengthening of the network in the direction of the contractions. This strengthening takes place by an accumulation of the substance of the network, which gives rise to


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fibril bundles. Why this should always take place first around the periphery of the cell is not clear. It is true, however, not only in the development of the heart mnscle and the voluntary mi;scle cells, but also in the evolution of the heart muscle in lower animals. It is possible that there is a relation between this peripheral disposition of the fibril bundles and the spindle-like form of the cells. The fibril bundles, on account of their position, are curved in correspondence with the outline of the cell. On contraction, therefore, the pull is not only in the long axis of the cell, but also at an angle to this. Thus the cells acting together exert an influence on one another, which would not be the same if the fibril bundles, which are probably the chief agents in contraction, were situated in straight lines in the long axis of the cell. If this be so, the force which acts at an angle to the long axis of the cell must control the whole contraction, just as two muscles opposing one another make a more delicate mechanism than a single muscle. It is possible that this is of advantage in the early stages of the development. An hypothesis concerning such a subject must necessarily be vague and unsatisfactory. All that can be said with certainty is that there seems to be both in the histogenesis and comparative histology of the muscle cell a tendency for the fibril bundles to be formed first at the periphery of the cell. If the fibril bundles are the special contractile elements, it seems that it is of advantage to have the mechanisms for contraction as near the outer part of the cell as possible. The same thing is seen in the adult heart muscle fibre, for although nearly the whole cell is filled with fibril bundles, those at the periphery are many times as large as the ones which are nearer the centre.

Ill— GROWTH OF THE HUMAN SARTORIUS MUSCLE.

In applying the process of development of the voluntary muscle fibre as described above, to explain a special muscle, I have endeavored to determine the I'elation between the growth of the muscle as a whole and the growth of the individual cells. The sartorius muscle was chosen for study because of its apparent simplicity of structure, and because its general characters in the adult vary within narrow limits. The fact that this definite and simple structure is developed gradually from a small group of embryonic cells, indicates that the growth takes place by a definite and simple process. In order to detei-mine the exact nature of this process I have made estimations of the number of fibres to be found in crosssections of the sartorius muscles taken from adults and from a series of human embryos.

Methods of Study. — Sections were taken from adult human sartorius muscles at the upper, middle, and lower thirds. Similar sections from the sartorius of a new-born babe were cut. Muscles were also used from a series of human embryos varying in length from 74 mm. (vertex to breech) to the stage shortly before birth. In these only the middle third was studied. Sections were cut in both celloidin and paraflBn, celloidiu being used mainly for the larger muscles. Various methods of staining were employed, but chiefly hematoxylin and eosin or safranin.

In obtaining the number of fibres found in a cross-section no effort was made to actually count them. All that was


aimed at was to obtain as accurate an estimate as possible with methods which would entail the least number of errors. The most simple procedure seemed to be to compare the area occupied by the muscle-section as a whole and the average area occupied by a single fibre. This ratio must represent approximately the number of fibres. Thus the exact area of the whole cross-section was obtained and from this was subtracted the area of the connective tissue, giving the area of true muscle substance. The average area occupied by a single muscle fibre was then determined. The number representing the area of the muscle substance divided by that representing the area of one muscle fibre must be the number of fibres contained in the cross-section.

The sections of the larger muscles, adult and new-born, were projected on a screen with a projection lantern, and the outlines of the muscle and connective tissue carefully traced on a sheet of paper fastened to the screen. A slide ruled in millimeters was projected at the same time in order to obtain the exact magnification. ' This gave only the amount by which the length of a line was magnified, and in order to obtain the magnification in area this number was squared. A planimeter was used to determine in square millimeters the area of the muscle bundles in the tracing. This number divided by the magnification in area gave the actual area of the cross-section of the muscle.

For the smaller muscles a somewhat different method was employed. The sections were projected by means of a camera lucida and Leitz 3 objective, on a paper ruled in square millimeters. An exact tracing was taken as before of the muscle and the connective tissue in the section. At the same time a scale of hundredths of a millimeter was projected with the same power in order to obtain the magnification. The area of the tracing was got by counting the millimeter squares contained in it. At the edges only those squares were counted outside whose centre the line of tracing passed. The area of the connective tissue was similarly determined and subtracted from the area of the entire section. This gave the area of the muscle substance contained in the section. As a check on this the area of the muscle substance was directly counted. The actual area of the muscle was got as before by dividing the area of the muscle tracing by its magnification in area.

The actual area of one muscle fibre was determined by projecting the section upon a known ruled area by means of a camera lucida and a Leitz 7 objective. With a scale of hundredths of a millimeter a square was projected whose sides were .1 mm. in length. Its area therefore was .01 sq. mm. With the same power the muscle fibres were projected into this square and traced off. The fibres falling in the square were then counted and the number was divided into .01 sq. mm. This gave the average area occupied by one muscle fibre.

These two determinations were made for each section, so that all that was I'equired to obtain an estimation of the number of fibres contained in the section was to divide the area of the muscle by that of the fibre.

Results of the Estimations. — The sections of the adult sartorius muscles were ])rojected with a magnification of 14.5


September-October, 1898.1


JOHNS HOPKINS HOSPITAL BULLETIN.


213


diameters, that is, the area was magnified by 210.25. lu the two muscles taken from the same subject the area in each case was greater in the middle third than in either the upper or lower third. In the right sartorius the area of the muscle tracing of the upper third was 19,880 sq. mm.; that of the middle third 24,490 sq. mm. and that of the lower third 18,390 sq. mm. In the left muscle the tracing of the muscle substance in the upper third contained 16,000 sq. mm., the middle third 22,760 sq. mm., and the lower third 18,250 sq. mm. In the new-born the muscle tracing of the upper third contained 2260 sq. mm., of the middle third 2430 sq. mm., and of the lower third 2040 sq. mm. These were all magnified to the same degree. This seems to show that the muscle substance in the sartorius is in the form of a spindle. There is a greater amount of muscle in the middle than at the two ends.

For comparison with the muscles of the embryos, only the middle of the sartorius was used in each case. The tracing of the middle third of the first adult sartorius contained, as mentioned above, 24,490 sq. mm. The magnification in area was 210.25, so that the actual area was 24,490-4-210.25, or 116.48 sq. mm. The number of fibres in .25 sq. mm. of the muscle section was found to be 305, so that the area represented by one fibre .25 -^ 305 = .0008196 sq. mm. The number of fibres, then; in the cross-section would be 116.48 divided by .0008196, which equals 142,118.

By a similar calculation the actual area of the section of the second adult sartorius muscle was found to be 108.252 sq. mm.


The number of fibres in .25 sq. mm. was 315, and the area occupied by one fibre was .0007936 sq. mm. It follows from this that the number of fibres in the section is 108.252 -f.0007936, which equals 136,406. The number of fibres in the sartorius of the new-born babe was estimated by both the methods described. Theresults were slightly different. With a magnification of 14.5 diameters, and measured by the plauimeter, the actual area was found to be 11.557 sq. mm. Magnified 14 diameters and projected on millimeter paper, the result was 12.316 sq. mm. The number of fibres in .01 sq. mm. was 98, and the area occupied by one fibre .000102 sq. mm. Then the number of fibres, according to one calculation, would be 113,304, and according to the other 120,745. This shows that the estimations are subject to an error of about 1 to 17, or somewhat less than 6 per cent.

Considering the individual variations, the number of fibres in the muscle of the new-born babe is approximately the same as that in the adult muscle. After birth, then, the growth in the number of fibres cannot be very great.

The largest human embryo studied was one which measured 200 mm. from vertex to breech. The actual area of muscle in the cross-section of the sartorius was 8.417 sq. mm. The area represented by one fibre was found to be .0000555 sq. mm. The number of fibres is 151,657. The greatness of this number can be accounted for only by supposing that the muscle would have been an unusually large one if it had become adult. It suggests, however, that there is little or no growth in the number of fibres after birth.


TABLE GIVING THE MEASUREMENTS, AND THE NUMBER OF FIBRES IN CROSS-SECTIONS, OF THE SARTORIUS

MUSCLES OF THE FOETUS AND ADULT.


Number of Subject.


Lenath of Body.


Dimensions of Muscle in Millimeters.


Area of Musclc-lracing in CrossSection.


Miignification in Areas.


Actual Area.


Number of Fibres in a known Area.


Area represented by one Fibre.


Number of Fibres.


Adult No. 74 (right) . .


180 cm.


580x18x9


24490 sq. mm.


210.25


116.48 sq.mm.


305


in .25 Bq. mm.


.0008196 sq. mm.


142118


Adult No. 74 (left)....


" "


580x21x8


22760 " f 2430 "


210.25

210.25


108.252 " 11.557


315


" " "


.0007936


136406 i 113304



50 "


140x7 52x6


1 2414 " 1212 "


196 144


1 12.316 8.417


98 180


" .01


.000102 .0000555 "


\



( 120745



Vertex Breech.


Nape Breecli.



Embryo No. A


200 mm.


130 mm.


151657


No. 98


170 "


106 "


42x6


1474 "


256


5.7578 "


223


" "


.00U04484 "


128408


" No.65


130 "


75 "


34x2.5


5901 "


5776


1.02164 "


442


" " "


.0000226


45205


No. B


102 "


65 "


28x3


6565 "


6400


1.02578 "


254


" "


.00003937 "


26055


No. 64


74 "


46 "


19x1.5


4142 "


10816


.382858 "


170



.00005882 "


6509


The younger embryos were studied in the same way. One measured 170 mm. from vertex to breech. The actual ai'ea of muscle in the cross-section of the sartorius was 5.7578 sq. mm. The area occupied by one fibre was .00004484 sq. mm. The number of fibres, then, was 128,408. This number is approximately the same as that determined for the new-born and adult subjects. The muscles described thus far contain practically the same number of fibres in a cross-section. The differences can be accounted for by individual variation and by the nature of the estimation.


In the sartorius of an embryo 130 mm. from vertex to breech, the actual area of muscle in a cross-section was found to be 1.02164 sq. mm. The area occupied by one fibre was .0000226 sq. mm. The number of fibres, then, was 45,205. There is a very decided difference between this and the muscle last described. The number is less than one-third of that present in the adult muscles and in those of older embryos. It seems fair to conclude that in embryos between 130 mm. and 170 mm. in length the fibres found in the cross-section of the sartorius muscle increase in number as well as in size.


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[Nos. 90-91.


In the sartorius of an embryo 103 mm. from vertex to breech there was found a still smaller number of fibres. The actual area of muscle in a cross-section was 1.03578 sq. mm. and the area occupied by one fibre .00003937 sq .mm. The number of fibres, then, was 36,055. The difference between 45,205, which was the number found in the embryo 130 mm. long, and 30,055 is too great to be accounted for in any way but by an actual growth in number.

The sartorius from an embryo 74 mm. from vertex to breech gave in the cross-section an actual muscle area of .383858 sq. mm. The area represented by one fibre was .00005883 sq. mm. The number of fibres, then, was found to be only 6509. This number is less than one-quarter of that found in the embryo 103 mm. long, and about one-twentieth of the number in an adult.

These figures are put together in the preceding table. The adult muscles are placed at the top, and following these the embryonic muscles in the order of their measurements.


®



®


®


<g)


X


Fig. 6. — Diagram illustrating the Growth of Muscle. It shows the possible growth in the number of cells in a cross-section of a muscle, without a correspouding increase in the number of cells in the entire muscle. At the right tlie cells are represented as cross-sections taken in each case on the plane A.

It seems clear from this table that the growth in number of fibres, or at least the increase in the number found in a crosssection, takes place at a definite period. This increase in the number of fibres cut in any given cross-section might be brought about in two ways. There might be an actual increase in the number of fibres in the muscle as a whole, or there might be merely a growth in length of the fibres. This would cause them to grow past one another, so that a greater number would be cut in any one cross-section. This is illustrated in the diagram above, Fig. 6. In I and II there is the same number of fibres, but in II they are longer and have grown past one another. As a consequence the section A contains many more fibres in II than it does in I.

It is very possible that both of these processes go on at the same time. All that can be determined, with such methods as have been used here, is the growth in the number of fibres found in a cross-section of the muscle. This growth begins at a definite place in the development of the embryo. If the


fibres ran the whole length of the muscle it would be a simple matter to determine the point at which the multiplication of the cells ceased; for then the number of fibres found in a cross-section would be the number contained in the whole muscle. In an embryo 140 mm. in length, however, longitudinal sections of the sartorius show that the fibres certainly do not run the whole length of the muscle. This is seen also in teased prepai-ations. All that can be said, then, is that at a certain stage in the development, namely, in embryos between 130 and 170 mm. in length, the increase in the number of fibres found in a cross-section ceases. Since this increase is brought about by the two processes spoken of above, it is probable that the actual multiplication of cells ceases some time previous to this stage. If this be true, there are as many fibres present in the sartorius muscle of an embryo 170 mm. long as there are in the adult muscle. After this stage the growth in size of the muscle must be a growth in the size of the fibre.

It is to be emphasized, however, that the estimations given here are not of the number of fibres in the muscle as a whole. They are merely estimations of the number found in crosssections, so that any suggestions as to the growth of the muscle as a whole are based on the supposition that the increase of the cells is uniform throughout the muscle. I have observed no indication whatever of special growing points in the sartorius muscle. In cross-sections the number of fibres is approximately the same in all parts of the muscle, although the tendons at each end make the number there somewhat less, as shown above. In the various embryos all the cells in any one section seem to be at the same stage of development. In longitudinal sections no growing points can be made out, and when karyokinetic figures are present they are not confined to any one part of the muscle. If the growth is proved to be uniform throughout the muscle, an increase in the number of the cells in the whole muscle must cause an increase in the number found in a cross-section. Indeed, the number found in a cross-section might increase after the actual number of fibres in the muscle had ceased to grow; for, as shown above, the cells in growing in length might pass one another and more of them would be cut in any section. If this be true, a small embryonic muscle, after a certain stage, becomes a large adult muscle, not by an increase in the number of cells, but by a growth in their size. This bears indirectly on other questions, and may prove of interest in connection with muscular hypertrophy. If the very enormous increase in size which the sartorius muscle undergoes during development can take place simply by a growth in the size of the individual cells, it is probable that such a small increase as is present in a muscle hypertrophied through exercise must be due to the same cause. It also seems probable that hypertrophy of the heart is due to growth in the size of the fibres rather than to an increase in their number. These are problems, however, which require special methods for their solution.

It is interesting to note the relation between the histogenesis of the cell and the growth in the number of cells in the sartorius. It will be seen on comparison of the figures given above, that the increase in the number of fibres ceases approximately when the fibre has become filled with fibril bundles, and the nuclei have become situated at the periphery of the


September-October, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


215


cell. Ill a hiuiiau embryo 170 mm. long the muscle cells resemble the adult cells in every way excejjt in size. This stage also marks the point at which the increase in the number of fibres found in a cross-section ceases. Embryos between 130 mm. and 170 mm. in length show the transition between the embryonic and adult types of muscle cells, and this is also the period at which the number of fibres stops growing. It will be remembered that in embryos 130 mm. in length the nucleus is centrally placed and vesicular in character, while in an embryo 170 mm. long the muscle cells contain only peripherally disposed nuclei. There is, possibly, a relation between the position of the nucleus and the power of the cells to produce new fibres.

The course of growth of the sartorius muscle may be epitomized somewhat as follows : At an early stage in the development, the cells are small and spindle-shaped, and scattered in loose bundles. At first there are no fibril bundles, and the nucleus is centrally placed. Subsequently the


fibril bundles appear around the periphery of the cell. The cells multiply and increase in bulk until the embryo is between 130 mm. and 170 mm. in length from vertex to breech. At this stage the bundles of cells become more compact, and the cells themselves are filled with fibril bundles as in the adult. The nucleus is situated at the margin of the cell. The fibres now grow in length and thickness, but probably no longer increase in number. In embryos smaller than 170 mm. in length there is a regular increase in the number of fibres found in a cross-section. After this, however, the number remains approximately constant.

The study of the sartorius as the type of a simple muscle can only be a step towards the explanation of more complex muscles. When accurate methods of estimation have been employed in the study of muscles of more intricate character, and the results considered in connection with the process of histogenesis of the muscle fibre, a more definite idea of the growth of muscle in general may be arrived at.


FURTHER OBSERVATIONS ON THE CHEMICAL NATURE OF THE ACTIVE PRINCIPLE OF THE

SUPRARENAL CAPSULE.

By John J. Abel, M. D.

[From the Pharmacological Laboratory of the Johns Hopkins University .'\


In my first paper on the chemistry of the suprarenal capsules, in which I reported in detail on researches carried out with the help of Di: A. C. Crawford, I was able to show that the blood-pressure raising constituent can be separated from aqueous extracts of the capsules in the form of a benzoate, and that this remarkable substance is not, as has been maintained, either pyrocatechin or an immediate derivative of it, and V. Fiirth,* in an interesting paper published after, announces the same conclusion. We also gave as our opinion that this substance is to be classed with the alkaloids, founding this opinion on facts stated at length in our paper.

It is my purpose to give in the following brief paper an outline only of certain new observations made in the past year on this chromogenic substance or blood-pressure raising constituent.f

The extract used had been prepared with warm water slightly acidulated with sulphuric acid, and it was then concentrated in vacuo until the extract from 50 kg. of fresh suprarenals was reduced in volume to about 10 liters. This condensed extract was then heated to 80°, the coagulated proteids were filtered off and the clear filtrate benzoated in fractional poi'tions. It was found to be unnecessary to remove the proteids entirely.


Hoppe-Seyler's Zeitschr. f. physiol. Chem., vol. 24, p. 1-42. f It is a pleasant duty to acknowledge that this rpsearch would have been impossible but for the liberality of Messrs. P. D. Armour & Co., of Chicago, who have supplied me with large quantities of a concentrated aqueous extract of the suprarenals of the beef prepared according to my direction. My thanks are also due to Prof. A. G. Manns, chief chemist of the firm, forthe care he has taken in preparing these solutions and for the interest he has taken in the scientific aspects of tlie subiect.


The crude, sticky mixture thus obtained, which consisted of the benzoates of our chromogen, of inosit, possibly also of carbohydrates, creatine and other substances, was then washed thoroughly with water and then dissolved as far as possible in warm glacial acetic acid. A considerable residue remained undissolved. The acetic acid solution was poured into much ether, and again a great deal of material was precipitated. The acid ether solution was first repeatedly shaken out with water, causing a further deposition of resinous matter, and then with a solution of sodium hydrate until all the acetic acid was removed and only a clear but slightly colored ether solution of a benzoate remained. These repeated washings caused copious deposits to fall out.

The ether solution was again washed with water and then once or twice with a 10 per cent, solution of sulphuric acid, followed with water. This washing with acid was now discontinued as it caused the benzoate of the chromogen to fall out in the form of a sticky resin.

It will be seen that by the above processes a number of foreign benzoates are removed; thus, the benzoate of inosit being insoluble in glacial acetic acid and that of grape sugar in ether.

When the benzoate of the chromogen had been treated as stated the ether was removed by distillation, and a yellowish, sticky benzoate remained which became brittle when allowed to dry in the air in thin layers. By boiling its alcoholic solution with animal charcoal, further purification was effected, so that when small quantities of this alcoholic solution were allowed to evaporate bunches of prismatic crystals were deposited. Many different solvents have been tried, but from none does it crystallize with enough difficulty to leave a mother-liquor.

Nevertheless, I have been able to learn something as to the


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[Nos. 90-91.


composition and natnre of the cliromogen, the assumed bloodpressure raising constituent. lu order to isolate this substance, the benzoate as obtained from the washed ether solution was decomposed with water in an autoclave under a pressure of 8-13 atmospheres. A clear, slightly straw-colored solution is thus obtained, which, when freed from benzoic acid and from a certain amount of a black resin which is deposited here as well as in other methods of decomposing the benzoate, gives all the well-known color and reduction tests of a fresh aqueous solution of the glands with one diiference, which is that the addition of a little ammonia and iodine water no longer gives the characteristic rose-pink color, but instead, a vivid green. In all other respects the chromogen appears to be unaltered. A little ammonia, however, is set free during the hydrolytic decomposition just described, but whether this is derived from our substance or from some benzoate still contaminating the benzoate of the chromogen cannot as yet be stated.

When all the benzoic acid has been removed from the solution of the benzoyl product as taken from the autoclave, the cautious addition of very dilute ammonia, drop by drop, causes a copious precipitation of a substance which falls out in a flocculent precipitate much as does casein when precipitated from milk with acetic acid. The precipitate rapidly darkens and must be removed with the help of a suction filter as rapidly as possible.

It is washed with a little water, then with cold absolute alcohol and ether, and immediately ground up in agate mortars while it is still moist with ether. On drying it becomes a light grayish powder. This is the free chromogen with such slight modification as has occurred during the hydi'olysis of its benzoate. When dry it is almost insoluble in water as also in a whole series of organic solvents ; it is very soluble in warm dilute acids, in cold glacial acetic acid and in acetic anhydride. Dilute solutions in slightly acidulated water give an intense green color with ferric chloride or with ammonia, and they reduce ammoniacal silver solutions. Such solutions, exposed to the air, gradually deposit a brown precipitate, and this goes on until but little of the chromogen is left.

The behavior of the substance toward the halogens, which all precipitate it from its solutions, and toward the numerous alkaloidal reagents, I hope to report on at some future date. I shall only say here that a little of the dried chromogen obtained by breaking up the benzoyl product with acids as described in my first paper and which still gives the rose-pink color with ammonia and iodine water, strikes a rich plum color when treated with a drop of sulphuric acid or with Mandelin's reagent, reminding one of the effect of similar tests on strychnine. The chromogen as derived from its benzoate by hydrolysis in the autoclave does not give this color, but an olive-green followed by pink, which gives place to dirty hues.

Strong alkalies decompose the substance, boiling it with alcoholic solutions of potassium hydrate and chloroform brings out the nauseating odor of a carbylamine. On attempting to isolate this volatile substance by distillation, it was found to be decomposed, and on again treating the distillate with alcoholic potash and chloroform, the carbylamine was regenerated, thus showing that a primary amine had been split off when the chromogen was treated in this way.


SKATOL : A DECOMPOSITION PRODUCT OF THE CHROMOGEN.

On fusing the substance with powdered potassium hydrate and then diluting with water, the penetrating odor of skatol rises from the solution. When this solution is shaken out with ether and the ether allowed to evaporate, little globules remain having an intensely foecal odor, and when these are dissolved in concentrated hydrochloric acid the solution at once takes on the fine characteristic pink color always seen when even small quantities of skatol are thus treated.

An alcoholic solution of these globules gives to a pine sliver, moistened with hydrochloric acid, a rich dark red color; a solution in benzol to which picric acid in benzol is added immediately deposits a picrate, not in crystals but in the form of reddish droplets, and an aqueous solution treated with sulphuric acid and potassium nitrite gives the whitish turbidity seen when skatol is similarly treated. Salkowski's reaction was also obtained, though imperfectly, as the production of intense colors in this test demands more substance than was left at my disposal.

The characteristic odor of this decomposition product, together with its chemical reactions, would make it appear that we have either skatol itself or one of the isomeric indols.

Some importance must be attached to this discovery, since, taken with the various reactions of the chromogen, the results of the elementary analyses and such facts as that dry distillation yields benzoic acid, amines, etc., and heating with zinc dust yields pyrol, it clearly enables us to classify the chromogen, in a preliminary way at least, among complex aromatic bases not very dissimilar from the alkaloids. The results of combustion analyses show that its empirical formula is C17H15NO4, thus approaching in elementary composition some of the alkaloids.

The composition of pseudomorphine, for example, is represented by CnHi9N04, that of cocaine by CnHsiNO., that of sanguinarine by CioHisNOi, and that of benzylideue collidine dicarboxyacid by CnHisNO., and among these alkaloids sanguinarine is noteworthy for its power to raise the blood pressure.*

In this connection, too, it is of interest to note that Stohrf has shown that skatol is liberated when strychnine is heated with calcium oxide, and that Hoffmann and KonigsJ have obtained indol from tetrahydroquinoline by passing its vapor through a tube heated to redness.

ANALYTICAL RESULTS.

The results of the elementary analyses are as follows:

0.145 gm. of substance, dried in vacuo at 100° C, gave 0.3675 gm. CO. and 0.0681 of H2O or 69.1 3,'?; C and 5.24,-?; H.

A second anlilysis made with 0.1863 gm. of substance, prepared at a different time and with slight modifications, gave 0.473 gm. of CO.2 and 0.0103 gm. of H=0 or 69.28^ C and 6.09^ H.

A nitrogen estimation, using substance prepared at the same time as that used in the second carbon and hydrogen analysis, gave the following results :


H. Meyer, Arch. f. exp. Pathol, u. Pharmakol., XXIX, 426. t Berichte d. Deutsch. chem. Gesellsch., vol. 20, p. 1108. t Ibid., vol. 16, p. 738.


Septembek-October, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


217


0.1784 gm. of substance gave 7.8 cc. of N at 21° C. and under a barometric pressure of 761 mm. of mercury. In this estimation, tlierefore, the N amounts to bfc.

Putting these results in tabular form, we have


I.


II.

69.28 6.09 5.00


C — 69.12 H= 5.21

N =

Calculating for an empirical formula, we find that the expression CuHisN'Oi meets the requirements, since theory demands for C 68.68

H 5.05 N 4.71 The agreement between the percentages demanded by this formula and the results obtained by analysis is as close as could be expected, since we are dealing with an amorphous substance and one in which the percentage of both H and N is very low.

In all of the above analyses a correction of 9.2 per cent, in the weight of substance given is made for ash. In spite of the fact that the beuzoate itself is entirely free of ash, the amorphous chromogen obtained from it has carried down much mineral matter derived from the utensils used iu the cleavage experiments and in subsequent manipulations.

The acetate of the new substance was also prepared and analyzed. The results thus far obtained are not fully in accord with the above formula, but this is diie to the fact that the acetate decomposes during drying at 100° C. in vacuo. Acetic acid appears to be given off under these circumstances, and thus the C, H and N" content is much changed from that required by the formula thus given. I do not doubt that when analyses are made with the avoidance of this loss the results will be concordant.

Not being able to repeat this part of the work at present, owing to lack of material, I here append the results of analyses made with an acetate which was constantly losing weight. The acetate was prepared by dissolving the free base in glacial acetic acid, and allowing this acid solution to flow in a thin stream into ether. The acetate is at once completely precipitated and may readily be collected, washed and dried. The percentages obtained on analyses were

C = 58.16

H= 5.82

]Sr= 5.04 whereas the diacetate CnHuNO^CiH.OO: requires

C = 60.43

H= 5.51

N= 3.36

The analytic data for the above percentages of C, H and N are as follows :

0.153 gm. of acetate gave 0.3263 gm. of 00= and 0.0802 gm. of HjO ; 0.2046gm. of the same material gave 9.1 cc. of Nat 20.5°C. and under a barometric pressure of 754.6 mm. of mercury.

The method of preparation of the acetate does not tend to diminish the ash, and fusing the substance on platinum foil showed its presence in at least as large amounts as in the free base. In the absence of direct estimates for ash, it was thought fair to assume its presence to the extent of at least 10 per cent., and the weights here given have been corrected in accordance with this assumption.


I have already remarked that an analysis of the benzoate of the chromogen as thus far prepared showed it to contain C = 72.54^ H = 5.54$i^, N=i3.46^.

The analytic data are as follows :

0.2966 gm. of substance dried iu vacuo at 80" C. gave 0.78895 gm. of CO^ and 0.14785 gm. of HjO. 0.29656 gm of the same material gave 8.7 cc. of N at 18.25° 0. and under a barometric pressure of 760 mm. of mercury.

The mouobenzoate of CmHhNO. is CHhNO-.CO.OoH^ and requii'es that C = 71.82j^

H= 4.74^ N= 3.49^ whereas our analysis gives

C = 72.54 H= 5.54 N= 3.46

This discrepancy in the carbon and hydrogen percentages is readily accounted for as the amorphous resinous benzoate analyzed is exceedingly difficult to dry to constancy of weight, and is, furthermore, perhaps not quite free from foreign benzoates. The results of analyses, nevertheless, point to the conclusion that we have the monobenzoate of the new base before us.

The above-named methods of isolating the active jirinciple are far from being as satisfactory as could be desired. The resinous substance found in the autoclave on decomposing the benzoyl product always retains a considerable amount of the base. This may be extracted with dilute sulphuric acid and may then be precipitated with ammonia. This precipitation is, however, incomplete — a considerable amount of the base always remaining in solution. A considerable loss also occurs during the washing of the free base with water and alcohol, the latter agent especially dissolves considerable of the moist precipitate. The high ash content of the free base and of the acetate is also a most undesirable feature of the methods above described. Had there not been a tolerably fair agreement in the analytical results for the free base, its benzoate and iicetate, with good reasons for the divergence in the case of the acetate, I should have hesitated to publish my results at this time.

I have lately found in sodium picrate a good agent for the complete precipitation of the base from its solutions in dilute mineral acids. The picrate is fairly soluble in a number of organic solvents, as, for example, alcohol, acetic ether and methylal, and may be precipitated from its solutions in these agents by the addition of much ether. On redissolving and reprecipitating a yellow picrate is obtained which leaves no ash when burned on platinum foil, and which, I believe, can be made to crystallize. It is my intention to give, in the near future, a more detailed description of the properties of this picrate with analyses and molecular weight determinations.

SUMMARY.

To summarize the results of this investigation in a few words : The active principle of the suprarenal capsule has been isolated iu the form of a powder of a light gray to brownish color, whose percentage composition is expressed by the formula CnHuNO*. A primary amine and a methylindol are easily split off from its molecule by treatment with powdered alkalies.

Should molecular weight determinations prove that the above formula correctly expresses the molecular weight of the new base, it will be seen that its molecule can contain


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[Nos. 90-91.


only one substituted benzene ring in addition to the nitrogenous complex of atoms from which the skatol is derived. Oxidation and substitution experiments are, however, still necessary before more definite statements can be made as to the constitution of this compound.

In its native state, as found in the suprarenal capsule, this substance differs by one chejjiical reaction only from its state as described in this paper. Chemically considered, the difference in composition between its native state and as here


described must be very slight. And yet this difference which is just marked enough to give a greater stability to the substance is also great enough, apparently, to deprive it of its power to raise the blood-pressure, for, jn the physiological experiments, thus far made, small quantities of the new base were found to be inactive in this respect.

I wish to express my thanks to my assistant. Dr. Walter Jones, for the valuable assistance rendered in making the analyses recorded in this paper.

THE LOBULE OF THE SPLEEN

Mall FP. The lobule of the spleen. (1898) Johns Hopkins Hospital Bulletin 9: 218-.

By Franklin P. Mall. (From the Anatomical Laboratory, Johns Hopkins University.)


When the whole vascular system of the spleen is studied in connection with the trabecular system, it is found that the two together outline distinct masses of spleen pulp about one millimeter in diameter. These may easily be likened to the liver lobules, and for this reason I name them the lobules or the anatomical units of the spleen.

If a piece of fresh spleen is washed out by crushing it between the fingers in flowing water, it is found that the trabeculse and veins outline spaces which were filled with pulp. They are best demonstrated by macerating the whole spleen in water at ordinary room temperature until the pulp is very soft. Then, by cutting off the small end of the organ, the debris may be washed out, leaving the capsule, larger veins and trabeculffi. A specimen obtained in this way may then be stained with acid fuchsin, washed with alcohol, distended and dried. Then with transmitted light the lobules are plainly seen as vesicles immediately below the capsule. By first injecting the spleen with either colored celloidin or agar-agar before macerating, the relation of the arteries and veins to the lobules can be determined. This is possible because neither the celloidin nor agar-agar is destroyed by the process of maceration. Thick sections made from such specimens may be immersed in xylol or mounted in Canada balsam.

It is found by studying numerous specimens of this sort, as well as those made by injecting cinnabar into the arteries and ultramarine blue into the veins, that the artery always penetrates the lobule and passes along its center, while the vein is intimately related to the trabecule and remains on the periphery of the lobule. In the case of the lobules lying immediately below the capsule, the artery enters the side as far away from the capsule as possible, as shown in the figure. The end of the lobule at which the artery enters I shall term the proximal side, while that opposite will be designated the distal side of the lobule. The deeper lobules of the spleen, then, have a distinct relation to the artery and not to the capsule. The Malpighian corpuscle usually lies in the proximal end of the lobule, but, in case it is very large, it may distend the lobule and cause it to bulge.

On an average there are 80,000 lobules in the spleen of a dog weighing 10 kg. In smaller spleens there may be as few as 25,000, while in larger spleens there may be 200,000. In all cases they are clustered together around the terminal branches of the artery in the same manner as the lobules of the lung are


around the bronchus and the lobules of the liver around the hepatic vein. In order to understand the structure of the spleen it is necessary to study one lobule only, and for its anatomy the relations of the lobules to one another.



Fig. 1 Diasram of the Lobule of the Spleen. A, artery in the

centre of the lobule; r, interlobular vein within the interlobular trabeculie ; Tr, intralobular trabecula- ; L, JIalpiijhian follicle ; C, intralobular collecting vein ; P, intralobular vein plexus which surrounds the pulp cords or histological units; Am, ampulla of Thoma.

The accompanying figure is a diagram of an average lobule drawn to scale. In no case can a picture like this be gotten from a single section, as the artery and two veins are never in the same plane. Moreover, the branches from the artery, as well as those from the vein, radiate from the main stem and pass in all directions. Practically all of the interlobular veins


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are covered by interlobular trabeculse, but tbere are numerous interlobular trabeculse which are solid. In the periphery of each lobule there are three main interlobular trabeculag, each of which sends three branches into each of the three surrounding lobules. The intralobular trabecule communicate with one another within the lobule, thereby dividing the lobule into about ten compartments. The relation of the veins to the lobule is much like that of the trabeculas. In fact, it is the relation of the trabecule to the veins which makes the lobule. The large veins of the spleen cannot be said to lie within the trabeculse, although their walls are thick, are continuous with the trabeculas and give rise to them. The points which mark the separation of the smaller veins from the trabeculse mark the boundary of the lobule (see diagram). As the venous branches leave the lobule they are at first independent of the intralobular trabecule, but near their exit they are related to them. The intralobular collecting veins also aid to divide the lobule into the ten parts, spoken of above. Of course the artery is distributed to the lobule from a direction opposite to that of the veins. The tendency is for veins and arteries of the same order to remain as far separated from one another as possible. The central artery of the lobule gives rise to .about ten branches, each of which passes into one of the ten compartments of the lobule and through its centre. All of the above can be demonstrated best with granular infections, thick sections and low magnification.

If an interstitial injection of the spleen is made with an aqueous solution of Prussian blue, or if the blue is injected into the vein, it is found in either case that the venous plexus of the lobule is completely filled. This plexus is indicated in the figure giving its relation to the surrounding structures. It divides the spleen pulp into small areas or the histological units as I call them. In fact, however, these areas are not isolated, but communicate with one another as do the cavities of a sponge. Since the histological units run together to form cords of spleen tissue, I term them collectively pulp cords. Thick sections which leave the venous plexus intact show the optical section of the pulp cords or the histological units, while very thin sections cut the venous plexus and demonstrate the pulp, cords. The terminal arteries ramify in the pulp cords and along their course, give off numerous small branches which end in a dilatation, the ampulla of Thoma. The beginning of the ampulla always lies in the centre of a pulp cord. As a rule a number of the minute branches arise from each terminal artery and radiate in all directions. I have been able to obtain complete injections of the vascular system of the spleen only after the organ has been distended to its maximum by ligating the vein half an hour before killing the animal or by making an artificial oedema with gelatin by injecting it into the veins. By both methods all the intercellular spaces within the pulp cords become enormously distended. In spleens prepared in either of the above ways the ampulla? and their communications with the veins may be filled by injecting an aqueous solution of Prussian blue into the artery. If carmine or some such fluid is used it will only add another color to the fluids in the pulp spaces. The blue, however, precipitates easily and with it, it is often easy to obtain complete injections. The specimen is made still better if the venous plexus is marked by injecting chrome yellow into the vein


before injecting the blue into the artery. The gelatin-spleens are best cut on the freezing microtome and mounted in glycerine, as alcohol causes too much shrinkage of the gelatin. The injections show that the ampullffi have a tendency to communicate with amptillje from neighboring arteries, while other branches comnnmicate directly with the veins. Yet judging from the amount of extravasation which is always present the walls of the ampullar must be very porous.

Carmine gelatin injected into either the artery or vein will cause an CBdema of the pulp; in case it is injected into the artery it will ultimately run out of the vein, while when injected into the vein it will never run out of the artery. When cinnabar is injected into the artery, the greater part of it passes directly over into the vein, while a small portion of the granules pass into the tissues. When it is injected into the vein a considerable quantity passes into the intercelltilar spaces of the ptilp cords, showing that the walls of the vein are pervious. Solutions of nitrate of silver injected into the artery show that the endothelial coat becomes incomplete at the beginning of the ampulla. The first two-thirds of the amptilla are lined with spindle-shaped cells lying upon a delicate framework of reticulum. Throughout the last third, at the junction with the vein, no cell boundaries can be demonstrated, nor can this portion of the amptilia be injected from the vein. In fact it appears as if this portion of the ampulla were cut up by fibrils of reticulum passing across it. Silver injected into the veins shows that the complete layer of cells ends at the point of junction of the intralobular plexus with the intralobular collecting veins. Throughout the plexus the cell walls are incomplete and the endothelial cells are spindle-shaped, the space between them being large enough to allow cinnabar granules to pass easily, tiltramarine blue granules with difficulty, and chrome yellow granules not at all. The openings in the veins are largest in the neighborhood of the Malpighian follicles.

The reticulum extends throughout the lobule, supplies the framework for the ampullse and the venous plexus, and is continuous with the reticulum of the lymph follicles surrounding the arteries. Its arrangement is such that an cedema distends the lumina of the veins out of proportion to those of the pulp spaces. The reticulum is very delicate and elastic. It can be stretched to double its length and when relaxed it will return to its former shape. It is easily destroyed with acid or with alkali, and is digested with pancreatin. This last reaction makes of it a new variety of reticulum. While this reticulum is so delicate and easily destroyed, the reticulum of the trabeculse and capsule is most resistant. In fact, it is more resistant than that of the lymphatic gland or of the mucosa of the intestine. We have therefore within the spleen two extremes of reticulum, the most resistant and the least resistant.

The microscopic anatomy shows that the ampulla} and venous plexus have very porous walls which permit fluids to pass through with great ease and granules only with difficulty. In life the plasma constantly flows through the intercellular spaces of the pulp cords, while the blood corpuscles keep within fixed channels. Numerous physiological experiments which I have made corroborate this view.

A more detailed account of the facts enumerated above, together with illustrations, is being prepared for publication.


220


THE DEVELOPMENT OF THE BILE-CAPILLARIES AS REVEALED BY GOLGI'S METHOD

By William F. Hendrickson. {From the Anatomical Laboratory of the Johns Hopkina University.)


As the diverticula of epithelial cells grow from the mid-gut and surround the omphalo-mesenteric veins to form the liver there is from the first a duct present, the primitive bile-duct. In the further growth of the liver these diverticula anastomose again and again to form the main bulk of the liver of the embryo. To what extent bile-capillaries are present in these masses may in part be determined by treating the livers of small embryos with Golgi's method, and at the suggestion of Dr. Mall 1 have made numerous tests with this method to determine its value in the study of the development of the bilecapillaries.

The lobule is formed rather late in the development of the liver. In the younger livers the portal and hepatic veins have each for themselves their own regions of tissue about them, which in no way interlace. A later shifting and new formation of vessels is required before we have any indication of a lobule. Human embryos of the fourth week have already formed the main bile-ducts and hepatic artery along the branches of the portal vein, but I have been unable to demonstrate any bilecapillaries in human or in pig's livers from embryos less than 5 cm. long.

Although it is probable that the bile-capillaries are formed directly from the lumina of the liver sprouts from the mid-gut, yet it is impossible to prove this by means of Golgi preparations. The pictures obtained by this method are just the reverse of those expected when the question is considered from the standpoint of embryology. The first bile-capillaries stained by Golgi's method are found immediately about large portal branches in embryos 5 cm. long. From this stage on the pictures show a gradual spreading in both peripheral and central direction until bile-ducts are reached on the one hand and the intralobular plexus on tlie other. It may be that the Golgi method stains only those bile-capillaries which contain secretion.

My successful specimens were obtained from human as well as pig's embryos 5 cm. long, and longer. A great many specimens were made from pig's livers, repeated tests having been made to stain the capillaries in the livers of young embryos. The great quantity of these embryos at my disposal allowed me to make many Golgi specimens of livers in which the artery, the portal vein, or both had first been injected in order to determine the vessel about which the first capillaries appeared. In addition to this I made serial sections usually about 50 /j. thick.

The first Golgi pictures are obtainable in the livers of pigs 5 cm. long (Fig. 1). Human embryos of the same size show a much more advanced network of bile-capillaries (Fig. 4). Yet repeated tests upon livers from pigs 5 cm. long always gave only a few capillaries in the immediate neighborhood of a large vein, which proved to be a branch of the portal vein. Specimens made by injecting either the portal vein or hepatic artery with a small quantity of Prussian blue before staining by Golgi's method always gave the same result, ('. e. that the bile


capillaries are first stained in the immediate neighborhood of the branches of the portal vein.

Fig. 2 is from a pig's embryo 6 cm. long. It shows the bile-capillaries somewhat more extensive, they having encircled the portal branch. In an embryo a little larger. Fig. 3, the capillaries have grown still more, for those encircling different portal branches nearly meet. In addition to this extensive spreading each main bile-capillary has upon it many small side twigs. It appears as if the first meshes enclosed bile-capillaries are cut up by these side branches shooting across from one capillary to the other as the meshes enlarge by the multiplication of liver cells. Only in some way like this could the proper number of bile-capillaries keep pace with the growth of the liver.

The process described in livers of pig embryos up to 8 cm. long must have all preceded the condition found in the liver of a human embryo 5 cm. long, for in the pig's liver and the human liver in these two respective stages the degree of development of the bile-capillaries is much alike. A glance at Figs. 3 and 4 will readily show this. The network of the human liver, however, is much larger than that of the pig, but this seems to be the case throughout development.

Fig. 5 represents the extent of the bile-capillaries in a pig's embryo 15 cm. long. We find here that the bile-capillaries growing about one of the branches of the portal vein have become continuous with those about like branches in the neighborhood. The only indication left of the manner of growth of the bile-capillaries is seen in the relative size of their meshes. The meshes next to the veins are smaller than those situated farthest from the vessel about which the bile-capillaries arose. This figure illustrates again the progressive subdivision of the meshes formed by the bile-capillaries. The meshes near the veins are more dense than those farther distant, and this is easily understood since we know that those around the veins appeared first.

In the human embryo 10 cm. long the bile-capillaries are again as far advanced as those in pig's embryos 15 cm. long. Their relative size and extent are shown in Fig. 6, which may be compared with Fig. 4, taken from a human embryo 5 cm. long.

Fig. 7 is from a pig's embryo 21 cm. long, and Fig. 9 from a human foetus at term. Both of these specimens show the network of capillaries distributed quite uniformly throughout sections, and at first thought it appears as if the growth of the capillaries was complete. But in the adult, both pig and human, the livers are considerably larger and the network is still smaller (Fig. 8).

If we had in the embryo's liver all the ludiments of the lobules of the adult liver it would not be so difficult to interpret these various pictures described above. In the livers of young embryos the portal and hepatic veins are in opposite ends of the liver, the portal being on the distal side and the hepatic on the proximal. When the liver is in this stage the



c


Fig. 1. — Piir, S cm. Ioue:.




Fig. '2, — Pijr, O cm.




c V"



Fig. 6. — ITuman, V) cm


Fig. T.— IMjf, 21



Fig. s.—Ailiilt pii;



Fig. il.— Human futiis at term.



Fig. 13.— Piur, li) cm



Fig. 10.— Piu-, .s cm.



Fiii. 14.— Piir, Hi cm.



Fig. ll.-Piij, Ki



Fiii. l.i.- Pis, -'!) .


Till; Jouss Hopkins Hospital Billetin Nos. 90-91.


September-October, 1898.]


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bile-capillaries are first stained about the branches of the portal vein, although these veins cannot be called interlobular at this time. In the further growth of the vessels the hepatic veins invade the region occupied by the portal and vice versa. This process goes on, by what method we know not, until the lobules are finally formed. It is evident then that in the growth of the liver, as in bone, we must have destruction going on hand in hand with growth. Not only is this true during embryonic life, but Dr. Mall also informs me that a similar process is taking place in the lobule after it is formed. In this latter instance tiie liver lobule is constantly undergoing destruction in its centre and being regenerated at its periphery.

These facts complicate our problem considerably and make it practically impossible for us to interpret our specimens correctly. It appears, however, that in the further development of the liver the bile-ducts grow longer and longer at the expense of the bile-capillaries. At best the Golgi specimens indicate this, and, therefore, I can describe this process.

In the liver of a pig's embryo 8cm. long, the bile-capillaries


immediately about the portal vein are somewhat more marked than those more distant. This is shown in transverse section in Fig. 10, and in longitudinal section in Fig. 11. This process is still more advanced in embryos 16 cm. long (Fig. 12), and in a measure we can speak of this large black capillary as a bileduct. At first the dilatation is even and regular (Fig. 11), but soon it becomes irregular, the meshes become smaller and smaller until a member of capillaries together form a distinct bile-duct. The successive stages of this process are shown in Figs. 13, 14 and 15, and the completed duct is shown in.Fig. 8. When the duct is completed the bile-capillaries communicate in great part only with its tip, and not all along its course as in the case of the younger ducts. This question, however, needs further investigation in normal as well as in diseased livers.

PLATE.

In all the figures the outlined and striated space is a branch of the portal vein. All the figures were drawn with the camera and are enlarged 53 times.


A STUDY OF THE MUSCULATURE OF THE ENTIRE EXTRA-HEPATIC BILIARY SYSTEM, INCLUDING THAT OF THE DUODENAL PORTION OF THE COMMON BILE-DUCT AND OF THE SPHINCTER.

By William F. Hendrickson.


(Prom the Anatomical Laboratory of the Johns Hopkins University .)


The idea that there is a sphincter muscle about the orifice of the ductus communis choledochus has been held since the time of Glisson. In the year 1887, however, Ruggero Oddi, an Italian, had cause to inquire more particularly into the subject. He found that no extended research had been made in this connection, and that the idea of a sphincter muscle of the common bile-duct was based for the most part on conjecture. Oddi accordingly undertook a careful study of the subject and used two methods : (1) maceration, (2) sectioning and microscopic examination.

With the maceration method he examined and described the sphincter muscle of the dog, which he regards as typical, and this description is followed by some observations regarding the differences observable in the sphincter muscle of the sheep, ox and hog. Oddi does not attempt to demonstrate the sphincter muscle in man by this method.

He studied also serial cross-sections of the duodenal portion of the common bile-duct of the dog and other animals, and describes them briefly.

The importance of such studies for the clinician interested in diseases of the biliary passages is obvious, and it is to be regretted that Oddi's material did not permit him to extend his studies to the bile-ducts of man. He states, it is true, that he has studied sections of the human bile-duct, and that he found sphincter fibres around the end of the bile-duct; otherwise his research deals entirely with tissues derived from animals.

In view of this fact a reworking of the subject with par


ticular reference to human beings has seemed desirable, and the present work was therefore, at the suggestion of Dr. Lewellys F. Barker, undertaken. This report includes, it is believed, as full an account of the musculature of the biliary passages of man as the methods employed will permit of, and also contains references to a number of points hitherto unstudied in the structuie of the biliary passages of animals.

I. — History.

II. — Methods employed.

(a) Maceration with a mixture of nitric acid, glycerine and water.

(b) Maceration with Ranvier's alcohol.

(c) Stained celloidin and paraffin sections.

III. — The Musculature of the Biliary Passages in the Dog.

(a) Gall-bladder.

(b) Cystic duct.

(c) Hepatic duct.

(d) Common bile-duct.

(e) Place of union of cystic, hepatic and common bileducts.

(f) Duodenal portion of common bile-duct.

IV. — The Musculature of the Biliary Passages in the Rabbit.

(a) Gall bladder.

(b) Cystic duct.

(c) Hepatic duct.

(d) Common bile-duct.


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[Nos. 90-91.


(e) Place of union of cystic, hepatic and common bileducts.

(f) Duodenal portion of common bile-duct.

V. — The Musculature of the Biliary Passages in Man.

(a) Gall-bladder.

(b) Cystic duct.

(c) Hepatic duct.

(d) Common bile-duct.

(e) Place of union of cystic, hepatic and common bileducts.

(f) Duodenal portion of common bile-duct.

VI. — Conchisions.

VII. — Index Lettering of the Figures.

I.— HISTORY.

For convenience the literature will be divided into two groups.

(a) That concerning the smooth muscle of the gall-bladder, cystic, hepatic and common bile-ducts.

(J) That on the structure of the duodenal portion of the common bile-duct.

ad (rt) In 1761 Duverney* described the gall-bladder of man and divided its wall into four coats, the second coat being the muscular. The fibres which composed it were diversely arranged, some being longitudinal, others transverse or oblique. The fibres near the neck of the gall-bladder showed a circular disposition, and might be regarded as a sphincter.

In 1829, Wilsonf declared that the presence of muscle fibres in the gall-bladder and the gross bile passages had not been demonstrated.

Koel)iker| considered the nrasculature of the large bile-ducts to be but very little developed in man. He could not find a trace of muscle in the hepatic duct or in its branches. Bundles of suiooth mu!j( ie were foiind, however, in the ductus choledochus and in the ductus cysticus, but not in suflBcient quantity to justify the description of a muscular coat.

Only in the gall-bladder was a true muscle coat to be seen; here the muscle bundles crossed in all directions; still those running longitudinally and transversely predominated.

Tobien§ stated that muscle fibres are present in the human gall-bladder and that they run in all directions. The cystic duct, similar to the hepatic duct of man, contains no muscle. The presence of a ring of muscle fibres in the cystic duct near the gall-bladder was, however, confirmed by him. This ring of


♦Duverney (J.-G.) Oeuvrea anatomiques. I'rvris, 1761, t. ii, p. 234.

f Wilson (C.) Observations on the mechanism of the biliary system. Edinb. M. & S. J., 1829, xxxi, 107-114.

tKoelliker (A). Ztsch. f. wissensch. Zool. Leipz., 1848, S. 61-62.

J Tobien (A. I,) De glandularum ductibus effercntibus, ratione imprimis habita telse muscularis. Dissertatio Inauguralis, borpat, 1853, S. 17.


muscle is made up of contiguous muscle fibres, no connective tissue penetrating between them. He cites Glisson* and Duverney as supporters of the view that a sphincter of the gall-bladder exists, and names G. H. Meyerf as being of the opposite opinion.

EberthJ found in man and in the cat and dog, smooth muscle in the gall-bladder only. In each case the muscle fibres run for the most part in a circular direction ; longitudinal and diagonal bundles are, however, present.

Luton§ describes the middle coat of the biliary passages as consisting of fibrous connective tissue, in which are some muscle fibres. In general the muscle fibres are not abundant, especially in the hepatic duct, cystic duct and common bileduct. In the gall-bladder he finds a thin muscular coat, the fibres of which take two courses, viz. longitudinal and transverse.

MacAlisterJI believes that muscle fibres are present in what he calls the fibro muscular coat of the human gall-bladder. The muscle fibres run both circularly and longitudinally, but those of the latter direction constitute only about one-fourth of the whole number. In his description of the valvular folds of the cystic duct, he states that some muscle fibres are present in the bases of the upper valvular folds, but they do not seem to exist in the lower folds, i. e. those nearest the common bileduct.

Paulet^ found in the connective tissue of the biliary passages some contractile cells. The nirmber present was not sufficient to form a continuous coat. Moreover, according to his statement the muscle fibres become less numerous as the calibre of the tube becomes larger. They are scanty in the cystic, hepatic and common bile- ducts of man. The gall-bladder also contains a certain number of smooth muscle cells, but never sufficient, at least in normal cases, to form a distinct coat.

According to Variot** the human gall-bladder contains a network of smooth muscle fibres, the interstices being filled with connective tissue. The common bile-duct exhibited in one case (human adult) discontinuous longitudinal muscular fasciculi; in another case (human adult) only a few circular bundles. In the dog, two superimposed strata of smooth muscle fibres were found which, very thick near the ampulla of Vater, became gradually thinner as the gall-bladder was approached. Between these strata of muscle is interposed a nervous apparatus analogous to that of the intestine.


Glisson (Francis.) Anatomia hepatis ; cui praemittuntur quaedam ad rem anatomicam universe spectantia. Et ad calcem operis subjiciuntur nonnulla de lymphse ductibus nuper repertis. 16°. Hagae, A. Leers, 1681.

f Meyer (G. H.) De musculis in ductibus eflerentibus glandularum. Berl., 1837, p. 31.

t Eberth (C. J.) Ztsch. f. wissensch. Zool., Bd. xii, 360, 1862.

§ Luton (A.) Biliaires (voies). N. diet, de med. et chir. prat., Par., 1866, v, 33-101.

II Mac.\lister (A.) Contributions to the comparative anatomy and physiology of the gall-bladder. Med. Press and Circ, Dubl., 1867, n. s. iv, 129 and 150.

1JPaulet(V.) Biliaires (voies). Dictionnaire encyclop^dique des sciences medicales. Paris, 1868, vol. ix, p. 295 ; 31-1.

Variot (G.) Sur les nerfs des voies biliaires extra-h^patiques. Jour, de I'anat. et physiol., etc., Par., 1882, xviii, 600-610.


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Sappey* in describing the structure of the human gallbladder states that with the connective tissue composing the tunica conjunctivale and which forms a loose feltwork structure, are mixed some very delicate elastic fibres and some thin fasciculi of smooth muscle, scanty in man but more abundant in some mammals. The human cystic duct contains a plexiform arrangement of smooth muscle fibres. The ductus communis choledochus exhibits a structure identical with that of the other bile-ducts. In the hepatic ducts the diameter of virhich is 0.5 mm. or more he sees smooth muscle fibres which extend throughout the whole extent of the biliary passages. These fasciculi even in the large branches are very delicate and much separated. They exhibit a plexiform arrangement.

Cruveilhier"! was not able to see the muscle fibres which other authors describe in the human gall-bladder, and ignored the possibility of the presence of muscle in the human cystic, hepatic and common bile-ducts.

Henle| believes the human gall-bladder contains smooth muscle fibres which interlace with one another. He finds no muscle in the human cystic, hepatic, and common bile-duets, and considers the accumulation of ring-shaped muscle fibres described by Tobien as a sphincter vesicffi fellae, to belong not so much to the cystic duct as to the neck- of the gall-bladder. Henle experimented upon a beheaded man to determine the contractility of the biliary passages but with negative results.

Testut§ finds in the human gall-bladder smooth muscle fibres interlacing in all directions and bound together by connective tissue. In the cystic duct, only longitudinal muscle bundles are seen. The common bile-duct contains in its walls smooth muscle, well developed near the ampulhi of Vater but on ascending the duct; this becofnes less and less prominent until the muscle is even entirely absent at certain points in the duct.

Gegenbaur|| states that in the connective tissue of all the human bile passages (cystic, hepatic and common bile-ducts) smooth muscle cells are to be found. In the wall of the gallbladder they form a very thin coat, network like in character. Sometimes an indistinct longitudinal and circular coat can be made out.

Schiifer and SymingtonTJ state that the human gall-bladder contains plain muscle fibres which assume for the most part a longitudinal direction but some run transversely. They believe that the cystic and hepatic ducts also contain longitudinal and circular muscle fibres.

ad {b) — The presence of a sphincter muscle about the duodenal extremity of the common bile-duct was suspected as early as 1681. In that year Glisson** gave the following description :


• Sappey (M. P. C.) Traite d'anatomie descriptive. Paris, 1889, t. ill, p 273.

tCruveilhier (J.) Traite d'anatomie descriptive. 5 ed., 8°, Par., 1867-74.

t Henle (F. G. J.) Handbuch der aystematischen Anatomie des Menschen. 8°. Braunschweig, 1856-73.

§Te8tut(L.) Traite d'anatomie humaine, etc. Paris, 1889-91.

II Gegenbaur (C. ) Lehrbuch der Anatomie des Menschen. 5. Aufl. 8°. Leipzig, 1892.

K Qualn's Anatomy. 10. ed. London and New York, 1892.

0p. cit.


"Quamprimum autem ductus hie communis utranque exteriorem intestini tunicam perrupit, adeo laxe eum interior tunica complectitur, ut digito hue illuc facillime dimoveri queat: hujusque mobilitatis ratione rem quamlibet ab intestine illapsuramarcet: quemadmodum id exploratu facile est, si mode, aperto intestino, acum aut specillum exiguum iliac immittere coneris. Videbis enim, vario hue illuc subterfugio, spem omnem penetratiouis eludere; nisi forte statim ipsum centrum illius, stylo tetigeris.

Prseterea, ne quid ab intestine in ductum hunc illabatur, ipsa insertionis obliquitas in causa est : quic quid enim illo vorsum tendit, atque ingredi eonatur, id simul eodem nisu interiores intestini tunicas versus exteriorem comprimit, ipsumque adeo aditum pra3cludit: idque eo magis, quo vis illata potentior fuerit.

Denique, regressus omnis in ductum communem prsepeditur a flbris anularibus, qua3 non modo orificium ipsum, sed & totum obliquum tractum obsident. Quemadmodum enim fibrae istse anulares sese facile extendunt, queties humor biliosus diutule repressus eepiaque jam adauctus ad exitum properat; ita quoque, elapse semel superfine humore illo, esedem penitus connivent, transitumque omnem impediunt, donee humoris plusculum denue cellectum fuerit, quod fores illarum effringat. Dari autem ejusmodi fibras anulares hinc constat: Si intestinum ex adverse orificii hujus aperueris, bilenique in illud digitorum opera adegeris, videbis statim ab exclusa bile orificium illud sponte sua denuo occludi; quod sane cirra ejusmodi fibrarum epem, fieri nequaquam posset. Similiter, si insertioni huie specillum indideris, idemque mex inde extraxeris; orificium jam dictum spontanes motu contrahi cernes. Ideoque crediderim aditum hunc eo nomine cum anisphinctere convenire, licet miuore cum molimine clausura illic peragatur: nempe, si quande ab incumbente humore copioso molestia aliqua illata fuerit, mediantibus fibris hisce anularibus transitum ei concedit, denuoque in angustiam pristinam sese centrahit.

Ductus communis in eve aliter, quam in homine in intestinum inferitur. Quippe in ilia, unicas integrse spatio inter intestini tunicas prorepit, priusquam in illius cavum aperitur; tumque fissuram efformat, qiise per intestini longitudinem deducitur. Fissura haec laxa & spongiosa protuberantia, ab interiore intestini tunica enata, utrinque pretegitur: adeo ut, si quidpiam altrinsecus in illam impingat, id earn protinus translabatur, hiatumque occludat. Ipsa tamen insertionis hujus obliquas in ovibus longitude, prsecipue impediniento est, quo minus aliquid ab intestinis in ductum hunc communem regrediatur; quoniam enim orificium ejus in eblongam fissuram desinit, fibris ejusmodi anularibus nihil opus erat. Neque etiam insertie haec in ovibus sque laxe hue illuc eberrat, atque in homine id fieri diximus: ac propterea, quoniam aliis jam dictis auxiliis destituitur, sequum erat, ut itineris longitudo, tunicarumque an iuvicem areta cempressio, illorum absentiam compensarent."

In 1869, Von Luschka* examined the intestinal portion of the common bile-duet of man and found a longitudinal open


Von Luschka (H.) Die Pars intestinalia des gemeinsamen Gallenganges. Vrtljschr. f. d. prakt. Heilk., Prag., 1869, ciii, 86-100.


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ing in the outer longitudinal coat, and a transverse opening in tlie inner circular muscular coat of the intestine which gave passage to the duodenal portion of the common bile-duct.

In 1887, R. Oddi* undertook to demonstrate the sphincter of the common bile-duct. He says: "I have found that no one has made a research upon this svibject, although some, either by imagination or conjecture, have assumed the existence of such an arrangement."

Oddi employed in his investigation the macerating fluid proposed by Marcacci — a mixture of equal parts, by volume, of concentrated nitric acid, glycerine and water. The duodenal portion of the common bile-duct (of the dog, sheep, ox and hog) was examined with the best results. Oddi did not examine human specimens with this method. He mentions the following points as the result of a study of macerated specimens from animals belonging to different species. The course of the common bile-duct which runs across the intestinal tunic varies with the animal. Around the last part of the common bile-duct, almost in proximity with the mouth of the duct, he sees a muscular ring ; this ring, after the removal of some delicate loops which run from its external surface to become lost in the muscle of the intestine, can be considered as independent.

Little by little, as the point of entrance of the common bileduct into the intestinal wall is approached, the fusion of the circular fibres of the common bile-duct with the intestinal wall becomes more intimate, so that the common bile-duct cannot any longer be elevated. This may be due to the fact that of the circular fibres of the common bile-duct some run off to become implanted on the circular muscle of the intestine ; like cords, fastened at the two poles of an oval, they go to become fixed at two firm points opposite one another in order to attain support. After these bonds have been cut the common bile-duct with its circular fibres can be isolated for some distance, up to the point where it plunges through the circular muscular fibres of the duodenum. Here the bile-duct raises the circular muscle fibres of the duodenum, forming a wedge-shaped opening. Oddi says it must be noted that in the animals examined by him, these fibres (sphincter fibres) did not appear always equally disposed, but necessarily assumed that form and disposition which could best adapt itself to the form and course of the common bile-duct in the intestine. Thus, in the sheep and the ox, where the common bile-duct runs parallel to the intestinal axis, they are hidden and parallel to the intestinal fibres; in the dog, in which case the common bile-duct runs obliquely to the axis of the intestine, they are oblique and less hidden ; while in the hog, where the common bile duct has a course like a " C ", they are so strangely disposed as to be difficult to describe.

Oddi studied microscopically, sections cut transverse or perpendicular to the axis of the intestine of various animals at different levels. The following descriptions of the dog and sheep are given as typical. In a section taken at the point where the common bile-duct has just entered the muscular wall of the intestine, there is seen externally the stratum


Oddi, R. Di una specials disposizione a sfintere alio sbocco del coledoco. Ann. d. Univ. libera di Perugia. Fac. di med. e chir., 1886-7, ii, 249-264, 1 pi. Also, Reprint, Perugia, 1887.


longitudinale of the muscular coat of the intestine, and just internal to this the stratum circuiare which presents a buttonhole-like arrangement of its fibres through which the common bile-duct is seen to pass ; the bile-duct is thus embraced by two muscular coats (formed by the buttonhole-like arrangement of the fibres of the stratum circuiare), which reunite at its poles. Between the poles of the common bile-duct and the angle of reunion of the two muscular layers, there remains a triangular space, the base of which is formed by circular muscle fibres which both on the exterior and on the interior are inextricably mixed with the two circular muscular layers above mentioned. At the side of the circular muscle fibres just described are seen longitudinal fibres quite noticeable in section.

If the section be taken a little nearer the middle of the course of the common bile-duct, it is seen that the internal muscular layer has become thinner, while the external has acquired greater volume. Between the two layers the section of the duct can be seen, surrounded by a true muscular ring which is not intimately related with the two intestinal muscular layers. The muscular ring of the duct seems, in the section, to be entirely independent.

A section near the mouth of the common bile-duct shows that the division of the circular muscular layer of the intestine no longer exists — the ring described remains only in slight contact with the inner surface of the fibres of the stratum circuiare of the intestinal muscular tunic. A continuation of the longitudinal fasciculi at the poles of the common bileduct is also seen.

Oddi next proceeds to give some points distinguishing the animals examined from one another. • A characteristic disposition of the muscle is, he says, proven for the rabbit. The muscular ring which envelops the common bile-duct appears in a section transverse or perpendicular to the long axis of the intestine. He emphasizes this fact, for it demonstrates, he thinks, the independence of these fibres from those of the intestine. In man, owing to the fineness of the muscle fibres, the disposition is not characteristic. Nevertheless, the circular as well as the longitudinal fibres (at the poles of the lumen of the common bile-duct) are very manifest. The circular fibres, however, cannot be followed for a great distance around, since, for the more part, they become lost in the connective tissue which supports the mucous membrane in its numerous anfractuosities. The fibres here mentioned have but little relation to the muscular layers of the intestine.

As to a special disposition of the muscular fibres at the mouth of the pancreatic duct, Oddi states that in the duodenum of a dog prepared by Marcacci's method of maceration, he was able to see at the mouth of the pancreatic duct (which is obliquely distant about two inches from the mouth of the common bile-duct) some special fibres disposed in a ring, very delicate and quite distinct from the intestinal muscular coats. This arrangement was confirmed by transverse and longitudinal sections taken at the mouth of the pancreatic duct.

II.— METHODS EMPLOYED. In the present investigation three methods were employed to demonstrate the smooth muscle of the biliary passages.


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(a) The most important of these, in some respects, is the method used by Marcacci* for demonstrating the muscuhiture of the papilla mammffi. The method consists in macerating the tissue to be examined in a niistiire of equal parts by volume of concentrated nitric acid, glycerine and water.

In applying it to the present study, the vertical portion of the duodenum was cut out and ligated at its two extremities. A cannula was introduced into the ductus choledochus and the above-mentioned mixture was injected into the intestine until its walls were well distended. The common bile-duct was next ligated and the entire specimen placed in a vessel full of the same macerating mixture. After a certain period of time the tissue was removed and placed in water. The intestine having been cut open on the side opposite the mouth of the common bile-duct, the mucous membrane was removed quite easily with forceps. The water was changed and the specimen allowed to remain thus for 24 hours. At the end of this time the specimen is ready for examination. The muscle fibres have the color and brilliancy of raw silk and, having absorbed water, stand out quite beautifully.

To demonstrate the muscle of the gall-bladder, cystic duct, hepatic duct and common bile-duct, the gall-bladder and hepatic duct were dissected from the liver; the hepatic duct was ligated and after ejecting the bile through the common bile-duct by pressure on the gall-bladder, the macerating mixture was injected up the common bile-duct until the walls of the gall-bladder were distended. The common bile-duct was then ligated and the whole mass placed in a vessel containing the same macerating mixture. The rest of the process is the same as for the duodenal specimen.

The period of maceration in nitric acid, glycerine and water has to be varied according to the delicacy of the specimen.

(b) Another method employed with advantage was that of maceration in Ranvier's alcohol. This method was found most useful in making permanent preparations of the gall-bladder. The gall-bladder, having been cut open, was allowed to macerate in Ranvier's alcohol for a week or ten days. The specimen was then removed and the epithelial cells brushed away with a stiff camel's hair brush. The serous coat and outer connective tissue coat were removed with forceps. The specimen was then stained with alum carmine or with hematoxylin and eosin and mounted in Canada balsam with the mucosal side down. This gives a bird's-eye view of the arrangement of the muscle in the wall of the gall-bladder.

(c) The third method employed was that of fixing, embedding, sectioning and staining the various parts. The specimens were fixed in absolute alcohol, formalin, or corrosive sublimate and imbedded in celloidin or paraffin. The principal stain used was that suggested by Van Gieson since the differentiation of minute quantities of smooth muscle from the surrounding connective tissue by this stain is quite exquisite. Other methods of staining were, however, employed for purposes of comparison.


Marcacci (A). II muscolo areolo-capezzolare. Gior. di R. Accad. di med. di Torino. 1883, 3. S., xxxi, 743-753. Also.TransI.: Arch. ital. de bid., Turin, 1883. iv, 292-254.


III.— THE MUSCULATURE OF THE BILIARY PASSAGES IN THE DOG.

(a) Gall-bladder. — Specimens macerated in a mixture of nitric acid, glycerine and water showed the arrangement of smooth muscle to be plexiform. The circular or transverse fibres are most numerous. The gall-bladders macerated in Ranvier's alcohol showed an arrangement exactly like the above. Longitudinal celloidin sections cut from the body of the gall-bladder, showed smooth muscle running in three directions, transverse, longitudinal and diagonal. Fig. 1.

Most of the muscle bundles run around the gall-bladder in a transverse direction, i. e. in a direction perpendicular to the long axis of the gall-bladder. The muscle bundles are not arranged in definite and regular coats; the transverse, longitudinal and diagonal bundles mingle without conformity to any rule. The muscle bundles are more or less separated from one another by a certain amount of connective tissue, but since the individual muscle bundles overlap, there are few if any places in this coat where muscle is entirely absent.

(J) Ci/slic duct. — Macerations in a mixture of nitric acid, glycerine and water revealed the presence of both transverse and longitudinal muscle fibres. In celloidin sections cut parallel to the long axis of the tube smooth muscle can be demonstrated running in three directions, transverse, longitudinal and diagonal. Fig. 2.

The absolute amount of transverse and longitudinal muscle is about equal. The diagonal muscle fibres are many fewer in number. The general arrangement of the smooth muscle bundles is plexiform. The connective tissue penetrates between the muscle bundles to a degree relatively greater than in the gall-bladder. Fig. 3 is taken from one of the valves of Heister. It is the largest fold found in tliis specimen and presents an arrangement of muscle which is much more accentuated in human specimens {vide infra). No such ai-rangement was found in the cystic duct of the rabbit.

In the cystic duct of the dog portions of the longitudinal muscle bundles curving around and running out into the valve can be made out. Other bundles of muscle, having origin apparently in the circular or transverse fibres of the cystic duct, run out into the valve. The report of the study of the Ileisterian valves of human beings is accompanied by a detailed account of this arrangement.

(c) Hepatic duct. — Longitudinal muscle fibres were found in specimens macerated in a mixture of nitric acid, glycerine and water. Longitudinal sections of the hepatic duct showed only longitudinal fibres. Fig. 4. The fibres are but few in number and the disposition of the muscle is such that there can be no talk of a continuous coat.

(d) Common bile-duct. — Macerations in a mixture of nitric acid, glycerine and water showed a few longitudinal muscle fibres. Longitudinal celloidin sections showed smooth muscle running in three directions, longitudinal, transverse and diagonal. Fig. 5. The longitudinal bundles are most numerous, the transverse bundles next in number, the diagonal bundles being least numerous. The muscle fibres do not form a complete coat; they are found scattered amongst much connective tissue.

(e) At the place of union of the cystic, hepatic and common


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bile-ducts, no extraordinary muscular arrangement was seen. Each duct preserved its normal structure, the wall of each gradually merging into that of the others.

(/) Duodenal por/io7i of the common bile-duct. — That portion of the duodenum which contains the duodenal papilla having been macerated in a mixture of nitric acid, glycerine and water as described above, was exariiined in the following manner: The intestine was cut along its longitudinal axis on the side opposite the duodenal papilla and laid open. The mucous membrane was removed and with it the muscularis mucosa. The appearances at this stage are represented in Fig. 6.

From the point where the common bile-duct enters the intestine A to the point B, the muscle fibres of the inner circular muscular coat of the intestine are seen to pass over the common bile-duct. From the point R, to the point O, an irregular arrangement of muscle bundles is seen to exist. This arrangement resembles in shape more or less that of a mark of interrogation placed in a horizontal position. The structure has its origin (1) partly in the fibres of the inner circular muscular coat of the intestine, (2) partly in fibres which lie under the inner circular muscular coat and which arise from the median line of the bile-duct and (3) partly from the ring of muscle surrounding the mouth of the bile-duct. The fibres after this origin run forward (i. e. towards the lower end of the duodenum) and, passing under the fibres of the inner circular muscular coat of the intestine, blend with the fibres of the outer longitudinal muscular coat.

Out of eight specimens I found no two cases in which this irregular arrangement was alike. A description of the mode of origin and termination of these muscle bundles is accordingly of but little value, although an exact determination was made in each case.

Continuing from the point to the mouth of the common bile-duct J/, one can see muscle fibres running around the end of the common bile-duct. A careful examination of this region shows that a complete ring of muscle surrounds the mouth of the common bile-duct. At the same time, close observation reveals a certain number of muscle fibres running ofl' from the two sides of this annulus of muscle. These latter are in reality part of the ring of muscle and after separating from the ring at its sides bend abruptly forward, i. e. towards the lower end of the duodenum. This ring of muscle with the lateral muscle bundles arising from it constitutes the sphincter of the ductus communis choledochus.

In Fig. 6 the muscle bundle seen coming off from the nonpancreatic* side (see X) of the annulus of muscle corresponds with the arrangement usually found. At first sight there seems to be no corresponding bundle for the other side (i. e. pancreatic side) of the muscle ring. It will be remembered, however, that the structure similar to a mark of interrogation had its origin in part in some fibres of the muscle ring about the mouth of the common bile-duct. These fibres of origin, in this case, take the place of the muscle bundle which runs off


The terms non-pancreatic and pancreatic are used here to discriminate between the two sides of the bile-duct. The pancreatic side is so called because the common bile-duct is usually joined on this side by the duct of Wirsung.


at the pancreatic side of the muscle ring. The fasciculus on the pancreatic side of the muscle ring must terminate, after running forward a short distance, as described above in connection with the termination of the structure resembling a mark of interrogation — by passing under the fibres of the inner circular muscular coat of the intestine and blending with the fibres of the outer longitudinal coat. The fasciculus on the non-pancreatic side of the muscle ring, after running forward a short distance, curves slightly to the pancreatic side and finally terminates by mixing superficially with the fibres of the inner circular muscular coat of the intestine. The manner of termination of these lateral fasciculi of the annulus about the mouth of the common bile-duct varies somewhat. They end:

(a) By mixing superficially with the fibres of the inner circular muscular coat.

(b) By passing more or less abruptly under the fibres of the inner circular muscular coat and becoming lost among the fibres of the outer longitudinal coat.

(c) One lateral fasciculus may resemble description given under (a) ; the other may resemble that given under (b). An illustration of this is given in Fig. 6.

After this preliminary study an incision was next made along the median line of the common bile-duct extending from the point A to the point R. The fibres of the inner circular muscular coat of the intestine were then peeled off the bile-duct on both sides of the incision. The structure shown in Fig. 7 was revealed. Along the median line of the common bile-duct, a number of muscle fasciculi can be seen to arise. From this origin the muscle bundles run down and forward (towards the lower end of duodenum) over both sides of the common bileduct. As the fibres on either side of the common bile-duct run forward they unite, forming a relatively large bundle of muscle on each side of the bile-duct and in direct contiict with it.

The manner of termination of these bundles of muscles (running parallel with the bile-duct) varies somewhat. They end :

(a) By running forward and around under the ampulla of Vater, becoming continuous with fibres of t)ie inner circular muscular coat of the intestine.

(b) By running forward, turning away from the bile-duct and blending with fibres of the inner circular muscular coat of the intestine.

(c) By running forward, passing under the annulus of muscle about the mouth of the common bile-duct and becoming lost among these fibres.

(d) One side ends according to (b) ; the other side according to (c).

The mode of termination in Fig. 7 corresponds to that described under (c).

At the point 0, Fig. 7, some fibres of the inner circular muscular coat bend around the common bile-duct forming a Ushaped curve. This is the place of entrance of the common bile-duct into the muscle of the inner circular muscular coat of the intestine.

The common bile-duct is finally teased completely away and the muscle fibres of the inner circular muscle coat are revealed. These muscle fibres are found to be present from the point A to the point M, Fig. 6. It will be remembered that fibres of


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the iuner circular muscular coat pass over the common bileduct from the point A to the point B. Removal of the remaining fibres of the inner circular muscular coat discovers the outer longitudinal muscle coat of the intestine. In Fig. 8, the point F represents the arrangement of the fibres of the outer longitudinal muscle coat of the intestine at the place of entrance of the common bile-duct into the intestinal wall.

In addition to this general description the following points deserve to be mentioned. In some specimens at the pancreatic side of the mouth of the common bile-duct additional muscle bundles more or less involved with some already described can be made out. The resulting structure suggests a point d'appui. One never sees such a point d'apjnii developed on the non-pancreatic side.

In all cases the course of the common bile-duct through the wall of the duodenum is slightly oblique with reference to the inner circular muscle coat of the intestine; in most cases the course is also slightly curved — the convex side being the pancreatic side of the common bile-duct.

The Duct of Wirsung. — Speaking relatively, the duct of WirBung was found in many cases to run among the muscle fibres of the point d^appui situated at the pancreatic side of the mouth of the common bile-duct. The duct of Wirsung joins the common bile-duct at its extreme end; the pancreatic and common bile-duct opening side by side. The annulus of muscle fibres aboi^t the mouth of the common bile-duct accordingly also embraces the mouth of the duct of Wirsung.

In Fig. 8, point W, the arrangement of the outer longitudinal muscle coat of the intestine at the point of entrance of the duct of Wirsung into the intestinal wall is illustrated.

A study of serial cross- sections of the duodenal portion of the dog's common bile-duct. — Two sets of serial sections were prepared and examined. The specimens were stained in bulk with borax carmine and embedded in paraffin. The following drawings are taken from sections at different points in the course of the common bile-duct through the intestinal wall. They begin near the duodenal papilla and pass back towards the point of entrance of the duct into the intestinal wall. (Figs. 9 to 13).

Fig. 9 is made from a cross-section taken through the duct of Wirsung and the common bile-duct near their junction. Most interest attaches to the appearances in the submucosa. Here are to be seen two oj)enings with irregular contours. The one to the right — the larger — is the lumen of the ductus communis choledochus. The other is the lumen of the duct of Wirsung. Surrounding these lumina, so as to embrace them, are bundles of smooth muscle. The figure shows one muscle bundle traversing the space between the two lumina and connected above and below with other muscle bundles in such manner as to form a double ring of muscle embracing the two ducts. The ring of muscle here shown corresponds to the muscle ring about the mouth of common bile-duct found in macerated specimens. Examination of second set of serial sections in this region showed the muscle ring embracing both the common bile-duct and the duct of Wirsung, but in this instance no distinct bundle of muscle could be seen traversing the space between the two lumina. Apparently no one has suspected, up to the present time, the existence of this double


muscle ring embracing the mouths of the common bile-duct and ihe duct of Wirsung.

On both sides of this double ring of muscle one can make out muscle bundles cut transversely. In two or three places the bundles of the muscle ring are connected with these transversely cut fibres. These bundles (transversely cut) as well as others seen below lying on the inner surface of the inner circular muscular coat of the intestine, represent sections of those lateral fasciculi which in macerated specimens are seen to have origin in the ring of muscle about the mouth of the common bile-duct and to bend around and run down in the duodenum (see X). Other sections show these lateral fasciculi terminating by mixing superficially with the muscle fibres of the inner circular mttscular coat. It is to be noted that the lumen of the common bile-duct is partially filled with folds of mucous membrane at this point.

Fig. 10 is taken at a point further away from the month of the common bile-duct. In this section only one lumen is present, that of the common bile duct. The lateral fasciculi which have origin in the ring of muscle about the mouth of the common bile-duct, and which bend around and run down the duodenum are, however, shown here quite well. The mass of muscle to which the lateral fasciculus runs (on the left) probably represents the jjoint d'appui noted in the macerated specimens.

Fig. 11 is taken at a point about midway in the course of the common bile-duct through the intestinal wall. The structures show the division of the inner circular muscular coat of the intestine. Part passes over and part passes under the common bile-duct. Where the two parts of the inner circular muscular coat unite on either side of the common bileduct to form the complete inner circular muscular coat again, muscle fibres can be seen running from the upper to the lower part. This occurs on both sides, and there is, therefore, a complete ring of muscle around the duct. This arrangement must not, however, be regarded as perfectly symmetrical. Furthermore, some sections in this region show a simple decussation of fibres of the upper division with fibres of the lower division of the inner circular muscular coat. This latter arrangement (decussation on both sides of the common bile-duct) seems to hold entirely for the second set of serial sections. On both sides of the lumen of the common bile-duct, muscle bundles in transverse section are seen. These represent those bundles of muscle which have origin in the median line of the common bile-duct and afterwards run forward parallel with the long axis of the tube (see N ).

Fig. 12 shows those muscle bundles which arise in the median line of the common bile-duct. They are seen here only on the right, running down over the side of the bile-duct (see iV) ; it should be noted, however, that this arrangement is bilateral. The bundles of muscle cut transversely represent those muscle bundles which run forward, parallel with the common bile-duct, after taking their origin in the median line of the bile-duct.

Fig. 13 is taken at a point where the bile-duct has almost left the intestinal wall. The inner circular muscular coat passes entirely over the common bile-duct at this point. At the sides are seen large masses of longitudinal muscle fibres. These are the fibres of the outer longitudinal muscle coat which


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have been pushed aside to allow passage to the common bileduct.

IV.— THE MUSCULATURE OF THE BILIARY PASSAGES IN THE RABBIT.

(rt) Gall-Madder. — The nitric acid, glycerine and water macerations show only transverse muscle fibres.

Specimens macerated in Itanvier's alcohol, and longitudinal celloidin sections reveal a muscular arrangement practically identical with that found in the dog. There seems, however, to be relatively more muscle in the gall-bladder of the rabbit than in that of the dog.

(5) Cystic duct. — Only transverse muscle fibres are seen in specimens macerated with nitric acid, glycerine and water. Longitudinal celloidin sections show the absolute amount of smooth muscle in the walls of the cystic duct to be small, and that the muscle fibres run in three directions, longitudinal, transverse and diagonal. The transverse muscle fibres are most numerous, the longitudinal fibres next in number and the diagonal fibres least of all. Connective tissue penetrates between the muscle bundles to a relatively greater degree than in the gall-bladder.

(c) Hepaiic duct. — No muscle fibres were found in macerations with nitric acid, glycerine and water. Longitudinal celloidin sections showed a very small amount of muscle. The muscle fibres follow three directions, longitudinal, transverse and diagonal. The longitudinal fibres are most niimerous. The transverse and diagonal fibres are about equal in number but there are very few of either variety. There is much connective tissue here between the muscle.

(rf) Common bile-duct. — Muscle fibres could not be detected in nitric acid, glycerine and water macerations. Longitudinal celloidin sections show longitudinal and transverse muscle fibres. The former are much more numerous than the latter. The absolute amount of muscle present in the walls of the common bile-duct is, however, very small.

(e) No extraordinary muscular arrangement was found at the place of union of the hepatic and cystic duets with the common bile-duct.

(/) The rabbit's duodenum was macerated in a mixture of nitric acid, glycerine and water. After the mucous membrane had been removed the structure represented by Fig. 14 was found. The course of the common bile-duct through the intestinal wall is parallel to that of the fibres of the inner circular muscular coat. This is just the reverse of what is found in the dog. At the first glance, one can see that the greater part of the duodenal portion of the common bile-duct is covered with muscle fibres of the inner circular muscular coat.

Some of these fibres of the inner circular muscular coat run up on the common bile-duct (see A), continue for some distance and terminate abruptly near the orifice of the duct (see R). Other fibres of the inner circular muscular coat run up on the duct, continue forward a short distance, but finally bend, some to one side, others to the opposite side (see C) and running down over the side of the duct, become continuous with the fibres of the inner circular muscular coat. The presence of some fibres of the inner circular muscular coat just under the ampulla of Vater is to be noted (see CS).


Fig. 14 also shows a sphincter muscle about the orifice of the common bile-duct (see S). This sphincter is composed of a muscular ring which surrounds the orifice of the duct. Some fibres instead of running completely around the orifice, run oflr at the side of the ring and bending forward become continuous with the fibres of the inner circular muscular coat.

The fibres of the inner circular muscular coat were next removed (except at OS}. The arrangement seen is represented in Fig. 15. The common bile-duct is seen penetrating the outer longitudinal muscular coat. The outer longitudinal muscle at the point of entrance of the common bile-duct (see A) covers some muscle fibres which run around the common bile-dTict embracing it. Immediately after penetrating the outer longitudinal muscular coat the bile-duct can be seen to be encircled with smooth muscle. Those muscle fibres nearest the point of entrance of the common bile-duct, run around or encircle the bile-duct without bending forward (see IE), but as the orifice of the duct is approached the muscle fibres which embrace the bile-duct, after running down over the side of the duct, bend forward more and more.

Thus it will be seen that in all cases, the muscle fibres described embrace the duct but with the difference pointed out above, namely, that those fibres nearest the point of entrance of the common bile-duct do not bend forward as they pass under the common bile-duct, while those nearer the orifice of the bile-duct do bend forward as they pass under it. All the muscle fibres just mentioned doubtless have a sphincter function, but if we regard the sphincter muscle of the dog we will find it homologous with the sphincter fibres S of the rabbit. Therefore, the rabbit has not only a sphincter similar to that of the dog, but it possesses also other fibres which subserve in all probability the same or a similar function.

The muscle fibres encircling the common bile-duct were now cut along the long axis of the duct. The mucous membrane of the di;ct was removed and an arrangement represented in Fig. 16 was found. At this point it is well to recall that the fibres marked CS in both Fig. 15 and Fig. 16 are those fibres of the inner circular muscular coat which lie immediately in front of and also under the ampulla. These muscle fibres (see Fig. 16, CS) run under the ampulla and there decussate irregularly, so that the fibres of the one side pass to the other side, and then curving upward and backward around the common bile-duct, embrace it. Here is seen the origin or termination of those muscle fibres which embrace the common bile-duct and bend forward as they pass under the bile-duct. Passing from this place of decussation, back toward the point of entrance of the common bile-duct into the intestinal wall, one finds the continuation of those muscle fibres which simply embrace the duct without bending forward as they pass under it (see Fig. 16, IR).

The muscle fibres of the outer longitudinal muscular coat, which lie in front of the ampulhi and under the fibres marked CS have no connection with the muscular arrangement of the duodenal portion of the common bile-duct. Further back, however, near the decussation of the fibres CS, the fibres of the outer longitudinal muscle coat seem to be more or less involved in the general decussation. Some of the fibres of the outer longitudinal muscle coat run up to the side of the bile


September-October, 1898.]


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229


duct, then bend around and run forward on it and at its side toward the ampulla. Others, when they reach the side of the duct, plunge inward and mingle with those bundles which embrace the common bile-duct.

Serial cross-sections of the duodenal portion of the common bile-duct of the rabbit. — Two sets of serial sections were prepared and examined. The principal fioints of interest are presented in the following cuts which are taken at difterent levels in the duodenal portion of the common bile-duct. The first figure corresponds to a section taken nearest the orifice of the common bile-duct, the others are taken at successively different levels throughout the length of the duct.

In Fig. 17, at first glance, the course of the common bileduct in the intestinal wall is seen to be parallel to the inner circular muscular fibres. The duct is situated in the submucosa of the intestine, and is seen to be surrounded by muscle bundles. The smooth muscle embraces the common bile-duct, but on each side of it some muscle fibres, instead of running under the duct, turn forward and the cross-sections of the individual smooth muscle cells indicate the fact that they have continued as a part of the fibres of the inner circular muscular coat (see JT). Between the mucous membrane of the common bile-duct and the inner circular muscular coat of the intestine are seen muscle bundles which run transverse to the course of the common bile-duct. These fibres correspond to that portion of the sphincter which runs under the common bile-duct. Comparison shows that the inner circular muscular coat (see CS) has lost few if any muscle fibres at this point. This is a fact which will have more importance in connection with the decussation of the fibres of the inner circular muscular coat. It should be noted that the fibres marked CS corresjjond to those marked CS in the macerated specimen. At this level of the common bile-duct the lumen is occupied to a considerable extent by folds of mucous membrane.

Fig. 18 has been taken at a level in the duodenal portion of the common bile-duct, further from the orifice than Fig. 17. The structures to be noted have passed from the submucosa into the tunica muscularis of the intestine. The large lumen of the common bile-duct is conspicuous (see B) and to the right, the first indication of the duct of Wirsung is met with. If we begin the description at the extreme left of the figure, just beneath the submucosa are to be seen a large number of muscle fibres in cross-section (see CI). These are present, but in diminished number throughout more than one-half the breadth of the section. These fibres belong to the inner circular muscular coat of the intestine which at this point does not quite cover the bile-duct.

Toward the extreme right are seen large bundles of transversely cut muscle fibres (see CF). Running to join these last named bundles, are muscle fibres cut diagonally and longitudinally. The longitudinally cut muscle fibres apparently arise from the outer longitudinal muscle coat of the intestine and running over the common bile-duct finally bend around and become continuous with the transversely cut inner circular muscular fibres CI. If we again examine the extreme left of the figure, there are to be seen fibres cut longitudinally (see LI) immediately under the inner circular muscle coat. These represent the outer longitudinal muscular coat. In this par


ticular section there is a division of the fibres of the outer longitudinal muscular coat. Some pass over the duct and then bend around as described above to become continuous further forward with the inner circular muscle coat. Others run as if to pass under the bile-duct but suddenly terminate. In their place one sees transversely cut muscle fibres which extend for a considerable distance to the right and then suddenly stop (see LF). Where these fibres (LF) stop we find longitudinally cut muscle which represents the outer longitudinal muscle coat of the intestine (see LI). Tlie explanation of the structures last mentioned is probably to be found in the circumstance that the muscle fibres of the outer longitudinal muscular coat on either side of the long axis of the common bile-duct bend around and, converging, run forward in the direction of the ampulla of Vater. The fibres marked LF represent those muscle bundles which run forward. The transversely cut muscle fibres marked CS represent fibres of the inner circular muscle coat. These are the continuation of the fibres marked CS in Fig. 17 and correspond to the CS fibres of the macerated specimen. At this level the decussation of the inner circular muscle fibres as described in the macerated specimen ought to be seen, and as a matter of fact this decussation corresponds to those muscle bundles of the figure which have not already been described. They run up on the right as diagonally cut muscle. The segments of diagonally cut muscle show that successive bundles have been cut. Running under the bile-duct is another large muscle bundle. To the left of the bile-duct are still other bundles of diagonally cut muscle. I believe that all these bundles come from the CS fibres of Fig. 17 and that their particular arrangement is due to the decussation and subsequent embracing of the common bile-duct by them. This arrangement will be better understood by referring to the macerated specimen. This series of sections did not siiow muscle running between the lumen of the common bile-duct and the lumen of the duct of Wirsung, to form a double sphincter. Examination of the second set of serial sections, however, at about the same level as that represented by Fig. 18, proved this structure to be present. Here were found muscle bundles arising on the outer side of the common bile-duct from the region of the decussation of the inner circular fibres and running inward between the common bile duct and the duct of Wirsving they finally were seen to terminate by blending with fibres on the inner side of the common bile-duct. These lastnamed muscle bundles had origin amongst the decussating fibres of the inner circular coat and then curved around the common bile-duct to the inner side of the same and finally blended in part with those fibres which have been described as running between the common bile-duct and the duct of Wirsung.

Fig. 19 is taken at a level still more remote from the duodenal papilla. Passing from the inner side of the intestine toward the outer side we see the mucosa of the intestine, the inner circular muscular coat of the intestine (see CI) and the outer longitudinal muscle coat (see LI). The lumen of the common bile-duct is prominent (see B) and to the right that of the duct of Wirsung. Around the bile-duct longitudinally cut muscle bundles are arranged. They embrace the duct and represent (1) independent muscle bundles embracing the duct


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and (2) fibres of the outer longitudinal muscle coat (shown to the extreme right in the drawing) which have run up on the surface of the bile-duct.

Outside the bile-duct and the muscle bundles embracing it are seen muscle fibres cut transversely. On the left, diagonally cut bundles are found running toward this transversely cut muscle. These diagonal bundles represent those fasciculi of the outer longitudinal muscle coat which have curved around at the side of, and also on, the common bile-duct and then have run forward toward the ampulla of Vater (see LF.)

In Fig. 20 the typical intestinal wall is shown. The common bile-duct is outside the intestinal wall and a few longitudinal and diagonal muscle bundles are to be seen in its wall. These must be regarded as stray fibres running up on the bileduct from the intestine and not as fibres of the proper fibromuscular tunic of the common bile-duct.

v.— THE MUSCULATURE OF THE BILIARY PASSAGES IN MAN.

(rt) (fall-bladder. — What has been said concerning the gallbladder of the dog may be repeated of the gall-bladder of man. Fig. -21.

(5) Cystic duct. — Macerations in a mixture of nitric acid^ glycerine and water showed the arrangement of smooth muscle to be plexiform. Longitudinal celloidin sections of the cystic duct demonstrated smooth muscle running in three directions, viz. transverse, longitudinal and diagonal. Fig. 32. The transverse bundles are most numerous ; the longitudinal and diagonal bundles are about equal in number. In that portion of the cystic duct nearest the neck of the gall-bladder, the amount of muscle is considerable, but this gradually diminishes in amount as .the common bile-duct is approached. At the junction of the cystic, hepatic and common bile-duct the quantity of muscle present is very small. These sections also show muscle fibres in those folds of the cystic duct which are known as the valves of Heister. The fact that muscle is present in these folds has been noted before by only one person (A. MacAlister) and he does not undertake to describe the course pursued by the muscle bundles.

In a set of serial longitudinal sections of the entire human cystic duct, I have found the arrangement represented by the following schema. Fig. 23. This schema, based upon study of the serial sections, shows :

(1) That the transverse muscle bundles of the cystic duct are not limited to the wall proper, but at the level of the valves of Heister also run around in the valve in a circular direction. It is just as if the wall of the duct had been invaginated at this level and as a result the circular muscle fibres were carried out into the fold thus formed.

(2) That most of the longitudinal muscle bundles of the cystic duct continue down the duct without entering the valve, but still there are some of these bundles which (having reached the level of the valve) bend around at almost right angle and run out into the fold.

(3) We have no evidence that the diagonal fibres take any part in the musculature of the valves of Heister.

We believe, therefore, that the transverse muscle bundles predominate in the valves of Heister. Those valves nearest the


common bile-duct are quite small and either contain very little muscle or none at all.

((:) Hepatic duct. — The description of the rabbit's hepatic duct applies without any addition to the hepatic duct of man. Pig. 26.

id) Common bile-duct. — The muscle fibres could not be detected with certainty in nitric acid, glycerine and water macerations. Longitudinal celloidin sections revealed a small amount of muscle. The direction followed was not only transverse but also longitudinal and diagonal. The number of transverse and longitudinal fibres was about equal; the oblique muscle fibres were least numerous. Much connective tissue was found between the muscle fibres. Fig. 27.

(c) Point of union of cystic, hepatic and common bile-ducts. — Each duct preserved its typical structure.

(/) Preliminary to the description o{ the duodenal portion of the human common bile-dtict, it will be well to state that many individual variations in structure occur but that these variations do not alter the general anatomical bearing of this region.

The following drawings have been made from a typical specimen macerated in a mixture of nitric acid, glycerine and water.

Fig. 28 shows the entrance of the common bile-duct B and the duct of Wirsuug W into the intestinal wall. AVe see a simple separation of the fibres of the outer longitudinal muscular coat of the intestine LI. The common bile-duct and the duct of Wirsung pass through this separation. At F we find muscle fibres arising from the outer longitudinal muscular jcoat. These fibres run up on the common bile-duct and becoming gradually less and less marked, finally disappear. This arrangement is bilateral. The fibres marked IE represent some bundles of muscle which (shown in Fig. 30, IE) form an indej)eudent ring of muscle around the common bileduct between it and the duct of Wirsung.

At H are seen muscle fibres which run almost entirely around the duct of Wirsung, but as these fibres aj)proach that side of the pancreatic duct nearest the common bile-duct, they turn abruptly and run up on the duct of Wirsung in a longitudinal direction. They gradually diminish in volume as they ascend the duct. This structure is bilateral. See also Fig. 30, H.

Fig. 29 represents the structures seen upon removal of the mucous membrane from the intestinal wall in the region of the duodenal papilla. The inner circular muscular coat of the intestine is represented by CI. The first point to demand attention is the penetration of the inner circular muscular coat by the common bile-diict. At the spot of penetration there is a simple separation of the muscle bundles of the inner circular nmscle coat. It should be noted that the human specimen differs from the arrangement found in dog. It will be remembered that in the latter animal, the inner circular muscle coat forms a tube-like structure which embraces the common bile-duct for a considerable distance. In man the common bile-duct plunges immediately through the muscle layer which composes the inner circular muscular coat.

At *S are bundles of muscle running around the common bile-duct (see also Fig. 30, S). These are iudepeudent rings of muscle which embrace the duct. Now, if we look further




><^£-^ W A^--'^-fe5^^s:



Fig. 1. — Loiiffitudiual section of the sall-bladik-r Of doff, x 30.


Fk;. 'Z. — Louffitudinal section of the cvstic duct of dog. x 30.


Fig. 3. — Longitudinal section of the cystic duct of dog, showing the musculature of a Heisterian valve, x 30.



Fig. 4. — Longitudinal the hepatic duct of dog.



Fig. T.--MM(eiatcd duodennl portion of the coniniciii bile-duct of dog. Part of the circular muscular coat of the intestine has been removed. X 4.



Fig. h. — Longitudinal sect: the common bile-duct of dog.



Fig. 8. — Macerated duodenal portion of the common bile-duct of dog. The relation of the common bile-duct to the longitudiual muscular coat of the intestine i.s shown. x4.



Fiti. C). — Macerated duodenal portion of the common bile-duct of dog. The mucous membrane, muscularis mucosEe and submucosa of the intestine have been removed, x 4.




^\




^^^>-^



Fig. 0. — Cross-section near the oritice the common bile-duct of dog. x 30.




if the duodenal portion of


TuE Johns Hopktxs IlosprrAi, Bulletin Nos. 90-91.









Fio. 10.— Cross-sectiou somewhat removed from the orifice of the duodenal portion of the common bile-duct of dog. x 30.


Fio. 11. — Cross-section near the middle of the duodenal portion of the common bile-duct of dog. x 30.





oooooooo/Kv




-Cn\v -^ /^ ^ "^




Fig. 13. — Cross-section somewhat removed from the middle of the duodenal pnrtion of the commim bile-duct of dng. x 30.



Fig. 13. — Cross-section at the entrance of the common bile-duct into the intestinal wall of dosf. x 30.



-"ll'I'Wit


-±1 'J


J"iG. 14. — Macerated duodenal portion of the common bile-duct of rabbit. The mucous membrane, muscularis inucosie and submucosa of the intestine have been removed. >:4.


Fig. 15. — Macerated duodenal portion of the common bile-duct of rabbit. The greater ]iart of the circular muscular coat of the intestine has been removed, x 4.


Fig. 10. — Macerated duodenal (lortiou of the common bile-duet of rabbit, showing the distribution of the CS and /if flbres. x 4.


llrndrickKOH, <lcl.



Fig. 17. — Crnss-sectiou near the orifice of tlie duodenal portion of the eommiin bile-duct of rabbit. x 40.


Fio. IS. — Cross-section somewhat removed from the orifice )f tlif duodenal portion of the common bile-duct of rabbit. x 40.



Fi<;. 19. — Cross-section near the (ntrauee of the common bile-duct Fig. 20. — Cross-section at flic entrance of the common bile-duct

into the iutestiual wall of rabbit. x 40. into the intestinal wall of rabbit. x 40.



Fig. 21 Longitudinal section of

the gall-bladder of man. x 30.


BendrickBon, del.



Fig. 23. — Longitudinal section of the cystic duct of man. x BO.



Lerei at which Fig. 34 is taken. Fig. 3.5.


Fig. 33. — The cystic duct of man, showing the Ileisterian valve ; also, a diagram of the musculature of the Ileisterian valve.



Fig. 34. — Oue of the longitudinal serial sections of the cvstic duct of man. See Fig. 23. x30.



Fui. 3(1. — Louifitudinul section of thehei.iatio duct of man. x oO.



Fig. 39. — Macei-ated duodenal portion of the common bile-duct of man. The mucous inembraue, muscularis mucosa aud submucosa of the intestine have been removed, x o.



Fiii. 3."). — One of the longitudinal serial sections of the cystic duct of man, showing the muRCuUitnre of a valve of Heister. See Fig. 33.



Fjg. 37. — Longitudinal section of the common bile-duct of man. x 30.



Fig. 28. — Macerated duodenal portion of the common bile-duct of man. The relation of the common bile-duct and the duct of Wirsung to the longitudinal muscular coat of the intestine is shown. x 5.



Fig. 30. — Macerated duodenal portion of the common bile-duct of man. AH of the intestinal coats have been removed, x 5.



Fig. 81. — Cross-section near the orifice of the duodenal portion of the common bile-duct of man. x 30.



Fig. 32.— Cross-section at the cntriiiic.' of the common bile-duct into the inlestinal wall of man.


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JOHNS HOPKINS HOSPITAL BULLETIN.


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back on the common bile-duct, near the point at which it penetrates the inner circular muscular coat, we observe muscle bundles 2!' which do not run entirely around the duct. These muscle bundles are very intimately mixed with the independent muscle rings which completely embrace the duct. The former, however, upon reaching the level of the inner circular muscle coat, turn abruptly forward and under the bile duct, and after running for some distance toward the duodenal papilla finally end in the connective tissue of the submucosa of the intestine (see also Fig. 30, JT). This arrangement is bilateral. The drawing shows that this arrangement of muscle about the common bile-duct begins at a point before the duct penetrates the inner circular muscular coat. In this particular specimen, a muscle bundle of the inner circular muscular coat curves around and becomes continuous with the fibres marked X. It may be well to note that the X fibres did not terminate in all cases according to this description. In several cases these fibres, after turning forward and under the common bile-duct, decussated with similar ones from the opposite sicie and after such decussation became continuous with the fibres of the inner circular muscular coat of the intestine. In one case the X fibres after turning forward suddenly plunged through the inner circular muscle coat and became continuous with the fibres of the outer longitudinal muscle coat of the intestine. ,

Another point observed in some specimens but not in this one is worthy of mention. In some specimens after dissecting away the <S' fibres, a few longitudinally and diagonally disposed fibres were seen. These had origin in those fibres of the outer longitudinal and inner circular muscle coat which lie over the common bile-duct when viewed as in Fig. 29. Finally in Fig. 29 a bundle of muscle fibres K can be seen on each side of the common bile-duct running parallel with it. These bundles arise on the surface of the common bile-duct (Fig. 30, K} and are covered by the F fibres of Fig. 28. In this case they run forward from under the inner circular muscular coat (see Fig. 29, K) and bend around beneath the common bile-duct, becoming continuous with each other, thus forming a loop around the duct of Wirsung, Fig. 30, K. In other specimens these ^fibres originate in the same way but terminate by running under the common bile-duct and decussating there with similar fibres from the opposite side.

Fig. 30 shows the muscular arrangement about the end of the common bile-duct and the duct of Wirsung after all fibres of the outer longitudinal and inner circular muscle coats have been removed. The common bile-duct and the duct of Wirsung have been drawn in the same position as they occupied in Fig. 28, but removal of the muscular coats of the intestine permits of a view of the various structures in profile. All the structures here shown have been described more or less fully under Figs. 28 and 29.

After an examination of serial cross-sections of the duodenal portioii.of the human common bile-duct, we have selected two of them for illustration since they represent the principal points. The first figure (Fig. 31) is taken near the level of union of the common bile-duct with the duct of Wirsung. The structures of interest are situated in the submucosa of the intestinal wall. The large opening — to the right — is the lumen of tlie ductus


communis choledochus; the narrow slit — to the left — represents the collapsed lumen of the duct of Wirsung. At the point X, muscle bundles cut in cross-section and sometimes diagonally are seen. These bundles represent those fibres of the sphincter muscle which do not run entirely around the common bile-duct. They become detached at the side of the duct from the sphincter proper and turn forward. These bundles then run forward, under the common bile-duct and gradually approach the bundles of the opposite side ; they finally end free in the connective tissue of the submucosa near the orifice of the common bile-duct. These bundles correspond to the X fibres of the macerated specimen. It is probable that the K fibres of the macerated specimen are also included among the bundles described above, but we have not been able to distinguish them in the sections from the others.

The remaining bundles of muscle about the common bileduct belong to the sphincter muscle proper : they correspond to the S fibres of the macerated specimen. A bundle of muscle fibres cut longitudinally is seen running between the lumen of the duct of Wirsung and that of the common bile-duct. I consider this to be a bundle of the sphincter muscle and believe that it corresponds to the "double sphincter" arrangement found in the dog and rabbit, and described above.

The second section (Fig. 32) represents the common bileduct just before it has penetrated the nii;scle coats of the intestine. Around the common bile-duct are seen muscle bundles cat transversely. These represent the K fibres of the macerated si:iecimen. No muscle fibres arising from the outer longitudinal muscle coat and running up on the common bileduct can, however, be demonstrated in this specimen.

VI.— CONCLUSIONS.

The principal results of this research may be briefly summed up in tabular form; under the various heads only the most general findings are mentioned.


(a) Gall-bladder


(b) Cystic duct


Transverse*

Longitudinal

Diagonal

Transverse

Longitudinal

Diagonal


Transverse

Longitudinal

Diagonal

Transverse

Longitudinal

Diagonal


Transverse

Longitudinal

Diagonal

Transverse

Longitudinal

Diagonal


Valves of Heister.


The transverse fibres of the cystic duct run around in the valves of Heister in a circular direction. The longitudinal fibres bend at a right angle and run out into the valve. Diagonal fibres apparently do not enter the valves of Heister.


(c) Hepatic duct Longitudinal


Transverse

Longitudinal

Diagonal


Transverse

Longitudinal

Diagonal


'These terms are used with reference to the long axis of the duct.


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JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 90-91.


Transverse

(d) Common bile- Longitudinal

duct Diagonal

(e) Place of union Each duct pre of the cystic, served its typihepatlc and cal structure ;

the wall of each gradually merging into that of the others.


common bile-ducts


(f) Duodenal por tion of the Common bile-duct


A sphincter muscle exists.


Transverse Longitudinal


Each duct preserved its typical structure ; the wall of each gradually merginto that of the others.


A sphincter muscle exists.


Transverse

Longitudinal

Diagonal

Each duct preserved its typical structure ; the wall of each gradually merging into that of the others.

A sphincter muscle exists.


VII.— INDEX LETTERING OF THE FIGURES.

B, Common bile-duct.

01, Circular muscular coat of the intestine.

CS, Fibres of the circular muscular coat of the intestine which have a distribution indicative of a secondary sphincter.

D, Diagonal muscle.

E, Epithelium.


QB, Next to gall-bladder.

IB, Independent rings of muscle embracing the common bileduct.

K, Fibres which arise on the common bile-duct and run around the duct of Wirsung to become continuous with similar fibres of the opposite side.

L, Longitudinal muscle.

LI, Longitudinal muscular coat of the intestine.

LF, Fibres of the longitudinal muscular coat of the intestine which turn and run forward toward the ampulla of Vater.

M, Mouth of the common bile-duct.

MI, Mucous membrane of the intestine.

JV^, Muscle bundles which have origin in the median line of the common bile-duct and afterwards run forward parallel with the long axis of the duct.

NB, Next to common bile-duct.

S, Sphincter fibres.

81, Submucosa of the intestine.

T, Transverse muscle,

W, Duct of Wirsung.

X, Those fibres of the sphincter which become detached latersjly and run down the intestine.

DEVELOPMENT OF THE INTERNAL MAMMARY AND DEEP EPIGASTRIC ARTERIES IN MAN

Mall FP. Development of the internal mammary and deep epigastric arteries in man. (1898) Johns Hopkins Hospital Bulletin 9: 232.

By Franklin P. Mall.

(From the Anatomical Laboratory of the Johns Hopkins University .)


The great importance of the fact that the main arteries of the vertebrates arise directly from the aortic arches has been shown repeatedly in ontogenetic and phylogenetic studies. Furthermore, it gives us a scientific basis for the explanation of the numerous variations which may occur while this simple system of arteries is being transformed into the complex system as found, for instance, in man.

While the modification of the aortic arches is taking place, certain arteries become larger, others disappear, while in others tlie direction of the circulation is reversed. The laws governing these changes have been discussed extensively by Thoma in his numerous communications. It is the law of use and disuse expressed in this instance by rapidity. For a given vessel at a given time in its development there is a certain rapidity of circulation through it at which it ceases to grow. If the rapidity of the circulation is increased the vessel becomes larger ; if it is diminished the vessel becomes smaller ; if the circulation comes to a standstill the vessel disappears altogether. This law is constantly at work throughout development in the grown animal and in all pathological changes. It does not appear to govern the firstgrowth of the capillaries but itgoverns the growth of the vessels after the circulation in them is once started.

Any one who has studied the growth of the blood-vessels extensively in living animals as well as in fixed preparations is well aware of the fact that blood-vessels are constantly being formed and destroyed. This process is so extensive that at almost any stage of the development of an animal we may safely say that more blood-vessels have disappeared than are present at that time.

With the above ideas clearly in view, I have studied the extension of the blood-vessels into the body- walls of the embryo to see whether or not some secondary system, regular like the aortic arches, appears to be subsequently converted into the


main arteries of the body- walls and the extremities. That the vertebral artery is formed by the union of a number of branches from the descending aorta has been shown by His,* by Froriepf and by Hochstetter.J These branches are the segmental arteries from the aorta while it is still in the branchial region. The aorta soon shifts away from the branchial region with the bending of the head and the development of the neck. While this is taking place the segmental arteries unite at their distal ends to form the vertebral artery while the communicating branches are gradually broken off as shown in Fig. 1, V, from a human embryo of the fourth week. This process continues down to the seventh cervical segmental artery, where it ceases. At this point the subclavian artery arises, Fig. 1, S, as shown by Hochstetter. From now on for a few segments the process is very diflBcult to follow, but further on throughout the thoracic region of the embryo the process is simple. This is easily accounted for by the perfect segmental arrangement of this portion of the body throughout its development.

There are, however, two other sets of segmental arteries in the thoracic region of the body which appear before this set is formed and gives rise to the arteries of the body-walls. The first set is already well developed in embryos at the end of the second week.§ They arise from the aorta and pass immediately to the umbilical vesicle, there to break up into a plexus which is collected by the omphalo-niesenteric veins. Soon these arteries disappear and the omphalo-mesenteric artery takes their place. These vessels are of course on the mesial side of the ccelom.


Hi8(W.) Anat. mensch. Embryonen. III. Zuf Geschiehte der Organe, Leipz., 1885.

fFroriep (A.) Arch. f. Anat. u. Physiol., Anat. Ablh., Leipz., 1SS6, S. 69-1.50.

t Hochstetter (F.) Morphol. Jahrb., Leipz., Bd. xvi, 1890.

? Mall (F. P.) J. Morphol., Bost., Vol. xii, 1896-7, Fig. 16.


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Before this first system has disappeared, and before the permanent intercostal vessels have appeared the second set of segmental arteries arises from the descending aorta, passes on the lateral side of the ccelom into the menibrana reuniens, as is indicated to us by a figure given by von Kiilliker,* as well as by the description of His.f Von Kiilliker pictures a cow's embryo with the whole membrana reuniens filled with a minute plexus of veins which radiate from the myotomes towards the umbilical cord, while His describes this same region in the human embryo as filled with branches of the umbilical vein which empty into the sinus reuniens above, and into the umbilical vein below. According to His's description they arise when the communication between the umbilical veins and the sinus reuniens is severed. Although the picture given by von Kiilliker does not correspond with His's description it does not contradict it, nor is it peculiar to the cow's embryo. I have in my collection a well-preserved human embryo (No. LXXVI), in which the membrana reuniens is filled with a plexus of veins much like



Fig. 1. — Arterial system of a humau embryo four weeks old (No. II). Enlarged 10 times. F, vertebral artery; P, pulmonary artery ; C, creliac axis; S, subclavian artery ; 4, fourth dorsal seijmeutal artery.

that in the cow's embryo. The specimen was taken from the uterus seven hours after the death of the woman, and without opening, the ovum was hardened in absolute alcohol. All the vessels down to the capillaries are filled with blood, thus making it an excellent specimen for the study of the blood-Tessels. It represents a stage somewhat more advanced than the one pictured by von Kiilliker, as the plexus of veins does not cover the whole membrana reuniens. The ventral wall over the heart near the liver contains no vessels, while the membrana reuniens covering the upper end of the heart is filled with a plexus of vessels which communicate with the capillaries of the mandibular arch. ., There is an extensive plexus through the arm and lateral body walls which extends through the menibrana


von Kolliker (A.) Grundrisa der Eutwicklungsgeschichte des MenschenundderhiJherenThiere. 8°. Leipzig, 1880. S.103, Fig. 85.

fHisCW.) Anatomie menschlicher Embryonen. Ill, Zur Geschichte der Organe. Leipzig, 1885, 8°. S. 206, also Fig. 130,


reuniens covering the liver, and finally encircles the cord and communicates with the umbilical veins.

The specimen just described is about 22 days old and, although I have six other good embryos between 14 and 28 days old, I find no such plexus in the membrana reuniens, although in all but one of them (14 days) the arm shows a rich plexus of capillaries filled with blood. In stages older than four weeks I find no blood-vessels in the membrana reuniens with the exception of that portion encircling the cord, where there is a rich network of veins. Although I have a number of excellent specimens of five or six weeks, the membrana reuniens over the heart and liver contains no blood-vessels until it is invaded by the ventral plate, which is accompanied by the development of the intercostal vessels. In pigs' embryos this extensive membrane is also free from veins, with the exception of the zone encircling the cord, which again has a venous plexus more marked, however, than in the human embryo.

It appears, then, that during the third week of development, while the umbilical veins still empty into the sinus reuniens, an extensive plexus is formed throughout the greater extent of the membrana reuniens, which receives blood from the aorta on its dorsal side, and empties it into the umbilical vein on its ventral side. As the umbilical vein changes its position to enter the liver, this circulation through the membrana reuniens is broken up as the much earlier circulation through the umbilical vesicle was broken up.

The earliest collecting vein for the descending aorta is the omphalo-mesenteric vein ; next, it is the umbilical vein, and finally, when the abdominal walls are comjileted, it is the cardinal. This in turn is partly converted into the vena cava inferior.

The permanent arterial system is already well outlined in embryo II (Fig. 1). The aortic arches and segmental arteries are sufficiently well marked to permit one to number them. The vertebral artery is in process of development, it being formed by a union of a number of segmental arteries, as shown by His, by Froriep, and by Hochstetter. The seventh cervical segmental artery gives rise to the subclavian artery. The lower cervical, all the dorsal and lumbar segmental arteries, are concerned in the development of the thoracic and abdominal walls. Fig. 1 illustrates the extent of the arteries. It shows a simple arrangement from the vertebral to the hypogastric artery. The lower lumbar arteries are not shown. A section of this embryo is given in Fig. 2. It shows the relation of a segmental artery to the myotome. The segmental arteries supply primarily the spinal cord and ganglia by two groups of branches, one near the middle line and one more lateral. A more ventral group of segmental arteries supplies the Wolffian body. The blood from all these groups of arteries is collected by the cardinal veins.

The lateral group gives rise to the intercostal arteries by first supplying the myotome, and, as this grows into the membrana reuniens by a process of budding, the vascular loop follows it. In so doing the loop is first on the dorsal side of the sympathetic and finally on its lateral side, thus making the sympathetic cord cross the intercostal arteries and veins on their ventral side, as is the case in the adult.

No sooner has the vascular loop extended to the lateral side of the sympathetic cord than it begins to anastomose with


234


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fNos. 90-91.


neighboring segmental loops, as single vessels near the subclavian and hypogastric arteries, and as a plexus midway between these two. Tliis gives us at tliis early period a complete lateral anastomosis from the subclavian artery to the femoral, as Fig. 3 shows. It remains only for this system to shift around towards the median line with the muscle, nerves and ribs to form the condition of things as found in the adult.



Fig. 2. — Section through a human embryo lour weeks old (No. II). Enlarged 55 times. 4, aorta ; FW, foramen of Winslow ; MB, membrana reuniens; L, liver; R, heart.

Fig. 3 shows that the upper and lower segmental arteries of the series do not correspond at this early time with the same in the adult. Above, the superior intercostal is missing, while below, there is only a small fourth lumbar artery present, and it arises from the middle sacral. Iliolumbar and circumflexiliac arteries are altogether wanting, and I should judge from the relation of the arteries in this embryo, that the arch formed by the iliolumbar and circumflex-iliac is of secondary origin and has nothing to do with the segmental arteries. That they form anastomoses with the lower lumbar arteries in the adult can be explained in other ways.

The hypogastric artery is present long before the segmental arteries are formed near its junction with the aorta, and on this account we can no more call the trunk of the common iliac artery segmental than we can apply the same term to the


descending aorta. We can only locate its origin in the neighborhood of the fourth lumbar artery.

Hochstetter has settled definitely that the subclavian is a branch from the seventh cervical segmental artery.* Between the seventh cervical and the third dorsal we have three segmental arteries. In Fig. 1 the segmental arteries in this region are all simple with the exception of the seventh, which sends a large branch into the arm. From this stage to the one pictured in Fig. 3 there is a jiimp, but in it we see the intermediate stage between Fig. 1 and the adult.



Fig. 3. — Arterial system of a human embryo six weeks old (No XLIII). Enlarged 5 times.

All of the arteries below the vertebral are destined to pass behind the sympathetic, and it is excluded only on account of its direction. In Fig. 3 the eighth cervical segmental passes on the ventral side of the nerve, which shows conclusively that it must either be a new artery or a secondary connection between the eighth segmental and the subclavian. Since the first and second intercostal arteries pass behind the sympathetic in this embryo and in front of it in the adult, we must accept Hochstetter's opinion that the superior intercostal is formed by secondary connections between the upper intercostals and the subclavian. If the old connection remains, it forms the arteria aberrans.

I stated above that the sympathetic lies in front of the subclavian, while in the adult it lies in a great part behind it. Hochstetter explains this change of position by a wandering of the trunk of the artery through the group of embryonic nerve cells. In earlyembryos the sympathetic system resembles a group of sprouts from the segmental nerves which cross the segmental arteries, and the sympathetic cord is of secondary formation. This cord grows very rapidly during the fifth and sixth weeks, to form a great mass of cells extending from the vagus gang


Hochstetter numbers the segmental arteries to correspond with the vertebrK above them. Throughout I number the arteries with their .accompanying nerves. He states that the subclavian arises from the sixth segmental, this being the same artery that I call the seventh cervical segmental.


September-October, 1898.]


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lion to the adrenals, connecting all of the branches with the segmental nerves to make of them rami conmiunicantes. This all goes on hand in hand with the descent of the heart into the thorax. At the same time the arm is rotating towards the ventral median line, and drags with it the subclavian artery. In so doing the subclavian is dragged into the sympathetic cord in its earliest stage, thus allowing the greater portion of the cord to be developed on its dorsal side. The portion of the sympathetic which from the first lies on the ventral side of the subclavian becomes the ansa subclavia.

The descent of the heart into the thorax on the inside with the descent of the arm over the clavicle on the outside of the body causes great tension on the upper intercostal arteries, and favors the new formation of blood-vessels in a more direct line. This is the reason why the main branch of the superior intercostal is a secondary and direct artery from the subclavian.

The simple diagram, Fig. 4, shows the origin of the main ai'teries of the trunk from the aortic arches and segmental arteries. This compared with Figs. 1 and 3 will explain itself. In the diagram the vessels which remain are black ; those which disappear, outlined; and those new formed, striated.

Resume : — While the aortic arches are forming, the arteries arising from the descending aorta pass on the mesial side of the coelom to the umbilical vesicle, and the blood passing through them is collected by the omphalo-mesenteric veins. Soon the segmental arteries arise, unite and shift backwards in the head region to form the vertebral artery. In the trunk they also unite within the lateral body-wall to form the internal mammary and deep epigastric arteries. Thisanastomosing arch, lying immediately below the tips of the ribs and the rectus abdominis muscle, wanders with them to the ventral middle line, the commrinicating branches forming the intercostal arteries. The whole course of the anastomoses between the tips of the segmental arteries takes on in its wandering the shape of the letter


Z (Fig. 4), the upper angle marking the origin of the subclavian. With the rotation and descent of the arm the subclavian is dragged partly through the sympathetic cord ; the origin of the superior intercostal is shifted, by the formation of a new anastomosis, from the dorsal to the ventral side of the sympathetic cord.



Fifi. 4. — Diagram to show the development of the arteries of the trunk from the aortic arches and segmental arteries. The arteries which remain are black; those which degenerate are outlined; those newly formed are striated. /. C, internal carotid; E. C, external carotid; J?. A., bulbus aortae ; P., pulmonary artery; A. D., descending aorta; v., vertebral; S., subclavian; F., femoral; C, umbilical; 7, seventh cervical; 3 and 12, third and twelfth dorsal.

The first vein collecting the blood from the abdominal aorta is the omphalo-mesenteric ; next the umbilical, and finally, the cardinal assumes this function.


TWO INSTANCES IN WHICH THE MUSCULUS STERNALIS EXISTED. WITH OTHER ANOMALIES

Henry A. Christian.


ONE ASSOCIATED


(From the Anatomical Laboratory of the Johns Hopkins University.)


During the past winter, two specimens of the musculus sternalis were found in the dissecting rooms of the Anatomical Laboratory of the Johns Hopkins University, and at the suggestion of Dr. Mall I make the following report of them. Both specimens occurred double in well developed white, male cadavers.

That the simple report of such anomalies can have little value in itself, is fully recognized ; but by recording such cases material will be accumulated, from which in the future generalizations can be drawn and perhaps some light thrown on the origin of such muscles as well as of the general body musculature. Realizing this I report the following two cases, which have perhaps an additional interest in that each represents a distinct form of this anomaly and one is further


associated with a series of variations confined to the regions from which the sternalis arises.

Specimen I. — The M. sternalis is well developed on both right and left sides. Unfortunately, however, an incomplete autopsy has partially mutilated the muscle of the right side, thus somewhat obscuring its true relations. However, as seen, the two muscles appear symmetrical and about equally developed. As shown in (Fig. 1) these supernumerary muscles have their origin in part by tendinous fibres arising from the lower two-thirds of the manubrium sterni medial to the origin of the M. pectoralis major, in part by fibres continuous with the tendinous attachment of the sternal portion of the M. sternocleido-mastoideus. The larger number of the fibres arising from the tendon of the M. sterno-cleido-mastoideus cross to


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[Kos. 90-91.


the tendon of the M. sternalis of the opposite side, those from the right side passing ventral to those from the left, while a part are continuous with the tendon of the same side. The tendon thus formed continues to the second intercostal space, where the muscle fasciculi begin and soon spread out into a fiat thin muscle about three centimeters in breadth. This muscle, slightly increasing in breadth, continues down to the fifth intercostal space, where it ends by an insertion into the fascia covering the M. rectus abdominis, a little below its point of origin. In its course the M. sternalis lies over the sternal origin of the M. pectoralis major and receives its nerve supply from a branch (anterior cutaneous) of the III intercostal nerve, which perforates the M. pectoralis major and becomes lost in the substance of the M. sternalis.

Specimen II. — On the right side the muscle arises from the tendon of the M. steruo-cleido-mastoideus and the thick fascia over the sternum (Fig. 2), extending as low down as the second rib. In addition a fasciculus arises from the second rib. This smaller fasciculus joins the main muscle on its lateral side in the region of the fourth rib. The main tendon becomes muscular at the third rib, from which place it continues down to be inserted into the fifth rib about three cm. from the sternum. In the third intercostal space this muscle receives a very minute filament from the anterior perforating cutaneous branch of the intercostal nerve, and also a larger twig from the outer cord of the brachial plexus. This latter nerve may be traced for 6 cm. running on the M. pectoralis major. It then pierces the M. pectoralis major over the third rib to continue upward between the M. pectoralis major and M. pectoralis minor to the upper border of the latter, where after passing beneath the acromial branch of the acromio-thoracic artery, it ends by joining the outer cord of the brachial plexus.

On the left side a much smaller fasciculus arises from the fascia over the first intersjiace. This soon becomes muscular, spreading out into a very thin muscle, which is inserted into the fifth rib. The nerve supplying this muscle can be traced to the anterior thoracic nerve, having a very similar course to that of the nerve supplying the muscle of the right side.

The musculus sternalis was noted by Cabrolius in 160i, and first accurately described by Du Puy in 1736. From the time of Du Puy down to the present, literature furnishes descriptions of about 175 well authenticated cases — a number apparently sufficient to enable us to safely generalize.* Unfortunately, however, none of these early descriptions note the


•The following will show the relative frequency of occurrence of this anomaly :

Wood 7 examples in 175 cadavers.

Turner 21 " " 650 "

Gruber 5 " " 95 "

Macalister 21 " "350 "

Le Double... 33 " " 722

Christian 2 " " 70 "

Total 89 " " 2062

About i\ per cent.


innervation. Although Hallet (1848) reported a case receiving its nerve supply from the III, IV and V intercostal nerves, and Malbranc (1876) by electrical stimulation on living subjects found a M. sternalis supplied from the intercostals, and another from the anterior thoracic, Cunningham was the first to fully recognize the value of the nerve supply in studying the origin of this muscle. This view is fully supported by recent studies in comparative myology as well as by the study of the development of the skeletal muscles. This information being recent the earlier writers make no mention of the nerve supply, and their reports are, from our present point of view, of scarcely more than historical interest, showing only the various forms that may occur. Since it appears that " all of the muscles arising from a myotome are always innervated by branches of the nerve which originally belonged to it" (Mall), it is evident that the origin of a muscle variation can only be studied to advantage when its nerve supply is given. Keviewing the literature from this standpoint I find that in but eighteen instances the nerve supply of the M. sternalis is given. To these I add two, making twenty in all, as shown in the accompanying table.

Can we infer anything as to the origin of this anomaly from these twenty specimens tabulated below ? That there have been many views as to the origin of this muscle, is shown by the various names (M. sternalis, M. presternalis, II. episternalis, M. sternalis brutorum, M. rectus thoracicus, M. rectus thoracis, M. rectus sternalis, M. accessorius ad rectum) which from time to time have been applied to it. The main hypotheses which have been advanced regarding the origin of this muscle are as follows :

(a) It is an upward extension of the M. rectus abdominis.

(b) It is a downward extension of the M. sterno-cleidomastoideus.

(c) It is a remnant of a panniculus carnosus and to be associated with the platysma myoides in man.

(d) It is an aberrant portion of the M. pectoralis major.

In 1876 Bardeleben concluded from the standpoint of morphology that not one but several different muscles had been described under the name of M. sternalis, and that of 130 cases, which he tabulated, 7 per cent, were varieties of the M. rectus abdominis, 31 per cent, of M. pectoralis major, 55 per cent, of M. sterno-cleido-mastoideus and 6 per cent, skin muscles.

Of the earlier cases reported, it is possible that some may have been genuine cuticular muscles, but that a muscle, which we would now class as M. sternalis, could have such an origin is not possible since it lies in a plane deeper than the platysma myoides, the representative of this class in man. Further to be an aberrant portion of this cuticular muscle, it should be innervated from above the brachial plexus, a condition which we have not as yet found to exist. That it is not a strictly downward extension of the M. sterno-cleidomastoideus, though the majority of the muscles are connected by their tendons of origin with the M. Sterno-cleido-mastoideus, we conclude from the fact that it does not have a similar nerve supply.


September-October, 1898.]


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TABLE GIVING THE ORIGIN, INSERTION AND INNERVATION OF THE MUSCULUS STERNALIS.


Observer.


side.


Fick,


R.


A. A. VI


S. 601.



2. Fick.


3. Fick.


4. Bardeleben,

A. A. IIIS. 324.

5. Bardeleben.


6. Bardeleben.

7. Bardeleben.

8. Bardeleben.

9. Bardeleben.

10. Bardeleben.

11. Bardeleben.

12. Shepherd,

Jour. Anat. and Phys. XIX-p.311.

13. Shepherd.


14. Shepherd.


20.


Wallace, Jour. Anat. and Phy. XXI-p. 153.

Christian, Specimen I.


Christian. Sj)ecimen 11.


R.


(R.


\ R.


\ R. ( L.


(?) L.


(L. I ! R.


15. Shepherd.


L.


16. Shepherd.


(L.



i R.

\


17. Shepherd.


(R.


(R. 1 L.


u.


Origin. Tendons of steruo-mastoid on both sides and upper digitations of pectoralis major on both sides.

Digitations of pectoralis major by means of two horizontal tendons to right and left at upper edge III rib.

Tendon left sterno-mastoid, few fibres from tendon right sternomastoid, manubrium sterni and upper digitations of pectoralis major of both sides.

Manubrium sterni and upper digitations of pectoralis major of both sides.


Tendon sterno-mastoid.


Right tendon sterno-mastoid. Both tendons of sterno-mastoid.

Right tendon sterno mastoid.

Manubrium sterni. Manubrium sterni.

Fascia of pectoralis major at II rib and left sterno-mastoid.

Right sterno-mastoid and some fibres from left pect. major.

Manubrium sterni.

Manubrium sterni.

Both sterno-mastoids and right pectoralis major.


Sterno-mastoid.

Sterno-mastoid and sternum opposite II and III rib.


Sternum opp. II rib.

Sterno-mastoid and right pector.

Pect. major over manubrium

sterni. Pect. major over manubrium

sterni.

Manubrium sterni. Manubrium sterni.


Right tendon sterno-mastoid and few fibres from left pectoralis •major.


Manubrium sterni and both tendons of sterno-mastoid.

Manubrium sterni and both tendons of sterno-mastoid.

Tendon of sterno-mastoid, fascia over manubrium sterni and a small fasciculus from II rib.


Fascia over I interspace.


iQsertlon. Rectus sheath at VI and VII ribs, digitations of ext. oblique arising from V rib and from fascia over sternum at level V rib.

Rectus sheath at VI and VII ribs and fascia of lowest digitations of pectoralis major.


Rectus sheath at V and VI ribs and fascia of pectoralis major and fasciculi to III, IV and V


Rectus sheath at VI rib, and a deeper layer to V rib and intercostal membrane between V and VI ribs.

Rectus sheath at VI rib and two thin fasciculi to left pectoralis major.

Rectus sheath at VI rib. Rectus sheath at VI rib.

Rectus sheath at VI rib.

Rectus sheath. Rectus sheath.

Rectus sheath at V rib.


Rectus sheath.

Rectus sheath.

Rectus sheath.

IV costal cartilage, border of sternum opposite V and VI ribs and aponeurosis of ext. oblique.

Ill costal cartilage and border of sternum.

Fasciculus into lower segment pectoralis fasciacontinuing with fibres of pector., lovcer end of sternum and ensiform cart.

Aponeurosis of ext. oblique.

III costal cartilage.

IV costal cartilage and fasciculus into fascia over pectoral is major.

A slip to fasc. over pect. maj. and a second to same lower down.

Pectoralis major and sternum opposite IV costal cartilage.

One fasc. to III cost, cart., a second to lower sternum and third to fasc. over pect. major.

Ill, IV, V and VI costal cartilages and border of sternum.


Rectus sheath at V rib. Rectus sheath at V rib.

V costal cartilage.


V' costal cartilage.


Remarks. Intra vitam contracted with sterno-mastoid inraisinghead.


Motion with sterno mastoid observed.


Nerve Supply. Ill and IV intercos.


IV intercos.


II, III and IV intercos.


Ill and IV intercos.


II and III intercos.

II and III intercosII and III intercos.

II intercos.

II intercos.

II intercos.

III intercos.

Ill intercos.

Ill and IV intercos.

Ill (?) intercos.

Int ant. thoracic. Anenceph.

Ant. thor. (?) Ant. thor. (?)

Int. ant. thor. and III intercos.

Int. ant. thor.

Int. ant. thor.

Int. ant. thor.

Int. ant. thor. Int. ant. thor.

Ext. ant. thor.

Ill intercos. Ill intercos.


Branch from Brachial plexus and a small twig from intercos.

Ant. thoracic.


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[Nos. 90-91.


Between the two remaining hypotheses there has been much discussion. Bardeleben advanced the theory that it belonged to the same plane of muscles as the M. rectus abdominis and M. sterno-cleido-mastoideus, and Testut the theory that it represents a connecting link between the M. obliquus abdominis externus and M. sterno-cleido-mastoideus, a condition normally found in the snake. However, Le Double claims that this latter condition does not hold and that the muscle found in the snake is represented in man by a deeper layer. It is probable that there is no exact analogue of this muscle in the lower animals. In some animals, as the Armadillo, beaver and Echidna the M. sterno-cleido-mastoideus extends down on the sternum (Turner) bxit not so far as the VI rib, and there is no connection with the M. rectus abdominis, which lies in a deeper plane. In all cyano-morphous primates (Keith) a M. supracostalis anterior occurs which is a digitation of the M. rectus abdominis arising from the I rib, but this lies beneath the M. pectoralis major. However there can be no doubt that Bardeleben was justified in his conclusion that a close relationship exists between the M. sternalis and the M. rectus abdominis since he and others have reported undoubted cases where the M. sternalis received its nerve supply from the intercostal nerves in a manner similar to the M. rectus abdominis.

This view of Bardeleben was generally accepted until P. S. Abraham reported some cases in anencephalic monsters, receiving nerves from the brachial plexus through the anterior thoracic branches. Soon after this Cunningham reported similar cases from adult cadavers. Such a nerve supply suggested a close relationship with the M. pectoralis major and from the fact of the long course of the nerve through and over the M. pectoralis major and from the recurrent course of many of the lower anterior cutaneous branches of the intercostal nerves perforating the fascia beneath the M. sternalis to run around the inner border of this muscle, it was concluded that it is an aberrant portion of the M. pectoralis major which had rotated inward and downward to this present position. This conclusion seems to be fully in accord with the facts and to be justided by the nerve supply which we regard as the link between present position and the myotome from which it arose. That this muscle is really often innervated from the brachial plexus is further shown by the contraction of the M. sternalis when the brachial plexus is electrically stimulated.

Here then we have two views as to the origin of this muscle, conflicting but both apparently well justified. Can these views be in any way harmonized ? From the twenty cases tabulated above it is readily seen that these muscles divide naturally into two classes, one with a fixed insertion into the middle ribs or margin of the sternum and supplied by nerves from the brachial plexus, the other with a less fixed insertion into the sheath of the rectus and a nerve supply from the perforating branches of the intercostal nerves, the origin of the two classes being very similar. From this we conclude that in the musculus Sternalis we have a muscle functionally always the same — probably antagonistic to the triangularis sterni— but that we have included under one term two distinct muscles, one closely related to the M. rectus abdominis, and the other an aberrant portion of the M. pectoralis major, the former supplied from the intercostal nerves and arising in the embryo


from thoracic myotomes, the latter supplied from the brachial plexus and arising from cervical myotomes. Therefore, from the standpoint of innervation and development we agree with the results obtained by Bardeleben that the name M. sternalis has been used as a general term and that it should be reserved for those presternal muscles associated with the M. pectoralis major, while the name M. rectus thoracis should be applied to those related to the M. rectus abdominis.

The cadaver from which specimen No. 1 was taken showed a number of additional muscle anomalies in the region of the course of travel which must have been followed by M. sternalis in its development. When one sees a marked anomaly he should look for and will frequently find associated variations. These may indicate the forces at work to produce variation, and for this reason I enumerate those which accompanied Specimen I.

Mnsadus deido-hrjoideus. — A M. cleido-hyoideus (Fig. 3) is found on the left side, occurring with no variations in the M. sterno-hyoideus, M. sterno-thyroideus or M. omo-hyoideus. It occurs as a thin narrow ribbon of muscle fibres more delicate than the M. omo-hyoideus. It arises from the body of the hyoid bone just above and overlapping the external third of the M. sterno-hyoideus and internal half of the M. omo-hyoideus. From this origin it passes downward and slightly outward to be inserted into the clavicle just posterior to the clavicular insertion of the M. sterno-cleido-mastoideus. Just before reaching the clavicle the muscle spreads out fan-like to be inserted by an aponeurosis about twice the breadth of the muscle and extending along the clavicle from a little internal to the middle point of the insertion of the M. sterno-cleidomastoideus to a point about one cm. external to its insertion.

Quite frequently the M. omo-hyoideus gives off a slip to be inserted into the clavicle and consequently this muscle may be regarded as an aberrant portion of the M. omo-hyoideus here entirely split off except at its very origin. Its nerve supply is apparently the same as that of the M. omo-hyoideus, a fact supporting this view of its histogenesis.

M. sterno-thyroideus. — On the left side the M. sterno-thyroideus is normal as to its size and attachment. The muscle of the right side is fully twice as broad as that of the left and somewhat thicker. Its origin from the sternum is normal. Its insertion is by three heads, each more or less distinct. Of these the inner is inserted as usual on the inferior surface of the oblique ridge of the thyroid cartilage and represents in size and insertion almost the normal muscle. The middle head continues up closely associated with the outer border of the M. thyro-hyoideus, which latter is somewhat narrower than the one of the opposite side. Most of the fibres of this head are inserted into the anterior inferior and middle border of the hyoid bone, while a few are inserted into the middle jiart of the superior border of the thyroid cartilage. The outer head consists of a distinct ribbon of fibres running up to be inserted into the deep cervical fascia and sheath of the carotid artery intimately blending with these structures. The main part of the muscle is supplied by a branch from the hypoglossal loop, while the middle and outer heads receive fibrils from a branch of the hypoglossal nerve given off above that to the M. thyro-hyoideus.

M. hyo-corninch hryngis {M. hyo-carfilnffo saiiioriniana'). —





w



^"Is'ii^'-'sktliti,



Fii:. 1.— Sketch sliowiu!;- the nttiiclinient of tlie M. steniali: in Spefimei] No. I.


FiK. 2. — The attachment of the M. sternalis in- Specimen No. II.


'.iii.i jV-'/'l


u-p




A^:-X^<ki,


\ u


Fio. :!.— The neck of Specimcu I, to tlie .M. cleido-hyoiilens to the clavicle.


the attachment of



Fig. 4. — The axilla of Specimen No. I, to show the slip from the M. latissimus di>rsi to thi' pcctoralis nn)jor.


Tin: .Ion\s Hopkins llo.-ini vi. Iill.l,i:n\ Nos. 9(l-91.


September-October, 1898.]


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Arising on the right side from the tendinous portion of the M. digastricus, where it is held down to the hyoid bone by a strong loop of fiiscia, is found a small muscle about one cm. wide, nearly cylindrical in shape and running downward and outward around the larynx for about 6 cm. to be inserted into the fascia about the cornicula laryngis (cartilage of Santorini). Its nerve supply consists of a fine fibril arising from the hypoglossal nerve.

M. trapezius. — The M. trapezius of the right side gives off a fasciculus about 5 cm. wide and 1.5 cm. thick which is inserted into the clavicle at the inner part of its middle third just external to the origin of the clavicular portion of the M. sternocleido-mastoideiis. This fasciculus extends upward to join the anterior border of the main portion of the M. trapezius about 10 cm. from its insertion into the occipital bone. No special distinct nerve supply could be found for this fasciculus.

M. latissimus dorsi. — On eacli side of the subject the M. latissimus dorsi (Fig. 4) possesses an accessory tendon of insertion. The larger normal tendon passes as usual beneath the axillary artery and brachial nerves while the accessory tendon passes over, thus forming an arch for the nerves and vessels. The regular head is inserted into the bicipital groove of the humerus while the accessory one is inserted along with the tendon of insertion of the sternal portion of the M. pectoralis major into the anterior bicipital ridge. The tendinous fibres of this latter are intimately associated with the pectoral tendon for about 2 cm. and then separating pass down as a rounded tendon to join the muscle fasciculi which come off from the main muscle about 6 cm. from its humeral insertion. The accessory head thus formed is about one-fifth the size of the other tendon, which is normal and 7.5 cm. in length.

The two heads form a triangle with the long and short heads of the M. biceps and M. coraco-brachialis as a base. Through this pass the axillary artery and vein, the median, musculo-spiral, ulnar, internal cutaneous and lesser internal cutaneous nerves. So far there is almost perfect symmetry in these structures on the two sides of the cadaver, but the nerve supply to each head is apparently different, though the ultimate origin of the individual nerve fibres from the cord may possibly be quite the same.

The accessory head of the M. latissimus dorsi of the left side is supplied and apparently solely supplied by a rather small nerve entering the muscle substance. This can be traced up to the lower border of the M. pectoralis minor, there to join a nerve which is unmistakably the internal anterior thoracic, since it supplies the M. pectoralis minor sending some of its fibres through this muscle to supply the M. pectoralis major. On this side of the body the internal anterior thoracic nerve arises by two divisions and probably receives fibres from the VII and VIII cervical nerves.

On the right side, at first sight, the accessory head would seem to receive its nervous supply from the II and III intercostal nerves, since two stout branches from these sources enter the muscle substance. However, on closer examination, these appear to pass through the muscle substance without giving off any fibres to the muscle and to end further on as cutaneous nerves. As no other definite nerve fibre could be traced to this head, it must be supplied by a fibre from the middle or long


subscapular nerve, running up in the muscle substance from the main muscle body. If this be the case these fibres would ultimately have about the same source in the cord as those supplying the accessory head on the left side as may be seen by comparing the diagrams of the two plexuses.* On the right side the long subscapular nerve arises from the posterior cord of the plexus just after this cord receives a branch from the inner cord. Thus this long subscapular nerve probably consists of fibres from the VII and VIII cervical nerves, the same nerves as those supplying fibres to the accessory head of the M. latissimus dorsi of the left side through the branch from the internal anterior thoracic nerve.

On neither side does the M. latissimus dorsi receive a slip from the tip of the angle of the scapula.

M. extensor carjii radialis accessorms. — This muscle occurs only in the right arm. Its origin is from the radial side of the M. extensor carpi radialis longior by a slip separating about 4 cm. from the origin of this muscle. About 5 cm. above the annular ligament this slip becomes muscular. Just above the ligament it passes under the tendon of the M. extensor carpi radialis longior to be inserted with the M. extensor carpi radialis brevior into the base of the metacarpal bone of the middle finger. It is innervated by a branch of the musculocutaneous nerve.

M. extensor digiti tcrtii. — Occurs only in left hand. Its origin is from the posterior shaft of the ulna below the origin of M. extensor indicis. Its tendon passes down with that of the M. extensor indicis through the same compartment in the annular ligament, and is inserted finally into the tendon of the M. extensor communis digitorum belonging to the middle finger and on its ulnar side. Its nerve supply is from the posterior interosseous branch of the musculo-spiral nerve.

Scapula. — On either side of the body, the tip of the acromial process is separate from the scapula, being connected to the spine of the scapula by a firm ligamentous band of connective tissue surrounding the proximal ends of bone lying in juxtaposition. The ends of the bones are covered with cartilage, and all are so firmly bound together that very little motion is possible.

All of these eight variations, in addition to the M. sternalis, are along the course the diaphragm takes in its excursion, during development, from the neck to its permanent location. It is to be noted that all this takes place before the embryo is four weeks old, and that at this time the muscles are just beginning to be formed from the myotomes.

Aug. 22, 1898.

Literature.

Bardeleben (K.) Der Musculus sternalis. Ztschr. f. Anat. u. Entwicklungsgesch., Leipz., Bd. i, 1875-6, S. 424-458.

Bardeleben (K.) Die morphologische Bedeutungdes Musculus sternalis. Anat. Anz., Jena, Bd. iii, 1888, S. 324-333.

Baker (F.) Some Unusual Muscular Anomalies. Med. Kec, N. Y., vol. xxxii, 1887, pp. 809-811.


Anatom. Laboratory, Johns Hopkins Univ. Nerve Records of Subject 94.


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[Nos. 90-91.


Cuyer (E.) Anomalies osseiises et musculaires. Bull. Soc. d'aiithrop. de Par., 4. s., t. i, 1890, pp. 557-570.

Cunningham (D. J.) The Musculus Sternalis. J. Anat. and Physiol., Lond., 1883-4, vol. xviii, pp. 208-210; also ibid, 1887-88, vol. xxii, pp. 391-407.

Fick (R.) Drei Falle von Musculus sternalis. Anat. Anz., Jena, 1891, Bd. vi, S. 601-606.

Gegenbaur (C.) Lehrbuch der Anatomic des Menschen, — Aufl., 8°, Leipzig, 1895, Bd. i., S. 390.

Jung (A.) Eine noch nicht beschriebene Anomalie des Musculus omohyoideus. Anat. Anz., Jena, 1872, Bd. vii, S. 582584.

Keith (A.) Notes on Supracostalis anterior. J. Anat. and Physiol., Lond., 1893-94, vol. xxviii, p. 333.

Lambert (0.) Considerations nouvelles a propos d'un nouveau cas de muscle presternal. Bull. Soc. d'anthrop. de Par., 1894, 4. s., t. V, pp. 237-241.

Le Double (A.) Sur trente-trois muscles presteruaux. Bull. Soc. d'anthrop. de Par., 4. s., t. i, 1890, pp. 533-554.

Michel (M.) Two Cervical Muscle Anomalies in the Negro. Med. Rec, N. Y., 1892, vol. xli, p. 125.

Mall (F. P.) Development of the Ventral Abdominal Walls in Man. J. Morphol., Bost, vol siv, 1898, pp. 347-366.


Perrin (J. B.) Notes on Some Variations of the Pectoralis Major, with its Associate Muscles seen during seasons 1868-9, 1869-70. J. Anat. and Physiol., Lond., 1870-71, vol. v, pp. 233-240.

Quain (J.) The Elements of Anatomy. 10th ed.

Shepherd (F. J.) The Musculus sternalis and its Occurrence in (Human) anencephalous Monsters. J. Anat. and Physiol., Lond., 1884-5, vol. xix, pp. 311-319.

Schultz (J.) Zwei Musculi sternales. Anat. Anz., Jena, 1888, Bd. iii, S. 228-234.

Testnt (L.) Les anomalies musciilaires chezrhomme espliqu^es par I'anatomie comparee; leur importance en anthropologie. 8°. Paris, 1884.

Turner (W.) On the Musculus sternalis. J. Anat. and Physiol., Lond., 1866-7, vol. i, pp. 246-253.

Walsh (J. J.) A Sternalis Muscle. Univ. Med. Mag., Phila., 1897-8, vol. X, p. 231.

Wood (J.) On Human Muscular Variations and their Relation to Comparative Anatomy. J. Anat. and Physiol., Lond., 1866-7, vol i, pp. 44-59.

Wallace (D.) Note on the Nerve Supply of the Musculus sternalis. J. Anat. and Physiol., Lond., 1886-7, vol. xxi, p. 153.


ON THE PATHOLOGICAL CHANGES IN THE SPINAL CORD IN A CASE OF POTT'S DISEASE

By Sylvan Rosenheim. {From the Anatomical Laboratory of the Johns Hopkins University.)


That scientific advances go hand in hand with improvements in the methods of research has nowhere been better demonstrated, perhaps, than in the study of the central nervous system. Early in this century much was accomplished by mere dissections and sectioning of the various parts of the nervous system, but the greatest strides have occurred since Weigert, in 1884, published his method of staining the myelin sheaths of the nerve fibres. Of the various methods employed to isolate the tracts in the spinal cord, that depending on the degeneration following severance of the connection between a nerve fibre and its trophic centre, namely, the cell-body from which it arises, has been one of the most important.

It is this method of study which has been utilized in the present case, in which the spinal cord was pressed upon by a tuberculous exudate. The methods of Weigert and Marchi have both been employed. It has been possible, by a combination of the two methods, to determine the extent of the degeneration following the compression, and to distinguish the more recent degenerations from those which occurred at an earlier date.

The case is also interesting in view of the light it throws upon some of the more recent problems in connection with the study of the spinal cord, especially

(1) The finer histological changes about the site of primary lesion, and

(2) The paths which descend in the dorsal funiculi. I wish to thank Dr. Barker for his aid in this study.


CLINICAL HISTORY.

The patient, H. H., a female, colored, jet. 15 years, entered Professor Osier's wards of the Johns Hopkins Hospital October 10, 1895, complaining of loss of power in the legs.

Family History. — Father and mother living and well. One of her brothers, who died at the age of 7 years, had contraction of the lower extremities, similar to that from which the patient suffers, one month before his death. Grandmother, on the paternal side, died of a " heavy cough " ; she was very emaciated before death. An aunt on the mother's side is a consumptive.

Personal History. — Patient has had no scrofulous breaking down. Menstruation not yet established. At the age of 6 years the patient was gradually attacked with loss of sensation in the feet, which was shortly afterwards followed by loss of power, and she was confined to her bed for three weeks, when she gradually regained power. She was able to run, walk and skip, and was in good health up to last February. Every winter she suffers from a cough, which lasts until the spring to return again the following winter. Thick white expectoration is associated with the cough.

Present Condition. — In February, 1895, the patient was attacked by influenza. She was ill until March 1st, when she was well enough to get up but found she had no power in the legs. Shortly after this the legs became flexed upon the thighs and the thighs upon the abdomen. This has been the condition for most of the time since, the muscles becoming relaxed only when the patient is asleep or very quiet. The


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bowels and bladder have been voluntarily controlled, micturition being frequent, about four times at niglit, five times during the day. The bowels are constipated, not moving sometimes for a week. About one month ago the movements of the bowels as well as micturition became involuntary. This lasted up to two weeks ago, when the involuntary condition ceased but the movements became frequent. Her mind has been clear all along. There has been no trouble with the eyesight, no pain in the head, and no pain in the back. The floor feels like a cushion. The upper extremities have at no time been afiected. There is no cough at present.

Physical Examination. — Bather thin but generally fairly well developed colored girl. Somewhat pale. Tongue covered with a white coat. Pupils equal. No nystagmus. Movements of the eyes normal. Chest is rather fiat; costal margin is prominent in right parasternal line. Over the upper right chest is a wound situated nearer sternum than axilla, measuring 5x2.5 cm. In the centre of this wound is a sinus in which a probe inserted passes upwards and inwards about 3 cm. to dead bone. Dead bone evidently in the sternum. Probe also passes behind sternum.

Lungs. — Front: Expansion very poor on both sides. Percussion fairly good. Breath sounds clear over right front. Slightly tubular in apex of right axilla. No rales are heard.

Back : Impaired resonance over both upper backs. At the left apex, breath sounds are somewhat tubular. At the base, percussion note is better, but everywhere expiration is somewhat blowing, particularly in left axilla. In this region vocal fremitus is absent, and breath sounds, as well as voice sounds, are distant.

Eight lateral decubitus: A distinct bulging can be seen in the left flank. It measures about 8x4 cm. On palpation it is distinctly fluctuating. Hypodermic needle inserted withdraws a thick, cloudy fluid which, on microscopic examination, is found to consist of broken down cells and granular debris.

There is no marked irregularity of the spine, and apparently no pain anywhere on firm pressure. No bed sores.

Heart. — Point of maximum impulse somewhat diffuse over fourth and fifth spaces from the sternum to nipple line. At the apex the sounds are clear. Soft systolic murmur in the second left space. Aortic area clear.

Abdomen. — Muscles held rigidly; spleen distinctly palpable.

Muscular Power and Sensation. — Muscular power in the arms good, flexors stronger than extensors. Reflexes present at elbow, but not so easily obtainable at wrist. Movements of the facial muscles fairly good. Legs are strongly flexed on thighs and thighs somewhat on abdomen. Almost constant clonus in muscles of left thigh. On attempting to straighten the legs, they are found quite spastic, and clonus is increased. Considerable wasting in the calf muscles, not so marked in the thighs. Patient cannot voluntarily flex the legs upon the thighs. When the legs are extended there is still slight clonus in left flank; not so much ir. the right.

Sensation markedly impaired. Sensations of heat and cold are almost entirely gone from the umbilicus down. Sensation of touch much impaired. There is a region of hyperaesthesia in the back, extending from a little above the ilia and stretching over the gluteal muscles.


The patient was operated on November 2, 1896. The lumbar abscess was incised and packed. The condition of the lower extremities did not improve. The patient gradually became weaker, and died February 13, 1897.

AUTOPSY.

The autopsy was made by Dr. Flexner February 14, 1897. The following notes have been extracted, by permission, from the protocol in the Pathological Laboratory :

Anatomical Diagnosis. — Ihiberculosis of the spine. Extradural exudate. Compression myelitis. Paraplegia. Tuberculosis of sternum. Intestinal tuberculosis. Paralysis of bladder. Pyo-cystitis, pyo-ureteritis, pyelitis, pyelo-nephritis, bronchitis. Lateral curvature of the spine to the left in lower part.

Muscles of feet and legs apparently very much atrophied. Thigh muscles also atrophied, the right more than the left.

On the right side, the pelvis is apparently thrown forward and rotated inward. Crest of the ilium is prominent, and right extremities are rotated inwards. The face shows no emaciation, contours rounded, lower jaw protuberant. The dura covering the brain is moderately adherent to the skullcap. The superior longitudinal and lateral sinuses contain recent clots. Pia and arachnoid are normal. No visible tuberculosis in the pia.

The spinal cord in two distinct situations is the seat of an extra-dural infiltration. The first begins about 2 cm. below the lower edge of the cervical enlargement and extends for a distance of about 5 cm. downwards; it is composed of dense caseous infiltration which averages 4-5 mm. in thickness. The second one begins above the lumbar region and extends over it and below it; it is thicker than the upper, but of the same nature. Both completely infiltrate the subdural areolar tissue.

The cord corresponding to the caseous infiltration is, in the cervico-thoracic region, distinctly softened. The roots of the spinal nerves (motor and sensory) pass through the exudate.

The exudate in the lumbar region has not compressed the spinal cord.

Heart. — Slight fatty degeneration in the intima of the aorta just above the valves.

Lungs. — Emphysematous and osdematous. Pus in bronchi.

Kidneys. — Capsule congested. Beneath the capsule and throughout the kidneys are white areas about the size of miliary tubercles. The kidney substance is soft and oedematous. On section, the cortex is greatly swollen. Striaj obliterated. Mucous membrane of the jielvis and ureters is congested, and shows ecchymoses.

Bladder. — Enormously distended ; contains thick pus. Walls thin.

Spleen. — Enlarged; substance soft on section. A few tubercles seen. Tubercles are occasionally met with in mesentery and omentum.

Intestines. — Swollen solitary follicles in the ileum with excavated centres. Ulcers near the valve, edges raised, surrounded by congested mucous membrane. Tubercles visible in the clear congested base.

Spine. — The bodies of the second, third and fourth thoracic vertebrae are eroded, softened, crumbly, and infiltrated with caseous pus. The transverse processes of the second and third


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lumbar vertebraB are similarly affected. The bodies of these vertebrje are only superficially diseased, however, and this affection is in the locality of the extra-dural exudate. Sternum eroded. Manubrium and gladiolus can be separated.

Muscles of the Back. — Along the spinal column the muscles are invaded by irregular sinuses and collections of pus-containing caseous material.

METHODS OF EXAMINATION.

The spinal cord was immediately put in a mixture of equal parts of formalin (5 per cent.) and Miiller's fluid. The brain, including the medulla, was put into 5 per cent, formalin.

Four slabs of tissue were taken from each segment of the spinal cord, two pieces across the entrance and exit of the nerve roots, and two pieces between the nerve roots, so that when, in the description, a certain segment is designated, a level between the nerve roots above and below the number of the segment mentioned is indicated. Of these four slabs, two pieces were used for Weigert's method and two for Marchi's method of staining, comparative information being thus obtained.

The degeneration of nerve fibres, as is well known, can be divided into two periods— that before and that after the absorption of the disintegrated myelin. The former corresponds to the breaking up of the myelin sheaths into fat droplets; these stain black in Marchi's fluid. The latter corresponds to the stage shown best by Weigert's method, in which there has been absorption of the myelin, and hyperplasia of the glia. Thus the method of Marchi shows those fibres which have only recently degenerated, while Weigert's method gives information regarding those that have been degenerated for some time. As will be seen later, the picture obtained by these two methods difiered considerably in parts. In general, the Weigert method revealed the greater alterations in this case, owing to the length of time which had elapsed since the beginning of the compression.

The roots of the spinal nerves on both sides, to as low a level as the twelfth thoracic inclusive (excepting the fourth cervical pair, which were accidentally lost), were likewise stained separately by the Weigert and Marchi methods.

For a more exact study of the pathological changes, especially in the softened region, additional stains were used — htematoxylin and eosin, hematoxylin and carmine, Upson's carmine. Van Gieson's stain, and Mallory's stain. Good results were also obtained by counter-staining Marchi specimens with Upson's carmine.

FINDINGS ABOUT THE REGION OF COMPRESSION.

As the protocol of the autopsy states there were two areas of extra-dural tuberculous exudate. The upper area alone led to compression of the cord.

The region of compression extends between the eighth cervical and the fourth thoracic nerves, thus involving about three segments of the spinal cord.

With low amplification (10 diameters), a section across the upper part of this region shows that the cord has been compressed dorso-ventrally, much more on the right than on the


left side. The outline of the gray matter is faintly preserved; the white funiculi contain many bands of sclerotic tissue, more marked in the dorsal funiculi. Many small holes in the tissue also occur here. About the middle of the site of compression the cord is much compressed laterally and broadened dorsoventrally. The gray matter is much distorted, the ventral horns being greatly shrunken ; the dorsal horns can be followed for only half their extent. The white matter shows much sclerotic tissue, the holes above mentioned and numerous dilated blood-vessels. In the region corresponding to the lower part of the lesion there is remarkable distortion of the spinal cord. In the ventral half a normal contour is approached, but the dorsal half narrows to a blunt point at the tip of the left dorsal horn. The ventral horns are much shrunken, the " dorsal horns are united for the ventral half of their extent; they then separate at an angle of about 60°, the right horn being much curved. The white matter abounds in sclerotic tissue and holes; the dorsal funiculi are destroyed in their ventral halves, their place being occupied by the united dorsal horns.

General Appearances at the Site of the Compressmi. . See Figs. XIII and XTV.

1. Although the disintegration of the white matter has been very extensive, numerous axis-cylinders staining deeply with acid fuchsin can be seen. The nerve fibres illustrate all stages of disintegration. Many are much swollen and of irregular shapes. Some are entirely devoid of myelin sheath. In other fibres the myelin sheath is still present, but the normal concentric rings are absent. In only a few fibres are the normal concentric rings preserved. Vacuoles are found in many of the nerve fibres. They occur in various parts of the myelin sheath, but are found especially just peripheral to the axis-cylinders.

The axones show various changes. Some are swollen and very irregular in shape. At times only part of the axiscylinder stains, giving rise to bizarre appearances. Some of the axis-cylinders refuse to take on the stain, and the nerve fibres are represented by homogeneous feebly staining masses. Many of the fibres have disappeared, leaving holes to represent them. In Marchi specimens, counter-stained in Upson's carmine, the disintegrated myelin is represented by smaller and larger black balls.

2. The neuroglia is much increased in amount (Fig. XIII). It helps to yield the intense red color seen in all the specimens stained in carmine. It occurs in fine and coarse bands in the lower part of the region of compression, giving rise to the reticl^]ated appearance of the white matter. It is also much proliferated in the gray matter in the middle region of the compression, the dorsal cornu having been converted into masses of sclerotic tissue. Here the ventral fissure is filled with dense connective tissue, and the sclerotic tissue in the white matter can be seen to radiate from this. Many neuroglia-uuclei are seen, some small and round, staining homogeneously with carmine, and surrounded by a small colorless area; others, larger, oval or irregular in shape and granular. Here and there, scattered in the network of neuroglia, are masses of ball-like material, which take on a slight pinkish color in specimens stained by Van Gieson's method. In some


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of these there is seen au irregularly shaped nuclear-like body, which takes on a faint pink stain.

3. The blood-vessels are numerous throughout the white and gray matter and in the fissures of the cord. They are much dilated and packed with blood corpuscles. Their walls stain intensely red in carmine, and around them are aggregations of cells with round and polymorphous nuclei. These vessels, with their thickened walls, give rise to the coarse bauds found at the upper part of the region of compression. There has been considerable hemorrhage at the lower part of the region of compression. Throughout the white matter are many extra vasated red blood corpuscles. They are massed in large heaps in the dorsal funiculi along the periphery and next to the broken up dorsal cornu. Scattered in the white and gray matter, are numerous polymorphous nuclear leucocytes. The blood-vessels at this level are much dilated and are full of corpuscles, most of them red.

4. The ganglion-cells show various changes in the region of compression. At about the level of the first thoracic and eighth cervical segments many of the cells are swollen, their protoplasm staining a homogeneous pink color in carmine. There is no trace of the normal tigroid masses, although these are well seen in sections from areas both above and below the compressed portion. The nucleus in some of the cells is displaced to the edge of the cell, being almost colorless, but containing a deeply staining nucleolus. The cell outlines are not sharp, and the protoplasmic processes are not seen. At the level of the second thoracic segment, only a few distorted ganglion-cells are to be seen. In Marchi specimens, counterstained in Upson's carmine, these stain a homogeneous pink color, and contain numerous small intense black granules. At the level of the third thoracic segment there are but a few indefinitely outlined cells devoid of Nissl bodies, but containing numerous black granules. At the level of the fourth thoracic segment the cells are again more numerous, but Nissl bodies are to be made out ouly in some, and in many the nucleus is displaced to the side of the cell.

5. There is a proliferation of the cells lining the central canal at the level of the first, second and third cervical nerves. The cells here are a couple of layers thick, in parts occluding the lumen of the tube. From the third to the sixth cervical segments, the lumen of the canal is patent and lined by a single layer of high columnar cells. From the sixth cervical segment down to the sacral cord there appears to -have been proliferation of these cells most extensive about the region of compression, being several layers thick there. The lumen is occluded from the first to the fifth thoracic segments. The cells in the proliferative area have lost their columnar appearance.

6. The holes, which have already been mentioned, ai"e found far above and below, but are much more numerous at the site of the compression. These holes have been described before by Krauss,* who attributes their occurrence, probably correctly, to the action of formalin on the tissues, which he thinks causes a contraction of the neuroglia. In this way, he says.


Krauss, \V. C. Formalin as a hardening agent fornerve tissues. Trans. Am. Micr. Soc, 1895, Buffalo, 1896, vol. xvii, pp. 331-335.


using a 10 to 15 per cent, solution of formalin, the hardened cord has a honeycomb appearance. The fact that these holes are more numerous around the region of compression, in the present case, makes it evident that a softened condition of the cord aids a great deal in effecting this appearance. Some of these holes are empty, some are partly filled by the products of disintegration and absorption of the nerve tissue. The following types and variations of the contents of the holes may be mentioned.

In or about the centre of a hole is a round body containing a nucleus, which stains well in nuclear dyes, surrounded by clear, homogeneous, non-staining, small globules. They are seen in specimens stained by all the methods used. They are the familiar compound granular corpuscles. Variations of this type occur, the granules taking on in carmine and Van Gieson siiecimens a faint pink tinge, giving the protoplasm of the cell a homogeneous or somewhat reticulated appearance. Vacuolic areas occur in these. This variation may be due to dissolving out of the fat.

In sections prepared by all the methods (including Marchi specimens, counter-stained in carmine) there are seen in the holes, bodies, some the size and shape of axis-cylinders, others much larger and of irregular shapes, which stain homogeneously and deeply in carmine, eosin and acid fuchsin. They are the so-called corj)ora amylacea.

There are seen in Marchi and Weigert specimens in the holes, small black droplets and larger black balls.

With Van Gieson's stain some of the holes are seen to be filled with indistinct globules of various sizes, which take on a faint yellowish tinge. In Weigert specimens, counter-stained in Upson's carmine, these are seen more distinctly, and take on a blackish coloration.

The picture presented is that of a myelitis of some duration, showing in different parts of the lesion the forms of white and red softening. The most common of the microscopical appearances are well known ; these consist in the disintegration of the myelin into fat droplets, swelling of the axiscylinders, swelling and disintegration of the ganglion-cells, together with an inflammatory exudation and an infiltration with blood corpuscles. Some of the fat granule cells seen are characteristic. Corresponding with the long duration of the inflammation there has been an extensive proliferation of neuroglia, giving rise to interlacing fibrils and dense sclerotic tissue.

MICROSCOPIC EXAMINATION OF CERTAIN LEVELS ABOVE THE LESION.— ASCENDING DEGENERATION.

The appearance of a section at a given level varies with the method of preparation. In the following descriptions the method is indicated, and when the degeneration field at any one level varies according to different methods several sections will be described. The degenerated fibres are shown in specimens stained by Marchi's method, as black droplets of irregular contour, which on high magnification are seen to take the place of the myelin sheaths of the nerve fibres. The appearance varies according to the magnification used. Some degenerations are so clearly defined as to be readily studied with a magnification of 10 diameters ; in others the degenerated


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fibres are so few and scattered, as to require a higher magnification.

The degeneration field is indicated in the Weigert preparations by a lightening or lack of color. Where only a few scattered fibres have undergone degeneration, it is often impossible by Weigert's method to determine their absence.

First Thoracic Segment. — Upper part stained by Marchi's method and Upson's carmine.

The shape of the cord is tolerably well preserved here ; the gray matter is of normal configuration, but is not very sharply marked off from the white substance.

Dorsal funiculi: These show degeneration over the whole cross-section, but not completely. The degenerated fibres are more closely aggregated in the ventral half, but eveu here there is much intervening matter, partly of a fibrous nature, which stains deeply with carmine. A few axis-cylinders are seen on the periphery. Throughout are many dilated blood capillaries.

Lateral funiculi: In the regions of the fasciculus cerebrospinalis lateralis (lateral pyramidal tract) and the fasciculus cerebellospinalis (direct cerebellar tract) are seen scattered degenerated fibres. The zone thus occupied does not quite reach the lateral horn of the gray matter. Neuroglia tissue is found between the degenerated nerve fibres, and throughout, but more numerous towards the periphery, are large holes, some empty, some filled with material, as before described. But few axis-cylinders are found, staining a bright red color. Extending ventralward from the region of the fasciculus cerebellospinalis is a marginal strip, reaching the ventral median fissure, containing a few degenerated fibres, the number being more numerous in front.

Eighth Cervical Segment. — Weigert-Pal preparation. The shape of this section closely resembles that of the last.

Dorsal funiculi : Seen by the naked eye the dorsal funiculi appear much lightened throughout, excepting a narrow strip on the periphery stretching between the tips of the dorsal gray horns. Microscopically, the degeneration is confirmed. One sees numerous minute holes, probably representing degenerated dorsal root fibres, greatest in extent along the middle third of the septum. Throughout, however, are found numerous well-stained fibres, and along the periphery they all appear of a normal color.

Lateral funiculi : Here the lightened or degenerated area occupies the peripheral half of the column, extending from the tip of the dorsal gray horn to opposite the lateral gray horn. Many holes appear in this region. No lightening occurs in the fasciculus ventrolateralis superficialis (Gowers' tract).

The Marchi specimens show degenerated fibres in practically the same areas in the dorsal funiculi. In the lateral funiculi degenerated fibres are scattered in the peripheral half, being very scattered in the fasciculus ventrolateralis superficialis.

Seventh Cervical Segment,^ e,\gQYi-2&\ preparation. See Fig.

vin.

Dorsal funiculi: The degenerated area no longer occupies the whole breadth of the dorsal funiculi. A relatively large area of healthy fibres intervenes between it and the dorsal


gray horn. Considering both sides of the degeneration together, the lightened area has the shape of a tennis racquet, the end of which next the dorsal gray commissure is slightly expanded. As at the preceding level, the majority of the degenerated fibres occur along the ventral half of the septum.

Lateral funiculi : The lightened area, less intense than in the dorsal funiculi, extends from the tip of the dorsal gray horn to the emergence of the ventral roots. In its dorsal part it occupies the lateral third of the lateral column ; in the region of Gowers' tract it is slightly broader, occupying about half the breadth of the column. The lightening seems to consist in a feebleness rather than a lack of staining. Between Gowers' tract and the direct cerebellar tract is a band of fibres staining more deeply.

The Marchi specimen shows a similar distribution of the degenerated fibres in the dorsal funiculi, with a few scattered degenerated fibres in the lateral part of the fasciculus cuneatus (Burdachi). In the lateral funiculi, there are but scattered degenerated fibres in the lateral pyramidal tract, direct cerebellar tract, and Gowers' tract ; they are most numerous at the periphery of the cord.

Fifth Cervical Segment, Weigert preparation. See Fig.

vn.

Dorsal funiculi : The degenerated area occupies now a little more than the fasciculus gracilis. Considering both sides together it is bottle-shaped, the part resting next the dorsal gray commissure being slightly expanded. The lightening is more marked in the ventral half.

Lateral funiculi : The degenerated area extends from the tip of the dorsal horn to the exit of the ventral root. Next the dorsal horn, it occupies the peripheral third of the lateral column for a short distance ; it then narrows, and opposite the lateral gray horn it again expands, occupying half the breadth of the column.

Marchi specimens stained in carmine show a marked increase in neuroglia among the degenerated fibres in the dorsal fasciculi. Here also are seen many axis-cylinders staining intensely red. Burdach's fasciculus contains a few scattered degenerated fibres. In the lateral column the degenerated zone is about the same shape as in the Weigert specimen, the direct cerebellar being more affected. In the region of the fasciculus veutrolateralis superficialis (Gowersi), the degenerated fibres are more scattered.

Third Cervical Segment, Weigert preparation. See Fig. V.

Dorsal funiculi: The lightened area is restricted to the fasciculus gracilis (Golli), occupying the dorsal threefourths. Considering both sides together the area is triangular in shape with the base at the periphery. There is a small peripheral part next the dorsal median septum which is scarcely at all lightened.

The entering dorsal roots on both sides show lightening, more marked on the right side. There is also lightening of Lissauer's fasciculus.

Lateral funiculi: The degenerated zone extends from the tip of the dorsal gray horn to the ventral roots, occupying the peripheral half of the lateral column. It is much more intense in Gowers' tract. In the region of the fasciculus cerebellospinalis (direct cerebellar tract) the degeneration is


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more marked a little inwards from the periphery of the cord. Nest the periphery there is a band of almost normally staining fibres. Notwithstanding the degenerated fibres in the dorsal roots, the collaterals entering the gray matter appear to be of normal number and to be well stained.

The Marchi specimen (Fig. VI) shows iu addition to the triangular area in Goll's fasciculus scattered degenerated fibres in the fasciculus cuneatus, more numerous on the periphery.

In the lateral funiculi it is to be especially noted that more degenerated fibres are visible in the fasciculus cerebellospinalis (direct cerebellar tract) than farther ventralwards. The degeneration of this tract is better defined here than in the sections lower down.

Second Cervical Segment, Weigert preparation. See Fig. III.

In the dorsal funiculi the degeneration is the same as that described for the third cervical segment.

In the lateral funiculi the fasciculus cerebellospinalis and the fasciculus veutrolateralis superficialis are degenerated iu about the same region as seen at the third cervical segment; the band of more deeply staining fibres along the periphery next the fasciculus cerebellospinalis is very well marked. Besides these degenerations there appears to be a slight lightening in the lateral funiculi extending along the outside of the lateral gray horn. It is not very marked, and blends with the area of healthy fibres separating it from the fasciculus of Gowers.

The Marchi specimens (Fig. IV) at this level show blackened fibres in the entering dorsal roots.

First Cervical Segment, Weigert preparation. See Fig. I.

Dorsal funiculi: A surprising change has occurred in the shape of the degenerated field. Considered as before, the triangle has lengthened dorso-ventrally, the apex again reaching the dorsal gray commissure. The shape is not strictly triangular, as there is a slight concavity on each side next the fasiculus cuneatus (Burdachi). The dorsal half of the area is not as much lightened as the rest.

Many unstained fibres are seen in the dorsal roots on both sides. Lissauer's fasciculus also shows considerable lightening.

Lateral funiculi : Here the degenerated zones are separated a little ventral from the tip of the dorsal horn by a band of less lightened tissue. The dorsal portion embraces Lissauer's fasciculus, and is separated from the periphery by a narrow strip of almost normally staining white matter. The ventral part starts a little behind a line drawn across the lateral gray horns, and extends to the emergence of the ventral roots, occupying the lateral half of the column. There is also a slight lightening next the lateral gray horn.

The Marchi specimen (Fig. II) from this segment represents a little higher level, namely, at about the lowest part of the decussation of the pyramidal tract.

In the dorsal funiculi a few degenerated fibres are seen on the dorsal periphery of the fasciculus cuneatus.

The degeneration in the fasciculus cerebellospinalis is well marked, the shape of the area difEering slightly from that last described, being much thickened next the tip of the dor


sal gray horn. In the region of the fasciculus ventrolateralis superficialis there are but few scattered degenerated fibres.

MICROSCOPIC EXAMINATION OF CERTAIN LEVELS

BELOW THE LESION.— DESCENDING

DEGENERATION.

Fourth Thoracic Segmeiit, Marchi specimen. See Fig. IX.

The entire degeneration is so distinct that the individual degenerated fibres can be seen with a magnification of ten diameters.

Dorsal funiculi: The degeneration assumes a peculiar shape, which may be considered as a union of a septal degeneration and a degeneration of the comma of Schultze. The former begins at a point on the dorsal median septum and running ventralwards broadens out to join the comma tract. The latter is separated by a narrow interval from most of the dorsal horn, but touches the dorsal gray commissure and the nucleus dorsalis (Clark's column), where it is broadest. From here it tapers oif going dorsal wards, extending about three-fourths of the distance between the commissure and the periphery in the fasciculus cuneatus. The degeneration though intense is not complete.

Lateral funiculi: The fasciculus cerebrospinalis lateralis contains many degenerated fibres, and also many holes as described before. Some degenerated fibres appear on the periphery in the region of the fasciculus cerebellospinalis. Besides these, there is a small zone of scattered degeneration in the fasciculus lateralis proprius, next to the pyramidal tract.

The ventral funiculi contain scattered degenerated fibres. Numerous holes appear in the ventral and lateral funiculi, being more abundant along the periphery.

In the Weigert specimen, the degeneration occupies practically the same area. The comma zone is more lightened than the area of septal degeneration in the dorsal funiculi.

Fifth Thoracic Segment, Weigert preparation. Fig. X.

Dorsal Funiculi : There is a narrow degenerated strip in the fasciculus cuneatus, beginning near the gray matter constituting the nucleus dorsalis (Clarkii) and extending dorsalwards half the breadth of the fasciculus. The lightening is jjlainly visible, but not intense.

In the lateral funiculi, there is typical degeneration of the fasciculus cerebrospinalis lateralis (lateral pyramidal tract).

Marchi Specimen : No blackened fibres are seen in the dorsal funiculi. The pyramidal degeneration occupies the same area as that in the Weigert preparation. In the ventral funiculi, there are a few scattered fibres extending from the ventral median fissure to the emergence of the ventral roots, occupying the lateral half of the funiculus.

Sixth Thoracic Segment, Weigert specimen. See Fig. XI.

It is to be noted that the strips of degeneration in the dorsal funiculi are seen for the last time at this level.

From this point on the pyramidal tract degenerates in its well known form, being restricted at the beginning of the intumescentia lumbalis to the lateral two-thirds of the lateral funiculus. Here it is separated from the gray matter by a band of sound fibres.


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SUMMARY OF THE ASCENDING DEGENERATION.

1. Dorsal Funiculi. — Starting at the level of the first thoracic segment the degenerated area occupies the whole of the dorsal funiculi but is not complete. Some fibres particularly on the periphery are spared. Traveling up, the degenerated area is narrowed by the entering dorsal roots, so that at the level of the seventh cervical segment it assumes the shape of the tennis racquet before described ; at the level of the fifth cervical segment it is bottle-shaped, occupying now little more than the region of the fasciculus gracilis (Golli). It is to be noted in comparing the Weigert-Pal and Marchi specimens that the parts shown to be most sclerosed by the former method, namely, the ventral and medial parts, show by the latter a lessened number of blackened myelin sheaths ; whereas the blacker parts in the Weigert's specimens, the dorsal part, show some blackened sheaths. In general, the distribution of the degeneration, as shown by the two methods, is the same. At the level of the third cervical segment the degenerated area is triangular in shape, occupying the dorsal three-fourths of the fasciculus gracilis. At the first cervical segment the degenerated triangle has lengthened dorso-ventrally, again reaching the dorsal gray commissure. In the medulla, the fasciculus gracilis is much degenerated, and the degenerated fibres can be followed directly into the nucleus funiculi gracilis.

Besides this typical ascending degeneration, there is to be seen in the Marchi specimens, at the level of the first, second and third cervical segments, a narrow marginal degeneration in the fasciculus cuneatus. Farther down at the fourth and fifth cervical segments a few degenerated fibres are seen in this region. It is also to be noted that the dorsal roots at the level of the first, second and third cervical segments are partially degenerated.

3. Fascicuhis Gerehellospinalis (^Direct Cerebellar Tract). — The degeneration of this fasciculus corresponds to a definite area at the level of the eighth cervical segment. Below, the degenerated fibres of this fasciculus are mingled with those of the lateral pyramidal tract and of the fasciculus lateralis proprius. At the lower part of the eighth cervical segment it occupies the lateral half of the lateral column, extending as far forward as a point opposite the lateral gray horn. In ascending, the area of this degeneration, as seen in the Weigert preparations, remains narrow in its dorsal half, broadening out a little dorsal to the lateral gray horn, where it joins the fasciculus ventrolateralis superficialis (Gowersi.) (In the Marchi specimens the zone remains narrow until it reaches the lateral gray horn.)

The shape has completely changed at the level of the third cervical segment. For a short interval in front of the tip of the dorsal horn it is very narrow, it then broadens, atid is compact and well marked midway between the dorsal and lateral gray horns. At this level there is a zone of darker staining fibres nest to the periphery in the Weigert specimen, a little ventral to the tip of the dorsal gray horn. The Marchi specimen shows a well defined degeneration there. Ascending, the degeneration lessens very much in the Weigert specimens. At the first cervical segment, a sound band of fibres is interposed between the periphery and the degenerated area, as seen in the Weigert specimens. Here the degenerated area con


sists of a small part projecting from the tip of the dorsal horn, and separated from the periphery by the band of sound fibres mentioned. In the Marchi specimen at this level the relations are very different from those met with in the Weigert preparations; the degenerated area, which is very well defined, is very broad next the dorsal horn, and narrows to a point as it extends ventralwards. This latter shape is preserved at the lower part of the medulla, as seen in the Marchi specimens.

3. Fasciculus Ventrolateralis Stiperficialis {Gowersi). — The description of this fasciculus corresponds to the Weigert specimens, as the degeneration of this tract is not well marked in the specimens prepared by the method of Marchi. The degeneration is first plainly visible at the lower part of the seventh cervical segment, where it extends from the direct cerebellar tract to the emergence of the ventral root. It occupies here the peripheral half of the lateral funiculus, but is not very well marked at this level. Ascending it undergoes but slight change in shape. At the third cervical segment it becomes more intense, and is separated from the direct cerebellar tract by a band of darker color (less degenerated). This relation is seen also at the first cervical segment.

SUMMARY OF DESCENDING DEGENERATION.

1. Fasciculus Cereirospinalis Lateralis {Lateral Pyramidal Tract). — The degeneration in this tract begins at the fourth thoracic segment, where it is well marked, and is slightly removed from the neck of the dorsal horn. Descending it becomes smaller, the interval between it and the dorsal horn becoming widened. Corresponding to the change in shape of the cord in the lumbar region, it becomes narrowed from side to side and broadened dorso-ventrally. The degeneration continues down to the conus terminalis ; at the lower sacral region it can be plainly seen in the Weigert specimens, but it is no longer sharply outlined.

3. Fasciculus Ventralis Proprius and Fasciculus Lateralis Proprius { Ventrolateral Ground Bundles). — The degeneration in the ground bundles is most evident in the Marchi specimens. It begins at the level of the fourth thoracic segment, where it occujjies the entire ventral and part of the lateral funiculus. It rapidly diminishes in size, and has entirely disappeared at the level of the seventh thoracic segment.

3. Septal Degeneration. — This is an intense degeneration extending along the dorsal median septum from the dorsal gray commissure to near the periphery of the cord. It can be made out in Weigert specimens for but one segment below the lesion.

4. Comma of Schultze. — This is seen beautifully at the level of the fourth thoracic segment, one segment below the lesion. The head of the comma almost touches the doi'sal commissure, and joins on the other hand the septal degeneration before described. The head is more intensely degenerated than the tail end, which does not reach the periphery of the cord. At the level of the fifth thoracic segment, the degenerated areas occupy two small strips in the fasciculus cuneatus reaching to the gray matter. The tract is last seen as a similar less intense degeneration at the sixth thoracic segment.


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COMPARISON OF THIS CASE WITH OTHERS IN THE BIBLIOGRAPHY.

A feature of tbis case, very little described and figured in the literature, is the appearance of the holes left empty by the degenerated nerve fibres. The peculiar pictures seen are to be regarded, in general, as different stages in the disintegration of the nerve fibres. V. Babes* describes and figures some of these, namely, the hyaline masses occupying part of the holes. He says that the latter are probably derived from swollen axis-cylinders. The study of the present case confirms this view, as all stages between the degenerating fibres and the hyaline masses can be seen. He also pictures the holes, which are, in his cases, entirely filled with fat droplets.

E. A. Honien,"!" in Babes' Atlas, describes the process of the degeneration of the nerve fibres as it occurs experimentally in dogs. According to him, the first change to take place occurs about four days after the lesion, and consists of a swelling and granulation of the axis-cylinders. These lose their power of staining with the usual dyes, but stain strongly with acid fuchsin. This, according to Homen, harmonizes with the theory which assumes the cell to be the trophic centre, since the axis-cylinder is the first to suffer from the disconnection of the nerve fibre with it. This statement differs from that of Miiller. MiillerJ noted in a case of myelitis of tuberculous origin, that certain axis-cylinders colored deeply in specimens stained by Van Gieson's method ; he found further that the myelin sheaths, corresponding to these intensely staining axis-cylinders, are those which stain by Marchi's method. He takes this as evidence of the strong vitality of the axis-cylinders, and says that they can withstand destructive influences for a longer time than the myelin sheaths. In the present case, many deeply staining axis-cylinders were seen about the site of compression in sections stained by Van Gieson's method. In specimens stained both by Marchi's and Van Gieson's methods, some of the axis-cylinders in the degenerated fibres refuse to stain, and others stain but feebly.

The changes in the axis-cylinder are followed by a fragmentation of the myelin sheath, which begins in the part of the myelin immediately adjacent to the axis-cylinder and extends peripheralwards (Homen). This harmonizes with the fact that in the present case vacuolar areas were frequently found surrounding the axis-cylinder. In ten or twelve days the fibres first affected are, Homen declares, broken up into a granular mass. About this time, or a few days later, there begins to be a reaction on the part of the neuroglia, manifested by karyokinesis and proliferation of the neuroglia cells. About the twenty-first day, the corpora amy


Babes, V. Verschiedene Formen der Entartung und Entzundung des Riickenmarkes. Atlas d. path. Histol. d. Nervensyst. Berl., 1896, Lfg. vi, S. 20-35.

t Hom^n, E. A. Die histologischen Veranderungen bei der (experimentellen) secundaren Degeneration des Riickenmarkes. Atlas (i. path. Histol d. Nervensyst. Berl., 1896, Lfg. vi, S. 5-19.

i Miiller, L. R. Ueber einen Fall von Tuberculose des oberen Lendenmarkes mit besonderer Beriicksichtigung der secundaren Degcnerationen. Deutsche Ztschr. f. Nervenh., Leipz., 1896-7, Bd. X, S. 273-291.


lacea first appear. About the same time a few leucocytes and compound granular cells are met with.

Dorsal Fvniculi. — This case confirms and adds to the history of secondary degenerations in this region. The ascending and descending degenerations concern fibres of both exogenous and endogenous origin. It has been long known that the fibres of exogenous origin after entering the dorsal funiculi bifurcate; the long ascending limbs of bifurcation are displaced so as to occupy a position more medial and dorsal as they pass up. Thus, a compression in the lower region of the cord causes an area of degeneration in the dorsal funiculi, which in ascending becomes gradually smaller in size, assuming in the cervical region a triangular shape with the base of the triangle at the periphery of the cord. The peripheral distribution of this and other long tracts led Flatau* to formulate the law "that the short fibres of the cord run in close relation to the gray matter, while the long fibres select a position nearer to the periphery of the cord."

What is exceptional in the present case is the fact that the apex of the triangular shaped degeneration does not reach the dorsal gray commissure at the level of the third cervical segment, whereas higher up in the region of the first cervical segment it has become lengthened dorso-ventrally, again reaching the dorsal gray commissure. In Schultze'sf cases, in two of which the lumbar cord was diseased, in one the cauda equina affected, and in the other there was a complete transverse lesion of the lower thoracic region, this dorso-ventral lengthening of the degenerated area was not seen. It is not pictured by Gombault and Philippe.J It is shown, however, in a case of Darkschewitch's,§ in which the cauda equina was jjressed upon by a pachymeningitis. In his case the dorsoventral lengthening was pictured high up in the cervical cord. The apex of the degenerated triangle in the fasciculus gracilis, in Spiller'sll case, in which the compression was exerted at the cervi co-thoracic junction of the cord, did not reach the dorsal gray commissure in a section taken just below the pyramidal decussation.

Concomitant with this dorso-ventral lengthening of the degenerated area, we find degenerated fibres in the dorsal roots of the first, second and third cervical nerves. The question naturally arises, is there any connection between these two facts. That this lengthening of the degenerated area is due to these degenerated dorsal root fibres is negatived both by the result of section of the cervical dorsal i-oots and


Flatau (E.) Das Gesetz der excentrischen Lagerung der langen Babnen im Riickenmark. Ztschr. f. kiln. Med., Berl., 1897, Bd. xxxiii, S. 55-152.

tSchultze. Beitrag zur Lehre von der secundaren Degeneration im Riickenmarke des Menschen nebst Bemerkungen fiber die Anatomie der Tabes. Arch. f. Psychiat., Berl., 1883, Bd. xiv, S. 259-390.

^Gombault, A. et Philippe. Contribution a I'etude des l<!'8ion8 systematiaees dans les cordons blancs de la moelle ^piniere, Arch, de med. exper. et d'anat. path., Par., 1894, t. vi, H. 365-424.

§Darkschewit8ch, L. 0. Zur Frage von den secuiidiiren Veranderungen der weissen Substanz des Euckenmarks bei Erkrankung der Cauda equina. Neurol. Centralbl., Leipz., 1896, Bd. xv, S. 5-13.

JSpiHer, W. G. A microscopical study of the Spinal Cord in two cases of Pott's Disease. .Johns Hopkins Hoepital Bulletin, Bait., June, 1698.


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[No8. 90-91.


the study of human cases, iu which either the cervical roots were degenerated or there was a lesion of the upper thoracic or cervical cord; these results teach us that the ascending branches of the cervical dorsal roots remain throughout their entire course in the funiculus cuneatus. That the degenerated fibres are not longitudinal association paths seems untenable in light of the case reported by Mme. J. Dejerine and J. Sottas* of medullary syphilis of the cord, extending from the third to the eleventh thoracic roots. The authors found the fasciculus gracilis entirely degenerated, and they concluded from this and other cases that the fasciculus gracilis is composed entirely of ascending dorsal root fibres, and that it does not receive in its course any fibres of endogenous origin. The dorso-ventral lengthening of the degenerated area is readily understood, if the view that some fibres of the fasciculus gracilis end in the gray matter of the upper cervical region is correct.

Comma of SchuUze.-f — Our knowledge concerning the endogenous paths iu the cord is not so satisfactory. The path, linown as the comma of Schultze, had been seen as early as 1866 by Bouchard, and later by Striimpell, but it was first made the object of especial study by Schultze in 1883. Among several cases of degeneration in the spinal cord from compression, he found the comma shaped area in only one instance, extending as two parallel lines, two and one-half centimeters below the lesion.

The origin of the fibres in Schultze's comma is still a disputed point. Schultze assumed that they came from the dorsal roots, and the same view has been held by Bruns, Lenhossek,


Dejerine, J., et J. Sottas. Sur la distribution des fibres Endogcnea dans le cordon posterieur de la moelle et sur la constitution du cordon de goll. Comp. rend. Soc. de biol., Par., 1895, 10 s., t. ii, pp. 405-469.

t The following bibliography dealing with the comma of Schultze has been consulted : —

Schultze. Beitrag zur Lehre von der secundiiren Degeneration im Elickenmarke des Menchen nebst Bemerkungen iiber die Anatomie des Tabes. Arch. f. Psychiat., Berl., 1883, Bd. xiv, S. 359-390.

Gombault et Philippe. Contribution a I'etude des lesions systematisees dans les cordons blancs de la moelle epiniere. Arch, de miSJ. exp6r. et d'anat path.. Par., 1894, t. vi, pp. 365-424.

Lenhossek, M. v. Der feinere Bau des Nervensystems im Lichte neuester Forschungen. Berl., 1893.

Hoche. A. Ueber Verlauf und Endingungsweise der Fasern des ovalen Hinterstrangsfeldes im Leudenmarke. Neurol. Centralbl., Leipz., 1896, Bd. xv, S. 154-156.

Also, XJeber secundiire Degeneration, speciell des Gowers' chen Biindels, nebst Bemerkungen tiber das Verhalten der Refiexe bei Compression des Ruckenmarkes. Arch. f. Psychiat., Berl., 1896, Bd. xxviii, S. 510-543.

Zappert, J. Beitriige zur absteigenden Hinterstrangsdegeneration. Neurol. Centralbl., Leipz,, 1898, Bd. xvii, S. 103107.

Midler, L. R. Ueber einen Fall von Tuberculose des oberen Lendenmarkes mit besonderer Beriicksichtigung der secundiiren Degeneration. Deutsche Ztsehr. f. Nervenh., Leipz., 1896-7, Bd. x, S. 273-291.

Campbell, A. W. On the Tracts in the Spinal Cord and their Degenerations. Brain, Lond., 1897, vol. xx, pp. 488-535.

Spiller, W. G. A Microscopical Study of the Spinal Cord.in two Cases of Pott's Disease. Johns Hopkins Hospital Bulletin, Bait., June, 1898.


Singer and others. Gombault and Philippe, Tooth, Marie and others maintain that they do not come from dorsal root fibres, as the comma is found degenerated in lesions of the cord itself. It is to be noted, however, that dorsal root fibres, that have already entered the cord, or their descending limbs of bifurcation, might be involved in a lesion of the cord itself.

That degeneration of the comma tract is, in this instance, not due to lesions of the dorsal roots outside the cord is proved by the present case, where all the root fibres are perfectly healthy for no less than eight segments above and for all the segments below the lesion. The fibres must arise then from the tracts in the ventral or lateral funiculi of the cord, from descending fibres of the dorsal roots which have already entered the cord, or from the cells of the cord. Now, as a matter of fact, no one has seen or imagined the least connection between the tracts in the lateral and ventral funiculi and the comma tract, or between the ventral roots and the comma path. Against the view that the bulk of the path is constituted of descending limbs of bifurcated dorsal root fibres is its long course, since, as shown by Hoche, degenerated fibres of the comma tract may be traced for ten segments below the site of the lesion, while it is generally believed that the descending branches of the dorsal root fibres run down but a short distance (von Lenhossek). The bulk of the path is then, in all probability, made up of fibres which arise in cells situated in the gray matter of the cord, a view which is made all the more probable by the close relation which has been proven to exist between this path and the gray matter.

Within the last year there has appeared an article by Zappert, iu which he supports the view that the path is composed of fibres partly of exogenous and partly of endogenous origin. He studied the cord of a luetic child which had died a few days after birth. There was inflammation of the pia mater in the cervical region, compressing the ventral and dorsal roots in this region and causing their degeneration. The cord itself was intact. Besides other degenerations, he found an intense degeneration of the comma of Schultze, reaching as far as the lower third of the thoracic cord. He therefore believes that the greater part of Schultze's comma is made up of fibres of exogenous origin.

The path is now recognized as a long path. Schultze, as mentioned, found it for only a short distance below the lesion. In tlie present case it was seen but for three segments below the lesion, probably because the AVeigert method is not delicate enough to demonstrate the sparsely scattered degenerated fibres lower down. Hoche, Bruce and Muir, and others, by means of Marchi's method, in cases of recent injury, have proven conclusively that the path extends for ten or more segments below the lesion; iu one case Hoche followed it down into the lumbar cord, although below, the fibres were very scattered.

The method used, and the fact that the authors did not follow the degeneration closely enough, led to the erroneous view of Gombault and Philippe, who tliought that the comma tract was connected with the oval field of Flechsig. They explained the change in position by saying that higher up the oval-field fibres are puslied aside, in a way analogous to the formation of the fasciculus gracilis.

Tlie fibres of Schultze's comma probably end, as pointed out by Hoche, in the gray matter of the dorsal horn, as they re


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remain next to it for their entire course. He was able to trace fibres for a short distance into the gray matter, but they were soon lost owing probably to a change in direction.

The septal degeneration whicli runs but one segment below the lesion is rather unusual. Hoche figured it somewhat as seen in the present case. Spiller, in a case of compression of the cord at the level of the first thoracic segment, found a diffuse degeneration of the ventral portion of the dorsal funiculi, which extended 3i cm. below the place of compression. Miiller also described an intense degeneration of the ventral half of the dorsal funiculi, which extended for several segments below the compression, which was due to a solitary tubercle of the spinal cord, extending between the first and second lumbar nerves.

Fasciculus Cerebellospinalis. — Of the views relating to the origin of the axones of this path, that most generally accepted is that they arise from the nerve cells of the nucleus dorsalis. Tooth* however concludes from his experimental work done on monkeys, that in the cervical region and possibly also in the upper thoracic region, fibres from the dorsal roots of the spinal nerves enter largely into the composition of this tract. Tooth admits that lower down the fibres do not come by way of the dorsal roots. If this view of Tooth is correct, it will possibly explain the different pictures of this path, in the present case, given by the methods of Marchi and Weigert.

The nucleus dorsalis, which then, everyone admits gives rise to the bulk of this fasciculus, extends from the seventh cervical to the third lumbar segment of the spinal cord. The lowest limit of the transverse lesion in this case, being at the level of the third thoracic segment, one would expect an extensive involvement of this tract. The degeneration of this tract is found to occupy in its lower part, the usual area ascribed to it, but it is not very intense. The interesting point in connection with it is the variation in the picture given by the method of Marchi from that revealed by the method of Weigert.

Up to the third cervical segment, as seen by both methods, the degenerated area occupies its usual position, extending veutralwards from the tip of the dorsal gray horn and outside the region of the fasciculus cerebrospiualis lateralis. At the level of the third cervical segment the field degenerated becomes more evident in the Marchi specimens. It will be remembered that the third cervical dorsal roots on both sides are degenerated. The view of Tooth, that the cervical dorsal roots take j)art in the formation of this fasciculus, would explain this tract becoming more evident here. If Tooth be correct, however, it is curious that such a host of observations as those recorded, have been constantly negative as regards this point. On the other hand, in the Weigert specimen, the intensity of the degeneration remains the same, and there appears a band of sounder fibres which lies on the periphery of the cord next to the tip of the dorsal gray horn. The third cervical roots as seen in the Weigert specimen also contain degenerated fibres. At the level of the first cervical segment the area of degeneration is very faint in


Tooth. Quoted from A. W. Campbell, Brain, 1897, op. cit. p. 8.


the Weigert specimens, and is separated from the periphery of the cord by a bundle of sound fibres. On the other hand, in the specimens prepared by the method of Marchi, the degeneration is very well marked. It is readily seen with a magnification of ten diameters. The first and second cervical dorsal roots are found degenerated by both methods. The shape of the degeneration, also, is somewhat different at the level of the first cervical segment in the Marchi specimens. Next to the tip of the dorsal gray horn it is very broad, occupying the peripheral third of the lateral column. In passing ventralwards it diminishes in breadth.

The shape of this tract as seen in the Marchi specimens corresponds "to that in the new edition of Quain* in a case of hemi-section at the level of the twelfth thoracic nerve. Hoche'sf pictures of this tract at the level of the first cervical segment do not correspond with that seen in the present case. His cases were instances of compression myelitis at the level of the first thoracic and between the fourth and fifth thoracic segments. He represents the fasciculus cerebellospinalis as starting in a point at the tip of the dorsal gray horn and increasing in width on going veutralwards to join Gowers' tract. In his cases the cord was examined from four to six weeks after the onset of compression.

Fasciculus Ventrolateral is Siqierficialis (Gowersi). — This tract is not so well understood as is the direct cerebellar. Its origin is not definitely known. Schiifer in Qnain's Anatomy states that it probably comes from cells in the dorsal horn in the lumbar region. CampbellJ believes that the axones probably arise from cells in the gray matter of the lumbar cord, possibly in the middle cell-column" of Wakleyer. Lenhossek§ says it arises partly from cells in the ventral horns and partly from cells in the middle zone of the gray matter.

One would therefore expect in this case to find considerable degeneration of this tract. This is not especially indicated in either the Weigert or Marchi specimens. In the latter only scattered degenerated fibres are found in the tract as far up as it was traced. The Weigert method revealed more alterations, and with it the degeneration seemed to be more intense at the higher levels of the cord. It was not, as mentioned by Schiifer, most intense immediately adjacent to the fascicuhts cerebrospiualis lateralis (lateral pyramidal tract), but a little ventral to this, opposite the gray horn. This appearance conies out best at the first cervical segment, where a sounder band of fibres is interposed between the degenerated Gowers' tract and the direct cerebellar tract.

The position of Gowers' tract in the figures of Hoche agrees fairly well with the present case as far as the first cervical seg


Quain (J.) The Elements of Anatomy. Edited by E. A. Schafer and G. D. Thane. 10 ed. The Spinal Cord and Brain, 1893.

t Hoche, A. Ueber secundiire Degeneration, speciell des Gowerschen Biindels, nebst Bemerkungen iiber das Verhalten der Reflexe bei Compression des Riickenmarkes. Arch. f. Psychiat., Berl., 1896, Bd. xxviii, S. 510-543.

j Campbell, A. W. On the Tracts in the Spinal Cord and their Degenerations. Brain, Lond., 1897, vol. xx, pp. 488-535.

I Lenhoss^k, M. v. Der feinere Bau des Nervensystems im Licbte neuester Forschungen, Berl., 1893.


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[Nos. 90-91.


meiit, the diflerence of methods being taken into consideration. Farther up the degeneration cannot be followed in the Weigert preparations, nor is it indicated in the Marchi specimens. It is generally conceded that the bnlk of Gowers' tract is ascending, so the fact that the degeneration of the direct cerebellar comes out well, and that of Gowers poorly or not at all, by Marchi's method, would seem to indicate that Gowers' tract degenerated sooner in this case than the direct cerebellar.

Rajjidity of Degeneration. — It may be worth while here to say a word concerning the results given by the Weigert and Marchi methods. ScliatTer* noted certain differences between the results of the two methods in a case of transverse lesion of the spinal cord. He employed both the Marchi -and Weigert methods, and obtained results which diflered from previous observations. He concluded from his work that after a transverse lesion of the cord, the fasciculus gracilis degenerates most quickly, the fasciculus cerebrospinalis lateralis next, while the descending degeneration in the dorsal funiculi, the ascending degeneration of the fasciculus cuneatus, the fasciculus ventrolateralis superficialis and the fasciculus cerebellospinalis follows later.

Whether all of SchafTer's conclusions are true or not remains to be seen, but the case here recorded lends support to some of his statements. The fasciculus gracilis is the most sclerosed of all the tracts, as is beautifully revealed by Weigert's method. Homenf states that after section of the spinal cord in dogs, the first degenerative changes are seen three or four days after the operation in the dorsal funiculi above the place of operation. The fiisciculus cerebrospinalis lateralis shows on the whole slightly more degeneration by Weigert's method than either the fasciculus cerebellospinalis or the fasciculus ventrolateralis superficialis, although the latter shows well marked degeneration at the highest levels of the cord. The Marchi method which reveals degeneration in actual progress, shows least of all in Gowers' tract throughout its entire course. The degenerated field in the dorsal funiculi corresponds in area to that in the Weigert specimens, but is of less intensity. An interesting point with regard to the fasciculus cerebellospinalis is the fact that different fields of degeneration are revealed by the two methods at the highest levels of the cord. Concerning the descending degeneration, the most striking feature is that the degeneration in the dorsal funiculi extends but one segment below the lesion. In the lateral pyramidal tracts, the black dots representing degenerated fibres, can be followed as far down as the lumbar cord, but here they are only sparsely scattered. The degeneration is however well marked at this level in the Weigert preparations.

The fact that the oval field of Flechsig (the descending septo-marginal tract of Bruce and MuirJ) was not indicated


SchafEer, Karl. Beitrag zur Histologie der secundiiren Degeneration. Arch. f. mikr. Anat., Bonn, 1894, Bd. xliii, S. 2.52-266. t HoQU-n, E. A. Atlas d. path.Histol. d. Nervengyst., Berl.,1896, Lfg. vi, S. 5-19.

X Bruce, A. and Muir R. On a Descending Degeneration in the Posterior Columns in the Lumbo-sacral Region of the Spinal Cord. Brain, Lond., 1896, vol. xix, pp. 333-345.


by the Marchi specimen would go to indicate that this tract also degenerates rapidly. In fact, the recent cases of Hoche, Bruce and Muir, and Scarpatetti,* in which this tract and the comma of Schultze were thoroughly degenerated, were instances in which death ensued within a month or two after the onset of compression. Thus the individual fibres were caught in the first period of degeneration by the Marchi method, whereas they would not have been shown by other methods. By the Weigert method, these paths in the dorsal funiculi are shown only where the fibres are massed together and there has been considerable sclerosis, as found by Gombault and Philippe, who thus discovered their median triangle. In the present case there was some lightening of these areas in the Weigert preparations.

LEGENDS FOR FIGURES.

The lettering for the tracts is the same throughout. Each of the drawings of the spinal cord represents a magnification of five diameters.

F. ca. I. — Fasciculus cerebrospinalis lateralis (lateral pyramidal tract).

F. vl. O. — Fasciculus ventrolateralis superficialis (Gowersi). F. els. — Fasciculus cerebellospinalis. F. c. — " cuneatus (Burdachi). F.g.— " gracilis (GoUi). F.L. — Lissauer's fasciculus. F. ». — Septal fasciculus.

Comma. — Schultze's comma fasciculus. F. p. ^ — Fasciculus proprius lateralis.

Fig. I. Level of the first cervical segment. Weigert-Pal preparation.

The degeneration of the tracts is indicated in this and the other Weigert preparations by a lightening in color.

Fig. II. Level of the first cervical segment. Marchi specimen.

Fig. III. Level of the second cervical segment. Weigert-Pal specimen.

Fig. IV. Level of the second cervical segment. Marchi specimen.

Fig. V. Level of the third cervical segment. Weigert-Pal specimen.

Fig VI. Level of the third cervical segment. Marchi specimen.

Fig. VII. Level of the fifth cervical segment. Weigert-Pal specimen.

Fig. VIII. Level of the seventh cervical segment. Weigert-Pal specimen.

FiQ. IX. Level of the fourth thoracic segment. Weigert-Pal specimen.

Fig. X. Level of the fifth thoracic segment. Weigert-Pal specimen.

FiQ. XI. Level of the sixth thoracic segment. Weigert-Pal preparation.

Fig. XII. Lumbar region of the cord. Weigert-Pal specimen.

Fig. XIII. Specimen from the region of compression. Stained by Van Gieson's method. Leitz objective yV (oil immersion), eye piece 3.

JV^. — Swollen irregular shaped nerve fibres, containing swollen deeply staining axones.

N.' — Nerve fibres containing vacuolic areas.


Scarpatetti, J. von. Befund von Compression und Tuberkel im Ruckenmark. Jahrb. f. Psychiat., Leipz. u. Wien, 1896-7, Bd. xv, S. 310-329.



(?. — Neuroglia, greatly increased in amount.

O.' Nuclei of neuroglia cells.

M. — Masses of globular material imbedded in the neuroglia, staining a pinkish color.

il.— Empty hole.

H/ — Hole containing a disintegrating nerve fibre.

H." — Holes containing masses of more or less globular appearance, staining a pinkish color. They are probably modified compound granular corpuscles.

H.'" — Holes containing material taking on a yellowish and pinkish coloration. Probably broken down nerve fibres.

C. — Compound granular corpuscle.

Fig. XIV. From various parts of the region of compression. Leitz objective x'j (oil immersion), eye piece 3.

1 and 2. Corpora amylacea — Van Gieson's stains.

3 and 4. Eighth cervical segment. Two large irregular holes, containing cells, the nuclei of which stain a deep red color. The protoplasm contains vacuoles, and in parts looks as if it were made up of small globules. These are probably modified compound granular corpuscles Upson's carmine.

5. Second thoracic segment. Hole containing one of the cor


pora amylacea, which are very numerous at this level. It stains a pink color. Marchi's fluid and Upson's carmine.

6. Same section as 5. Shows several degenerating fibres. In one the axone stains a faint pink color ; in another the axone is barely outlined. Numerous black globules of myelin are seen. The rest of the myelin has a faint yellowish color.

7. A nerve fibre is shown here, with a vacuolar area around the axis-cylinder.

8. Marchi specimen counter-stained in Upson's carmine. Hole containing a degenerating nerve fibre. Tlie axone stains a fairly good pink color. The myelin sheath is represented partly by black granules, partly by a yellowish staining mass.

9. Haematoxylin and eosin. Hole containing three compound granular corpuscles. The nuclei stain black and are granular.

10. Eighth cervical segment. Van Gieson's stain. Swollen ganglion-cell. The protoplasm stains a homogeneous pink color. The nucleus is almost colorless ; the nucleolus stains a deep pink color.

11. Weigert-Pal specimen counter-stained in Upson's carmine. Large hole containing several large black masses, surrounded by ball-like masses, which are outlined by darkly staining rings.


THE TREATMENT OF OTOMYCOSIS BY THE INSUFFLATION OF BORACIC ACID AND OXIDE OF ZINC

By Samuel Theobald, M. D., Clinical Professor of Ophthalmology and Otology, Johns HojMns University.


Seventeen years ago, in an article published in the American Journal of Otology,! I called attention to the value of a powder containing equal parts of boracic acid and oxide of zinc in the treatment of otomycosis aspergillina. In this article objection was urged to the use of alcohol, the agent most commonly employed for the destruction of aural fungi, on the ground that it not infrequently causes considerable pain when instilled into the auditory canal and tends to aggravate the inflammation of the canal walls and tympanic membrane usually present in otomycosis. A distinct gain, it was pointed out, would be made if a renredy could be found which would effectually destroy the parasite and at the same time exert a beneficial influence upon the inflammation excited by its presence; and such a remedy, it was claimed, had been found in the boracic acid and oxide of zinc powder.

Experiments were described which showed the specific action of boracic acid in destroying aspergillus and other fungi, and the drying effect of the oxide of zinc was held to render more effectual the germicidal action of the acid. At the same time, there was abundant evidence to show that the combination of the two, used as suggested (by insufflation), was one of the most efficacious remedies that we possess in overcoming diffuse inflammation of the external ear.

Although in the interval that has elapsed since the publication of this paper, I have used this remedy in all the cases of otomycosis that I have met with, and have never known it fail to destroy effectually the parasite — a single application often accomplishing this result, and more than two applications being seldom needed — I should not feel warranted in bringing the subject again to the attention of otologists but


Read before the American Otological Society, July 18, If fVol. Ill, No. 2, p. 119.


I


for the fact that the majority of them, to judge by the textbooks, still seem to adhere to the practice, which, I think, should long since have become obsolete, of treating these cases by alcohol instillations.*

That alcohol is a suitable agent to pour into a diffusely inflamed and painful auditory canal will hardly be maintained by any one; while its relative inefficiency in destroying aspergillus seems to be shown by the statement of Politzer, that the instillations should be kept up for "a year" to prevent a return of the growth,! and that of Hovell, who says they should be repeated " two or three times a day " until the parasite is gotten rid of, and continued at intervals of a week for " several mouths " in order to guard against a relapse.J As opposed to this, we have the one, two or, at most, three applications of the zinc and boracic acid powder, at intervals of 2-1 or 48 hours, immediately and effectually eradicating the parasite, and at the same time, almost invariably, greatly benefiting the attendant inflammation.

The addition of bichloride of mercury or boracic acid to alcohol, as has been recommended, probably increases its parasiticidal effect, but certainly does not lessen its irritant action. Boracic acid and iodoform, mentioned among other agents by Gleason, ought to be efficacious, but, for the sake of our patients and their friends, iodoform should not be used if a less objectionable remedy will accomplish the same purpose. Chinoline salicylate and boracic acid, 1 part to 8 or 1 to 16, recommended by C. H. Burnett,§ is highly extolled by Eobert Barclay.ll I cannot speak of the value of this remedy from


•Compare Politzer, Dencb, McBride, Hovell, Gleason. f Diseases of the Ear, p. 187. t Diseases of the Ear and Naso-pharynx, p. 195. § Medical & Surg. Reporter, Phila., Vol. LXI, p. 539. 1 Burnett's System of Diseases of the Ear, Nose and Throat.


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[Nos. 90-91.


personal experience, but I am prepared to believe that it must yield favorable results from the large proportion of boracic acid which it contains.

The boracic acid and oxide of zinc powder is open to the single objection that it is a somewhat insoluble comjioiind, but this is not a serious objection, especially if it be blown into the ear, as it should be, only in sufficient quantity to cover lightly the walls of the meatus aud the tympanic membrane. The parasite destroyed and the inflammation subdued, the removal of that portion of the powder which may have adhered to the membrane and canal walls may be safely left to nature, which, through the outgrowth of the epidermis, will accomplish this completely within the course of a few weeks.

A brief description of a single typical case, recently under observation, will suffice to illustrate the action of this remedy and the manner of its employment.

Mr. X, of Baltimore, consulted me in the latter part of May last, because of an uncomfortable " full feeling," attended by slight pain, in the left ear. The history of the case indicated that there had been a slight dermatitis in each auditory canal for a considerable time. The symptoms complained of in the left ear were found to be due to the presence of aspergillus nigricans, which had excited a well-marked diffuse inflammation of the deeper portion of the canal walls and the tympanic membrane.

By the aid of the syringe, probe and forceps the aspergillus was removed as completely as possible aud the meatus was freed of a considerable quantity of exfoliated epithelium. The ear was then dried and the boracic acid and zinc powder blown in lightly. On the following day, although the unpleasant symptoms were entirely relieved, the treatment was repeated as a matter of precaution. This completed the cure, which a lapse of three weeks has shown to be radical.


BOOKS RECEIVED

Atlas and Abstract of the Diseases of the Larynx. By Dr. L. Griinwald, of Munich. Authorized Translation from the German. Edited by Charles P. Grayson, M. D. 1898. 12mo. With 107 Colored Figures on 44 Plates. 103 pages. W. B. Saunders, Philadelphia.

On Cardiac Failure and its Treatment, with Especial Reference to the Use of Baths and Exercises. By Alexander Morison, M. D., F. E. C. P 1897. 8vo, 256 pages. The Rebman Publishing Co., London.

Hay Fever and its Successful Treatment. By W. C. Hollopeter, A. M.,M. D. 1898. 12mo, 137 pages. P. Blakiston's Son & Co., Philailelphia.


A Report on Vaccination and its Results, Based on the Evidence Taken by the Royal Commission during the Tears 1889-1897. Vol. I. The Text of the Commission Report. 1898. 8vo, 493 pages. New Sydenham Society, London.

A Text-Book upon the Pathogenic Bacteria. For students of medicine, and physicians. By Joseph McFarland, M. D. Second edition, revised and enlarged. 1898. 8vo, 497 pp. W. B. Saunders, Phila.

An American Text-Book of the Diseases of Children. By American teachers. Edited by Louis Starr, M. D., assisted by T. S. Westcott, M. D. Second edition, revised. 1898. 4to, 1244 pp. W. B. Saunders, Philadelphia.

The Diseases of the Stomach. By William W. Van Valzah, A. M., M. D., and J. Douglas Nisbet, A. B., M. D. 1898. 8vo, 674 pp. W. B. Saunders, Philadelphia.


Twelfth Annual Report of the State Board of Health of the State of Ohio, for the year ending October SI, IS07. 8vo, 308 pp. 1898. The Laning Printing Co., Norwalk, Ohio.

Preliminary Report of an Investigation of Rivers and Deep Oround Waters of Ohio, as Sources of Public Water Supplies. By the State Board of Health. 1897-98. 8vo, 259 pp. J. B. Savage Press, Cleveland.

Second Catalogue of the Library of the Peabody Institute of the City of Baltimore, including the additions made since 1882. Part III, E-G. 1898. 4to, 2006 pp. Baltimore.

An American Text-Book of Gynecology, Medical and Surgical, for practitioners and students. By H. T. Byford, M. D., etal. Edited by J. M. Baldy, M. D. Second edition, revised. 1898. 4to, 718pp. W. B. Saunders, Philadelphia.

A Text-Book of Materia Medica, Therapeutics and Pharmacology. By G. F. Butler, Ph. G., M. D. Second edition, revised. 1898. 8vo, 860 pp. W. B. Saunders, Philadelphia.

King's College Hospital Reports; being the annual report of King's College and the medical department of King's College. Edited by N. Tirard, M. D., F. R. C. P., et al. Vol. IV. {Oct. 1st, 1896-Sept. .30th, 1897). 1898. 8vo, 358 pp. Adlard and Son, London.

The Office Treatment of Hemorrhoids, Fistula, etc., without operation. By Charles B. Kelsey, A. M., M. D. 1898. 12mo, 68 pp. E. R. Pelton, New York.

Twentieth Century Practice. An International encyclopedia of modern medical science by leading authorities of Europe and America. Ed. by Thos. L. Stedman, M. D. Vol. XV. Infectious Diseases. 1898. 8vo, 658 pp. Wm. Wood & Co., New York.

The Principles and Practice of Medicine. By William Osier, M. D. Third Edition. 1898. 8vo, 1181 pp. D. Appleton & Co., New York.

The Mineral Waters and Health Resorts of Europe. Treatment of chronic diseases by spas and climates with hints as to the simultaneous employment of various physical and dietetic methods. Being a revised and enlarged edition of "The spas and mineral waters of Europe." By H. Weber, M. D., F. R. C. P., and F. P. Weber, M. D., F. R. 0. P. 1898. 8vo, 524 pp. Smith, Elder & Co., London.

A Clinical Text-Book of Medical Diagnosis for Physicians and Students. By Oswald Vierordt, M. D. Authorized translation with additions by F. H. Stuart, A. M., M. D. Fourth American edition, from the fifth German, revised and enlarged. 1898. 8vo, 603 pp. W. B. Saunders, Philadelphia.

WALTER S. DAVIS, M. D.


At a meeting held at 4.30 o'clock Wednesday afternoon, on the twenty-eighth of September, in the office of the superintendent of Johns Hopkins Hospital, presided over by Dr. H. M. Hurd, the following resolutions were adopted :

Whereas, we have lost our beloved comrade and fellow-worker, W.\LTER S. Davis ;

Be it Resolved, That we, the Medical Faculty of the Johns Hopkins University and the stafif of the Johns Hopkins Hospital do express to his family our most heartfelt sympathy in their great bereavement.

His enthusiasm in the profession was unbounded and always a stimulus to his co-workers ; but we shall remember him particularly for his sterling character, his ever cheerful disposition, and his fidelity as a friend, aud,

Be it further Resolved, That a copy of these resolutions be conveyed to his family and published in the Bulletin of the Johns Hopkins Hospital. THOMAS S. CULLEN,

JAMES F. MITCHELL, GUY L. HUNNER.

Committee.


The Johns Hopkins Hospital Bulletins are issued monthly. They are printed by THE FRIEDENWALD CO., Baltimore. Single copies may be procured from Messrs. CITSITINO & CO. and the BALTIMORE NEWS COMPANY. Baltimore. Subscriptions, §1.00 a year, may b» addressed to the publishers, THE JOHNS HOPKINS PRESS, BALTIMORE; single copies will be sent by mail for fifUen cenU each.


BULLETIN


OF



THE JOHNS HOPKINS HOSPITAL.


Vol. IX.- No. 92.]


BALTIMORE, NOVEMBER, 1898.




GOIsTTEIsTTS.


The Diajnosis of the Condition of each Kidney by Inoculation of the Separated Sediments into Guinea-pigs in Suspected Renal Tuberculosis. By Edward Reynolds, M. D., - - - 253

Laparotomy for Intestinal Perforation in Typhoid Fever. By Harvey W. Gushing, M. D., 257

Spontaneous Hsemorrhagic Septicsemia in a Guinei-pig, caused by a Bacillus. By George H. VVbaver, M. D., - - - - -270

Antitoxic Relation between Bee Poison and Honey (?). By G. H. Stover, M.D., ------- 271


Proceedings of Societies :

The Hospital Medical Society,

Broadbent's Sign [Dr. Camac] ; — Aortic Aneurysm [Dr. Brown] ; — Discussion of Mr. MacCallum's Paper on Pathology of Heart Muscle [Dr. Flkxner] ; — Epidemic Cerebrospinal Meningitis — Exhibition of Specimens [Dr. Livingood].

Notes on New Books,


274


Books Received, ----------------- 275


THE DIAGNOSIS OF THE CONDITION OF EACH KIDNEY BY INOCULATION OF THE SEPARATED SEDIMENTS INTO GUINEA-PIGS IN SUSPECTED RENAL TUBERCULOSIS.

By Edward Reynolds, M.D., Boston, Mass.


The direct inspection of tlie air-distended bladder which we owe to Kelly, with its sequelae of easy exploration of the ureters, has already led to great advances towards an accurate knowledge of the urinary diseases of women, and at the present moment, when so much is opening up before us, any new step towards exactness of diagnosis seems worth reporting.

Little is yet known of the natural history of renal tuberculosis; indeed, it is for comparatively few years that we have known that tuberculosis can be primary in the kidney, and the great mass of the profession has not yet realized that this disease is often localized for many years in one kidney before invading the rest of the urinary tract; but in the last three years we have been accumulating a considerable amount of clinical evidence in support of these views, namely, that though renal tuberculosis does in the end kill when untreated, it is often nevertheless so strictly localized in one kidney that the patient may be restored to perfect health after this is removed by nephrectomy. Among the many cases of this nature which we now have may be cited a remarkable one by Vineburg* and three by Kelly. f I am myself able to add three unpublished cases, two of my own and one very remarkable


•Medical Record, Feb. 6th, 1898.

f Johns Hopkins Hospital Bulletin, Feb.-Mar., 1896.


case which I saw in consultation after a nephrectomy by another surgeon. Those who have ever seen how these patients are transformed in nutrition and general health, by the removal of the offending kidney, will be slow to listen to arguments against the ojjeration for cases in which the disease is unilateral, but it is of course justifiable only in such cases, and our success must therefore rest on our power of diagnosing the disease while it is limited to one kidney, and thus confining the operation to cases which are capable of cure by nephrectomy. For this purpose we must not only be able to establish the diagnosis of renal tuberculosis, in advance of the constitutional breakdown of the patient, but must also be able to satisfy ourselves with some positiveness of the health of the other kidney; and striking testimony to the advances which have been made in this subject during the last few years is to be obtained by inspection of the most recent text-books on medical diagnosis. Thus one, which shall be nameless, in the course of three pages devoted to renal tuberculosis, gives under diagnosis only these three clues: the presence in the sediment of the urine of little, yellow, cheesy masses of degenerated tuberculous material ; the presence of pus and other signs of chronic pyelitis from no assignable cause other than tubercle, and, lastly, the presence of tuberculosis in other organs. Even the latest edition of Osier, in which the section on this subject


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[No. 92.


has been considerably rewritten and evidently brought up to date, may be summarized as saying that there is but little chance of making a diagnosis unless we are put upon the track by finding tuberculosis in other organs, though this acute writer does mention the special methods of examination employed by gynecologists and the hope for the future which they afford.

It is apparent that these medical descriptions refer to what we from a surgical standpoint should call advanced disease. Our surgical specialty has already led us to the possibility of establishing the diagnosis at a very much earlier stage than this.

Though such a diagnosis can be made only by physical examination, a suspicion of tubercular or other renal disease will often be excited by the symptomatology, and this must therefore be briefly reviewed. The early symptoms of the disease will vary greatly both in character and in intensity in different cases, and from time to time in the same case, but will consist typically of pain and tenderness over the abdomen on the affected side, frequency of urination, and sometimes hematuria. These symptoms are, however, equally characteristic of simple pyelitis, renal calculus and new growth in the pelvis of the kidney. There are, indeed, no differences of kind in the symptomatology of these diseases in their early stages, though there are differences in the degree in which the several symptoms are likely to be present.

All these diseases are characterized by dull pains over the kidney and along the course of the ureter on the affected side. The pain is often bearing-down in character, and therefore a uterine origin is usually assigned to it; is usually increased by standing ; and is always more or less associated with frequency of micturition, occurring at night as well as in the day-time. Ill all of them the call to micturate is a very urgent one; the pain on micturition is usually leferred to the meatus ; and all are liable to more or less tenesmus at the end of micturition. In all the pain may be increased by jarring or jolting (as in driving over rough roads).

This whole group of symptoms is, however, in reality symptomatic of the amount of inflammation present, and therefore varies with this subsidiary feature of the case. They are often though not always more marked in renal stone than in tlie other diseases.

All the diseases enumerated may be accompanied by hematuria, but this is rare in simple pyelitis ; it is more likely to be profuse in tuberculosis or a new growth than in stone.

In all, the patients are almost equally liable to attacks of mild renal colic, due usually to inflammatory obstruction in the ureter. They differ from the pains excited by the passage of a calculus in being less severe and not followed by the appearance of the stone. These attacks are perhaps less common in new growths than in the other diseases under consideration. Not infrequently, at intervals in the course of these chronic renal diseases (and especially in tuberculosis and simple pyelitis), the inflammatory symptoms will be found to be most marked on the sound side. This is probably because each exacerbation of the disease in the affected side leads to an increased elimination of toxic materials from the functionally more active kidney; and this excites a transitory and some


what acute inflammation in the mucous membrane of the urinary apparatus on the sound side.

This transposition of symptoms I have seen so frequently (I may say almost constantly) that I am sure it must always be guarded against. The side on which the patient tells us that the symptoms were first noticed is usually the diseased side.

The inquiry into the history should be followed by palpation, both abdominal and bimanual. In all these lesions we find, on palpation, a tenderness which may extend from top to bottom of the urinary tract on the affected, and even on both sides, but which is usually most marked at one or more of three points: namely, over the kidney; at the spot where the ureter crosses the brim of the pelvis, in which ease it is often limited to a spot the size of the finger-tip, midway between the umbilicus and the anterior superior spine of the ilium (McBurney's point or its fellow); and, finally, over the vesical end of the ureter at the side of the cervix, which examination may even detect an enlargement or induration of the ureter. These tender points are again symptomatic of the amount of inflammation present, and therefore usually vary with the amount of pain.

A study of the history and the results of the gynecological examination usually enables us, then, to suspect, and sometimes permits us to postulate, a diagnosis of some renal disease of a surgical nature, but it does not enable us to say what, nor always on which side it is. The special examination now steps in and the real diagnosis begins here.

If a visual examination of the bladder shows that the vesical mucous membrane is substantially normal except in the interureteral region, and that a strongly localized inflammation is present there, the source of that inflammation is probably to be found in the passage of a vicious urine from one or the other ureter. If one ureteral orifice is abnormal in appearance, this probably marks the diseased side. The next and most important step is the catheterization of the ureters and a microscopical and chemical examination of the urine secreted by each kidney. But here the results must be interpreted with the greatest care, as recent advances have made it certain that most of our past opinions on the results of urinalysis must be revised in the light of the new knowledge. This is especially true of renal tuberculosis; the large amounts of degenerated pus and bits of necrotic material which are commonly described as characteristic of the disease being, in fact, found only in locally advanced cases, while the urinary signs of early tuberculosis are usually limited to the detection of pus and the bacilli by the microscope.

In the more advanced of the class of cases which are still quite operable we are indeed almost sure to find more or less degenerated pus, but the amount of it varies greatly from time to time, and is not infrequently insignificant. The detection of tubercle bacilli in the sediment of the urine is of some positive value (it is absolute if its confusion with the smegma bacillus is sufficiently carefully excluded; and it should therefore be absolute in the sediment of the urine obtained by ureteral catheterization). Its absence is of no diagnostic value whatever; e.g. I have had a highly trained expert uuike repeated negative reports on the urine from a


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bladder in which tubercular ulcerations were actually visible aud in which a subsequent report was jaositive.

It is probable that the discharge of the bacilli with the urine is not uniform, and no man can exjiect to search a sediment so thoroughly as to detect the bacillus with certainty if only a few are present; but it is held that if a fresh sediment is injected into the peritoneum of a guinea-pig, the presence of only one or two bacilli will be enough to cause infection in this very sensitive animal. The generally accepted opinion that this is the most delicate test for tuberculosis known, and the great surgical importance of using the most delicate test possible for the determination of the condition of each kidney separately in suspected renal tuberculosis, has then been my reason for injecting the sediments obtained from the kidneys by ureteral catheterization into separate guinea-pigs in each of three cases of suspected renal tuerculosis.

If this test is to be of real surgical value two points must be determined with regard to it: 1. Will it give us positive evidence in the early stages of the disease? 2. How absolute is the negative evidence obtained by the negative results from the other kidney in the same case? But neither of these questions can be answered by anything but an extended experience.

One case was positive as regards one kidney only, both the others were wholly negative, though each woman showed evidence of surgical disease in one of her kidneys. I have put off the publication of this report for several mouths in the hope of reporting the ultimate results in the equally important negative cases, but as both patients are still deferring operation* I am publishing the one positive result in the hope of inducing others to try this very delicate test, and also because the individual case is of itself of much interest from the slight development of the disease in the kidney which was removed, and from the very satisfactory improvement in the patient's condition since operation, which certainly so far supports the negative result obtained from the examination of her remaining kidney.

On March 31, 1898, I saw, with Dr. Percy C. Proctor, of Gloucester, Mass., Mrs. P., thirty-one years old, ten years married, multipara, of tuberculous family history, but with good personal history until the beginning of the present illness.

Eight years ago, after suffering for some months from backache and bearing-down pain, she suddenly began to pass bloody urine, which gradually returned to the normal after a duration of some weeks. Though partially relieved of her backache after the attack, she has been a semi-invalid ever since. Four years later, in October of 1894, she had a second, similar attack, and on the 17th of February, 1898, a third attack, the haematuria beginning with equally little warning. The pain has always been relieved during the attacks, but has always returned after their cessation, and has never been affected by the act of urination. During these attacks she has passed urine about every half hour daring the day, but only


While the paper was in press both negative cases came to operation, and both proved to have non-tubercular disease. Both will be published in detail later.


once or not at all during the night. In the intervals between the attacks she has had no frequency or other abnormalities of urination, (. e. the symptomatology was indistinctive.

On palpation no tenderness could be detected. On examination under ether her genital organs were essentially normal, and a careful visual inspection of the bladder showed no abnormality whatsoever, except that a stream of thin blood trickled steadily downward from the right ureteral orifice, while from the left spouted intermittently a normal looking urine.

The ureters were catheterized and the specimens were submitted to Dr. J. B. Ogdeu, Assistant in Chemistry in the Harvard Medical School, whose reports of the examination of the urine and of the inoculations which he made at my request are here appended:

"On March 22, 1898, two specimens of urine from the right and left ureters — case Mrs. P. — were submitted to me by Dr. Edw. Reynokls, for examination.

Urine from Right Ureter. — Amount received 10 cc; color, bloody ; reaction, alkaline ; specific gravity could not be taken as quantity of uriue was not sufficient ; urea, 1.01 percent.; albumin, between i and i of 1 per cent. The sediment, which was abundant, con-' sisted chiefly of normal blood. After the blood had been destroyed by means of distilled water, which had been acidulated with acetic acid numerous leucocytes, a few small round and caudate cells (probably ureteral) and rarely a brown granular cast were found. No crystalline elements detected.

Urine from Left Ureter. — Amount received 3cc.; color, pale, slightly turbid ; reaction, acid ; specific gravity could not be taken; urea, 0.95 per cent.; albumin, a trace. The sediment contained frequent normal and abnormal blood globules ami few leucocytes, many medium and small round cells, and numerous small caudate cells as from the ureter. An occasional granular and brown granular cast, and uric acid crystal.

The clinical examination of these specimens did not reveal much toward deciding as to the most probable cause of the clinical symptoms. The uric acid crystals suggested a possible cause of the trouble, but as it was several hours after the urines had been collected before a microscopical examination could be made, they were probably secondary (formed and deposited after the collection of the urine).

The considerable quantity of normal blood in the urine from the right ureter was apparently of traumatic origin, and was the probable cause of the alkalinity of the urine. The presence of numerous leucocytes in the sediment led to the question: Are there more leucocytes than can be accounted for by the amount of blood present? This I was unable to fully decide, although they appeared to be present in somewhat larger numbers than would be expected in that quantity of blood.

The tubular disturbance shown by the presence of casts, although slight, appeared to be more marked in the left kidney than in the right.

Since the question of a tuberculosis of the urinary tract had been raised as a possible cause of the symptoms in this case, it was considered advisable to make as thorough and complete an examination of the urine for tubercle bacilli as was possible, and at the same time, if a tuberculosis existed, to determine wbether one or both kidneys were diseased. Accordingly the sediments of both specimens were washed twice, by decantation, with distilled water, in order to free them fiom albumin and other soluble urinary constituents, a centrifuge being used to settle tbe sediments after each addition of water. Each sediment was then divided into two portions ; one portion was injected into a guinea-pig, and the other was reserved for microscopical examination for tubercle bacilli.


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The injections into the guinea-pigs were made as follows : The barrel and needleof asmall Koch syringe were thoroughly sterilized by dry heat; the abdominal wall of a guinea-pig was thoroughly cleansed and then i cc. of the sediment of the urine from the right ureter was injected into the abdominal cavity. The barrel and needle of the syringe were cleansed and again sterilized. The abdominal wall of another guinea-pig was cleansed, after which ice. of the sediment of the urine from the left ureter was injected into the abdominal cavity.

The pigs, following the injections, showed only slight disturbance, from which they recovered in a few days, and were apparently quite well for the eight weeks they were under observation. An examination of the- pigs between the fifth and sixth weeks showed that the one which had been inoculated with the sediment of the urine from the rigtit kidney had, in both groins, enlarged glands, wliich were hard and quite nodular. The one injected with the sediment of the urine from the left kidney showed no enlarged glands and was apparently in a healthy condition. Both animals were then placed under the care of Dr. W. F. Whitney.

On the same day that the inoculations were made the portion of sediment which had been reservo'l for microscopiral examination was centrifugalized, and the sediment placed on cover-glasses was carefully dried, stained and examined. No tubercle bacilli could be found in the limited number of preparations at hand. The - amount of sediment furnished by these small specimens was originally comparatively slight, and since some of the sediment had been used for the inoculation experiments, too little remained for as thorough a. microscopical examination as is often necessary for the detection of tubercle bacilli in the urine."

The patient was kept absolutely in bed on a non-stimulating diet, but the hsematuria continued until the latter part of April, when the bleeding ceased and the pain in the backreturned. As I thought it advisable to give her some weeks in which to regain condition, the pigs were left undisturbed till some weeks later, when I received the following letters from Dr. W. F. Whitney, curator of the Warren Anatomical Museum and Pathologist to the Massachusetts General Hospital. .

"May 2G, 189-;. The guinea-pig inoculated with the urine from the right kidney of Mrs. P. was killed to day, and showed cheesy abscesses in the glands of both groins, in the pus from which a few scattered tubercle bacilli were found. There were also characteristic miliary cheesy nodules in the spleen, as well as a few scattered areas in the liver. Tlie condition is perfectly characteristic of inoculated tuberculosis."

June 13, 1898. The guinea-pig inoculated with the urine from the left kidney of Mrs. P. on March 22, 1898, was killed June 9, 1898, and found to be perfectly normal."

As I always think it a pity to disturb the ureter of the sound side by catheterization immediately before an operation, in renal cases, I made no further ureteral examination, but the urine secreted in 24 hours was now collected and submitted to Dr. Ogden, whose report upon it follows :

"On June lOth an examination of the twenty-four hour urine showed the following :— Twenty-four hour quantity, 1150 cc; color, pale, turbid; reaction, acid; sp. gr., 1013; urea, 1.13 per cent, or 12.99 grammes in 24 hours; albumin, a slight trace ; bile and sugar absent. The sediment consisted chiefly of pus which was free and in clumps. Considerable squamous and scaly epithelium and a few blood globules; a few small round cells. An occasional hyaline and granular cast with renal cells and little blood adherent.


The greater part of the pus seemed to come from the same source as the squamous and scaly epithelium, in other words, probably from the vagina. I could not be certain that some of the pus did not come from the bladder or from the diseased kidney. There was still evidence of a tubular disturbance (shown by the casts) which had more the appearance of a mild renal congestion than any primary disease of the kidneys.

The sediment of this twenty-four hour urine was thoroughly examined for tubercle bacilli, but with a negative result."

June 24th I removed the right kidney by lumbar nephrectomy. The kidney was brought to the surface with great ease and rapidity and was so wholly normal in appearance that nothing but the absolute certainty which I thought myself to possess of its diseased condition would have induced me to remove it. The ureter was thoroughly normal in appearance, was cut some two inches below the kidney, closed in by catgut sutures, and dropped into the wound. On splitting the kidney after its removal the tubercular disease was at once evident, in the shape of numerous miliary tubercles on the mucous membrane of the pelvis.

The very beaittiful painting which is here reproduced was made for me by Miss Florence Byrnes, artist to the Harvard Medical School.

Dr. Whitney kindly examined the kidney, and his report and the letter which he sent me are inserted below:

"The kidney was of normal size. The capsule stripped off easily, showing the surface marked by numerous small, superficial cicatricial depressions. The cortical part was slightly narrow and pale. In the papillary region were a few scattered minute opaque dots, and the pelvis was quite thickly covered with them, and markedly injected. Microscopic examination : The epithelium of the cortical tubules was low and irregular, and the cicatricial depressions were marked by a round-cell infiltration and disappearance of the tubules at that point. The opaque dots were composed of small round and epithelioid cells with an occasional giant cell. The centres were cheesy degenerated. The diagnosis is a miliary tuberculosis of the pelvis and kidney."

Makblehead, Mass., August 13, 1898. Dear Dr. Reynolds: — I enclose the report of the kidney which you desired. The case is certainly favorable, as the local lesions are comparatively slight, and it is interesting that, with so little ulceration and loss of substance, a positive result should have been obtained from the inoculation with the urine.

Yours sincerely,

W. F. Whitney.

The patient's convaleseucefrom the operation was rapid and satisfactory. She passed from thirty to forty ounces of urine uninterruptedly and never had a bad symptom. 1 have not seen her since, but a letter from Dr. Proctor, dated October 10, 1898, informs me that she is now passing forty ounces of normal urine with no evidence of renal irritation in the sediment. She has gained in flesh and color and is greatly improved in general condition.

The negative results of two examinations of the sediment for tuberculosis, made by an expert at widely separate times, and the positive result of the inoculation of a guinea-pig by one of these same sediments, with the confirmation of this positive result by inspection of the kidney in question, and the improvement of the patient's health after the operation, form certainly a picture of considerable clinical interest, more


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especially, as this is, so far as I am aware, the first case in which this test has been used for the esamiiiatioa of each kiduey separately.

As so little is known of frequency of unilateral and primary renal tuberculosis I had hoped that an examination of the records of a large number of autopsies, performed upon subjects who died from other diseases than tuberculosis, might yield something of interest, and accordingly requested Dr. John T. Bottoinley to examine the pathological records of the Boston City Hospital for some years past. He looked over 3300 reports which were consecutive except for the omission of deaths from tubercular disease in other organs of the body, but found only two cases of primary renal tuberculosis, both unilateral, one of which died from fracture of the spine, the other of uremia.

His abstracts of the cases are as follows:

Case I. Surg. Eec. C, Vol. 23, Page 248. Male, 48 years. No venereal diseases, case of scalp wound, alcoholism, and fractured spine.

Autopsy Eec, Vol. 16, Page 56. Autopsy showed that right


kidney was about normal size ; upper third replaced by several sacs, each corresponding to a pyramid and its accompanying cortex ; each sac had a thin, firm capsule which was filled with opaque, white, cheesy or putty-like material, a little gritty to the touch. In one of the lower pyramids was a similar sac ; no evidence of any inflammation ; microscopic examination negative ; pelvis and ureter normal. Bladder and ai>pendage8 were normal except a few small calcified nodules in prostate.

Anatomical diagnosis. Stenosis of aortic valve. Chronic passive congestion of spleen and kidneys. Chronic tuberculosis of right kidney. Fracture of spine.

Case II. Med. Rec, Vol. 175, Page 249. Female, 45 years, married. Always well till three months before ; all symptoms pointed to disease of the kidney.

Autopsy Rec, Vol. 3, Page 125. Autopsy. No truly normal tissue remained of left kidney. The entire wall was composed of abscesses of varying sizes, containing a thick almost cheesy pus. Peri-nephritic fat adherent to the wall, also to diaphragm ; nothing important in other organs.

[The second case could probably have been saved by nephrectomy had the diagnosis been made a few months before. She, however, entered the hospital in the year 1880 and in a dying condition.]


LAPAROTOMY FOR INTESTINAL PERFORATION IN TYPHOID FEVER.

A RFPORT OF FOUR CASES, WITH A DISCUSSION OF THE DIAGNOSTIC SIGNS OF PERFORATION. By Harvey W. Gushing, M. D., Resident Surgeon, The Johns Hojjhins Ebspifal


The present communication is based upon four recent cases of laparotomy foi- perforating typhoid ulcer, in one of which the abdominal ca\ ity was opened on three successive occasions with recovery.

The fact that surgical intervention offers practically the only hope in tlieso cases seems to be studiously overlooked, if we are to judge by the paucity of occasions in which laparotomy has been performed for this condition.

On a recent visit to the military hospital at Fort McPhersou, the writer was told that of thirty autopsies held upon fatal cases of typhoid which had occurred there, perforation was found to have been the cause of death in six instances, one being of the appendicular variety. This would attribute to perforation aloi.e 30 per cent, of the fatalities, a percentage which corresponds with that of Hare of Brisbane, and is almost twice that of Murchison (11.38 per cent.), and three times the figures given by ]ir. Fitz (6.58 per cent, in 4680 cases). In none of these cases had operative intervention been advised, nor do I know of a single instance of operation for the relief of typhoid perforation on any of the possible 2000 cases which have died from typhoid in the field hospitals and elsewhere during the late war.

H the recent statistics of Gesselewitsch and Wanach (Centralblatt f iir die ( rreuzgcbieten der Medizin und Chirurgie, Bd. I, No. 6, p. 382, IS'.IS) are to be relied upon, namely, that lO per cent, of the entire number of fatalities in typhoid are due to perforative peritonitis, we may credit 200 of these deaths to this cause alone. According to the statistics from Fort McPherson and those of Hare, 400, or double the number, would be accounted for in this way.


In a recent communication Dr. Nicholas Seun writes: "Strange as it may seem, having seen hundreds of cases of typhoid fever during the war, I was called upon only once to operate for perforation. In that instance the patient was moribund, and I refused to operate. I have reason to believe that this complication was frequently overlooked."

We have four widely different but quite characteristic histories to report:

In Case I an early diagnosis and immediate operation, before peritonitis set in, led to recovery.

In Case II general purulent peritonitis with three perforations was present, and it should be considered that the relief of the general peritonitis, and not typhoid perforation which had taken place many hours before, was the objective point of operation.

In Case III what may be considered as pre-perforative symptoms of peritonitis were present and were neglected. Perforation subsequently occurred with, unfortunately, a virulent streptococcus infection, which proved fatal despite early laparotomy.

Case IV illustrates one of the strange attacks which closely simulate perforation. No lesion was found at the operation, and the exploration had no appreciable effect upon the subsequent course of the fever.

Case I. Surgical No. 8009. Typhoid perforation at end of second week. Laparotomy. Suture of perforation. Drainage. Fcecal fistula after 3 days from second perforation. Spontaneous closure of fistula. Seven days later symptoms of perforation. Laparotomy, No perforation found. Obstruction over


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looked. Two days later laparotomy for acute mtestinal ohstruction with closure of second perforation. Recovery.

Herbert H., aged 9, was brought into the medical wards of the Hospital on the 8th of August with the history of having been ill since the first of the month with "pain in his head and stomach." His mother and one brother were also in the hospital, and one brother had just died of "typhoid" at home. On entrance, the temperature was 104.2°, the pulse rapid, the spleen enlarged and the general appearance typhoidal. There was some tenderness noted in the lower right quadrant of the abdomen. There was no Widal reaction obtainable at this time, nor had there been in the case of his brother and mother, who had had a very mild type of fever. The patient was put on the usual bath treatment. August 9th, leucocytes 8400.

Dr. Thayer's note on August 11th says: "Abdomen is a little full. Patient does not flinch on pressure."

There is no further note of unusual interest. The boy was dull, and seemed to be having a rather severe attack. He complained much of pain in his abdomen on being given his tubs.

On the morning of August 13th (five days after admission) the patient was found to be complaining of abdominal pain. He had vomited twice and his pulse rate had increased. The leucocytes were 9600.

He was seen, in consultation with Dr. Thayer, at 1 P. M. At this time his respirations were 34 ; his pulse 165, rather thready and of poor quality ; temperature 105°. He was crying out and complaining of general colicky abdominal pain. He was very restless ; his expression pinched ; his color quite cyanotic, with lips blue and extremities blue and cold. The abdomen was quite soft and there was no muscle spasm. There was considerable general tenderness, which seemed more marked on the right side. Pressure per rectum in the recto-vesical cul-de-sac seemed to cause especial pain, but no more marked on one side than the other. There was some apparent increase of dulness in the flanks, but no shifting dulness. There was no obliteration of liver dulness. The leucocytes were 16,000. The patient was immediately transferred to the operating-room.

Before the administration of anaesthesia the temperature was 105° (there had been no fall up to this time) and the pulse 170.

Operation /.—August 13th, 1898, 1.30 P. M., four hours after first symptoms, under primary chloroform ansestliesia.

Median laparotomy. Partial evisceration. Clostire of perforation. Toilet of peritoneum with salt solution irrigation. Drainage.

An incision was made in the median line below the umbilicus. On opening the peritoneal cavity a considerable amount (perhaps 200 cc.) of sero-purulent fluid escaped, coming chiefly from the pelvis. Cultures were taken from this fluid and it was also immediately examined in cover-slip preparations. It contained a great number of polymorphonuclear leucocytes, but no micro-organisms could be found. The serosa of the intestine was everywhere greatly congested, but evidently the greatest reaction was in the right iliac fossa, where the loops of the ileum were especially injected and covered with a slight fibrinous deposit. The general cavity to the left was walled off with gauze and the loops of the ileum drawn from the wound. The last foot of the small intestine showed several greatly thinned areas corresponding to Peyer's patches. In the centre of one of these areas, the surroundings of which were quite bluish in color, was a small perforation about two millimetres in diameter, from which fluid fasces were flowing. It was about 25 cm. from the caecum and situated in the free


surface of the bowel. A few centimetres beyond this were two more patches, which seemed very thin and practically covered by little more than serosa. A few fine, filmy adhesions held the omentum to this part of the bowel.

The perforation was closed by a circular suture of fine silk taken about the edge of the thinned area, which was fortunately small, measuring about one centimetre in diameter. A similar inversion of the two thin neighboring patches would have been attempted, but the patient's condition at this time demanded immediate attention and the idea was abandoned. His pulse was almost imperceptible and his respirations were very shallow. Hypodermic injections of strychnia were given and an infusion of a litre of salt solution in the pectoral region. The exposed coils of intestine were irrigated and the abdominal cavity was flushed out with salt solution. A strip of bismuth gauze was left in for drainage, leading down to the site of the suture, and another to the two thinned Peyer's patches. The omentum was pulled down over the gauze. The abdominal wound was then partly closed. The operation lasted but twenty minutes from the beginning of ansesthesia till the final closure.

The cultures taken from the fluid found free in the peritoneal cavity remained sterile. No cultures were taken from the material flowing from the perforation.

The patient rallied well from the operation, and in eight hours the pulse had fallen to 112, and the temperature to normal. There was no vomiting, and he slept most of the time for the next twenty-four hours, taking liquid nourishment (albumen water) well, during his waking intervals. Three hundred cubic centimetres of salt solution were given per rectum every four hours for thirst. On the following day the temperature again became elevated ; the day after the leucocytosis disappeared, and for the following ten days the clinical picture was that of an ordinary typhoid in the third week. A faecal fistula developed on the second day, discharging typical peasoup faeces. It was impossible to tell, at that time, whether this discharge came from the broken down suture or from one of the neighboring thinned Peyer's patches, to which the drain led. (It was subsequently proved to come from the latter.)

The boy complained a good deal of abdominal pain at times, and of pain on micturition, but there was no abdominal rigidity or other symptoms of peritoneal inflammation. He was given regular ice sponges, after which he would sleep for long intervals. The fscal fistula ceased to discharge after a few days. There was considerable diarrhcea at this time (cf. Clinical chart).

August ISlh. (6 days after opei-afion I.) A positive AVidal reaction was obtained by Dr. Schenck for the first time (in ten minutes in a dilution of 1 to 40). Cultures from the rectum, taken through a high rectal tube, showed only the bacillus coli communis. The patient had a pinched look and was very peevish. The pulse was weak and dicrotic. A crop of rose spots was present on the abdomen.

August 25th. {\^ days after operation I.) On the evening of this date, after a very good day, the patient became suddenly much worse and vomited several times. At 9 P. M., when seen in consultation with Dr. Thayer, he was quite


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collapsed and very restless. His abdomen was slightly distended. He was hiccoughing and complaining of abdominal pain. He looked pinched and the extremities were cold and sweating. His leucocytes were only 4000.

A definite diagnosis of perforation was made and steps taken for immediate operation. An hour later the temperature had fallen four degrees to 98.6°, and the leucocytes had increased to 13,000.

Operation II, August 25, 1898, 10.30 P. M.; two hours aftei first symptoms ; under chloroform anaesthesia. Median laparotomy. No cause for symptoms demonstrable. Closure tvifh drainage.

The abdomen was opened beside the first incision, avoiding the site of the fistula. There was no free fluid. The bowels were not injected except to a slight degree in a few places, corresponding to some of Peyer's patches. No evidence whatever of a perforation could be found. There were no adhesions except about the loop of ileum which led to the old sinus and which was surrounded by quite firm omental adhesions. These were not broken up. There was no particular distension of one coil more than another. (There was nothing to suggest the thought of obstruction, and I must confess it did not occur to me. I supposed that I had overlooked a perforation somewhere, but the patient's condition precluded further search.) The wound was closed, with a small drain leading to the omental adhesions.

The operation lasted thirty-five minutes from the beginning of ausesthetizatiou. Cultures taken from the site of the adhesions remained sterile.

The patient's condition did not seem to be materially affected by the operation. The collapse, with cold sweating extremities, the sudden onset of abdominal symptoms, with hiccough, vomiting and pain, the drop of temperature without signs of hfemorrliage and the rapid rise in the leucocytes made operative intervention imperative.

During the following twenty-four hours the condition became progressively worse. All attempts at feeding were followed by immediate vomiting, and euemata were but partially retained. The patient had voided no urine for 18 hours. The lips were parched ; the tongue dry and coated. By the early morning of August 37th (30 hours after operation II) the distension had become more pronounced, and on close inspection, with a candle placed beside the exposed abdomen, a slight visible peristalsis was to be made out, which first demonstrated that obstruction, and not peritonitis, (despite the leucocytosis at this time of 20,000) was responsible for the symptoms, and it was learned that the irrigations, preceding the enemata, since the time of collapse, had not been stained with faecal matter as had previously been the rule.

The child's condition, however, seemed to forbid operative intervention. He was vomiting without effort, restless and in collapse more pronounced than at any time previous. The radial pulse could not be counted. He was given small doses of morphia and strychnia and hot compresses over his abdomen, which quieted him considerably, and four hours later an operation was determined upon.


Operation III, August 37th, 8.30 A. M. (34 hours after operation II), under chloroform ansesthesia.

Median laparotomy. Acute intestinal obstruction due to adhesions about a second perforation. Obstruction relieved. Perforation sutured. Closure with drainage.

The recent wound was re-opened. There was no sign whatever of peritonitis. The small intestine, which was greatly distended, was turned out of the abdomen together with that loop of ileum and its surrounding omentum, which had become adherent to the anterior parietes, as a consequence of the drainage at the first operation. In this omental mass was an acute kink of the bowel, about ten centimetres proximal from the old suture, the distal part of the bowel and the colon beyond being completely collapsed. The original suture was intact. At the exact situation of the kink, and covered by the omentum which caused the obstruction, was a second perforation, apparently corresponding to the thin Peyer's patch seen at the first operation.

On freeing the obstructing omentum, gas and faeces in great amount escaped from this perforation, greatly diminishing the distension. The perforation was about 1 cm. in diameter, with rounded edges, showing everted mucous membrane, so that evidently the whole floor of the ulcer had given way. It was closed easily by a single purse-string suture of fine silk. The bowels after irrigation with salt solution were replaced. A small drain of bismuth gauze was inserted down to the wad of omentum, from which cultures had previously been taken. (In these cultures Dr. Clopton found an abundant growth of the bacillus coli communis, of proteus vulgaris, bacillus lactis aerogenes and an organism culturally closely akin to the bacillus typhosus.) The abdominal wound was partially closed.

The operation lasted twenty-five minutes from the beginning of auajsthetization. The patient's pulse could not be counted. He was given 500 cc. of salt solution in each pectoral region and also per rectum.

Throughout the day the child's condition remained most serious. Distension was pronounced with active, visible and painful peristaltic cramps. He was given small doses of morphia, and large hot bichloride fomentations, for which he seemed very grateful, were at short intervals placed over the whole abdomen. He vomited only twice after returning to the ward, and soon began to retain his nourishment. Twelve hours after the operation, flatus first began to pass from the lower bowel. On the following day, though considerable meteorism remained, the bowels moved three times, and considerable diarrhoea persisted for the four or five succeeding days. As the clinical chart shows, the patient, though greatly emaciated and very feeble, returned to his typical typhoidal condition which ran its course in the next ten days.

Convalescence was very tedious. The child had a series of superficial indolent staphylococcus albus abscesses over the back and shoulders which had to be opened, and a protracted bloody mucous diarrhoea set in which kept him thin and weak. The abdominal incision broke down after the third opei'ation, and was slow in healing. He has, however, made a complete recovery.


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In Case I, therefore, we have what is most unusual, a child with early perforation. The symptoms at onset were typical, and the condition was readily diagnosed. The early vomiting was a great help, while the prostration, abdominal pain, tenderness and the leucocytosis made the picture complete before the onset of peritonitis.

The history of preceding abdominal pain for some days before the actual occurrence of perforation is interesting and, in the light of the subsequent cases, important, in that it most probably was associated with a slight local peritonitis due to the near approach of an ulcer to the general peritoneal surface. From what will be said later it seems possible that clinical symptoms arising from this condition are not uncommon and that they may be utilized in foretelling a perforation, or at all events in putting the attendant on his guard so that the patient may be kept more than ordinarily quiet and tubs omitted, especially if they are disagreeable and resisted.

Among other points of unusual interest is the fact that so prompt intervention was rendered possible, owing to the discernment of Dr. MacCallum, who had charge of the ward, and that the perforation was closed before there was any evidence of peritoneal infection, the cultures from the free fluid remaining sterile.

The subsequent perforation of a neighboring ulcer showed that it would have been desirable at the first operation to have turned in by a suture those patches which seemed thin, and threatened perforation, as was done by Sifton* in his case with recovery, and also by W. Hill.f In view of the fact, however, that there were several of these areas, and that it did not seem justifiable to further prolong the operation, a strip of gauze was placed leading to the two worst looking patches. Whether the trauma of the gauze was itself responsible for the subsequent perforation, or, whether by forming adhesions, it saved the general cavity from the escape of intestinal contents through a perforation, which would have occurred in any case, must remain undetermined.

The leucocytosis which at the first operation afforded an apparently certain indication was completely misleading at the second. Here, although in two separate counts the leucocytes were 20,000 there was found no inflammatory reaction to account for the increase. I do not know whether obstruction is usually associated with leucocytosis or notj


Sifton, H. A.: Chicago Clinical Review, Vol. IV, p. 368, 1894-5. t Reported by Keen: Surgical Complications and Sequela of Typhoid Fever, 1898, p. 238, Case 40.

t In a condition of obstruction at the hepatic flexure, following a recent operation for acute appendicitis the patient had a leucocytosis of 44,000 without peritonitis, whereas during the acute stage of his appendicitis tlie leucocytes had been only 23,000. A differential diagnosis between peritonitis and obstruction is most difHcult. Bogart's case was similar to this one, an obstruction simulating general peritonitis. Damner Harrison (Brit. Med. Jour., Oct. 20, 1894, p. 8C5) operated on a typhoid case for perforation, and found an obstruction. Barbe {Etude clinique sur certaines formes des perforations de I'intestin grcle : Importance du diagnostic precoce. These de Paris, 1895) calls attention to similar cases. No record of the number of leucocytes is given by these writers. The high degree of leucocytosis, such as was present in the writer's two


It is also noteworthy that the perforation was not associated with an early drop in temperature, contrary to the supposed rule, whereas one of the first symptoms of the obstruction was a fall of four degrees. The importance of immediate intervention was evidenced at the first operation. Practically the same symptoms appeared twelve days later without perforation. As was found subsequently these symptoms were due to an acute obstruction, and at the second operation, which was performed immediately after the onset of symptoms, the real condition was overlooked because at this early period distension of the proximal bowel which would naturally have suggested obstruction had not yet taken place. The question of justifiability of such an immediate intervention on the first symptoms of perforation will be considered later, as well as the difficulty of distinguishing between acute obstruction and perforation in their early stages.

It was learned from this case that a median incision was a bad one as the lesions occur in the right iliac fossa almost as naturally as do appendicular ones. It is also apparent that the mere performance of laparotomy in the course of typhoid fever, provided it is made before the occurrence of septic extravasation, is in itself attended with little more risk than a similar procedure in febrile states, the only apparent drawback to it being the necessary omission of any bath treatment during the subsequent progress of the fever.

I have found in the literature only one instance in which more than one laparotomy has been performed in an attempt to combat intestinal perforation and its sequels. In Bogart's* interesting case a perforation in the ileum, which was closed by the tip of the appendix, occurred in a third attack of fever. Death resulted three days later from obstruction at the hepatic flexure of the colon, an operation for the relief of which was abandoned. Of this case Keen| says : '• I can scarcely think that we would ever be justified in re-opening the abdomen in such a case. Possibly a very exceptional case might justify such a procedure, but a typhoid patient rarely escapes with his life even after one operation and could not be expected to survive a second. The same remark would apply to any new perforation which might occur. Such cases must unfortunately be left to their fate ; but if the surgeon has been careful to search for and suture any impending perforation he has done much to prevent such a disaster."

Dr. Keen's last remark holds true, but it is hard to agree with the statement that a patient should be left to his fate, no matter how desperate the condition, provided surgical intervention offers any chance of relief, forlorn though it may be. The great vitality of some of these patients is illustrated as well by this case as by the remarkable one of Dr. Finney's in which after two relapses, an otitis media, a pleurisy, and phlebitis subsequent to the operation, there was eventually a complete recover}'.


cases, may possibly be of some diagnostic value in differentiating between these conditions, though in a manner entirely opposed to the usual interpretation.

Bogart, J. Bion : Laparotomy for Perforating Typhoid Ulcer of the Ileum, etc. Annals of Surgery, Vol. 1, 1896, p. 596.

f Keen, W. W.: Surgical Complications and Sequelae of Typhoid Fever, p. 232, 1898.


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Case II. General Ko. 33,970. — Typhoid perforafmi in the fifth iveelc. Laparotomy under cocaine ancesthesia. General peritonitis. Suture of three 2^erf orations in ileum. Deatli four hours after operation.

September 3, 1898. William N., aged 18, was brought to the medical wards of the hospital with the history of a febrile attack of three weeks' duration. The patient's mother and sister died at home during his stay in the hospital of " malignant typhoid."

The patient was dull and stupid, and presented a typical typhoidal appearance. The medical note on the abdomen at entrance is as follows: "Abdomen. Peculiarly mottled, especially in inguinal regions, a bluish discoloration, taches bleuiUres. Walls somewhat tense ; grooves obliterated ; everywhere tympanitic. Slighttenderness across upper abdomen in umbilical and epigastric regions. Spleen enlarged, edge readily palpable. Liver. Relative dulness at upper border of 6th rib; absolute in 6th space and extending to costal margin ; towards left extending 3 cm. below xyphoid ; edge palpable."

Sept. 5th. The abdomen was noted by Dr. McCrae as being natural.

Sept. 10th. The patient has well-marked diarrhoea with colicky pains.

Sept. 11th. Widal reaction positive in dilution of 1 to 100.

Sept. 12th. Dr. McCrae. "Patient has been complaining of abdominal pain. Abdomen is slightly distended, tense. Rose spots present. Liver dulness present. No abdominal tenderness on palpation. Leucocytes 7500 at 10 A. M." 4 P. M. Patient vomited twice in early afternoon after nourishment. Leucocytes 8400 at 8 P. M.

Sept. 13th. "Patient has been very ill for 48 hours. Eyes are sunken. He has somewhat the look of collapse. Abdomen is somewhat full with respiratory movements present. The walls are very tense and tender on palpation. Liver dulness absent in mammary line, present in mid-axillary line."

The patient vomited after nourishment at 10 and 12 o'clock last night.

The leucocj'tes on this date were as follows :

Leucocytes at 9 A. M. 6000

" " 10 " 7200

" 11 " 8800

"12.15 P.M. 6400

" "1.30 " 6000 operation performed.

" " 2 00 " 70C0

At 1 P. M. a note by Dr. Thayer is as follows : Patient lying on back. Tongue beefy, eyes sunken and wide open. Respirations shortand shallow. Patienthasaperitoniticfacies. Green vomitus in sputum cup. Pulse small, 152. Abdomen tense, full and tympanitic. AVith patient on his back there is no hepatic flatness in the mammary line and none till one almost reaches the axillary line. There is dulnebs in either flank which disappears when the patient lies on the opposite side. Frequent vomiting during the examination. There is a well-marked friction throughout the right axilla which is heard all the way down to the costal margin. With patient lying on his left side there is no hepatic flatness anywhere.

The patient was immediately taken to the operating-room.

Operation at 1.30 P. M. under cocaine anaesthesia. Closure of three perforations in ileum. Irrigation and drainage for general septic peritonitis.

A linear infiltration of the skin with Schleich's solution was made in the right linea semilunaris. On opening the abdominal cavity there was an e.xplosion of gas followed by the escape of a large amount of stinking material looking like pea-soup stools. The bowels were of a dark bluish color, dis


tended, covered by a thick plastic lymph and everywhere bathed in the foecal extravasation.

The CEecum was located, and the first loop of ileum when drawn out showed three large ragged holes about IJ cm. in diameter and with fine bridges across them made by threads of submucosa.* They were closed with Halsted mattress sutures. The appendix and colon were free from perforations. The patient was given a few whiffs of chloroform ; the bowels were turned out, and the abdominal cavity cleaned as thoroughly as possible and irrigated with salt solution. Drainage was left in to the bottom of the pelvis and to the site of the suture.

The operation lasted 20 minutes.

Needless to say his condition was desperate with a pulse of 160 and respiration 60.

The patient rallied somewhat after the operation under stimulants and salt infusion, but remained in a state of euthanasia, often seen in severe septic infections, and died four hours later. Unfortunately no post-mortem examination could be made.

The cover-slip preparations taken from the general cavity at operation showed a great diversity of organisms, some cocci, but mostly bacilli of various shapes and sizes, and a great number of pus cells. No streptococci were seen. Nothing was grown out on culture but the bacillus coli communis.

This case well illustrates the practical hopelessness of operation when perforation, at its onset, has been overlooked, and the operation delayed until the stereotyped symptoms of extensive extravasation, such as obliteration of liver dulness and evidences of shifting free fluid, have appeared. It is such cases as this which render the operative statistics for perforation so uniformly bad. Abbe'sf case, however, makes recovery seem never impossible after operation.

The complete absence of abdominal tenderness and of leucocytosis unfortunately was misleading, but the preceding diarrhoea, abdominal pain and vomiting under ordinary circumstances would have led to early exploration had it not been for the fact that so many of the house cases this fall have complained of adominal pain and tenderness associated with diarrhoea. This point will be referred to later.

The importance of making cover-slip preparations as well as immediate plate cultures from the abdominal contents in cases of peritonitis is well shown by the fact that the bacillus coli communis overgrew all other organisms in what the cover-slips had shown to be a polyinfection. Careful investigations, such as those of FlexuerJ, show what a variety of organisms may be present. Undoubtedly the colon bacillus being more in evidence is frequently held resj)onsible for peritoneal infection due to more virulent but culturally less vigorous organisms. In one of Flexner's cases (Case IV) there was obtained from the peritoneal cavity the bacillus typhi abdominalis, bacillus coli communis, proteus vulgaris,


•Such as are shown in Keen, op. cit., Plate V, Fig. I.

t Abbe, Robert : Perforating Typhoid Ulcer. Peritonitis. Operation. Recovery. Medical Record, Vol. XLVII, p. 1, January 5, 1895.

JFlexner, Simon : Certain Forms of Infection in Typhoid Fever. Johns Hopkins Hopital Reports, \'ol. V, 1895.


k


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staphylococcus aureus and the streptococcus pyogenes. I know of no other case in which the bacillus typhosus has been obtained in culture from a general peritonitis following perforation. The organism in our Case I, though akin to it, was not positively identified. Korte* isolated the bacillus from a general peritonitis which originated however from a ruptured suppurating mesenteric gland. Klein also is said to have obtained it, but from a localized peritonitis.

Case III. Surgical No. 8131. — Typhoid perforation at end of fourth week after prolonged abdominal symptoms. General streptococcus per itotiitis. Laparotomy. Suture of perforation. Death after eight hours.

Sept. 5, 1898, Peter B., colored, aged 31, was admitted to the medical wards complaining of having had " pain in his head and stomach and general weaknpsB" since August 23rd. He had had some diarrhoea and abdominal pain during this time, but had not taken to his bed.

The note on the abdomen at entrance is as follows : "Abdomen looks natural ; no distension ; costal and iliac grooves are well marked ; respiratory movements are present. Some tenderness on palpation, especially in right inguinal and iliac region. Liver dulness begins at the sixth rib and extends to costal margin. Spleen is just palpable." Blood count. Red corpuscles 4,820,000. White corpuscles 5,600.

The Widal reaction was positive in dilution of 1 to 100. The patient was very ill and delirious at times, and on the night after admission jumped ten feet out of the ward window without, however, injuring himself. A slight leucocytosis was found a few days after admission which, coupled with his abdominal pain, occasioned suspicion, and he was watched very closely.

On several occasions the writer saw him in consultation with Dr. McCrae, but the complete absence of objective abdominal symptoms and the fact that there were several patients in the wards with similar subjective symptoms made us hesitate about operative intervention. For ten days he pursued a usual typhoid course, though the leucocytosis at one time reaching 15,200 persisted (cf. Clinical chart) and abdominal pain was constantly complained of. There was no diarrhoea. He was given the usual bath treatment.

Dr.McCrae's note the morning of the 17th inst. states : "General condition good. There is no delirium. Tongue is still coated. Patient frequently lies with knees drawn up. He states that he has very slight abdominal pain this morning. Abdomen is flat, soft on gentle palpation. Patient complains of severe pain when pressure is applied. Muscles at times are rigid, at others soft.

I am inclined to believe that his perforation took place the following night coincident with the drop in temperature (cf. Clinical chart). His pulse at midnight was recorded at 120 and his respirations at 36. By a strange misfortune during rounds the next day at noon he seemed very much better. His pulse was 76 and respirations 22, possibly as a result of the recent tub, and there seemed to be no change in his abdominal condition.

He was quite delirious during the day. There was no nausea or vomiting His leucocytosis had disappeared. At midnight of this day Dr. McCrae found him in considerable pain, lying on his back with his knees drawn up. He was dull and answered questions slowly and unintelligently. Respirations 44. Pulse 120. There was some vomitus on the floor beside the patient's bed. This was the first vomiting that had been noted.

Respiratory movements were absent from the abdomen. There


Korte, W.: Erfahrungen fiber die chirurgische Behandlung der allgemeinen, eitrigen Bauchfellentziindung. Verhandlungen der deutsch. Gesellschaft fur Chirurgie, 21ter Congress, p. 164, 1892.


was no fulness but general tenderness on palpation, especially in the right iliac fossa. There was distinct dulness, which was movable, in the right flank. The liver dulness began at the 7th interspace and extended to the costal margin. His leucocytes were 4300.

September 19th. Operation at 1 A. M. Ether anmsthesia. Laparotomy. General peritonitis. Suture of perforation in ileum. Irrigation. Gauze drainage.

The incision was made through the right rectus sheath, and the muscle drawn toward the median line. On opening the abdominal cavity bubbles of gas and sero-purulent fluid escaped. Cover-slips from this fluid were immediately examined and found to be full of streptococci with an abundance of other pleomorphic organisms.

The ileum was quite distended. For about two feet from the Cfficum, as it was withdrawn, it appeared injected and pretty extensively covered with a delicate, fibrino-plastic lymph which could be readily peeled off in sheets. This pellicle was in many places glistening and quite transparent. There were no adhesions. About 10 cm. above the caecum in the centre of a dark bluish area measuring about li cm. in diameter was a small perforation which was partially occluded by a pouting nubbin of red mucous membrane and from which there seemed to be escaping very little of the intestinal contents at this time. The perforation and thin patch were turned in with Halsted sutures. There was not a great amount of extravasation or free fluid present, certainly not enough to have given shifting dulness.

The eventrated bowel was irrigated and the fibrin wiped off with wet salt sponges. The general cavity was wiped dry with salt sponges. Drainage was inserted to the bottom of the pelvis and to the site of suture and a neighboring thin Peyer's patch.

The patient stood the operation, which lasted 30 minutes, fairly well. There was no vomiting during or after the anesthesia.

Death supervened 8 hours after the operation. The temperature remained high. There was no vomiting and nourishment was taken frequently. Nutritive and stimulant enemata were given and retained. The clinical picture was one of acute general toxaemia, such as streptococcus infection sometimes produces.

From the peritoneal fluid at operation Dr. Clopton obtained in cultures an abundant growth of the streptococcus pyogenes, the bacillus coli communis, the bac. lactis aerogeues and a yeast fungus.

Autopsy. Eleven hours after death. Dr. Nichols.

Anatomical diagnosis. Typhoid fever. Perforation. General fibriuo-purulent peritonitis. Operation. Healing ulcers in ileum, caecum and appendix. Slight ileo-colitis. Suppurating peritoneal gland. Acute splenic tumor. Cloudy swelling of kidneys, etc., etc.

The protocol need not be given here in full. The lesions in the organs were typical of typhoid infection. The peritoneal surfaces were quite generally involved in an inflammatory process with thin adhesions and without the production of much fibrin or pus. The free fluid had a sero-purulent character. There was a second threatening perforation a short


"ExWv"'S «\"'^


I



PUOTOGUAl'II OF THE ILKIM I'l' C'aM; 111.


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distance above the ileo-csecal valve. The mesenteric glands were all swollen, soft, and one showed an area of suppuration the size of a pea. There were two or three small round healing ulcers in the csecum and appendix. The following description is taken directly from the protocol :

The Ileum presents a remarkable appearance. The very edge of the ileo-cEecal valve has preserved its mucous membrane. Above this the mucous membrane has been completely destroyed over a large surface by single, confluent, often suspicious looking ulcers. One has reached the size of 7 cm. in length by 4 cm. in breadth. (This is well shown in the photograph.) The central part of this has a small clot adherent to it, and corresponds to a hajniorrhagic area on the serosa, looking like an imminent perforation situated 4 cm. above the ileo-cajcal valve. These ulcers have the same general characteristics, their edges are raised, seem opaque, congested and partly hismorrhagic. Their base is clean and apparently extends down to the transverse musculature. It is of bright red color, and transverse striae can be plainly seen. About the edges and often running in small strands across the base is a pink, delicate, new growth of epithelium. The general direction of these ulcers is longitudinal. This extensively ulcerated area does not extend much further than 11 cm. from the valve. Fourteen centimetres above the valve is a similar ulcer, puckered and inverted by the silk sutures where the perforation had occurred. This ulcer was not larger than a five-cent piece.

There are about five small, similar ulcers at various distances apart above this. The whole mucous surface is somewhat congested and there, are .small sub-mucous ecchymoses. Peyer's patches and the solitary follicles are not swollen to any appreciable extent.

Bacteriological Report — Dr. Harris. — Cultures from the abdominal cavity gave the streptococcus pyogenes. From the spleen and gall-bladder was obtained an actively motile bacillus, which decolorized by Gram, and in cultural characteristics corresponded to the bacillus typhosus. From the liver, kidney and peritoneal gland an organism was obtained which was identified as the bacillus coli communis. Also from the pelvic exudate, lung and peritoneal gland was obtained a bacillus corresponding to the bacillus lactis aerogenes.

This case would appear to be of special importance in that it exemplifies the existence of a definite recognizable condition spoken of above as the pre-perforative stage of ulceration. It seems not unnatural to suppose that, owing to the extreme degree of ulceration of the ileum or possibly of the appendix, some inflammation of the serosa, limited by adhesions, may have taken place. This would account for the abdominal pain, tenderness and leucocytosis of several days duration and the disappearance of the latter after perforation had actually occurred. Doubtless it would have been better to have operated early, and have sutured or drained from any suspicious patch.

These preliminary abdominal symptoms undoubtedly somewhat disguised those of perforation with extravasation when it subsequently actually occurred, and the abdomen unfortu


nately was not opened until after evidences of general peritonitis had begun to appear.

How often a streptococcus peritonitis has been the cause of death in the fatal operative cases cannot be told, and it is a matter of regret that bacteriological reports showing the variety of peritonitis present in these cases are not more often noted. Keen* says : " There is but a single instance, so far as I know, of a bacteriological examination of the contents of the peritoneum in typhoid perforation." Undoubtedly peritonitides of this nature are very fatal, and the abundance of long streptococcus chains, found in cover-slip preparations during the operation, gave immediately a bad prognosis to what seemed otherwise a favorable case.

The extent of peritonitis macroscopically was one such as is not infrequently recovered from in those more fortunate cases in which streptococci are not the paramount infective agent. As Durham f has emphasized, " the more virulent the infection the less marked are the local signs of peritonitis."

A streptococcus infection in typhoid is undoubtedly a very severe complication and Vincent J believes that it carries with it an extremely grave prognosis. Doubtless, considering its frequency in autopsy records of perforation, it has been present in many of the fatal cases which have succumbed after operation. Eeports by Flexner,§ Fraenkelll and others show how frequently streptococci are obtained from the peritoneal exudate at post-mortem examinations after typhoid perforations. Tavel and LanzT[ in their extensive report on peritonitis, recognize the frequency and importance of streptococcus infections, but they seem to have encountered no cases of typhoid perforation at the surgical clinic in Bern, nor has Korte** in his recent paper added any to his two previously published cases.

It is strange with the degree of ulceration found and the abundance of streptococci present, that there was no diarrhoea in this case. The steady drop in the leucocytes, after the perforation and with the onset of general peritonitis, is a most interesting feature and recalls the condition in Case II, where with the purulent peritonitis no leucocytosis was presen t, though it will be observed that no count was made in the latter case at the time of probable perforation or just before it. It is quite well recognized that in appendicitis the leucocytosis, which may be high (30,000 to 30,000) before, drops after perforation, and


•Op. cit.,p. 220.

f Durham : On the Clinical Bearing of Some Experiments on Peritoneal Infections. Med. Chir. Trans., London, Vol. LXXX, p. 191, 1897.

^Vincent, M. H.: Etude sur les resultats de 1' association du streptocoque et du bacille typhique. Annales de 1' Institute Pasteur, Vol. VII, p. 141, 1893.

^ Flexner, Simon : Certain Forms of Infection in Typhoid Fever, .lohns Hopkins Hospital Reports, Vol. V, 1895.

II Fraenkel, Euj!. : Zur Aetiologie der Peritonitis. Miinchener med. Wochenschrift, Bd. XXXVII, s. 23, 1890.

H Tavel, E. und Otto Lanz : Ueber die Aetiologie der Peritonitis. Mitteilungen aus Kliniken und medicinischen Instituten der Schweiz, 1898.

Korte, W.: Weiterer Bericbt iiber die chirurgische Behandlung der diffusen eiterigen Bauchfellentzundung. Mitteilungen aus den Grenzgebieten der Medizin und der Chirurgie, Bd. II, 1897, p. 145.


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with the onset of general peritonitis often disappears completely.

I am inclined to believe that in these suspicious cases the tubs should be discontinued. The late appearance of vomiting and its single occurrence shows the unreliability of this symptom for the diagnosis of perforation.

Case IV. Surgical No. 8154. — Typhoid fever in foiirlli week during relapse. Supposed perforation. Exploratory lajxirotomy negative. Recovery.

Maggie P., aged 15, was admitted to the medical wards, August 8, 1898, in the first week of typhoid fever. The fever pursued a typical course (cf. Clinical chart) without abdominal symptoms, with no leucocytosis and with a positive Widal reaction. A moderately severe phlebitis of the left leg appeared unassociated with leucocytosis on the 33rd day. There was considerable swelling of the leg, and tenderness over the femoral vessels. The temperature reached 10i°, but in a few days dropped to normal, and remained down twelve days. The patient was up in a wheel-chair, and without symptoms.

On September 22nd (the 52nd day after onset) a relapse of the fever came on abruptly, the temperature rising suddenly to 103° and on the following day to 105°. There was some nausea and vomiting, without abdominal tenderness or pain, but associated with a leucocytosis of 16,000. This condition persisted for the succeeding 48 hours, and therightiliacfossa was noted as being slightly resistant. Some tenderness was noticed in the right calf.

On September 24th, the child began to complain of abdominal pain. She was seen in the evening in consultation with Dr. McCrae, but there were no objective abdominal symptoms at that time. The condition was much as on the preceding day. There was some tenderness in both calves on pressure.

September 25th, 1.30 A.M., the child awolfe crying out with a sudden sharp pain in the abdomen " unlike anything she had previously had." Some nausea and slight vomiting followed. Leucocytosis 11,000. Two hours later, 3.30 A. M., the patient was again seen by the writer. She was complaining of colicky pain in the abdomen. Her thighs were kept flexed. There was some slight distension present. The liver dulness did not reach the costal margin by a finger's breadth. The walls were somewhat tense, and with moderately deep pressure in the right iliac region muscle spasm was elicited and the patient would cry out with pain. The chief rigidity, however, was above the level of the umbilicus. Her leucocytes had dropped to 8200. She vomited about 20 cc. of nourishment given her just before.

Operation September 25th, 6 A. M., four and one-half hours after the first appearance of symptoms.

Exploratory laparotomy. Negative findings. Closure loithout drainage.

An incision was made in the right iliac region. There was no free fluid in the general cavity ; no injection of the peritoneum. The appeudi.x, ileum and ascending colon appeared normal and without adhesions. The Peyer's patches in the ileum were swollen and hard, being felt like buttons through the bowel. The gall-bladder was not distended or inflamed. The pelvic viscera were negative. No thrombi could be palpated in the internal iliac veins. There were no suppurating glands felt in the mesentery. The abdominal wound was closed. The operation lasted only fifteen minutes.

The patient showed no ill effects from the operation. There was no subsequent nausea or vomiting; her leucocytosis dis


appeared, and she passed through an uneventful relapse of fever (cf. Clinical chart).

In the light of our previous experience with Cases II and III and with such symptoms as sudden acute abdominal pain, nausea and vomiting with increasing distension, some rigidity and tenderness and leucocytosis (especially a falling leucocytosis), the writer did not dare take the responsibility of withholding operative intervention even though there was some doubt as to the diagnosis. The possibility of an extension of the phlebitis to the internal iliac veins, thus causing some abdominal pain and tenderness, was thought of, but with the preceding phlebitis of September 23nd there had been no leucocytosis, pain or vomiting. The fact that the chief rigidity was above the level of the umbilicus suggested a gall-bladder complication, which in itself would have demanded exploration. The general appearance of the child was not that of collapse following perforation. There was no marked change in pulse, temperature or respiration with the above-mentioned symptoms. Nevertheless, I believed much less responsibility to be associated with an exploratory laparotomy than with running the risk of neglecting a i)erforation until signs of peritonitis should occur.

The precise cause of the patient's symitoms remains undecided. She was a very nervous child, ai:d there had been some children with acute abdominal affections in the ward during her previous period of convalescence.

Similar cases have been reported. Herrington andBowlby* report an operation on a young girl convalescing from typhoid who had even more marked symptoms of perforation with collapse than those related above. There is no mention of a leucocyte count. A laparotomy revealed no peritoneal lesion. Convalescence was uninterrupted.

General Considerations on Operation for Typhoid Perforation. — In recent years several tables have appeared in which are included all of the supposed authentic cases of operation for this particular complication in typhoid, notably those of Finney, Keen and Monad and Vanverts.

Statistics, however, always misleading, are especially so when they concern a question involving so many considerations as are included under the one head of " Results of Operation for Typhoid Perforation."

In the first place two distinct varieties of perforation may be recognized in which the operative prognosis is widely different. In one, the appendicular form, the process takes place in a quiet corner of the abdomen usually remaining localized, owing to the formation of adhesions, for perhaps a long time. In these cases some pre-existing chronic appendicular trouble may predispose toward perforation in the same way as does an ulcer of typhoidal origin in this situation. The condition, then, is practically one of acute perforative appendicitis occurring in the course of typhoid, and has the same prognosis and surgical features as similar conditions unassociated with


Herrington, W. C, and Bowlby, A. A. : Typhoid Fever Convalescence; Symptoms of Perforation, Laparotomy ; no Lesion found; Recovery. Med. Chir. Transactions, London, Vol. LXXX, 1897, p. 127.


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typhoid which give a certain percentage of recovery in uuoperated cases.

In the other variety the perforation almost always occurs in the freely moving bowel, usually in the lower foot of the ileum.

I believe that Dr. Fitz* first clea'-ly distinguished between these two varieties of perforation in typhoid, emphasizing the fact that many cases would be called appendicitis which, when occurring during typhoid fever, are classed as perforations. Undoubtedly the appendicular cases are much more common thau has been ordinarily supposed. Fitz finds, however, only 3 per cent, in 167 cases. Of the 20 cases of perforation in the pathological records of the Johns Hopkins Hospital there have been 3 appendicular perforations which, grouped with a single case out of the nine of which I am personally cognizant, makes 9.6 per cent, which have occurred in the appendix.

To further quote from Dr. Fitz's paper : " The probability of its occurrence (perforative appendicitis) furnishes the best solution to the prognosis of intestinal perforation in the latter disease (typhoid fever). Most cases of recovery from symptoms of perforation of the bowel iu typhoid fever are those in which an attack of appendicitis is most closely simulated, while the fatal cases of perforation of the bowel in typhoid fever are, in the great majority of instances, those in which other parts of the bowel than the appendix are the seat of of perforation."

It is of course important to recognize the fact that either of these conditions may be present, but a differential diagnosis can hardly be made, and were such possible, operative interference is as surely indicated as in any acute apj)endicitis. The prognosis in the appendicular varieties, for the reasons given above, is naturally more favorable, but in all cases the earlier surgical intervention is sought the better for the patient. This applies especially to the variety in which the perforation is in the free bowel. Here, also, adhesions presumably form as the nicer approaches the serosa, but inasmuch as they are attached to a movable part of the bowel they cannot be relied upon to hold, and extravasation usually soon takes place. It is with perforation of the ileum that we are chiefly concerned, and in looking for information upon this subject we are hampered because we find commingled iu the statistician's tables, two very different and widely separate conditions, one, the results of operation for typhoid perforation, the other, the results of operation for general peritonitis following typhoid perforation.

The mortality following operation for general septic peritonitis, due to extravasation of intestinal contents, is necessarily high. Could these cases be excluded from the tables we should find that operative interference in typhoid perforation is associated with a moderately low mortality.

A consideration of our cases, and of some heretofore reported, emphasizes the necessity of early operation upon the first symptoms of perforation, or possibly upon recognizable pre-perforative symptoms, without waiting for the usual signs of peritonitis. It is far better to operate early, needlessly if it so


• Fitz, R. H. : latestinal Perforation in Typhoid Fever : Its Progress and Treatment. Trans, of the Assoc, of Am. Phys., Vol. VI, p. 20n, 1891.


eventuate, rather than to wait until symptoms of peritonitis appear and actually demonstrate a perforation by its dread and practically inoperable sequel of general septic infection of the peritoneal cavity.

Any abdominal symptoms occurring in the course of the fever are as urgent indications for a surgical consultation as is the appearance of pain and tenderness in the right iliac fossa under all occasions, and only when this is fully realized will the mortality of these cases approach the low percentage reached in operations for acute perforative appendicitis or perforating gunshot wounds of the abdomen. Delay in these two latter conditions is no longer thought of, and equally prompt intervention ou the first abdominal symptoms in the course of typhoid, without waiting for actual evidence of peritonitis, will similarly reduce its high death-rate. It is hard to understand Dr. Keen's advocating delay until symptoms of shock have passed away and his preference of the second twelve hours for operating, when one appreciates that extravasation, perhaps of virulent organisms, is with all probability continually taking place while we are waiting.

There are of course certain cases, of which Dr. Osier* makes mention, in which perforation gives rise to no signs whatever as the patients are desperately ill and the local features are masked by the severity of the toxtemia. The diagnosis is usually made at such times on the autopsy table. Hospital cases, however, are usually carefully watched and some symptoms almost invariably should give warning of the complication, if not before, certainly at the time of perforation.

The figures, however, as they are given, including cases of all descriptions, even those condemned before they reach the operating room, present a comparatively low mortality.

Westf all's statistics (1898) given by Keenf are the most recent, and show 19.36 per cent, of recoveries in 83 collected cases. Those of FinueyJ (1897) include forty-five fairly authentic cases, with eleven recoveries, making his statistics somewhat better with 26.22 per cent, of recoveries. Monad and Vanverts§ consider the mortality to be much greater, namely 88 per cent., contrasted with a supposed 95 per cent, of deaths in unoperated perforations. With this small margin, however, they strongly recommend operation.

It is probable that the last figures morenearly represent the truth, as there are presumably many cases lost from tardy operations, which are never reported, and in the more favorable statistics given above there are doubtless some cases included which are of questionable typhoid origin.

Only in recent years has it become possible by bacteriological examination and by the serum reaction to conclusively demonstrate the nature of certain fevers. The writer recently operated on a perforated appendix associated with a general fibrino-purulent peritonitis due to a colon infection in a patient who subsequently had for three weeks a typical typhoid


Osier : Practice of Medicine, 3d edition, 1898, p. 26. •f Surgical ComplicationsandSequelsof Typhoid Fever, 1893, p. 234.

I Finney, J. M.T.: The Surgical Treatment of PerforatingTyphoid Ulcer. The Annals of Surgery, March, 1897.

gMonad, Ch. et J. Vanverts : Du traitement chirurgical des p^ritonites par perforation dans la lievre typhoide. Revue de Chirurgie. T. XVII, 1897, p 169.


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[No. 92.


chart and a general typhoidal appearance without leucocytosis, and with no abdominal symptoms. This would undoubtably in former years have been considered an ajipendicular typhoid perforation. Only after persistent negative results with the Widal reaction could we believe the case to be nou-typhoidal.*

Another case, which would certainly have been considered a perforation in an ambulatory typhoid had not careful microscopical and bactei'iological study been made of the tissues, is as follows :

The patient, Fred. H., aged 26, having been discharged from the work-house the day previously, entered the hospital January 25, 1897, after 12 hours of acute abdominal distress. He had all the symptoms of general peritonitis, and at operation a single perforation was found in the ileum the size of a five-cent piece and about ten inches above the ileo-csecal valve. He died 6 hours later, and the necropsy revealed an acute splenic tumor, parenchymatous degeneration of the liver and kidneys, but no other intestinal lesions characteristic of typhoid. There were no focal necroses in the liver, and the bacillus typhosus was nowhere obtained in cultures.

This case of perforation of the ileum, evidently not typhoid, presents such similarity to the notable one of Miculicz, which is usually admitted to have been of typhoid origin, that I cannot but believe the latter also was due to a perforation not resulting from typhoid fever, though its exact nature must remain uncertain. Doubtless many others of the tabulated perforation cases would likewise be discarded as " not typhoid " could they be scrutinized in the light of more recent and positive methods of diagnosis.

Diagnosis. — The question of early diagnosis of typhoid perforation is unfortunately but little touched upon in the recent monographs upon the subject, which give little more than a stereotyped picture of pain, collapse, vomiting and abdominal tenderness, a symptom complex which is enough of course in ordinary cases to assure one of the condition. We have seen illustrated by the above cases, however, that this picture is but rarely complete, and the difficulties in the way of the recognition of perforation are frequently so great that it may be overlooked entirely. Two of them also show that other conditions may give the characteristics typical of perforation when this complication has not occurred.

The complete symptomatology is usually given as follows. During the course of the fever, usually in the third week of a severe attack, most often in male adults there appears, with sudden onset, abdominal pain usually in the right side, associated with more or less tenderness and rigidity. Vomiting follows with more or less irregularity. The onset may be associated with a chill and pyrexia, or with cold extremities, collapse and a drop in temperature often of several degrees. The pulse becomes small and wiry. Leucocytosis is supposed to make its appearance, and soon more or less abdominal distension sets in with increase of vomiting, shifting dulness in the flanks, obliteration of liver dulness, a gradual return of i)yrexia if there has been a fall, with rapid feeble pulse, restlessness and


Thi8 case subsequently came to autopsy and a tuberculous enteritis was found. The appendicular perforation was probably through a tuberculous ulcer.


thirst, all indicative of general peritonitis, with death supervening in 24 to 48 hours.

Of these symptoms, especially those associated with the onset, a few remarks will be made.

Abdominal pain and tenderness. — It is a well -recognized fact that the character of the symptoms in typhoid fever seems to vary in different years within considerable limits. An unusually large number of the cases which have been treated in our medical wards this fall have had abdominal pain and tenderness which have frequently been associated with diarrhoea. This has been so pronounced a feature that several cases have been seen in surgical consultation for symptoms which have subsequently disappeared. A sudden acute onset of increased abdominal pain is an all important symptom which unfortunately may be absent, or owing to a patient's stupor be overlooked. Any complaint of pain, however, of less abrupt onset, associated with tenderness, must arouse the greatest suspicion on the part of the attendant. I cannot but believe that the condition which has been spoken of above as a pre-perforative stage of ulceration often exists. A little localized inflammation of the serosa, with or without the passage of microorganisms and leading to a slight adhesive peritonitis, usually of omentum, can give rise to these symptoms and produce an associated slight leucocytosis. This is precisely analogous to what occurs in the pre-perforative stage of appendicitis which, however, is of less urgent nature because in the case of the appendix which is fixed and does not move about freely in the general cavity, as do the coils of ileum, the adhesions are less likely to be dislocated and a general peritonitis, which would result from this separation, is avoided. This is as true of appendicular perforations in typhoid as of those occurring at other times. I believe that this pre-perforative stage may be frequently recognized as in Case III reported above. Doubtless m some of the successful cases of operation for perforative peritonitis such a pre-perforative stage has been met with. This was notably so in Dr. J. B. Murphy's case,* where no perforation was found, but merely a local inflammatory reaction about one threatening ulcer. Several of the other successful cases illustrate a preextravasation stage where adliesions had reinforced the serosa before it gave way entirely and had temporarily prevented extravasation. Among such cases may be mentioned Watsou's,t Bogart'sJ and our first case at the third operation.

Under rare conditions when the adhesions are firm, which, for the reasons mentioned above, is more likely to occur when the appendix is the seat of threatened perforation, the base of the ulcer may completely penetrate the bowel and yet the general cavity be protected. A local abscess may result, or the adhesions may floor the ulcer and subsequent healing take place over them so that recovery follows withoitt operative intervention.

This is the usual explanation of recovery following symptoms of perforation, in cases which have not been subjected to operaration. In the case of Buhl,§ qtroted by Fitz, at an autopsy


•Westcott's table, Case No. 41. Keen.

t Watson : Boston Med. and Surg. Journ., Vol. CXXXIV, 1896.

t Bogart : Op. cit.

I Zeitschr. f. rat. Med., 1857, N. F. VIII, S. 12.


NOVEMBEB, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


267


following death from haemorrhage, a pre-existing perforation was found to have been closed by omentum. This was twentythree days after the occurrence of symptoms of perforation. Dr. Hare* of Brisbane, says : "At present it is an open question whether the treatment should be medical or surgical ; whether indeed laparotomy is justifiable." He reports an interesting case in which symptoms of perforation had occurred. The patient subsequently died, some time later, with dysenteric symptoms, and the ileum was found surrounded by adhesions, which were especially dense at the point corresponding to a supposed perforation. I do not think, however, that this case is at all conclusive. A threatened perforation with perhaps the escape of some organisms through an intact serosa, which Dr. Welch has proved to be possible, would have accounted for the localized peritonitis. Had the perforation been complete, doubtless the adhesions would not have long sufficed to confine the extravasation. In his second case of supposed recovery after perforation an operation, had it been offered in the first hours of symptoms, would with greater probability have insured success. Mr. Gairdner'sf interesting cases also would show that a fatal peritonitis without an absolutely complete perforation may take place. He reports five such instances.

The protection by adhesions in this way is too precarious a thing to be relied upon, and that they should hold for any length of time is something which can never be anticipated. The recognition of this pre-perforative stage I would emphasize as all important.^

This is the period in which, if possible, an operation should be performed, and as it may endure but a short time, the opportunity should be immediately seized. Such a condition existed in Bogart's case§ in which he found a perforation of the ileum closed and the ulcer floored by the adherent tip of the appendix. He speaks of the presence of sero-puruleut fluid in the general cavity which doubtless was free from organisms as it was in our Case I, which was operated upon before extravasation of intestinal contents had taken place. An opportunity of operating in this stage was unhappily neglected in Case III.

An analogous pre-perforative stage was recognizable in the following case, one of dysentery, upon which the writer recently operated, though too late. The patient had been in the medical wards for some days with a severe amoebic dysentery. He developed considerable abdominal pain, tenderness and leucocytosis, with some rigidity of the parietes. Several


» The Cold Bath Treatment of Typhoid Fever, 1898, p. 178.

tGairdner: Peritonitis in Enteric Fever. The Glasgow Med. Journal, Vol. XLVI, p. 114, Feby., 1897.

t Under "pre-perforative stage" let it be understood that the whole period is included between the first involvement of the serosa with the customary formation of adhesions at that point, until these adhesions, which may for a time constitute the floor of the ulcer after the serosa has given way, have themselves become broken down and general extravasation has taken place. This period as in perforating appendicitis may last a longer or shorter time and is associated with pain and tenderness and a possible rise in leucocytosis owing to the localized peritonitis. i Bogart, J. Bion : loc. cit.


days later, while having a rectal irrigation, sudden evidence of perforation and extravasation occurred with acute paiu and collapse. At the operation, three hours later, bis abdomen was full of fifices, which were pouring from a large opening in the sigmoid flexure. The autopsy revealed an extraordinary degree of ulceration of the colon with a complete loss of substance in the bowel in several places, but all of these ulcerated areas, except the one found at the operation, were completely floored by protecting omental adhesions.

As iu the three typhoid cases reported above, here too was a distinctly recognizable pre-perforation or pre-extravasation stage of intestinal ulceration which demanded operative relief before final signs of perforation with extravasation had rendered the chances of giving it most desperate.

Undoubtedly, signs exist which are often considered trivial, but which may aid us iu anticipating a final perforation by indicating early laparotomy.

Temperature and Pulse. — A prouounced drop in temperature is a not infrequent symptom, associated with the onset of the perforation. It must, however, be clearly distinguished from the great fall in surface temperature, which is often pronounced and gives rise to the cold and clammy extremities so characteristic of the collapse of onset. This latter condition, however, may be associated with a rise of central temperature. In some of the cases cited by Fitz this collapse was the only symptom indicative of perforation.

The suilden fall of the central temperature, wheu it occurs, is such a pronounced feature that more importance has been ascribed to it than it deserves. Dieulafoy* considered it au almost infallible sign. He says : " La perforation intestinale, au cours de la fievre typhoide se traduit dans la tres grande majorite des cas, par uue chute hru^ve de la temperature." He thinks the appendicular attacks occurring in the course of the fever show, ou the coutrar}', a rise in temperature, and may thus be distinguished. Lerebonllet.t however, takes exception to this statement in a thorough discussion, and believes it to be exceptional. Gesselewitsch and WanachJ also emphatically assert that many cases are accompanied by a rise in temperature. One can merely state that when present it is a characteristic symptom, but that it may be absent. It also, of course, frequently occurs in other conditions such as haemorrhage, and our Case I further illustrates its unreliability as there was no drop with the perforation, but a prouounced fall with the obstruction and after each operation. It may possibly be a means of distinguishing, as Dieulafoy suggested, between a perforation with extravasation into the free cavity and one protected by adhesions giving merely a local inflammatory reaction.


•Dieulafoy: De rintervention chirurgicale dans les peritonites de la fievre typhoide. Bull, de I'Academie de Medicine. Oct. 27, 1896.

tLereboullet : Sur le diagnostic et le traitement des perforations intestinales dans la fiuvre typhoide. Bull, de I'Acad. de M^d. Nov. 3, 1896.

t Gesselewitsch and Wanach : Die Perforations Peritonitis beim Abdominal Typhus und ihre operative Behandlung. Mitteilungen aus den Grenzgebieten der Medizin und Chirurgie, Bd. I, H. 1 und 2, 1898.


268


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 92.


The disparity between pulse and temperature may be a marked feature, the former being small and rapid during the drop in temperature. The respiration likewise is apt to be more rapid and shallow with less marked abdominal movements.

Of symtoms other than those associated with a threalening perforation or with its immediate occurrence little need be said. A cliill sometimes occurs, but more often with the circumscribed and appendicular varieties, when, too, the temperature is more apt to rise. Vomiting is an important symptom when present, but its frequent absence makes it an unreliable one. The acoustic phenomenon of Levaschoff, a sound caused by the passage of gas through the perlbration with each descent of the diaphragm, has not been generally confirmed. Later signs, such as siiifting dulness from free fluid, distension, obliteration of liver dulness and other indications of abundant extravasation of gas and faeces, such as were present in Case II, make the diagnosis of a long standing perforation as easy as its prognosis is unfavorable. Even many of these stereotyped indications of general peritonitis may be misleading. In Case III shifting dulness was a marked feature, and yet but little free fluid was present. Similarly a distended colon may cause partial obliteration of liver dulness, but even with perforation and extravasation too small an amount of gas may escape to produce it.

Leucocytosis. — Of great interest and of great diagnostic importance in these cases would seem to be the presence or absence of leucocytosis.

The final interpretation, however, to be given to this symptom is far from being made. Dr. Finney says: " Of all the socalled diagnostic signs of perforating typhoid ulcer most reliance is to be placed upon the development of an attack of severe, continued abdominal pain, coupled with nausea and vomiting, and at the same time a marked increase in the number of white blood corpuscles." We have seen, however, in some of our cases a fall and not an increase in leucocytes, which must receive consideration.

The fact that " there is not only no increase in the proportion of colorless corpuscles during the fever, but that on the contrary there is rather a tendency toward a diminution in number at the height of the disease," was emphasized by Thayer* in 1892. The occurrence of leucocytosis therefore is quite properly in most cases supposed to be coincident with the presence of some septic complication other than the surface ulcerations of the intestinal tract. Cabotf is inclined to the belief that in all the cases in which leucocytosis exists constantly, some complication really is present though it may be unrecognized. He cites two cases with a leucocytosis of 2i,000 and 18,000 respectively, occurring at the time of perforation. He further states: "It occasionally happens in very exhausted patients that complications fail to produce any leucocytosis, the patient (as in some cases of pneumonia or purulent peritonitis) being unable to react against the infection " (p. 170). This statement, I think, needs some qualification.


Thayer, W. S.: Two cases of Post Typhoid Anaemia. With Remarks on the Value of Examinations of the Blood in Typhoid Fever. Johns Hopkins Hospital Reports, Vol. IV, No. 1, p. 88.

tCabot, R. C: Clinical Examination of the Blood, p. ](!8, 1897.


Using the cases above reported, in all of which careful leucocyte counts were made, we are confronted by quite a diflerent picture. In Case II the complete absence of leucocytosis was the unfortunate cause of a deferred operation. I doubt not, however, that a leucocytosis, which subsequently disappeared, was present at the onset of the peritonitis.

In Case I there was an early and recognized leucocytosis appearing, however, before any signs of general peritonitis had developed; and in the peritoneal fluid comparatively few white cells were present and no micro-organisms.

In Case III, a preceding leucocytosis associated with abdominal pain and tenderness, which, as has been stated, was probably indicative of a mild local peritonitis about the extensively ulcerated bowel, was completely wiped out concomitant with the occurrence of general peritonitis and the appearance of great numbers of leucocytes in the extravasated peritoneal fluid.

In the case of dysenteric perforation, mentioned above, the leucocytosis had previously been constantly high. A few days before the perforation it was 47,000. At the time of perforation it was 41,000. An hour later it had fallen to 30,000 and at the time of operation it was 27,000, a drop of 20,000 in three hours. At the operation the lower bowel was matted together with adherent omentum, this local inflammatory j^rocess doubtless being the cause of the preceding leucocytosis. The general cavity was full of fajcal and purulent fluid, in which were great numbers of polymorphonuclear leucocytes, eosinophiles and mononuclears in about the proportions found in the blood. Many of these cells were crowded with organisms and disintegrating. There is but one natural conclusion to be made from this sudden diminution of the number of white cells in the peripheral circulation coupled with their appearance in the peritoneal exudate.

Similarly in appendicitis the writer has frequently seen, after a high percentage of leucocytes present during the acute stage, a drop in their number occurring in association with the onset of peritonitis, as characteristic as that which occurs with the subsidence of the acute attack and recovery.

In Cabot's table XXI of counts made in general peritonitis, there are 4 without leucocytosis, the numbers varying between 4600 and 6000. Of those with leucocytosis, as well as in his cited dysenteric case with 24,000 leucocytes there is no recognition of a possible fall in number such as occurred in the cases cited above after the onset of general peritonitis.

Cabot* says : "A steadily increasing leucocytosis is always a bad sign and should never be disregarded even when other bad symptoms are absent." I would add that a decreasing leucocytosis may be a much worse sign, and should never be disregarded. This is especially of importance in those typhoid cases in which the "other bad symptoms" are diflBcult to estimate on account of the dull condition of the patient.

From these data on leucocytosis the following conclusions may be drawn :

1. The appearance of leucocytosis in the course of typhoid fever points toward some inflammatory complications in its early stage.


<0p. cit., p. 197.


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2. If this complication be a peritonitis and remain localized, associated possibly with a pre-perforative stage of ulceration (cf. Case III) or with a circumscribed slowly-forming peritonitis after perforation, it may be and usually is signalized by an increase of leucocytes in the peripheral circulation.

3. If, however, a general septic peritonitis follow, the leucocytosis may be but transitory and overlooked, as it disapijears concomitantly with the great outpouring of leucocytes into the general cavity.

The various forms of operative procedure advocated in these cases it is not the object of this paper to discuss. They are fully set forth in the recent monographs on the subject by Finney, Gesselewitsch, McOosh, Keen, and Farrar Cobb.* CONCLUSIONS.

The diagnosis of intestinal perforation in typhoid fever may present many difiBculties. No abdominal symptoms either subjective or objective occurring in the course of the fever should be regarded as trivial, and a sudden change of any sort in the patient's condition should lead first of all to the suspicion of this most serious comiJlication. A distinction should be drawn between the two varieties of perforation, the appendicular and those occurring in the free bowel, as their symptoms, course and prognosis vary considerably. Many cases, however, even those of perforation from the free bowel, present what may be recognized as a pre-perforative stage which in some cases calls for a laparotomy in anticipation of a complete perforation with extravasation. The presence of leucocytosis is not an infallible sign of perforation as it may disappear with the onset of general peritonitis. It is most valuable in this anticipatory stage.

When the diagnosis is made operation is indicated, whatever the condition of the patient. As Abbe's case esemplities, no case may be too late. A precocious exploration from an error in diagnosis is not followed by untoward consequences such as must invariably be expected after a neglected and tardy one.

Our present knowledge amply corroborates the statement of Miculicz made at Madgeburg in 1884: "If suspicious of a perforation one should not wait for an exact diagnosis and for peritonitis to reach a pronounced degree, but on the contrary one should immediately proceed to an exploratory operation, which in any case is free from danger."

Discussion". Dr. Finney. — There are a number of points in Dr. Cushing's most interesting paper to which I should like to call attention. Some of the points he has made are new, and I think a distinct addition to our knowledge of the subject. This is a subject in which I have been, personally, very much interested and have recently had occasion to go over the literature of the operation pretty thoroughly. I have myself operated upon four cases with one recovery; the other three were practically moribund at the time of operation. They were forlorn hopes, but as Dr. Abbey's case recovered, and since we have nothing to lose by operating in such cases, we may occasionally gain something. Next to Dr. Cushing's case, which must take the palm for having recovered under the greatest difBculties, I think my

Farrar Cobb: Septic Peritonitis and its Surgical Treatment. Boston Medical and Surgical Journal, Sept. 8, 1898.


case a good second. Dr. Cushing's patient had three successive laparotomies, and subsequently recovered. My case had but one operation, but he had almost every complication that a typhoid patient can have.

In regard to the question of leucocytosis, we expressed the hope a year or two ago (the suggestion being first made by Dr. Thayer) for much of diagnostic value in the blood count of these doubtful cases. It has been of some value, but just how much remains to be seen. Dr. Cushing mentions the fact that in one case the increased number of leircocytes suggested perforation, and in another the rapid decrease in leucocytes was suggestive, if not of perforation, at least of a critical condition of the patient. The question of the value then of the blood count and its diagnostic significance remains to be determined.

In Dr. Cushing's third case I find the only one, in about a hundred which I have collected, occurring in a negro, and he died.

The question of a pre-perforative stage, as Dr. Cushing has called it, is very interesting and important if it can be really diiferentiated. It is a point which will be further investigated with a great deal of interest. As to statistics, it depends entirely upon how many doubtful cases one admits into one's series. In our previous report we found 36.3 per cent, of recoveries. Then Dr. Keene's very exhaustive work appeared in which he reduced the percentage to 19.6 per cent., but since then there have been a number of cases that will, I am glad to say, bring up the percentage somewhat. I have not a complete history of some of these cases as yet, but I think it will average between 30 per cent, and 35 per cent. The distinction which Dr. Cushing has drawn between operating for the relief of a perforating typhoid ulcer, and a general septic peritonitis following such a perforation, is a very good one.

After all, early operation is the main point in this as in many other operations. If we can get these cases early enough we shall have a much larger percentage of cures, and there, as Dr. Osier has suggested, the physician and surgeon must work together and try in every way to increase our diagnostic ability. So far as the technique of the operation is concerned, I believe there is not much to be gained, and we have reached the point in dealing with these cases where we haven't much to hope for in that direction, but must turn in the direction of an earlier diagnosis for any marked improvement in our statistics.

Dr. Osler. — I think Dr. Cushing is to be congratulated upon his excellent results. Certainly to save one case in three of perforation is much more than we can do on the medical side, for they all die with us, except a few cases of appendical perforation.

Dr. Cushing has pointed to the difficulty of diagnosis, and I do not know of any more difficult problem than to determine in some cases the existence of perforative peritonitis. The local symptoms may predominate, and I would ask whether in the case of the young girl the general symptoms of collapse, change in countenance, pulse, etc., were present or not?

There are many other points in connection with this question that I would like to discuss, but the programme is a long one and there will probably be other speakers. I would, however, refer to one point mentioned, the great importance, when the autumnal crop of typhoid cases is in hospital, that the house surgeon and house physicians should often make rounds together.


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[No. 92.


SPONTANEOUS HilMORRHAGIC SEPTICMIA IN A GUINEA-PIG, CAUSED BY A BACILLUS.

By George H. Weaver, M. D., Chicago.


(From the Pathological Laboratory of Ruih Medical College.)


Tlie bacillus here described was obtained from a large female guinea-pig, which died suddenly without apparent cause in the animal room attached to the pathological laboratory of Rush Medical College.

Upon examining the body, the condition of the uterus first attracted attention. The right cornu was swollen to a diameter of 1 to 1.5 cm. for 5 cm. of its length. The covering of peritoneum exhibited marked vascular injection, but no exudate. The opposite cornu was of the normal size and appearance of the unimpregnated uterus. On opening the uterus from in front the cavity was found empty. The mucous membrane of the right cornu presented numerous scattered hiemorrhagic areas, which became confluent in front. On the posterior surface, about midway between the bifurcation and apex of the horn, was an area 1^x2 mm. in diameter, slightly elevated, firm, and of a dirty blackish-brown color.

The spleen was enlarged and soft ; the kidneys and liver pale. The heart was distended with blood. The lower lobe of one lung was firm, airless, and of a dark red color. In the opposite lung was a smaller area of firm consistence, of a deep red color, slighily depressed below the surface. On section the solidified portions were yellowish in color, and airless.

Cultures upon agar-agar, from the uterine wall, spleen, kidneys, heart-blood, and pneumonic area gave an abundant growth of the bacillus to be described below. Portions of the organs, hardened in alcohol, and stained with haematoxylin and eosin, and with Loeffler's methylene-blue, were examined with the following results:

Uterus. — The mucous tissue is largely destroyed in the right cornu at the site of the necrotic area. The superficial layer consists of necrotic cells, some with fragmented nuclei, some containing blood-pigment. In some places are areas of hjemorrhage with wellpreserved blood-cells, the infiltrated tissue staining poorly. The tissues beneath the serosa are much swollen, and the capillaries here much dilated. The muscular coat is much thickened from enlargement of the fibres and separation of them by fluid exudate. There is no round cell infiltration in any part of the organ. Sections stained with methylene-blue show abundant bacilli, corresponding to those obtained in cultures, in the necrotic uterine lining. They have penetrated but a short distance into the tissues and are not found in the deeper layers of the mucosa, nor in the muscular or serous layers.

Lungs- — The lesions in the lungs are those of a bremorrhagic pneumonia. The exudate is in part made up of small round cells (multinuclear). In other parts it is almost entirely ha;morrhagic, containing few or no leucocytes. In these latter areas the blood is, for the most part, well preserved, and some round cells contain pigment. When stained with methylene-blue and eosin, numerous bacilli are found in the ha;morrbagic areas. In places they are so numerous as to be easily recognized in mass with the low power. In the areas where the exudate consists of small round cells, few bacilli are to be found.

Liver. — Extensive fatty degeneration of the liver cells extends throughout the lobules.

Kidney —The epithelium of the convoluted tubules is swollen and cloudy. The glomeruli are distended with blood, in some escaped blood being seen free in the capsules. There are a few small areas of haemorrhage in the cortex.

-Sptecn.— There is a hyperplasia of the cells, and many large cells containing pigment.


DESCRIPTION OF ORGANISM.

Cultural Peculiarities. — In gelatine plates at room temperature, after 48 hours, the deep colonies appear to the naked eye as pin-point sized, white growths, and with a No. 3 Leitz objective, as round or slightly oval, pale yellowish, with an even outline and finely granular. After the same length of time the superficial colonies appear to the naked eye as about 1 mm. in diameter, glistening white, slightly elevated, with even or finely serrated edges. With the No. 3 Leitz objective they are translucent, with finely serrated edges, and uniformly and finely granular.

On agar-agar after 48 hours at 37° C. the superficial colonies were quite characteristic. The colony consisted of three zones. The centre was transparent or translucent white. About this was a zone of opaque white, while a third peripheral zone was transparent like the centre. The edges were finely irregular, and the colonies about y\ inch in diameter.

The growth upon an agar-agar slant was abundant, white and porcelain-like.

On gelatine there was a fine granular growth along the line of puncture, and at the surface a fine growth which did not spread over the surface, nor become elevated.

On Loeffler's blood-serum mixture there was an abundant creamy, white growth, with gas production in the water of condensation. In glucose-agar there was abundant gas production. Bouillon was rendered diffusely cloudy. On potato there was a yellowish-white growth, elevated aud with an irregular surface, which after a few days tended to extend over the surface beyond the site of inoculation.

Litmus-milk was turned faintly pink in 24 hours at 37° C, and in a week had lost some color, but there was no coagulation. There is no odor to the cultures, and no production oi indol or phenol.

The growth is not so luxuriant when oxygen is excluded. Growth is rapid at a temperature of 37° C, less so at 20° C. Slow growth occurs at as low as 7° C.

Morphology and Staining Projiertieg. — The bacilli from cultures upon agar-agar, and blood serum, are non-motile. They stain readily with the aniline dyes. With carbol-fuchsin there is often a nxore intense staining at the poles, which is not present in specimens stained with Loeffler's methyleneblue. The bacilli are short, two to four times as long as thick, with rounded ends. They resemble the bacilli of chickencholera. They occur singly, often in pairs, but never in long strings. They are decolorized by Gram's method. No spore formation was observed.

Effects upon Animals. — Guinea-pigs and mice (house and white) died in from 15 to 36 hours after subcutaneous inoculations. The fatal dose of a 24-hour bouillon ctilture, at 37° C, was 0.5 cc. in guinea-pigs, and from 15 to 45 drops in mice. In guinea-pigs, at the autopsy, there was found a reddish,


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gelatinous exudate extending into the tissues to some distance from the point of inoculation. The adjacent lymph glands were swollen and very red. The serous cavities usually contained a blood-stained fluid exudate. The viscera of the abdomen and thorax did not show much macroscopic change except a swelling of the spleen, and perhaps an increased amount of blood in the lungs. Cultures from the blood in the heart, the various viscera, and serous cavities, always showed large numbers of bacilli everywhere. Sections of the various organs after hardening in alcohol allowed the bacilli to be demonstrated in the smaller vessels and capillaries. The tissue changes were not marked. There was fatty degeneration of the liver cells ; distention of the capillaries in the glomerular loop in the kidney, with haemorrhage into the capsule; areas of haemorrhage in the spleen, and areas of haemorrhagic pneumonia.

In mice there was at times some (Edematous infiltration at the point of inoculation, but usually none. The internal organs were macroscopically little changed, except an enlargement of the spleen and a reddish mottling of the lungs. Smear preparations and cultures showed the bacilli to be present in all the organs and in the blood in the heart. In


sections stained with Loeffler's methylene-blue the smaller vessels and capillaries of the various organs contained numerous bacilli. The tissue changes consisted in an increased amount of blood in the spleen, and fine areas of haemorrhagic pneumonia in the lungs. In the pneumonic areas the bacilli were numerous.

Rabbits are almost entirely immune. After subcutaneous inoculations a local reaction occurs, but recovery follows. One young rabbit died after an injection of a very large quantity, probably from intoxication rather than from infection.

White rats and pigeons were entirely refractory.

This bacillus is an example of the bacteria classified by Hueppe as the cause of true haemorrhagic septicaemia. They are usually short bacilli, which appear as diplococci because of the deeper end-staining. They do not spread over the surface of the gelatine, and usually do not grow on potato. They cause a true septicaemia, and invading the general vascular system cause a haemorrhagic diathesis. A sharp line cannot be drawn between these and bacteria, which also cause multiple necrosis by growth in certain small areas.

This organism resembles some of those already described, but varies in its effects upon animals, and in other vital properties.


ANTITOXIC RELATION BETWEEN BEE POISON AND HONEY (?).

By G. H. Stover, M. D., Denver, Colo.


Miss M., aged 35, single, consulted me on September 9, 1895, on account of the rather unusual swelling of her right cheek following a bee-sting received some days before; the whole right side of the face was considerably swollen and she felt some constitutional symptoms.

After treatment for five days she recovered, and on her final visit made the interesting statement that, while in the past


she had never been able to eat honey, indeed, was nauseated by the smell of it, even, since being stung she had developed a craving for it, and found that she could eat it with complete satisfaction and with no ill results.

Will some of the immunization experimenters throw light on this occurrence?


PROCEEDINGS OF SOCIETIES,


THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Broadbent's Sign.— Dr. Camac.

It is with regret that I announce that the patient with adherent pericardium, who exhibited very strikingly the Broadbent Sign, is unable to be here to-night. As the phenomenon has been demonstrated to this Society at a former meeting I trust it will not be amiss to have reference to the sign without showing the case.

Broadbent* describes this sign of adherent pericardium as follows : ". . . Marked systolic retraction of some of the lower ribs on the lateral or posterior aspect of the thorax may sometimes be seen. This phenomenon is best seen when the patient is sitting up in a good light and the movements of the chest are carefully observed from a short distance off, first from the


•Adherent Pericardium. R. C. P.


John F. H. Broadbent, M. D., M.


front and then from the lateral aspect. When a pulsatile movement is seen over the lowest part of the left side of the chest posteriorly, it may at first sight appear to be expansile. On a more careful scrutiny it will be found that there is a tug on the false ribs during the cardiac systole and a sharp rebound during diastole, which can be felt as well as seen when the hand is laid flat upon the chest-wall at the spot ; it is more marked when a deej) insjiiration is made ; it may be seen occasionally, not only on the left side, but also on the right, especially if the patient leans over to the left. Here, it is not possible that the heart can be directly fixed to the chest-wall at the points of retraction by pericardial adhesions, as the lung tissue intervenes ; but the explanation seems to be the following: The heart is, by means of the pericardium, adherent not only to the central tendon of the diaphragm but probably also to a large area of the fleshy or muscular portion of the diaphragm, and, it may be, to the anterior thoracic wall as well ; as it contracts it drags upwards and inwards the less resistant


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[No. 9x'.


fleshy part of the diaphragm towards the central tendon or anterior chest-wall ; hence the points of attachment of the digitations of the diaphragm to the lower ribs and costal cartilages are dragged inwards and downwards. It will always be found in such cases that the retracted positions of the chestwall correspond to the floating ribs or costal cartilages of the lower ribs at the points of attachment of the diaphragm. (Systolic recession of the left subcostal angle and epigastrium does not necessarily imply the presence of pericardial adhesions.)"

"The above is a most important diagnostic sign of adherent pericardium wAm^rfsem^, and is quite distinct from recession of the lower ribs in inspiration."

Twice in the course of the description Broadbent infers that this is not a constant sign of adherent pericardium. He says at the beginning of the description that the sign " may sometimes be seen," and again at the conclusion that it is a most important sign " when present." It is to the explanation of this inconstancy that one's attention is drawn.

I have been unable to find in any work upon anatomy an accurate description as to the extent of pericardial attachment to the diaphragm. The general arrangement of the pericardium would suggest a hammock in which the heart is slung, attached above to the cervical fascia and below to the diaphragm, the diaphragmatic attachment involving largely the central tendon.

McClellan* gives the following description : The pericardium " is intimately adherent to the middle leaflet of the tendon about the opening for the inferior vena cava, and more loosely connected to the m\\&c\\\&r part on the left side ". . . . "These connections " (together with those of the deep cervical fascia already mentioned) "of the pericardium are of great interest, for if the entire diaphragm descends in respiration it must draw with it the heart sac, and therefore exert more or less strain upon the vessels at the base of the heart. The author inclines to the belief that the central portion or tendon of the diajohragin does not descetid, although the lateral muscular portions do. On one occasion, after the excision of the sixth, seventh and eighth ribs on the right side, he was able to examine the upper surface of the diaphragm during the forced efforts of inspiration under ether, and on another, after the evacuation of the contents of an enormous abscess, involving the left lobe of the liver, he could easily introduce his hand into the abscess cavity and detect the lateral upheavitig of the diaphragm and the rapid pulsation of the heart. In the latter case, during the straining of the patient in the act of vomiting, it was observed that the diaphragm descended and ascended with spasmodic contractions, Itit only upon the sides, there being apparently little if any change in the relations of its central tendon."

These observations would lead to the conclusion that the action of the diaphragm is like that of a flying bird, the central tendon being the motionless body, while the muscular portions would suggest the flapping wings.

Here, too, would seem to be the explanation of why, in extensively adherent pericardia, this sign may be absent. For


Regional Anatomy. Vol. I, pp. 272-273, George McClellan, M. D.


if the pericarditis have involved that portion of the pericardium

attached to the muscular diaphragm, which is constantly engaged in respiratory acts and attached to the false ribs, the tug on these ribs will be more pronounced than had it involved that portion attached to the central tendon, which is stationary and not engaged in respiratory acts. This explanation is further borne out by Broadbent's observation that the sign "is more marked when deep inspiration is made," the diaphragm being thus I'endered more tense and consequently better suited to allow the heart to tug upon the ribs.

May we then say that those cases of adherent pericardium, in which Broadbent's Sign is absent, are such as have the least extent of involvement of that portion of the pericardium attached to the muscular diaphragm ?

While this may appear anatomically correct it can only be conclusively proven by careful measurement of the diaphragmatic attachment of the pericardium in both healthy and adherent pericardia.

Aortic Aneurysm. — Dr. Brown.

This case came to the hospital about a month ago complaining of pain in both sides of the back, especially the left, and the epigastrium. He came from healthy stock that did not indulge in alcohol to any extent, but his own personal history was different, as he had indulged largely in alcohol and had been exposed many times to venereal disease though he denied lues. He had been a hard worker. The present attack commenced nine months ago with a definite pain in the lower part of the back, at first rather slight and not enough to prevent the performance of his usual duties. Later it increased and at last became so intense that work was impossible; by this time the pain had radiated to the right side occasionally. He had no marked cough and very few other symptoms except the pain, but that was so great that sleep was difficult and it was necessary to maintain firm pressure to secure relief. He obtained this by standing up and pressing the epigastrium or the lumbar region against the edge of the table.

When he came into the hosi^ital the physical examination showed a systolic and a diastolic murmur with marked pulsation in the left side of the chest which lifted up the sternum and was well marked in the axillary line. There was no point of expansile pulsation in this area. In examination of this area no tumor was seen, bttt one of the examiners described a tumor felt by ballottement, though all others were unable to feel it. Over the pulsating area both sounds of the heart were heard, but there was no diastolic shock. An examination of the arteries showed very marked sclerosis, and pulsation of the abdominal aorta was obtained with diflBculty. The pain has lessened markedly since he came into the hospital.

Perhaps it will be of interest in connection with this case to say something of the etiology of the trouble. When we consider the etiology of aneurysm we have mainly to discuss the question of arterio-sclerosis. In this there are many factors, one of the most important being that of heredity. In this case that point applies but very slightly. Next comes the diffusion of certain poisons throughout the system, among which the most important are alcohol, and the poisons of gout, rheumatism and


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syphilis. Exactly how these poisons act it is impossible to say definitely, but probably some at least act upon the adventitia of the arteries, and cause changes there which are finally compensated by hyperplasia of the intima. We simply have to take the etiology of arterio-sclerosis to work out the anatomical etiology of aneurysm. Given a man with weak arteries, and let him live a quiet life with little strain, he probably will not develop an aneurysm, but allow that man to do very hard work in which the strain upon the arterial system is very great and you have a great possibility of producing the disease.

In the question of diagnosis of aneurysm of the aorta there are various signs and symptoms according to the different portions affected. The aneurysms of the aorta may be divided into those of the ascending thoracic branch, of the arch, of the descending thoracic branch and of the abdominal aorta. In the first we have more signs than in any of the others. There is very marked pulsation, sometimes a tumor, though often few pressure symptoms, while, in the case of the transverse arch, the pressure symptoms are more marked, but the physical signs are less so. As we go into the descending portion of the thoracic aorta we may have more of the pressure symptoms, while as we proceed to the lower thoracic and upper portion of the abdominal aorta the symptoms become less because the chances of pressure are diminished. An aneurysm can be simulated by so many other conditions in the abdomen that Dr. Osier has said in his work that without the discovery of an expansile tumor, which can be grasped, a definite diagnosis cannot be made in many cases.

As regards the treatment, it is indeed multiform. Diet of a very dry character with rest in bed is given with the hope of diminishing the pulsation and increasing the formation of fibrinous elements in the blood. Various operative treatments, such as wiring of the sac and electrolysis, have been performed with the object of coagulating the fluid contents of the sac, with slight success, however, in most cases.

We attempted to clear up the diagnosis in this case by means of an X-ray photograph, but it was not much of a success. In looking up the subject of the application of X-ray photography to aneurysmal cases, however, I find that many have given it up, as better results are secured by use of the fluoroscope, carefully watching for a pulsating tumor. Whether the pulsating tumor will be shown by the fluoroscope in this case it is difficult to say, as fluoroscopic and radiographic work in the chest and abdomen are very difficult, but the signs and symptoms in this case are strongly in favor of its being a case of aneurysm, probably of the lower portion of the thoracic aorta.

Discussion of Mr. MacCallnin's Paper on Patliology of Heart

Muscle. — [See Bulletin for Aug., p. UU.]

Dr. Flexner: Mr. MacCallum's acquaintance with the embryology and histogenesis of the heart muscle made the pathology of the same muscle a peculiarly suitable subject of study. One must admire the technical method whicli resolves the muscle fibres into structures almost as complex as organs. Of much interest is the part played by these elementary constituents in the pathology of the fibre. In addition to the demonstration of the minuter changes in the fibres, the light shed on the nature of fragmentation of the heart muscle —


whether due to irregularities in contraction or degeneration — is considerable. The necessary conclusion from these studies is that there is at least one form of fragmentation which cannot be regarded as agonal in origin — the one preceded by what Mr. MacCulluii denominates sarcolytic degeneration. Whether in the light of this study we are to agree with the French writers who woitld make of this condition a disease |)cr se is another question and one still to be answered.

The study of fibrous myocarditis must interest those who pay attention to histogenesis. The facts elicited are, to say the least, unexpected, and an explanation of the order of the degeneration does not seem apparent.

Epidemic Cerebro-Spinal Meningitis— Exhibition of Speci nifrns. — Dr. Livingood.

The present case is of interest as being one of several cases of epidemic spinal meningitis occurring in Baltimore which has come to autopsy. Some of you here present witnessed the autopsy. I do not think it necessary to go into minute details of the lesions generally met with in epidemic meningitis, as they have just been given in detail in Councilman, Mallory and Wright's monograph, which is accessible to you. I shall therefore confine my remarks to the case under consideration.

The patient was a boy aged 13 years. He was moderately well nourished ; there was no external eruption; the skullcap was of average thickness; the external (hard) meninges were injected ; the vessels of the cortical pia were also injected, but there was no excess of fluid or any exudate in the cortical moderated. The exudate covered the basal portion of the brain, and existed in the form of a thick, adherent, creamy membrane, extending over pons, medulla and throughout the spinal canal. The ventricles were dilated, especially the lateral ventricles, and in the most dependent parts contained a turbid fluid. The walls of the ventricles were softened and somewhat macerated. The only other organs of interest besides the brain are the lungs. The right lung was free from adhesions ; no pleurisy. The lower lobe was deeply congested, and contained four or five small areas of consolidation each the size of a marble. On section these were coarsely granular and variegated, pale or red, in cidor. The upper lobe contained about its midportion and near the pleura a consolidated focus the size of an orange. The pleura was congested over it and covered with a fibrinous membrane. The contained bronchi were dilated and contained purulent contents. On section it also was coarsely granular and variegated in appearance.

The bacteriological examination consisted in the study of cover-slips from the exudate in brain and cord and the consolidated foci in the lungs, and the examination of cultures from these several sources. The films made from the meningeal exudate showed only doubtful organisms; those made from the lungs showed many bacteria, chiefly within cells, which were in the form of diplococci, in many ways resembling the gonococcus, except for the absence of the buscuit-like flattening. In other cells the forms resembled more the lanceolate coccus. Tested by Gram's method most of the cocci gave up the dye ; only those presenting lancet shapes seemed to retain it.

The cultures were interesting. Lumbar puncture made during life gave a positive result in that films and cultures


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[No. 92.


showed diplococci agreeing with the meningococcus intracelluliiris of Weicliselbaum and Jaeger. At tiie autopsy cultures from tlie heart's blood, lungs, (consolidation) spleen, kidney, liver, brain and spinal meninges were made. Positive results were obtained only from the lung and meningeal exudate. The plate from the exudate over the medulla contained very few colonies of the meningococcus. The organisms isolated from the lung proved to be the micrococcus lanceolatus.

The meningococcus as obtained from the exudate presented the usual characteristics as given by Weicliselbaum, Jaeger and Councilman, and did not retain the dye when treated by Gram's method. The culture from the lung failed in so far as the meningococcus was concerned, which was believed to be present there from the study of 81ms, and which was shown by Councilman to be capable of setting up pneumonic conditions. As the subject of the nature and classification of these organisms has so recently been reviewed in the Bulletin (J. H. H. Bulletin No. 83), I shall not take up your time in restating the present views concerning them.


XOTES ON NEW BOOKS.


The Psych'ology of Suggestion. By Boris Sidis, M. A., Ph.D., Associate in Psychology at the Pathological Institute of the New York State Hospitals. With an Introduction by Prof. William James, of Harvard University. {D. Appleion & Co., New York, 1898)

Dr. Sidis, after devoting a chapter to the discussion of the meaning of the term "suggestion," all previous definitions of which he finds unsatisfactory, submits the following :

" By suggestion is meant the intrusion into the mind of an idea ; met with more or less opposition by the person ; accepted uncritically at List; and realized unrefiectively, almost automatically."

Thus, if I ask a friend to lend me five dollars, it is a suggestion only in case he is reluctant to do so, and, nevertheless, finally gives me the money without thinking of his prospects of reimbursement. If he lends it to me willingly, or with the expectation of getting it back, or if he declines to let me have it at all, it is not a suggestion. This seems like a pretty arbitrary limitation, and it would be easy to show, by citations, that Dr. Sidis, in practice, dispenses with every one of the limitations wliich he imposes on the intruding idea.

It does not follow, because a writer fails in the definition of his subject that he may not have something of interest to say about it. Dr. Sidis has made many interesting observations, and presents the facts in regard to hypnotism and allied conditions, with which, naturally, the book is largely occupied, clearly and temperately. But, as might perhaps be expected from such a beginning, his inferences are not always warranted by the facts on which they are based.

The book is divided into three parts, the first treating of suggestibility, normal and abnormal, the second of t'le self, or personality, the third of the relations of suggestion to social phenomena.

In the first part the author undertakes to determine the laws of normal and abnormal suggestibility. The former he concludes to be as follows :

"Normal sugiestibility varies as indirect suggestion, and inversely as direct suggestion."

In ordinary language, this means that if you want a normal person to do something, the surest way to do it is to conceal your


wishes from him, while insinuating the idea of the action into his mind. So stated, it is evident at once tliat It is not a universal or even a general law. Dr. Sidis must be mure unfortunate than most people in his acquaintances if their knowledge that he would like them to do so and so would not be some inducement to them to do it even uncritically and somewliat against their inclinations.

The law of abnormal suggestibility he formulates as follows :

"Abnormal suggestibility varies as direct suggestion, and inversely as indirect suggestion."

That is, in dealing with an abnormally suggestible person, the more explicit and imphatic the commands are made, the more likely they are to be executed. Dr. Sidis evidently has the hypnotic condition in mind, but it is l>y no means true that persons in this state are always insusceptible to indirect suggestion. As Dr. Sidis himself points out, the fallacy in the accounts given by Bernheim, Charcot and others of the various stages of the hypnotic state is due to the fact that the symptoms had been indirectly and unconsciously suggested to the patients by the operator. But hypnotism is not the only condition of abnormal suggestibility. In " negativism," or "contrariness," the patients may be led to do anything desired by telling them to do just the opposite.

The fact is, that in a normal condition, every suggestion, direct or indirect, tends to be carried out, but, on the other hand, it is apt to suggest, indirectly, conflicting ideas, which may inhibit it. In the hypnotic state, on the contrary, the conflicting considerations would seem to be largely or completely in abeyance.

In the second part, on " The Self," Dr. Sidis considers the nature of personality and the relations of what he calls the subconscious subwaking or secondary self, as manifested in such conditions as hypnotism, double consciousness and hysteria, to the primary or waking self. This is much the most interesting portion of the work. Theaccount of thecaseof Rev. Thomas C. Hanna, who suffered complete loss of memory as the result of an accident, and of the means and steps by which the lost connection was recovered, is of remarkable interest, and the more detailed account which is promised will be most welcome to all readers of the book who are students of such sulijects.

Perhaps the most original contribution of facts to be found in the book is the account of experiments tending to show that some degree of the abnormal acuteness of the senses which is a wellknown phenomenon in many cases of hypnotism and hysteria is subconsciously present, to a certain extent in the normal condition. Thus, the author found that when words, letters or figures were shown at such a distance that they appeared as a mere confused blur, if the subjects of the experiments were required to guess what was shown them, their guesses were correct in a much larger proportion of cases than could be accounted for by chance. If his results in this direction are confirmed by subsequent investigators, they would seem to constitute a distinct advance in this department of psychology.

Although the tendency of the book is to show the subconscious presence, in normal conditions, of mental phenomena which are usually thought of as peculiar to abnormal states. Dr. Sidis doesnot seem fully to appreciate the fact that there is really no sharp distinction between our conscious and subconscious selves, but that they are constantly passing into and out of each other. AVithout attempting to criticise his discussion of the essential nature of personality, it may be said that our conception of our own personality in any given case is made up of our present sensations and feelings and our memories of the past. Only a small portion of all our experiences occupy our attention at any given moment ; many can be readily called up ; many more are lo.st beyond the possibility of recollection. We have entirely forgotten how we first learned to walk and to talk, for instance, although the knowledge then gained still abides with us. In the states of abnormal consciousness which the author has in minil, great blocks of the knowledge which is ordinarily at our command may be, for the time being, as much out of


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reach as tne rerollection of the events of infancy. And just as we accept the account of others as to the events of times which have passed from memory, and incorporate them in our conception of our personality, so the hypnotic subject may accept the statements of the operator as to who and what he is, and govern himself accordingly.

As a physical basis for tlie phenomena of association and dissociation of states of consciousness, the author assumes the truth of the theory of contractility of the neuron. However convinced he may personally be of its correctness, it is hardly fair to his nonprofessional readers to give no liint of the fact that it is, thus far, a mere hypothesis, without, as far as at present appears, even the possibility of experimental verification, and open to very grave theoretical objections.

In the chapter on "Subconsciousness and Insanity," Dr. Sidis brings out clearly the analogy between posthypnotic suggestion and morbid impulses and imperative conception. Paranoia is much less satisfactorily treated.

In the third part of the book, treating of the psychology of crowds and mobs, and of crazes" of various sorts, the mistake is made of confounding quite distinct phenomena. The influence exerted on susceptible persons by the presence of a multitude filled with a common emotion may very probably be, in some respects, analogous to the hypnotic condition, but there would, doubtless, have been a stampede for the Klondike if every one of those who went had supposed he had private and exclusive information of the riches to be gained there.

On the whole, the book, while containing much of interest, is valuable rather for its facts than its reasonings.

The Disea.'es of the Stomach. By William W. Van Valzah, A. M., M. D., and J. Douglas Nisbet, A. B., M. D. Illustrated. {Philadelphia: W. B. Saunden, 189S.)

The stomach is a very important viscus, notwithstanding the fact that recent surgical successes have shown that under certain special conditions it can be dispensed with in the economy. Its importance is sufficiently in evidence when valuable text-books on its ailments follow each other with the rapidity which they have within the last two or three years. The present volume, while not supplanting the valuable treatises that have preceded it, has merits of its own, and is apparently well suited for a textbook on its subject.

The authors' plan of their work is a simple one, giving first the general methods of diagnosis and the general medications, then following this successively by sections on the dynamic affections of the stomach, including under this head all the symptomatic disorders that present, so far as known, no characteristic pathological anatomy, on the anatomical diseases which are, on the other hand, thus characterized, and finally ending with a section on the vicous circles of the stomach," on the action of gastric disorders in producing or in being produced by disease elsewhere. This classification may be open to some criticism, hut, on the whole, it seems fairly well adapted to afford a general view of the morbid conditions in which the stomach plays a chief or principal part. It is not esi)ecially original in its contents, and will hardly displace the recently published and excellent work of Hemmeter as a favorite with the American physician, hut, as already said, it has its merits, and is well worthy of being an addition to any medical library.

Public Health Reports. (Formerly abstract of Sanitary Reports.) Issued by the Supervising Surgeon-General of the Marine Hospital Service. Vol. XII, Nos. 1-53. (Washington: Government Printing Office, 1898.)

This volume contains the reports of sanitary inspectors. United States consuls, and others on health conditions in foreign parts, translations from foreign languages of papers on special epidemics.


and statistics of municipal health authorities here and abroad, of commissioners of emigration, etc., etc.; altogether a vast amount of valuable information upon sanitary matters. The woik is a very useful one for reference in regard to these subjects, and the series of three volumes must form a very valuable record of sanitary statistics throughout the world, while the monthly publication of the parts that compose them is a useful current record.

The Archives of the Roentgen Rays. (Formerly Archives of Skiagraphy.) The only journal in which the transactions of the Roentgen Society of London are officially reported. Edited by W. S. Hedley, M. D., and Sidney Rowland, M. A. (London: The Eebtnan Publishing Co., 1898.)

The title of this journal sufficiently indicates its nature and scope. It is elegantly printed and illustrated, and should be well received by those who use the Roentgen rays in physical or medical rt-search. The only thing one can say against it is, that with the widening range of utility of Roentgen's discovery in surgery and medicine, a less expensive journal issued more frequently would be still more welcome to the medical profession. .4n actinoscopic adjunct is becoming almost essential to a surgeon's outfit, or at least such must be available to him, and there is every reason to believe that new utilities will be found, as time passes, for this method.


BOOKS RECEIVED.


Tenth Report of the State Board of Health of the State of Maine for the Two Tears Ending Dee. Zl, 1897. 395 pages. Svo. 1898. Kennebec Journal Print, Augusta.

Practical Urinalysis and Urinary Diagnosis. A manual for the use of physicians, surgeons, and students. By Charles \V. Purdy, M.D , LL. D. Fourth revised edition. Svo. 1898. 3(55 pages. The F.A. Davis Co., Phila.

Essentials of Materia Medica, Therapeutics and Prescription Writing. Arranged in the form of questions and answers. Prepared especially for Students of Medicine. (Saunders' Question-Compends, No. 7.) By Henry Morris, M.D. ]2mo. 1898. 288 pages. W. B. Saunders, Phila.

A Primer of Psychology and Mental Disease. For use in trainingschools, for attendants and nurses and in medical classes. By C. B. Burr, M. D. Second edition, thoroughly revised. l"mo. 1898. 116 pages. The F. A. Davis Co., Phila.

The Care of the Baby. A manual for mothers and nurses, containing practical directionsfor the management of infancy and childhood in health and in disease. By J. P. Crozer Griffith, M. D. Second edition, reviseil. Svo. 1898. 404 pages. W. B. Saunders, Phila.

Transactions of thf Association of American Physicians. Thirteenth Session. Held at Washington, D. C, May 3, 4 and .5, 1^98. Vol. XIII. 1898. Svo, 484 pp. Printed for the Association. Phila.

Operative Gynecology. By Howard A. Kelly, A. B., M. D. Vol. II. 1893. 4to, 5.57 pp. D. Appleton & Co., New York.

Lehrbuch der AUgemeinen Pathologic und der pathologischen Anatomie. Von Dr. E. Ziegler. Zwei Biinde. Neunte neu bearbeitete Auflage. ZweiterBand. Specielle pathologische Anatomic. 1898. Svo, 1024 pp. Gustav Fisclier, Jena.

The Pocket Formulary for the Treatment of Disease in Children. By Ludwig Freyberger, M. U., Vienna. IB mo. 1898. 208 pages. The Rahman Publishing Co., Limited, London.

Trarisactions of the Michigan State Medical Society for the Tear 189S. Volume XXII. Svo. 189S. 450 pages. Published by the Society, Grand Rapids.


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[No. 92.


THE JOHNS HOPKINS MEDICAL SCHOOL. SESSION 1898-1899.


PACULTY.


Wii


iiBL C. Oilman, LL. D., President.

LiAM H. Welch, M. D., LL. D., Dean and Professor of Pathology. Remsen, M. D., Ph. D , LL. D.. Professor of Chemistry. ,Li*M OsLER, M. D., LL. D., F. R. C. P., Professor of the Medi.


iple


nd Pr


of


Henry M. Hurd, M. D., LL. D., Professor of Psychiatry.

William S. Halsteii. M. D., Professor of Surgery.

HowAK.) A. Kbllv, M. D., Professor of Gynecology and Obstetrics.

Fkanklin p. Mall, M D.. Professor of Anatomy.

lOHN J. Abel, M. D., Professor orPharmacology.

William H. Howell, Ph. D., M. D., Professor of Phy>iology.

WiLLiAU K. BuO'.KS, Ph. D., LL D., Professor of Comparative Anatomy and Zoology.

John S. Hillings, M. D., LL. D., Lecturer on. the History and Literaiure of Medicine.

Alexanuek C. Abboti, M. D., Leciurer on Hygiene.

Chables Waruell SriLES, Ph. U , M. S . Leciurer on Medical Zoology.

RoiiKRT Fletcher, M. D., M. R. C. S.. Eng., Lecturer on Forensic Medicine.

William D. Booker, M. D.,Clinic.iI Profes-or of Diseases of Children.

loHN N. Mackpnzie, M, D., Clinical Professor of Laryngology and Rhinology.

Samuel I'heobalu, M. D., Clinical Professor of Ophthalmology and Otology.

Hbkrv M. Thomas. M. D., Clinical Professor of Uiseases of the Nervous System.

Simon Flhxn»r. M. D , Associate Prosessor of Paihology


J. Wh


I Wi


1 F. Ba


AMS, M. D., Associate Professor of Obstel !R, M. B , Associate Professor of Anatomy. R, M. D., Associate Professor of Medicine. , M. D., Associate Professor of Surgery. , Ph. D., Associate in Physiology.


William W. Russell, M. D., Associate in Gynecology.

Hrnrv J. Berkley, M. D., Associate in Neuro-Pathology.

J. Williams Lord, M. D, Clinical Professor of Dermali^logy and Instructor in A;

T. Caspar (mlchkist, M. R C. S., Clinical Professor of Dermatology.

Robert L. Ranuolph, M. D., Associate in Ophihalmology and Otology.

Thomas B. Futchrr, M. B , Associate in Medicine.

Joseph C Bloougooi., M. D., Associate in Surgery.

Thomas S. Cullen, M. R., Associate in Gynecology.

Ross G. Harrison, Ph. D., Associate in Anatomy.

Reid Hunt, Ph. U., M. D., Associate in Pharmacology.

Frank R. Smith, M. D., Instructor in Medicine.

Oeorgh W. Dobbin, M. D., Assistant in Obstetrics.

Waltpr Jonrs, Ph. D. , Assistant in Physiological Chemistry and Toxicology.

Sydney M. Cone, M. D . Assistant in Surgical Pathology.

Harvey W. Cushing, M. D., Assistant in Surgery.

Henry Barton Jacbs. M. D.. Instructor in Medicine.

High H. ¥ ung, M. D , Instructor in Genito-Urinary Diseases.

Charles R. Bardeen, M D., Assistant in Anatomy.

Stewart Paton, M. D., Assi-tant in Nervous Diseases.

Norman McL. Harris, M. B., Assistant in Bacteriology.

Albert C. Crawford, M. D., Assistant in Pharmacology.

J. W. Lazear, M. D , Assistant in Clinical Microscopy.

Henry O. Rkik, M. D , Assistant in Ophthalmology and Otology.

Elizabeth Hubdon, M D., Assistant in Gynecology.

Wali BR S. Davis, M. D., Assistant in Clinical Microscopy.

J. L. Walz, Ph. G., Assistant in Pharmacy.


GENERAL STATEMENT.


Tlie Medical Department of the Johns Hopkins University was opened for the instruction of students October, 1893. This School of Medicine is an integral and coordinate part of the Johns Hopkins University, and it also derives great advantages from its close afBliation with the Johns Hopkins Hospital.

The required period of study for the degree of Doctor of Medicine is four years. The academic year begins on the first of October and ends the middle of June, with short recesses at Christmas and Easter.

Men and women are admitted upon the same terms.

In the methods of instruction especial emphasis is laid upon practical work in the Laboratories and in the Dispensary and Wards of the Hospital. While the aim of the School is primarily to train practitioners of medicine and surgery, it is recognized that the medical art should rest upon a suitable preliminary education and upon thorough training in the medical sciences. The first two years of the course are devoted mainly to practical work, combined with demonstrations, recitations and, when deemed necessary, lectures, in the Laboratories of Anatomy, Physioiogy, Physiological Chemistry, Pharmacology and Toxicology, Pathology and Bacteriology. During the last two years the student is given abundant opportunity for the personal study of cases of disease, his time being spent largely in the Hospital Wards and Dispensary and in the Clinical Laboratories. Especially advantageous for thorough clinical trainiug are the arrangements by which the students, divided into groups, engage in practical work in the Dispensary, and throughout the fourth year serve as clinical clerks and surgical dressers in the wards of the Hospital.

REQUIREMENTS FOR ADMISSION.

As candidates for the degree of Doctor of Medicine the school receives :

1. Those who have satisfactorily completed the Chemical-Biological course which leads to the A. B. degree in this university.

2. Graduates of approved colleges or scientific schools who can furnish evidence : {a) That they have acquaintance with Latin and a good reading knowledge of French and German ; (6) That they have such knowledge of physics, chemistry, and biology as is imparted by the regular minor courses given in these subjects in this university.

The phrase "a minor course," as here employed, means a course that requires a year for its completion. In physics, four class-room exercises and three hours a week in the laboratory are required; in chemistry and biology, four class-room exercises and five hours a week in the laboratory in each subject.

3. Those who give evidence by examination that they possess the general education implied by a degree in arts or in science from an approved college or scientific school, and the knowledge of French, German, Latin, physics, chemistry, and biology above indicated.

Applicants for admission will receive blanks to be filled out relating to their previous courses of study.

They are required to furnish certificates from officers of the colleges or scientific schools where they have studied, as to the courses pursued in physics, chemistry, and biology. If such certificates are satisfactory, no examination in these subjects will be required from those who possess a degree in arts or science from an approved college or scientific school.

Candidates who have not received a degree in arts or in science from an approved college or scientific school, will be required (1) to pass, at the beginning of the session in October, the matriculation examination for admission to the collegiate department of the Johns Hopkins University, (2) then to pass examinations equivalent to those taken by students completing the Chemical-Biological course which leads to the A. B. degree in this University, and (3) to furnish satisfactory certificates that they have had the requisite laboratory trainiug as specified above. It is expected that only in very rare instances will applicants .who do not possess a degree in arts or science be able to meet these requirements for admission.

Hearers and special workers, not candidates for a degree, will be received at the discretion of the Faculty.

ADMISSION TO ADVANCED STANDING. Applicants tor admission to advanced standlug must furnish evidence 11) that the foregoing terms of admission as regards preliminary training have been tulfllled, (2) that courses equivalent In kind and amount to those given here, preceding that year of the course for admission to which application Is made, have beeii satisfactorily completed, and i:J) must pass examinations at the beginning of the session in October in all tlie subjects that have been already pursued by the class to which admission is sought. Certiflcates of standing elsewhere cannot be accepted in place of these esaraiualions.

SPECIAL COURSES FOR GRADUATES IN MEDICINE.

Since the opening of the Johns Hopkins Hospital in 1889, courses of instruction have been offered to graduates in medicine. The attendance upon these courses has steadily increased with each succeeding year and indicates gratifying appreciation of the special advantages here afforded. With the completed organization of the Medical School, it was found necessary to give the courses intended especially for physicians at a later period of the academic year than that hitherto selected. It is, however, believed that the period now chosen for this purpose is more convenient for the majority of those desiring to take the courses than the former one. The special courses of instruction for graduates in medicine are now given annually during the months of May and June. During April there is a pi-eliminary course in Normal Histology. These courses are in Pathology, Bacteriology, Clinical Microscopy, General Medicine, Surgery, Gynecology, Dermatology, Diseases of Children, Diseases of the Nervous System, Genito-Urinary Diseases, Laryngology and Rhinology, and Ophthalmology and Otology. The instruction is intended to meet the requirements of practitioners of medicine, and is almost wholly of a practical character. It includes laboratory coursee, demonstrations, bedside teaching, and clinical instruction in the wards, dispensary, amphitheatre, and operating rooms of the Hospital. These courses are open to those who have taken a medical degree and who give evidence satisfactory to the several instructors that they are prepared to profit by the opportunities here offered. The number of students who can be accommodated in some of the practical courses is necessarily limited. For these the places are assigned according to the date of application.

The Annual Announcement and Catalogue will be sent upon application. Inquiries should be addressed to the

REGIST RAR OF THE JOHNS HOPKINS MEDICAL SCHOOL. BALTIMORE.

The Johns Hopkins Hospital Bulletins are issued monthly. They are printed by THE FRIEDENWALD CO., Baltimore. Single copies may be procured from Messrs. CUSHINO & CO. and the BALTIMORE NEWS COMPANY. Baltimore. Subscriptions, Sl.OO a year, may be addressed to the publishers, TEE JOHNS HOPKINS PRESS, BALTIMORE ; tingle copies will be sent by mail for fifteen cenU each.


BULLETIN


OF



THE JOHNS HOPKINS HOSPITAL.


Vol. IX.- No. 93.


BALTIMORE. DECEMBER, 1898.




GOlSTTElSrTS.


PAGE

Medicine in the Nineteenth Century. By T. Clifford Allbutt, M. D., ----- _-----.-- 277

On Refractory Subcutaneous Abscesses caused by a Fungus Possibly Related to the Sporotricha. By B. R. Schenck, M. D., ----..____.--. 286

CE lematous Changes in tlie Epithelium of the Cornea in a Case of Uveitis following Gonorrhojal Ophthalmia. By Edwaed Stieren, M. D., ---------------- 290


PAGE.

Proceedings of Societies :

The Hospital Medical Society, 292

Primary Focal Htematomyelia from Traumatism [Dr. Peakce Bailey] ; — Two Cases of Pylorectomy [Dr. Finneyj ; — The Non-Medical Treatment of Epilepsy [Dr. Hurd].

Notes on New Books, ----- 297

Index to Volume IX, - - - - - 299


MEDICINE IN THE NINETEENTH CENTURY.

By T. Clifford Allbutt, M. D., Regius Professor of Physic, Cambridge University.


{Delivered before the Johns Hopkins University, Oct. 17, 1898.)


Were we asked to describe in a phrase the tendency which distinguishes our age it might be replied that it is the study of origins. In the later thirteenth and early fourteenth centuries, for example, men's minds were fixed for the most part on the validity of dialectic, were bent rather upon securing mental surefootedness and sharp and true weapons of thought than upon the verification of premises. For instance, Albertus Magnus, with the utmost fairness, marshalled from the writings of his adversaries thirty arguments in ftivor of the doctrine of the oneness of the soul ; so that on the death of the individual his share is merged again in the whole, and loses whatsoever personality it may seem for a time to have assumed ; on the other hand for the doctrine of the persistence of individual souls after death he found thirty -sis valid reasons; thus the essential multiplicity of the soul was proved. Again Raymond Martini found eighteen reasons for the eternity of the world, and eighteen against it; the doctrine hung anxiously in the balance until he discovered seven other reasons which fortified it ; he scrupulously admitted indeed that the last seven were not altogether apodeictic, but " with the reinforcement of faith " they suiBced to sustain it. Thus again for these disputants Aristotle and Galen were not so much chosen as received as guides, and their scriptures accepted as bibles. Now althougli it is not fair to press this character as a conspicuous feature of


the greatest minds of the latter half of the thirteenth century, for Thomas of Aquino, for example, regarded Aristotle as a pagan sage to be treated with no more than resj)ect, and it is still less true of Roger Bacon, the greatest of them all ; still it was the fashion of that time to look rather to agility and sureness of logical fence than to genesis and verification. To one of our own time who turns to their pages, or of John Henry Newman in our own time, the quickness and subtility of their arguments, the keenness and variety of the language which they elaborated by incessant exercise in such dialectic, make a most interesting study. Therein indeed the reader may find cause to regret that in modern times we have too often allowed these instruments of close and strong logic to fall into rust and neglect, though in our own time again we shall not thus speak of our greatest minds ; to confine ourselves to our own race, argument more sure and penetrating than that of Newton, of Faraday, or of Darwin, for example, is not to be found in any century. Still the common mind of our time is set rather towards the investigation of premises — of origins; we look less to the closeness of our web of arguments, and take less heed to every logical stitch than our forerunners, who took their causes for granted and thought only how to fight for them. Yet although we may escape too cheaply in respect of logical processes on one way, we must travel at least as warily, namely, on the


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[No. 93.


method of experiment. Generally speaking, facts are now preferred to arguments, and as facts so far from being the fixed and flinty tilings they are supposed to be, are shifty and protean, we require from those prospectors who proclaim the discovery of facts a minute demonstration of their methods, and we do not allow any agility in verbal fence to put us off this prime demand. Show us your clews, take us over the tracks you say you liave surveyed, bring us into the ambush of nature which you think you have discovered ; for howsoever finely you may talk about them we shall not believe you until we in our turn have followed you on the path. This at any rate is the attitude of those who pursue the exact sciences, and it is with the sciences, whether of experiment or observation, that not weonly but also our fathers of the thirteenth and fourteenth centuries were concerned.

It may be urged that surely these sciences are the labor of our times, not of earlier times when sages spent their time in sophistry ! Yet such an assertion is scarcely justified. Sucli is the essential kinship of man in all ages that by whatsoever names he calls them, or by whatsoever methods he pursues them, his search is after the ends of science; I mean his argumentative search, for I am not at present speaking of artistic creation. When we turn to the speculations whether of the Greeks, or, after them, of Western nations, we find that they concerned themselves with the same subjects as those of the modern thinker; they argued of cosmogonies, of the elements of nature, of ethics, of law, of the virtues latent in natural objects, and so forth. The antagonism between the conceptions of creation and of development is not, as too often we think, a division of our own time only ; in cruder forms, but still in full distinction, these opposing theories were familiar to philosophers of the fourth century before Christ as well as of the thirteenth century after Christ. The explanations given in such days as those differed widely from ours, but they were explanations, and were discredited only because they turned out to explain too little. Even to-day the experimental method can only be applied to the exact sciences; to the moral sciences and to medicine, for example, dialectic must still be largely applicable. In the study of medicine the experimental method has but a narrow field ; observation takes a higher place in its pursuit, but dialectic has also no inconsiderable part, and we shall do wrong if we allow instruments fashioned under other conceptions of method to fall from our hands under the attraction of the richer results of the modern methods of the exact sciences. While ethics and politics must largely depend on dialectic and mechanics, let us say but little on it — though mathematics is indeed in itself a sublimated dialectic; medicine, occupying a middle position, must keep both weapons furbished. For instance, a true conception of causation is largely a matter of dialectic, and however ingenious our experiment and observation we cannot afford to be ignorant of the laws of causation and of thought, and of the language in which these abstract ideas are to be expressed. For this language, I repeat, we are indebted to our forefathers of the thirteenth and fourteenth centuries as well as to Hume and to Mill. I have hinted that we are too prone to think, indeed to vociferate, that a fact is a fact, forgetting that inference is of the essence of every proposition ; inference sticks to fact as closely as shadow to substance.


A statement of the plainest facte implies a cement of inference, and he who has learnt to handle ideas will thus far have a great advantage in every research. Looseness in words and lack of lucid and orderly expression of ideas in the records of modern medicine is lamented by Dr. Da Costa in his address to the Association of American Physicians and Surgeons, May 4, 1897, and in a recent leading article the London Times laments the same defects in English lawyers of the day and urges the need of a more formal education in this great accomplishment. Those who decry dialectic decry also what they are pleased to call " theory." That such and such a teacher is too " theoretical " is a stone thrown in many a classroom, and often no doubt it hits the mark. It is true that to pursue philosophy as a study in itself has been a source of mischief or of bewilderment in many schools, as in Germany and in Scotland. Nevertheless we are now beginning to find that long practice in theoretical, that is in abstract, thought has giveu both Germans and Scotchmen a strength in dealing with modern and more fertile problems which Englishmen at any rate somewhat jealously and somewhat impotently admire. In England we are apt to retort that we are saved by our adhesion to the inductive method. If such an one — and now I may pass beyond my own land — be asked what he means by induction it turns out that he means, or thinks he means, a mosaic of concrete observations. Not only does he fail to realize that even these are bound together, as I have said, by a cement of inference, but perceiving, as he unconsciously must, that such short links do not carry him far in explaining things, he takes refuge in assertions which indeed are broad enough but have taken on appearance of solidity from their established currency. Mrs. Gruudy is not unknown even in the sphere of abstract propositions; use and convention may make the hollowest surmises respectable and their acceptance comfortable. It is by no means true that the ordinary man hates abstract propositions; he loves many of them, as for instance that the weather depends on the phases of the moon; that most bodily discomforts arise from disorders of the liver, and so forth. There is no proposition, however wide and abstract, which he will not swallow with avidity if it be brought from the pages of an old almanac ; nay, easy as knowledge outgrows such outworn opinions he will yet strive to extract some truth from their arid sources — to prove that there is "'something in them after all." What the ordinary man hates is not the abstract proposition but the making of abstract propositions. He inherits any ready-made theory gladly, but he resents being called upon to make one himself, or even to adapt his mind to such novelties; he has never been practised in this gymnastic and it jades him. He dislikes it as we dislike any unaccustomed exercise, as we love an old coat or an old pair of shoes.

I need not occupy your time, gentlemen, by pointing out that the inductive method consists of two jjrocesses at least — in observation and imagination; in imagining again and again from a short series of facts the probable course of a longer series ; and then in testing the truth of all or any such notions until the right one is hit off. Such surmising requires an alert imaginative or theorizing faculty. To pursue the study of philosophy for itself alone has only a gymnastic value, and leads, as I have said, to routine and sterility; but I repeat


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also that past exercise iu this faculty, barren as it seemed for awhile, turns out, when carried into more fertile fields of research, to have given to such students a suppleness and sureuess of argument which we may well envy. The AngloSaxon brain contains, as its literature has shown, the sanest and strongest imagination of any in the world; but thus far in the world's history it has been rather a pioneering brain, a fighting brain, whether with man or Nature; and immediate material results have been prized to the disadvantage of the more prophetic powers. The Anglo-Saxon has fought rather for bread to-day than for cake to-morrow ; nevertheless, the future will be for those who can combine the practical spirit with a mind exercised in the arms of theoretical and dialectical precision.

What we have learned, then, is that speculation in former times has been valuable as exercise rather than as achievement; that, although the deductive side of our method of thought is better adapted to exposition, the inductive bias is for most men the safer way in research. In the words of Klebs (Allgem. Pathologic, vol. i, p. 4), we must learn not that the construction of hypotheses is bad, but that "Diese Hy pothesenbildung nicht das Spielzeug einer weitschweifenden Phantasie sein soil, sondern das Werkzeug ernster wissenschaftlicher Arbeit."

Among the lessons of this kind which we have painfully learned during the last two thousand years two stand out perhaps as the chief; these are, first, the barrenness of all conceptions based upon causal entities; secondly, the constraining need of verification. First, concerning causal entities, there has been a tendency of late to bring back into physiology the notion of "vitalism" or "vital force," and to scoff at those who would apply the word " mechanical " to the processes of life. It may well be that the connotations of the word mechanical embarrass us in the use of it to signify the complex phenomena of life ; on the other hand, we are on safe ground so long as we endeavor from the simpler phenomena of physics to rise continuously to conceptions of the more complex phenomena of life ; at any rate, we must not desert this track so far as it goes, and within these limits there is plenty to discover. But, under whatsoever name, to import an occult principle as a cause is to return to the most sterile rhetoric of the middle ages. Unable to shake themselves wholly free from the personification of natural objects, a personification which had gradually been removed from the objects themselves to their supposed causes, the ancients assumed such a principle to govern the movements of the celestial bodies ; and even to this day we are apt to speak of force as something or entity acting on matter. That physical forces acting as simple molecules can account for the complex phenomena of life no one wishes to assert; no one will assert that they can account for the phenomena of chemistry in which the molecules, though less complex than the living, are far more complex than those studied in physics. But if we are to assume a vital principle in the animal cell assimilating food, then what need is there of a study of any other forces ? The fact is, we are too impatient to await the unravelling of the manifold composition of forces in a highly compound niolecnle, an investigation which is only possible by long and un


wearied series of experiment. No one attributes the virtues of chemical molecules to " chemism " ; nor the vastly more complex functions of societies to a principle of socialism. Products differ from factors as sugar differs from a mixture of carbon, hydrogen and oxygen, and as an organism differs from the unrelated activities of an aggregate of nucleated cells. The phenomena of life are wholly conditioned by the peculiar complexity of its molecule, and with the size and complexity of the molecule the synthesis of forces increases in a multiple ratio.

We may speak, then, of a molecule as a highly elaborate construction of matter, or we may regard it as a highly elaborate system of forces, and this view of life, which brings its phenomena into line with the subject-matter of other sciences, is one, at least, of the achievements of our own time which we shall do well to preserve.

Another conception which now rules our thoughts far more profoundly than ever before in the history of mankind is that of law in the course of Nature. Far indeed from a new idea — for that Nature works by fixed laws, first conceived by the sages of Ionia, had penetrated the minds of thinkers of the fifth century before Christ, and moulded the thoughts of Hippocrates. This great conception, by means of which alone a knowledge of Nature and an empire over her become possible, was afterwards obscured for many centuries ; it was left, indeed, for our own day to grasp the idea in its full meaning. The lonians were not free from a tendency to personify these laws, and even to-day we may hear the Laws of Nature spoken of as agencies by which Nature is compelled, rather than as our formulas for invariable sequences. Yet it is no exaggeration to say that, even in its ontological form, a true conception of natural law was a greater achievement of the mind and more important in the advance of knowledge than the doctrine of the conservation of energy or the conception of evolution — ideas which we are wont to regard, and rightly to regard, as consummate achievements of modern philosophic theory. Again, the perception that activity of thought can only be true and just in the best sense when it is in vital and incessant connection with the activities of the phenomena on which it is engaged, is an invaluable quality of modern thought.

An accomplished Oxford tutor, lately taken from us, said of another department of knowledge : " One always comes back to the feeling that the truth in the ultimate problems is not got by thinking (in the ordinary sense), but by living." What Nettleship experienced in the study of ultimate problems is no less true of proximate problems.

It was for lack of this touch of nature that the older universities of Europe fell out of line with life. Whether for the analysis or for the harmony of knowledge, we cannot keep before us the quality, depth, complexity and manifold interaction of natural processes without incessant converse with them in their flow. We cannot retain a conception, nay, not even an apprehension, of the infinite vastness and variety of the work of the eternal loom by taking thought alone, by discussing them as if we were gods. Our minds can only be edified with Nature's bricks; beside her work the worlds we build out of our own heads are but doll's houses. Philosophy,


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as a mere literature, ends, as I have said, in conjectural systematizing, in speculation upon speculation, in a visionary gymnastic. Oxford scorned the " base and mechanical pursuits " of Boyle, and the wiseacres who so spoke of that great man are dead and forgotten. Medicine in Germany was almost grotesque until the day of Rokitansky and Miiller. Moreover, ideas thus engendered are not only hollow and arid, but they have all the rigidity and inertia of inanimate things; they become as shells which happily may be sloughed off but never have part in new development, and meanwhile are strangling the very germs of it. Ardent enquirers in touch with nature are thwarted or extinguished, and Nature, indifferent as ever to man's self -sufficient conceits, goes her own way like a wild dam eating up her own offspring. Not only ai'e notions engendered without the seed of Nature contrary to the truth ; they are also antagonistic to the discovery of the truth. As Dr. Daremberg says, " Les idees sont plus entetees que les faits." Is it not one of the marks of our own age that man is not only now freed fi'om the bondage of authority, not only is he now free of the kingdom of pure thought, but he is also brought into touch with Nature ; now Nature is to be his inspiration, not his destruction.

Even in my young days the first chapter of Genesis was generally held in its literal meaning as a string of aifirmative propositions ; and for many previous generations the advance of true conceptions of biology had been continually thwarted thereby. In medicine as well as in natural history we are dependent on true biological conceptions, for without them we are apt to lie content with empiricism.

Again, with evolution has arisen a living conception of progress ; mankind, no longer dreaming about a golden age in the past, is set with its face to the future ; the golden age is in the future, not in the past, and the happiness of the human race is to be won by reading the secrets of natural law, and by strenuous effort. Yet this dream of a lapsed golden age, like all such myths, held some truth in it; a truth which, in the revolution of the standpoint from past to present and future, fell into neglect. The study of the past is now returning in a new spirit, in that stiody of origins which, as I have said, is a feature of our generation ; and the neglected lesson that we cannot afford to foi-get the travail of any age is seen in a new light. Tradition is recognized as the mould into which our activities have run as an embodiment of human experience; and we are learning the humble lesson that modern man is perhaps no greater in faculty than his forefathers ; that if we have entered into new and more fertile fields it is by means of our inheritance rather than by means of greater faculties. If the average modern man be as highly endowed as the greater ancients some few of them, such as Archimedes or Aristotle for example, were perhaps richer in mental gifts than the greatest of modern men. If this be so it will appear that tradition is a larger part of progress than we are disposed to admit. If the transmission of acquired faculties by inheritance be not altogether disproved, it is proved at any rate that such inheritance is a much smaller factor in progress than we had assumed. It seems certain indeed that its sphere is at best a very small one ; and that we stand at the apex of the pyramid not by virtue of better building but because we were born


with the pyramid below us. To cohtemii or to subvert the ideas of our fathers is then to cut the ground from below our own feet ; to destroy that accumulation of the results of former labors which in commerce we call capital, and which in things of the mind we call tradition. There is no evidence that we are greater even by virtue of a more highly organized brain ; there is no evidence that we are a new and more gifted variety of man ; we are greater because we are born richer in circumstance, richer in the gifts and endowments whether handed down to us in material shapes or as learning from past ages. If in certain ages of the world tradition has held too large a j)lace in the admiration of men, and has laid too heavy a hand on freedom and originality of thought, we may yet appreciate the due value of tradition in our own advance, and our duty to our descendants in preserving for them all that seems good in our own time, while our minds play freely nevertheless, and are not smothered by its weight. For as Plato says in the Ion: "There is a stone which Euripides calls a magnet, but which is commonly known as the stone of Ileraclea. This stone not only attracts iron rings, but also imparts to them a similar power of attracting other rings ; and sometimes you may see a number of pieces of iron and rings suspended from one another so as to form a long chain, and all of them derive their power of suspension from the original stone. In like manner the Muse first of all inspires men herself ; and from these inspired persons a chain of other persons is suspended, who take the inspiration." May we not accept this beautiful figure which Plato imagines of poetry to signify all tradition by which man is enriched and advanced. " Through all these," he says, " the God sways the souls of men in any direction which he pleases, and makes one man hang down from another." It is in our great seats of learning, such as this in which I am now speaking, that men forge and hand down to their children the cosmos of inherited experience in which we dwell and about which we breathe an atmosphere which forms and inspires without our being conscious of its presence. If we may counsel that our minds shall come to Nature "disencumbered, clear and plastic," this counsel has regard to the accidents of mental occupation, not to the edification which began in the cradle and ends only as the faculties of assimilation in each of us are outworn. You will thus be prepared to know that our great ancestors among the ancients, however vast their mental endowments, could not have built up true doctrines. The empirical method is the necessary porch of entrance into science ; and there can be no true generalizations till facts have accumulated in quantity sufficient for the foundation of them.

To Hippocrates little was possible beyond superficial clinical observation ; anatomy and pathology were slowly to be built up by harassed and painful men in many a broken century to come. But Hippocrates, thus confined to clinical observation, could describe such general movements as fever calculate, and the phases of disease in time — as acute and chronic, as subject to crises, and so on ; and again, on this chemical basis he formed the great conception of diathetic diseases, so that thenceforth many diseases were no longer regarded as isolated events, but as terms in series. Wliile we admire the breadth of these conceptions we admire also the genius which all attain to them when


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DO other kind of enquiry was then open ; for it was not until the time of the school of Alexandria that anatomy and pathology could be said even to begin. Nosological detail, as we daily study it, was out of his reach. The method of experiment was not even formulated, though Littre has reminded us that Hippocrates made the profound observation that no study of the brain could have led us to foresee that wine would produce so peculiar a disturbance of its functions. It was left to Galen to bring empiricism, clinical observation, normal and morbid anatomy, and even experimental methods together in one coordinate study, soon however to be eclipsed in the darkness of the middle ages. Even to this day physicians have not assimilated the lesson that disease is not an entity but a particular state of the body and has no more of a separate or objective existence than, let us say, the constellations of the Great Bear or Charles's Wain.

I need not at this day remind you that progress in any one science depends on what may be called the accident of jjrogress in ancillary sciences and arts. I have always thought it a remarkable instance in this sense that the stupendous advance of modern surgery waited upon two main conditions, namely, on the discovery of anaesthetics and on those researches of Pasteur which laid the foundation of modern bacteriology. When 1 was a boy surgeons operating upon the quick were pitted one against the other like runners on time. He was the best surgeon, both for patient and onlooker,who broke the three-minutes record in an amputation or a lithotomy. What place could there be in record-breaking operations for the fiddle-faddle of antiseptic precautions":' The obvious boon of immunity from pain, precious as it was, when we look beyond the individual, was less than the boon of time. With anesthetics ended slapdash surgery; anaesthesia gave time for the' theories of Pasteur and Lister to be adopted to practice. It is within the memories of some of us how the great performing surgeons scoffed at Lister's first essays — happily this great man has lived himself to see his own splendid vindication. How the improvement of the microscope lifted physiology and pathology into new realms of discovery is a familiar story, but one perhaps not fully comprehended by those who have not learned how the want of this instrument arrested the work of Harvey in his labors on the problem of generation, as well as on the circulation of the blood ; or, on the other hand, how its use by forwarding the work of Bichat founded modern physiology afresh; how by the microscopic discovery of the human egg the mystery of generation was unveiled by v. Baer in lS'i7; how by forwarding the work of Schleiden and Schwann the realm of the cellular pathology was opened out, afterwards to be cultivated so successfully by Virchow.

Illuminated by such cross-lights new fields of clinical medicine, which on the old method of Hippocratic observation Sydenham had carried perhaps to its extreme limits, stood revealed by the labors of the great French school of Laenuec and Magendie, of Louis, Andral, Cruveilhier, Trousseau and Charcot. Laennec gives me the impression of being one of the greatest physicians in history ; one who deserves to stand by the side of Hippocrates and Galen, Harvey and Sydenham. But without the advances of pathology Laennec's work could not have been done; it was a revelation of the morbid anatomy of the internal organs during the life of the patient.


It were too long a task for us now to turn to other fields to note how the discoveries of the great chemists of the last two generations threw light upon pathogeny ; how those of the biologists gave a new meaning to the study of human morphology. You know already how natural knowledge advancing from many quarters was extended, and especially in the realm of medicine which we are now contemplating. Each great branch of natural knowledge has its own Hinterland which it surveys for the common good. Nor shall we forget that a like activity in other departments of human intellectual enterprise has enlarged the conceptions of physicians even where the facts stood aloof from their ordinary conversation. As Locke and Hume told for medicine in the eighteenth century, if indirectly yet none the less enormously, so in our own century Lyell, Darwin, Spencer and others, by profoundly modifying the whole attitude of our minds towards Nature, have given to physicians a new standpoint from which to survey their particular world.

It would now seem that even in medicine the experimental method, which seemed forbidden to her, is making its way after all. If pathology never can become a science of direct experiment in the sense that physiology is so, it makes use of it as a second line of advance. If we cannot produce a pneumonia we can study the results of cutting a nerve. In physiology the number of variables is embarrassing, yet in medicine it is far greater. No two cases of a disease are alike — temperament, race, season, circumstances, all variables, conspire to modify cases and inferences.- It will always, indeed, be impossible in any branch of the biological sciences to isolate conditions and to repeat them as in chemistry and physics. Yet, as I have said, an approximation to such means is manifested in the bacteriological laboratory where pure cultures are separated, their toxines tested in proportion to body weight, antitoxins calculated, and immunities predicted.

It would seem to be, in the study of immunities, that the physician will first attain the reward of scientific research in prediction. A science which cannot predict quantitatively is in an inchoate stage. Multiplication of corpuscles, like the increase of cell growths in a hypertrophied heart or kidney, is but a case of compensation — a measure of resistance to disturbance.

Whether we regard it from the static or the dynamic point of view, the conception of the vis medicatrix nature gains newer force every day. Our blood and other corpuscles are microbes, their serums are factors in natural processes, and are regarded as healthy or unhealthy as they happen to be convenient or inconvenient at the moment of observation. Glands, such as the liver and kidney, are aggregations of microbes specialized for particular functions, and generate juices which are factors of nutrition, and not only of negative, but, as we have learned so well in respect of the thyroid, of positive influence in the balance of its manifold processes.

From experiment and observation we find that this reserve energy of the body in its various parts is enormous. How large is the view of the province of therapeutics thus presented to us we may see in the rapid advance of what I may call physiological remedies. As hygiene is to the state of health, so is physiological medicine to that of disease. By


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physiological medicine I mean the use of the ordinary functions of the body in counteraction of contingent or inherent perils.

It is a common but I think a shallow reproach to modern medicine, that, with all the advance of our knowledge of pathology, therapeutics stands where it did in the time of our fathers, or has even fallen back, in so far as a certain sceptical distrust of empirical remedies has discouraged the continued use of remedies which the wisdom of our fathers had discovered by practice and observation. It is said that we will not use the most respectable of traditional remedies unless we have some notion of its mode of operation. It is possible that the invaluable work which a scientific scepticism has done for us, not in therapeutics only, has been attended by some destructive effects which are to be regretted. I think, however, it would be diflficult to bring forward many instances of the kind in our own case ; while, on the other hand, the pruning and clarifying which our practice has undergoue far outweigh any such temporary disablements. The truth is that the cry itself is a shallow one. I will not stay to assert that modern surgery, the brilliant progress of which is in all our mouths, is progress in therapeutics, the division between surgery and medicine being a division of convenience, a division to which a mere practical and temporary usefulness only is to be attributed. Are we to forget, for instance, how the prognosis of peritonitis, of obstruction of the bowels, of pleuritic effusions, of encephalic tumors, of perityphlitis, of pelvic diseases, of ovarian ascites, and so forth — a prognosis in troops of cases turned from sadness to hope — is not to be called progress in therapeutics because not infrequently the method is carried out by the skill of another hand ? It might as well be asserted that the modern scheme of feeding in fevers, because it is carried out by trained nurses, is no therapeutical progress. Nor will I admit, even in the sphere of drug therapeutics, that our progress is contemptible.

When we regard the additions nuide to our hypnotics, the discovery of the value of the nitrites, of the bromides, of arsenic in pernicious anemia, of the salicylates, of the antipyretic, hypnotic and antalgesic group, of the antiseptic treatment of diseases of the skin, of the antitoxic treatment of diphtheria, of the thyroid treatment of myxcedema; when, again, we realize the greater precision of our use of the older empirical i-emedies, as of digitalis, in the preciser administration of remedies in syj^hilis, in the injection of alcohol and ether, of apomorphiue, of ergotine of strychnine, of hyoscine, of cyanide of mercury ; when, once again, we think how much more accurately we discriminate our means in the treatment of phthisis, of dyspepsia, of fevers, of palsies, central or peripheral, we may confidently take encouragement and meet those adversaries in the gate who say that therapeutics has made no considerable progress. At the same time, we may well take to heart the lesson which such criticism may teach us. While we have learned that empirical knowledge, although a power against ignorance, is of less avail against the more ordered and living knowledge of a maturer science, on the other hand, for this very reason, we are now, perhaps, apt to despise unduly the traditional remedies which rest their claims to usefulness more on empirical than on reason


able grounds. For in the use and practice of all methods we must remember that medicine is an art, that it is something more than an applied science.

Our art has always been, and probably long must be, in advance of scientific direction and explanation. Moreover, as in all arts, more than knowledge is needed, namely, common sense, rapid and firm decision, and resourcefulness — faculties by no means resting upon intellectual conceptions, but on a certain virility of character not to be got from books. It is no uncommon experience to see physicians of high intellectual subtlety, of great learning and of a pretty wit, lose themselves in the practice and even in the exposition of their profession, because in them the critical faculty exceeds the practical. Indiscriminate doubt, however valuable an attitude of mind in the laboratory, is mischievous in the field of action, where a keen determination to make the best of imperfect instruments, to use any accredited means rather than none should be the dominating impulses — impulses which enlist also on the side of the physician the hope and animal si^irits of the patient ; for, after all, the practice of medicine contains no small element of " suggestion." Furthermore, the fastidious spirit, which I have endeavored to indicate, is, on the whole, opposed to progress, as, even in thought, it lends itself too readily to irresolution, and irresolution is the quick way to indolence. On the other hand, I need not warn you that practice without continual scientific re-edification soon degenerates into stereotyped and sterile routine.

Once more, when we are twitted with the discovery of manifold new diseases, without the discovery of any means of dealing with them, we may reply that not only are we discovering the course and ends of these destructions, not only are we discriminating between this series of symptoms of dissolution and that, but we are engaged, as I will remind you again, in the study of origins. We are no longer satisfied to contemplate the wreckage of disease, but we are earnestly hunting out the processes in which such and such deviations from health took their being.

The study of origins, then, is not only the new method of modern criticism, of modern history, of modern anthropology, of our reading of the evolution of the universe itself from elements which even themselves are falling under the same analytic inquiry, but the study of origins is leading to a revolution in our conception of therapeutics, as of all these other studies ; a revolution which as yet we have not fully understood. This revolutionary conception is that death is not to be driven away by the apothecary, not by auy cunning compilation of drugs, but is to be prevented by the subtler strategy which consists in knowing all the moves of the game. Few and simple are the diseases which can be expelled by leechcraft, as we expel a worm. The medicine of the future will consist in setting our wits to nature, in recognizing that when evils have befallen us there is no counsel, and that in the simple beginnings of things are the time and place to detect where stealthy nature, atom by atom, builds and unbuilds, feeds us or poisons us. To disentangle the clue we shall not pull at it anyhow ; we shall anxiously seek the beginning of it, thence to unravel its windings.

There is an old saw that Nature takes as much trouble to


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make a beggar as a king. She does not make diseases to sit so loosely that they can be expelled by violence or bound by a charm Much of curative medicine, in the vulgar sense, will thus be swallowed up in preventive medicine. We shall not wait till we are half dead before we take in hand our disorders; abnormal processes, not their results only, will be our fruitful study.

Another feature of modern therapeutics is the use of Nature against herself. We learn, as I have said, to play the game; we are not content to sleep at our posts till we must fight desperately, against a checkmate, but we keep in touch with the enemy all through, and use the same means. Thus, by the side of preventive medicine, we learn that hygiene, in its largest sense, is also to be our guide. Instead of trusting to prescriptions for alleged specifics, which have no little kinship with magic and antidotes, we ally ourselves with Nature's own forces. For example, if we cannot prevent infantile palsy, which soon, perhaps, we may do, we shall attempt its cure, not by idle drugs, but by strengthening the physiological factors of life ; by the use of massage, electricity, warmth, and so forth. As we further discover the physiological factors of life, we learn to supplement the failing juices of a gland from other sources in the economy; by learning the distribution of heat in the body, we find that fever can be controlled by conductions of heat by cold baths and otherwise ; by a better knowledge of the mechanics of the circulation, we arm ourselves with means for regulating its currents by baths and gymnastics and the like. Even iu the sphere of drugs themselves we are, year by year, deposing this drug and that from the place of specifics, as in the case of quinine, and putting them iu the ranks of preventive agents, and, with respect to others, we are carrying our study of origins into their qualities, as well as into the healthy or morbid processes over which they have power. Tlie relation of atomic weight to physiological effect, the experiments by which, on slight substitution of one molecule for another, we convert compounds from cne kind into another and widely diverse kind, from convulsants, for example, into narcotic or paralyzing agents, we throw light not only on their own properties but also on the secret processes of the animal body itself. I will not stay to illustrate in the same way the parallels between the members of different series, nor the advances, of late the least active, by the way, of physiological chemistry, and of chemotaxis, and of the study of the behavior of serums and the like within the more comprehensible range of the test tube. Such considerations impress us again and again with the importance of the union of practical and laboratory or theoretical work iu the same jiersou and in the same schools. No scientific observer who has not made medicine more or less a practical study can be as well equipjied as otherwise he would be to investigate such subjects as these.

The modern hospital must be the modern laboratory of medicine. As in the sixteenth century the great laboratories of anatomy sprang into existence, in the seventeenth the laboratories of physics, in the nineteenth the chemical (Liebig), the physiological (Ludwig), the chemico-physiological (Hoppe-Seyler), the pathological (Virchow), the hygienic (Fettenkofer), so the clinical laboratories initiated but


the other day in Germany by v. Ziemsseu, Curschmann, and in the United States by Pepper, are the factories out of which the new medicine is to come— the medicine which, penetrating into the intimate processes of Nature, learns to turn Nature to her own correction. The clinical laboratory is to be the sceue of the study of the origins of disease.

What are the aids and dangers of "specialism" in these advances? Against this tendency iu modern studies and practice an outcry has been raised which, if a little unintelligent in its way of expression, has not been without justification. In advancing civilization the ajj plications of thought, as well as those of labor, must be divided and strbdivided. The activities of the mind are at least as multiform as those of the traveler in the world, and it is impossible for all explorers to follow each other over all ways. As pioneers increase in number and in adventure the more are they divided from each other, the more diflScult is it for each to make himself master, even by report, of the work of all. This general law is as true for medical inquiry and for medical practice as for electricians or naval engineers. Not only so, but we may say that, in the sciences, men are not traveling over one world only, but over many. If within each world of mathematics, physics, chemistry, and so forth, explorers separate and travel out of sight of each other, what shall be said of the remoteness of explorers in these several worlds ? Yet these several worlds of the sciences are not as Mars to us, but as the various kingdoms of the earth. What goes on in each is of the utmost importance to all, and as civilization advances becomes not of less importance, but of more and more. Herein lies the justification of what I have called the outcry against specialism. The protestants have perceived this inter-relation of all knowledge, and they have foi'eseen both the narrowness of spirit and the lameness of practice which must come of such a disintegration of parts of such an isolation of efforts. Nay, they may not improperly conceive that a less amount of knowledge, duly systematized, may be of more value in affairs and in philosophy than more knowledge in scattered parcels. If the outcry has been somewhat unintelligent, this has been not iu the perception of the kind of injury to learning. This is to be credited to them as a virtue. But in the want of perception that some division of labor is inevitable, the protestants have seemed to care less for the advance than for the system of learning, and, indeed, to have set practice in some antagonism to learning.

We shall henceforth perceive, I trust, that this new movement comes from the deeps ; that it is not by withstanding the very conditions of modern progress that we shall secure its balance, its concert and its sanity. Happily, evolution will be found still to consist not in differentiation only, but also in integration. As labor is divided, an organization of knowledge must proceed step by step with the division. Specialism will have its disadvantages, as all exclusive aspects of things have them. In practice, specialism will have its charlatanry, as omniscience has had it. It is only by the increase of discernment and education in society at large that the genuine and humble children of Nature will be known, and it is by progress in its best sense that such discernment and education are to be extended. 1 do not hesitate to say that even within


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my own lifetime these qualities in the relation of society towards onr profession have not only increased, but have waxed abundantly, and thus is a medium formed in which the remoteness and alienation of specialized workers finds a corrective. The worker in all subjects, even in the larger operations of ordinary trade, learns that he, too, must think of the whole as well as of parts and details. Even money cannot everywhere be broken up into small change; commerce can no longer be a piecemeal affair. In the tradesman, indeed, is engendered a mind in favor of breadth of view, and even in the man in the street is begotten a hazy notion that there cannot be, as in ancient Egypt, a physician for every part of the body. There is no mean in Nature but Nature makes that mean ; if these qualities of intellectual concert, of scientific formation of mind, of breadth and sagacity are needed, they will be found, and the way to them will be found also. Indeed, such conceptions of education are gaining apace on the general mind, though their full bearing is not yet understood. It is this very breadth of mind which is aimed at by educational reformers, by those who prize education before mere acquisition, who assert that, with the greater complexity and definiteness of knowledge, associations of workers and certain harmonies in their results must be brought about.

Those, then, who resent the specialization of science, as of other fields of human work, although they are wrong in their way of opposition, have hold, nevertheless, of an important truth, and they agree with the Thracian King Zamolxis, who was also a god. Zamolxis observed that "as you ougiit not to attempt to cure the body without the head, or the head without the body, so neither ought you to attempt to cure the body without the soul, and this,"' he said, "is the reason why the cure of many diseases is unknown to the physicians of Hellas, because they are ignorant of the whole, which ought to be studied also, for the part can never be well unless the whole be well." (Cliarmides.) Although then we cannot hope that every physician shall be a man of science, we may secure that he shall have the scientific habit of mind, for thus, as we have seen, he will be habituated to lay out his knowledge systematically, to trace phenomena to their sources, and to see his own facts in their due relation to other facts. This is the philosophic temper which cannot be learned from books and rarely without tradition and converse with gifted men.

Some disciples are more apt to receive this grace than others ; some men, many learned specialists, are incapable of wise scientific judgment; no examination can test it; no memory can secure it; it is in part a product of time, which accepts what is good and i ejects that which is transitory. It is to be assimilated from organs of knowledge, such as universities, and not from mere polytechnic institutions. It is the highest reward of the teaching from a living source, for, as Professor Butcher says, "the test of life is to impart life."

Too many students pass through their schools without an awakening of their minds. They believe their superficial knowledge to be exhaustive, and they become the mouthpieces of ready-made opinions.

I should be an ill bird were I to say anything to-day in depreciation of the value of lectures, of my own wares. In bygone times I have said much in depreciation of tliem, urg


ing that they are survivals of a time when books were scarce and dear, and when knowledge was looked upon as spoonmeat. I have helped forward the cry that the laboratory must be the future living source of knowledge and of inspiration. While men were blind to this new truth it was necessary to urge it to the hindrance of other needs which men were not likely to forget. Now that the battle is won, and the laboratory is everywhere with us, we may turn again to consider what there is in older methods which we would not willingly lose. In lectures we may still find the virtues which flow from living converse with thoughtful men who have been over the field of our studies before us, who can show us how their minds worked, how they systematized their knowledge, how they came to see it in the light of other researches, how they inspired it with human interest. For such ends as this we must have no mere retail dealer in knowledge for our lecturer. In all universities it .is now recognized that, except for tutorial work, the lecturer to beginners must be the leader in his faculty. He it is who can give the true first set to the thoughts of young men who are entering into the subject of their lives ; older men and advanced work may well be undertaken by demonstrators.

Thus far I have considered specialism and breadth in respect of the education in our profession, but a larger problem lies before us, namely, that wider culture which lies beyond the confines of all professions. One of the difiicult conditions of our own generation is the urgent pressure on young men and boys by reformers and anxious parents who desire, not unreasonably, to mold their sons into money-making machines at as early a date as possible. When I took my degree at Cambridge our course was, in the first place, to take an arts' degree, at that time only to be had in the arts. Thereafter came the natural-science studies, with their tripos, and after that again the clinical studies proper to our professional life. This course occupied us up to the age of twenty-five, at least, and in some respects it was a far better education than we now bestow. Now, from the first hour of the medical student's arrival in Cambridge he is too often turned at once into the narrower channel of his special calling, and he even tries to pick up a precarious instruction in clinical work while he is ostensibly at work on the preliminary sciences. Nay, such is the pressure of the times, parents and teachers are getting impatient even with this rate of speed, and are insisting that even at school time is wasted in classical and other broader studies which might be utilized for science, and that men should come up to the university ready to "specialize" farther still. Among other strong arguments in favor of this reform is this : That whoso means to practice surgery should acquire manual dexterity, and that this advantage cannot be acquired by the ordinary man unless he begin to educate his plastic fingers in early youth. This argument I will dismiss in a word by saying that, in my opinion, every man should be educated in a handicraft or mechanical art of some kind during his early youth. The importance of this element of education is curiously forgotten even by such a mechanical race as the English and American. So much for surgery; the boy who has learned to use a lathe or to make a chest of drawers will have fingers apt enough for surgery.


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There is, moreover, another means of education most useful in early life, namely, that of measurement. At every national school youths of both sexes should learn to measure accurately to thousandths of an inch and to hundredths of a grain ; thus the eye is taught with the hand, and, what is of more importance, the mind is trained to know what accuracy means. These occupations, invaluable in training of character and skill as they are, would add nothing to the burden on a growing brain.

Of the sciences, those of memory and observation only should have a place. The mind of youth is in a stage when the imagination, rather than abstract thought, should be cultivated. To collect natural objects, and thus to be drawn into the haunts of animals, into the habitations of plants, and to see the structure of the earth, excites and enlarges the imagination and strengthens the memory at a time when these faculties are ripe for culture. I have never happened to meet a young man, educated in abstract science at school, who seemed to me to have used his time to the best advantage. If, for the present, it has led to success in the narrowest sense, I think we are entering even now into a generation when success must be based on a larger education than this — on an education in letters and in the humanities, as well as in the laws of the material universe. Rousseau well said we should not teach children the sciences, but give them the taste for science.

We are apt to forget that even in these days of science, advancing by leaps and bounds, that still the greater part of man's life is spent in the expression of his thoughts and in converse with mankind. He should, therefore, have learned to handle the ideas which concern himself and his fellows, not only in their material conflict with Nature, but also in those higher spheres of history, ethics, politics and social aspiration for which alone man can be said properly to live. If we regard the mastery of modern man over Nature in any other light than as clearing for us a larger base for a reconstruction of societies which shall be more wise, more humane, more beautiful in spirit than in the past, there would be nothing but sadness in the contemplation of modern life, with its "gay afflictions, golden toil." No doubt we must rebuild our material home, but we ourselves also must be born again. (Newman).

The uses of learning Latin and Greek lie in this — that in these studies, more than in any others, the ideas which concern man in his highest endowments of mental, spiritual and social life are manifest, and not only so, but are manifested in languages the most virile and beautiful the world has known. Latin and Greek are called dead languages. If so, the Hermes of Praxiteles and the Venus of Milo are corpses. Latin and Greek contain in perfection of form not modern science, but that for which modern science exists — the best that man has lived and thought. It would be a narrow pedagogy which should assert that strong and penetrating thought, and noble and chastened imagination are to be found only in Latin and Greek ; we may be thankful, indeed, that the English language is or has been as noble an instrument, and enshrines at least as fine a literature. Yet it has been said long before our time


that to know one literature only is to wander in the sphere of letters without a scale of relative dimensions — to lose the faculty of comparison for lack of standards of comparison. To learn to speak a language like a parrot is but to train a mechanical memory. Latin and Greek, however, although they contain the finest records of human thought and action, are, as I have said, not the only shrines of letters, and the noble literatures of France, Germany or Italy may take the place of either of them, and carry the additional advantage of common usefulness.

But do not let us forget that our calling derives its honor not from its power of repairing the carnal body ; were this its only title to respect it would take a low place in the hierarchy of professions. Those professions which deal with the ends which alone make life worth preserving — such as that of the law of religion, philosophy and of the fine arts — would in such case regard our occupation but as a higher kind of farriery. The glory of our profession, from the hour when Hippocrates, in that oath wherewith like a trumpet, the notes of which reverberate still through the ages, summoned us to take our place in the forefront of the fight, has been that we are concerned not only for mankind, but for men. The ideal side of a physician's life is that he brings healing or solace to his human fellow. The Greek philosopher, like the modern socialist, would sacrifice man to the State ; the priest would sacrifice man to the Church; the scientific evolutionist would sacrifice man to the race. Yet, while all these elements of cooperation and of aspiration work together for good, we thankfully see that, after all, the tendency of civil evolution, as of Christian ethics, is to use society as a means for man himself, as a means to purify and to elevate the individual soul. The physician, then, is more than a naturalist; he is the minister not only of humanity at large but of man himself. Thus it is that the humblest of us, and he who labors in the darkest and most thankless parts of our cities, is never a drudge; in the sight of the angels he is illustrious by the light of his service to men and women. The man of science can tell us delightful things about birds, flowers and wild life, for all life is various and touching; he can tell us queer and uncomfortable things about our insides, amazingly useful things about steam and electricity, but at bottom, when the marvel is over or the material gain is won, all this grows stale. Ideas concerning the harmony of the spheres, concerning cosmic evolution, concerning the inhabitants of Mars, are prodigious; they may uplift iis sometimes with a sense of the greatness of man's inheritance, but alone they are cold and unsatisfying. The child of his age feels that a sonnet of Wordsworth, a flash of Browning's lamp into man's heart, an idyll of Tennyson give us thoughts worth more than all the billions of whirling stones in the universe. In strengthening and cherishing this inner life of his brother and sister, happily, the physician has many fellows, but the physician alone among them all holds sacred the lamp of the personal life for its own individual sake; he alone forgets Church, State, nay, even the human race itself, in his tender care for the suffering man and for the suffering woman who come to him for help.


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[No. 93.


ON REFRACTORY SUBCUTANEOUS ABSCESSES CAUSED BY A FUNGUS POSSIBLY RELATED

TO THE SPOROTRICHA.


By B. K. Schenck, M. D.


On November 30, 1896, A. W. presented himself at the surgical cliuic of the Johns Hopkins Hospital with an infection of the right hand and arm of an unusual nature. The primary point of infection was on the index finger, whence it extended up the radial side of the arm, following the lymph channels, and givingrise to several circumscribed indurations, which were in part broken down and ulcerated.

One of these indurated areas was incised, and deep in the tissues a thimble full of gelatinous, puriform material was found. A culture from this fluid was made on gelatin. At the end of four days there was a growth of the staphylococcus epidermidis albus, besides which several other distinct, white colonies, raised from the surface of the medium appeared. Cultures made on agar from the latter colonies showed after three days in the thermostat, an abundant growth of an organism, not resembling the bacteria and evidently present in pure culture.

On December 7, under aseptic precavitions, an indurated area just above the elbow was incised, a,nd a small piece of tissue removed for microscopical examination. Two cultures were taken on slant agar from the puriform contents of this nodule. In three days both tubes showed a growth in pure culture of the peculiar organism previously obtained.

On December 14, Dr. Finney made the following note : " Ulcerated area, size of finger nail, over dorsal surface of second joint of index finger — right hand. Edges much undermined. Sero-purulent, gelatinous discharge on surface. A second, similar ulceration between second and third metacarpal-phalangeal joints. An indurated line, 1 to 1.5 cm. in diameter, follows along dorsum of hand and forearm, with here and there ulceration.

On the arm there are two indurated points, which have been excised, the highest one being in the middle of the arm. At the junction of the upper and middle thirds of the forearm there is an indurated spot, the size of a bean, situated to the outer side of the main line.

Epitrochlear gland not involved. Axillary glands palpable, but not especially enlarged."

Dr. Finney then removed with aseptic precautions a second, larger piece of tissue for microscopical examination.

The patient gave the following history : Age 36. Marked family history of tuberculosis. Patient has suffered from phthisis for jiast twelve years.

During the latter part of August, 1896 (3 months before visit to the Johns Hopkins Hospital Dispensary), while working at the iron worker's trade in St. Lonis, the patientscratched the index finger of right hand, on a nail, while reaching into a red lead keg. Shortly after this a small abscess formed which was opened with a pin. A slight amount of watery fluid escai>ed, which patient thinks did not look like pus. In about three weeks the ulcer between the second and third metacarpal-phalangeal joints appeared. This was treated at the St. Mary's Dispensary (St. Louis). The inflammation traveled up the arm, and in about seven weeks after the


From the Pathological Laboratory, Johns Hopkins University and Hospital.)


infection seven similar abscesses had formed. These were opened, and a watery discharge escaped. About this time a " waxen kernel," size of a walnut, appeared in the axilla. It was not especially tender and disai>peared in two days. While in St. Louis the arm was bandaged daily with bichloride and carbolic dressings. The patient thinks that he had no fever, and says the pain was very moderate. Being unable to work he returned to his home in Baltimore late in November.

Physical examination on entrance showed evidences of advanced tuberculosis of the lungs, and the sputum contained numerous tubercle bacilli.

The infection involving the hand and arm proved very refractory to treatment, the last lesion, at point of primary infection, not granulating until late in February, 1897.

The organism which was assumed to be in etiological relationship to the above-described lesions was obtained in three cultures from two different foci of the disease: Once from one of the lesions in the forearm, admixed with the skin coccus, and twice from one of the lesions in the arm, in pure culture.

Cultural Characteristics. — Cultures were made on all our common media, including plain, glycerine and sugar agars, plain and sugar bouillon, plain and acid gelatin, milk and potato. With the exception of the milk all the cultures developed luxuriantly.

Agar. — At 37° C. the growth is first apparent at the end of 48 hours, when the tract of the needle is marked by a faint line, slightly opaque, which under a low magnifying power is seen to be made up of minute colonies, with feathery outline, resembling somewhat minute snowflakes. At the end of 73 hours, the line of inoculation is sharply marked by an opaque, white, moist growth, having well-defined edges, raised from the surface of the media. Here and there at the periphery are isolated colonies. As the age of the culture increases — about five days — the growth extends very much in thickness and but little peripherally. The surface is corrugated, the edges lobulated and sharply defined (Plate I, Fig. b).

In cultures of ten days and older the growth is very thick ; the surface is rough, corrugated, and stained a dark brown color, the shade at the periphery being deeper than in the centre. The medium also becomes stained.

Colonies of three days appear to the naked eye as round, raised, ntoist dots, 0.5 to 1 mm. in diameter. Under the low power they appear to be made up of a feltwork of minute fibrilla3, dense in the centre, lighter at the periphery, with a feathery outline." Scattered through this meshwork are many minute dots, consisting of the couidia.

Colonies of ten days are characteristic. They are round, sharply circumscribed, and elevated from the surface of the medium. The surface of the colony is brownish, and marked


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by radiating lines proceeding from centre to periphery, evidently caused by the drying and shrinking of the growth (Plate r, Fig. a).

By a comparison of the development on glucose, lactose and saccharose agars, little difference is to be made out during the first two weeks. lu cultures older than 14 days, however, the growth continues longer and becomes heavier on glucose than on plain agar, and in all the sugar media there is more discoloration both of the growth and of the substratum.

Gelatin. — The growth in stab cultures develops slowly. It is much more abundant in the upper part and spreads laterally over the surface, while the development in the depth is feeble, being scarcely perceptible in the lower third. At the end of six days there is slight liquefaction of the medium. The organism grows somewhat more luxuriantly in acid gelatin, and the liquefaction is greater.

Bouillon. — -Growth in bouillon is fairly abundant in three days, and appears as little, cottony tufts which settle to the bottom of the tube, leaving the supernatant fluid perfectly clear. As growth proceeds, it tends to spread up the side of the tube. The reaction of the bouillon is not altered.

Polnto. — At the end of 48 hours the growth is abundant. It is elevated, the surface is moist and the edges lobulated. After several days the surface of the growth becomes rough and wrinkled, the edges discolored and the potato darkened.

Milk. — There is no change produced in the tint of litmus milk at the end of seven days, and no coagulation takes place. The organism does not seem to thrive in this medium, film preparations showing only very small numbers.

Fermentation Tests. — Stab cultures in glucose, lactose and saccharose agars show no gas bubbles. Glucose, lactose and saccharose media, made from sugar-free bouillon, prepared according to the method of Theobald Smith, placed in fermentation tubes, give an abundant growth in the aerobic bulb, the anaerobic tube remaining clear. There is no gas formation.

Relation to Oxygen. — No growth develojis in culture placed in the Buchner jar.

Vitality. — Growth which has remained on potato for eleven months again develojjs when placed in sterile bouillon. Agar cultures retain their vitality for at least nine months. To test the resistance to low temperatures, portions of growth from bouillon were placed in sterile water and allowed to remain in cold storage, at a temperature of 28° F., for ten weeks, after which they proved to be alive. In these cases actual congelation did not take place. When frozen for this length of time, however, they lose their vitality.

The vitality of cultures is destroyed by exposure to a temperature of 60° C. for five minutes.

The optimum temperature for development is between 20° and 37° C.

Morphology and Development. — For many of the points relating to the morphology and development of the organism, I am indebted to Dr. Erwin F. Smith, of the United States Department of Agriculture, Washington, who has given much time to the working out of the more difficult and obscure points pertaining to its life history and classification.


I take this opportunity of acknowledging the great value of his help and advice, and of expressing my appreciation of his kindness.

Cover-glass preparations made in the ordinary way, from agar and bouillon cultures, show two forms : (!) a thread-like, branching form, or mycelium, and (2) oval, spore-like forms, or conidia. In an unstained specimen the mycelium is seen to be made up of a doubly contoured thread, branching irregularly, but not very profusely, and never dichotomously. The protoplasm appears granular. The diameter of the threads presents considerable differences, with an average of 1.5 to 2 microns. The conidia are elliptical or ovate, many of the latter forms being distinctly ajjiculate. They are also doubly contoured and granular. The spores from the solid media are rounder and smaller than those developing in bouillon. They vary in length from .3 to 5 microns.

The organism stains well in all the basic dyes, and is not decolorized by the Gram method. Stained preparations show marked irregularities in the coloring, especially of the mycelium. The conidia frequently show a small unstained area near the smaller pole of the spore.

In smears made from agar or bouillon it is not possible to determine the relation which the conidia bear to the mycelium. Occasionally, however, one or two spores are seemingly attached by the smaller end to the side or end of the mycelium. This relation can be much more clearly brought out by observing their development in hanging-drop cultures, the description of which I quote from Dr. Smith's report of April 13th. The drawings are also reproduced from Dr. Smith's sketches. "When a little of the bouillon containing the colorless, elliptical or cylindrical conidia was inoculated into hanging drops of alkaline beef broth, and set away under a moist bell jar for forty-eight hours, there was an abundant growth of the fungus, the spore-bearing branches of which, being undisturbed, retained their spores in the normal condition, and the appearance of the fungus under such conditions is shown in the sketches (Figs. 1 to 3). Here from three to six or more spores were to be found, quite commonly clustered at the tips of the spore-bearing branches. Naturally, if the fungus had been disturbed by shaking or lifting out into a drop of water, most of these spores would have been readily washed away, leaving only one or two, that is, leaving such appearances as are shown on the drawings made directly from the bouillon cultures" (Figs. 4 and 5).

The life history of the organism was studied from bouillon cultures and from hanging drops. The conidia germinate by sending out one or more straight, unbranched germ tubes, sometimes from the end, again from the side. These germ tubes give off spores of the same character, the attachment being either terminal or lateral, by means of short pedicles or sterigmata (Figs. 6 and 7i. Other seemingly similar spores push out into the branched mycelial forms, which in turn produce a new generation of conidia.

The existing classification of the fungi is a purely artificial one and is incomplete in many particulars. On this account it is often very difficult to determine where an organism is to be classed. Dr. Smith has kindly gone over the points in


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regard to the classification of this organism, and his conclusions are as follows :

" It is a couidial fructification only, and on this account it is impossible to give more than a guess as to its position in the natural system of classification. To determine this the perfect spore form would have to be obtained. It can only be put into a form genus, in other words, into some artificial system of classification, until the natural one is known. It seems to me that it might be classified in either of these genera, according to the system given in Saccardo's Sylloge Fungorum, which is the commonly accepted standard of the artificial classification.

(1) \t\s wot wwWke i\\e Botrytisbassiaiia, the muscardine, or calicino disease of silk-worms, and might therefore be regarded as a Botrytis. Against this classification, however, it is the fact that the spore-bearing branches are not erect, which is a rather trilling distinction. It might also be classed as (2) Sporotrichum, but inasmuch as it becomes dusky when it is old it might also be classed as (3) Trichospormm. Saccai-do separated out the dusky forms of Sporotrichum into a separate genus under this name. The mere difference in color, as we know from cultures of many fungi, is often a vei-y trifling matter, the early stages of a fungus often being white and the later stages dusky or even brown. On this ground I think that his distinction is of no value, and I think that we may throw out the genus Trichosporium altogether. As regards the other two, my own judgmeut would be that it fits best into Sporotrichum. In his Sylloge Fungorum Saccardo describes more than one hundred species of Sporotrichu?n, but most of them are described very imperfectly, and I cannot identify this fungus as belonging to any one of them."

The tissues removed for microscopical examination present the characteristics of a chronic abscess, consisting of inflammatory and cicatricial tissues. On the inside is a layer of necrotic material, nest a zone of leucocytes, and outside newlyformed connective tissue, in which are several minute secondary abscesses.

Numerous sections stained by theWeigert and Gram methods failed to reveal any micro-organisms whatever. Sections stained for the tubercle bacillus by the carbol-fuchsin method were also negative.

Animal Experiments. — 4 dogs, 6 guinea-pigs, 1 rabbit, 1 wild mouse and 3 white mice were employed. The results were as follows :

Dog I. The external jugular vein was opened, and 1 cc. of a suspension in salt solution of the orgauism was introduced. The dog remained well, and was killed on the 30th day. Nothing unusual was made out at the autopsy. All cultures were negative. The microscopical examination of the organs revealed nothing abnormal.

Dog II. Inoculated subcutaneously on the abdomen with 2 cc. of a 36-hour plain bouillon culture. On the next day there was an induration at the point of inoculation, followed in 24 hours by the formation of a tumor about 3 cm. in diameter, which on palpation gave evidences of fluctuation and tenderness. This remained practically unaltered for ten days, and then gradually became smaller and firmer to the touch.


The dog remained apparently well, but was killed on the 28th day. Nothing was made out in the internal organs, and cultures from these were all negative. The tissues around the point of inoculation were excised and found to consist of firm scar tissue, in the centre of which was a small cavity containing a few drops of a gelatinous fluid. Agar tubes, inoculated with several loops scraped from the walls of the cavity, showed on one six colonies and on the other eight colonies of the organism. Bouillon cultures were also positive. However, no organisms could be demonstrated in cover-slips.

Microscopical sections through the wall of the cavity showed advanced cicatricial tissue. Numerous sections, stained according to the Gram and Weigert methods, failed to reveal the organism.

Dog III. Inoculated subcutaneously over the abdomen in a manner similar to Dog II. A second series of injections was made over the thigh in order to ascertain whether or not enlargement of the inguinal lymphatic glands would follow. Induration developed at the jioints inoculated, followed in two days by fluctuation and tenderness, the process increasing until the end of the first week, when the tumors became firmer and smaller. At no time were the inguinal glands palpable. Dog killed on the 21st day. The internal organs appeared normal ; cultures from them remained sterile. Microscopical examination of the organs negative. At the local lesions nodules of fibrous tissue, containing small cavities similar to those in Dog II, were found. These little pockets contained a scanty amount of gelatinous material.

Smears from the cavities were negative.

Cultures from both lesions were positive, the organisms being rather few in number. They were, however, more abixndant than in cultures from Dog II.

Microscopical examination of the fibrous tissue revealed the same condition as already mentioned and micro-organisms could not be demonstrated.

Dog IV. Inoculated subcutaneously in a similar manner, the induration and swelling took place as before, and on the fourth day, when the process seemed to have reached its height, the lesion was excised. The nodule was larger and less firm than the preceding ones, the cavity was greater and was completely filled by a thick, yellowish-red, gelatinous material, smears from which showed fibrin and red-blood corpuscles in small amounts, large numbers of polymorphonuclear leucocytes and a few objects similar in size and shape to the couidia characteristic of the organism introduced. None of these bodies were seen in leucocytes, all being extracellular.

Cultures from the walls of the cavity showed a very abundant characteristic growth of the organism.

Microscopical examination of the excised tissue shows the lesiou to be a focus of inflammation. The walls are made up of the subcutaneous areolar tissue, forming a loose mesh work, the spaces of which are filled with coagulated albuminous material and leucocytes. The pus cells also infiltrate the connective-tissue stroma. At the edges of the cavity the connective tissue is denser and the infiltration of the leucocytes more marked. The cavity is lined by a mass of coagulated serum and necrotic pus cells. In specimens stained with hannatoxylin and eosin, it is not possible to make out the organisms ; but sections


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stained by the Weigei't method reveal them in hiri;e iiumljei-^, situated principally between the inner layer of cell detritus and the adjoining zone of infiltrated connectis-e tissue which forms the wall of the cavity. For the most part they are associated in clumps of from six to thirty elements, but many occur singly and in groups of two or three. They occur mainly close to the edge of the cavity, but now and then may be situated singly or in clumps in the connective tissue stroma.

The organisms are of irregular shapes and sizes. In form they are round, oval and club-shaped, the last predominating. Tlie smallest round forms are from one to two microns in diameter, while the long, club-shaped forms vary from two to four microns in length. These club forms are of irregular diameter, swollen at one end and tapering at the other; the staining is slightly irregular, there being often a small area near the centre taking the stain less intensely. The oval antl round appearing forms correspond in size to the varying diameter of the club forms, and give one the impression of being cross-sections of the latter. These organisms are frequently seen within the bodies of both leucocytes and large connectivetissue cells. Many, however, are extracellular (Plate II, Figs. 1, 2, 3).

In the dog then, the inoculation of fluid cultures, either intravenously or subcutaneously, produces no evident constitutional symptoms and no internal pathological changes. When introduced subcutaneously there is a local lesion at the point of inoculation, consisting of a circumscribed inflammation and abscess formation. When allowed to remain for from three to four weeks absorption of the contents of the abscess takes place, and a mass of scar tissue containing a small cavity alone remains. In the cavity organisms are present probably in very small numbers as is shown by the failure of cover-slip preparations and the small number of colonies developing in cultures.

If, however, the nodule is excised at the height of the process, signs of active inflammation are obtained — an exudation of serum and white-blood corpuscles having taken place, as well as an inflltration of the adjacent connective tissue with leucocytes. The micro-organisms are abundantly present, being seen in cover-slips, and developing luxuriantly upon cultures, while sections from the lesions stained by the Weigert method reveal them in large numbers.

Rabbit. — One rabbit was inoculated intravenously with 1 cc. of a 36-hour plain bouillon culture. The animal developed no evident symptoms and remained apparently well for five months.

Giiinea-pigs. — Six guinea-pigs were inoculated without result. In three the organisms were introduced subcutaneously. No induration followed at the point of inoculation. In three the inoculation was into the peritoneal cavity. No appreciable symptoms resulted. Five of these six animals died at periods ranging from six days to seven weeks after the inoculations, but in none was anything to be seen at autopsy, and all cultures from the organs were negative. At the time of these experiments numerous guinea-pigs kept at the pathological laboratory died of some unknown cause, and apparently the death of these animals was not due in any way to the organisms introduced.


J//(r. — While Mouse I. Inoculated subcutaneously with 0.3 cc. of a suspension made in sterile bouillon, from agar growth. On the second day the mouse appeared ill, sat in the corner of the cage, refused to eat and scarcely moved when the cage was shaken. Death took place on the sixth day. At the point of inoculation there was an area 0.5 cm. in diameter, raised, soft, and gelatinous in consistency, and paler than the surrounding tissues. This involved the subcutaneous tissue and muscle. On section the intestines were hemorrhagic and the spleen enlarged. The other organs appeared normal.

8mear preparations from the point of inoculation showed abundant oval and long forms of the micro-organisms, the latter varying from two to four microns in length. These stain irregularly, having usually a more or less clear area at one end. The same forms were present in smears from the lungs and liver, but in much smaller numbers. Those from the peritoneal cavity, spleen and heart's blood were negative.

Cultures from the local lesion, lung and liver showed the micro-organism in pure culture. The culture from the spleen was contaminated, while those from the kidney and heart's blood remained sterile.

Microscojnml examination of the tissues. — Point of inoculation. The subcutaneous connective tissue is infiltrated with large numbers of the organisms situated in clumps, some around the blood-vessels, and others having no apparent relation to the blood-supply. The leucocytes are fairly abundant, and often contain several organisms within their protoplasm. Numerous larger phagocytic cells appear. Deeper down in the tissues the organisms are very abundant, and lie in large masses between the muscle bundles. The organisms do not invade the muscle, and there is no apparent increase in the muscle nuclei. Sections stained in haamatoxylin and eosin show hyaline degeneration of the muscle fibres.

Liver. — In the liver many organisms appear in the larger blood-vessels and capillaries. Throughout the organ are minute focal necroses and degenerated liver cells, the organisms being in the capillaries of the diseased area and occasionally within the necrosed liver cells, and in leucocytes. The organisms have the same characteristics as those above described.

Sections of the lung and spleen appear normal except for the presence of the organisms in small numbers both within and without cells. They appear for the most part in small clumps containing numerous elements, but also occur here and there singly.

No pathological changes were made out in the kidney sections and no organisms could be demonstrated.

Lymphatic glands. — The lymphatic structures throughout the body showed the most striking and characteristic appearances. The organisms were readily demonstrable in the peribronchial, perinephritic and peritoneal glands, which contained immense numbers of them. They presented the same characteristics as before, and occurred for the most part outside of and between the lymj^hatic cells, although at times they are seen within the cells (Plate II, Fig. 4).

White Jlouse II. Inoculated in a manner similar to Mouse I. Death occurred on the 10th day. The autopsy revealed


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the same soft, semi-caseous area at the point of iuoculatiou and a similar htemorrhagic condition of the intestines.

The microscopical findings were the same as in the previous experiment.

Mouse III. A wild mouse was inoculated with 0.3 cc. of a 36-hour bouillon culture. Animal appeared to be unaffected until the fourth week, when it became less active and refused to eat. Died on the 38th day. Around the point of inoculation there was a very extensive indui-ation, the tissues being hard, shrunken and dry. This sclerosed condition involved the whole posterior third of the back extending down the thighs and to the root of the tail. Internally the intestines were adherent and the testicles involved in the cicatrix.

Cover-slips and cultures were negative.

Microscopical examination of the tissues removed from the local lesion showed exceedingly dense scar tissue. No organisms were demonstrated. Examination of the organs was negative.

SUMMARY.

The condition in the human subject reported here seems sufficiently unusual to warrant publication.

It is further of interest in view of the evidence given, which would indicate that the skin abscesses and indurated lymphatic glands were due to infection with a micro-organism, differing markedly from the bacteria, but agreeing with certain of the fungi.

The cultural characteristics of the organism are similar to those of many fungi and yeasts, and the imperfect life history which could be determined renders it not improbable that it may belong to the genus sporolricha. But for the present the exact classification of the parasite must be left undecided.

The experiments upon the dog and the mice prove the pathogenicity of the organism, and indicate that, under dif


ferent circumstances, it may remain local in its development and effects (dog), or it may invade the internal organs and produce a sort of pya?mia (mouse).

The etiology and pathology of many fungoid affections in man and animals receive a new interest in the light of the more recent studies of the pathogenic yeasts and their possilile relation to tumor formations. It may be mentioned that the pathological conditions met with did not in any instance suggest any otiier than a simple inflammatory jjrocess.

I take pleasure in acknowledging my indebtedness to Dr. Flexner for advice and assistance in the course of the study recorded here.

EXPLANATION OF FIGURES. Plate I.

Fig. a. Colonies of 10 days. Glucose agar. From lung of white mouse I.

Fig. b. Growth on glucose agar. 3 days. Photograph by Dr. J. F. Mitchell.

Fig. c. Cover-glass preparation from glucose agar. X 1000. Photograph by A. H. Eggers.

Figs. 1 and 2. Growth in hanging drop of bouillon. 60 hours.

Fig. 3. Same. 4 days. Reproduced from camera sketches by Dr. E. F. Smith.

Figs. 4 and 5. Cover-glass preparations from bouillon.

Fig. 6. Swollen and germinating conidia, from hanging drop of bouillon. 30 hours.

Fig. 7. Germ tubes with conidia attached, from hanging drop of bouillon. 3 days.

Plate II.

Figs. 1, 2 and 3. Sections of wall of abscess in subcutaneous tissue dog. Leitz obj. i ^Fig. 1), i (Fig. 2), and J. (Fig. 3).

Fig. 4. Peribronchial lymph glands of white mouse. Carmine and Weigert's stain. Leitz obj. J inch.


Oedematous Changes In The Epithelium Of The Cornea In A Case Of Uveitis Following Gonorrhceal Ophthalmia

DECEMBER, 1898.

Edward Stieren, M. D , Pittsburgh, Penna.


Oedema of the corneal epithelium with various changes and distortions of the epithelial cells due to pressure of fluid in the intercellular spaces, has been observed by many workers in the pathology of the eye, and has been described and depicted more or less thoroughly since Arlt's' original observations in 1855. He described the oedematovts changes taking place in the cornete of eyesafl'ected with choroiditis accompanied by increased intraocular tension.

Fuchs,'*' Fridenberg," Hirnbacher and Czermak,' Klebs" and other observers have seen these changes occurring in glaucomatous and staphyloniatous eyes.

Some experimental work has been done; Leber, Gutmann, and others have produced artificial oedema in the corneal epithelium. Leber" succeeded by injecting oil of turpentine under the anterior epithelium in producing, without any roughening of the surface, a corneal opacity which closely resembled


the haze of glaucoma. On microscopical examination he found numerous vacuoles in difi'erent layers of the epithelium with a pronottnced dilatation of the intercellular spaces. More recently, Gutmann^ by injections of a solution of asphalt in chloroform, demonstrated a communication between the lymph space.'! of the corneal matrix and the finer system of channels in the anterior epithelium, and produced a condition similar to that found by Leber.*

The corneal oedema of glaucomatous eyes (causing haziness and the appearance of rainbow colors around a flame at night)


Bizzozero, in his excellent article, first demonstrated the presence of a series of intercellular spaces or clefts forming a system of minute channels for transporting nutritive fluids to the individual cells and containing a small amount of viscid cement substance. Pfluger'^ and Grubor'" have also described the nutrition of the corneal epithelium through these channels.




Fig. 2.




Sections from local lesion. — Dos;



Peribrouchial lynijih arlands. — Mouse.


Pl.^te II.— To face p. 2'.K).


is due to the increase in intra-ocular pressure, the tension of the tunics being suddenly or gradiially raised, while the centrifugal flow of fluids is impeded or entirely shut off, resulting in an accuinnlation of fluid in these intercellular space'. These are now transformed from mere channels into dilated lacuna;. This at least seems the most plausible theory, although Fuchs' thinks it possible that the oedema can be caused by pressure osmosis, the aqueous humor being forced by the intra-ocular pressure through Desceniet's membrane (esi)ecially as this is often broken down in inflammatory glaucoma) into the corneal substance proper and thence through the lymph channels in the nerve sheaths and of the corneal matrix into the epithelial interce hilar spaces.

In the case I wish to describe there is j)resent an oedema causing marked changes in the epithelium which cannot be ascribed to increased intra-ocular pressure, since this was never present. Before entering into the microscopical appearance of the sections, a clinical history of the case is of decided inijjortance, and is as follows :

John A., se[. 35 years. American ; occujiation, commission merchant, was first seen in June, 1894, confined to bed with gonorrhce.il rheumatism and gonorrhceal ophthalmia of both eyes. 'J"he right eye was the worse of tiie two, the central part of the cornea at this time breaking down in an ulcer; the ulcerative process went on to perforation, allowing the aqxieous humor to escape and the iris to come in contact with the cornea, when the ulcer finally healed over and left a central opacity, adherent to the iris and about 4 mm. in diameter. The treatment consisted in the application of 2 per cent sol. argenti nitratis, atropin, cold compresses to eyes continually, with the internal administration of salicylates. The disease in the left eye ran the usual course and made a good recovery without any corneal involvement. The patient was seen from time to time after this, and in March, 1896, he made his appearance with the right eye painful, and the left eye a little sensitive to light; insjtection showed considerable ciliary injection of the right eye, the globe was tt-nder to touch; an ophthalmoscopic examination was impossible on account of the adherent iris and corneal opacity. Enucleation was advised as sympathetic ophthalmia was feared, the inflammation extendiug, without doubt, along the entire uveal tract. The eye was removed shortly afterwards, that is about two years after the contraction of gonorrhceal ophthalmia.

MICROSCOPICAL EXAMINATION.

Sections through the limbus, cornea, iris and ciliary body show evidence of a marked inflamnuition involving all these structures. In addition to the changes in the corneal epithelium, which will be described below, the corneal matrix shows marked sclerotic changes, and numerous large blood-vessels coursing through it. The iris shows an acute inflammation as well as sclerosis, but in the sections examined it is nowhere adherent to the cornea. Between the iris and cornea there is considerable inflammatory exudate. The ciliary body shows marked sclerotic changes. The inflammatory processes, chronic and acute, are much more marked in one side of the eye than in the other.

The epithelial layer of the cornea is markedly thickened, the thickening being most pronounced at the limbus on the less


involved side. For a distance of about 4 mm. from this point towards the other side the epithelium tapers down gradually and almost uniformly to the thickness of normal corneal epithelium. Although there is a slight hyperplasia present in all this area, the cells are larger than normal and there exists a certain dimness of outline in the individual cells, while their nuclei are swollen.

Beyond this point the cells begin to lose their characteristic appearance. At first this is most marked in the basement eel Is ; their approximation is not so jterfect, the intercellular spaces are dilated, the length of the cell is increased ; the nucleus is pushed towards the top of the cell, while its base retains its normal attachment to Bowman's membrane. Here the more superficial layers are not much disturbed, except that the cells and their nuclei are slightly enlarged and the cell outline is not so sharply defined.

As we proceed across the field the above changes in the basement row become more exaggerated ; the cells are drawn out longer and become narrower, while the position they formerly occupied is encroached upon by the dilating intercellular spaces. Their protoplasm stains lighter than normal. The more superficial cells are pushed forward. These changes become more marked toward the left (the more involved) side of the section, apparently due to persistent pressure of fluid. Round and oval vacuoles occupy in places the former sites of cells, now broken down. In some instances they contain broken down cell debris and degenerating nuclei.

These spaces occur for the most part in the basal layers ("Fusszellen " of Rollet and Lott), but are also present in the more superficial ones, a most interesting factor, however, being the manner in which the most superficial layer of cells remains intact under these circumstances. In several instances a vaciiole extends from Bowman's membrane below to this supeificial layer above, and this latter appears to be reinforced by a mass of broken down cell substance forced against its posterior border. Polymorphonuclear leucocytes appear in considerable numbers in the intercellular spaces in the more affected regions of the epithelium. When these spaces or vacuoles are not present the basal row of cells has the appearance of a uniform row of " palisades,"* while the cells above tliem and lying horizontally appear as rows of " arcades."*

Fuchs* observed that in glaucomatous eyes the vacuoles were most numerous at the points of nerve channel entrance into the basal row of cells. This cannot be demonstrated in the present case.

In the substan/ia cornea propria evidences of a most active inflammation are present. Round-cell infiltration is nuuked, with the formation of new blood-vessels in every field. Descemei's membrane for the greater part is intact though most of the cells are flatter than normal. Where it has broken down the sites are marked by the presence of numerous polymorphonuclear leucocytes.

The anterior chamber is filled with the coagulated remains of a thick fluid inflammatory exudate, dotted with mononuclear and polymorphonuclear leucocytes. The iris is gfnerally infiltrated with round cells and polymorphonuclear leucocytes.


Apt terms need by Klebs.



and in nn-iii tlieie are vast accuniulatioiis cf llit-iii. 'i'lie bloodvessels are enlarged. The tissue elements are considerably broken down and contain ninch free pigment.

As we approach the ciliary attachment of the iris the round cells become more numerous and there is much thickening, due to new fibrous tissue. Schlemni's canal is much reduced in calibre by an inflammatory deposit on its interior, and surrounding it are numerous mononuclear and polymorphonuclear leucocytes. Between the fibres of the ciliary muscle and of the corneal matrix in this region there are deposits of fibrous tissue. These secondary inflammatory alterations are much more marked on the side in which the cedeiiui of tlie cornea is found. To these altei'ations the oedema is probably due.

It seems not improbable that the lymph spaces conducting from the cornea into Schlemm's canal have been occluded either by the sclerotic changes in the tissues, by the accumulation of inflammatory exudate, or by mechanical pressuie.

At any rate the absorption of corneal fluids has been checked in this region. A stasis in this locality would cause accumulation of fluid in the intercellular spaces of the epithelium.

In addition to the occlusion of the channels of absorption it is not improbable that another factor in causing the oedemti has been the severe acute inflammation attacking the cornea and neighboi'ing structures, and thus tending to cause an increased outflow of fluid from the blood-vessels. There is nothing to indicate, however, that the intra-ocular tension was at any time much increased.

In conclusion, I wish to express my gratitude to Dr. C. R. Bardeen for his timely assistance in preparing this article, and to Ur. R. L. Randoli)h for his careful review of the same. To Dr. Heckel of Pittsburgh, I am indebted for the clinical history of the case and for the specimen from which the sections were prepared.

DESCRIPTION OF PLATE.

Fig. 1. Zeiss, ocular 4, objective AA, 65 diameters.

Alcohol fixation, celloidin section, hfematoxylin and eosin stain. The section passes througli the cornea, sclera and iris near the corneal margin. In the corneal epithelium, represented at the right above, may be seen the a-ilematous spaces described in the text. The many blood-vessels passing through the substantia propria show the severe alteration which the


main body of the curiiea has undergone. The ai.terior chamber is filled with an inflammatory exudate. Inflammatory changes in the iris are obvious.

Fig. 2. Zeiss, ocular 4, objective DD, 370 diameters.

Alcohol fixation, celloidin section, stained with Bende's iron hiematoxylin and with congo red. A vertical section passing through the corneal e])ithelium, from a region slightly nearer the centre of the cornea than that shown in Fig. 1. The marked alterations in the epithelial cells, described at some length in the text, are here clearly shown. A few leucocytes appear among the epithelial cells.

BIBLIOGRAPHY

I. Arlt: Die Krankheiten des Auges. Prague, 18.55. 3. Archiv fur mikr. Anat., Vol. XXXII.

3. Birnbacher and Czermak: Beitritge znr pathologischen Anatomie und Pathogenese des Glaucoms. v. Graefe's Archiv, XXXII, II.

4. Bizzozero: Ueber den Bau geschichteter Plattenepithelien. Moleschott's Untersuchungen, XI.

5. Pick : Diseases of the Eye.

6. Fridenberg: The formation of Vacuoles in Corneal Epithelium. New York Eye and Ear Infirmary Reports, Vol. VI.

7. Fuchs : Lehrbuch der Augenheilkunde.

8. Fuchs: Ueber glaucomatose llornhauttriibung. v. Graefe's Archiv, XXVII, III.

9. Genersich: Zur Lehre von den Saftkaniilchen in der Cornea. Wiener medicin. Jahrbiicher, 1871.

10. Gruber: v. Graefe's Archiv, XL, IV.

II. Graefe und Saemisch : Ilandbuch der ges. Augenheilkunde, IV.

13. Klebs: Ueber odenialose Verilnderungen des vorderen Hornhautepithels. Ziegler's Beitriige, Vol. XVII.

13. Leber: Ueber die intercellularen Liicken des vorderen Hornhautepithels iin normalen und pathol. Zustande v. Graefe's Archiv, XXIV, L

14. Pfliiger : Zur Erniihrung der Cornea. Klin. Monatsbl. fiir Augenheilkunde, Mar., 1882.

15. Schweigger: Lehrbuch der Augenheilkunde. Berlin, 1885.

16. Smith: Glaucoma, etc. System of Dis. of the Eye. Norris and Oliver, Vol. III.

17. Weichselb.ium : Grundriss der pathologischen Histologie. Wien, 1893.


PROCEEDINGS OF SOCIETIES

THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY. Meeting of November 7, 1898.

I'riinary Focal Hieuiatomyella from Traumatism. — Dr.

Pearck Bailby, New York.

The definition was self-explanatory with the exception of the word primary, which was used by the author as indicating that the hremorrhage was the result of force exerted directly upon the spinal cord without the intervention of a fracture or dislocation of the spine. Primary traumatic hajmatoniyelia is thus differentiated from the haemorrhages which complicate crushes of the cord brought about by compression. After a brief historical introduction, and after expressing the belief


that this affection was more frequent than is generally recognized, the questions of causation, pathological anatomy, symptoms, diagnosis and prognosis were severally considered. With the exception of pistol-shot wounds, sudden flexions and extensions of the neck were the best established causes. The author believed the lesion was produced by an actual stretching of the cord, with resulting laceration of blood-vessels and to a certain extent of centrally situated nerve fibres; he rejected the explanation proposed by Thorbun that a momentary displacement of a vertebra was the immediate causative agent. The pathological anatomy of the condition consists in a focal ha?morrhage confined chiefly to the gray matter always in the cervical or upper thoracic region ; the blood sometimes burrows for considerable distances up and down the cord. The extravasation on its absorption leaves a cavity which may remain patent or be filled up by new tissue. Secondary degenerations are usually not pronounced. The symptoms are in general those of other spinal cord traumatisms, though usually less severe and less numerous; but the motor and sensory symptoms have distinguishing characters. The distribution of the motor symptoms depends upon the extent and situation of the clot. Tiiere may thus be spinal hemiplegia, or monoplegia, or (probably) brachial diplegia, or paralysis of the legs, or paralysis of b3th arms and legs. The paralysis at first, unless the lesion is very small, is flaccid in all its characters; later it assumes the central neurone type in the legs with places in the arms of peripheral neurone type. The sensory symptoms consist, in addition to pain in the neck, of a dissociated anesthesia, that is, anesthesia for temperature or for pain or for both, with perfect preservation of tactile sensibility. A case was reported in which this peculiar clinical condition was absolutely distinct, biit in which, as shown by subsequent microscopical examination, the blood had exceeded to a certain extent the confines of the central gray niatter of the cord. The sensory anomalies of primary focal haamatomyelia from traumatism are usually transitory, unless the case is exceptionally severe. In reported cases the analgesia has disappeared before the thermoansesthesia.

In the anther's cases thermoanaesthesia was the only sensory anomaly present.

Diagnosis depends chiefly upon this dissociated anajsthesia ; light is further thrown upon it by the transitory paralysis of most muscles and by the general rapid improvement of the patient.

The prognosis is better than for any other form of injury to the cervical region of the spinal cord. Several cases were cited from literature to show how rapid recovery may be. Two personally observed cases were also reported. In one, after complete paralysis of arms and legs, with loss of power of the sphincters, resulting from a diving accident, the patient could use his hands, and walk unassisted up four pairs of stairs, in less than two months; in the other, a man who, as the result of a fall of thirty feet, was completely paralyzed in the legs, with retention of urine, was able to go to work (night-watchman) in two months.

The treatment is the same as for other varieties of spinal cord injuries, except that any operative measures are strongly contraindicated.

Dr. Pkeston. — I have been very much interested in Dr. Bailey's clear presentation of this subject. It is an extremely suggestive paper. As he was reading the paper I could not help wishing I had had this particular knowledge many years ago. It has been my fortune or misfortune to see quite a large number of these cases of spinal injury, for the City Hospital is located in the centre of our city, and many cases of sudden injury are brought in there.

One of the most puzzling questions connected with these cases is that referring to the advisability of surgical interference. I have been always of the opinion that where we can be sure that there is direct injury to the column there should be prompt interference. I can recall now, however, a certain


number of cases in which I advocated opei'ation and where the after results proved that it would have been better not to have opened the column. Again I can recall cases that I am sure would have been benefited by an operation. We had no definite symptoms to decide the question as to whether there was simply this focal injury or whether we had an injury which involved the bones and portions of the spinal cord, particularly the white columns. The hopes that were raised a dozen years ago by surgical exploration of the brain have not been borne out. We have had to limit the sphere of surgical interference, but I think neurologists are now looking strongly to some sort of surgical interference in injuries of the spinal cord. I think, perhajis, there may be some slight predisposing cause here in Baltimore to haamorrhagic myelitis. At any rate we see a large number of such cases. Dr. Osier has just whispered the suggestion that it is due to the smooth pavements of Baltimore.

We can now, after what Dr. Bailey has told us, differentiate clearly between cases of focal hasmatomyelia and cases in which the cord has been injured. The loss of pain and temperature sense and the preservation of tactile sensibility are two valuable points in the diagnosis. He has also given the neurologists help in enabling them to give a favorable prognosis in these cases, which is a boon to men practicing upon a class of cases where few die and none get well.

Dr. Barker. — I am grateful to have had the opportunity of listening to a paper so rich in personally studied matter and first-hand experience.

The difference in the etiology of spinal haemorrhages and of cerebral hemorrhages is obvious from what Dr. Bailey has said. While nearly all spinal haamorrhages are due to trauma, relatively few cerebral hemorrhages are thus produced, the majority of the latter being dependent upon chronic arterial disease. A spinal hemorrhage due to vascular disease is one of the rarest of pathological findings.

If I understood Dr. Bailey correctly he referred in one part of his paper to the possibility of occurrence of an anesthetic area in which no painful sensations resulted on the application of heat, though pain could be elicited by ordinary methods of stimulation. 1 have been convinced myself in the study of sensations that "heat-pain " is due to the stimulation of jjain nerves and not to the stimulation of " temperature nerves," i. e. the warm points or cold points. In areas on the circumscribed area of elective sensory paralysis on my own left arm where pain sensations are the only ones which can be elicited by any method of stimulation, a test-tube heated above a certain temperature, after a certain latent period, will always cause pain not preceded or accompanied by any temperature sensation. The studies of von Frey demonstrate conclusively the existence of points in the skin which when stimulated give rise to painful sensations, but not to thermal or tactile sensations. In the case I have studied all the warm-points, cold-points and pressure- or tactile-points in certain areas are thrown out of function and the pain-points alone yield a response. Ice and heat applied to these areas cause painful sensations, but no feeling of cold or warmth. One interesting feature of the heatpain and cold-pain as studied upon surfaces supplied only with pain nerves is tlie latent period of the pain. When one carefully applies a piece of ice or a hot test-tube to such an area he has no sensation at all at first ; only after the lapse of some seconds does any sensation result. There is first disagreeableness which soon goes over into distinct pain. Ordinarily when a hot test-tube is applied to normal skin the part is jerked away quickly. This is due to the fact that there is such violent stimulation of the heat-points that we are warned that if we do not remove the arm pain will result. We say that it hurts, but as a matter of fact we are not hurt but only warned that we shall feel pain unless the heat be removed. The same is the case in applying a piece of ice. If the ice remains in contact long enough we have " cold-pain," but the first effect on normal skin is a violent stimulation of the cold-points with a startling sensation of cold. I have wondered if heat-pain and cold pain are ever really absent in areas where pain-sensations can be elicited by the application of ordinarily painful stimuli, such as pricking with a needle. I am of the opinion that the prolonged contact of ice or hot water would give rise always in such cases to the sensation of pain. May it not be that the existence of heat-pain and cold-pain is often overlooked in cases in which the cold-points and warm-points are thrown out of function. Many, of course, still hold that heat-j)ain and cold-pain are due to over stimulation of temperati;re nerves and not due to the stimulation of specific pain nerve, but this view is irreconcilable with our present physiological and pathological knowledge.

I would add a few words with reference to the relation of hEematomyelia to syringomyelia and central glioma. Since the investigations of Minor, early in this decade, the attention of all neuro-pathologists has been directed towards this dissociation of sensation or elective sensory paralysis in cases of central hsematoniyelia. As Dr. Bailey has said there can be but little doubt in most cases with regard to diflerential diagnosis, for the symptoms follow so directly upon the trauma that one can scarcely make a mistake. The pathology of these cases, however, is somewhat more puzzling than their clinical history. A number of cases have been studied in which in addition to haemorrhage, or the signs of old hfemorrhage, cavity formation with gliosis (or gliomatosis) in the periphery of the cavities has been observed. Some pathologists assert that after haematomyelia not only may partial obliteration of the hajmorrhagic cavities by glia tissue occur, but tliese cavities may become lined later by glia cells and thus give lise to syringomyelia or even be the starting point of a central gliomatosis. Minor goes so far as to suggest that such cavities secondary to hemorrhage may possibly at once or later become connected with the canalis centralis, receive an ependymal lining from this and so give rise to the appearance of a malformation of the cord. One cannot help being somewhat skeptical with regard to such a point. It is certainly not to be forgotten that in so-called gliomata in which the main constituents are cells of the ependymal type multiple cavities are frequently found, and there seems to be a special tendency to haemorrhage in such cases. In a case of this kind where such multiple cavities exist with surrounding gliosis or ependymal tumor formation a slight trauma might produce a hffimorrhage, and the symptoms would be those of hsematoniyelia. Clinically this might


present the typical picture of primary haematomyelia, but pathologically it would have to be considered as hEematomyelia secondary to the new growth.

I would also like to ask Dr. Bailey if he has, in his experience, met with any case of bilateral gummata giving rise to dissociation of sensation of the syringomyelic type.

Dr. Bailey. — Replying to an inquiry from Dr. Osier I would say that I think undoubtedly many of the cases once called concussion of the spine were cases of intra spinal haemorrhage.

In regard to Dr. Barker's inquiries I have never personally seen analgesia in these cases except for thermal stimuli, but I did not examine to see whether after a certain time of application of heat the patient complained of pain. We held the water on for a few seconds only.

As to the ependymal lining of the gliosis that occurs after cavity formation I have only had the opportunity of seeing one case in which I could trace the whole process. The man was an active man and healthy in every other way. In his case there was a large growth in the central part of the spinal cord, but it was in no way connected with the central canal. The central canal is the part of the gray matter that seems to escape most frequently in haematomyelia, and in the case to which I made reference this canal was normal and there were no ependymal cells lining the cavity.

As to bilateral gummata, I have no doubt they could give rise to dissociated ana3sthesia as many other processes do, such as pachymeningitis.

In the cases I have examined the knee-jerk has been absent for two or three weeks, but entirely returned at the end of two months. As to the cause of the absence of knee-jerk I am sure I do not know.

Two Cases of Pylorectomy.— Dr. Finney.

The first case is that of a man about 50 years of age who presented himself at the Hospital on July 15, '98, complaining of distension of the stomach, daily vomiting, and constipation. His family history was negative. For about one year he had noticed a pain in the stomach, accompanied by a full feeling, and had lost weight, falling from 126 pounds to 95 pounds in the course of the year. He began to vomit after eating his meals, and has vomited twice daily about a quart, more or less, of light brown, sour material. He says that he has vomited materifil which he had eaten the day before, or even two days previously. The day before entering the hospital he vomited a little bright red blood.

On examination he appeared rather emaciated, had a temperature of 99.4°, pulse of 62, with a volume full and firm, pupils equal, skin moist and mucous membranes of good color. There was considerable arteriosclerosis. His heart sounds were regular, and there was no murmur. His abdomen was soft and not distended. Waves of peristalsis were seen moving from left to right. To the right and just above the umbilicus a hard mass could be felt, about the size of one's thumb, which moved up and down with respiration. Examination of the contents of the stomach showed no free hydrochloric acid, and microscopically no tumor cells.

The diagnosis of carcinoma of the pylorus was made, and an


December, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


295


operation advised. He was operated upon July 20th. The stomach was irrigated daily, for a day or two beforehand, and rectal feeding only, for 24 hours previously. A small incision was made under cocaine anesthesia, as I had promised him I would make an exploratory incision first, to find out what the trouble really was before giving him a general anaesthetic. Under cocaine then, I made an incision about 4 inches long in the median line, exposed the tumor so that I could see and feel distinctly its outlines, also an enlargement of some of the mesenteric glands, and thus confirmed our previous diagnosis. Ether was then administered and the operation proceeded with. The median incision was enlarged, and also a lateral one was made through the right rectus. We found a hard, scirrhous mass about the pylorus, which was a little larger than it had appeared through the abdominal wall. This was removed without any particular difficulty except that the duodenum was very adherent to the head of the pancreas, and we had some difficulty in arresting hjemorrhage after its separation. By dividing through the duodenum the growth was removed with a portion, perhaps one-third, of the stomach, which I have here. Several enlarged mesenteric glands were also removed. The stomach was sutured in the usual manner, grafting the duodenum into the stomach after partially closing the cut end. There was no difficulty in doing this. I used the mattress suture of Dr. Halsted, and closed the abdomen without drainage. He made an uninterrupted recovery.

The patient is present to-night, having kindly come from Pennsylvania to attend this meeting. He has gained 30 pounds in weight since July 15th. You may be interested in seeing the man and examining the condition of the wound at present (exhibiting the patient). You will see that the scar is very firm, and there is no weakening of the abdominal walls due to the section of the rectus.

Case II. Case II is that of a man 56 years of age who came to the Hospital on October 12, '98, and was operated upon in the clinic. His family history is also negative. About 4 months ago pain began in the epigastric region, starting first in the left hypochondrium, beginning about one-half hour before meals, and relieved after eating. He never suffered with it directly after eating. It was not much worse when he came to the Hospital than at the time he first noticed it, and now it passed over the whole upper portion of the abdomen. There had been some nausea and vomiting, with rapidly increasing weakness for the past few months. He had lost in weight he thought about fifteen pounds. He looked as if he had lost more than that, as he was rather emaciated. Nothing was made out on physical examination except that in the abdomen to the right of the median line, in the upper umbilical region, there was a slight tumefaction. On turning to the right in the recumbent position this mass moved to the right about 1 cm., and when turning to the left it moved to the left 3 cm. Here is a drawing showing the location of the mass and the relative position before and after dilatation of the stomach..

Analysis of the stomach contents showed no free hydrochloric acid, and a faint trace of lactic acid. This case was also diagnosed as cancer of the stomach, probably of the pyloric end, and involving a portion of the stomach. He was


operated upon October 21st under ether. Incision was made in the median line, the stomach was delivered and packed about with gauze. The adhesions were not so marked as in the other case, although the omentum bothered us considerably by being adherent below, and the larger portion of it had to be ligated and divided. Some glands felt to be enlarged, below the stomach in the omental fold, were removed, I think about four in all. There was no particular difficulty about the operation, the same procedure being employed here as in the other case, with this exception, in the second operation I removed much more of the stomach, taking out at least twothirds, and sutured the duodenum to what was left of the stomach. The growth in this case extended much more along the lesser curvature of the stomach than along the greater, so that I took out an additional V-shaped piece here, and thus facilitated the subsequent suture very much. The procedure is an old one, having been suggested first by Billroth. After suturing the cut edges where the V-shaped piece had been removed, the opening in the stomach was found to match the lumen of the duodenum exactly, and I then had a simple circular suture of the intestine, and made use, in performing it, of the dilatable rubber bags of Dr. Halsted.

The first case made an uninterrupted recovery. He complained of nothing after the operation save hunger, and so bitterly did he complain of this that we gave him some milk thirty hours after tiie operation. The second was one of those unfortunate cases that happen now and then, in which the operation was a great success, but the patient died. The operation was very satisfactory, the enlarged glands we had felt were removed without difficulty, and, as it proved subsequently at autopsy, all the enlarged glands were removed. The case did well surgically, there were no symptoms of peritonitis and no pain, but he rapidly developed a typical pneumonia in the right lung, which extended to the left, and on the fifth day he died. The autopsy showed an extensive double lobar pneumonia.

Cover-slips from the abdomen wei-e negative. There was not a single adhesion between the abdominal wound and the site of operation, and the peritoneal cavity was perfectly dry. It was unfortunate that this man should have developed a pneumonia, as apparently all the growth had been removed.

Dr. CuSHiNG. — One of the most striking features of Dr. Finney's report lies in the closure of the abdominal wound without drainage after a long operation necessarily associated with more or less soiling of the peritoneal cavity. Of course the peritoneum will take care of a certain number of microorganisms provided no nou-absorbable material such as a bit of necrotic tissue or faecal matter is left behind. In these operations high up in the intestinal tract, however, another most important and encouraging factor must be taken into consideration, namely, the organisms or better, lack of organisms, which the peritoneum has to take care of. In Dr. Finney's first case unfortunately no cultures were taken from either diiodenum or stomach. In the last case in which the healing was so perfect and clean, cultures taken from the duodenum at the time of operation remained sterile and cover-slip ])reparations were negative. It is astonishing to consider that the duode


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nil in should be free from micro-organisms especially in a case of this sort where there has existed a condition of chronic disease. My attention was first attracted to this subject a year ago after operating upon a case of perforating gunshot wound of the abdomen in which, though twenty-seven hours after the accident, but a slight degree of peritonitis was present. There were four perforations present in the upper part of the jejunum. On looking over the cases of gunshot wound with intestinal jjerforation which had previously been operated upon in the hospital, I found, strangely enough, that the only ones which had recovered were those of jejunal perforations. Since that time we have been observing very carefully indeed the bacteriology of all cases in which the upper part of the alimentary canal is opened on the oj)erating table and have found the duodenum sterile on several occasions. This I think is an all-important prognostic feature of these cases, and I do not know that it has ever been emphasized before. In conjunction with Dr. Livingood I spent several weeks last spring upon some experimental work with animals which gave us very much the same results as we had observed clinically. It apparently is possible in some instances to render the greater part of the intestinal tract surgically clean before operation, that is, free from pathogenic micro-organisms. I hope soon to publish the results of our observations.

Dr. Cone. — As Dr. Flexner is not here to speak of the pathology of Dr. Finney's cases I might say a word. Most of us have been over the pathology of the last case. It showed only in a few areas the invasive character of the epithelium, but the glands were typically invaded with adeno-carcinoma. The gross appearance of the specimen from the second case was that of scirrhus carcinoma involving nearly the entire circumference of the stomach, showing no ulceration, but the mucosa had been worn off. Frozen sections showed masses of spindle cells and round cells which made us think of sarcoma although it is one of the rarest tumors of the stomach. There were tumors of very few epithelial cells in teased sections.

These tumors of the stomach may be classified as follows : medullary, scirrhus, colloid and diifuse carcinoma. The last case was most interesting because it shows how the stomach may be invaded by a growth that cannot be determined microscopically from an examination of the tumor itself, but one must go further and look at the glands which show typical adeno-carcinoma.

Dr. Finney.— I would like to say a word as to the anesthetic used in these cases. In the last case the patient impressed us as being a poor subject for a long, depressing operation. The operation varies in length from one to three hours, depending upon the difficulties with which one meets, and the rapidity of the operator. A patient who is under an anaesthetic for two hours must of necessity be affected to some extent. It has been proven, first by Dr. Halsted in his breast operations for cancer, that haemorrhage is the prime factor in shock in most cases. That rule holds good in most instances except in opei-ations in the peritoneal cavity. In the latter instance the element of time certainly plays an important jiart, and so if we have a long, depressing operation upon a


patient who has lost many pounds in weight, we have a patient already pulled down, and in a condition to stand very poorly any marked strain. The question of choosing an anaesthetic then becomes a very serious one. If one could do these operations satisfactorily under cocaine it would be a great gain, but when it comes to an operation of this sort where you have to handle the stomach so much, and do so much violence to the solar plexus, so to speak, you must use a general anaBSthetic. I debated in my own mind the relative advantages and disadvantages of chloroform and ether, and decided in favor of the latter. I believe that the ether played a very important part in the production of this patient's pneumonia. We need a new anesthetic for cases of this sort. Neither ether nor chloroform is an ideal aussthetic, particularly for cases of this kind.

The Non-Medical Treatment of Epilepsy. — Dr. Hukd.

Within a few years past a new departure has been made in the treatment of epilepsy. The former treatment by medicine alone has been unsatisfactory, and remedy after remedy has been used and discarded. Surgical operations also have been performed, in some instances with good results, but in a great majority of instances with little benefit.

In epilepsy we do not deal with the epileptic paroxysm alone but with a complexus of symptoms, among which the epileptic convulsion may be regarded as the last of a series of morbid processes.

The majority of epileptics possess an extremely weak nervous system, perhaps inherited, and the individual patient is always unduly susceptible to disturbing influences. It has been known for a long time that the causes of epilepsy varied. In many instances epilepsy has been thought to be due wholly to disturbances of digestion, but it is now pretty evident that we have to deal with a more serious trouble. It is not primary digestion alone but often secondary digestion which is at fault. There is some defect in metabolism as a result of which the system becomes poisoned. The neurotic organization to which I have referred being unduly responsive to the. action of this poison is overwhelmed by it and we have an epileptic paroxysm. It was formerly thought that if some remedy could be found to control the paroxysm, epilepsy was cured, but now we know that remedies which merely control the paroxysm do very little to cure tlie disease. It is like tying the hands of a maniac to cure his excitement. The general eftect of the bromides and of similar remedies has not been to prevent the generation of the poison in the system, but merely to restrain its manifestation in an epileptic attack. Such restraint may be effective for a time, but finally the poison becomes so overwhelming that a paroxysm can no longer be restrained, and a furious convulsion follows which probably equals in force the sum of the minor paroxysms which had been prevented by the remedy. It has been found by experience that the condition of such a patient is worse than if he had more frequent but milder convulsions.

It has been found in institutions for the insane that the effect of large doses of bromide upon insane epileptics lias been to deaden their sensibilities, to increase their growing dementia and to render them more furious and dangerous ; and the


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majority of physicians who have to deal with this class of patients long ago concluded that it was unwise to attempt to cure these patients by remedies which were given to check convulsive seizures.

Recent observations have indicated the character of the poisonous substances which enter the circulation and produce the epileptic seizure. They are probably leueomaines, but their exact relations to the disease have not been fully worked out and much remains to be done to determine the means of preventing the formation of these poisons in the system. There has however grown out of these investigations a system of providing for epileptics which promises much for the future. In this system it is not intended to substitute hygienic and moral influences for medical treatment or to decry medical treatment, but rather to relinquish the idea of depending upon drugs alone in the treatment of epilepsy.

Within the past few years provision has been made in many States for the care of epileptics in large colonies. The epileptic is not a pleasant member of the home circle whether he is sane or insane, and he seldom does well if treated at home in the family, being difficult to control and unable to co-operate in curative measures. In New York, Ohio and to some extent in other States institutions for their special treatment have been started. In the msjority of instances this treatment consists in giving the epileptic the largest possible amount of open-air life and in controlling his diet so that the amount of nitrogenous food may be carefully regulated. It is equally essential that the growing epileptic shall have something to do. It has been fouud that patients fed upon drugs with nothing to do have frequent epileptic seizures, while, if kept employed in the open air the seizures are less frequent. An attempt is now made to give them useful labor every day under medical control with the theory that a physician should in every case prescribe the kind and amount of labor and the time of day it should be performed. Many epileptic patients are prone to seizures immediately after meals, especially if allowed to fall asleep. It is necessary therefore in all matters which relate to the labor of the patient that the medical man shall say when and how the patient shall exercise.

As the result of such treatment patients who have been subject to daily or weekly seizures often without any medicine, go a month, sometimes a year, or longer without a convulsion.

From our present knowledge the best treatment for an epileptic is an open-air life, carefully selected food and a judicious amount of labor.


NOTES ON NEW BOOKS.


Atlas of Legal Medicine. By Dr. E. vohHofmann. Translated by

Frederick Peterson, M. D., and Aloysius O. J. Kelly, M. D.

56 plates in colors and 193 illusirations in black. (TT. B. Saunders,

Philadelphia, 1898.)

The previous volumes of the present series of Atlases have been reviewed in these pages as they have appeared. The series is a very valuable one, and well illustrates the importance of colored drawings in representing natural objects in the domain of medicine. To pathologists, and especially to coroners' physicians, the present volume will be found of service. It is manifestly quite


impossible to do more than draw attention to the salient features of the work, for to do it justice in a review a record of the various medico-legal conditions described would be necessary. The object of the Atlas is to show the appearances met with in organs and the body in general in case of death from violence or unexplained causes, which come under the jurisdiction of coroners or their physicians. As in this country we do not have a specially trained set of legal physicians, the opportunity to become familiar with many of the objects treated of in the volume is open to few ; and therefore as a work of reference in doubtful instances, or as affording an opportunity to siudy the effects of poisons, etc., upon the organs, the Atlas will fulfil a useful purpose.

Annual and Analytical Cyclopaedia of Practical Medicine. By Charles E. de M. Sajous, M. D., and one hundred As.sociate Editors. Volume I. {The F. A. Davis Co., Publishers, Philadelphia, 1898.)

The Annual of the Universal Medical Sciences comes to us now in a new form, that of an Analytical Cyclopaedia of Medicine. The change is explained by the editor, aiid would seem to better fit it for the use of the practitioner of medicine to whom the original "Annual " often failed to give the desire<l information. The general appearance of the pages is somewhat novel, as tlie newer literature upon etiology, treatment, etc., is interpolated at irregular intervals in the general text, occupying a smaller sized type. Thus each subject is treated in a complete fashion as in any modern textbook, and may be read as such by confining the attention to the large type only, while the recent additions to the subject may be obtained in the course of this reading, or separately by consulting the matter in small type. It is expected that the entire domain of medical subjects will be embraced in six volumes. The present volume covers the subjects from "Abdominal Injuiies to Bright's Disease." The list of associate editors embraces some of the best known names in this land and foreign countries.

The Methodist Episcopal Hospital Reports, Vol. I, 1887-1897.

Edited by Lewis Stephen Pilciier, M. D., and Glentworth

Reeve Butler, M. D., (New York: Published by the Hospital,

1898.)

This handsome volume contains a history of the Hospital from its beginning, together with the usual scientific medical reports from the officers of its medical staff. Thelongestof these contributions are those on the several diseases of the female genital organs and on operative methods, by Dr. L.S. Pilcher, on the injuries of the cranium and spine and on appendicitis, by Dr. George R. Fowler, on fracture by Dr. J. P. Mathews ; and there are besides a number of minor reports, all of interest and value. It appears that from the first the surgical side of the Hospital has received the largest patronage — over two-thirds of the total number of patients suffering from diseases requiring surgical relief ; hence the predominance of surgical papers in this volume. The medical side is, however, also well represented by valuable reports by Drs. Butler, Mathews, Shaw and others.

The volume is beautifully printed, and the illustrations are especially good, and even the half-tones are intelligible and useful, which is not always the case in works of this kind. In these as well as in other respects the authorities of the Methodist Episcopal Hospital have set a high standard for their future reports.

The Anatomy and Functions of the Muscles of the Hand and of tlie Extensor Tendons of the Thumb. By J. Francis Walsh, M. D. Essay awarded the Boylston Prize for 1897, Department of Anatomy and Physiology, by the Boylston Medical Committee, Boston, Mass. (Philadelphia: Charles H. Welch, 1897.) The merits of this careful and thorough study of the anatomy of

the human hand are directly evidenced by the fact that it is the


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[No. 93.


Boylston Prize Essay of last year. It is a thorough critical study of the gross anatomy of a very important region which can hardly fail to have some practical bearing on some of the surgical questions tiiat may from time to time arise on the musculature of the hand. The theoretical value of such studies is of course beyond question.

Medical and Surgical Reports of the Boston City Hospital. Ninth Series. Edited by Charles F. Folsom, M. D., W. T. Counx-ilman, M. D , and Herbert L. Burrell, M. D. (Boston : Published by the Trustees, 1898.)

About half this volume is taken up with the discussion of diphtheria in some of its aspects, and the papers are of decided value and interest. In Dr. Jenks' study of the nervous system in this disease, tlie microscopic examinations were largely confined to the pneumogastric nerve, though the spinal cord was also examined in some cases and the brain in one or two. It is to be desired that a more thorough investigation of the higher nerve centres should be made in this disease than seems to have been done so far.

The other papers in this volume, are all apparently meritorious, as might be assumed from the names of the editors. Those on formaldehyde as a disinfectant, and on the anaesthetics used in the eye, are among the longest and are of considerable practical interest.

Ill the surgical abstract accounts are given of several cases of foreign bodies in the digestive tract, tliat are of interest in connection with some occasional hospital experiences, and as showing how such bodies are liable to behave under certain conditions. In one case a plate with three false teeth was passed safely in the natuial way; in another a similar plate and teeth lodged in an enlargement of the oesophagus, and was only detected there by the dangerous hemorrage it produced. In still another case a fish bone ulcerated through the peritoneum, causing an extensive abscess between it and the abdominal wall.

The volume is a worthy addition to a valuable series.

Epidemic Cerebro-Spinal Meningitis and its Relations to Other Forms of Meningitis. A Report of the State Board of Health of Massacliusetts. {Boston: Wright & Potter Printing Co., State Printers, 1898.)

This report, by Professor Councilman and Doctors Mallory and Wright, will take rank with the best scientific literature and become an authority upon this disease. It gives a historical sketch of the disorder, and full reports of over one hundred cases; its bacteriology, symptoms and complications; its diagnosis and relations to other forms of meningeal affections. Altogether, the report is one of the best monographs of its kind and compass on a single disease.

The relations of cerebro-spinal meningitis to mental disorders are only very briefly touched upon. Considering the fact that meningitis figures amongst the alleged causes of insanity so frequently, this is a little noteworthy here ; the more so since the authors elsewhere express the opinion that "all infections of the meninges other than by the diplococcus intracellularis are fatal." There are many who will hardly accept this conclusion, but those who do can not avoid admitting that cerebro-spinal meningitis, due to the infection of the diplococcus intracellularis, is one of the more potent and frequent causes of insanity.

The report has a lengthy bibliography attached, but it "contains some omissions," to use a Hibernicism, some of which, it would appear, might have been included, the references certainly being noteworthy enough to have been included in the literature. As, however, the list given only contains those works and articles mentioned in the text, and is not represented to be a complete bibliography of the more important memoirs on the subject, this


hardly calls for criticism. The report itself will most certainly be often quoted in the future and take a most honorable position in the literature of its special theme.

Doctor and Patient: Hints to Both. By Dr. Robert Gaesunq, Vienna. Translated, with the permission of the author, by A. S. Levetds, with a preface by D. J. Leech, M. D., F. R C. P., etc. (Bristol: J. Wright & Co., 1898.)

This is a work of a class that has had several representatives in this country, but it has a special value as showing low nearly alike the professional conditions are in all countries. The Vienna professor might have written his book for an English-speaking public in the first place, and hit nowhere amiss. The fact is, the doctor and patient stand in the same relations to each other over the whole civilized world, and the same ethical queatiot s, troubles and trials exist in one place as well as in another. Here we have in our cities the dispensary evil, and in our country generally too large a freedom of medical education and practice, whidi are only partly peculiar to us; in the older countries also we hear of the overcrowding of the profession, and the medical proletariat spoken of by Dr. v. Ziemssen in a recent address is an evil in Germany as well as here. There they have, moreover, the socialistic unions, cheapening medical practice, as in England. The "Battle of the Clubs" is an apparently perennial question for discussion in the medical journals. Another custom of medical practice which is generally reckoned with us as hardly commendable or profitable to the physician appears, judging from this little work, to be common enough in Austria as to be accepted as perfectly normal, viz. the regular season contract with patients and their families. If tliis is the usual or even common practice it is rather to our European confreres' disadvantage.

The ethical tone of the work is, as might be expected, the very best, and it is one that will be profitable for occasional reference by the old practitioner as well as valuable to the beginner in the medical profession.

A Text-book upon the Pathogenic Bacteria for Students of Medicine and Physicians. By Joseph McFarland, M. D. Second Edition. 1898. 497 pages. 8vo. (W. A. Saunders, Philadelphia.)

We had occasion to review the first edition of this work in August, 1896. In this edition parts have been rewritten and new chapters have been added, which have much enhanced the value of the work. In the light of our present knowledge the omission of cerebro-spinal meningitis under the section on acute inflammatory processes is much to be regretted. In the chapters dealing with general technique, the author at times recommends measures which are now somewhat obsolete, and some proce<lure8 are faultily described. We do not think that the majority of bacteriologists would coincide in Dr. McFarland's remarks concerning the action of light upon bacterial growth, and to many they would seem quite erroneous upon the whole. Contrary to the statement in the book we have invariably found the house-mouse highly susceptible to anthrax ; also the growth of staphylococcus pyogenes aureus is by no means most typical upon nutrient agar-agar, but upon potato, when grown at room temperature. The statement regarding the streptococcus pyogenes and the diplococcus )>neumonije having no growth upon potato, we believe to be exceptionally the case and not the rule. The author's view that the pseudo-diphtheria bacillus is but an attenuated variety of the true bacillus diphtheriae is now considered untenable. Several of these errors were pointed out in a review of the first edition. Until they are corrected the book cannot be entitled to the praise it otherwise might readily command. Tlie arrangement of the book as a whole is good, and the matter of its various sulijects is commemlably planned and dealt with, while its photograjdiic reproductions and general make-up are of a high order of excellence. N. ^IacL. H.


1)eceMber, 1898.]


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INDEX TO VOLUME IX OF THE JOHNS HOPKINS HOSPITAL BULLETIN.


Abel, John J. Further observations on the chemical nature of the active principle of the suprarenal capsule, 215 ; — Secondary melano-sarcoma of the liver following sarcoma of the eye (discussion), 53.

Adeno-myoma of the round ligament, further remarks, 142.

Allbutt, T. ClifEord. Medicine in the nineteenth century, 277.

Anderson, H. B. See Flexner, Simon, and Anderson, H. B.

Aneurism, cases of, 38, 63.

Antitoxic relation between bee poison and honey (?), 271.

Aortic aneurysm, 272.

Bacillus typhosus in the gall bladder seven years after typhoid fever, 95.

Baer, \V. S., Dawson, P. M., and Marshall H. T. Regeneration of the dorsal root of the second cervical nerve within the spinal cord, 144.

Bailey, Pearce. Primary focal hsematomyelia from traumatism, 292.

Barker, Lewellys F. Cerebro-spinal meningitis (discussion), 33 ; — Hsematozoan infection of birds (discussion), 18; — A microscopical study of the spinal cord in two cases of Pott's disease (discussion), 132 ; — Observations on the epithelium of the urinary bladder in man (discussion), 158 ; — Presence in the blood of free granules derived from leucocytes, etc. (discussion), 19 ; — Primary focal hiematomyelia from traumatism (discussion), 293 ; — Regeneration of the dorsal root of the second cervical nerve within the spinal cord (discussion), 145.

Bladder, the successful treatment of extra-peritoneal rupture of, 5.

Bloodgood, Joseph C. The transplantation of the rectus muscle in certain cases of inguinal hernia in which the conjoined tendon is obliterated (a preliminary report), 96.

Bombaugh, Charles Carroll. Medical fees in ancient Greece and Rome, 183.

Booker, William D. The bacteriology of yellow fever (discussion), 120.

Books received : 22, 44, 65, 122, 148, 172, 252, 275.

Broadbent's sign, 271.

Brown, Thomas R. Aortic aneurysm, 272 ; — On the specific gravity of the urine during ansesthesia and after salt-solution enemata, 190.

Bucknill, Sir John Charles, 180.

Camac, C. N. B. Broadbent's sign, 271.

Carcinoma metastases in bone from a primary tumor of the prostate, 114.

Catheterization of the ureters in the male through an open cystoscope with the bladder distended with air by posture, 62.

Cerebro-spinal meningitis, 27.

Christian, Henry A. Two instances in which the musculus sternalis existed. — One associated witli other anomalies, 235.

Clark, J. G. Papilloma of the Fallopian tube, 163.

Cocaine anaesthesia in the treatment of certain cases of hernia and in operations for thyroid tumors, 192.

Cone, Sidney M. A case of carcinoma metastases in bone from a primary tumor of the prostate, 114 ;— Acase of osteitis deformans (discussion), 136 ; — -Two cases of pylorectomy (discussion), 296.

Correspondence: Does Wilhite's story of the negro boy incident in the discovery of anaesthesia " lack probability " 7— Letter from Dr. Wilhite, 83 ;— Letter from Dr. Young, 87 ;— Hydraulic pressure in bladder contracture, Ferd. C. Valentine, Hugh H. Young, 191-192.

Councilman, AV. T. Cerebro-spinal meningitis, 27.

Cullen, Thomas S. Further remarks on adeno-myoma of the round ligament, 142 ; — Hydraulic pressure in genito-urinary practice (discussion), 110.

Gushing, Harvey W. Cocaine anaesthesia in the treatment of certain cases of hernia and in operations for thyroid tumors.


192; — Laparotomy for intestinal perforation in typhoid fever, 257 ; — Two cases of pylorectomy (discussion), 295 ; — Typhoidal cholecystitis and cholelithiasis, 91.

Dawson, Percy M. Observations on the epithelium of the uiinary bladder in man, 155; See Baer, W. S., Dawson, P. M., and Marshall H. T.

Development of the bile capillaries as revealed by Golgi's method, 220.

Development of the internal mammary and deep epigastric arteries in man, 232.

Diabetes in the negro, 40.

Diagnosis of the condition of each kidney by inoculation of the separated sediments into guinea-pigs in suspected renal tuberculosis, 253.

Diaphragm phenomenon— the so-called Litten's sign, 35.

Discussion : Dr. Abel, Secondary melano-sarcoma of the liver following sarcoma of the eye, 53 ; — Dr. Barker, Cerebro-spinal meningitis, .33; Hjematozoan infection of birds, 18; A microscopic study of the spinal cord in two cases of Pott's disease, 132; Observations on the epithelium of the urinary bladder in man, 158 ; The presence in the blood of free granules derived from leucocytes, etc., 19; Primary focal hsematomyelia from traumatism, 293 ; Regeneration of the dorsal root of the second cervical nerve within the spinal cord, 144;— Dr. Booker, The bacteriology of yellow fever, 120 ; — Dr. Cone, A case of osteitis deformans, 136 ; Two cases of pylorectomy, 296; — Dr. Cullen, Hydraulic pressure in genito-urinary practice, 110 ; — Dr. Gushing, Two cases of pylorectomy, 295 ;— Dr. Finney, Laparotomy for intestinal perforation in typhoid fever, 269; — Dr. Flexner, Cerebro-spinal meningitis, 32; Forty-six intubated cases of diphtheria treated with antitoxine, 147 ; A microscopical study of the spinal cord in two cases of Pott's disease, 133 ; — Dr. Osier, The bacteriology of pertussis, 82 ; Gases of aneurism, 63 ; Diabetes in the negro, 64 ; Laparotomy for intestinal perforation in typhoid fever, 269 ; — Dr. Preston, Primary focal hsematomyelia from traumatism, 293 ; — Dr. Randolph, Cerebro-spinal meningitis, 35 ; — Dr. Russell, Hydraulic pressure in genito-urinary practice, 146 ; — Dr. Sternberg, The bacteriology of pertussis, 82 ; — Dr. Thayer, Hsematozoan infection of birds, 18 ;— Dr. Theobald, Cerebro-spinal meningitis, 34 ;— Dr. Welch, The bacteriology of pertussis, 82; The bacteriology of yellow fever, 119 ; Cerebrospinal meningitis, 31 ; Hoematozoan infection of birds, 18 ; The presence in the blood of free granules derived from leucocytes, etc., 19.

Endothelioma of the cervix uteri, 186.

Epidemic cerebrospinal meningitis, 273.

Epilepsy, the non-medical treatment of, 296.

Epithelial tissue, on certain activities of, 1.

Epithelium of the urinary bladder in man, observations on, 155.

Finney, J. M. T. Laparotomy for intestinal perforation in typhoid fever (discussion), 269 ; — Two cases of pylorectomy, 294.

Fletcher, Robert. A tragedy of the great plague of Milan in 16.30, 175.

Flexner, Simon. Cerebro-spinal meningitis (discussion), 32 ; — Forty-six intubated cases of diphtheria treated with antitoxine (discussion), 147 ; — A microscopical study of the spinal cord in two cases of Pott's disease (discussion), 133 ; — Note on the osteoid tissue found in the tubercular exudate in the thoracic region of the cord, 133 ; — Pathology of heart muscle (discussion), 273 ; — Round ulcer of the stomach. Erosion of gastric artery ; postmortem perforation, 41.

Flexner, Simon, and Anderson, H. B. The results of the intratracheal inoculation of the bacillus diphtherise in rabbits, 7 2.

Forty-six intubated cases of diphtheria treated with antitoxine, 146.


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Foster, Michael. University education, 69.

Fragmentatio myocardii and myocarditis fibrosa, on tiie pathology of, 194.

Futcher, Thomas B. Diabetes in the negro, 41.

Glossitis in typhoid fever, 118.

Gwyn, Norman B. The diaphragm phenomenon — the so-called Litten's sign, 35 ;— On infection with a para-colon bacillus in a case with all the clinical features of typhoid fever, 54.

Hfematozoan infettion of birds, 18.

Halsted, W. S. Inflated rubber cylinders for circular suture of the intestine, 25 ;— Miniature hammers and the suture of the bile ducts, 67.

Hamburger, Louis P. Secondary melano-sarcoma of the liver following sarcoma of the eye, 50.

Hendrickson, William F. The development of the bile capillaries as revealed by Golgi's method, 220 ; — A study of the musculature of the entire extra-hepatic biliary system, including that of the duodenal portion of the common bile-duct and of the sphincter, 221.

Herpes iris, the histo-pathology of, 165.

Histogenesis of the striated muscle fibre, and the growth of the human sartorius muscle, 208, 273.

Holocain, conclusions from clinical and bacteriological experiments with, 154.

Human intestine, development of, and its position in the adult, 197.

Hunner, Guy L. Cases of aneurism, 38, 63.

Hurd, Henry M. The non-medical treatment of epilepsy, 296.

Hurdon, Elizabeth. Endothelioma of the cervix uteri, 186.

Hydraulic pressure in bladder contracture (correspondence), 191.

Hydraulic pressure in genito-urinary practice, especially in contracture of the bladder, 100, 146.

Inflated rubber cylinders for circular suture of the intestine, 25.

Intratracheal inoculation of the bacillus diphtheria; in rabbits, 72.

Johns Hopkins Hospital Medical Society Proceedings: Aortic aneurism, Dr. Brown, 272; — Bacteriology of yellow fever, Dr. Sternberg, 119 ; Discussion, Dr. Welch, 119 ; Dr. Booker, 120 ; — Broadbent's sign, Dr. Camac, 271 ;— Cases of aneurism. Dr. Hunner, 38 ; Discussion, Dr. Osier, 63 ;— Cocaine anassthesia in the treatment of certain cases of hernia and in operations forthyroid tumors. Dr. Gushing, 192 ;— Diabetes in the negro, Dr. Pancoast, 40; Dr. Futcher, 41; Discussion, Dr. Osier, 01; — Discussion of MacCallum's paper on pathology of heart muscle. Dr. Flexner, 273 ;— Epidemic cerebro-spinal meningitis — exhibition of specimens, Dr. Livingood, 273; — Exhibition of specimen of round ulcer of the stomach. Erosion of gastric artery, post mortem perforation. Dr. Flexner, 41 ; — Forty-six intubated eases of diphtheria treated with antitoxine. Dr. Watson, 146; Discussion, Dr. Flexner, 147 ; — Hydraulic pressure in genito-urinary practice (Dr. Young), Dr. Russell, 146; — The non-medical treatment of epilepsy. Dr. Hurd, 296 ; — On the hjematozoan infection of birds, Dr. W. G. MacCallum, 18; Discussion, Dr. Welch, Dr. Thayer, Dr. Barker, Dr. MacCallum, 18 ; — On the pathology of fragmentatio myocardii and myocarditis fibrosa, J. B. MacCallum, 194 ; — On super-arterial pericardial fibroid nodules, Mr. Knox, 62 ; — The presence in the blood of free granules derived from leucocytes and their possible relations to immunity. Dr. W. R. Stokes and Dr. A. Wegefarth, IS ; Discussion, Dr. Welch, 18 ; Dr. Barker, Dr. Stokes, 19 ;— Primary focal hiiematomyelia from traumatism. Dr. Pearce Bailey, 292; Discussion, Dr. Preston, Dr. Barker, 293 ; — Regeneration of the dorsal root of the second cervical nerve within the spinal cord, Messrs. Baer, Dawson and Marshall, 1 14 ; Discussion, Dr. Barker, 145 ; — Two cases of pylorectomy. Dr. Finney, 294 ; Discussion, Dr. Gushing, 295 ; Dr. Cone, 296 ; — A word of warning as to the indiscriminate use of cocaine in the treatment of diseases of the eye, Dr. Theobald, 193.

Jones, Harry C. The rise of the theory of electrolytic dissociation,


and a few of its applications in chemietry, physics and biology,

136.

Kelly, Howard A. The catheterization of the ureters in the male through an open cystoscope with the bladder distended with air by posture, 62.

Knox, J. H. Mason. On super arterial pericardial fibroid nodules, 62.

Koplik, Henry. The bacteriology of pertussis, 79 ; Discussion, Dr. Osier, Dr. Welch, Dr. Sternberg, 82.

Laparotomy for intestinal perforation in typhoid fever, 257.

LeiJrosy in the United Slates, 45.

List of students receiving the degree of Doctor of Medicine, June 14, 1898, 153.

Litten's sign, 35.

Livingood, Louis E. A case of sarcoma of the oesophagus, 159; — Epidemic cerebro-spinal meningitis — exhibition of specimens, 273.

Lobule of the spleen, 218.

Localized sclerosis of the aorta of probable syphilitic origin, 140.

Loeb, Leo. On certain activities of the epithelial tissue of the skin of the guinea-pig, and similar occurrences in tumors, 1.

MacCallum, John Bruce. On the histogenesis of the striated muscle fibre, and the growth of the human sartorius muscle, 208 ; — On the pathology of fragmentatio myocardii and myocarditis fibrosa, 194.

McCrae, Thomas. Glossitis in typhoid fever, with report of a case, 118.

Mackenzie, John Noland. The physiological and pathological relations between the nose and the sexual apparatus of man, 10.

Mall, Franklin P. Development of the human intestine and its position in the adult, 197 ;— Development of the internal mammary and deep epigastric arteries in man, 232 ;— The lobule of the spleen, 218.

Marshall, H. T. S«« Baer, W. S., Dawson, P.M., and Marshall, H. T.

Medical fees in ancient Greece and Rome, 183.

Medicine in the nineteenth century, 277.

Microscopical study of the spinal cord in two cases of Pott's disease, 125.

Miller, G. Brown. The presence of the bacillus typhosus in the gall bladder seven years after typhoid fever, 95.

IMiniature hammers and the suture of the bile ducts, 67.

Mitchell, J. F. The successful treatment of extra-peritoneal rupture of the bladder, comiilicated by fracture of the pelvis, by operation and the continuous bath, report of case, 5.

Musculature of the entire extra-hepatic biliary system, including that of the duodenal portion of the common bile-duct and of the sphincter, 221.

Nose, the physiological and pathological relations between the nose and the sexual apparatus of man, 10.

Notes on new books: — Anders, J. M., Practice of medicine, 20; — The archives of the Roentgen rays, 275 ;— Ball, M. V., Essentials of bacteriology, 88 ; — Bulletin of the Ohio Hospital for Epileptics, 121 ;— Choksy, Khan Bahadur N. H., Report on bubonic plague, 195 ;— Christison, J. Sanderson, Crime and criminals, 21;— Crothers, George D., Elements of Latin, 122 ;— Ehrlich, P., and Lazarus A., Die Anremie, I. Abtheilung, Normale und pathologische Histologic des Blutes, 147 ;— Epidemic cerebro-spinal meningitis and its relatiors to other forms of meningitis, 298; — Garrigues, Henry J., A text-book of the diseases of women, 122;— Garsung, R., Doctor and patient, hints to both, 298;— Gould, George M., The American year-book of medicine and surgery, 1898, 88 ;— Guy's Hospital reports, vol. li, 1895, 44;— Hemmeter, John C, Diseases of the stomach, 120; — von Hofmann, E., Atlas of legal medicine, 195, 297 ;— Uloway, II., Constipation in adults and children, 121;— Jakob, .\tlas of methods of clinical investigation with an epitome of clinical diagnosis.


December, 1898.]


JOHNS HOPKINS HOSPITAL BULLETIN.


301


etc., 171;— James, .T. Brindley, Rheumatism and its treatment by the use of the percusso-punctator, 22 ;— Klemperer, G., The elements of clinical diagnosis, 172;— McFarland, Joseph, A textbook upon the pathogenic bacteria, 298;— Mallory, Frank Barr, and Wright, James Homer, Pathological technique, a practical manual for the bacteriolojical laboratory, 64 ; — Medical annual and practitioners' index, 1898, 171 ;— Medical and surgical reports of the Boston City Hospital, ninth series, 298 ;— Methodist Episcopal Hospital reports, vol. i, 1887-1897, 297;- Park, Roswell, An epitome of the liistory of medicine, 19; — A treatise on surgery by American authors, vol. ii, 42; — Penrose, C. B., A text-book of diseases of women, 21;— Public health reports, vol. xii, 1898, 275;— Ruddiman, Edsel A., Compatibilities in prescriptions, 22 ; — Sajous, Charles E de M., Annual and analytical cyclopredia of practical medicine, vol. i, 297; — Sidis, Boris, The psychology of suggestion, 274; — Simon, Charles E., A manual of clinical diagnosis, 43;— Sutton, J. Bland, The diseases of women, 22; — Tussey, A. Edgar, High altitudes for comsumptives, 44; — Transactions of the Chicago Pathological Society, 1895-97, vol. ii, 21 ; — Transactions of the Indiana State Medical Society, 46th annual session, 1895, 21; — Transactions of the Michigan State Medical Society, 1897, vol. xxi, 22;— Van Valzah, William W., The diseases of the stomach, 275; — Waller, A. D., Exercises in practical physiology, 22; — Walsh, J. Francis, The anatomy and functions of the hand and of the extensor tendons of the thumb, 297.

Obituary : — Louis Eugene Livingood, M. D., 172. Walter S. Davis, M. D., 252.

Oedematous changes in the epithelium of the cornea in a case of uveitis following gonorrboeal ophthalmia, 290.

Osier, William. The bacteriology of pertussis (discussion), 82 ; — Cases of aneurism, 63 ; — Diabetes in tlie negro (discussion), 64 ; — Laparotomy for intestinal perforation in typhoid fever (discussion), 269 ; — Leprosy in the United States, with the report of a case, 45.

Osteitis deformans, a case of, 133.

Osteoid tissue found in the tubercular exudate in the thoracic region of the cord, 133.

Otomycosis, treatment of, by the insufflation of boracic acid and oxide of zinc, 251.

Pancoast, Omar D. Diabetes in the negro, 40.

Papilloma of the Fallopian tube, 163.

Para-colon bacillus, on infection with, in a case with all the clinical features of typhoid fever, 54.

Pardee, Lucius Crocker. The histo-patholrgy of herpes iris, with report of iwo cases, 165.

Pathological changes in the spinal cord in a case of Pott's disease, 240.

Penrose, Clement A. Localized sclerosis of the aorta of probable syphilitic origin, clinical report and necropsy in two cases, 140.

Pertussis, bacteriology of, 79.

Presence in the blood of free granules derived from leucocytes, and their possible relations to immunity, 18, 19.

Preston, G. J. Primary focal hsematomyelia from traumatism (discussion), 293.

Primary focal hsematomyelia from traumatism, 292.

Proceedings of societies, 18, 38, 62, 119, 144, 192, 271.

Pylorectomy, two cases of, 294.

Randolph, Robert L. Cerebro-spinal meningitis (discussion), 35 ; — Conclusions from clinical and bacteriological experiments with holocain, 154.

Refractory subcutaneous abscesses caused by a fungus possibly related to the sporotricha, 286.

Regeneration of the dorsal root of the second cervical nerve within the spinal cord, 144.


Reik, H. 0. Supplementary report on the sterilization of instruments by formaldehyde, 82.

Remarks at the presentation of the candidates for the degree of Doctor of Medicine at the commencement of the Johns Hopkins University, June 14, 1898, 151.

Reynolds, Edward. The diagnosisof the condition of each kidney by inoculation of the separated sediments into guinea-pigs in suspected renal tuberculosis, 2.53.

Rise of the theory of electrolytic dissociation and a few of its applications in chemistry, physics and biology, 136.

Rosenheim, Sylvan. On the pathological changes in the spinal cord in a case of Pott's disease, 240.

Round ulcer of the stomach, 41.

Russell, W. W. Hydraulic pressure in genito-urinary practice (discussion), 146.

Sarcoma of the oesophagus, 159.

Schenck, B. R. On refractory subcutaneous abscesses caused by a fungus possibly related to the sporotricha, 286.

Secondary melano-sarcoma of the liver following sarcoma of the eye, 50.

Solid tumors of the ovaries complicating pregnancy, 56.

Specific gravity of the urine during anfesthesia and after salt-solution enemata, 190.

Spiller, AVilliam G. A microscopical study of the spinal cord in two cases of Pott's disease, 125.

Spontaneous hEemorrhagic septicsemia in a guinea-pig, caused by a bacillus, 270.

Sterilization of instruments by formaldehyde, 82.

Sternberg, George M. The bacteriology of pertussis (discussion), 82; — Bacteriology of yellow fever, 119.

Stieren, Edward. Oedematous changes in the epithelium of the cornea, in a case of uveitis following gonorrhceal ophthalmia, 290.

Stover, G. H. Antitoxic relation between bee poison and honey (?), 271.

Super-arterial pericardial fibroid nodules, 62.

Suprarenal capsule, further observations on the chemical nature of the active principle of, 215.

Swan, William E. The management of solid tumors of the ovaries complicating pregnancy, with report of a successful case, 56.

Thayer, William Sydney. Hsematnzoan infection of birds (discussion), 18.

Theobald, Samuel. Cerebro-spinal meningitis (discussion), 34; — The treatment of otomycosis by the insufflation of boracic acid and oxide of zinc, 251 ; — A word of warning as to the indiscriminate use of cocaine in the treatment of diseases of the eye, 193.

Tragedy of the great plague of Milan in 1630, 175.

Transplantation of the rectus muscle in certain cases of inguinal hernia in which the conjoined tendon is obliterated, 96.

Two instances in which the musculus sternalis existed, 235.

Typhoidal cholecystitis and cholelithiasis, 91.

University education, 69.

Urquhart, A. R. Sir John Charles Bucknill, 180.

Valentine, Ferd. C. Hydraulic pressure in bladder contracture (correspondence), 191.

Watson, Wm. T. A case of osteitis deformans, 133 ;— Forty-six intubated cases of diphtheria treated with antitoxine, 146.

Weaver, George H. Spontaneous hemorrhagic septieamia in a guinea-pig, caused by a bacillus, 270.

Wegefarth, A. See Stokes, W. R., and Wegefarth, A.

Welch, William H. The bacteriology of pertussis (discussion), 82 ; — The bacteriology of yellow fever (discussion), 119; — Cerebrospinal meningitis (discussion), 31 ; — H;ematozoan infection of birds (discussion), 18; — The presence in the blood of free granules derived from leucocytes, etc. (discussion), 19; — Remarks at


302


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 93.


the presentation of tbe candidates for the degree of Doctor of Medicine at the commencement of the Johns Hoplcins University, June 14, 1898, 151.

Wilhite, J. O. Does Wilhite's story of the negro boy incident in the discovery of anaesthesia "lack probability"? (letter), 83.

Word of warning as to the indiscriminate use of cocaine in the treatment of diseases of the eye, 193.

Yellow fever, bacteriology of, 119.

Young, Hugh H. Does Wilhite's story of the negro boy incident in the discovery of anaesthesia " lack probability " ? (letter), 87; — Hydraulic pressure in bladder contracture (correspondence), 192 ; — Hydraulic pressure in genito-urinary practice, especially in contracture of the bladder, 100.


ILLUSTRATIONS.


Epithelium (Figs. 1, 2), 2.

Rod-like nuclei (Fig. 3), 4.

Transplanted skin (Fig. 4), 4.

Presection-stitches (Figs. 1, 2), 26.

Rubber cylinder inflated (Fig. 3) ; Rubber cylinder pushed into bowel (Fig. 4), 26.


23.


Bag inflated with air (Fig. 5), 26.

Mitchell-Hunner stitch (Fig. 6) ; Distended bag and all mattress stitches placed (Fig. 7), 26.

Collapsed bag withdrawn (Fig. 8) ; Circular suture complete (Fig. 9), 27.

The hammer in suture of the common bile-duct (Figs. 1, 2, 3), 68.

Sizes of the hammers (Figs. 4, 5), 69.

Bacillus pertussis, 80.

Reik's formalin sterilizer, 82.

Halsted's operation, second stage (Fig. 1), 97.

The wound ready for the insertion of the deep sutures (Fig. 2), 98.

Halsted's operation, deep sutures inserted (Fig. 3), 99.

The transplanted rectus muscle included by the deep sutures (Fig. 4); Diagram of the position of the transplanted rectus muscle (Fig. 5), 100.

Halsted's acorn urethral nozzle (Fig. 1); Nozzle for intravesical irrigations (Fig 2), 101.

Equipment for irrigations ; Method of holding nozzle for bladder irrigations, 109.

Charts of cases of chronic cystitis. 111.

Chart of case of severe chronic cystitis, 112.

Chart of case of chronic cystitis, 113.

Section just below the pyramidal decussation (Fig. 1) ; Section from the mid-cervical region (Fig. 2) ; Section from the region of greatest compression (Fig. 3) ; Section from the lower part of the compressed area (Fig. 4), 132.

Section below Fig. 3 (Fig. 5); Section from the midlumbar region (Fig. 6); Section from the niid-cervical region (Fig. 7) ; Osteoid masses (Fig. 8), 133.


24. Osteitis deformans. Skiagraph of left knee-joint (Fig. 1) ;

At 36 yrs. of age (Fig 2) ; At 62 yrs. of age (Fig. 3), 134.

25. Side view (Fig. 4) ; Head view (Fig. 5 ) ; Skiagraph of left

tibia (Fig. 6), 135.

26. Periosteal new bone with thickened periosteum and tumor

(Fig. 1) ; From the medullary cavity of bone (Fig. 2), 148.

27. Nuclei and cells (Fig. 1); Single cells with "teeth-like mar gins "(Fig. 2), 158.

28-29. Herpes iris (Figs. 1 to 6), 170.

30. Execution of Piazza and Mora, 178.

31. Costume of a physician, 179.

32. Costume of a physician, 180.

33-34. Endothelioma of the cervix uteri (Figs. 1, 2, 3), 188-189.

35. Reconstruction of embryo No. II (Fig. A), 198.

36. Reconstruction of embryo No. IX (Fig. B), 199.

37. Reconstruction of embryo No. X (Fig. C), 200; Recon struction of embryo No. VI. (Fig. D), 200.

38-42. Development of the human intestine (Figs. 1-18), Plates I-V, 206.

43. Scheme of the intestine (Fig. E), 207.

44. Longitudinal section of adult human heart muscle (Fig. 1).

Cross-section (Fig. 2), 209.

45-46. Cross-sections of voluntary muscle (Figs. 3-5), 210-211.

47. Diagram illustrating the growth of muscle (Fig. 6), 214.

48. Diagram of the lobule of the spleen (Fig. 1), 218.

49. Development of bile capillaries (Figs. 1-15), 220.

50-53. Serial longitudinal sections of human cystic duct (Figs. 1-32), 230.

54. Arterial system of a human embryo four weeks old (Fig.

1), 233. "

55. Section through a human embryo four weeks old (Fig. 2),

234 ; Arterial system of a human embryo six weeks old (Fig. 3), 234.

56. Diagram of development of the arteries of the trunk

(Fig. 4), 235.

57. Attachment of the M. sternalis (Figs. 1, 2), 238; Attach ment of the M. cleido-hyoideus to the clavicle (Fig. 3) ; The slip from the M. latissimus dorsi to the pectoralis major (Fig. 4), 238.

58-59. Drawings of the spinal cord (Figs. 1-14), 250.

60. Photograph of the ileum, 263.

61. Miliary tuberculosis of kidney, 256. 62-63. Temperature charts, 269.

64. Plate I. Colonies of 10 days. Glucose agar (Fig. 1) ; Growth

on glucose agar 3 days (Fig. 2), 290 ; Plate II. Cover-glass preparation from glucose agar ; Growth in hanging drop bouillon (Figs. 1, 2, 3) ; Cover-glass preparations from bouillon (Figs. 4, 5) ; Swollen and germinating conidia from hanging drop of bouillon (Fig. 6); Germ tubes with conidia attached (Fig. 7); Sections of wall of abscess in subcutaneous tissue of dog (Figs. 8, 9, 10) ; Peribronchial lymph glands of white mouse (Fig. 11), 290.

65. Section of cornea, sclera and iris (Fig. 1); Section of

corneal epithelium (Fig. 2), 292.


December, 1898,]


JOHNS HOPKINS HOSPITAL BULLETIN.


303


PUBLICATIONS OF THE JOHKS HOPKINS HOSPITAL.


THE JOHNS HOPKINS HOSPITAL REPORTS. Volume I. 423 pages, 99 plates.

Report in PnthologrT.

The Vessels and Walls of the Dog's Stomach; A Study of the Intestinal Contraction;

Healing of Intestinal Sutures; Reversal of the Intestine; The Contraction of the

Vena Portae and its Influence upon the Circulation. By F. P. Mall, M. D. A Contribution to the Pathology of the Gelatinous Type of Cerebellar Sclerosis

(Atrophy). By Henry J. Berkley, M. D. Reticulated Tissue and its Relation to the Connective Tissue Fibrils. By F. P.

Mall, M. D.

Report in Derniatolog:y. Two Cases of Protozoan (Coccidioidal) Infection of the Skin and other Organs. By

T. C. Gilchrist, M. D., and Emmet Risford, M. D. A Case of Blastomycetic Dermatitis in Man; C^omparisons of the Two Varieties of

Protozoa, and the Blastomyces found in the preceding Cases, with the so-called

Parasites found in Various Lesions of the Skin, etc.; Two Cases of MoUuscura

Fibrosum; The Pathology of a Case of Dermatitis Herpetilormis (Duhring). By

T. C. Gilchrist, M. D.

Report in Pathologr* An Experimental Study of the Thyroid Gland of Dogs, with especial consideration

of Hypertrophy of this Gland. By W. S. Ualbted, M. D.


Volume II. 570 pages, with 28 plates and figures.

Report in Medicine.

On Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with

Gallstones. By William Osler, M. D. Some Remarks on Anomalies of the Uvula. By John N. Mackenzie, M. D. On Pyrodin, By H. A. Lafleur, M. D. Cases of Post-febrile Insanity. By William Osler, M. D. Acute Tuberculosis in an Infant of Four Months. By Harrt Toulmin, M. D. Rare Forms of Cardiac Thrombi. By William Osler, M. D. Notes on Endocarditis in Phthisis. By William Osler, M. D.

Report in Medicine.

Tubercular Peritonitis. By William Osler, M. D,

A Case of Raynaud's Disease. By H. M. Thomas, M. D.

Acute Nephritis in Typhoid Fever. By William Osler, M, D.

Report in Gynecoiogry.

The Gynecological Operating Room. By Howard A. Eellt, M. D,

The Laparotomies performed from October 16, 1889, to March 3, 1890. By Howard

A. Kellt, M. D,, and Hunter Robb, M. D. The Report of the Autopsies in Two Cases Dying in the Gynecological Wards without Operation ; Composite Temperature and Pulse Charts of Forty Cases of

Abdominal Section. By Howard A. Kelly, M. D. The Management of the Drainage Tube in Abdominal Section. By Hcnter Robb,

M. D. The Gonococcus in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Peritoneum;

Ovarian Tumor; General Gynecological Operations from October 15, 1889, to

March 4, 1890. By Howard A. Kelly, M. D. Report of the Urinary Examination of Ninety-one Gynecological Cases. By Howard

A. Kelly, M. D., and Albert A. Ghribkey, M. D. Ligature of the Trunks of the Uterine and Ovarian Arteries as a Means of Checking

Hemorrhage from the Uterus, etc. By Howard A. Kelly, M. D. Carcinoma of the Cervix Uteri in the Negress. By J. W. Williams, M. D. Elephantiasis of the Clitoris. By Howard A. Kelly, M. D. Myxo-Sarcoma of the Clitoris. By Hunter Robb, M. D. Kolpo-Ureterotomy. Incision of the Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gynecological Operations. By

Howard A. Kelly, M. D.

Report in Snrgery, I,

The Treatment of Wounds with Especial Reference to the Value of the Blood Clot in the Management of Dead Spaces. By W. S. Halbted, M. D.

Report in Nenrolog'y, I.

A Case of Chorea Insaniens. By Henry J. Berkley, M. D. Acute Angio-Neurotic Oedema. By Charles E. Simon, M. D. Haematomyelia. By August Hoch, M. D.

A Case of Cerebro-Spinal Syphilis, with an unusual Lesion in the Spinal Cord. By Henry M. Thomas, M. D.

Report in Pathologry* I*

Amoebic Dysentery. By William T. Councilman, M. D., and Henki A. Lafleub, M. D.


Volume III. 766 pages, with 69 plates and figures.

Report in PatliolosT*

Papillomatous Tumors of the Ovary. By J. Whitridge Williaub, M. D. Tuberculosis of the Female Generative Organs. By J. Whitridqb Williams, M. D.

Report in Patliologry*

Multiple Lympho-Sarcomata, with a report of Two Cases. By Simon Flexner, M. D,

The Cerebellar Cortex of the Dog. By Henry J. Berkley, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman. M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Russell, Ph. D.

Heart Hypertrophy. By Wm. T. Howard, Jr., M. D.

Report in Gynecoiogry.

The Gynecological Operating Room; An Fjctemal Direct Method of Measuring the Conjugdta Vera; Prolapsus Uteri without Diverticulum and with Anterior Enterocele; Lipoma of the Labium Majus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Source of Error in Gynecological Diagnosis; Operation for the Suspension of the Retroflexed Uterus. By Howard A, Kelly, M. D.

Potassium Permanganate and Oxalic Acid as Germicides against the Pyogenic Cocci. By Mary Sherwood, M, D.

Intestinal Worms as a Complication In Abdominal Surgery. By A. L. Stavblt, M. D,


Gynecological Operations not involving Coeliotomy. By Howard A. Kelly, M. D. Tabulated by A. L. Stavely, M. D.

The Employment of an Artificial Retroposition of the Uterus in covering Extensive Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdominal Pelvic Operations. By Howard A. Kelly, M. D.

Photography applied to Surgery. By A. S. Murray.

Traumatic Atresia of the Vagina with Hamatokolpos and Hxmatometra. By Howard A. Kelly, M. D.

Urinalysis in Gynecology. By W. W. Russell, M. D.

The Importance of employing Anaesthesia in the Diagnosis of Intra-Pelvic Gynecological Conditions. By Hunter Robb, M. D.

Resuscitation in Chloroform Asphyxia. By Howard A. Kelly, M. D.

One Hundred Cases of Ovariotomy performed on Women over Seventy Years of Age. By Howard A. Kelly, M. D., and Mary Sherwood, M. D.

Abdominal Operations performed in the Gynecological Department, from March 5, 1890, to December 17, 1892. By Howard A. Kelly, M. D.

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


Volume IV. 504 pages, 33 charts and illustrations.

Report on Typhoid Fever.


Report in NenroXogy.

Dementia Paralytica in the Negro Race; Studies in the Histology of the Liver; The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of the Submaxillary Gland of M'i-^ mnsculus; The Intrinsic Nerves of the Thyroid Gland of the Dog; The Nerve Elements of the Pituitary Gland. By Henry J. Berelet, M. D.

Report in Surg-ery,

The Results of Operations for the Cure of Cancer of the Breast, from June, 1889, to January, 1894. By W. S. Halsted, M. D.

Report in Gynecology.

Hydrosalpinx, with a report of twenty-seven cases; Post-Operative Septic Peritonitis; Tuberculosis of the Endometrium. By T. S. Cullen, M. B,

Report in Fntliolosry,

Deciduoma Maligrnum. By J. Whitridqb Williams, M. D,


Volume V. 480 pages, with 32 charts and illustrations.

CONTENTS

  • The Malarial Fevers of Baltimore. By W. S. Thayer, M. D., and J. Hewetson, M. D. A Study of seme Fatal Cases of Malaria. By Lbwellys F. Barker, M. B.
  • Studies in Typhoid Fever. By William Osler, M. D., with additional papers by G. Blumer, M. D., Simon Flexner, M. D., Walter Reed, M. D., and H. C. Parsons, M. D.

Volume VI. 414 pages, "vvith 79 plates and figures.

Report In Nenrologry.

  • Studies on the Lesions produced by the Action of Certain Poisons on the Cortical Nerve Cell (Studies Nos. I to V). By Henry J. Berkley, M. D.

Introductory. — Recent Literature on the Pathology of Diseases of the Brain by the Chromate of Silver Methods; Part I. — Alcohol Poisoning. — Experimental Lesions produced by Chronic Alcoholic Poisoning (Ethyl Alcohol). 2. Experimental Lesions produced by Acute Alcoholic Poisoning (Ethyl Alcohol); Part II. — Serum Poisoning. — Experimental Lesions induced by the Action of the Dog's Serum on the Cortical Nerve Cell; Part HI.— Ricin Poisoning.— Experimental Lesions induced by Acute Ricin Poisoning. 2. Experimental Lesions induced by Chronic Ricin Poisoning; Part IV.— Hydrophobic Toxaemia.— Lesions of the Cortical Nerve Cell produced by the Tosine of Experimental Rabies; Part V.— Pathological Alterations in the Nuclei and Nucleoli of Nerve Cells from the Effects of Alcohol and Ricin Intoxication; Nerve Fibre Terminal Apparatus; Asthenic Bulbar Paralysis. By Henry J. Berkley, M. D.

Report in Pathology.

  • Fatal Puerperal Sepsis due to the Introduction of an Elm Tent. By Thomas S. CULLEN, U. B.
  • Pregnancy in a Rudimentary Uterine Horn. Rupture, Death, Probable Migration of Ovum and Spermatozoa. By Thomas S. Cullen, M. B., and G. L. Wilkins, M. D.
  • Adeno-Myoma Uteri Diffusum Benignum. By Thomas S. Cullen, M. B.
  • A Bacteriological and Anatomical Study of the Summer Diarrhoeas of Infants. By William D. Booker. M. D.
  • The Pathology of Toxalbumin Intoxications. By Simon Flexner, M. D.


Volume VII. About 500 pages with illustrations. (In progress.)

I. A Critical Review of Seventeen Hundred Cases of Abdominal Section from the standpoint of Intra-periloneal Drainage, By J. G. Clark, Jf. i>. II. The Etiology and Strncture of true Vaginal Cysts. By Jamkb Ernest Stokes, M. D. III. A Review of the Pathology of Superficial Burns, with a Contribution to our Knowledge of the Pathol'iK-'caf'ChanKcs in the ()rgan3 In cases of rapidly fatal burns. By Charles Kussell Bardeen. M. D. IV. The Origin, Growth and Fate of the Corpus Luteura. By J. G. Clark, M. 1>. V. The Results of operations for the Cure of Inguinal Hernia. By Joseph C. Bloodgood, M. D. VI . Additional Studies in Typhoid Fever. By William Osler, M. D., and others. Thr price of a set bound in cloth [Vols. I-VIX] of the Hospital Reports is $33.00. Vols. X, II and III are not sold separately. The j^i^ic^ «/ Vols. IVf r, VI and VII is $5.00 each.

No. 93.

THE JOHNS HOPKINS MEDICaL SCHOOL. SESSION 1898-1899.

FACULTY.

Daniel C. Oilman, LL. D., President. Henry J. Berkley, M. D., Clinical Professor of Psychiatry.

William H. Welch, M. D., LL. D., Professor of Pathology, J. Williams Lord, M.D., Clinical Professor of Dermatology and Instructor ia A

Ira Remsen, M. D., Pli. D , LL. D., Professor of Chemistry. T. Caspar Cilchkist, M. R C. S., Eng. Clinical Professor of Dermatology

William Osler, M. D., LL. D., F. R. C. P., Professor of the Principles and Practice of Robert L. Randolph, M. D., Associate in Ophthalmology and Otology

Medicine, and Dean of the Medical Faculty. Thomas B. Futchee, M. K., Associate in Medicine.

Henry M. Hurd. M. D., LL. D., Professor of Psychiatry. Joseph C. Bloodgood, M. D., Associate in Surgery.

Willi,... 3. Halsted, M. D., Professor of Surgery. Thomas S. Ciillen, M. B., Associate in Gynecology.

Howaru A. Kelly, M. D., Professor of Gynecology. Ross G. Harrison, Ph. D., Associate in Anatomy.

Franklin P. Mall, M. D., Professor of Anatomy. Reid Hunt, Ph. D., M. D., Associate in Pharmacology.

loHN J , Abel, M. D., Professor of Pharmacology. Frank R. Smith, M. D., Instructor in Medicine.

WiLLlA>i H. Howell, Ph. D., M. D., Professor of Physiology. John G. Clark, M. U., Associate in Gynecology.

WiLLl> : K Broc.KS, Ph. D., LL. D., Professor of Comparative Anatomy and Zoology. George W. Dobbin, M. D., Assistant in Obstetrics.

John S. rili.LiNGS, M. D., LL D., Lecturer on the History and Literature of Medicine. Walter Jonfs, Ph. D., Assistant in Physiological Chemistry and Toxicology

Albxan .rr C. Abbott, M. D., Lecturer on Hygiene. Sydney M. Cone, M. D.. Assistant in Surgical Pathology.

Chaelt Wardbll Stiles, Ph. D., M. S., Lecturer on Medical Zoology. Harvey W. Ci-shing, M. D., Assistant in Surgery.

Robert Fletcher, M. D., M. R. C. S., Eng., Lecturer on Forensic Medicine. Henry Barton Jacbs, M. D., Instructor in Medicine.

William D. Booker, M. D., Clinical Professor of Diseases of Children. Htgh H. Young, M. D., Instructor in Genito-Urinary Diseases.

loHN N. Mackbnzie, M D., Clinical Professor of Laryngology and Rhinology. Charles R. Hardeen, M. D., Assistant in Anatomy.

Samuel rHEoE-vLD, M. D., Clinical Professor of Ophthalmology and Otology. Stewart Paton, M. D., Assistant in Clinical Neurology.

Henry "l. Thomas. M. D., Clinical Professor of Neurology. N..rman McL. Harris, M. B., Assistant in Bacteriology.

Simon Flkxnfr. M. D., Professor of Pathological Anatomy. Albert C. Crawford, M. D., Assistant in Pharmacology.

J. Whitrcdce Williams, M. D., Associate Professor of Obstetrics. J. W. Lazbar, M. D, Assistant in Clinical Microscopy.

Lbwbllys F. Barker, M. B , Associate Professor of Anatomy. Henry O. Reik, .M. D., Assistant in Ophthalmology and Otology.

William S. Thayer, M. D.; Associate Professor of Medicine. Elizabeth Hukdon, M. D., Assistant in Gynecology.

JohnM. T. Finney, M. D., Associate Professor of Surgery. Otto G Ramsay, M. D., Instructor in Gynecology.

George P. Dreyer, Ph. D., Associate in Biology. William G MacCallum, M.D., Assistant in Pathology.

William W. Russell, M. D., Associate in Gynecology. J. L. Walz, Ph. G., Assistant in Pharmacy.


GENERAL STATEMENT.

The Medical Department of the Johns Hopkins University was opened for the instruction of students October, 1803. This School of Medicine is an integral and coordinate part of the Johns Hopkins University, and it also derives great advantages from its close affiliation with the Johns Hopkins Hospital.

The required period of study for the degree of Doctor of Medicine i? four years. The academic year begins on the first of October and ends the middle of June, with short recesses at Christmas and Easter.

Men and women are admitted upon the same terms.


Cite this page: Hill, M.A. (2024, March 28) Embryology The Johns Hopkins Medical Journal 9 (1898). Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/The_Johns_Hopkins_Medical_Journal_9_(1898)

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