The Johns Hopkins Medical Journal 16 (1905)

From Embryology
Embryology - 1 Apr 2020    Facebook link Pinterest link Twitter link  Expand to Translate  
Google Translate - select your language from the list shown below (this will open a new external page)

العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Historic Disclaimer - information about historic embryology pages 
Mark Hill.jpg
Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

The Johns Hopkins Medical Journal - Volume 16 (1905)

http://www.archive.org/details/johnshopkinsmedi16john

The Johns Hopkins Medical Journal


THE Johns Hopkins Hospital BULLETIN

VOLUME XVI

Vol. XVI. - No. 166.

BALTIMORE, JANUARY, 1905.

CONTENTS - JANUARY

Some Newer Aspects of the Pathology of Fat and Fatty DegeDer atioD. By Henrt A. Christian, M. D., 1

Fabricius Guilhelmus Hildanus; The Father of German Surgery.

By Walter B. Platt, M. D., 7

The Importance of Testing the Ocular Muscle Balance for Near, as

well as for Distant Vision. By Samuel Theobald, M. D., 10 Infantile Paralysis of the Abdominal Muscles ; with Report of a

Case. By William Bdrgess Cornell, M. D., 11

The Diagnostic Value of Tuberculin in Orthopedic Surgery. By

W. S. Baer, M. D. and H. W. Kennard, M. D., IS


A Practical Method of Demonstration. By W. J. Calvert, M. D., 19 The Eflfect of the Bile upon the Ester-Splitting Action of Pancreatic

Juice. By Albion Walter Hewlett, M. D., 20

A Case of Right-Sided Infantile Hemiplegia, with a Description of the Pathological Changes Found in the Brain and the Spinal

Cord. By Robert Reuling, M. D., ai

Notes and News, 34

Notes on New Books, 25

Books Received, 26


SOME NEWER ASPECTS OF THE PATHOLOGY OF FAT AND FATTY DEGENERATION.'

By Henry A. Christian, M. D., of Boston,

Instructor hi rathology, the Medical Svjiool of Harvard University, and Second Assistant Visiting Pathologist, the

Boston City Hospital.


During the past few year.s numerous investigators have been engaged in the study of fat in tissues. New methods of investigation have been evolved, new fax;ts discovered, errors in previous work detected, and gradually, as a result, our ideas as to the occurrence of fat in the body, its sources, and its significance have changed. From the laboratories of the chemist, the physiologist, the pathologist, and the e.xperimental biologist contributions to our knowledge of the subject liave come. These researches are of great interest, the methods used often very ingenious, and the results of much importance in the proper interpretation of pathological findings. Consequently it has seemed to me preferable to review this afternoon some of this more recent work and to discuss its interpretation rather than to limit myself strict!}' to the

narrow field in which I myself have worked. The subject wjiicli I have selected is tlien a broad one and necessarily in tlic time at my disposal I must confine my remarks to its more important phases and even these can be discussed in but a superficial fragmentary fashion.


• A lecture delivered to the post-graduate classes of the Johns Hopkins University, May 9, 1904.


STUDIES IN TYPHOID FEVER.

SERIES I-II-IIl.

Volumes IV,


and VIII of the Johns Hopkins


The papers on Typhoid Fever, edited by Professor William Osier, M. D., and printed Hospital Reports, have been brought together and bound in cloth.

The volume includes thirty-five papers by Doctors Osier, Thayer, Hewetson, Blumer, Flexner, Reed, Parsons, Finney, Cushing, Lyon, Mitchell, Hamburger, Dobbin, Camac, Gwyn, merson and Young. It contains 776 pages, large octavo, with illustrations.

The price is $.5.00 per copy. Address The Johns Hopkins Press, Baltimore, Maryland.


Jaxuary, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


FABRICmS GUILHELMUS HILDANUS: THE FATHER OF GERMAN SURGERY/


By Walter B. Platt, M. D.


The father of German surgery, or as he has been called the Ambroise Pare of Germany, was born on June 25, 15G0 in Hilden, Germany, not far from Dtisseldorf, as plain Wilhelm Fabry. Early in his professional career he latinized his name after the fashion of the day, making it Fabricius Guilhelmus Hildanus, now often called simply Hildanus, to distinguished him from another Fabricius. As Latin was the international tongue of letters, religion, and what there was then of science in Europe, this was not as absurd and pedantic as it now seems. The fraternity of letters was far less national than at present, and students and scholars went from la;id to land seeking the knowledge they could not otherwise obtain. For these reasons most of the important works of Hildanus were written in Latin.

His father was clerk of one of the courts, a man of parts we hear, and at least respectable and respected. Hildanus himself speaks of his father as "homo literatus."

The father dying when Hildanus was but a year old he was left to the care of his mother who speedily remarried. Of our surgeon's boyhood we know little except that he seemed to have unusual vitality, vastly enjoyed swimming, and suffered a paralysis of the tongue at the age of twelve in consequence of swimming too long in cold water. It was many years before he perfectly recovered his speech. Left with little or no means early in life the good poet Utenhof assisted him, sent him to school in Cologne, and as he grew older urged him to become a phj'sician. Medicine was not at all to his taste and from the first he preferred surgery. In 1576 when but 15 years of age he entered the service of a surgeon named Dumgens at Neuss, with whom he remained four years, after which he joined himself to the surgeon of the Duke of Cleve. Xow began a series of wanderings from place to place.

Going to Metz in 1585 he went thence to Geneva where he operated on a strangulated hernia. Two years later he married Marie Colinet, who turned out to be a helpmeet indeed. Leaving Switzerland in 1588 he returned to Hilden for 3 years, going thence to Cologne where he practiced from 1591 to 1596.

Besides practicing surgery arduously, he cultivated the science of medicine in its broadest sense, and wrote many monographs and descriptions of surgical procedures. In 1593 he published what is perhaps the best known of his writings at the present time, " De Gangrena et Sphacelo." He also described the most important of the valvular folds of mucous membrane of the rectum, and demonstrated its function.

We find him again at Lausanne in Switzerland in 1596 where he worked hard at his anatomy and made many autop


'Read before the Johns Hopkins Hospital Historical Club, March 14, 1904.


sies, but he could not remain very long in one place and went back to Cologne in 1597 where he remained 3 years. He was in Lausanne again in 1600, whence he fared to Payern. In 1607 he published a work on dysentery, and constructed a model of an eye for the itse of students.

His family had the bubonic plague in 1613 and most of his children died of it. After he thought he was at last rid of it, the plague reappeared in his house after nn intermission of months.

About this time von Hildanus became a great sufferer with a neuralgia or gouty headache, which he finally traced to a particular kind of wine of which he was very fond. He also was a martyr to gout.

Those who are afflicted in a similar way may console themselves with the thought that they are in good company for numbers of our greatest (as well as our laziest) men have had the gout. Hildanus now lived in Berne for a season. In 1619 he finished " Observationum et Curationum Chirurgicarum Centuria? IV," and ^Tote his hundred letters to his friends.

He wrote " Observationum et Curationum Chirurgicarum CenturifE VI," his last, in 1623, and in 1630 on a " Christian way to Eat." In 1624 he wrote upon the value of anatomy.

In 1626 he wrote his well-known work on Stone, and two years later was very ill with the gcut.

After this it is quite natural, that he should write upon the " Preservation of the Health "' by the use of certain warm springs.

We think we can see the steady progress of gouty nephritis as in 1631 he had bronchitis, and was often annoyed by asthma.

He died on February 14, 1634, aet. 74 years.

Of all his children, but one, a son, survived his father.

Hildanus was a deeply religious man, a very conscientious operator, not at all vain; on the contrary he was always dissatisfied with his work, while the amount he accomplished was prodigious. He always declined to operate when he thought the outlook a fatal one. His letters were very numerous. He is said to have corresponded with 150 physicians and other learned men. Although very modest he did well financially, unlike most men of his type. He always showed great mental activity.

HiLUAXUS.

In the time of Hildanus, Wesling writes from Venice comparing German surgery with that of Venice, saying " Surgery has a somewhat better status here, although even here there are those called surgeons who come from the dregs of the population, so that if Venice had to take the field, about 2000 dirty barbers and enema givers would enlist as suro'eons."


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 166.


Ilildanus gives a few examples of the state of surgery in his time as follows:

" A cabinet maker who was watching the drilling of an artillery battery, was wounded in the breast by the discharge of a blank charge from standing too near, in consequence of which the covering of the chest was torn away down to the ribs. A barber surgeon who was summoned, seeing a bare rib, seized it with a pair of forceps, and tried with all his force to drag it away, tliinking it some part of the ramrod. Fortunately a bystander drove the barber away, applied a suitable dressing to the exposed ribs, and in time the man recovered."

Hildanus says " In spite of all their ignorance, the surgeons thought they knew better than educated physicians "' and he relates how in one case where he "had refused to amputate the limb of a man who had senile gangrene, a barber did the operation, amputating the thigh which of course speedily became gangrenous at the seat of operation, whereupon the patient died; " Hildanus writes further: " Christian pity often makes me weep over the doings of those men who plaj' so recklessly with human life." (Archiv f. klin. Chirurgie, 1865, vi, by Meyer Ahrens.)

Although a surgeon, Hildanus knew his anatomy better than most professors of that branch, and laid great stress upon a thorough knowledge of this subject. He called anatomy the " key " to every department of medicine, and the " rudder " to all medical practice.

He demanded that priests should have some knowledge of it, and that lawyers should likewise have an acquaintance with anatomy that they might apply torture with more effect and discretion to criminals, so as to avoid sudden death, or a confession of crimes which had not been committed. He saw the importance of some education of midwives in anatomy that they might know enough to call in a physician before it was too late to do any good.

At the end of the 16th and beginning of the 17th centurv it was difficult to obtain bodies to dissect in Switzerland. In the year 160] when he demonstrated the valvulaj Bauhini (of the rectum) on a cadaver, it is related that he carefully preserved the fat of the subject to send to a French phvsician who wished to use it as a therapeutic agent.

Hildanus' first good anatomical preparation was a maceration, showing the blood-vessels of the abdominal viscera, notably those of the liver, kidneys and genito-urinary system.

According to the custom of his time, he finds all manner of curious analogies between tlie human body, and the universe in general.

He makes gruesome remarks upon the advisability of so applying torture to criminals as not to fracture the scapube by bending back tlie arms too far, something he has often seen, since men thus treated would be apt to confess to crimes they had never committed.

Like a true scientific surgeon he attached great importance to a knowletlge of pathological anatomy. He took an especial interest in congenital malformations, making a number of drawings in these weird creations. He made moreover a collection of bones showing the healing of fractures, and in a


letter to Prof. Paw he eulogized the value of Comparative Anatomy, Botany and Chemistry.

Like most physicians of his time he ^^•as a believer in the medicinal virtues of various disgusting agents, such as portions of vipers, and of dried toads. Mineral water baths were objects of his admiration as healing agents, and he wrote a monograph in 1629 on the preservation of health by the use of certain thermal springs. He wrote much about the plague or what he thought was the plague, which destroyed so many human lives and spoke of the inefficacy of any known treatment, although he felt sure that those who had issues in their arms did not die of it.

Hildanus was a great believer in the use of minute varieties of instruments, and spent much time and ingemiity in devising them. One of these was a bullet extractor, consisting of a tube which was introduced down the track of the bullet until it reached the ball when a cork-screw-like device was protruded. This was supposed to enter the ball, so as to allow of its removal by traction. He treated the bites of rabid animals with all sorts of irritating mixtures, but also with the actual cautery.

He combated the idea advanced at that time, that in cranial fracture the depressed bone should not be elevated, and invented a somewhat impracticable instrument to raise the depressed fragments. He makes frequent use of egg albumen as a styptic, discusses polypi, and describes the operation for the removal of the breast for cancer. As far as thci anatomical part of it is concerned he operated much as we did 20 years ago. The use of caustics in these cases which had a charm for many patients and physicians, he deplored.

Concerning the radical cure of inguinal hernia, he remarks the extreme rarity of such cures in his time, but details one in a well-known personage where such a result was achieved by several months rest in bed in a horizontal position and the continual use of a truss.

It is interesting to note that Ilildanus was a firm believer in the virtues of issues, and fontanelles, devices to secure snp]niration, as a means of warding off disease by providing an outlet for " vicious humours " which were supposed to he their cause.

He invented a suspensory bandage, and urinals to be worn by the patient when going about, and also club-foot apparatus. Fabricius was aided by a help-meet indeed, who was skillful in the art of obstetrics, for his wife was often present in difHcult cases.

At the beginning of the I'lth century no one thought of calling in a physician until midwives had utterly failed. It was then usually too late to do much for the patient, for these midwives were a wretchedly ignorant lot. In a Treatise on Lithotomy published in Basel 1629, Hildanus warns all ignorant persons not to undertake to cut for stone, and in the course of his discussion of the operation he says, "The patient should prepare himself in all ways for death before the operation, he should make his will and ask for prayers in church." That Hildanus had an exalted ideal of a surgeon will l:>e seen when we learn that " he should before all, fear God, be


Jaxuary, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


true, pious, upright, not given to cursing or swearing, he should not be addicted to drinking, whores or gambling." The patient should avoid all physicians who gossip or chatter much, or who boast of their powers as if none were equal to them."

Furthermore he says " a surgeon should not be merely an empiric guided alone by his e.xperience, but should have studied more in the science and groundwork of his profession."

Hildanus operated for stone in the male bladder usually by a lateral incision in the perineum, but they were sometimes removed through the rectum, while in women he removed them either bj' way of the vagina or urethra. When patients came to the surgeon with very large stones, Fabricius advised that operation be declined, and that they be turned over to their spiritual advisers.

Stones in the bladder at this time were often removed in several sittings, the incision being the first sitting, when unless the stone presented at the opening, delay was advised until it did, when an attempt was made at extraction. If this did not succeed, another wait was advised, the patient being put through a course of medical treatment tending to relax the opening and eject the stone.

Meyer Ahrens mentions a " stone-cutter " of Ulm who operated between 1610 and 1626 upon 3000 cases of stone in the bladder and hernia, who was absolutely opposed to operating for stone in several sittings.

Perhaps the most famous work of Hildanus was one upon Gangrene, Hot and Cold, published in 1593, in which he advises that operation must be done by all means in sound tissue and if the gangrene be in the foot the amputation should be 4 to 5 fingers' breadth below the knee. If the gangrene be above the knee, as near as possible to the gangrenous part. He dwells much on the preparation for the operation by purgatives, by supporting the heart's action and sometimes by venesection. He advises that arteries be tied only in strong and full-blooded individuals. At that time, Harvey's discovery of the circulation of the blood had not been made, and the tourniquet was not used. Pressure forceps, which had narrow beaks, were used to compress arteries. When arteries were ligated we have the authority of Meyer Ahrens for the statement that this was done by applying ligatures over artery forceps. After the amputation, compression was applied to the parts.

In an essay " De Combustionibus " he makes 3 degrees of burns, and in treating of gunshot wounds he discusses the proijlem, whether or not we ought to take into consideration the heating of the bullet by its passage out of the gun, or in passing through the air, or whether a poisoning of the wound takes place from the gunpowder used.

A Latin edition of his works was published in Frankfort, 1646.

Work of Fabricius Hildanus.

His works are mostly in Latin, some in French and a few in German.


His best known work that on Gangrene is in old French and was written in 1597. Accurate language was not then the fashion, and more stress was laid on regimen then, than now. His work on stone in the bladder has this title: " Lithotoraia Vesicse, that is, an accurate description of the stone in the bladder, showing the causes and pathological signs thereof, and chiefly of the method whereby it is to be artificially taken out, both of men and of women, by rectum. Written first in High Dutch by Guilhelmus Fabricius Hildanus; first translated into Latin by his Scholler and Communer, and now done into English by N. C. for the general good of the nation and particular use of the Society of Barber Surgeons, London, 1610."

" To the worshippful Companie of the Barber Chirurgians, John Norton wisheth encrease in skill, fortunateness in practice, and all other happinesse. How dangerous in practice the Curation of the Stone by section is, it is evidently evinced not only by reason, if we consider the structure and temperature of the part affected, but by experience also ; seeing so few attempt it, and so many doe die who submit themselves to this manner of curation, although the operator perform his part: wherefore too great caution cannot be had in going about this operation."

Chapter 1st of this work by Hildanus begins thus : " The divine Hippocrates, Father of Physicians, hath not without cause in his book ' De Arte,' left us this aphorisme : ' The Physician which can discover the disease, may be able also to cure it, advising thereby all prodent sonnes of art that they should use all diligence and care to get an exact and accurate knowledge of the disease before they intend or think to prescribe an order for the cure.' "

He then advises surgeons to read up, "first the ancients, Hippocrates, Galen, Paulus, Aegineta, but the later writers also, Vesalius. Fallopius, Aquapendente, Ambroise Pare and others, to find out the theory and intention," for he says: " This advise I doe not causelessly set downe in the enhance of this translate. For I know there are some giddy headed and unadvised chirurgians which upon each slight signe and uncertaine suspitian of the stone commonly apply the incision knife to the bladder, boring and searching there, yet in the end, find no stone at all." Again to define a stone he says : " I say the stone is a preternatural, grosse, slymie, coagulated humor, brought into a stone of a thick matter, by a preternaturell lieate and hidden quality of the bladder."

Chapter 3.

" Because every faithful Chyrurgion and Physitian is, bound before God' the Chief Physitian, not only to cure the sick, but by his good councel to keep those that are cured in their healtii ; not only to take away the stone, but to provide against the breeding of any new ones ; therefore it is required principally that the Chyrurg know and be taught how and from what causes the stone in the Body of Man and especially in the Bladder, is generated and coagulated together."

He thinks that those who cut men for stone and find none, should be severely punished "and to be paid in their own


10


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 166.


coyne, for it is written ' an eye for au eye and a tooth for a tooth ; ' " also " Besides all this it is chiefly required that the Lithotomist and Cutter of Euptures should be well versed in the Anatomical part of physick."

We see that Hildanus was an advocate of the higher education of physicians and of their divine right to practice, by the following : " In which words the scripture doth distinguish who are lawfully called to this work and approved by the learned from those who not after the wonted manner enter in at the gate, but like thieves creep in at the windowes and back doores, and by whom the sick men are deprived of their health with their goods and estate.

Such are idle and unskilled Mountebanks, Juglers, vagabonds, executioners, and other detestable villanes of this sorte, whom many would scarce trust for a farthing, whereas in the meantime they trust them with their health, both of their body and soule: So farre the Divell hath blinded man."

" Who so ever therefore should be ungratefull to a faithfull and industrious Physitian, being ordained by God, whether in word or deed, much more by keeping back his reward (of which sort I have met with many) he may easily perswade himself that God will be avenged of him for the labour and trouble which the godly, honest and faithfull Physitian hath undergone for the sick mans sake."

Just before operation "the help and assistance of Almighty God is first to be seriously and devoutly implored by a lawful Minister (if any be present) or in his absence by some of the bystanders who if he please may use one of the prayers prefixed before my treatise De Gangrena et Sphacelo."

The patient is then to jump, or if an infant it is to be shaken, " that the stone may fall down toward the neck of the bladder."

Hildanus ad\ases a perineal lateral operation, and not to attempt to remove a large stone, but to abstain from operation where the patient has no chance of surviving, " for this is better and more commendable in a faithful and diligent Chvrurg


than {as some usually doe) to draw the languishing Patients as it were to the shambles."

He relates one of his surgical experiences as follows : " It so befell me at Paterniam when I was about to cut off the thigh of a man of forty yeares of age, and ready to use the saw and cauteries. For the sick man no sooner began to roare out, but all ranne away except onely my eldest sonne, who was then but little and to whom I had committed the holding of the thigh for forme onely; and but that my wife, then great with child, came running out of the next chamber and clapt hold of the Patients Thorax, both she and myself had been in extreme danger."

He then discusses the folly of employing diuretics before the operation.

If we summarize the character and work of Hildanus we see in him a very talented yet modest man of strong vitality and convictions, exceedingly industrious, truly religious, devoted to his profession, restless and migratory in his instincts; a man of great personal magnetism, who by his numerous intelligent observations and skillful operations, more than all his predecessors is entitled to be called the Father of German Surgery Bibliography (partial list).

Fabricius Hildanus : Traite de la Gangrene et du Sphacele, Geneva, 1597. De Combustionihus, 1610.

Observ. et Curationum Chirurgicarum, 1610.

De Vulnere quodam gravissimo et periculoso, 1614.

De Conservanda valetudine, item, de thermis, 1629.

Lithotomia vesica; An accurate description of the

Stone in the bladder, London, 1640, J. Norton.

Opera Observ. et curationum medico-chirurg.

His 600 Observations and his One Hundred Letters.

For Biography see Meyer Ahrens in Archiv f. klin.

Chirurg., Berlin, 1865, also Monit. d. hop. Par., 1857.


THE IMPORTANCE OF TESTING THE OCULAR MUSCLE BALANCE FOR NEAR, AS WELL

AS FOR DISTANT VISION.

By Samuel Theobald, M. D.,

Clinical Professor of Ophthalmology and Otology, Johns Hopkins University; Ophthalmic and Aural Surgeon

to the Johns Hopkins Hospital, Baltimore.


With increasing experience in dealing with asthenopic eyes, I am more and more impressed with the importance of making in every such case a careful test of the muscle balance for near, as well as for distant vision.

Although in recent years so much attention has been paid to anomalies of the ocular muscles, the significance of the muscle balance in near vision does not seem to have received the recognition which its importance demands. The fact


that there is often marked discordance between the behavior of the muscles in distant vision and in near vision appears not to have impressed itself upon systematic writers upon diseases of the eye; and, indeed, it is evident that not all of them are informed as to what is the normal behavior of the muscles when tested for the reading distance.

What constitutes orthophoria in distant vision everyone knows; but, in spite of the fact that it was long ago pointed


January, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


11


out, everyone, it would seem, does not know that, as determined by the vertical diplopia test, the normal state at 12 or 13 inches is an exophoria of 2° or 3° or even of -i", and that a muscle balance which in distant vision indicates orthophoria is indicative really of a heterophoric condition when found at the reading distance.

In my papers upon " Subnormal Accommodative Power " ' I have emphasized this point, and have also set forth what, as I view it, is the peculiar significance of esophoria which is present in near vision only, or which is more pronounced in near than in distant vision.

The results which I have obtained in this condition, to which I gave the name subnormal accommodative power, by following the rules laid down in my papers — prescribing at times for young asthenopic emmetropes convex glasses of considerable strength for near work, and for j'oung hypermetropes stronger glasses for near than for distant vision or combining with their near lenses esophoric prisms — have been so eminently satisfactory that this jiractice is now as much a matter of course with me as the correction of astigmatism or of hypermetropia itself.

The opposite condition, in which there is present a considerable amount of actual exophoria at the reading distance, vi'ith normal muscle balance in far vision, a condition by no means rare, is of scarcely less importance, and calls as emphatically for glasses especially adapted for near work, that is to say for lenses which, in addition to correcting such refractive error as may be present, take into account the inuscular fault.

Occasionally, in dealing with this condition of discordance between the far and near muscle balance, and having in mind the convenience of the patient, I prescribe bifocal lenses; and, when they see one of my, perhaps, fifteen- or sixteen-year old patients thus equipped, some of my brother oculists are doubtless not a little surprised.

It is not my present purpose, however, to dwell upon these differences of lateral muscle balance to which I have alluded. It was the observation recently of several cases of hyperphoria, which was present in near vision only, and which proved to be


' Trans. Am. Ophthalmolog. Soc, 1891 and 1894.


an important factor in the causation of the asthenopic symptoms, that prompted me to write this paper.

Thanks to Maddox, wc are able now to detect the existence of hyperphoria, and to determine its degree, much more easily and exactly than was formerly possible. With the aid of his multiple rod, and with the further assistance of Dr. Schild's well-contrived little electric light,^ which I have the pleasure of showing you, I now find it no hardship to test for this defect in near as well as in distant vision. And the outcome of this is, I have learned that differences exist between the vertical muscle balance in far and in near vision much oftener than I had supposed. Indeed, I have not only found cases such as I have mentioned, in wliicli hyperphoria was present in near vision only, but I have met with a few instances, not, however, marked in degree, in which there was hyperphoria in one direction in distant vision and in the opposite direction in near vision — a right hyperphoria, for example, at 20 feet and a left hyperphoria at the reading distance.

I am, therefore, as I said at the outset, more than ever convinced of the importance, in every case of asthenopia, of testing the muscle balance for near vision. Frequently this test shows nothing that is significant ; but, on the othsr hand, it occasionally reveals a fault which must be taken into account if our patient is to obtain complete relief.

I may add, in conclusion, that in determining the balance of the muscles in near vision I use the simplest contrivances — for the vertical diplopia test, a prism of 7° taken from my trial case, and upon a card attached to a rod 12 inches in length a small object calculated to stimulate accommodation, such as an asterisk; and for discovering hyperphoric faults, a multiple Maddox rod with a Schild electric light. The Schild light, if one wishes, may be used instead of the asterisk in the vertical diplopia test ; but I do not feel quite sure that it prompts the patient to accommodate as accurately as the asterisk does.

The employment of these tests, which usually give entirely trustworthy results, requires but a very few moments, and the information which they afford is, I am sure, much too valuable to be ignored.


2 Described in the Ophthalmic Record, June, 1904.


INFANTILE PARALYSIS OF THE ABDOMINAL MUSCLES; WITH REPORT OF A CASE/

By Wm. Burgess Cornell., M. D., Clinical Assistant, Sheppard and Enoch Pratt Hospital, Toivson.


The commoner distribution of the residual muscular palsies in acute anterior poliomyelitis of infants is too well-known to Justify repetition. Nearly every monograph or text-book on the subject gives tables showing the relative frequency of the muscular involvement, but very few consider the ques


^From the Neurological Dispensary, Johns Hopkins Hospital.


tion of the abdominal muscles. In looking over the literature, so few cases have been found as to justify the conclusion that a residual paralysis of the abdominal muscles in infantile paralysis is rare.

It is a matter of common record that the paralysis at onset is more widespread than at any subsequent time. On this account, coupled with deficient observation, it is possible that


12


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 166.


many cases showing participation of the abdominal muscles are overlooked. This seems the more probable wlien we consider the statement made in many text-books that the trunk muscles, though often paralyzed at first, rarely remain so, together with the fact that, especially in dispensary practice, the patients are not seen for some days or weeks after the onset. In the absence then of adequate data on the occurrence of abdominal involvement in the initial paralysis we may provisionally state that if frequent, the tendency in the vast majority of eases is to rapid recovery. The rarity of a residual paralysis in this region may be judged from a consideration of some of the monographs on infantile paralysis.

Seeligmiiller (1) in his series of 75 did not have a case of either back or abdominal paralysis.

Sinkler (2) gives in his 340 cases 32 as having involvement of "trunk," none of these, I am informed, included abdominal muscles, but showed impairment only of the muscles of the back, which in every instance was temporary.

Starr (3) in his text-book makes only passing reference to the subject, but gives 4 in his series of 117 cases which showed involvement of " trunk." He believes probably one-third of the trunk cases have paralysis of the abdominal muscles. He has seen 6 such cases, but I am not informed whether they were temporary or permanent. I have been able to collect the following cases which resemble more or less the one I report.

Duchenne fils (4) in his series of 75 cases mentions one a boy of 10 months, who 6 months previously had a generalized paralysis. The movements returned to the upper extremities, but the legs showed a flaccid paralysis in most of the muscles. On the right the muscles of the abdomen and trunk were for the most part atrophied, giving a dorsal scoliosis with convexity to the right. The abdominal walls on the affected side were thin and gave no response to electrical stimulation. When the infant cried there was contraction only on the left, while on the right the abdomen bulged out in a hernia-like prominence. The child was lost sight of and the final outcome was not learned. Duchenne states, " this observation of atrophic paralysis of the muscles of the trunk and abdomen is the only one I Icnow of, and I have not been able to find a similar one in the literature on the subject."

Birdsall (5) has reported one case in which the paralysis was also unilateral.

Bernheim (6) and Leiner (7) have each described one. The former, one of the oblique muscles; the latter, a case very similar to mine, except that the patient was 12 j^ears old.

In the large number of cases of poliomyelitis seen at the Johns Hopkins Hospital Dispensary, the following is the only one, so far as I am aware, showing a residiial paralysis of the abdominal muscles. The case lends an additional interest in that it presented the crossed type of paralysis of the extremities, which appears only in a very small proportion of the cases.

Isaac H., Russian Jew; aet. 21 months; admitted to the Johns Hopkins Hospital Dispensary, August 6 (No. 062260). The family history is negative. The child was said to be


healthy until present attack. From appearances he must have been surrounded by squalid conditions. Two weeks previous to admission or about July 23, he had an attack of fever lasting three days. During this time the child slept almost constantly. Afterwards it was noticed that the infant could not sit or stand, and that the right leg and left arm were paralyzed. By August 9 the movements had returned to both affected members, the hand to a less degree. By Augiist 20 the child could walk, using both arm and leg fairly well. No note was made on the condition of the abdomen prior to September 15 when the paralysis was first noticed. There must have been asymmetry from the first, which became more apparent as the muscles grew more flaccid and atrophic. November 15. Present Condition. — The child is fat and healthy looking, complexion ruddy. Weight 27.5 pounds, height 31 inches, head, occipto-frontal circumference, 19.7 inches (Holt gives 26.5, 32.5, and 18.9 as corresponding figures for a boy of 2). The head is somewhat square-shaped, with undue prominence of frontal and parietal eminences, while the vertex tends to flatness. Chest is well-formed, symmetrical, and expands equally both in quiet and deep breathing. The diaphragm and intereostals are normal. There is no rickety rosary; no bracelets. There are no visible signs of paralysis in arms or legs except the left arm seems slightly smaller and measures 0.5 cm. less than the right, at its middle point. The forearms measure alike. The biceps tendon, radial biceps, ulnar and triceps reflexes are present, equal and normal. The thighs and legs measure alike. The knee-jerks are lively and equal. Tendo Achillis reflex normal. Scratching the soles of his feet produces flexion of all the toes and of the foot, alike on both sides. It is difficult to test accurately the relative muscular strength, but all movements in arms and legs seem symmetrically strong. The infant walks well, but favors the right leg somewhat, rotating it outward so as to step off the inner side of foot.

Abdomen. — The relative liepatic dulness begins 3 cm. above the costal margin and extends 8 cm. downward in nipple line. In mid-line by dipping, it extends 8 cm. below the ensiform bone. Spleen is palpable. Palpation and percussion are otherwise negative. In dorsal decubitus the abdomen is full, but is more prominent on the right. Abdominal skin reflex is present on left, absent on right. Umbilicus is in mid-line. As the child cries and raises tlie intra-abdominal pressure, the right side balloons out very markedly. On palpation the muscles may be felt to contract under the hand on the left, but not on the right side. In the erect position the conditions are intensified. The left abdomen is now seen to be quite prominent. (Patient's sister states that the belly was quite large before the illness, and we may infer a mild previous rickets.) The asymmetry is much more evident in this position, and as the child cries, the right side balloons out to the full limit of the flaccid and paralyzed wall. Pig. 1 shows this condition in profile. Fig. 2, as well as Fig. 1, shows the greatest protrusion is in the lower right quadrant. Fig. 3 is f; profile of the left side, the child is" soVibing, which amounts


THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY. 1905.



Flo. 1. — Maximum protrusion iu prulilf


Flu. 2. — ilaximum protrusion, llirppquarters face.



Fiu. 3.— Profile of left side.


Erratum.— This plate should luivo bfon inserted in the Bllli;tin for January, 1005, opposite luige 12.


Jaxuart, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


13


for The indistinct outlines and gives this side a somewhat fuller appearance than in reality. The paralyzed mnscles are the obliqiu; the transversalis, and half of the rectus abdominis on the right. An attempt was made to test their electrical reactions, but as the child unfailingly cried every time the current was applied, nothing definite could be k'arned. As the pictures show, there is no lordosis. There i?, however, a slight scoliosis in the hmibar region, with convexity to right.

In conclusion I wish to thank Dr. Thomas, from whose clinic I report this case, and Dr. Cushing for kind help.


Eeferexces.

1. Seeligmiiller: Gerhardt's Handb. d. Kindcrkrankheit-cn, 1880, Vol. Y.

2. Sinkler: Keatiug's encydop. of Childr. Dis., 1890, Vol. IV.

3. Starr: Organic Nervous Diseases, p. 214.

4. Duchenne: Archiv. Gen. de Med., July, 1864, p. 4.j.

5. Birdsall: Cit. Jacobi in Pepper's Syst. Med., 1S8G, Vol. V, p. 1121.

6. Bernheim : Corresp. Blatt f. Schweizer Aertze, 1903. s. 793.

7. Leiner: Berl. Klin. Woch., 1903, s. 513.


THE DlAGiNOSTIC VALUE OF TUBERCULIN IN ORTHOPEDIC SURGERY.

By W. S. B.vek, M. D.,

Instnuior in Orthopedic Surycrij, The Jolins HopJiins University,

AND

H. W. Kennard, M. D., Assistant In Orthopedir Surgerij, The Johns Hopkins University.


For the permanent cure of tuberculosis in any form we must be able to recognize the presence of the disorder while it is still in its incipiency. Any means, therefore, which will afford us an opportunity to attain this end at an earlier date than ordinarily we are accustomed to do, will go far toward lessening the death rate, will increase the percentage of cures, and cannot fail to be of the greatest benefit to mankind.

Koch (1) in 1890 described such an agent in tuberculin, and in his earliest articles (2) definitely stated its diagnostic, as well as its therapeutic value. But amid the enthusiasm of the medical profession over a discovery that produced a specific for the cure of tuberculosis, practically no attention was at first paid to its diagnostic properties. Year by year, however, despite the disfavor into which it speedily fell as a therapeutic agent, tuberculin has gradually pushed its way to the front again until today it is recognized as one of the most important diagnostic agents in beginning tuberculosis.

We do not propose in this paper to speak of its therapeutic or diagnostic properties in incipient pulmonary or glandular tuberculosis. Much has been written on these subjects by Friinkel (3), Mettetal (4), Casselbery (5), Finkh^r (6), Guttman, Otis (7), Trudeau (8), Tinker (34), and others. Here we would rather refer to the results in a series of cases which, we believe, go to show the great value of tuberculin as a means of diagnosis in bone and joint tuberculosis. Take, for instance, disease of the spine. In \ery early cases how many of us are there who have not too often been in doubt whether we were dealing with tuberculosis, rachitis, rheumatism, syphilis, spondylitis deformans, or simply a sprain? Is it not sometimes difficult in diseases of the hip to differentiate tttberculosis from sraovitis, gonorrhojal arthritis, rheumatism, osteo-mvelitis, co.xa vara, or fracture? The


same may be said in disease of the knee, ankle and other joints. We are fully convinced that in the proper use of tuberculin we have a perfectly harmless method, simple in its application, which will almost invariably tell us of the presence of tuberculosis long before it can be detected by any other means; nay more, tuberculin not only shows us that we are dealing with a tuberculous process, but also in the great majority of instances points out the location of the focus.

The tuberculin used by us came from the laboratory of Dr. Trudeau, to whom we are greatly indebted for a liberal supply. His manner of preparing it is very similar to that of Koch. The tuberculin is a 50 per cent glycerine e.^tract of the bouillon on which the ttibercle bacilli have been grown. The fiasks are inoculated from a well developed culture of activel}' growing bacilli, and are then kept in the incubator for six weeks at a temperature of about 37° C. For the tuberculin the contents of flasks are chosen which show a well developed growth over the surface of the bouillon. From one liter of these about 100 cc. of tuberculin are procured. The cultures, being boiled for fifteen minutes, are filtered through paper; the fluid is then put in a porcelain vessel and boiled slowly down to the required concentration (usually 1/10). This concentrated remainder is then passed through a Berkefelder filter. The filter is thoroughly cleansed before and after each filtration and the tuberculin is passed through while it is moist from its last cleansing with sterile water. We have now obtained our stock solution. For injection this soltition is mixed with Yi per cent carbolic acid solution, so as to give the strength required and should always be freshly made.

Our mode of applying the test is as follows : The temperature of the patient is taken every two hours for a period of


14


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 1G6.


twenty-four liours jjrecediiig the injection. The ordinary liypodermic syringe is used with a needle slightly longer than usual. The needle is inserted deep into the deltoid muscle, thorough aseptic precautions being observed. The puncture wound is covered with sterile gauze, wliich remains on for twenty-four hours. The temperature is taken every two hours for the ensuing 2-±-48 hours. If the time selected for the injection be between 8 p. m. and midnight, we can neglect the temperature until 6 a. ni. the next morning, as the reaction does not begin until six or eight hours later and the patient need not be disturbed during the night. If possible, the temperature during 24-48 hours preceding the injection should be normal. If, however, pyrexia is present during this period, a positive reaction is still recognizable by means of the local signs. A rise of at least 2° F. is required to constitute a temperature reaction. Using this method, we have injected at their homes forty patients in private practice and from the orthopedic dispensary clinic at the Johns Hopkins Hospital. A synopsis of these cases with their reactions will be found in the foUowinor table :


W. F., \V. M., W. M., W. M., W. M., W. F., W. M., W. M., W. M., W. M., C. M., W. F., W. M., W. F., W. M., W. F., W. M., W. F., W. M., W. M., W. M., W. F., W. F., W. M., W. F., W. M., W. F., W, M., W. F., W. F., C. M., W. F., W. M., W. F,, W. M., W. F., W. F., W. F., W. M., W. F.,


se.


Radiograph.


!>< years. . . 32 years . . .


No No


16 years . . . 37 years . . .


No Tes


24 years . . .


Yes


3 years


No


8 years ....


No


2.5 years . . . 16 years . . .


No No


a years .... 10 years. . . . 12 years. . . .

3}4 years. . . 7 years


No Yes Yes Yes Yes


8 years

16 years. . . .


Yes Yes


17 years. . . .


No


29 years ....


No


l.'i years . . .


Yes


12 years . . .


Yes


5 years


No


3 years


No


32 years. . . .


Yes


6 years .... 43 years....


Yes 1 No 1


12 years . . .


No


4 years


No


6 years


No


3 years

30 years. . . . 9 months. . .


Yes Yes

No


16 years. . . .


Yes


10 years . . .


Yes


23 years. . . . 10 years. . . .


Yes Yes


S years. . . . 4 years


Yes

Yes


20 years. . . .


Yes


2 years

81 years


Yee Yes


Provisional Diag'nosis.


Potts disease Potts disease


Potts disease

Rachitis Potts disease

Scoliosis

Potts disease

Tuberculosis of hip joint

Tuberculosis of hip joint

Effusion into joint


Effusion into joint ?

Fracture

Tuberculosis of hip joint

Coxa-Tara

Tuberculosis of both hip joints


Tuberculosis of hip joint Tuberculosis of hip joint Tuberculosis of hip joint Tuberculosis of hip joint Tuberculosis of hip joint Gonorrhceal rheumatism Tuberculosis of knee joint

9

Tuberculosis os knee joint Chronic synovitis

Tuberculosis of ankle joint Tuberculosis of ankle joint Old fracture os calcis Green stick fracture tibia Tuberculosis of ankle joint


this test has been applied in the wards of the Johns Hopkins Hospital where tuberculin has been employed continuous! v for the past six years. In looking over the series of cases we find that twenty-five gave a positive and fifteen a negative reaction. Of the twenty-five patients in whose cases a positive reaction was obtained, six were subsequently operated on and all proved to be tuberculous. In eighteen of the remaining nineteen cases the diagnosis has been verified by the suljsequent history and response to treatment. The only remaining case, while proven to be tuberculous l)y its positive reaction to tuberculin, both general and local, is of such recent date that the subsequent history is not as yet available. In regard to the fifteen patients who did not react, one was operated upon and no evidence of tuberculosis was found ; of the other fourteen, eight have recovered under non-tuberculous treatment; the remaining six are improved and all suspicion of tuberculosis has been removed. Eadiographs were taken of fifteen out of the twenty-five cases which reacted to tuberculin. Of these fifteen cases, six showed a focus, in five the disease was suspected only, and four showed no lesion. The


Mgm. 1.5. Mgm. 3.5, positive

Mgm. 2. Mgm. 4, negative

Mgm. 1, negative

Mgm. 5, negative

Mgm. 3. Mgm. 5, negative

Mgm. 2, positive

Mgm. 2, positive

Mgm. 2. Mgm. 6, negative

Mgm. 5, negative

Mgm. 2, positive

Mgm. 3 and 4, positive

Mgm. 5, positive

Mgm. 3, positive

Mgm. 5, positive

Mgm. 5, positive

Mgm. 3, positive

Mgm. 2, negative

Mgm. 2 and 5, negative

Mgm. 2 and 4, positive

Mgm. 3 and o, negative

Mgm. 1 and 3.5, negative

Mgm. 1.5 and 2.5, negative

Mgm. 2, positive

Mgm. 3 and 0, negative

Mgm. 4, positive

Mgm. 3, positive

Mgm. 2.5, positive

Mgm. .5, positive

Mgm. 1, positive

Mgm. 5, positive

Mgm. 1.3, positive

Mgm. 3 and 5, positive

Mgm. 2.5, positive

Mgm. 5, negative

Mgm. 2 and 5, negative

Mgm. 5, positive

Mgm. 2, positive

Mgm. 4, negative

Mgm. 3, positive

Mgm. 3, positive


Potts disease

Syphilitic spine

Osteo-arthritis spine

Osteo-arthritis spine

Osteo-arthritis spine

Potts disease

Potts disease

Scoliosis with sciatica

Osteo-arthritis spine

Tuberculosis of hip joint

Tuberculosis of hip joint

Tuberculosis of hip joint

Tuberculosis of hip joint

Tuberculosis of hip joint

Tuberculosis of hip joint

Tuberculosis of hip joint

Effusion into joint

Sciatica

Tuberculosis of hip joint

Coxa-vara

Coxa-vara

Synovitis of hip

Tuberculosis of both hip joints

Coxa-vara

Tuberculosis of hip joint

Tuberculosis of hip joint

Tuberculosis of hip joint

Tuberculosis of hip joint

Tuberculosis of hip joint

Tuberculosis of hip joint

Tuberculosis of knee joint

Tuberculosis of knee joint

Tuberculosis of knee joint

Chronic synovitis

Chronic synovitis

Tuberculosis of ankle joint

Tuberculosis of ankle joint

Old fracture os calcis

Tuberculosis of lower end of tibia

Tuberculosis of ankle joint


These cases were selected almost invariably in order to clear up the diagnosis. Our results show the ease with which tuberculin may be used in private practice and the accurate data that can be obtained under such circumstances. We have not included here the large number of cases in which


reasons for this will be discussed later. For convenience we have arranged the patients in groups according to the joint involved. A few cases of especial interest will now he discussed briefly.

Case 1. White; female; aged one year and six months;


January, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


15


admitted to the clinic January 10, 1900. Three days before she had a slight fall. Although she had previously walked for four months she now prefers to crawl; cries and is fretful. Examination showed only a slight restriction to hyperextensiou of the back; no kyphosis. Seat of pain not to be located. Two physicians connected with the dispensary had seen her just before admission, one suggested rachitis of the spine; the other malnutrition. Two injections of tuberculin were given. The first (1.5 mgm.) was followed by a rise of temperature to 100° F. The reaction was considered suggestive. A few days later 3.5 mgm. were given, and seventeen hours later the temperature was 100.5° F., having been normal ptevious to the injection. The child refused nourishment, and was very restless. On examination of the back, the resistance to hyperextension was greatly increased; the child refused to stand; the knee-jerks were increased. Here then was a positive reaction both general and local. On the following day the temperature had returned to normal and the general and local signs were exactly as those which had been present previous to the injection. The child was treated for Pott's disease with plaster jackets and a Taylor back brace. The note of her condition three years after the beginning of treatment is as follows : " The child is practically well with a slight kyphosis of the third lumbar vertebra, having passed through a typical Pott's disease during this period."

In this case tuberculin gave us a positive diagnosis at a time when the clinical symptoms were not sufficient to warrant a positive decision, and allowed treatment to be instituted in time to prevent deformity.

On the other hand, the negative value of tuberculin is shown in the following case :

Case 2. White; male; aged thirty-two; admitted to orthopedic clinic October 5, 1901. Eeferred by the nervous clinic with a diagnosis of tuberculosis of the spine. Fainihj history, negative. Previous history. Lues ten years ago. Present illness. The patient has complained of pains in his back radiating to the abdomen for the past five months. The pains are present during the day and night. The back is becoming stiff in the lumbar region, and the patient finds it difficult to pick up objects from the floor; there has been a continuous loss of strength, and the man is not steady on his feet. Loss of weight, fifteen pounds. Examination: The patient walks with an unsteady gait; holds his back perfectly rigid. There is some obliteration of the lumbar curve, but no actual kyphosis. The knee-jerks are markedly increased. Ankle clonus is present. There is considerable pain attending a jarring of the heel. A probable diagnosis of tuberculosis of the spine was m.ade and the patient was treated by means of plaster jackets for the first few weeks. He thought he improved a little ; but later the pain grew worse at night. The symptoms of paralysis increased and the man lost weight rapidly. For six weeks we persisted in the treatment, but the patient gradually grew worse. On December 2S. 1901, he was given 2 mgm. of tuberculin. There was no general or local reaction. On December 30, 4 mgm. were given. No reaction followed, either eeneral or local. This caused us to change


our diagnosis and for the first time to think seriously of his specific history as an etiological factor. Treatment with inunctions and potassium iodide internally was then begun. Within a month the patient gained three pounds in weight; the pain ceased almost entirely; no ankle clonus could be obtained and his knee-jerks became far less lively. He continued to wear a laced plaster jacket as a means of support. On May 1, 1903, four months after the initiation of the syphilitic treatment, he felt perfectly well ; no brace was worn ; the back was not stiff; all symptoms had disappeared. Fifteen months after beginning the treatment, he reported for observation and seemed well in every respect. Specific treatment, however, was continued. This case shows the value of tuberculin in eliminating tuberculosis and arriving at the true etiological factor.

Again let us contrast two cases of disease of the hip-joint.

Case 13. Boy; white; age 3-^^ j'ears; admitted to the orthopedic clinic March 3, 1903, complaining of a slight limp. Mother died of jnilmonary tuberculosis. He had had diphtheria two years previously. Present sickness. Four months ago he liad a slight fall on the floor while playing and since that time has had a limp which has slightly increased. There are no other subjective symptoms. Examination shows a slight limp. There is an apparent shortening of V^ cm. jSTo other deformity. Possible flexion, of 85° and possible abduction of 30°. No resistance to hyperextension, adduction, internal or external rotation. No muscle spasm. Very slight atrophy of thigh and calf.

In this case the diagnosis was not plain ; it was by no means a well defined case of tuberculosis of the hip. The radiograph showed that the distance from the trochanter to the head of the femur was slightly less than on the other side. There appeared to be a slight roughness of the acetabulum and the trochanter possibly showed a slight rarefaction.

On March 25, 1903, at the patient's home, 3 mgm. of tuberculin were given in the usual manner. Fourteen hours afterward the tem.perature had reached 101° F. This was accompanied by loss of appetite and extreme restlessness. All the local signs were decidedly increased. Pain in the hip and knee was complained of. There was distinct muscle spasm. The leg assumed a position of slight flexion and there was a decided limitation of all the motions. On the following day the hip had retiirned to its former condition and the general symptoms had disappeared. Here the reaction was positive. The radiograph, owing to the age of the child, did not show a definite focus, but under the influence of tuberculin the local signs presented such a definite picture that there could be no doubt as to the tuberculous nature of the affection.

The absence of a positive reaction on the other hand in diseases of the hip of a non-tuberculous character is shown in the following case :

Case 20. White; male; aged 12 years; admitted May, 1902, complaining of a limp. Family and previous history unimportant. Present illness. In October, 1901, the boy was hurt on the thigh while playing foot-ball and began to limp. There was no history of night cries and no pain. He


16


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. IGG.


was put up in a plaster spica and given crutches, which he used for six weeks. A tentative diagnosis of hip disease was made by a prominent surgeon. After the cast was removed ho continued to limp. He was seen by us in May, 190.2, six months after the original injury, and on examination the leg showed marked outward rotation, slight apparent shortening. Flexion was limited to 60°, abduction to 15°, and no rotation was allowed. No pain and no muscle spasm. The diagnosis was made of slight coxa vara, non -tuberculous in origin. Three and five nigni. of tuberculin were given at an interval of two days with absolutely no local or general reaction. The diagnosis of coxa vara was thus confirmed by a negative reaction to tuberculin and a radiograph, which showed no tuberculous focus, but a slight bending of the neck of the bone. The treatment consisted in massage and passive motion, both of which would have been contra-indicated had the joint been tuberculous. It is now eleven months since he was first seen by us. There is very little limp; the possible flexion is now 90°, possible abduction 80°.

The last case that we will discuss in detail seems to be of particular importance :

Case 32. White; female; aged l(j years, admitted, February, 1903, complaining of pain in tlie left knee on pressure and while standing. Family history. Father and mother both dead of pulmonary tuberculosis. Previous history, unimportant. Present sickness. Three weeks ago she had a slight fall while skating, to which no attention was paid. Since that time there has been a slight limp. The only symptom she presents is pain on pressure over the patella. There are no other local signs of disease. On February 3, 1903, she was given 3 mgm. of tuberculin. Eighteen hours afterwards the temperature had reached its maximum of 100.8° F., after which it rapidly fell to normal. There were general symptoms of nausea, headache and loss of appetite. Of greater importance we think were the local signs, for, whereas before the injection, there was only pain on pressure over the patella, there was now a slight rise of local temperature; the motions were restricted in extreme flexion and extension, and even the slightest pressure over the patella would cause exquisite pain. On the following day the temperature was normal ; the general symptoms had disappeared and there remained locally only the slight pain as before the injection. The radiograph showed a slight focus of disease, about li^ cm. in length and 1/2 cm. broad, situated in the internal condyle, running toward the joint. The tuberculous nature of the disease having been so early established by means of the tuberculin, and its extent ascertained by radiography, it was decided to see if the focus could not be removed and a stiff joint avoided. Accordingly the joint was opened for inspection, and on the top of the internal condyle directly under the patella a circumscribed raised area of inflammation was found about li/o em. in diameter, which sliowed, however, no tubercles to the naked eye. This area was left alone, the joint was closed, the area of diseased bone immediately beneath this seat of inflammation was removed (extra-articular) and proved to be tuberculous. Tlie leg was then put in plaster. Three weeks later pressure


over the patella elicited no pain and the motions of the joint were found to be good.

This case illustrated exceptionally well the diagnostic value of tuberculin in the earlier cases of tuberculosis. In this instance its employment rendered operative interference jsossible without the destruction of the function of the joint.

As a rule, when tuberculin is given, definite general and local signs are present whenever tuberculosis is present, and are generally absent whenever tuberculosis is absent. The smallest focus of tuberculosis will give a positive reaction and hence the diagnosis can be cleared up at a much earlier date than is possible by any other means.

During the twelve years that tuberculin has been used the dosage has varied with different observers. This in itself accounts for the failure in numerous instances to detect the presence of tuberculosis. Such small doses were used that small foci did not give either a general or a local reaction. Grasset (9) says that 3/10 to 5/10 mgm. are useful, while White (10) reports that doses of 1 to 8 mgm. are not to be relied upon. Mettetal (4), using tuberculin in children, gives doses from .1 to .5 mgm. On the other hand, if the dose be too large, even normal individuals may react. According to Koch (11), 10 mgm. may cause such a reaction. He obtained a reaction in himself with a dose of 25 mgm. Often such small doses were given in quick succession that a tolerance was created against a larger dose. So varied are the factors on which the dosage depends, the age of the patient, the seat of the focus, the strength of the tuberculin, its deterioration, and individual susceptibility, that no hard and fast rule can be given. Madison (12) in his recent article follows an initial dose of 4 mgm. by 7 to 10 mgm. when necessary. It has been our custom in small children to give an initial dose of % mgm. followed at intervals of two daj's with 2 two 4 mgm., when necessary. In older patients, 2 mgm. are used as an initial dose, followed in two days by 4 and 6 mgm. as a maximum. In no case have we found it necessary to give more than 6 mgm.

As to what constitutes a positive temperature reaction, all observers are agreed in requiring a rise of at least 2° F. The initial rise generally takes place within the first twenty-four liours and the pyrexia usually lasts over a period of twentyfour hours. The temperature may rise even as high as 104° iir 105° F.: the curve of the pyrexia may be atypical, being prolonged over the usual twenty-four for forty-eight hours or more; or the time of the onset may be delayed, but this is due no doubt in most part, as claimed by Madison (12), to deterioration of the tuberculin.

A definite group of symptoms always accompanies the fever; headache, anorexia, nausea, occasional vomiting, restlessness, etc. To those, however, who are dealing witli joint and bone tuberculosis the local symptoms are of far more interest and of equal importance. Previous to the injection of tuberculin the local seat of dise.ise should be examined carefully for all signs of the suspected trouble, such as the permanent deformity, possible motions, muscle spasm, local temperature and pain. In response to the tuberculin, if


January, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


ir


tuberculosis be present, we shall have all the local signs of the disease distinctly increased, that is, motion will be more limited, deformity will be greater, tenderness and muscle spasm will be exaggerated, and local temperature may be increased ; in fact, the local signs alone are so characteristic of a tuberculous process that the diagTiosis can be made from these alone.

Koch (1) and ]Maragliano (13) have laid stress upon tlie local signs observed in lupus, glandular and pulmonary tuberculosis. Klebs (14) mentions local reactions occurring in disease of the bones and joints, while Friinkel (3) says, " Tuberculin is especially useful in surgical tuberculosis, paxticularly as in such cases the local phenomena can be so easily observed." On the other hand, Frazier and Biggs (1.5) are tlie only observers, so far as we know, who claim an entire absence of a local reaction in tuberculosis of bones and joints. We can only say that in every case that has come under our personal observation the local phenomena, where a positive reaction was obtained, have been of a most pronounced character. The selective action of tuberculin for tuberculous tissue is well recognized, and whenever a patient with a suspected joint gives a general but no local reaction, the probabilities are strongly in favor of the view that the joint in question is non-tuberculous. It is evident, therefore, that the local signs should be carefully observed, as well as those of a general character, in order to definitely locate the tuberculous process.

Is the use of tuberculin harmfail in its effects?

A few months after its discovery, Virchow stated that in his opinion it might be harmful. This view has been concurred in by Ambler (16) and Knopf (17) on theoretical grounds. Head (IS), Heron (19) and Ewald (20) have reported cases in which very weak patients have died after a large injection ; but the evidence is by no means conclusive that death was due to the injection.

On the other hand, the great majority of observers, among wliom may be mentioned Friinkel, Slettetal, White, Lathan (21), Neff (23), Osier (33), Klebs, Martin and Eobbins (24), France (23), Elder (26), and Voges (27), are unanimous in their statements that, when tuberculin is used in proper doses, there are no harmful effects. We have never seen a case in which any permanent damage had been done by tuberculin. A dose which is too large may produce a fever that is prolonged beyond the usual twenty-four hours, and the local signs may persist for a longer time than usual, but within a day or two the temperature always returns to normal and the local signs become similar to those before the injection.

Is tuberculin a specific in the diagnosis of tuberculosis?

According to some observers, syphilis, leprosy and actinomycosis react to tuberculin. Mettetal (4), Billroth (28) and

von Eiselsberg (29) have seen cases of actinomycosis which gave a positive reaction, but Mettetal definitely states that the reaction was atypical. Goldschmidt (30), Babes and Kalendro (31) state that leprosy may react. In 109 autopsies of lepra reported by Abraham (32), 30 per cent showed tuberculous lesions. It seems highly probable, therefore, that


most of the reactions reported in leprosy were due to an accompanying tuberculosis. In regard to syphilis. Beck (33) states that one-half of such cases react to tuberculin, while Otis (7) in 35 cases in which the diagnosis was carefully made, found only 12 per cent that reacted, and he considers Beck's figures as entirely too high. Friinkel, on the other hand, thinks the probability of obtaining reactions in uncomplicated cases of syphilis very doubtful. He reports a case of a syphilitic ulcer, which gave a general, but no local reaction to tuberculin. The ulcer was cured by inunctions and potassium iodide internally, and again the patient gave a general reaction to a dose of 1 mgm. He considers that there he was dealing with syphilis complicated by hidden tuberculosis.

The only patient in our series (Case 2) in whose case a reaction to syphilis was in question, failed to react to 2 and 4 mgm. of tuberculin and entirely recovered under specific treatment. From the cases of syphilis reported by various observers, it seems probable that a small number give a reaction, but further evidence is necessary to show that there is na associated tuberculosis in these eases. Broadly speaking then, it may be said that tuberculin is practically a specific in the diagnosis of tuberculosis.

The radiograph has come to j)lay an enormous role in the work of the orthopedic surgeon. It is one of the most helpful means which we possess to point out lesions of bones and joints and yet it has its limitations, especially in the very cases in which we most need its help. By far the greater number of our patients with bone and joint tuberculosis are children. The structure of their bones and the relatively large proportion of cartilage in such cases does not lend itself te differentiation by means of radiography as readily as in adults. It has often been our experience in children that even when the clinical signs were sufficient to make a diagnosis of tuberculosis, the best radiograph would fail to present a picture of the disease process or would do it so imperfectly as to make us doubt its existence. In such cases tuberculin would invariably give us both a general and local reaction. On the other hand, tuberculin plus the radiograph forms a combination of diagnostic agents which are of the greatest value, especially in adults, as is shown in case 32, where tuberculin gave the diagnosis and the radiograph showed the location and extent of the focus.

The application of the tuberculin test is in reality a most simple procedure, much easier than a blood count and no more difficult than an ordinary injection. Naturally, the method is more accurate in hospital work, owing to the aid of a competent nursing staff, and yet with a little more exertion on the part of the physician, private and dispensary cases need but little more care. The same physician who examine-3 tlie case before injection should also do so at the height of the reaction. The temperature must be carefully taken and recorded every two hours. It is generally agreed that tuberculin is nn unstable product and deteriorates if not kept in a cool, dark place. The Vo per cent carbolic acid solution should be made up freshly before each injection. The majority of observers


18


JOHNS HOPKINS HOSPITAL BULLETIN,


[No. 166.


agree that it may be used if not kept more than three days. Madison (12) believes that a fresh bottle of the stock solution should be opened once a month. In his opinion the failure of tuberculous cases to react and delayed reactions are primarily due to deterioration of the tuberculin.

The reliability and harmlessness of the test may be judged by the immense number of observations upon cattle where autopsies can be obtained and results verified. Voges (27) in eight thousand autopsies upon cattle has shown that the test is accurate in 90 per cent. Koch, with an experience of three thousand cases, considers the test almost absolute.

Our own work, when taken in conjnction with that of others, would appear to justify the following conclusions:

1. Tuberculin is the best and most reliable diagnostic agent for incipient tuberculosis of bones and joints.

2. Its proper administration is attended by no permanent harmful effects.

3. The dosage is variable and it is rarely necessary to exceed a dose of 6 milligrams.

4. The local signs are of equal, if not greater, importance than the general reaction, in bone and joint tuberculosis.

5. Tuberculosis practically always reacts to tuberculin.

6. Diseases other than tuberculosis may possibly react to tuberculin, but the evidence on this point is not conclusive.

7. The diagnosis of tuberculosis can be made earlier and with more certainty by means of tuberculin than by radiography.

8. The tuberculin test is applicable to private and dispensary as well as to hospital practice.

References.

1. Koch: Deutsche Med. Wchnsehr. 1890, Bd. 16, Nr. 46 a.

2. Koch: Deutsche Med. Wchnsehr. 1891, Bd. 17, h. 1189. 101.

3. Frank-el: Berl. Klin. Wchnsehr. 1900, Nr. 2, Bd. 37, p. 255.

4. Mettetal : Valeur de la Tuberculine dans le diagnostic de la tubeculose de la premiere enfance. Paris, 1900.

5. Casselbery: Med. News, N. Y. Oct. 12, 1901. Vol. 79, p. 515.

6. Finkler and Guttmann: Quoted by Martin and Bobbins. Brit. Med. Jour., Feb. 5, 1898, p. 358.

7. Otis: Med. News, N. Y., Aug. 24, 1901. Vol. 79, p. «S1.

8. Trudeau: Med. News, N. Y., May 29, 1897. Vol.70, p. 687.

9. Grasset and Vedel: La Semaine Med., Fev. 26, 1896.

10. White: Boston Med. and Surg. Jour., 1897. Vol. 137, p. 123.

11. Koch: Deutsche Med. Wchnsehr., 1891.

12. Madison: American Medicine, Dee. 20, 1902, Vol. IV, p. 972.

13. Maraglieno: Berl. Klin. Wocli. Nr. 19-20, 1896.


14. Klebs: Boston Med. and Surg. Jour., Feb. 10-17, 1898, Vol. 148, p. 121.

15. Frazier and Biggs: Univer. of Peun. Med. Bull., March, 1901.

16. Ambler: N. Y. Med. Jour., Feb. 12, 1898, Vol. 67, p. 205.

17. Knopf: Jour. Amer. Med. Assn., Dec. 9, 1899. Vol. XXXIII, p. 1445.

18. Head: St. Paul Med. Jour., Sept., 1899, Vol. I, p. 651.

19. Heron: Brit. Med. Jour., July, 1901, p. 213.

20. Ewald: Berl. Klin. Woch., 1891, Nr. 4, p. 109.

21. Latham: Lancet, London, 1901.

22. Neff: Am. Jour. Insan., Baltimore, Vol. LV, No. 3, 1899.

23. Osier: Brit. Med. Jour., July 27, 1901, p. 213.

24. Martin and Bobbins: Brit. Med. Jour., London, 1898, Vol. I, p. 357.

25. France: Jour. Mental Sciences, London, January, 1900, Vol. XLVI.

26. Elder: Med. Record, N. Y., April 19, 1902, Vol. LXI, p. 629.

27. Voges: Quoted by Frankel, Berl. Klin. Woch., 1900. 28. Billroth : Quoted by Knopf : Jour. Am. Assn., Dec. 9, 1899, Vol. XXXIII, No. 24, p. 1446.

29. Yon Eiselberg: Quoted by Knopf: Jour. Am. Assn., Dec. 9, 1899, Vol. XXXIII, No. 24, p. 1446.

30. Goldschmidt: Berl. Klin. Wchnsehr., 1891, p. 28.

31. Babes and Kalendro: Deutsche Med. Wchnsehr.. 1891, p. 115.

32. Abraham : Allbutt's System of Medicine, Vol. Ill, p. 59.

33. Beck: Deutsche Med. Wchnsehr., Nr. 9, 1899, p. 137.

34. Tinker: Johns Hopkins Hospital Reports, Vol. XI, p. 535.


INSTRUCTION IN PSYCHIATRY AND NEUROPATHOLOGY.

A limited number of graduates in medicine can have an opportunity for work in the laboratory of the Sheppard and Enoch Pratt Hospital.

Instruction in neuro-pathology will be given by the director of the laboratory, and those attending the course will be permitted to attend the clinical and other conferences of the medical staff. Clinical forms of insanity will be discussed, as well as the hospital and home care of the Insane.

Physicians taking this course will also have, an opportunity to attend the neurological clinics at the Johns Hopkins Hospital'.

For particulars, apply by letter to Dr. K. N. Brush, Physicianin-Chief and Superintendent, Sheppard and Enoch Pratt Hospital, Station " A," Baltimore.


January, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.



A PRACTICAL METHOD OF DEMONSTRATION.

By W. J. Calvert, M. D., University of Missouri, Golumhia, Mo.


The problem of demonstrating either the normal or abnormal relations of organs has presented many difficulties which have given rise to many devices such as serial sections of the body, schematic drawings, models, etc., all of which are of value, but none of which are entirely satisfactory. In addition many of the larger drawings and most models are expensive and are beyond the reach of many institutions and most individual students.

Wherever practicable full sized drawings are the most desirable as the student then is not required to mentally convert a one-fourth, one-half or a three-fourth sized drawings to one of full size.

For full sized outline drawings the tracing-cloth and blueprint method extensively used by architects and engineers is very satisfactory. Four original drawings are necessary. One each of the anterior, posterior, right and left sides with the outlines of the several organs projected on each are sufficient. From these, full sized outlines of the thorax, abdomen or pelvis, as desired, may be traced in a relatively short time and the outlines of an abnormally placed organ, etc., may be traced in at will. When the tracing-cloth outline is completed, blue-prints can be made for a few cents each by men who are to be found in every city. In this way as many drawings as is desired may be made and each member of a class can afford to buy a blue-print, which, when worn out, may be replaced at little expense.

One distinct advantage is that the drawings are not schematic, but are as accurate as measurements allow. In addition tliey are easily made, cheap, and can be replaced when worn out. They are of especial advantage for demonstrating individual cases to societies, classes and for lecture work.

The materials required are a drawing board, a few thumb tacks, tracing-cloth, India ink and ordinary pens.

If desired, the outlines of the bones or organs may be colored or may be blackened with a soft lead pencil which can be erased later.

From the drawings on cloth, photographs may be easily made for reproduction,

For the original outline drawing of the print which illustrates this article I am indebted to Dr. Potter of the St. Louis University.


THE JOHNS HOPKINS HOSPITAL BULLETIN.

The Hospital Bulletin contains 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 XV is now completed. The subscription price is $2.00 per year. The set of fifteen volumes will be sold for $75.00.



Reduced from life size. Heavy binck intenuiited line indicates lesions.


JOHNS HOPKINS HOSPITAL BULLETIN.


[N"o. 166.


THE EFFECT OF THE BILE UPON THE ESTER-SPLITTING ACTION OF PANCREATIC JUICE/

A PRELIMINARY COMMUNICATION.

By Albion Walter Hewlett, M. D. (From the Physiological Laboratory of the Cooper Medical College, San Francisco, Cal.)


That the bile assists in the digestion and absorption of fats has long been recognized, but the manner in which it does this has never been fully worked out. The presence of bile favors the emulsification of fats and this indirectly aids the fat-splitting action of the pancreatic juice, because the finer the emulsion the greater is the surface of fat presented to the action of the fat-splitting enzyme. Little regard, however, has been paid to the possibility that the bile might assist the enzyme in any more direct manner. Pawlow ' indeed asserts that the presence of bile so changes the medium that the fatsplitting proceeds two or three times as fast as it would if no bile were present. Bruno, a pupil of Pawlow, estimates the acceleration of the lipolytic action as ten to twenty times.' <xlassner, working on pancreatic Juice obtained from a human pancreatic fistula, found that the addition of bile to the pancreatic Juice increased its action upon olive oil about one and one-half times.* The manner in which the bile assisted the pancreatic lipase was not especially considered by these investigators.

At the suggestion of Dr. W. E. Garrey, I have endeavored to ascertain more definitely the elfect of bile upon the estersplitting action of pure pancreatic secretion. The latter was obtained from dogs by means of secretin injections " or by injections of both secretin and pilocarpin. In this manner varying amounts, up to forty cubic centimeters, of pure pancreatic Juice were obtained from each of a series of dogs and the action of this secretion was tested upon a variety of esters with and without the addition of bile.

Pure pancreatic Juice decomposes ethyl butyrate surprisingly slowly if we compare it with the action of pancreatic extracts upon the same ester." If one or two cubic centimeters of pancreatic Juice be diluted up to five cubic centimeters with water and if the mixture be allowed to act upon 0.25 cc. of ethyl butjTate for twenty-four hours at 37° C, the difference between the acidity produced and that produced by an equal amount of boiled pancreatic Juice is usually about 0.1-0.2 ec. of a 1/20 normal solution, although it may in some instances run up to 1.0 cc. or slightly more. Unboiled bile also decomposes ethyl butyrate very slowly, not differing appreciably


' This research has been completed by the aid of a grant from the Rockefeller Institute for Medical Research.

Pawlow: The M'ork of the Digestive Glands. Trans, by W. H. Thompson, p. 159.

' Die Galle als wichtiges Agent bel der Verdauung. Inaug. Diss. St. Petersburg, 1897-98. Ref. in Jahresber. Thier-Chemie. Vol. 27, p. 441.

Ztft. f. physiol. Chem., Vol. 40, p. 465. ° Bayliss and Starling: The Mechanism of Pancreatic Secretion. Jour, of Physiol., Vol. 2S, p. 325.

'Kastle and Loevenhart: Am. Chem. Jour., Vol. 24, p. 491.


in this respect from boiled bile. If the bile be added to the pancreatic Juice, however, the cleavage of the ethyl butyrate proceeds with great rapidity and in twenty-four hours an acidity amounting to 7.0-16.0 cc. 1/20 normal solution will be produced. Similar results were obtained when ethyl acetate or amyl acetate were used in place of ethyl butyrate.

The ordinary fats are insoluble in water and they arc therefore but little suited to a solution of the problem at hand, because any acceleration in the action of the pancreatic Juice, which the bile would cause, might be attributed to its emulsifying action. This difficulty however, is, overcome if a soluble triglyceride, such as triacetin, be used, for then the question as to the degree of emulsification is eliminated. It was found that pure pancreatic Juice, even without the addition of bile, splits triacetin much more readily than it does ethyl butyrate, ethyl acetate, or amyl acetate. In one experiment the acidity produced in an hour at 20° C. amounted to 0.5 cc. 1/20 normal solution and in twenty-four hours to 12.6 cc. On the addition of bile, the decomposition proceeded at a much more rapid rate Just as it did in the case of ethyl butyrate. The acidity produced in one hour amounted to 13.0 cc. and in twenty-four hours to 18.6 cc. The acceleration, therefore, was very marked during the first hour, and the reason that this acceleration was less apparent after twenty-four hours probably lay in the fact that the reaction was approaching an equilibrium.

The addition of bile also accelerates the action of the pancreatic secretion upon emulsions of olive oil, but to what extent and why this occurs has not as yet been fully determined.

Which constituent of the bile possesses this peculiar property of accelerating the ester-splitting action of the pancreatic Juice? Boiling the bile does not destroy this property and we may therefore infer that it is not due to an enzyme. Furthermore, this property resides neither in the cholesterin, in the pigments, in variations in reaction, nor in variations in the amount of calcium salts present. Precisely the same accelerating effects may, however, be produced by the addition of lecithin to the pancreatic Juice. Thus in one experiment the pure pancreatic Juice by its action on triacetin for twenty-four hours produced an acidity amounting to 4.3 cc. 1/20 normal solution;, the same plus two cubic centimeters of bile produced 19.5 cc. acidity, and plus two drops of a strong alcoholic solution of Merck's lecithin produced an acidity of 19.9 cc. A commercial preparation of the bile salts will also accelerate the ester-splitting of the pancreatic Juice, but it seems that the more the bile salts are purified, the less effect they have in this respect, so that it is possible


Jancaky, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


21


that the action of the crude preparation is due to a contamination with lecithin.

Yarions possibilities present themselves as to the manner in which the bile assists the ester-splitting action of the pancreatic juice. In the first place, does it act by converting a proferment into a ferment, an action analogous to that exerted by the enterokinase of the intestines upon the proferment of trypsin ? ' In considering this question, we must remember that if this hj-pothesis were true, a small amount of bile would be just as effective as a larger amount provided it acted for a sufficiently long time, and that if sufficiently small amounts of bile were added to the pancreatic juice the rate of cleavage could be shown to progressively increase as more and more of the proferment were converted into the ferment. It was found as a matter of fact that these conditions are not realized in the case of the action of bile upon the pancreatic juice. Another possibility is that there is a substance in the pancreatic juice, itself inert, which combines with some constituent in the bile to form the fat-splitting enzyme. Such a condition would be analogous to that described by Kyes ' for cobra venom. Alone this exerts little if any hsemolytic action; plus lecithin the action is most marked. The pancreatic juice, however, is moderately active


Bayliss and Starling: The Proteolytic Activities of the Pancreatic Juice. Jour, of Physiol., Vol. 30, p. 61. »Berl. klin. Wochenschr., 1902, Nos. 38-39.


even without the addition of bile. It would, therefore, be necessary to suppose that the pancreatic juice normally contains a trace of lecithin, but that this is not sufficient to render active any considerable portion of the fat-splitting ferment. It seems to us more probable that the bile acts as an accelerator upon the fat-splitting ferment, and indeed this is more in accord with the modern view that all ferment action is in the nature of an acceleration. We know that the esters will slowly decompose in pure water and the same is true if they are placed in boiled pancreatic juice. If the secretion be unboiled, i. e., if the ferment be present, the decomposition proceeds at a somewhat more rapid rate, and if to this, bile be added, the decomposition is still further accelerated. We do not know exactly how this last acceleration is brought about, although other similar accelerations are known to us. Thus hydrogen dioxide will slowly decompose in water. If ferric sulphate be added to the water, the decomposition is moderately accelerated. Cupric sulphate alone produces little if any effect upon the hydrogen dioxide, but if it be added to the mixture of hydrogen dioxide and ferric sulphate the reaction is enormously accelerated. Substances which act in this manner have been termed zymoexcitors. It seems probable, therefore, that the bile increases the ester-splitting action of the pancreatic juice by virtue of a zymoexcitor which it contains and that this zymoexcitor is in part, at least, lecithin.


A CASE OF RIGHT-SIDEl) INFANTILE HEMIPLEGIA, WITH A DESCRIPTION OF THE PATHOLOGICAL CHANGES FOUND IN THE BRAIN AND THE SPINAL CORD.

By Egbert Keuling, M. D., Baltimore, Md.


Although the literature of infantile cerebral palsies and their complicated symptomatology is voluminous and their pathology at the present time has at least a good working foundation, it is nevertheless surprising how comparatively few instances have been rejjorted where the brain and spinal cord in these affections have been studied in their entirety. For this reason the following case is presented, inasmuch as a complete examination of the central nervous tissues was possible; unfortunately a clinical history and a satisfactory neurological examination were not oljtained.

Sensory changes, however, are of rare occurrence in similar cases; in the present with exception of certain occasional pains in the affected memljers, a typical example of right-sided hemiplegia with marked contractures and osseous changes, due to its long standing (25 years), little was ascertained.

E. ]\I., single, aged 28, white, born in the United States, was admitted to the lying-in wards of the University of Maryland Hospital in 1900. She complained of severe abdominal pains, and weakness. An abortion had been accomplished a few days preceding her entrance to the hospital. For the following notes and the use of the material I am much indebted to I)rs. Alan and Stokes.

It was evident at the first examination that tlie patient had


a septic infection. All means to combat this were tried ; iacluding irrigations. Her temperature ranged high and fairly regular for three days after admission, then became irregular, rigors were noted, and delirium of an unusually violent type soon set in. On the fifth day a soft systolic mtirmur appeared, best heard at the apex; the following day a very faint friction over the body of the heart suggested pericarditis. Soon a praisystolic murmur appeared, all pointing to a septic endocarditis. The abdomen was fairly distended and very sensitive in its lower quadrants.

The uterine discharge was ill-smelling and characteristic of septic endometritis. A few minute petechial hemorrhages appeared in the skin on the chest and abdomen. The urine throughout contained a considerable amount of albumen and casts; later some blood. She died on the tenth ilay after admission.

Clinical Notes. — Nothing is known as to her family historv. When two years old she was taken ill with convulsions and on their cessation the right-sided paralysis was evident. Sv]iliilis in later life could be fairly well excluded. She was immoral and had been the mother of one illegitimate child born at term. Epileptic convulsions have occurred from childhood, at what age thev began is not known; thev have been


22


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 166.


lefS frequent since maturity. While in the hospital she had two severe general convulsions of an epileptic type, with frothy sputum. Her speech was considerably affected, a distinct hesitancy and lack of motor innervation was noted by all that saw her during the first days of her illness; as to the existence of a sensory aphasia this remains unprovcn. No athetoid movements were noted.

Autopsy. — Thirty hours after death. Body of moderately well nourished woman; little subcutaneous fat. Eigor mortis present. Abdomen moderately distended and highly tympanitic; skin over the same has a glossy appearance and the umbilicus is flattened. Faint bluish discoloration in left iliac region. Cornea in good condition and pupils regular. No external signs of advanced decomposition. A few petechial hemorrhages in lower chest and on the abdomen. A small linear scar over the right eye. Tongue very dr\' and covered with sordes, no scars found. No apparent facial asymmetry.

There is a striking difference in the appearance of the right and left upper extremities. The muscles of the right shoulder girdle and the entire right upper extremity are markedly wasted, the biceps muscle is practically a thick fibrous band, the humerus is also atrophied. The right arm is strongly flexed against the side of the chest and the forearm across it, the hand with its fingers flexed into the palm and indenting its surface, lies near the mid-body line over the xyphoid cartilage. Unless adhesions and muscle were torn the extremity could not be placed to the side of the body. An average difference of from 2.5 to 3 cm. is found in measuring the circumference of the right arm and forearm in comparison with the left extremity. The riglit lower extremity is also atrophied throughout, less markedly so than its upper fellow, it lies in a natural position, excepting that the foot is in a rigid, talipes equinus position, points sharply downwards while the toes are drawn dorsalward^. The tendo achillis was tense. The atrophy of muscle tissue seems most pronounced in the tibialis anticus and gastrocnemius. A shortening of 6 em. in the right lower extremity was found and in approximating the two feet the toes of the right foot touched only the left internal malleolus.

On making the usual longitudinal incision a cousideraljle amount of ill-smelling gas escapes from the abdominal cavity and on moving the intestines gurgling sounds are heard. An intense acute fibrino-purulent peritonitis, with occasional hemorrhages exists; the adliesions can be broken readily however. Pus is present between a few coils of the smaller intestines more being found in the pelvis where also a nmcopurulent, slightly blood-stained fluid exists. The uterus is about the size of the organ at the 4th month of gestation, its muscle tissue is soft and friable. The perimetrium is injected. Uterine vessels are thrombosed, especially the veins. The pelvic glands are much enlarged. On section a raised patch about the size of a dollar is seen in the left half of the uterine endometrium, presenting a beautifi;l example of so-called diphtheritic inflammation. The kidneys show an acute parenchymatous nephritis and thrombi in many vessels. The liver is about normal size, and shows an acute parenchyma


tous necrosis. The spleen is moderately enlarged, very soft and vascular, the splenic corpuscles being obliterated. The heart shows its pericardial surface covered with a thin fibrinopurulent exudate the surface being still moist; the pericardial vessels are injected. A mass of thin, fresh adhesions attach almost the entire pericardial surface to the chest and lung pleura. A small amount of cloudy yellow fluid is in the sac. The heart is slightly dilated, its muscle is soft. On section a striking example of acute fibrinous exudate covers the leaflets of the mitral valve; this is raised above their surface and small fragments break off on handling the organ; the exudate extends slightly over to the endocardiimi and to the attachment of the papillary muscles. About the aortic valve a similar acute inflammation is in its incipiency. The lungs have a moderate pleuritic inflammation on the left side, especially near the cardiac region, also several patches of broncho-pneumonia and numerous emboli in the pulmonary vessels.

Description of the Brain. — On removing the calvarium, one is struck by the marked asymmetry of the two hemispheres; the left being much smaller than the right, this being true of the left hemisphere throughout. On removing the brain it is evident that the entire skull cavity is smaller than normal and the bi-ain below the average size. The left anterior and middle fossre of the skull are considerably smaller and more shallow than those on the right side, this being especially true of the middle fossae. The posterior fosste show, however, a reverse condition in that the right is smaller and more shallow than the left; the reason for this will be clear after considering the further examination of the brain. The dura mater over almost the entire left motor region was of a milky color, extending over the lower posterior central gyri and anterior occipital lobe. This membrane is much thickened and shows evidence of an increase in its vasdular supply; in the region of the first, second, and third frontal convolutions a considerable retraction of the dura occurred amounting to the formation of a distinct cavity over the thii*d frontal gyrus. When the removal of this cloudy portion of the dura was attempted, it proved intimately adherent to the brain surface.

Three small cysts were opened from which clear strawcolored fluid escaped, two in the first frontal and one in the second frontal regions. The dura and other membranes appeared about normal over the remaining brain surface. At the longitudinal fissure the left hemisphere showed a retraction of about 1.5 cm. below the level of the upper border of the right hemisphere while its anterior frontal tip was retracted an equal distance from its fellow on the right hemisphere. The only apparent change in the gross specimen of the cerebellum was an atrophy of the right hemisphere in its entirety, the left being normal. This atrophy was evident at first glance. There were no localized retractions of cerebellar tissue. The entire left half of the medulla showed a well-marked atrophy. The right half of the spinal cord below' the decussation of the pyramidal tract was also atrophied. In the cord this atrophy was visible in the gross


THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1905.



THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1905.


PLATE II.



January, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


23


specimens as far down as the sacral region. The brain and sections of the spinal cord were placed in 10 per cent formalin.

The following is a description of the figures :

Fig. 1. This is a semi-diagrammatic drawing of a longitudinal section of the brain which passes through the lower second frontal region and includes the ventricles, the central nuclei as well as the internal and external capsules. For the more correct interpretation of the changes at the site of the lesions in the cortex and the changes in the capsular fibers and internal nuclei, sections stained by the Weigert-Pal method were used and the changes as seen under a dissecting microscope were added to the remaining entirely diagrammatic drawing.

One is immediately struck by the smaller dimensions and evident retraction of the entire left hemisphere. An almost total destruction of the tissue in the second frontal gyrus including the Island of Reil is found. A condition of a variable degree of microgyri is also evident in the cortex in the left frontal region. At the site of the lesion the blood vessels are increased and vessels of a larger size than are ever found in the normal gyri are found. The fibrous tissue infiltration is marked and its fibers rather coarse. The entire bundle of fibers making up the left internal capsule is about one-half the thickness of the right internal capsule. In the Weigert specimens by far the majority of the fibers of the left capsule stain only faintly, a few normal staining fibers being interspersed among them. The left lenticular caudate nuclei, especially the latter, are atrophied, also the left optic thalamus. The left lateral ventricle is moderately dilated.

Fig. 2. Weigert-Pal specimen of normal gyri taken from the right second frontal region, corresponding to the site of the lesion in the left frontal hemisphere.

Fig. 3. Weigert-Pal specimen with second Van Gieson staining. The section is from the site of the lesion in the second left frontal convolution. It shows a destruction of the greater portion of the gyrus; numerous cross-sections of blood vessels are seen, especially veins; coarse bands of connective tissue support these and replace to a certain extent the destroyed tissue. The formation of small cavities is seen, some lined by the dura, others by fibrous tissue. Considerable blood pigment is found on examining this specimen under the higher power and altogether there is no reasonable doubt but that a hemorrhage into the cortical substance was the cause of the pathological changes with formation of scar tissue and secondary atrophy of the pyramidal tract, internal nuclei and right hemisphere of the cerebellum.

Fig. 4. Weigert-Pal specimen from the region of the right internal capsule including portions of the optic thalamus, the lenticular and caudate nuclei. These appear normal and in marked contrast to the corresponding left region.

Fig. 5. Weigert-Pal specimen of the region of the left internal capsule including portions of the lenticular and caudate nuclei and optic thalamus. The atrophy of the internal capsule and optic thalamus is so evident in the drawing that further description is not needed. The ova! and round clear spaces in the substance of the nuclei represent the enlarged perivascular spaces and lymph spaces about the nerve cells due to the retraction of the surrounding tissue.

Fig. 6. Represents the upper surface of the cerebellum. The well-marked atrophy of the right hemisphere is shown. This atrophy of the cerebellar hemisphere opposite to the side of the lesion has been described in several cases of cerebral infantile paralysis and it may be of interest to review briefly some of the opinions as to its cause. If we remember the existence of a fronto-cerebellar tract whose fibers pass from the motor region of one cerebral hemisphere to the cerebellar hemisphere of the opposite side, this change will be clear.

Gordinier gives the following description of this fronto-cerebellar tract. (Gordinier's Anatomy of the Central Nervous System, page 222.) " The fronto-cerebellar tract occupies rather more than the inner fifth of the crusta. The fibers of this tract come from the prefrontal lobe, and pass between the lenticular and caudate nuclei, occupying a large part of the anterior limb of the internal capsule, and a course downward on the inner side of the pyramidal tract, ending in the ventral portion of the pons Varolii; about the nerve cells of the nucleus pontis of each side are joined by fibers from the cortex of both cerebellar hemispheres, chiefly, however, with the cerebellar hemisphere of the opposite side. The fibers are the axones of the cells of Purkinje of the same and the opposite side, the latter fibers having crossed in the raphe, thus establishing a connection between the frontal


lobe of the one side and both cerebellar hemispheres, but chiefly with the cerebellar hemisphere of the opposite side."

Fig. 7. Weigert-Pal section through the upper medulla showing the superficial and deep pontine fibers. As this section is above the decussation of the pyramidal tract, the degenerated fibers are found on the left side, in fact, the left half of the medulla is atrophied and even more so than represented in the drawing. The left pyramidal tract shows an advanced degeneration of its fibers so that few of them take up but a faint staining. The floor of the 4th ventricle is shallow and the nucleus of the hypoglossal nerves is seen close to the central raphe and just under the ventricular surface. In the deep pontine fibers of the left half of this section some atrophic changes are found.

Fig. S. Weigert-Pal section through the medulla in the olivary region. In this section the atrophy of the left half of the medulla is still marked and more so than in figure 7. The left pyramidal tract is markedly atrophied and only a very few fibers stain at all. A few atrophic fibers are also seen in the lateral portion of the medulla above the large bundle of the pyramidal tract, these, no doubt, represent a subdivision of pyramidal bundles. The deep pontine fibers on the left side also show degenerative changes.

Pig. 9. Weigert-Pal section through the lower dorsal segment of the spinal cord. This shows a well marked degeneration of the right pyramidal tract as represented in the drawing by the lighter area in the postero-lateral portion of the cord. This area gradually shades into normal tissue and a narrow zone of normal fibers lies in the periphery of the cord, being fibers of ascending tracts. This degeneration in the crossed pyramidal tract on the right half of the cord can be traced to the lower sacral segment. Strange to say in none of the specimens from the medulla or spinal cord could a direct pyramidal tract be demonstrated and in reviewing the literature one finds that other observers have found it absent; no doubt, in such instances, all the motor fibers pass into the cord as a crossed tract. Sacki and Schmaus (Pathologie des Central Nervensystems, 1903, page 44), say: "We have previously mentioned the degenerative changes in the anterior direct pyramidal tract which lies on either side ,of the anterior sulcus of the cord. But this bundle does not at the present day hold the same importance it held in former years, in fact, it is at times impossible to demonstrate it in human beings." It is the best seen in lesions affecting the motor tract either in the internal capsule or crus cerebri or better still in those of the medulla or uppermost segments of the dorsal cord. Sacki and Schmaus also claim this tract has never been clearly demonstrated in lower animals. The following description of the anatomical relationships of the pyramidal tracts is taken from Gordinier's Anatomy of the Central Nervous System, page 91.

The motor fibers of the cord which are located in the direct and crossed pyramidal tracts arise from the motor areas of the brain, and represent the neuraxones of the large pyramidal cells, which are abundantly found in the third layer of the cortex. Their course from the cerebral cortex to the medulla will be described later. When they reach the medulla they occupy a large area on each side of the anterior median fissure, and at the first or second cervical nerves large bundles of fibers, or axones, representing about eighty per cent of the whole number, pass obliquely across to the opposite side, entering the posterior part of the lateral column of the cord, hence the name ' crossed pyramidal tract.' These crossed fibers become vertical and extend downward, gradually decreasing in size until they reach their termination at the level of the third or fourth sacral nerve, a small number of fibers continuing downward to terminate in the filum terminale. The neuraxones which do not cross representing about twenty per cent of the motor fibers, pass downward in the area of the cord adjacent to the anterior median fissure on the same side; hence they are called the direct or uncrossed pyramidal tract. They usually cease about the level of the mid-dorsal region. The motor neuraxones, like most of the long fibers of the columns of the cord, give off at different levels side branches or collaterals, which leave the parent stem at right angles. The axones, with the collaterals composing the crossed pyramidal tract of each side, pass forward and inward, entering the gray matter, where they break up about the motor nerve cells into innumerable fine filaments or aborizations. The neuraxones and collaterals of the direct pyramidal tract end, according to Lenhossek, in fine brush-like expansions about the motor nerve cells of the anterior horn of the same side. On the contrary, undoubted clinical and experimental evidence is at hand to prove that the greater portions of the fibers cross over through the anterior commissure to end about the motor nerve cells existing in the opposite anterior cornu. Most of the fibers of the direct pyramidal tract seem destined to the arm; hence the relation of the arm is almost exclusively with the opposite side. The fibers


24


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. IGG.


of the tracts, direct and crossed, conduct impulses ot voluntary motion from the motor areas of the brain to the muscles. If the fibers of the motor tract be destroyed by severing their connection with the cells of the motor area of the brain, there will result a motor paralysis of the opposite side of the body and a descending degeneration from the point of lesion throughout the entire extent of the tract. In the cord the degenerated areas will be the direct pyramidal tract of the same, and the crossed pyramidal tract of the opposite side. This degeneration is complete, involving the termination of the axones and collaterals, about the nerve cells of the anterior cornua. and is due to the loss of trophic or nutritional influence, which results from the severance of the nerve fibers from their mother cells, in the motor areas of the cortex. The peripheral portions of the tract on the contrary remain normal, because its nutrition is dependent upon the motor cells of the anterior cornu whose neuraxones form the peripheral portions of the tract." For a more complete discussion of the subject of infantile cerebral palsies, especially their relationship to the acute exanthemata and infectious diseases in general, the reader is referred to the article of Freud (Nothnagel's Specielle Pathologie und Therapie, Vol. IX, Part 3) ; that of Osier (Medical News, 1888, No. 2, 3, 4 and 5); Strumpell, Ueber die Acute Encephalitis der Kinder (Jahrbuch fiir Kinderheii Kunde, XXII, 1884); Strumpell on primary acute encephalitis (Deutsches Archiv liir kiln. Medicin, Vol. XLVII); also P. Marie, hemiplegie cerebrale infantile et Maladie infectieuses (Progres med., 5 Sept., 1885).


BALTIMORE, FEBRUARY, 190 5.

CONTENTS - February

  • On the Teaching of Anatomy as Illustrated by Professor Barker's Manual. By Fkanklin P. Mall,
  • The Anatomical Laboratory of the University of California. By Joseph Maushall Flint, M. D.,
  • Anatomical Material— its Collection and its Preservation at the Johns Hopkins Anatomical Laboratory. By Franklin P. Mall,
  • The Development of Grave Robbing in England. By G. Canby Robinson, M. D.,
  • On Flechsig's Investigations on the Brain. By Florence R. Sabin, M. D
  • A Note on the Developmental Relations of the Kidney and Ureter in Human Embryos. By Augustus G. Pohlman, M. D.,
  • Abnormalities in the Form of the Kidney and Ureter Dependent on the Development of the Renal Bud. By Augustus G. Pohlman, M. D.,
  • On the First Appearance of the Renal Artery, and the Relative Development of the Kidneys and Wolffian Bodies in Pig Embryos. By Eben C. Hill, (iO
  • High Bifurcation of the Brachial Artery with Reunion at the Elbow. By Minerva Herrinton, 65
  • Fixation of Tissues by Injection into the Arteries. By Burton D. Mters, M. D., 66
  • A Convenient Still to Make Absolute Alcohol. By William J. Calvert, M. D 68

Announcement Concerning Graduate Instruction in the Medical Department of the Johns Hopkins University. By W. H. Howell, M. D., 70

Summaries or Titles of Papers by Members of the Hospital or

Medical School Staff appearing Elsewhere than in the Bulletin, 73


ON THE TEACHING OF ANATOMY AS ILLUSTRATED BY PROFESSOR BARKER'S MANUAL^

By Franklin P. Mall.


Professor Barker has given us a profound work upon the nervous system and an excellent English edition of Spalteholz's superb Atlas of Human Anatomy. To these he now adds a laboratory manual of anatomy, one of the best dissecting-room guides which has ever been published.

With the exception of those in a few medical schools the dissecting-room is a pretty poor specimen of a laboratory, due mainly to the lack of competent instructors. The course is generally " go as you please," and in order to accomplish anything it requires students of ability and earnestness with a power to plan ahead, and for them Barker's Manual will be a great aid. From it they will receive guidance, which other


'A Laboratory Manual of Human Anatomy. By Lewellys F. Barker, M. B., Tor., Professor and Head of the Department of Anatomy, in the University of Chicago and Rush Medical College. Assisted by Dean De Witt Lewis. A. B., M. D., and Daniel Graisberry Revell, A. B., M.B., Instructors in Anatomy in the University of Chicago. 8vo. 583 pages and 298 illustrations, many in colors. (Philadelphia; J. B. Lippincott Company, 1904).


wise could be received only from competent teachers. The Introduction to the Manual points out to the student the wellknown methods for unraveling the human body, by which they obtain knowledge at first hand. " Careful practical work in the dissecting-room is the only means a medical student has of obtaining an independent view of the gross structures of which the body is composed. He should learn to see what comes under his eye. He should try by his own independent activity to see all that is there, for the student who learns to see only what he is told to see, or what is pointed out to him, will be spoiled for the study and the practice of medicine." Professor Barker seems to ignore wholly that anatomy ( ?) which consists of memory feats brought about by drill masters who have prepared the student for no one knows what. " The very first dissection," he says. " may be all-important as regards the subsequent dissections. He who fails in his earliest dissection to acquire the habit of working according to a definite method, seldom learns later to become an exact, quick, and careful dissector. It is almost hopeless to try to make a


30


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


man do exact and clean work in the dissecting-room after he has once formed inaccurate and dirty habits. ... If a dissector permit himself to expose structures roughly, to isolate them incompletely, and to clean them imperfectlj', so that his dissection becomes indistinct, bad-smelling, and repulsive-looking, he will quickly lose interest in his work, slice the part desperately, neglect it, stay away from it, and fail utterly to benefit by it. . . . The thorough dissector is much more likely to become a fine discriminating physician and an effective, progressive surgeon." Not one word do we read in this excellent book about memorizing names, systems of mnemonics, quizclasses and final examinations. Nowhere do we read that the 5000 questions which were placed before me while a medical student gives the " royal road " to knowledge.

The book is written as a guide to earnest students who, with the aid of good teachers, desire to dissect the human body and thereby obtain a conception of it. If a student wishes to study anatomy he is most successful when he obtains his knowledge through actual experience in the dissecting-room, and to do this he must learn to imravel the structures of the body, and to see, classify and describe what he has done. While working thus he is naturally led into the literature of the subject which, when drawn upon later in life, should enable his imagination to see the part described in three dimensions of space.

The methods of isolating the structures of the human body have been well established, and certain rules for dissection have been formulated. These rules are well known to anatomists, and it is best for the students when they are taught them by the most experienced teachers. To do this the teachers must accompany the students in their daily work, and imless this is the ease the ship will run upon the rocks, even if the nautical almanac and the quadrant are in the hands of the sailors. It is the ideal of the instructor, the word here and the word there, that means so much to the student. The great bulk of the time of the student is to be occupied by his own work — dissecting, reading, drawing, comparing and reflecting — and here the Manual may help out immensely. In it the thousand and one hints are given, and questions are answered in order, as in a dictionary. Professor Barker has written what the teacher says many times, and I shall be much gratified if, in future, it saves me some words.

In arranging the material. Barker has followed closely the order given in Cunningham's Manual, thus enabling the student to use both books at the same time. The steps and technique are to be gotten from Cunningham, while the hints and directions for study are found in Barker's Manual.

It is possible to classify the teaching of anatomy in America under four heads.

The first and lowest order is found in those schools which give a course of crude lectures on anatomy with a dissectingroom in which the work is not directed, but is done in a superficial way. Often the students do not dissect at all. At best they use a brief guide or a quiz compend which enables the students to " learn enough " to pass the examinations. Barker's Manual will be of no use — will be wholly lost— to


both students and professors in medical schools which conduct their course in anatomy in this way.

The teaching of anatomy is of a higher order when it follows closely some text-book, especially Gray, when it has lectures and recitations and enough work in the dissecting-room to enable the students to identify the grosser structures, thereby giving enough information to enable the students to pass State examinations. Most of the medical students desire courses of this order. Barker's Manual will be of little value to them, but it is to be highly recommended to their teachers, for through them it will do the greatest good.

In a third and higher order of medical school, about twenty of which may be counted, the course is given to aid the students in their subsequent medical studies. Practical things are pointed out in lectures, and emphasized again in the dissecting-room, and finally the student is examined upon them. Both students and teachers work pretty hard, and at the end of the course all feel that much good has been done.

A professor told me recently that he made his course " truly practical " by teaching only the essentials which he learned, by canvassing all of the clinical teachers. What they considered essential was taught, and what was considered unessential was excluded from the course. This practical knowledge he drilled into his students by means of lectures, quizzes, and thorough work in the dissecting room, and the results were most satisfactory to all concerned. To him and to his better students I most cordially recommend Barker's Manual. It will give them something to think about, and by that very effort will do them much good.

In the fourth order of anatomical course it is considered that there are others to be satisfied besides the teachers in a few practical branches, — there are the teachers in the other sciences, physiology, neurology, pathology, as well as anatomy itself. A student told me recently that he had been studying one thing to help him in another all of his life, and he was dead tired of it; he now desired to study things that were worth studying for their own sake. For him anatomy could not be considered an ancillary science. In presenting a science to students no attitude can be defended, except that in which the science is studied for its own sake. In so doing the development of the student cannot possibly be ignored, for understanding and self-development go hand in hand.

" Many students in the past have entered the dissectingroom with an utter lack of independent power of observation, of examination and of description, and yet these three qualities are absolutely necessary for the man who is to engage successfully in the practice of medicine. While it is to be hoped that the advance in the requirements for admission to professional schools, leading as it does to observational work in physics, chemistry and biology preliminary to the work of the medical course, will bring the students to our laboratories of anatomy better prepared than hitherto for the independent observation of anatomical structures, there can still be but little doubt that many students will learn how really to study and observe first in the dissecting-room. How important it is that the habits formed at this early period of the profes


February, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


31


sional course should be such as will be of value to the student later, such as he would desire to have throughout his professional career I If he have learned to be exact and steady, systematic and thorough, cleanly and artistic in his work in the dissecting-room, how much better for him than if at the outset of his career he become satisfied with superficial observation, with interrupted and irregular activity, with disorder and uncleanliness ! The habits formed in the anatomy building have their effect upon the whole life of the physician. The student in the beginning should aim not so much at rapidity as at method. Wlien he has once formed the habit of proceeding always according to a careful method, the rapidity will quickly follow.

" It is sometimes asked : ' Why should the medical student spend so much time and take so much pains in making a careful and beautiful dissection? Is it not time wasted to work out the smaller branches of the nerves and bloodvessels ? ' Experienced teachers who require thorough work are not disturbed by such inquiries. Those who have had the best opportunity for judging assert that it is only when a man succeeds in making a fine dissection that he gains an interest and pleasure in an occupation, which may not at first be attractive to him. Further, the impotance of working out the finer structures lies not always so much in the actual knowledge of these structures gained by the student, as in the acquisition of the habit of thoroughness of observation and investigation. The medical student who in the dissectingroom dissects out only the main trunks of the vessels and nerves, or only the structures which, at the moment, seem to physicians and surgeons of greatest practical import, is likely, as a clinician, to be satisfied with the detection of the more obvious and superficial symptonas, to the overlooking of the less prominent sj^mptoms and the more obscure physical signs."

It is especially for students and teachers of anatomy in the best medical schools that Barker's Manual will be of great value.

It is generally admitted that the most valuable training in anatomy is obtained in the dissecting-room, and it is in this place where the best teaching can be done. The instructor, text-books and manuals are only aids to be used as guides. The main effort must be on the part of the student, for it is he who is to obtain the knowledge through his senses. He must unravel the structures, arrange and classify them, reflect over them and express them, best by means of drawings, in order to get the most out of his work. His work is easy in proportion to his power to see in three dimensions of space, and to aid this models and pictures are to be used. It happens, also, that anatomy has an extensive language of its own and he must acquire some of this in order to express his knowledge of the subject in words, as well as to gain command of its extensive literature. While a few will excel, every student must be able to do this in part at least, before he is proficient in anatomy.

It is relatively easy to dissect the human body successfully, and when a student can attach names to the structures he has


dissected he is usually satisfied. The second step, studying the part is the difficult one, one that is mastered by but few students. The movement in anatomy in America during the past twenty years has been to make the study inductive, just as Huxley would have it, and in order to bring this about students have been introduced to anatomy in the dissectingroom rather than in the lecture-room. My own experience is that nearly all students can be made good dissectors in less than a week, and many of them in a day, but it takes a number of weeks before they are able to get the full benefit of their own dissections. If, with pictures to aid the imagination, they can look ahead and if, with pencil they draw what they have dissected, they have accomplished much for they work independently. Such students the instructor can aid with advice, he can discuss next steps with them, he can aid them in reading and in drawing, all of which he does with the greatest of pleasure. But many students do not have this gift and to teach them is difiicult. Barker's Manual not only helps them, but does not retard the talented students. Superficial students can never use it as a quiz-compend, nor can it be memorized. In the description of the back, for example. Barker says on page 45 :

" Refiect the two triangular flaps of skin, taking none of the fat of the superficial fascia with it. Have your atlases open before you. Having ascertained the region in which the medial set of cutaneous vessels and nerves is likely to be found, with the knife make a small cut through the superficial fascia down to the deep fascia. With the special heavy probe recommended, separate an area of the superficial fascia until you encounter the trunk of a blood-vessel or a nerve coming through the deep fascia from below to enter the superficial fascia. It is common to find a nerve, an artery and a vein together. Carefully separate the structure or structures found from the superficial fascia, tracing the blood-vessel or nerve as far as possible and cleaning it thoroughly. In this way, isolate all the superficial blood-vessels and nerves in the medial and lateral areas in which they occur. The nerves and blood-vessels will be found emerging through the deep fascia. Their course and ramifications in the superficial fascia are to be traced out without removing the fat or disturbing the relations of the structures any more than is necessary in exposing them. It should be borne in mind that it is only the natural relations that are of importance, and not the artificial relations due to dissection. Hence, each structure should be studied as it is worked out, instead of its study being deferred until after it is isolated and cleaned. When the cutaneous nerves and vessels and superficial glands have been thus exposed, a drawing of these should be made; or the drawing may be made concurrently with the dissection, being then an aid to the determination of the exact relations.

" The deep fascia should be cleaned (by careful removal of the superficial fascia by blunt dissection) and its extent, nature and attachments studied. The fascise should then be removed piece-meal. In cleaning the surface of the muscles, place the body in such a position that the muscle-fibers will be rendered tense and carry the knife in the direction which


32


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


permits removal of the fascia with the least disturbance of the underlying muscle. Care should be taken to avoid giving a ragged appearance to the surface of the muscle. As soon as the trimk of a nerve or blood-vessel is found, ascertain its name from a study of the illustration in your atlas. Look up this name in the index to your Systematic Human Anatomy and refer to the author's description. When handling a nerve, blood-vessel or indeed any structure, form the habit of repeating to yourself its name; this practice is extremely helpful in fixing the association between the structure and the name which is the sign for it. Also, when reading, write down every new term met with and learn its meaning, both literal or etjrmological and applied or derived."

After this there follows a list of nerves, arteries, veins and muscles in the order of their appearance, with reference to figures in the Manual as well as in Spalteholz's Atlas and other books. The subject is presented just as if the reader really wanted to study anatomy. It is illustrated with 298 figures, in great part taken from Toldfs Atlas, and from Poirier and Charpy^s Anatomy.

Throughout the Manual the new nomenclature is used with the old names, when they differ much, placed in brackets. Both English and Latin terms are given. In my opinion, it would be better if only the anglicized new nomenclature were given, much as has been done in Cunningham's Anatomy. The international terms (Latin) can be found easily by referring to Spalteholz, which is to be used in connecMon with this Manual. However, it is very desirahle that the new nomenclature shoiild be used, for then the student commands a language of anatomy which is not only English but is also international.

The names in anatomy were introduced by many authors during past centuries, which naturally led to the formation of numerous synonyms. Over a century ago this chaotic condition was deplored by Sommering (Bau des menschl. Korpers, S. XII, 1800), who then suggested that anatomists construct a imiform nomenclature as the botanists had done. But each new attempt brought only a new set of synonyms, for there was no Linnaeus in anatomy who could do the work. The numerous names then, as at present, made the study of anatomy very much more difficult than it would be were the terminology simple and rational. At that time, Dumas (1797) attempted to make it rational, however, with


out success, as is the case with Wilder's nomenclature in recent years. A great authority, as a congress, was necessary to bring about this reform. Henle (Anatomic, S. VII, 1858) revised the list of names very markedly, placing the synonjmis in foot-notes, not "using them indiscriminately as pedants love to do. His reform did much good and also caused much confusion; we have to thank him, however, for the terms, dorsal, ventral, sagittal, frontal, medial and lateral. I^ater, Owen added to them the terms, distal and proximal.

Finally, the suggestion of Hyrtl (Anatomic, S. 35) bore fruit. He proposed that the Naturforscher Gesellschaft, from which the Anatomische Gesellschaft sprang, take up the subject and give the nomenclature of anatomy a thorough scientific and philological revision. This was finally done, under the leadership of His. The international committee, with Sir William Turner, Cunningham and Thane to represent England, supported by the Academies of Berlin, Munich, Vienna, Leipsic and Buda-pest, and the Anatomische Gesellschaft, after six years of hard work, finally rendered a satisfactory report (see His, Nomina Anatomica, 1875), which has been accepted generally by the anatomists of the world. In our language we have a number of comparative anatomies, two very important atlases (Spalteholz and Toldt), a text-book (Cunningham, in part), and now Barker's Manual which uses this terminology. Students, physicians and some professors think something radical has been done, and fear that if they accept it they must ujilearn something, — they know not what,- — but when they realize that it is the Italian, the German, the Swede and others must change their terminology much more than the Englishman, they will welcome the new language. It differs less from our terminology than from that in any other language. The His nomenclature (BNA) has reduced the 30,000 anatomical terms to 5000, and of them 4500 are the same as the English terms. Of the 500 terms which differ from the old, the change is usually slight. Nearly all of the radical changes were made in the neural terms, and in general these have been accepted by all writers. Had Barker anglicized the names of BNA, but few readers of the Manual would notice that he has used the new nomenclature.

It is to be hoped, in the interest of anatomy and scientific medicine, that Barker's Manual wiU receive a wide circulation.


THE ANATOMICAL LABORATORY OF THE UNIVERSITY OF CALIFORNIA.

By Joseph Makshall Flint, M. D.


In the past few decades many papers have been published upon the ends and aims of anatomy, as well as upon its pedagogical methods and the construction of laboratories in which it is taught. These articles cover this field thoroughly and well. It seems, therefore, quite unnecessary to make another contribution to this, already, large literature. Hitherto, most of the larger anatomical institutes have been constructed anew


where the director has had an opportunity to express his ideas entirely unhampered by already existing structures. As it is sometimes necessary, however, to reconstruct or readapt buildings already in existence for the use of an anatomical department, our experience in the University of California may have some new interest and possibly some practical bearing. Here, it was essential to rearrange the quarters in a


February, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


33


building, planned for the medicine in vogue before the extensive introduction of the laboratory system. It may be well to state, however, that these rooms lent themselves admirably to our needs. It is, indeed, probable that most quarters supplied with adequate space and light could be transformed into a serviceable laboratory adapted to the needs of modern anatomy. In the rearrangement of the space at our command, attention was paid to the following objects: First, the necessities of teaching and, secondly, facilities for research. Under these two heads and their ramifications, all the needs of anatomy may be supplied. It was deemed wise to provide space and equipment for a class of 50 students, although our maximum attendance in any one class has thus far been but 42.

Naturally, in anatomy, as in other educational branches, the chief essentials of equipment are men and not rooms nor microscopes. In this country, for some reason, it has been difficult to preserve a proper ratio between staff work and equipment. In some institutions splendid equipments are insufficiently manned, while in others it is often true that good men are handicapped either by a lack of materials with which to do their work or else are overburdened with excessive routine. Perhaps we are in what one college president terms " The Stone Age," in which our university resources are too apt to crystallize into bricks and mortar instead of contributions to the various fields of science. According to A. G. Mayer's ' recent study on the material and intellectual development of American imiversities, things have not improved much in the last decade ; but in the case of the medical branches of university life, there has been a noticeable exception. In recent years, particularly in the so-called scientific branches of medicine, several well-equipped and well-manned laboratories have been established. Indeed, there seems to be a general tendency to conduct the first two years of medicine at least upon a university basis. This means, in addition to routine teaching, a portion of the energy of the department must be spent in productive scholarship. In the University of California members of the anatomical staff are expected to devote one-half of their time to research.

The building, in which the Medical Department of the University of California is sheltered, was constructed for the University by the State of California, in 1898. It consists of a substantial three-story building, constructed of granite and buff brick, situated on Parnassus heights and commanding a magnificent view of the Pacific Ocean and the bay of San Francisco. The old quarters allotted to anatomy were on the top floor, where one large dissecting-room with roof light and a few smaller rooms were allotted to the students in anatomy. Additional space on the lower floors was obtained for an histological laboratory, store-rooms, and photographic-room. Adequate room in the basement for the embalming and preservation of anatomical material was arranged in the first plan of the building.


Material versus Intellectual Development of our Universities. Science, Vol. XX, 1904.


DISSECTING-ROOMS.

The large dissecting-room was provided with roof light, a tarred floor and rough brick walls. In the conversion of this space to more modern dissecting-rooms several points concerning anatomy in this coimtry had to be borne in mind. In the first place, anatomical material was often poorly preserved and frequently scant in quantity ; in the second, by tradition, students who crossed the threshold of a dissecting-room assumed at times that they were absolved from all standards of good conduct. Hats were worn; students dressed ia outlandish costumes. Smoking was generally permitted, and boisterous conduct, accompanied by the throwing of material were not infrequent occurrences. To break this tradition and to obtain in a measure the morale and seriousness characteristic of the students in other departments of the university, we profited by the experience of Professor Mall of the Johns Hopkins University, who, in the construction of his laboratory, went on the assumption that students should be divided into small groups and should be provided with dissecting-rooms, which resemble a modern laboratory more than they do a stable. Accordingly, the large dissecting-room was re-covered with a new floor, and was cut up into a series of small rooms, each, with a capacity of from 1 to 4 tables, thus segregating small groups of students. In this way fewer distractions occur and one obviates the inevitable noise that occurs when even larger bodies of well-behaved students are quartered in the same laboratory. The rooms, moreover, were fitted with especial care to make them clean, neat, and attractive, hoping in this way to obtain the effect of a pleasant environment upon the work of the students during the periods of dissection. The large room was 35 by 110 feet, and was subdivided into eight small dissecting-rooms, a research room and a museum. The largest of these small dissecting-rooms is 30 by 21 feet, with a comfortable capacity of four tables and a maximum of six, while the smallest is 12| by 15 feet, and holds one dissecting table conveniently. The remainder are so arranged as to hold from one to three tables. The rooms are provided with heavy tables with zinc tops, draining toward the center into a bucket suspended beneath the table. Adjustable arm-rests and book-stands also form part of the equipment. As soon as the body is cut in parts, students are no longer forced to work together, and in consequence one or two small tables with book-stands are provided in each dissecting-room. There is a sink with running-water and a large drip-board to hold parts while they are being moistened, or for the study of the viscera. Each room has, besides, an articulated skeleton for convenient reference and a blackboard upon which schemata may be drawn and relations studied. During the period of dissection the student is held responsible for his material, which must be carefully wrapped in cheesecloth at the close of each laboratory period. These wrappings are moistened in a solution of carbolic acid, glycerine and water, made according to the following formula:

Water 1000 cc.

Glycerine 30 cc.

Carbolic Acid 20 cc.


34


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


This procedure prevents desiccation and, at the same time, acts to a certain extent as a preservative.

The Museum.

No space vv'as available for use as a museum and, accordingly, the entrance hall to the dissecting-rooms was left large


ing, has proved most fortunate. In the experience of most laboratory workers, students in the attendance upon regidar courses very rarely avail themselves of the opportunities afforded by a museum. The interest in such specimens is not suiBcient to overcome the inertia of any but the best students. But if exhibition cases are so placed that they must be passed in going to and from the regular work, specimens



RESEARCH


DISSECTING ROOMS


DEPARTMENT »T ANATOMV

Fig. 1.


for this purpose. Its dimensions are 20 by 32 feet and it contains sixteen unit museum cases for the exhibition and storage of models that are used either for demonstration or teaching purposes. Here also are kept the most interesting variations which have been found from time to time in the dissectingrooms, as well as examples of research work which has been done by students and members of the teaching staff. The latter are valuable for the purpose of demonstration, and often act as a stimulus for more serious students to engage in research work. The location of the museum in this hall, which was forced upon us by lack of space in other parts of the build


are frequently studied when, under ordinary circumstances, they would not be seen. In the course of a year's work, students register many thousands of visual impressions simply in passing back and forth. The museum is provided with two large unit tables for the study of its preparations, but these are naturally exposed to the noise caused by students in transit. Were I to build a laboratory anew, I should consider as one of its most important features the placing of the museum in the main thoroughfare of the laboratory. At the same time it would be advisable to have at one side an exhibition room where specimens could be studied in quiet. During the three


February, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


35


years that the laboratory has been opened, students have developed a morale which enables us to trust them with the models. And, considering the amount of handling they have had, the breakage has been remarkably small. Among other things the museum contains the usual sets of teaching models of His manufactured by Ziegler of Frieburg, and Steger of Leipzig.

Preparation of Materials.

The embalming-room is situated in the basement, and is reached by a private driveway, which secures privacy in the reception of cadavera. The embalming-room is provided with a hydraulic-pressure apparatus, modeled after the one in the anatomical laboratory of the Johns Hopkins University. It consists of an ordinary water-boiler, provided with controlled outlets and intakes, a pressure gauge and a pipe at the top to conduct compressed air. The embalming and injection fluids



- l\



"


STORAGE ROON



1 LMBALIilNG ^

noon 1 ( ) fn{


STORAGE Roon



^^H ^B^^B


Fio. 4. — Plan of Embalming and Stokagk Rooms.

are forced from aspirator bottles, through rubber tubing canulse, into the body at any desired pressure. The material received by this department comes almost exclusively from the Almshouse. The subjects are, as a rule, very old, and owing to the activity of certain religious organizations which insist on the burial of females, consist almost exclusively of males. The embalming is done through both distal and central ends of the femoral arteries. At first, we embalmed from one side alone, but experience soon showed that the advanced degree of arterio-sclerosis in these subjects often made it impossible to preserve both extremities well unless the injection is made through both femorals. The fluid is forced into the vessels from the injection flask under a pressure of about five or six pounds to the square inch, by means of a series of Y-tubes terminating in cannula. After the body is injected it is allowed to remain for 24 hours, and then coloring matter is forced into the vessels. At first both arteries and veins were injected ; subsequently the venous injection was abandoned, as the inevitable tearing of small veins in order to clean up a


dissection gave it a very dirty appearance. With the single arterial injection, these vessels stand out clearly differentiated from the collapsed veins, which can be easily seen and preserved in an average dissection. After the vascular injection is complete, the calvarium is opened and the brain removed for use in the course in neurology, in which each student sections at least one complete encephalon. Several methods of embalming have been used. The earliest was an arsenicformalin mixture which preserved the body excellently; but, like most formalin embalming fluids, tended to make the arms and legs stiff and rigid. The abduction of the extremities necessary for the dissection of the axilla and perinseiun frequently ruptured the pectoralis major and the abductors of the legs. Moreover, this material frequently became discolored, the differentiation between the muscles and the surrounding structures was not distinct, and flnally they seemed to be particularly liable to infection with moulds. Struther's fluid was also used, and in many instances gave great satisfaction. In cadavera preserved by this method the differentiation of the fascia is exquisite; but, in many of them, the coagulation of the myosin is incomplete, leaving the smaller muscles soft and friable. Thus it became quite difficult to preserve them without tearing or distortion throughout the dissection of a part. The carbolic mixture advocated by Mall we employ now almost exclusively. By its use the preservation and differentiation of the various structures seems on the whole best. Moreover, bodies preserved by this method are practically odorless, and can be left exposed to the air for months during dissection without either moulding or undergoing putrifaction. The material has been preserved in two ways, one in wood alcohol vapor and the other by means of immersion in a 3 per cent solution of carbolic acid. For both purposes, zinc-lined wooden tanks are used, varying in capacity from 7 to 14 bodies. The most convenient tanks, in our experience, are 50 inches wide, 27 inches deep, and 6 feet 4 inches long. These tanks have a capacity of 14 bodies. After a careful comparison it seems that the wood alcohol vapor, while efficient, is more expensive and also has the disadvantage of allowing an extreme mummification of the extremities to take place. In bodies, however, where the hands and feet have become almost completely desiccated, or where the skin is tough and leathery, after they have been exposed to the vapor of wood alcohol for a period of two years, we have succeeded in restoring flexibility to the extremities by means of immersion in hot water. When bodies are in this condition, we place them for a period of 12 to 48 hours in a porcelain bath-tub full of water at a temperature of about 60° Centigrade. The fluid is taken up and the hands and feet rapidly soften. By far the best of our material, however, has been that preserved by immersion in a 3 per cent solution of carbolic acid. At present we have over 100 bodies stored in this way, some of which have been in the fluid for eighteen months. The skin becomes particularly well fixed, rendering it useful in the preservation of material from desiccation through a large portion of the period of dissection. The method also has the advantage of being economical. A string


36


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


is tied around the neck of each subject to which is attached the body number held upon a cork. This floats upon the surface of the tank. It is possible, therefore, by simply referring to our card catalogue of anatomical material to recover any body at will. Above the tanks is a rail suspended from the ceiling ; a wheel to which is attached a block and tackle travels on this track. It is a simple matter for one person to handle and care for the material by means of this tackle. An elevator runs


also intended to simplify as much as possible the routine work of the department. It is in charge of the technical assistant who prepares the sections for class work and keeps the stock solutions, reagents, and stains always in good condition. The room is provided with large vmit tables, lockers for reagents and apparatus, thermostats, glass tubing and rodding, the still, and a large sink with numerous gas and water attachments, microtomes, museum jars for stock specimens, blast



HISTOLOGY


Fig. 9. — Plan of Histological Laboratory.



PROJECTIOIN R.0OM


Fig. 11. — Plan of Projection Room.


from the storage-room in the basement to the dissecting-rooms on the top floor. In the embalming-room, there is also a macerating tank, for the preparation of skeletons from the finished dissections.

The Preparation Eoom and the Eesearch Eooms.

On the top floor, in a wing opposite the amphitheater and dissecting-rooms, are the research rooms and preparation room. The latter is large and has abundant light from three sides as well as the roof. It was planned with the idea of its being the main working center of the laboratory. In this room are the commoner materials and reagents for all ordinary work and the simpler forms of research. The preparation room is


apparatus, vises, etc. Acid corrosions are made on extension shelves just outside of the windows, which do very well in lieu of a hood. There is also a large scale stand provided with coarse and fine balances.

The research rooms are occupied by individual members of the staff, and have, besides the usual water and gas supply, the equipments which the several members require for their own special work.

Histological Laboratory.

The histological laboratory is situated on the second floor, and was made by tearing down two partitions and converting three rooms into one. The room faces the north and abun


THE JOHNS HOPKINS HOSPITAL BULLETIN, FEBRUARY, 1905.



Pig. 2. — Dlssecting Room.



Fig. 3. — Model Room.


THE JOHNS HOPKINS HOSPITAL BULLETIN, FEBRUARY, 1905.



Fig. 5. — Emisalmixg Roo.m.



Fig. G. — Stok.vge Ta.xks .^.nu Elevator.


THE JOHNS HOPKINS HOSPITAL BULLETIN, FEBRUARY, 1905.



Pig. 7. — Pukpauatiox Room.



Fig. 8. — Phiv.\te Room.


THE JOHNS HOPKINS HOSPITAL BULLETIN, FEBRUARY, 1905.



Fig. 10. — Hi.sTOLOGic'Ai. L.\I!i)1(at(ihy.



KiG. 12. — PlIOTOGRAPHIC ROOM.


February, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


37


dant light was obtained by cutting two extra windows in the alcove. Students are seated either at wall-shelving or at long tables. The room has a capacity for fifty students at one time. There are two large sinks, a large paraffine oven with apartments for each member of the class. On the opposite side of the hall is a small room used for the storage of charts and microscopes. Each student is provided with a wall locker to which he carries a key. This locker contains his microscope, reagents and working equipment; a small wooden tray with holes that exactly fit the reagent bottles makes it easy for him to remove his reagents from the locker to the desk. Each locker outfit contains the simpler reagents and stains, while those that are only used occasionally are kept on the shelves above the sinks. The microscope outfit consists of a Leitz 1-A stand, with the 1, 3, 5 and yV objectives and the 0, 1, 3 and 4 oculars. Each student has, as well, a dissecting microscope for teasing purposes and low power work. The general equipment of the room consists of a stereoscopic microscope for demonstration purposes, microtomes for both paraffin and celloidin sections and a well-stocked cabinet. Most of the histological models are kept in the general model room. We have used bromide enlargements for our charts in microscopic anatomy. These are made from plates or figures from the literature illustrating the objects which it is desirable to show. They are very clear and are much cheaper than charts made by an artist.

Projection Eoom.

The projection room is in the basement where the inconvenience of its situation is compensated for by the existence of brick piers erected independently of the building. These facilitate the making of photographs without the occasional annoying tremor caused by passing tram-cars. The walls and ceiling of the projection room are black, while the windows are protected with two sets of opaque curtains which entirely exclude the light when the room is used for projection. The room is equipped with a complete Zeiss microphotographic apparatus, consisting of bellows, plate-holder, microscope, condensers, filters, stand, etc., etc. The Zeiss apparatus is the property of the Department of Pathology and is used by both departments in common. Owing to the fact that there is no electric current in the building we were at first forced to use a cluster of Welsbach lights for microphotographic work. And while fairly successful pictures could be taken with this illumination, they were not wholly satisfactory, as the peripheral illumination through the higher powers of the microscope was vague. More recently we have employed a 3-burner acetylene lamp. With this light, we succeed in obtaining clear pictures with high magnifications. Successful projections up to 100 diameters can also be obtained by its use. The acetylene generators are now manufactured so they are safely, cheaply, and easily operated. Besides the Zeiss apparatus there is a large 8 x 10 copying camera, fitted with a 5-foot draw and bellows. This is equipped with a Zeiss protar lens. There is also a small Zeiss camera, 5x7, with a complete series of lenses for various grades of minor work.


Adjacent to the projection room is the dark-room, provided with a maze-doorway, by means of which it is possible to enter and leave the dark-room at will without closing a door. The light for the dark-room is situated in the projection room, thus it is easy to keep the former cool. A light-tight ventilator has also been arranged in the transom of the door in the dark-room, giving with the maze-entrance a constant current of air. It is possible, therefore, when occasion requires, for this room to be in use six or eight hours a day without having the air become either close or oppressive. I have tested the dark-room by leaving half a plate exposed for ten minutes in the doorway, while the other half was developed immediately for comparison. At the expiration of the time stated, absolutely no fogging was observed in the half of the plate used for the test.

Unit System of Furniture.

As far as possible, the laboratory is furnished throughout on the unit system. Wall cases, museum cases, dissecting tables, laboratory tables, operating tables, wall shelving, sinks, book-stands, animal cages, etc., are all constructed on a unit system, making the rearrangement of the laboratory furnishings easy and practical. The furniture is stained a cherry red, while the table tops, sink tops, etc., are all stained with anilin black. Although the preparation of furniture by this latter method is rather tedious, the results amply justify the extra expenditure of energy. They are a dead black in color, are not acted upon by acids, alkalies, alcohols or any of the reagents used in ordinary anatomical work. After this treatment the furniture always looks well, and is easily kept clean. The process is so simple that an experienced painter is unnecessary, as any janitor can prepare the woodwork by this method. Three solutions are necessary:

Solution No. 1. cc.

Anilin Oil 1.5

HCl 1.5-1.75

Water 1000

There should be sufficient HCl added to make the solution slightly acid. It is shaken until the oil globules no longer float on the surface, which occurs when the solution is slightly acid.

Solution No. 2. cc.

Sodium Chlorate 100

Copper Sulphate 100

Water 1600

Solution No. 3. cc.

Chromic Acid 5

Water 100

Paint with solutions No. 1 and No. 2 alternately three or four times, allowing each successive coat to dry thoroughly. One or two coats of solution No. 3 will then turn the wood perfectly black. After the surface is entirely dry, it may be rubbed down with boiled linseed oil or better with a 5% solution of paraffin in benzine. If the paraffin solidifies or crystallizes out, the surface of the table may be warmed with a Bunsen burner and the melted paraffin rubbed into the wood.


38


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


ANATOMICAL MATERIAL-ITS COLLECTION AND ITS PRESERVATION AT THE JOHNS HOPKINS

ANATOMICAL LABORATORY.


By Franklin P. Mall.


In 1893 when the Medical Department of the Johns Hopkins University was opened, it was announced that the course in gross anatomy would be largely practical and that the work would begin on November 15. At the beginning of the session, in October, it was found that no cadavers were on hand, nor were the chances in favor of obtaining them good, for during the previous year but 49 subjects came through the regular channels, to supply the some 1300 students in the different medical schools of Baltimore. The problem now changed from teaching anatomy to obtaining cadavers for a new school, and only complicated the situation by adding more students to a number already far too large to be supplied. I soon learned that during the fall of the year the demand for cadavers by the seven schools was far greater than the State supply and that the additional irregular subjects did not ease the situation very much.

Several years before, a case of burking, followed by a scandal, aroused public opinion sufBciently to enable the Legislature to pass a law regulating dissection, after the bill had been introduced a second time and pushed with great vigor. This law, unfortunately, is a broad compromise, one which will not compel the leading officials to deliver the bodies of the unclaimed dead to the Anatomical Board, nor does it make it a legal offense to remove a corpse from the Public Cemetery. So in order to become operative in the direction in which the law was intended, i. e., to give the bodies of paupers to the medical schools for dissection and thereby to prevent trafficking in them, it is necessary to have the good-will of the Health Commissioner and a strong Anatomical Board. At first a few bodies were delivered to the Anatomical Board but, aa a rule, the pauper dead were claimed and buried at the expense of the city, or if " unclaimed " were also often buried by the city because it was difficult to determine whether the deceased had been a resident of the State for a year prior to his death. So by this intei-pretation of the law the Health Commissioner saw his way clear to send 49 cadavers to the Anatomical Board during the college year 1892-93.

During October, while waiting for dissecting material, I experimented upon dogs with all kinds of embalming fluids in order to have the best possible method for cadavers when obtained. I may add that during the six weeks these experiments were being made the bodies of all the dogs putrefied with the exception of those embalmed with carbolic acid. At this time the weather was unusually hot, even for Baltimore, and I made a sufficiently large number of experiments to decide in favor of a carbolic acid mixture as the best embalming fluid. This experience proved to be valuable, for we have ever since been able to embalm our subjects well and in


turn the method has spread to many of the medical schools of America.

We were to begin to dissect on November 15, and before the date arrived the students began to worry, for they knew we had no subjects, and they also knew that they were not to be obtained. I myself felt very much the same in case we depended upon the State to send cadavers, and all preparations were made to go to larger cities for aid, which is easily obtained with a large purse. While these preparations were being made we postponed work until the 16th, and then the 17th, when, late in the evening, a subject was left in the basement. The next day one came from the State, and a few days later another appeared in the basement. This made us safe until Christmas, or until Easter, provided we dissected carefully and preserved the specimens well.

Towards Christmas, when all of the dissecting-rooms of Baltimore were under way, it was found that cadavers were more abundant and we did not fail to take what came, embalm them well with carbolic acid and place them in a large ice box which had been constructed in the meantime. By spring the box, which was built to hold five cadavers, had in it twenty and the further supply was not taken.

By this time it became apparent that in future it would be well to have an abundance of subjects on hand, and during the second year of the Medical Department an Anatomical Laboratory was built in which was placed an ice machine with a cold-storage vault large enough to hold 60 subjects. During the summer just 50 subjects were received, which together with 8 on hand nearly filled the vault. We also found that it was much cheaper to operate an ice machine than it cost to keep the large ice box filled with ice during the previous summer.

Shortly after the cold-storage apparatus was in operation the Anatomical Board proposed that all the subjects received by it during the summer should be stored in the Anatomical Laboratory. Heretofore these had been buried and were just so much loss to the Board. The Table on the following page shows in a measure the advantages of this arrangement by the gradual increase in the number of cadavers from year to year. 1 gather from the records of the Board that the total number of adult subjects delivered by the State have averaged 300 a year during the past five years, thus multiplying our supply sixfold, since we receive and preserve every subject. Furthermore, there are the bodies of about 300 infants which are also used extensively, making 600 in all, which would be enough to supply the demand were there not a gradual increase of the total number of medical students in Baltimore from year to year.


Febkuabt, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


39


TABLE GIVING THE RACE AND SEX OF THE CADAVERS ARRANGED IN HUNDREDS.

The dates of the reception of each hundredth subject, the number of autopsies, the source of the cadavers, and the number of bodies returned to friends are also given. The first cadaver was received on Nov. 17, 1893.



Cja











55


Race not given.


Negro.


European.



1


1


a .


" H








if


3


tH-3


Z.-^ ^








>t


•^ p

^•a











a;-? SS


D a


9.^


o-g P








1


= - 0)


=2


= 5


«ll


Male.


Female.


Male.


Female.


Male.


Female.


s

3


Isi


3


z5


Ooa








<i


2;£g


z3


100


Oct. 12, '95


41


11


30


16


9


3


30


46



200


Aprilie, '97


3


2


42


21


26


7


25


27



300


Oct. 18, '9T


3



40


21


32


4


43


60



400


May 26, -98


3



37


26


31


3


44


38


1


BOO


Oct. 10, '98



1


38


31


25


6


44




600


Mch. 18, '99





48


16


29


7


63


i



TOO


July 26, '99


3


8


43


31


31


4


34



1


800


July 13. '00



10


43


19


26


3


31





900


Feb. 27, -01


1



36


26


28


8


33



3


1000


June 10, '01


1



64


18


23


4


49



4


1100


Oct. 31, '01





60


21


24


6




2


1200


July 3, '02





43


31


24


3


41



5


1300


April 6. '03





43


21


27


10


43



10


1400


Nov. 9, '03


1


1


47


26


23


3


41



3


1600


April 13, '04





44


37


26


4


30



6


1600


Aug. 13, '04





44


23


27



33



6


1641


Oct. 1, -04





17


8


13


3


13



3


In 1897 a new Health Commissioner, Dr. Jones, was appointed and his order was " that all bodies should be turned over to the Anatomical Board for disposal, and if they were not wanted should be buried in the Public Cemetery." Although the cadavers received at the Johns Hopkins are not the total number received by the Anatomical Board during the year, they are in a measure a proportion of the whole, for they include a certain per cent of those collected during the winter and all of those of the summer. During the four years preceding Dr. Jones' appointment the Anatomical Board sent to the Johns Hopkins for storage an average of 44 subjects, while during the time he was Commissioner of Health the average rose to 185, which has been maintained ever since. Shortly after Dr. Jones' appointment I was elected Chairman of the Anatomical Board (October, 1898), and immediately took steps to complete the work Dr. Jones had begun. Orders were issued to the medical schools not to accept cadavers from outside sources, for there was an abundance of them on hand, and a form of receipt was introduced by which a cadaver could be traced had it gone astray. So since that time no cadavers have been procured from outside sources for dissection, for the " go-between " has had neither stock nor buyer, for all of the unclaimed dead go directly to the Anatomical Board.

The receipt enabled the Anatomical Board to keep the accounts up to date from a business standpoint. Before this there was no great haste in rendering bills nor in paying them, but from now on accounts were balanced once a month and any discrepancy could easily be corrected, for the details were still fresh in mind. Since the trafBcking in dead bodies was effectually broken up in Baltimore, the one source of danger. i. e. sending bodies beyond the borders of the State, had to be watched and it was this receipt which proved to be of value in finding and convicting an offender several years later (see


Devine case). From this time on the receipts became ofiBcial and are stored in the Health Department.

The business side of the Board is now in good running order, being in the hands of a secretary appointed by the Chairman of the Board, who in turn is elected annually by the Board. When I became Chairman, Dr. Warfield, my predecessor in ofBce, handed over to me bills for nearly $1000, one-half of which had been paid in advance by him. I immediately sent out bills and thereafter made a settlement once a month, collecting from the schools receiving them $4 for each whole cadaver and $2 for each autopsy. At the end of the first year we had no debts and $123 in the treasury, and a )'ear later $673, which has been increasing in amount ever since.

We are now obtaining all of the cadavers within the scope of the law, are dividing them according to legal requirements, have our treasury in good condition, are watching those who desire to cut into our supply (a certain type of burial society), and cooperate with the Health Department. Now, instead of having a column in our records of which we can give no account, we can account for every cadaver and often bodies are temporarily stored with us to be returned to friends when so ordered by the Commissioner of Health. During 1903 fifteen such bodies were returned, and during 1902, one which we had had in storage for eight months.

It is evident from what has been said above that the collection of cadavers for dissection was greatly facilitated when they were carefully embalmed and stored, for by so doing they could be collected during the summer, or whenever in excess, and kept until there was a demand for them. From a small beginning with an ice box holding five cadavers, a vaidt was built, and shelved to hold sixty cadavers. Later, the shelves were removed and the bodies were stacked, which proved to be better for the bodies, at the same time increasing the capacity of the vault six-fold. During these ten years we have had considerable experience in operating a small ice machine, in aiding to construct new plants elsewhere and in the different methods of embalming cadavers with carbolic acid. The problem presents different aspects according to the intelligence of the embalmer and the number of subjects to be embalmed each week. If there is a small number, say 50 a year, it is a question in my mind whether it is economical in time and expense to preserve cadavers by means of coldstorage. If the number per year is over 100, i. e.. at least 50 to be stored constantly, refrigeration has decided advantages.

At first the bodies were injected with 2 liters of a solution of equal parts of carbolic acid, glycerine and alcohol. I constantly came back to this solution, for it is easily handled and but small quantities are needed. But it is found that with so small a quantity but little of it reaches the feet, while most of it lodges in the viscera. So the quantity was gradually increased until from 4 to 6 liters were used, which means about 3% of carbolic acid to the body weight. Even with this quantity enough acid rarely reaches the feet, so it was necessary to change the method and inject the embalming fluid into the legs. At first but one femoral artery was used,


40


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


but in such cases it was diiBcult to force enough of the fluid into the arteries of the foot of the opposite leg. So, thereafter, cannulas were introduced into the femoral arteries of both legs, and the legs were first injected and then the body. In making these injections a constant pressure is used, from 150 to 200 mm. Hg., for this is much more certain than the irregular pressure given by a syringe.' In cadavers preserved in this way all parts are well embalmed, provided clots of blood have not blocked any of the arteries. Most of the muscles are coagulated in cadavers prepared as described above, and this is desirable in case they are to remain in the dissecting-room for a long time. If less acid is used the muscles retain their normal color and consistency, but the preparation becomes infected easily and decomposes in warm weather. Furthermore, the moisture required to keep the preparations from drying hastens the decomposition.

It was also found that the hands, feet and face dried easily in the dissecting-room, and especially in cold-storage, and to prevent this the body was carefully wrapped immediately after the embalming process was ended. First the hands, feet and face were smeared witli vaseline and wrapped with bandages of tissue paper which is ordered from the mills in rolls 5 inches wide and 3 inches in diameter. Then these bandages and the rest of the body were smeared with vaseline and the whole carefully wrapped with bandages of cheesecloth about a foot wide. It is well to wrap the legs and arms separately in order that they may be exposed easily for dissection, the rest of the body remaining wrapped, for the covering is an additional protection in the dissecting-room. Such bodies may be retained in cold-storage indefinitely without drying, although the thorax and abdomen gradually lose much of their moisture.

Immediately after embalming and before the body is wrapped the arteries are injected with pigment. For this purpose it is desired to have granules which fill the finer arteries but do not enter the capillaries. The axteries of the first 200 cadavers were filled with red-lead and plaster-ofParis, but it was found that the injection was often incomplete and in addition the action of the carbolic acid caused the color of the lead to turn black. Experiments were then made with all kinds of granules and fluids and it was soon found that granules of ultramarine blue mixed with shellac and alcohol proved to be the best. The granules are cheap, are just small enough to pass to the finest arteries; the solution is injected cold, and can be kept in stock constantly. It sets in the course of a month which is no disadvantage, for we rarely dissect fresh bodies. No attempt is made to distend the larger arteries, but it is desired to fill the many smaller arteries, as those of the periosteum and of the skin. Keiller accomplishes the same with chrome-yellow and gelatin but his cadavers are embalmed with a formalin solution which


'Professor Keiller (Phil. Med. Jour., Dec. 29, 1900) distributes the carbolic acid evenly by injecting a large quantity of aqueous solution into the carotid, and also hypodermically, until the whole skin is distended. His results are practically identical with ours, differing only in the per cent of acid to the bodyweight.


causes the gelatin to become insoluble and tough. Apparently his results and ours are about the same.

About 1000 cadavers were embalmed by injecting each with 5 or 6 liters of a 33% solution of carbolic acid as described above. The vessels were colored with the ultramarine shellac solution. They were then vaselined and wrapped and kept in cold-storage until needed. But it was found that occasionally an extremity was not well embalmed and frequently the epidermis would macerate and peel off with a subsequent putrefaction of the skin. Often it would soften and peel off, especially from the hands and feet after they had been kept wrapped for a long time in the dissecting-room. To obviate tliis the parts had to be watched and in case the artery was fotind plugged it was picked up and injected a second time. The skin was also treated with a solution of glycerine, carbolic acid and water and in extreme cases with the original embalming fluid. This, however, was found to be inconvenient and unsatisfactory, so we began systematically to try and remedy the defect. Struthers ° had already met this difficulty by painting the cadavers with carbolic acid and glycerine (1 to 8) a number of times, say 3 or 4, to embalm the skin from without, or in other instances by injecting the same solution hypodermically. This is inconvenient when many cadavers are to be painted, especially when but a few of them are to go to one's own dissecting-room, so I began by immersing the whole body in different solutions of carbolic acid after the arteries had been injected. It was noted above that in embalming a cadaver it is best to inject exactly 3% of pure carbolic acid to the weight of the cadaver in order to obtain the best results, and upon experimentation I found that the same strength gave the best results in a tank. A 4% solution is too strong and in a 2% solution the skin macerates and the epidermis falls off. Dr. Bardeen also obtained the same results with embryo pigs which are used in great number in our laboratory, and recently Keiller has confirmed Struthers' results with hypodermic injections. Keiller, however, uses large quantities of an aqueous solution of carbolic acid and injects it until the body is very cedematous. In all cases the principle and the results are the same.

The experiments with the vat were frequently made upon the subjects between Nos. 900 and 1300, at first upon single cadavers and later with 10 at a time. It was found that cadavers which were evenly embalmed, epidermis included, with a 3% solution of carbolic acid and wrapped with carbolized vaseline could be kept upon an open shelf in a warm room at Baltimore for at least 6 months and still be perfectly good for dissection. A cadaver prepared in this way cannot be detected from others by its quality or appearance. It should be possible to keep them indefinitely in an aseptic room with an atmosphere saturated with moisture. But to make the method easy two large tanks holding about 4000 liters each were constructed, which were half filled with a 3% solution of carbolic acid. Each holds about 15 cadavers. First, one was filled with cadavers that had been embalmed in the usual


'Struthers, Edin. Med. Journ., Oct., 1890.


February, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


41


way, and then the other. All the cadavers are then taken from the first tank, vaselined and wrapped and placed in coldstorage. The water of the first tank has lost some of its carbolic acid which is to be replaced. An easy method to ascertain this loss is to determine how much carbolic acid 100 cc. of the filtered solution will take up and to compare it with the amount required to saturate 100 cc. of water. If at a given temperature it takes 4 cc. of the straw-colored carbolic acid to saturate 100 cc. of water and 8 cc. to saturate 100 cc. of the filtered fluid under test, then one per cent must be ^dded to the tank to bring it back to a 3% solution. When the first tank is full of bodies the second is emptied, the bodies being wrapped and stored and the fluid of the tank strengthened. And so on. At the rate we receive cadavers they remain in these tanks from 3 to 6 weeks, long enough to allow the carbolic solution to penetrate them from 3 to 4 centimeters. I may add that we use the straw-colored carbolic acid (strength 92 to 97%) which is cheap and is as good for the vat and for the arteries as is the more expensive crystalline form.

Beginning 18 months ago (with No. 1300) each cadaver was embalmed with 6 liters of a 33% solution of carbolic acid, injected with about 2 liters of shellac alcohol and ultramarine blue, immersed in a 3% solution of carbolic acid for 3 to 6 weeks, vaselined and wrapped, and preserved indefinitely in cold-storage. At present we are constructing an underground vault to be carefully cemented with water-proof cement and large enough to hold 150 bodies. In case cadavers can be kept indefinitely in a 3% solution of carbolic acid, I see no reason why our cold-storage apparatus should be replaced when it is worn out.

It appears to me that carbolic acid is by all odds the best preservative for cadavers for dissection. It is easily injected and diffuses rapidly and extensively. So great is the power of diffusion that the heads of autopsy subjects, which are not injected, are preserved by the carbolic acid which diffuses from the trunk. It is also the best solution in which to keep cadavers. It is also antiseptic, so much so that I have never seen the slightest sign of an infected wound in out dissectingroom, and does not injure the instruments. It is not necessary to pay any attention to slight wounds for they heal more rapidly in the dissecting-room than elsewhere, when the bodies are embalmed with carbolic acid. Finally, it is inexpensive. A gallon of straw-colored acid costs but 40 cents, and half this amount is enough to preserve a cadaver for several years, and the other half will make enough 3% solution to immerse it.

Alcohol and glycerine are also excellent preservatives, and possibly more glycerine would improve the embalming fluid somewhat. It is especially valuable in keeping the dissection from drying too rapidly while the student is at work. However, in order to prevent drying the student swabs the dissection whenever necessary with a 10% solution of glycerine in alcohol (see Gerrish's Anatomy), with which he is supplied. By this method it seems to me that the glycerine reaches the right place, while when it is injected much of it is wasted.


When the student leaves his work he covers the dissection with a dozen thicknesses of moist (not drenching-wet) cloths, and all is again covered with water-proof sheeting which is prepared by saturating domestic or duck with boiled linseed oil as recommended by Keiller.

When the subjects are ready to be stored each is marked with a special tag, which cannot be duplicated, and is delivered on the desk of the instructor in charge of the vault when the cadaver is sent out of the laboratory or to the dissecting-room. The first 1000 are maTked A, the second 1000 B, and so on. Each body is also recorded in a book, which the janitor keeps, and upon a card, which is here reprinted, for the instructor in charge. Once a year an inventory is taken and the cards are stamped with the inventory date. Thus every precaution is taken to keep track of the bodies.


JOHNS HOPKINS UNIVEKSITY

ANATOMICAL LABORATORY


No Name

Length Weight

Date of Death 190 Cause of Death.

BeceiVed 190


Transferred to.


SEX


COLOR


AUTOPSY


QUALITY


Male Female


White Black Mulatto


Yes No


Vat

Medium

Lean


Injected with quarts of at inches pressure.

Arteries injected with at inches pressure.

Put in % Carbolic vat 190

Transferred to Cold Storage 190

Embalmed by

At first it was impossible for me to obtain easily the names and data of the bodies, but I had the color, sex and quality carefully recorded. These records often proved to be of value while making studies and in identifying bodies in case they were sought by friends. After No. 767 the names and ages are recorded. The cause of death is given after No. 901. The length and the weight of the body together with the intermediate color, mulatto, is recorded after No. 1448.

The Table on the following page gives a list of the cadavers which have been stored up to October 1, 1904. It shows how many bodies were used within the first year after they were received, within the second, and so on. The more recent subjects are all rated to October 1, 1904, so the 15th and 16th hundreds appear to have been used, while in reality most of them are still on hand. It will be noticed that under 400 a subject was kept for 5 years, and in the dissecting-room this cadaver proved to be as good as any of the fresher ones. A number were kept 4 years and in no case did the students suspect that they were dissecting subjects which we had had on hand so long. Under 500 a subject was kept 7 years and this we still have on hand. Generally, it is our aim to dissect cadavers which we have had on hand for two or three years, while the fresher cadavers are sent by request to other medical schools. Our experience demonstrates conclusively that cadavers preserved in cold-storage for several years are more satis


42


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


factory for dissection than are fresh ones, and there is no reason why they cannot be preserved in this way indefinitely in case they are packed closely to prevent evaporation. This we now accomplish by stacking all of the old cadavers on one side of the vault with an air-space around the pile, and then the fresh cadavers are laid closely on a platform on the other side of the vault, and when this has frozen a second layer is placed over it, and so on. The wrapping prevents the subjects from freezing together firmly.

TABLE SHOWING HOW LONG THE CADAVERS WERE KEPT IN COLD STORAGE BEFORE BEING DISSECTED.

They are grouped in hundreds. The first column gives the number that were used during the first year. The records are carried to October 1, 1904.


Number of









cadavers in hundreds.


lyear.


2 years.


3 years.


4 years.


6 years.


6 years.


7 yrs.


100


69


25


2


3


1




200


72


19


8


1





300


71


22


5


2





400


67


23


9



1




500


31


49


19







600


49


40


9


2






700


74


26








800


41


59








900


39


59


2







1000


29


61


9


1






1100


80


13


6


1






1200


76


19


5







1300


51


36


13







1400


27


73








1500


100









1600


100









1641


41








••


A Word Regarding Cold-storage. — The first cold-storage apparatus for the preservation of anatomical material was installed by Professor Huntington at Columbia University, about 1893. His apparatus was operated from a large central plant and was by no means inexpensive. Our vault was the second and was constructed early in 1895. The problem at the Johns Hopkins was different, for it was necessary to put


in all of the machinerj^, which on account of the additional expense could not be operated during the night. In order to make this possible the brine tank was set up witlun the vault and from this the brine was pumped through pipes along the ceiling. When the machine was not in operation the large amount of cold brine within the vault was adequate to absorb much of the heat which entered, thereby keeping the temperature well below the freezing point. We found that we had planned so well that it was necessary to operate the machine but once or twice a week during the winter and but six hours a day during the hot summer to keep the temperature well below 32° F. all the time.' Had the surface of the brine tank been larger it would have been possible to keep the temperature of the vaidt below 32° without circulating the brine through pipes suspended from the ceiling. So at my suggestion a number of recent apparatuses have been constructed with three or four very narrow brine tanks set around the side of the vault, without any brine circulation. By this arrangement it is found that the temperature of the vault can be kept with ease below the freezing point. Vaults constructed in this way are to be found at the University of Pennsylvania, at Cornell University and at the University of Wisconsin. The vault at the University of Wisconsin is the most recent and was designed by Prof. Miller. It is built of porcelain brick, no wood being used in its insulation and all sides of the vault are lined with narrow brine tanks extending from the floor to the ceiling. Throughout it is a dry vault, which favors its insulation, so much so that during the hottest weather its temperature rises but 3° in 24 hours, with the ammonia turned off. As far as I can see it should last indefinitely, for the compressed ammonia is supplied from a distant plant, so there is no machinery to get out of order. Under these conditions cold-storage vaults are certainly much more desirable for the preservation of cadavers than carbolic acid vats.


' See Mall, Arch. Anz. XI and Johns Hopkins Hospital Bulletin, 1896.


THE DEVELOPMENT OF GRAVE ROBBING IN ENGLAND.^

By 6. Canbt Eobinson, M. D.,

Pennsylvania Hospital.


In England, by Act of Parliament in 1540, four executed criminals were given yearly to the Barber-Surgeons for dissection, and twenty-five years later. Queen Elizabeth granted the bodies of four felons executed in Middlesex to the College of Physicians of London " that the president or other persons appointed by the college might, observing all decent respect for human flesh, dissect the same." In 1663 Charles II increased the number of criminals to be annuallv dissected to


' Extracts from a paper read before the Johns Hopkins Hospital Historical Club, October 10, 1904.


six, and in 1752, Act of 22, George II required dissection or hanging in chains of bodies of all executed murderers in order that " some further Terror and peculiar mark of Infamy might be added to the Punishment of Death." This Act, although no doubt an aid to the advancement of anatomy for the time being, produced in England a deep-rooted association of the dissection of the body after death with some serious crimes committed before death, and so strengthened the public feeling against the dissection of unclaimed pauper dead. This was a potent factor in hindering the passage of an anatomy act in England.


Febeuaet, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


43


Let us now consider the growth of the Anatomical Schools in London and Edinburgh, and trace there the fight between a deep-rooted instinct to protect the dead and the scientific spirit which demanded subjects for dissection.

The teaching of anatomj' in England, which was first attempted in a well ordered manner a short time before 1600, was conducted entirely by a few corporate bodies of which the Company of Barber-Surgeons and the College of Physicians of London were the most important. The bodies of criminals provided by law were used. These Public Anatomies, as they were called, when held by the Company of Barber-Surgeons, took place in the Hall of the Company, and were conducted with much pomp and ceremony. Attendance upon them was compulsory to the members of the Company, they being fined when absent. The Public Anatomies were held usually four times a year, and three bodies were dissected each time, one to show the muscles, one to show the bones, and one to show the viscera. Private anatomies were forbidden by the Company. In those days when executions were much more frequent than to-day, and when the method of teaching was such that a few bodies sufficed, the law provided a sufficient number. Even at this time, however, certain broad-minded, thoughtful people, having in mind the great benefits to mankind to be derived from a widespread knowledge of anatomy, bequeathed their bodies for dissection, in order to aid in the spread of this knowledge, and to abate the public feeling against dissection.

In the seventeenth century, under the influence of such teachers as William Harvey, interest in anatomy began to increase very much, and gradually more men arose who, like Vesalius, wanted to investigate things for themselves. And so we find that in the first part of the eighteenth century, about 1715, private schools of anatomy began to be established in London. This meant of course that subjects for dissection had to be provided by other than legal means, and here was the commencement of the systematic robbing of graves.

The business of providing the anatomical schools with subjects by grave robbing gradually became a well organized trade in London. The character of the men engaged in this most repulsive and dreadful occupation, can be well imagined. The century ending in 1832, when sufficient material was provided in England by the Warburton Anatomy Act, presents indeed a gruesome page in the history of anatomy. The master pen of Robert Louis Stevenson has described this night prowling grave robber in words that help us to realize what a depraved creature he must have been. " The Eesurrection Man — to use a by-name of the period — was not to be deterred by any of the sanctities of customary piety. It was part of his trade to despise and desecrate the scrolls and trumpets of old tombs, the paths worn by the feet of worshippers and mourners, and the offerings and the inscriptions of bereaved affection. To rustic neighborhoods, where love is more than commonly tenacious, and where some bonds of blood or fellowship unite the entire society of a parish, the body-snatcher, far from being repelled by natural respect, was attracted by the ease and safety of the task. To bodies that had been


laid in earth, in joyful expectation of a far different awakening, there came that hasty, lamp-lit, terror-haunted resurrection of the spade and mattock. The coffin was forced, cerements torn, and the melancholy relics, clad in sackcloth, after being rattled for hours on moonless by-ways, were at length exposed to uttermost indignities before a class of gaping boys."

The deeds of one of these resurrection men has come down to us from his own pen in the form of a diary. It was published in 1896 by Bailey, Librarian of the Royal College of Surgeons of London, and the book contains besides the diary which gives it its title, " The Diary of a Resurrectionist," an account of the resurrection men in London and a short history of the passing of the Anatomy Act. It is from this book that much of the following material has been gathered.

After several anatomical schools had been established in London, there was much rivalry between them for material. This gave the gangs of body-snatchers an independence of which they naturally took advantage, and a great amount of tact was sometimes necessary to keep them in good humor. When as dawn of day was approaching, these ghouls would stealthily knock at the lonely back entrance which admitted them with their gruesome burdens to the anatomical school, the rule was to pay cash and ask no questions, and with as few words as possible to let them hurry indoors while the cover of night could conceal their muddy clothes and grimy hands, the marks of their profession.

The " Eesurrection man " was in a position to do much harm to an unpopular school, and Jie had many ways of doing it. It is told that one teacher, Mr. Brookes, whose school had incurred the displeasure of the re.«urrectionists, awoke one morning to find a partially decomposed human body on his door steps, put there by these disgruntled robbers to arouse public indignation against him. On another occasion a subject for dissection was delivered to Mr. Brookes in a sack. Upon investigation the subject was found to be alive, and was probably so introduced into his house for purposes of robbery.

The means used for protecting the graves against the stealing of their contents were numerous. High walls were built on which loose stones were placed, watch towers, as may be seen in the cemetery outside of Dublin, were erected, and " mort safes " or graves covered by strong iron gratings, were used. One enterprising manufacturer published a long advertisement in the daily paper, extolling the merits of Lillie's Iron Coffin. The advertisement commenced by saying that " Hundreds of human bodies will be torn from their graves this season to supply the demand of the anatomical schools of London and Edinburgh." At Crail a house was erected in 1826 in which bodies were put to remain until partly decomposed and so useless for anatomy, and then buried.

This trade in human corpses was not carried on entirely by men, for we find that several of its tricks could be properly performed only by women. A spring gun was sometimes put over a new grave. The sorrowing mother or bereaved widow would appear a few hours after the funeral, and would go to the grave to let fall her mournful tears upon the freshly turned up mound, and incidentally to cut the wires leading to


44


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


the spring gun. Then too a woman was especially useful for going to an anatomical school, and there with much grief to find her child or husband, whose body she had heard had been stolen. Nearly overcome by her great sorrow she would have the body removed, to be carried to the next anatomical school and resold, the gang thus gaining two prices for it.

Bodies did not always reach the grave awaiting them, but were sometimes stolen before burial and were sometimes sold by the grave diggers themselves.

As ordinary means of protecting the graves often failed, and as the custodians of the burying grounds could usually in those days be bribed or made intoxicated, a private watch was sometimes instituted over a new-made grave. Between the watchers and the gang of grave robbers, violent fights sometimes took place. An account of such a fight is to be found in an Irish newspaper of 1830, entitled " Desperate Engagement with Body-Snatchers." " The remains of the late Edward Barrett, Esq., having been interred in Glasnervin Churchyard on the 27th of last months (January), persons were appointed to remain in the churchyard all night, to protect the corpse from the ' sack-'em-up gentlemen,' and it seems the precaution was not unnecessary, for on Saturday night last, some of the gentry made their appearance, but soon decamped on finding they were likely to be opposed. Nothing daunted, however, they returned on Tuesday morning with augmented force, and well armed. About ten minutes after two o'clock three or four of them were observed standing on the wall of the churchyard, while several others were endeavoring to get on it also. The party in the churchyard warned them oif, and were replied to by a discharge from firearms. This brought on a general engagement, the ' sack-'em-up ' gentlemen fired from behind the churchyard wall, by which they were defended, while their opponents on the watch fired from behind the tomb stones. Upwards of 58 to 60 shots were fired. One of the assailants was shot, he was seen to fall ; his body was carried off by his companion. Some of them are supposed to have been severely wounded as a great quantity of blood was observed outside the churchyard wall, notwithstanding the ground was covered with snow. During the firing, which continued upwards of a quarter of an hour, the church bell was rung by one of the watchmen, which, with the discharge from the fire-arms, collected several of the towns-people and the police to the spot, several of the former, notwithstanding the severity of the weather, in nearly a state of nakedness; but the assailants were by this time defeated and effected their retreat."

So we see that this trade, as one would expect, was not without its perils. Conflicts in the cemeteries over bodies were not uncommon, but the fights were usually between two rival parties of resurrection men, and the rivalry between the different gangs that haunted the various burjdng grounds was intense. In fact it was largely owing to information that these men gave to the police against their competitors that body-snatching reached such great publicity.

The amount of money that could be made in this nefarious trade was an inducement for men to forsake honest but poor


paying trades for it. A body-snatcher testified before the Anatomy Committee of the House of Parliament that during the dissecting season of 1809 and 1810 his gang of six or seven men had disposed of over 300 bodies at the average price of £4, 4s., or about $20.00, thus reaping an income of about $6000.00, or nearly a thousand dollars apiece. The teeth of the subjects were generally sold to dentists, from which source an extra sum was derived.

When anatomical material could not be obtained in plenty by robbing the graves alone, worse crimes were added, in order that the ghouls might have their money. The state of affairs into which this business had grown may be shown by a brief glance at conditions in Edinburgh in the first part of the nineteenth century.

Under the Monros, father, son and grandson, who had held successively the University Chair of Anatomy from 1720 to 184G, the School of Edinburgh rose to first rank. Schools of anatomy outside the University, where extramural teaching was done, were established. One of the most successful of these was conducted by Dr. Robert Knox, who had, during 1828 and 1829, a class of 505 students. The demand for subjects in Edinburgh was of course very great. Bodies brought from £10 to £20 each, and were even imported from England, Ireland and France.

In 1828 Edinburgh was stirred to its foundations by a realization of the extent to which the traiBc in human corpses had grown. This realization was brought about by the facts made public in connection with the famous Burke case, an account of which I quote from Hartwell.

" On the second of November, 1828^ it was noised about in Edinburgh that a woman had been murdered on All Hallow Eve for the sake of her body, which was found in the dissecting room of Dr. Knox. In the investigation which followed, it was discovered that William Hare, the keeper of a low lodging house in the West Port, and one of his lodgers, William Burke, had within less than a year, committed sixteen murders, and disposed of the bodies of their victims to the teachers of anatomy. The Burke " method was to suffocate the victim, already dead drunk. Throttling was not resorted to ; the nose and mouth were kept tightl}' closed, and smothering was soon effected. It was impossible to connect Knox with these villains in any way, except as a receiver of stolen goods for the benefit of the public. Hare turned State's evidence, but Burke was found guilty, hanged and dissected. His skeleton adorns the Anatomical Museum of the University of Edinburgh."

Horrible as this crime was, it was not the last to be attached to and to besmirch the name of anatomy in Great Britain, as London was to see another crime almost as dreadful. Another atrocity was needed to arouse the law makers of England to the realization that some efficient means of protecting the graves must be provided. A crime came to light in November, 1831, in London, which created a sensation, Bailey saj's, equal to that raised in Scotland by the atrocities of Burke and Hare.

Three men, Bisliop, Williams alias Head, and May, accom


Februaht, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


45


panied by a porter, brought a subject for dissection, a boy of 14, to Iving's College. The appearance of the body aroused the suspicion of Hill, the dissecting-room porter, and apprehending foul play, he notified Mr. Partridge, the demonsti-ator of anatomy. The porter's suspicions were confirmed by Mr. Partridge. He produced a fifty pound note and said he could not pay them until it had been changed. In the meantime he communicated with the police, who took the men into custody.

In December, 1831, the three men were found guilty of murder and sentenced to death.

The body proved to be that of an Italian boy who made a living by showing white mice. He had been enticed, so the men confessed, into their dwelling in Nova Scotia Gardens, where he was drugged with opium, and then let down into a well until suffocated. They also confessed to the murder of a woman named Fanny Pigburn, and a boy whose name was supposed to be Cunningham. Both of these bodies they sold for dissection.

Fifty thousand copies of the Dispatch containing their confession were sold, and at the execution many persons were injured in the crowd.

The English public were deeply stirred by these crimes. Something had to be done to protect the graves, and to do away with the gruesome traffic that had grown to such a point that the villains engaged in it did not stop short of murder to obtain their merchandise. Various legislative schemes were proposed and one bill providing anatomical material had passed the House of Commons to be defeated in the House of Lords. In August, 1832, however, the famous Warburton Anatomy Act finally passed through both Houses of Parliament to become a law. This Act provided that a license for the study of anatomy should be issued to proper persons and


that the bodies of unclaimed pauper dead might be turned over to those holding licenses for anatomical purposes. Burial was required of all bodies by anatomists six weeks after they were received. It was no longer a misdemeanor for one holding a license to have a body in his possession, and there was a very important clause repealing the law, requiring dissection of all executed criminals. Inspectors, one for each country, England, Ireland and Scotland, were appointed by it. This law was a great success and Bailey says of it, " after the passing of the Act the resurrection man, as such, drops out of history; his occupation was gone, and one of the most nefarious trades that the world has ever seen came completely to an end."

We cannot speak at this time of the methods used for obtaining anatomical material in this country, where the settling of the problem is more complex, as a separate law is necessary for each State. It is pleasant, however, to briefly recall the fact that, after a fight of some years, Massachusetts, our most cultured State, passed a liberal anatomy act, legalizing the dissection of unclaimed pauper dead, in February, 1831, a year and a half before the passage of the Warburton Anatomy Act in England, and was the first English speaking community to have such a law.

Although it cannot be denied that body-snatching still exists to a slight extent in this country, yet most of the States have good anatomical laws, which efficiently provide material for dissection. As the robbing of graves passes out of existence, there disappears also the dread and horror with which the public has regarded for hundreds of years the study of anatomy, as the public has learned to appreciate the great importance of sound anatomical training as a firm foundation for all branches of scientific medicine.


ON FLECHSIG'S INVESTIGATIONS ON THE BRAIN/

By Florence E. Sabin, M. D., Associate in Anatomy, Johns Hopkins University.


The first report made to the Central Committee for the Investigation of the Brain consists of a paper by Paul Flechsig which marks an epoch in the history of the nervous system. This work lays the foundation of our knowledge of the paths in the brain and their relation to the basal ganglia. The work represents the study of serial sections of 56 human brains between the stage when myelinization first begins, four months before birth, and the time when every portion of the cortex shows some medullated fibers and the main paths are laid down, namely, four months after birth. This entire


' Flechsig: Einige Bemerkungen iiber die Untersuchungsmethoden der Grosshirnrinde insbesondere des Menschen. Dem Centralkomite fiir Hirnforschung vorgelegt. Bericliten der mathematiscli-physischeii Klasse der Kbnigl. Sachs. Gesellschaft der Wissenschaften zu Leipzig, Jan. 11, 1904.


period represents eight months. Through the study of these brains Flechsig divides the cortex into 36 areas, of which the first 12 are myelinized before birth and the rest after birth. The sequence of the numbers represents the time of medullation, and as will be seen the time of birth is not a fundamental division. In general the study of these diiierent zones shows that the first areas in the cortex to become medullated are primary sensory areas representing smell, touch and muscle sense, sight, hearing and taste. The next group of centers to become medullated have at first only fibers wdthin themselves, that is, neither projection fibers nor association bands, so Flechsig calls them automatic centers of unknown meaning. The rest of the areas have association bands and it is most interesting tliat the earlier zones of this group develop as a marginal zone around the primary sensory areas and first


46


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


receive short fibers from them. They are undoubtedly connected with the sensory areas in function. The last three zones develop long association bands first and are the great association centers. This will be summed up in the following classification.

I. Primary areas.

1. Areas with primary sensorj' projection fibers. 1, 2, 4,

5, 6, 7, 8, 15.

2. Areas without primary projection fibers; mostly auto matic unknown areas. 3, 9, 10, 11, 12, 13.

II. Association areas.

1. Intermediate or border zones, with short fibers. 14,

16-33.

2. Terminal or central zones, with long fibers. 34, 35-36. The following is the list of zones, which is to be compared

with the figures :

Areas Medullated Before Bieth.

1. Lamina perforata anterior (trigonum olfactorium).

2. Upper third of the posterior central gyrus and the pos terior surface of the corresponding part of the anterior central gyrus. Lobulus paracentralis. 2. Middle third of the posterior central gyrus.

3. Septum pellucidum with the diagonal Bandelette of

Broca.

Primary cingulum of Flechsig.

Cortico-petal fibers of the fornix inferior. 4". Uncus (gyrus hippocampi) inner center for smell. 4. Subiculum cornu Ammonis.

5. Borders of the fissura calcarina.

Polus occipitalis. Gyrus descendens. Lower third of the posterior central gyrus (2"= and 5*").

6. Gyrus fornicatus, posterior half of the under surface,

fornix longus.

7. Oblique gyrus of the gyrus temporalis superior.

7. ( ?) Upper half of the posterior gyrus of the island.

8. Part of the gjTUS frontalis I.

8*". Adjacent part of the gyrws fornicatus.

9. Upper part of the cimeus.

10. Inner surface of the polus temporalis.

11. Oblique gyrus of the pars triangularis of the gyrus fron talis inferior, outer part of the pars orbitalis.

12. Gyrus subangularis.

Areas Medullated After Birth.

13. Gyrus supra angularis.

14. Part of the gjTus temporalis superior.

15". Gyrus temporalis between S^ and the genu corporis collosi.

15. Part of the gyrus frontalis superior adjacent to 8.

16. First parietal gyrus adjacent to 2.

17. Border of 5.

18. Foot of the gyrus frontalis medius. IS*". Foot of the gyrus frontalis inferior.


19. Gyrus supra marginalis.

20^. Anterior half of the third occipital gyrus.

2I2. Posterior half of the first parietal gyrus near 9.

22=. Part of the island.

23^. Gyrus occipito-temporalis.

24i. Second occipital gyrus.

25. Gyrus fornicatus, a small portion beneath and behind.

26^. Gyrus rectus adjacent to 11.

27. Middle part of the gyrus frontalis inferior.

28. Pole of the gyrus frontalis superior.

29. Eest of the gyrus supra marginalis.

30. Upper portion of the gyrus frontalis medialis.

31. Zone between the second occipital and second temporal

32. Under portion of the island.

33. Gyrus fornicatus near the praecuneus.

34. Gyrus angularis.

35. Inner surface of the gyrus frontalis superior, and the

adjoining part of the gyrus fornicatus. 35. Gyrus frontalis II.

36. Temporalis II and III.

It is interesting to note that the first fibers to medullate in the brain are the primary sensory paths which extend from lower centers to the cortex. There are seven of these sensory areas on the cortex corresponding with the numbers 1, 2, 4, 5, 6, 7 and 8. No. 15 is a later extension of the primary zone 2, 2, 2<= and 8. Analyzing these seven zones we find that 1 and 4' are primary olfactory areas connected by a band of medullated fibers with the olfactory bulb; 2, 2, 2", 8 and subsequently 15 represent the cortical zone for the sensory nerves of the skia and muscles, and have for subcenters the optic thalamus and globus pallidus; 5 is the area for sight and has its subcenter in the lateral geniculate body; 7 is for hearing and has its subcenter in the medial geniculate body, while 6 is possibly the primary sense area for taste and has its subcenter in the thalamus and globus pallidus. Thus these primary areas represent smell, touch, muscle sense, sight, taste and hearing.

The primary sensory areas have certain characteristics in common: (1) The first fibers to medullate in each one are the sensory paths from some subcenter. Later other fibers develop of the types of motor fibers, callosal fibers, arcuates and association bands, but each area has its own sequence in regard to these later systems. (2) The size of each area is proportional to the nerve or nerves supplying it, for example, the area for the skin and muscle nerves is the greatest, while the area for sight is greater than the area for hearing. (3) These primary zones can be definitely outlined in the early stages by the structure of the cortex. Moreover, the structure of the different areas is so characteristic that they can all be told apart. The structure of each area corresponds with the structure of its sense organ, for example, the man}' layers of the visual area correspond with the retina; the olfactory area has the fewest layers corresponding with the simple olfactory mucous membrane, while the islands of cells in the subiculum


February, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


47


cornu Ammonis, which are visible with the unaided eye possibly correspond with the taste buds. The area for hearing can be outlined macroscopically, for the cortex is twice as thick there as in the rest of the gyrus. The large central sensory area has a structure less characteristic corresponding with the simpler types of nerve endings. Thus each area is to be considered as a repetition in the cortex of a peripheral sense organ.

We will now take up in detail each sensory area. The first portion of the cortex to become medullated is the lamina perforata anterior (1) receiving fibers from the olfactory bulb. Later the olfactory fibers extend to the uncus (4). The cortex of these two areas is simple in structure and the medullated fibers penetrate the cortical layers. The olfactory system, which lies in the hippocampal zone, is the first to develop association bands. The first of these is numbered 3 in the list and is a band connecting the lamina perforata anterior with the globus pallidus by way of the septum pellucidum. A second band runs from the uncus through the subiculum to the cornu Ammonis. The Ammon's horn also receives an early bundle from the lamina perforata anterior by way of the inferior fornix (3). In a 9^ months' foetus Flechsig found four bands of medullated fibers to Ammon's horn. The motor fibers of the system which begin in the large pyramidal cells of Ammon's horn and made the chief part of the fornix inferior, develop much later, 3 months after birth.

The great sensory area representing touch and muscle sense for the entire body begins to medullate next after the olfactory area. The structure of the cortex of this zone is less characteristic than the areas of special sense. But it contains in one part certain large sensory endings which Eamon y Cajal has shown are found nowhere else, while in another part it contains the characteristic giant pyramidal cells which give rise to the fibers of voluntary motion. It is the largest and most complex of the areas in regard to its primary sensory bands ; that is, a number of sensory bands appear in the following order: 2, 2, 2^ and 5^ then later 8, 8^ 15 and 15'^. The sensory paths from the legs are the first to reach the cortex. They end in the paracentral lobule and in the upper third of the posterior central gyrus, extending on to the posterior surface of the corresponding anterior gyrus. The corresponding motor fibers develop from the area of the large pyramidal cells of the adjacent anterior central gyrus. Thus the sensory and motor areas are not mixed except in the sulcus. In contrast with the areas for smell, sight and hearing, the central sensory area develops motor fibers after the sensory ones. Moreover, each area develops the motor bands in the same sequence as the sensory. For example, the area 2 develops its motor fibers before 8 has medullated sensory fibers. The sequence of the types of fibers for this area is: (1) sensory, (3) motor, (3) callosal, (4) horizontal and arcuates, (5) association bands.

Flechsig has analyzed some of the sensory bands of this area, throwing much light on the relations of the basal ganglia. The following is the list of these bands: (a) Fibers from the globus pallidus to zone 2; (b) fibers from the ventro


lateral nucleus of the thalamus to zone 2; (e) a large band from the globus pallidus to zone 2; (d) fibers from the cupshaped nucleus and center median of Luys to zone 2; (e) from the ventro-lateral nucleus of the thalamus to zone 2"=, and (f) from the dorso-lateral nucleus of the thalamus to zones 8 and 8.

The cortical area for sight (5) is around the fissura calcarina, the gyrus descendens and the occipital pole. The calcarine fissure is so deep that the area is much greater than appears. The structure of the cortex of this zone is so characteristic that the area can be sharply outlined. The association bands are late in developing, and the motor fibers run with the primary optic radiation. The primary optic radiation comes from the lateral geniculate body.

The cortical zone 6 may represent taste. It receives fibers from the thalamus in part near the pulvinar. Flechsig thinks that taste is also represented in the central sensory area. Zone 6 is connected with the subiculum cornu Ammonis and is much like it in structure.

The fibers for hearing are the first to become medullated in the temporal lobe. These fibers come from the medial geniculate body and end in a small portion of the gyrus temporalis I, not more than 1 to 2 gem. in area. The next fibers to medullate are callosal and arcuate fibers. Possibly Tiirck's bundle, which develops later, is the motor path for the area analogous with the pyramidal tract.

Turning now to the second group of the primary areas, 9-13, none of these areas have projection fibers nor are they connected with the primary sense areas. Flechsig calls them automatic unknown centers. All but one, 13, develop before birth.

The group of association centers 14, 16-36 is full of interest. They all develop after birth and all begin with association bands. The division of this group into intermediate and terminal zones is both anatomical and physiological. Around each primary sensory area develops a border zone of association centers; moreover, generally speaking the earlier sensory areas receive the earlier border zones. These border zones receive their first fibers from the corresponding sensory area, and later develop other association bands. The border zone for the central sensory area is 16, 18, 18, 19, 22, 26, in which it will be noted that 16 corresponds with 2, 18 with 2, etc. The border zone for the optic area consists of 17, 20 and 24. Certain of the border zones are late in developing; for example, the one is the island of Eiel, 32, and the prsecunea 33, which may be the border zone for smell and taste.

The last three of the association centers 34, 35 and 36 do not develop in relation to any one primary sensory area, but rather they are in the center of a whole group of the border zones. 34 is the posterior association center, 35 the anterior or frontal area, and 36 the temporal. These centers are the last to develop and have long fibers.

Flechsig points out the enormous amount of work to be done in following the further development of the paths in the brain. The areas of the cortex do not stand out so sharply as the fiber bands become more complex, but even in


48


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


the adult it can be made out that the primary sensory areas have the most oblique and horizontal fibers, these being sensory conduction paths to other parts of the brain. The enormous numbers of fiber bundles in the adult, as well as the fact that many bundles turn abruptly in their course, makes it necessary to use pathological and special secondary degenerations as methods of research. The material is rare and the difficulties of obtaining it so great that only through cooperation between the members of the central committee and physicians and hospitals can we hope for great progress.

Flechsig takes up the results of the studies of degenerations and shows that the central sensory area as usually outlined is a mixture of true and false observations. The paths which degenerate from this central area are :

1. Cortico-spinal paths, the pyramidal tracts.

2. Cortico-bulbar paths, part in the lemniscus medialis.

3. Cortico-prontal paths, Arnold's bundle.

4. Cortico-thalamic paths (lateral nucleus).

5. Thalamo-cortical paths (ventro, lateral, central and

cup-shaped nuclei).

6. Lenticular nucleus — cortico-paths.

7. Paths to the substantia nigra.

8. Cortico-quadrigeminal paths.

9. Paths of the red nucleus.

10. Paths of the nuclei of the posterior columns by way of the lemniscus medialis.

Of these 1-5 are proved for the human brain; 9 and 10 degenerate indirectly. Beside these fibers callosal and association bands degenerate. None of the pyramidal tract fibers arise in the posterior central gyrus, but rather in the lobulus paracentralis and the two upper thirds of the anterior central gyrus. The motor fibers from the lower third of the anterior central gyrus, the zone of the cranial nerves, run with the lemniscus medialis.

The fibers from the cortex to the pons and medulla (3 and 3) are not well known. They lie internal to pyramidal fibers in the pes. There are numerous bands connecting the optic thalamus and the cortex, 4 and 5. Through analyzing the degenerations, Flechsig confirms the points brought out in development, namely, that the sensory fibers end in the posterior and the motor fibers begin in the anterior central gyrus. The parietal lobe area (16) does not give degenerating projection fibers. The globus pallidus shows but few fibers which degenerate from the cortex, but the substantia nigra has many.

The study of degeneration of the optic area confirms the evidence of development. The primary optic radiation (Flechsig) which runs in the area of Vicq d'Azyrs' stripe degenerates upward from the lateral geniculate body and pulvinar to the. occipital cortex. The fibers that degenerate downwards lie next the callosal fibers. In this connection Sherrington and Griinbaum's experiments on apes are most interesting, for they showed that stimulation in the region of Vicq d'Azyrs' stripe causes movement of the eye muscles; that is to say, the motor path for the eye muscles comes from the optic center of the cortex, just as the pyramidal tract


starts near its corresponding sensory center. No projection fibers degenerate from 17, 17, 20 and 9.

The errors in regard to degeneration from the temporal lobe are due to not analyzing its diiierent portions. Tiirck's bundle connects only with zone 7. It has two bundles of fibers ascending and descending and they come from different parts of the zone:

The results of degenerations in the association areas are complicated and unsatisfactory.

Flechsig now takes up the question of the relation of the motor and sensory fibers in each zone. He suggests the name of projection fields for the seven primary zones. The motor and sensory bands for each projection zone are as follows :

1. The olfactory projection zone has bands from the tractus olfactorius to the lamina perforata anterior and the uncus and descending fibers to the globus pallidus and to the ganglion habenulce by means of the tasnia thalami optici.

2. The central projection zone is the end station (indirect) of the lemniscus medialis and the superior cerebellar peduncle and the origin of the pyramidal tract for the cord and Arnold's bundle for the pons and medulla. 3. The uncus and gyrus hippocampus have several cortico-petal paths from the olfactory tracts and internal capsule and a ' motor path in the inferior fornix. Field 6 has an early sensory path from the internal capsule, and a later one from the thalamus. The optic area receives sensory fibers from the lateral geniculate body and thalamus and sends motor fibers to the superior Cjuadrigeminal body. The sensory fibers of the ear path come from the medial geniculate body and the motor fibers run in Tiirck's bundle. The rest of the cortex is without projection fibers and if one considers the optic thalamus all parts of it have been related to the projection areas — the upper part of the thalamus to the central, the posterior to the visual, a part of the posterior and inner zone to hippocampal zone and the frontal part to the central zone and hippocampus.

The relation of the sensory and motor fibers within the projection fields is known only for the central field. The convincing experiments of Sherrington on the gorilla are confirmed in man by the myelinization. Sherrington found by careful stimulation of the cortex and subsequent extirpation of the areas that the motor fibers come from the anterior central gyrus only and not the posterior. This relation for the other zones is as yet unlvuown.

In connection with aphasia, Flechsig shows that Broca's field is a complex of several zones, and Wernicke's area corresponds with Flechsig's primary hearing center. The existence of complicated centers for the various phases of spoken and written language, as well as word memory, is unquestioned and there are probably multiple centers in the zones of 16-36, indeed probably a considerable part of the zones 16-36 are associated with these complicated phenomena, but to definitely locate these areas on theoretical grounds without basis of fact hinders rather than helps the development of our knowledge.

A general view of this work of Flechsig's shows that in the brain there are primarily projection centers which are the


THE JOHNS HOPKINS HOSPITAL BULLETIN, FEBRUARY, 1905.


Z' •"




Sf^iT-'S




I -



^i»Oh, I >,



5 5

g N

^ ►J




i:^


'v'i



' ;ip«3...


^


0^m


2 N

^ Q


. Q



areas which represent the various sensory paths and their corresponding motor tracts. They are the first to meduUate, the first to develop, the first to have callosal fibers and the first to send association bands to other parts of the brain — so they are in all respects primary and fundamental. There next develop a few automatic centers of unknown meaning. The third step consists in laying down a marginal zone of association centers around each primary projection center. Each center has a group of these which develop in the same sequence as the corresponding primary center. Certain of these association areas are closely related to one projection center; for example, 16 is related to 2, but others, as for example the gyrus angularis, represent several projection centers, sight, hearing and taste, for its destruction causes a disturbance of all three of these senses. The primary projection centers are not directly connected with others; for example, no fibers run from the optic to the hearing center, etc., and the connections are made wholly through the association zones 16-36. Finally, the great association centers 34-36 are


not independent isolated areas, for the great anterior association area stands in close relation to the central projection area representing the body and in slight relation to the olfactory area, while the others are more closely related to the areas of special sense.

Flechsig closes this inspiring work with some suggestions for the work of the future, the outlook for which he has made brilliant and possible. There is the field of the early development, begun by His, before medullation begins; then the whole subject of the development of the association bands. The primary relations of the fundamental association bands in their relation to the primary association centers can all be worked out on animals, perhaps especially well in the lower vertebrates. Flechsig ends with the suggestion that the whole gross anatomy of the cortex for which we have now but the outline of markings which are not fundamental, as for example the sulcus of Eolando, can now be reworked in the light of our new knowledge.


A NOTE ON THE DEVELOPMENTAL RELATIONS OF THE KIDNEY AND URETER IN HUMAN EMBRYOS

Pohlman AG. A Note on the developmental relations of the kidney and ureter in human embryos. (1905) Johns Hopkins Hospital Bulletin 16: .

By Augustus G. Pohlman, M. D.,

Assistant 'Professor of Anatomy, University of Indiana.


The first signs of the permanent kidney (metanephros) is found in a dorsal outgrowth of the Wolffian duct close to its orifice in the cloaca. The Wolffian duct (segmental) reaches the caudal part of the enteron in embryo 76' (4.5 mm.). It is of even caliber throughout its course, dilating slightly as it enters the cloaca. As the duct comes into relation with the cloaca, two varieties of epithelium meet, the mesodermic epithelium of the duct and the entodermic of the gut. There must of necessity be an epithelial plate separating the duct from the cloaca, but it probably disappears with its formation.

In the slightly older embryo 80 (5.0 mm.) the duct has given off a small shoot which arises dorsally and continues the lumen of the duct into the mesodermic tissue as yet undifferentiated, in which the whole is embedded. The lumen of this bud, the renal bud, is somewhat larger than that of the duct proper and is dilated toward its blind end. The surrounding tissue has become condensed about the end of the bud and is easily recognized by its different arrangement and by its darker stain with carmine. The renal anlage is placed at the second sacral vertebra as nearly as can be estimated, in the uncertainty of the vertebra at this stage and the difficulty in fixing the direction which might be called the right angle to the bent vertebral column. This position does not change until an older stage is reached as was verified in the models of embryo 3 (7.0 mm.) by Professor Mall and embryo 163 (9.0 mm.) by Professor Bardeen.

The renal anlage may be divided into two distinct parts in embryo 2 (7.0 mm.) ; a segment not surrounded by specialized mesodermic tissue, the future ureter, and a segment capped by the specialized tissue, the renal mesenchyme, the kidney and all the derivatives of the bud included within the kidney substance. The two anlages, the right and left, point dorsally from their position on the Wolffian ducts and even converge toward the middle line, and approach each other so closely that it is a matter of 50 microns separating them. The buds are at the same level and the ureter and kidney segments are of equal size.

In embryo 88 (9.0 mm.) the distal end of the bud undergoes a division into an upper and lower sprout which are enclosed in the renal mesenchyme and represent the future upper and lower pelves of the adult kidney. The renal mesenchyme in the meantime has developed in a vertical direction and is bean-shaped. Stationary up to this stage the kidney now begins a rapid wandering to its future permanent position in the body.

The sharp division into an upper and lower sprout is lost in embryo 114 (10.0 mm.). The renal mass is distinctly bean-shaped in reconstruction and rather flattened from side to side. The hilum is situated ventrally. The ureter has elongated but is still in relation with the Wolffian duct dor


' This and other similar figures refer to the catalogue number in the Anatomical Collection of the Johns Hopkins Medical School.


sally. The kidneys are placed with their upper ends at the brim of the pelvis, the one a little higher than the other. The hilum of the kidney is well marked although the organ is as yet not vascularized. The two kidneys are placed with their long axes parallel and measure from tip to tip about 0.6 mm. and are about 0.2 mm. apart.

The upper border of the developing kidney reaches the third lumbar vertebra in embryo 144 (14.0 mm.). The ureter still emerges from its ventral aspect, but the relations at the lower end have changed. The ureter is rotated to a lateral position on the Wolffian duct and that portion of the duct which lay between the bud and the cloaca has disappeared (?), bringing the orifice of the ureter directly at the cloaca or into the duct at the cloaca. The kidney is without blood supply and lies behind the Wolffian body.

In embryo 43 (16.0 mm.) the kidney lies higher than in the preceding embryo. In addition it has imdergone an axial rotation bringing the hilum to its mesial border, i. e., turned about 90° toward the middle line. The ureter has acquired a distinct orifice into the ventral segment of the cloaca lateral to the orifice of the Wolffian duct. The cloaca is completely divided at this stage.

The kidney arrives at its normal height in embryo 22 (20.0 mm.). The rotation is maintained and the kidneys, except that they lie closely together, are in the adult position. The vascularity is as yet problematic. In the meantime the ureter has lost all connection with the Wolffian duct and has grown into a higher and more lateral location as a fixed structure. The Miillerian ducts in this embryo are unusual in that the left duct has reached the urogenital sinus while the right lies a full slide higher up. The kidneys are about 1.0 mm. apart.

Chronologically: The Wolffian duct joins the cloaca at 4.5 mm.; the renal buds appear at 5.0 mm.; the renal buds may be differentiated into two segments, the ureter and kidney, at 7.0 mm. when they lie opposite the second sacral vertebra ; at 10.0 mm. the upper border of the kidney is at the brim of the pelvis; at 14.0 mm. the ureter lies lateral to the Wolffian duct and the upper pole of the kidney is at the third lumbar vertebra ; at 16.0 mm. the kidney has passed the midluuibar line and has been rotated through 90° on its long axis while the ureter has a separate orifice in the urogenital sinus; at 20.0 mm. the ureter and kidney are in the relative noimal position and the Miillerian ducts have gained the sinus.

The rotation of the kidney and the displacement of the ureter at the lower end, although they occur at the same time, are distinct processes. This may be demonstrated in cases of incomplete double ureter where the ureter is divided into two segments somewhere along its course. The ventral segment proceeds from the upper pelvis of the kidney, while the dorsal branch is connected with the lower pelvis. If there were any connection between the rotation of the kidney at the midlumbar line with the lateral displacement at the lower end of the ureter, there would be evidences of such rotation along the course of the anomalous branches of the ureter, but we


find the position of the two segments, the one ventral to the other maintained even in the adult with no manifestations of any rotation in an embryo with similar malformation. Comparing this variation with cases of complete reduplication of the ureter we find the relation of the two segments the same, one ventral to the other, although there is displacement of the ventral ureter in that its orifice lies between that of the dorsal ureter and the Wolffian duct. This crossing of the two ureters is only found at the lower end and does not affect the course of the ureter above. Again in all cases where there is congenital displacement of the kidney and lack of rotation or mal-rotation, the orifice of the ureter is not necessarily affected and in those cases in which the ureter is widely displaced in the female through downgrowth of the Miillerian


I \ ' ^ I ! \ I ] \ \

s

hi

[1 1 U-i

I J „ JjX

. iq

6 — I , — I 4/—1 — i

/' /


113 S3 144 43


ducts, the kidney position and ureter course are normal otherwise.

In the accompanying chart are found curves to represent the wandering of the kidneys; the age in weeks is shown on the right, the size in centimeters on the left, and the number of the embryo plotted below. The uppermost curve is derived from the vertex-breech measurement of the embryos in question, the second and dotted curve the size of the kidney from tip to tip multiplied 10 times, the lowest curve the distance between the two kidneys also multiplied by 10. The kidney does not grow as rapidly as the body up to embryo 32 and then gains on the body size until at 130 mm., the kidney is about 1-lOth the vertex-breech measurement. The distance between the kidneys remains practically the same until 88, then grows apart rapidly (the period of wandering) until 74 is gained when it remains about the same until 224 although the difference between these two embryos, 74 and 224, is 21.0 mm., or in time, about ten days. The kidnevs


rEBEUAEY, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


51


then grow apart even more rapidly than during the period of wandering. This quiescent time I hold to be the stage of vascularization.

It was stated in an earlier part of this article that the kidney is not vascularized until it has reached its normal height, and that it attains this position in an embryo of about 20.0 mm. This corresponds to the curve. Mr. Eben C. Hill of Johns Hopkins University has also verified this matter in the pig and the fact that the renal artery may sometimes give off the suprarenal and spermatic strengthens the point made.

The idea that the primitive upper and lower sprout of the bud correspond to the upper and lower pelves of the adult kidney is entirely compatible with the findings in the embryo


and the adult. My report on the complete doubling of tha ureters in embryos, Mall 173 and Keibel-Piper have confirmed the same in the most important stages in the embryology of this form of anomaly. The form of the pelvis and ureter is undoubtedly dependent on the development of the renal bud while the kidney form is controlled by the mesenchyme.

I wish in closing to express my indebtedness to Professor Mall for the use of all the numbered embryos and of his model of embryo 2, to Professor Bardeen for the loan of his models of embryos 163 and 144, to Professor Keibel for embryo Keibel-Piper and to Mr. Hill for data of his findings in the pig

ABNORMALITIES IN THE FORM OF THE KIDNEY AND URETER DEPENDENT ON THE DEVELOPMENT OF THE RENAL BUD

Pohlman AG. Abnormalities in the form of the kidney and ureter dependent on the development of the renal bud. (1905) Johns Hopkins Hospital Bulletin 16: .

By Augustus G. Pohlman, M. D.,

Assistant Professor of Anaiomy, University of Indiana.


The vague references to the embryologj' made in the usual reports of renal variations are possibly a result of the anatomist not interesting himself sufiiciently in what might be termed " abnormal variations." The eases are written up by the clinicians, who necessarily orient themselves as to the development of the tract from the text-books, as no scheme has as yet been worked out to wliich he may refer in his attempt to classify or account for the interesting and important anomalies of the kidney and ureter. Even the excellent papers of Bachhammer and of Schwarz are lamentably hidden by the obscurity of their titles.

Cases of renal malformation are comparatively rare, but they occur frequently enough to be of interest to the clinician as well as to the anatomist and pathologist. I need only mention the cases of single or misplaced kidney; to the removal of a single unilateral kidney or to the obstruction of the pelvic inlet by a misplaced organ, to illustrate the importance of a thorough knowledge of the anomalies of the urinary tract. It naturally falls upon the shoulders of the anatomist to classify variations, and as these abnormalities are usually the result of faulty development, the basis of the classification must be an embryologic one. That such a classification will include all the anomalies is quite out of the question at present. There will always be a few which cannot be explained, but the number will grow proportionately less as our knowledge of embryology advances. Before the development of the kidney and ureter had been worked out, speculations regarding the origin of abnormalities were far removed from the present accepted ideas.

The first great diJficulty met with in the classification of variations from a developmental standpoint is to make the system clear and embracing, and to present the matter in such a form that it may be of use to someone beside the writer. This scheme must be based on facts in the embry


ology which have been verified personally, and the possible results compared with actual cases. Here again an element of error is met with in that many of the reports are crude and superficial, and too much credence must not be given to them. The exceptions are surprisingly few, and in the field covered in this paper are limited practically to one observer.

The literature referred to is necessarily small, as it was not deemed advisable to conceal any merit the classification might possess by involved references and case citings. Only those anomalies will be considered where both kidneys are present. This subject is excellently covered in the articles by Ballowitz, Moore and Morris, and the possible causes mentioned in my paper in "American Medicine."

I am obliged to set another limit to this paper in that I shall consider only those anomalies which have their origin before the third month. This excludes all congenital abnormalities which depend on the excretory function of the kidney for their manifestation — congenital cystic kidney, congenital hydronephrosis, etc., also the minor variations which are of relatively little importance, as persistent lobulation, etc. In the variations to be mentioned, the kidney is quite normal excepting in its form, and in the form of the pelvis and ureter.

The development of the renal bud has been thoroughly worked out. I will mention the article by Keibel on its earlier stages and that by Hauch on its later development. My own findings have been a confirmation of what has already been demonstrated by many investigators. I will review the embryology of the kidney and ureter by referring to the conditions present in embryos chosen from the Mall collection, from the earliest stage in the development of the tract to an age in which the kidney and ureter have assumed their relatively normal shape and position. The embryos are arranged according to their size, but the figures do not correspond exactly to those mentioned in other articles. It will be remem


52


JOHNS HOPKINS HOSPITAL BULLETIN.


[Fo. 167.


bered that all embryos of the same age are not always of the same size, and allowance must also be made for shrinkage in fixation and embedding.

The embryos are normal and in perfect series. The relations of the kidney and ureter were not only studied from the sections but modeled as well. The review presents the general development of the tract concisely and in sufficient detail for the objects of this article.

In embryo Mall 164 (3.5 mm.) the cloaca is relatively spacious. The Wolffian duct has not yet reached it and the stage is therefore too young for a study of the urinary tract.

The Wolffian ducts reach the cloaca in a trifle older stage, embryo Mall 76 (4.5 mm.), and empty well to the front in the lateral wall. There are no signs of the development of the renal buds.

The renal buds appear dorsally on the Wolffian ducts (embryo Mall 80 — 5.0 mm.). They arise near the cloaca and their blind ends are already capped with renal mesenchyme developed from the surrounding undifferentiated mesodermic tissue.

In embryo Mall 3 (7.0 mm.) the buds have elongated markedly and the cap of renal mesenchyme to each bud is more distinct and confined to the distal and blindly ending part. One may already separate the developing tract into two segments; the one surrounded by mesenchyme, the kidney; the other from a portion which is not, the ureter. The blind end of the bud shows no signs of dividing. The masses of mesenchyme are placed at the level of the second sacral vertebra.

The blind end of the bud shows the first signs of sprouting into an upper and lower division in embryo Mall 163 (9.0 mm.). The splitting occurs within the mesenchyme which has increased in size particularly in the vertical diameter.

The definiteness of the upper and lower division is lost in a slightly older stage, embryo Mall 114 (10.0 mm.), and the condition may more properly be spoken of as a common pelvis to the developing kidney. The two masses of mesenchyme have already assumed the typical bean shape and lie close together with their long axes parallel. The ureter emerges ventrally from each but is still dorsally placed on the Wolffian duct, although the segment of the duct between the cloaca and the ureter has shortened. The upper border of the kidney is at the brim of the pelvis.

Embryo Mall 144 (14.0 mm.). The kidney lies opposite the third lumbar vertebra and has begun an axial rotation, bringing the hilum toward the middle line. The ureter has also assumed a lateral position on the duct, and the segment of the duct between the ureter and the cloaca has practically disappeared. It may be said that the ureter has a distinct orifice into the urogenital sinus (ventral segment of the cloaca).

In embryo Mall 43 (16.0 mm.) the ureter has an orifice lateral to the Wolffian duct. The kidney is completely rotated and the hila point toward each other. The upper border of the kidney is opposite the first lumbar vertebra.

The kidnev reaches its normal height about the end of the


second month and then receives its blood supply, the vascularization coming directly from the aorta and occasionally from the suprarenal artery. The vessels seem to choose the nearest route and go to the hilum, the branch from the suprarenal sometimes entering the upper pole.

The ureter grows away from the Wolffian duct, embryo Mall 22 (20.0 mm.) and empties higher and more laterally. Keibel describes a trigone in his embryo Lo (24.0 mm.). The ureter assumes its relatively normal position in the same stage in which the kidney reaches its normal height or about the end of the second month. The two processes are, however, quite distinct. The change in the position of the kidney is due to the development of the distal part of the bud and its surroundings, while the change in the position of the ureter is related to the growth at the lower end of the Wolffian liuct. It is interesting to note that the ureter normally loses its connection with the Wolffian duct before the Miillerian duct reaches the urogenital sinus.

The earlier development of the renal bud may be represented by three simple figures upon which the diagrams used in the later discussion of the variations will be based. Figure 1 represents the first budding from the dorsal side of the Wolffian duct at a short distance from the cloaca; Figure 2, the first subdivision of the bud within the renal mesenchyme (stage of embryo Mall 163) ; and Figure 3 shows Figure 1 (stage of embryo Mall 2) viewed from above. The figures are schematic, but give a fair idea of the relations found in the models of these embryos.

I take the liberty of repeating the tabulation of the steps in the development of the tract as published in " American Medicine : "

I. The renal bud arises dorsally on the Wolffian duct after the duct has reached the cloaca and at a short distance from its entrance.

II. The two buds grow dorsally, lying close together, each being capped with a mass of renal mesenchyme.

III. Each bud divides into an upper and lower sprout at some distance from the Wolffian ducts.

IV. The kidney wanders upward from a position in front of the second sacral vertebra, rotates at the midlumbar region, and finally reaches its normal height about the end of the second month.

V. It becomes vascularized after it has reached its normal height.

VI. The ureter changes its position on the Wolffian duct from dorsal to lateral and comes to empty distinct from it.

VII. The ureter loses its relation to the duct entirely and opens higher and more laterally.

It may appear that something is taken for granted when it is assumed that the iipper and lower sprout of the renal bud found in an embryo of 9.0 mm. are represented in the adult by the upper and lower pelves of the kidney, especially when the division into an upper and lower sprout is replaced in an older stage by a " common pelvis." However, the assumption is a fair one : there are two sprouts, an upper and a lower, and correspondingly two pelves; in doubling of the


Febeuaet, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


53


ureter the ventral ureter always arises from the upper pelvis as would be expected from the development; and finally, this assumption makes it easy to account for the anomalies to be considered later.

This idea that the upper and lower pelves of the kidney are determined in the earlier stages of its embryology, is contrary to the views held by some that the division of the pelvis into an upper and lower segment is due to the development of the renal parenchyma. The formation of the kidney parench}Tna is secondary to the development of the ureter and its derivatives, and the idea that the growth of the kidney mechanically divides the pelvis is not substantiated in the formation of the anomalies nor does it even allow for the persistence of the lobulation normally present in the beef kidney.

It is granted in this article that the kidney is derived from a double anlage, the renal mesenchyme directly dependent on the renal bud, and that the division into an upper and lower pelvis is determined in the early embryology. It is upon these assumptions that I have based a scheme to be followed in the classification of anomalies of the tract.

No one has observed these variations at the time they were forming, and hence the scheme is merely a hypothesis. However, granting that certain changes do occur normally, is not a hypothesis that will account for the variations from this normal, and simplify the complex embryology of the developmental faults, better than no system whatever? Many renal variations are so rare that it is doubtful whether they will ever be observed in the earlier stages. Even some of the more frequent anomalies as doubling of the ureter has been reported but once in young embryos (Soulie). It was my good fortune to find two cases of complete double ureter in two embryos under the third month. One was discovered quite accidentally, and the other was found in working through the Mall collection. Two cases in over sixty embryos studied.

In all the anomalies to be mentioned none are directly pathologic because all the subjects attained an old age or died from causes quite apart from an abnormal kidney. This is no more than natural, for if the kidneys were not normal at birth, the chances for the individual reaching the age of puberty would be small. The variations are therefore only of inteiest from an anatomic point of view and indirectly of importance to the surgeon. The malpositions of the kidney have a greater interest to the clinician and it is my purpose to present that side of the subject at some later date. The clinical aspect is dealt with in a very thorough manner by Morris.

Anomalies of the kidney may be unilateral or bilateral, and for convenience sake the paper may be divided into three sub-headings :

A. Changes in form of the ureter.

B. Changes in form of one kidney.

C. Changes in form involving both kidneys.

Changes in form of the ureter may be present in changes in form of the kidney or they may be found in normal kidneys. The abnormalities of the ureter are dependent on the renal bud, while the anomalous kidneys result from an abnormal


development of the renal mesenchyme, again influenced by the renal bud. The term abnormal refers merely to form and not to function.

A. Variations in the Form of the Ureter and Pelvis. A 1. Incomplete Double Ureter.

Should the renal bud divide too early, or the division extend into the ureter segment (see Fig. Al), that splitting found in the ureter itself would remain a permanent one and any variation might exist as a result from an exaggeration of the usual upper and lower pelves to an incomplete reduplication of the ureter. An incomplete double ureter may be defined as two ureters with a common orifice.

The more complete the division of the ureter segment, the more complete the reduplication. The pelves of the kidney would always be distinct, and it is fair to assume that each subpelvis would follow the rule for the usual normal, and divide into an upper and lower segment (to be dealt with later under A 4).




Am


The ureter from the upper pelvis will normally lie ventral to the ureter from the lower one, as will be evident from the diagram. There are exceptions to this which have a slightly different origin and these will be considered under B 2.

Cases of incomplete double ureter are the most frequent of all renal variations, and are met with yearly in almost every dissecting room. I refer the reader to the article of Schwarz, p. 172, for a review of a number of reported cases, and also to the figures in the paper of Hauch.

The rule for incomplete double ureter may be stated as follows: The pelves of the kidney are always distinct, the ventral ureter arises from the upper pelvis and there is one orifice which is usually normally placed. It is important to distinguish the incomplete double ureter from the complete variety, and in the report of cases the distinction is not often made. Fig. A 1 of the plate represents a very common type of this anomaly.

A 2. Complete Double Ureter.

Should the splitting of the renal bud be so complete that it is affected by the shortening of the segment of the Wolffian


64


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


duct lying between it and the cloaca, it is possible for each division to acquire a distinct orifice in the duct as is shown in Fig. A 2. This would result in complete double ureter.

The explanation seems a more likelj' one as the complete double ureter conforms to the rules laid down for the incomplete variety. The only differences are found at the bladder end because of the two distinct orifices.

Cases of complete double ureter are rare but the anomaly has been reported quite frequently in the adult. It was my good fortune to discover two cases in embryos under two months old; one in embryo Piper, the property of Professor Franz Keibel under whom I began to study the development of the human urogenital system, and the other, embryo 175 of Professor Mall's collection. I am indebted to both Professor Keibel and to Professor Mall for the loan of the embryos mentioned in this paper, and also to Mr. Max Broedel for extremely useful suggestions regarding the anomalies of the kidney, and the privilege of mentioning one of his own cases.

Embryo Mall 175 (13.0 mm.). This embryo is cut at twenty microns and stained in carmine. It is well preserved and entirely normal. The sex from the histology of the sex gland is male. The epithelium at the urogenital sinus is loosened a little but not sufficiently to interfere with the conformation. A model of the lower ends of the ureters and of the WolfBan duct was made X 50.

The left kidney and ureter are entirely normal. On the right side, the kidney is also normal but the ureter is completely double. The ureter from the upper pelvis is a trifle smaller and lies ventrally to the ureter from the lower pelvis. This relation is maintained until the ureters approach the WolflSan duct when the dorsal ureter swings laterally. The relation at the urogenital sinus from the midline is : Wolfiian duct, ventral ureter and dorsal ureter.

As to the openings in the sinus, it is extremely difficult to say whether all three have a common orifice, or the ureters an orifice distinct from the Wolffian duct, or all three have separate openings. If the usually conceded fate of the lower part of the Wolffian duct is accepted — that it " unfolds " and enters into the formation of the bladder — any one of these possibilities may be held to be the correct one. Personally, I consider the case one of complete reduplication at a stage in which the lateral orifice is just beginning to shift to a higher and more lateral position.

Suffice it to say, that the two ureters change their relation as they approach the urogenital sinus, and that the dorsal ureter (the one from the lower part of the kidney) comes to lie lateral to the ventral ureter. This would probably be the same if the doubling were complete or nearly complete.

It will be noted that the change in position of the ureter from dorsal to lateral is at about the same time that the kidney undergoes axial rotation. Should the processes connected with the change in relation of ureter from a dorsal to a lateral position on the Wolffian duct be in any way connected with the rotation, the place of the crossing of the ureters would not be found at the lower end, and in cases where the kidney does


not reach a normal height, where no rotation has taken place,

the ureter would be abnormally situated — which is not the case. For these reasons, it is best to ascribe the changes in the position of the ureter to a development of the lower end of the tract and perhaps to the Wolffian duct as well.

Embryo Piper-Keibel (24.0 mm.). The same condition is found at a later stage in the development. The embryo was cut at fifteen microns and also stained in carmine. The sex is male. On the right side, there is a complete double ureter with two well defined orifices in the bladder. The ureters hold the same relation as that described in the Mall embryo and the ventral ureter swings mesial to the dorsal one as they approach the urogenital sinus. Owing to the development of the bladder, the lateral ureter opens higher and more laterally. It was found to lie in the normal position on comparison with the orifice on the other side. The ventral ureter was probably placed in a position of disadvantage for it lay in the path of the resultant of the forces — between the lateral ureter and the Wolffian duct.

I find a reference in an article by Weigert where in speaking about complete double ureter, he says : " In alien Fallen entsprach die tiefere liegende Offnung in der Blase dem Ureter, der vom oberen Nierenbecken kam, die andere dem, der vom unteren entsprang." This agrees perfectly with my findings in the embryos and with the cases cited in the literature, with a single exception. This is a case reported by Hudson, who pictures a specimen of complete double ureter in which the ventral ureter empties higher than the one from the lower part of the kidney. The specimen was drawn after removal from the body, and it would be a most natural proceeding to uncross the ureters.

There is also an exception to the rule that the more ventral ureter comes to lie mesial to the more dorsally placed one, for according to Weigert : " In den anderen vier Fallen fand eine vollkommene Kreuzung statt, indem der vom oberen Nierenbecken kommende Ureter, der bis dahin medial vom anderen Lag, nunmehr an dessen vordere und laterale Seite zu liegen kam, und in dieser Lagenmg bis an die Blase hinanging. Nach der Kreuzung und namentlich in der Nahe der Blase lagen die Ureter sehr dicht bei einander."

Exactly how this is meant is not quite clear to me. It is quite impossible to account for the condition in which the mesial ureter comes to open higher, and I am tempted to await other cases before giving up the idea that the ureter with the higher orifice must lie lateral to the more mesial opening. In a case reported by Hyrtl the orifices are described as lying side by side.

In one of Weigerf s cases, he mentions the relation of the ureter from the lower pelvis as lateral to the one from the upper part of the kidney. The case is also pictured after the removal of the organs from the body and would be quite possible. The other two exceptions will be explained under B3.

The rule for complete double ureter may be stated: that the relations of the two ureters and pelvis are the same as in incomplete reduplication, and the ureter from the upper


February, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


55


pelvis has the lower orifice in the bladder and lies somewhere between the higher opening of the dorsal ureter and the opening of the genital duet. The literature is reviewed by Schwarz, p. 175, and a report of twelve cases is found in the article by Weigert. The doubling according to the latter is usually on one side only.

A 3. Common Pelvis.

Should the division of the renal bud into an upper and lower sprout be suppressed, or should the later stage of common pelvis persist, there would be no involvement of the ureter and the form of the pelvis would not affect the shape of the kidney because that organ would have its normal origin — from one mass of renal mesenchyme. I find such cases cited by Hauch : " Man sieht die dicken plumpen Formen (casts of the pelvis), die sich garnicht in Calyces teilen, sondern einen l^icht konvexen ausseren Eand haben, an welche sie die Fornices fast ohne Calyxbildung aufnehmen" Fig. 31, 33.

This must be considered a persistence of the stage of common pelvis. It is also found in pathologic conditions, and is, according to Broedel, the first sign of a beginning hydronephrosis which mechanically transforms the upper and lower pelvis into a single one. This is entirely in keeping with the view that the division is due to the development of the cortex. That the damming back of the urine may have this effect is perfectly possible, but that the condition mentioned by Hauch is a variation in the development, is also a fact.

The variation is but a slight one and has no clinical importance or particular anatomic significance.

A 4. Bhtltiple Pelves and Ureters.

The sprouting of the renal bud takes place at the upper and lower poles and the question naturally arises, in case there are two pelves, the one above the other as is normal, does each pelvis divide into an upper and lower subpelvis as is the rule for the adult form? If we represent the state of afilairs in a stage corresponding to an embryo 9 mm. long by a subdivision of the anlage for a doubling of the ureter, one sprout might divide and the other not as shown in Fig. A 4 a., or both might divide as in A 4 b.

In the former condition the lower pelvis would show the normal division in a kidney with complete or incomplete double ureter and two pelves, the upper simple and the lower divided. This I hold to be very imcommon, and know of no case. In the article by Hauch (Fig. 78) there is illustrated the cast of the upper part of the iireter and pelvis of a kidney in which the double subdivision is clearly shown.

The form of the kidney, if it has been developed from one mass of renal mesenchyme, is not affected by abnormalities of the pelvis, and in this I agree with Hauch : " Diese aussere Form der Niere hat keine oder nur sehr wenig Bedeutung fiir die Form des Nierenbeckens ; ich verglich die Ausgiisse der verschiedenen, oben besprochenen Nieren mit den Abbildungen von deren Ausseren und sah, wie alle die


verschiedenen Formen der Pelvis von des ausseren Form der Niere durchaus unabhdngig sind."

The doubling of the ureter is always in one plane and the parts are arranged from above down. In case an exaggeration of the condition represented in Fig. A 4 b. be found in the adult, it would correspond to the description of that of Eichmond, in which there were four divisions to the pelvis. Four distinct ducts led from either kidnej', and at a point some four inches below the hilum, united into a common pelvis and afterwards were replaced by a normal ureter with normal opening in the bladder. Although the fact was not mentioned, it may be taken for granted that the pelves were distinct and that the rule for incomplete double ureter held. The division in such a marked manner is extremely rare and may be counted the least common of the variations in the form of the ureter.

The anomalies thus far discussed only affect the form of the ureter, and as has been seen, are determined in the early development of the renal bud. All these variations may be present in abnormalities in the form of the kidney with the exception of the common pelvis. In all marked congenital variations in the form of one kidney the uieter is either completely or incompletely doubled.

B. Variations in the Form of one Kidney.

It is of course understood, that the kidney form varies to some extent as it is moulded more or less to fit in its surroundings, and that these minor differences are not included in the scope of this article. Only those anomalies are to be considered which are directly dependent upon the development of the renal bud and mesenchyme. It was mentioned that as long as the kidney was developed from one secondary anlage, its form would be normal no matter what the abnormality of the ureter. It must be inferred therefore that the kidney may be derived from more than one secondary anlage if anomalies in the form are found.

Should the sprouting of the renal bud begin early, or the division be placed at different points, or the sprouts be more divergent than is usual, each division might stimulate a mass of mesenchyme, and there would be a double secondary anlage for the kidney. These anlages are naturally placed one above the other and might remain distinct as shown in Fig. B 1, or might fuse at an earlier or later date as represented in Fig. B2.

Granting the condition in B 1 persistent, there would be complete doubling of the kidney, two distinct kidneys on one side with complete or incomplete double ureter, and whether the ureter be completely or incompletely double, the form of the kidney would be the same.

B 1. Free Supernumerary Kidneys.

A case is reported by Thielmann which gives an excellent illustration of doubling of the kidney with incomplete double ureter. The anomaly is described in great detail and I present the essentials which concern us.


56


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


The left kidney was normal but a trifle large. The right kidney was smaller, but also normally formed and placed. The third kidney was situated upon the right common iliac artery, was oval in shape, and a little flattened. The ureter from the upper kidney (the right) crossed it ventrally and received the ureter from the lower kidney which ran upward to meet it at an acute angle. The openings of the right and left ureters were apparently normal.

The blood supply of the upper kidneys was usual. The lower kidney received an artery from the aorta which entered ventrally, one from the right common iliac dorsally, and one from the hypogastric at the lower pole. The anomaly was found in a sailor who had never experienced any discomfort, and whose death was in no way connected with the kidney abnormality. The renal substance was normal.




Bn Figs. B and C.

A similar case is reported by Hyrtl with complete double ureter. In both cases the lower organ was misplaced and pointed hilum ventrally.

B 8. Fused Supernumerary Kidneys.

In case the two masses of mesenchyme fuse, three possible results are evident: (a) that the fusion of the two secondary anlages may be so complete and at such an early date that the two parts may act in the same way that one mass does (A 1 and A 2), the abnormality of the ureter being merely visible from the outside; (b) demarkation between the two may be well developed and the kidney form otherwise normal ; (c) the fusion may occur at such a late date that one part was rotated before the other became fused to it and this relation would necessarily hold in the adult form.

B 2 a. Complete Fusion.

Barlet describes a specimen of supernumerary kidneys in a letter to the Lancet in the following manner : " On examining the kidneys it was found that the subjects possessed three, two on the left side and one on the right. The two on the left side were fused together, one being on top of the other, and externally showed two ureters springing separately along their whole length, opening into the bladder by two distinct orifices, the one being about one-fourth of an inch above the other. On section there was distinct demarkation of the two kidneys which was not visible from the exterior. All three kidneys were normal in appearance and had no connection with the cause of death."

Here is undoubtedly the same condition found in A 2, with both of the sprouts capped by a separate mass of mesenchyme which fused at an early period. It is not mentioned what the


relation of the two ureters was, but it is fair to assume that they followed the rule laid down for the complete double ureter. The specimen appeals to me as a strong piece of evidence to disprove the division into an upper and lower pelvis by the growth of the parenchyma.

B 2 c. Fused Supernumerary Kidneys with One Mass Rotated.

In the discussion of the cases with double ureter, mention was made that two specimens had been reported by Weigert where the ureter from the upper pelvis did not occupy a ventral position. In the cases cited he found the upper part of the kidney rotated in the usual waj', the hilum pointing toward the middle line, while the lower part had the hilum ventrally. He does not mention that these were supernumerary organs, and the following is therefore only inferred from like findings to be taken up later.

The two masses of renal mesenchyme, the secondary anlage for the two parts of the kidney, remained separate until one was rotated at the midlumbar region when the lower and non-rotated part was fused to upper. This would present a result which would correspond with the Weigert cases, and account for the exception to the general rule for double ureter.

Cases of supernumerary kidneys are very rare. Hepburn reports a doubling on both sides in pig, and Amick a similar finding in man. There are still other varieties which will be discussed in a later part of the paper.

C. Changes in Form Involving Both Kidneys.

Thus far only the changes in the form of one kidney have been considered. There are also changes in form which affect both organs, and these are naturally due to a fusion of the two normal masses of renal mesenchyme (Fig. C). It was stated in a very superficial way in the article in "American Medicine " that it might be possible for the two renal buds to lie so closely together that they might be surrounded by one mass of mesenchyme, and that it would be difficult to distinguish this variety from cases of more or less complete fusion. This statement is withdrawn and I do not hold it possible now for two renal buds to stimulate one mass of mesenchyme; there must be two.

The fusion taking place between the masses will, of course, be a permanent one and the condition receives different names, depending on the position and the degree of fusion, but the class as a class is known as the horseshoe kidney. The varieties depend on the manner and degree of fusion.

It was mentioned that the two masses of mesenchyme lie in front of the second sacral vertebra in an embryo of 7.0 mm. (embryo Mall 2) and are at the same level. The renal buds may not lie at the same level and this is due to a slower growth and later date of appearance of one bud as was dealt with in a previous article. I find that one kidney lies a trifle higher than the other in embryo Mall 114, although both organs are still in the true pelvis. Similarh', it is quite possible to conceive that they might lie one above the other or one in front of the other.


February, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


57


C A. Where the masses of mesenchyme are placed at the same level, they may lie :

a. In the same relative position.

b. One ventral to the other.

C B. Where the two masses are placed one above the other :

a. One slightly in advance of the other.

b. The upper pole of one fused to the lower pole of the other.

C A a. Should the two masses of mesenchyme lie in the same relative position and at the same height, three possibilities as to the point of the fusion may be inferred : 1. Fusion at the upper poles. 3. Fusion at the lower poles. 3. Fusion centrally.

C A b. Should the two masses lie one in front of the other, the dorsally placed organ would fuse to the ventral one iu such a manner that the hilum of the former would attach to the dorsum of the latter.

C B a. Should one mass of mesenchyme be placed a trifle higher than the other, the relation would be maintained in the fusion, and if one kidney were displaced, it would be the lower one, as would be dealt with more completely in a later paper.

C B b. Should the fusion occur end-to-end, the displacement, as above, will be found in the lower organ.

C A a 1. Fusion at the Upper Poles.

In this form of horseshoe kidney the concavity is directed downward, and according to Arneill, is the most uncommon variety. The fusion occurs probably before the organs have grown out of the true pelvis, or as soon as a distinct upper and lower pole have been formed to each mass of mesenchyme (9.0 mm.). The ureter system, being developed from the renal bud, is usually quite normal. The arrangement of the parenchyma joining the kidneys is not known, but there is undoubtedly a more or less definite line of demarkation between the two parts. The earlier the date of the fusion the more indefinite this line would be, and in cases of very late fusion, at about the time that the kidney arrived at its normal height, the growing together might be limited to the capsule. As a rule the capsule is common to both organs.

In a specimen placed at my disposal by Mr. Broedel, there is in addition to other abnormalities a horseshoe kidney fused at the upper poles. The case is unique for this variety of kidney in that the fusion is hehmd the aorta. It will be interesting to work out the arterial defect that allowed the developing masses to slip behind the aorta. The suprarenals, strange to say, were also fused. The blood supply to these organs was naturally abnormal.

Fusion at the upper and at the lower poles not infrequently reaches the normal height, and if the growing together is not too marked, the hila may be rotated to the normal position. C A a 2. Fusion at the Lower Poles.

The most common variety of horseshoe kidney is found in the fusion at the lower poles. It probably has its origin at the same time as the preceding form, and why it should be


more common is not known. Many cases have been reported, and as it is only necessary to establish a type in this article, I content myself with referring the reader to the work of Morris on the Surgical Diseases of the Ureter and Kidney, Vol. I, p. 56, where an excellent example of this anomaly is pictured.

The specimen mentioned shows a well-marked bridge of renal tissue connecting the two kidneys at the lower poles. Morris states that the ureters usually lie ventral to the connecting bridge but may lie behind it in case the ureters lie behind the bridge of tissue, the fusion will have been a late one — after the kidneys have been rotated.

The case of Nixon is also alluded to where a similar malposition to that described in the Broedel case was found — fusion at the lower poles and the connecting renal substance behind the aorta. The embryologic defect, probably in the arteria sacra media, which allowed this malposition, would be the same in either case, and will be considered in greater detail in a later paper on the malposition of the kidney.

C A a 3. Fusion Centrally.

The central fusion of the two masses of mesenchyme has received the special name of " disc-kidney." The fusion may be so complete that it is difficult to distinguish any line of demarkation between the two kidneys, and the only grosser structure by which the two organs might be identified would be the two ureters opening into the bladder at either side of the middle line.

The case of Haller, pictured in Morris's work, p. 61, is a typical disc-kidney. The organ is situated in the middle line and the two ureters emerge ventrally. A form of fusion which approaches the disc-kidney in its completeness will be mentioned later.

C A b. Fusion of a Ventrally Placed Kidney to a More Dorsal One.

The only possibility which remains under A is that in the dorsal growth of the two buds, one came to lie farther back than the other and that fusion took place in this position.

In a case mentioned by Morris, there is a variety of fusion which does not resemble any form of horseshoe kidney thus far described. " The two kidneys formed an irregularly shaped mass which weighed thirteen ounces, and was lying on the front of the promontory of the sacrum. It was not horseshoe-shaped and the vessels and ureters were arranged most unusually. The central part of the mass was fissured by a sulcus, in wliich the ureter for the left kidney coursed downwards and the vein for the same upwards, passing into the vena cava just above the junction of the two iliacs. In the right lialf of the mass the ureter and vessels, instead of being situated centrally, were on its outer side; the ureter

being in front of the vessels as on the left and as is usual in fused kidneys." " The renal substance, to the naked eye, was healthy."

I think this explanation of the anomaly could be made: That the two masses of mesenchyme were normally placed


58


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


excepting that one was in front of the other, and that a fusion occurred between the front edge of the dorsal mass (about the hilum) and the touching edge of the ventrally situated mesenchyme. Both organs were in the pelvic inlet and a later rotation, probably a piirely mechanical one to gain room, turned both ureters toward the same side. The one would in this case undergo a normal rotation and the other, one in the opposite direction. In the specimen of two kidneys pictured by Morris, one must have been placed a little in front of the other.

C B a. Fusion of a Lower Kidney to a Higher One.

In all the variations in the form of the two kidneys thus far considered the two organs were placed at the same level. In embryo Mall 114 (10.0 mm.) one kidney was found lying a trifle higher than the other, although both organs were still in the true pelvis. Should a fusion occur the lower kidney would remain in the lower position.

This type of fusion is found in a case of horseshoe kidney placed at my disposal by Dr. W. H. Lewis. The two kidneys lie on the midline and the right organ is a trifle higher than the left. The mass is somewhat irregular, but the two kidneys are well divided by a longitudinal fissure. The ureters emerge ventrally and empty normally in the bladder. The mass was in a low position and lay upon the bifurcation of the aorta.

These minor differences in height are difficult to tell from disc-kidney, but as a rule the two parts are more distinct. When the difference in the height is more marked, and the organs lie above the point of rotation, the lower kidney is usually displaced and crosses to the opposite side — crossed dystopia (see McMurrich's article).

The fusion of a higher kidney to a lower kidney may be any variety from a disc-kidney to an end-to-end fusion which is discussed in the next sub-heading. The blood supply to these organs is more or less abnormal, depending on the degree of the malposition. Normally placed horseshoe kidneys may have a normal blood supply.

C B b. End-to-end Fusion.

In a case reported by Broesicke, two kidneys were fused end-to-end and both organs were placed to the left of the middle line. The arrangement of the ureters was strikingly abnormal. The upper ureter arose from the mesial surface of the mass and the lower one from the lateral side. The openings of the ureters in the bladder were normal. The specimen is one of " sigmoid kidney." Broesicke agrees with Schultze that the anomaly is explained on the basis of the embryology.

Here the two masses of mesenchyme were placed one above the other and fused after the rotation of the upper kidney took place. The case is similar to the variety discussed under B where the upper half of the kidney rotated and then became fused to the lower part.

These end-to-end fusions are all of relatively late stages. Should the two masses fuse at a very early date, there would


be difficulty in distinguishing the two kidneys. The mass would be different from the centrally fused horseshoe kidney in that the ureters would be placed one above the other. This form of kidney is reported by Morris and pictured on page 49. The variety is interesting in the discussion of the causes of the rotation.

C C. Fusion of Supernumerary Kidneys of Opposite Sides.

Granting that the doubling of the kidney may be found on one or both sides and that fusion between the masses of mesenchyme on the same and opposite sides may take place, a number of combinations may occur which are represented in the scheme below. Naturally all these cases have not been reported, but this does not preclude the possibility of their being found. It must be remembered that fusion between a normal mass of mesenchyme on one side and two masses on the other may also occur, and the resulting form is easily deduced from the scheme.

In the first series, the upper and lower masses are presented as remaining free :

a. Horseshoe kidney with free supernumerary kidneys

below.

b. Horseshoe kidney with free supernumerary kidneys

above.

c. Double horseshoe kidney (no cases reported).

In the second series, the upper masses are fused to the lower :

d. Horseshoe kidney with fused supernumerary kidneys

below.

e. Horseshoe kidney with fused supernumerary kidneys

above.

f. Fusion of all four parts (e and f reported).

In the third series, the organs are placed at different levels :

g. Horseshoe kidney with free supernumerary above and

below. h. Horseshoe kidney with fused supernumerary above

and below, i. End-to-end fusion of all four parts (none reported).

C C e. Horseshoe Kidney with Fused Supernumerary Kidneys Above.

A specimen is described by Oleson of four kidneys in a human being. The mass was fused at the lower poles, and on each side there appeared to be a division into two. From the report it is gathered that the ureters were incompletely doubled, and that the author Identified the two supernumerary organs above.

C C f . Fusion of All Four Parts.

Morris pictures an anomalous kidney mass, p. 54, the case of Batallus, which I take to be the fusion of four kidneys. The mass presents " a quadrilateral appearance " and each ureter divides into two. There is, of course, a question as to the definiteness of this statement, but the case seems to conform, and there is no reason why double kidneys on either side should not behave like a central fusion of the disc-kidney variety.


Febeuaet, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


59




o





CI


01


t

CI


CI


ecg



Ci 3




There are some abnormalities which are not included in this paper, and only those have been mentioned which seem to find an explanation in the development of the tract. The embryology of these anomalies is not very complicated when


one follows the development closely. The supernumerary kidney, like the double ureter, has a distinct importance in the study of normal embryology, and serves to substantiate the rule which was assumed in the first part of this article.


60


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


that abnormalities in form are dependent on small variations in the development of the renal bud and mesenchyme before the embryo reaches a size of 10.0 mm.

The letters and numbers of the figures in the plate correspond to the numbers and letters in the paper, and to simplify matters, all those which have been reported are marked with an (r). In the schemas of the horseshoe kidneys, the one ureter has been pictured black, and in the supernumerary kidneys the ureters have been omitted and the one side made black; the concave side representing the hilum in each.

Literature.

Amick, M. C: Four Kidneys. Cincinnati Med. Report, 1871, IV, 551.

Arneill, J. E. : Anomalies of the Kidney. Eef . Handb. Med. Sci., Vol. V, 319.

Bachhammer, J. : Ueber einige seltene Varietaeten des menseh. Koerpers. Arch. f. Anat. u. Phys., 1879, 139.

Ballowitz, Emil : Ueber angeb. einseit. volkommenen Nierenmangel. Virchow^s Archiv, Vol. 141, 309.

Barlet : Double Kidney. Lancet, 1904, 124.

Batallus: (Cited by Morris).

Broesicke: Ein Fall von congenitaler S-formiger Verwachsung beider Nieren. Virchow's Archiv, Vol. 98, 338.

Haller : ( Cited by Morris ) .

Hauch: Ueber die Anatomic u. Entwick. der Nieren. Anat. Hefte, Heft 69, Bd. 22, 2.


Hepburn, David: Abnormal Kidneys from Domestic Pig. Jr. of Anat. and Phys., Vol. 29.

Hudson, L. : Double Ureter. Lancet, 1903, Vol. II, 1006.

Hyrtl, J. : Ein wahrer Een tertius. Oesterreich. med. Wochensch., 1841, 965.

Keibel, Franz. Zur Entwick. des menseh. Urogenitalapparates. Archiv f. Anat. u. Phys., 1896, 55.

McMurrich, J. P. : A case of crossed dystopia of the kidney with fusion. Jr. of Anat. and Phys., Vol. 32, 652.

Moore, F. C. : Unilateral Eenal Aplasia. Jr. of Anat. and Phys., Vol. 33.

Morris, Henry : Surgical Diseases of the Ureter and. Kidney. 2 Vols, 1901.

Nixon: (Cited by Morris).

Oleson, E. B. : Case of Horseshoe Kidney. Annals of Surgery, 1894, 731.

Pohlman, A. G. : Concerning the Embryology of Kidney Anomalies. American Medicine, June 18, 1904.

Eichmond, W. S. : Abnormal Ureters. Jr. of Anat. and Phys., Vol. 19.

Schwarz, C. : Ueber abnorme Ausmundungen der Ureteren und deren chirurgische Behandlung. Beitrage z. klin. Chir., Vol. 15, 159.

Soulie: Le Progres medical, 1895, 382.

Thielmann, C. : Drei Nieren im Leichname eines Menseh. Archiv f. Anat. und Phys., 1835.

Weigert, C. : Uber einige Bildungsfehler der Nieren. Virchow's Archiv, Vol. 70, 490.

ON THE FIRST APPEARANCE OF THE RENAL ARTERY, AND THE RELATIVE DEVELOPMENT OF THE KIDNEYS AND WOLFFIAN BODIES IN PIG EMBRYOS

Hill EC. On the first appearance of the renal artery, and the relative development of the kidneys and wolffian bodies in pig embryos. (1905) Johns Hopkins Hospital Bulletin 16: .

Bt Eben C. Hill. Frovi the Anatomical Laboratory of the Johns HopJcins University.


A review of the literature on the development of the kidneys and Wolffian bodies in pig embryos, shows but little concerning the blood supply and the relative size of these organs. Perhaps the most extensive study is found in Keibel's Normentafel, in which the anlages and subsequent development of these glands are traced histologically. Here, however, no measurements except those of the embryos are given. In the accounts of the embryology of the arterial system there is no work which shows the relative development of the blood supply to these two glands. At the suggestion of Dr. Pohlman, I measured these organs in pig embryos, and made a number of arterial injections. These injections demonstrate the first appearance and development of the renal artery and afford an opportunity to compare the blood supply of the kidney and Wolffian body in pig embryos ranging from 20 mm. to 75 mm. in length. The measurements show the relative size of these glands at various stages from 20 mm. to 132 mm.

Material and Methods. — The abundance of material from the slaughter houses offered every facility for numerous meas


urements and repeated injections upon live pig embryos, while the valuable collection of human embryos belonging to Professor Mall afforded opportunity to compare the human fetal development with that of the pig. The pig embryo is especially adapted for the study of the Wolffian bodies because of the relatively larger development of this organ in the pig than in man or rabbit.

Measurements. — As each uterus was opened the vertexbreech lengths of the embryos were made and measurements of the kidneys and Wolffian bodies were taken. These measurements were then averaged and the results were used in plotting the curves of their relative development. In cases where the growth of these organs was abnormal, their measurements were not included in the averages.

Injections. — In making injections, India ink, diluted to one-third of its commercial strength, was used.' In certain instances, pure water formed a precipitate, when added to the


^Taguchi's method modified. Arch. f. Mikr. Anat., 1888.


February, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


61


commercial ink, but this could be easily remedied by the addition of a small amount of weak ammonia. Lamp-black solutions proved to be most unsatisfactory, because of the difficulty in obtaining solutions of similar consistency. Frequently, also, this injection mass would clog the needle of the sj'ringe. All injections were made through the hypogastric artery before the embryo was removed from its surrounding membranes. In this way the organism was protected from undue pressure and from injury in handling. During the operation, the embryo still attached to a portion of the uterine wall was immersed in warm water. A ligature was passed around the umbilical cord close to the wall of the uterus, thereby preventing infusion of the injection mass through the uterine tissues. The hypogastric vein was then pricked with a needle, thus reducing the pressure in the circulatory system consequent upon the entrance of the injection fluid. All injections were made with a fine hypodermic syringe by piercing the hypogastric artery close to the abdominal wall. To obtain an even flow it was necessary to have a perfectly adjusted syringe devoid of all capacity markings. With such a syringe an even pressure of about one drop in three seconds was maintained with little difficulty. By watching the femoral arteries the progress of the fluid was followed and an injection without extravasation was obtained. After the injection, the membranes were removed and a measurement of the body length was taken. Then an abdominal incision was made and the liver and portions of the intestines were dissected away, exposing the kidneys and Wolffian bodies. In the smaller stages it was necessary to displace the Wolffian body m order to obtain a measurement of the kidney, as at this time it is completely hidden by the larger gland. The positions of these organs relative to the vertebral column were also noted, though this was more easily discerned after clearing.

Clearing. — To clear the specimens, the Schultz method, modified by Dr. Mall, was used. The specimen was first thrown into 95 per cent alcohol until completely shriveled. As a rule forty-eight hours were sufficient to accomplish this result. Then the upper portion of the embryo, just above the twelfth thoracic vertebra, was dissected off, leaving the Wolffian bodies and the kidneys attached to the body wall. Thus during the clearing in a 3 per cent solution of sodium hydroxide, which followed, the action of the reagent could be watched and controlled. This usually took from four to eight hours. When the tissues had become translucent in this medium the specimen was transferred to 20 per cent glycerine for a week or more, and was then placed in absolute glycerine where it became transparent. Upon complete clearing the vertebral column was shown quite prominently and its position relative to the kidneys and Wolffian bodies was noted. In this absolute glycerine the organs became so firm that the remaining portions of the body wall were removed and the specimen was then placed between watch crystals for microscopic study. Injections were also attempted through the liver while the embryo was alive, but the vascularization of the Wolffian bodies is such that venous injections were most unsatisfactory. The causes of this will be taken up later.


TABLE SHOWING THE LENGTH IN MILLIMETERS OF THE KIDNEYS AND WOLFFIAN BODIES OF PIG EMBRYOS.

The measurements were made from vertex to breech, and include all of the embryos in each uterus. In case of asymmetric development of these glands in any embryo averages were made of the lengths of both organs.

Relative Size of the Kidney and Wolffian Body at Different Stages.


Vertex-Breech.


Kidney. WoltBan Body.



20


1.2


7.3



21


1.2


7.3



20


1.1


7.4


Uterus 1


23


1.2


7.2



22


1.3


7.1



21


1.0


7.3



20


1.2


7.2



28


2.5


9.0



28


2.6


8.0


Uterus 2


29 27


2.5 2.4


8.5 9.2



28


3.0


7.0



29


2.T


8.7



30


2.8


8.6



32


3.2


8.8


Uterus 3


30 33


3.5 3.4


8.7 8.8



29


2.9


8.9



34


3.5


8.7



' 31


3.9


9.2



33


4.0


9.1


Uterus 4


33


3.8


9.0



35


3.7


9.1



. 33


4.1


8.9



- 38


5.0


10.0



39


5.5


9.5



38


5.5


10.0


Uterus 5


38


5.0


10.0



39


5.0


10.0



39


6.5 abnormally


8.3 abnormally



L


large.


small.



r 39


5.5


10.0



39


5.5


9.5


Uterus 6


38


5.7


9.5



39


5.5


10.0



40


5.6


10.2



f 40


5.8


10.0



41


5.9


10.0



40


5.9


11.0



42


5.9


11.0


Uterus 7

41 43


6.8 6.0


10.0



11.2



41


5.8


10.5



42


3.9


11.3



39


5.6


11.5



. 41


5.9


10.0



(- 49


8.0


11.5



48


7.0


12.0



48


6.5


11.1


Uterus 8


49 48


6.0 7.0


12.0



10.0



49


7.3


11.0



48


7.5


11.5



. 49


8.0


10.5



f 49 1 49


7.3


11.0



7.8


10.5


Uterus 9


49


6.8


12.0



1 48


8.0


10.0



1^ 50


7.8


10.5



• 57


9.2


11.5



57


9.0


11.4



56


9.2


11.2


Uterus 10


58


9.0


11.5



57


0.3


11.0



59


9.5


11.5



. 58


9.0


11.4


62


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


Vertex-Breech. 60


Uterus


13

70 67 67

f 68 67 68


Uterus


14 ^


69

67

68

. 67

f 84.5 84.5 84.0


Uterus


15

85.0 84.5 84.0 85.0

85.0


Uterus


16


84.6 84.4

90.0 91.0


Uterus


17

90.0 89.5 90.1

94.3 94.5


Uterus


18


94.3 94.0 94.4 94.3

'112.2


Uterus


" 1


112.5 111.9 112.0

120.6


Uterus


20

121.0 120.8 120,7

132.4 132.6


Uterus


21

r


131.9 133.0 132.5

155.1


Uterus


22


156.9 157.2 155.5


Kidney. Wolffian Body.


9.2



11.5


10.6


abnormally


9.8 abnormally



large.


small.


9.5



11.4


9.4



11.5


9.4



11.5


9.3



11.0


9.5



11.7


9.0



11.3


9.5



11.0


9.7



10.5


11.5



11.5


11.5



11.0


11.0



12.0


11.5



11.0


11.4



11.5


11.5



11.0


11.7



11.8


11.5



12.0


11.5



11.4


11.4



11.5


11.2



11.2


11.5



11.7


11.6



11.4


14.4



10.0


14.5



10.0


15.0



10.0


14.6



9.5


14.2



11.0


U.O



11.0


17.2


abnormally


8.0 abnormally



large.


small.


14.5



10.2


14.7



10.0


14.3



10.5


15.0



9.7


15.3



9.5


15.0



9.7


14.6



10.0


15.0



9.6


15.7



9.2


15.9



9.0


15.6



9.0


15.5



9.8


15.7



8.7


15.6



8.9


18.3



7.1


18.4



7.0


18.0



7.1


18.0



6.7


19.4



5.6


19.6



5.4


19.5



5.5


19.5



5.5


20.0


At this stage the Wolffian


20.3


bodies have


become so atro

21.0


phled at the anterior end


20.5


that accurate measurements


21.0


are Impossible.


23.6




23.8




24.0




23.8




That a balancing of function exists between these two glands is suggested by the fact that an embryo having an unusually large kidney development has correspondingly small Wolffian bodies.

In the accompanying diagram, the curves are constructed from the foregoing measurements and represent the growth of the kidney and Wolffian body as compared with the general development of the embryos. In the case of the WolfiSan body it is impossible to properly depict the atrophy of this gland by a curve, because the degeneration which occurs mainly in the cephalic end is marked rather by a decrease in width than in length.

Embryological Development of the Wolffian Body and Kidney. — As is well knovra, the Wolffian body finds its anlage in the Wolffian duct which is developed as a solid mesoblastic cord of cells, lying close to the vertebral column in the abdominal cavity. This cord of cells acquires a lumen and penetrates the urogenital portion of the cloaca. Adjacent to the anterior end of this duct on the outer side lie the mesoblastic cells which later become the Wolffian body. The rapid growth of this gland from the 7 mm. stage to that of 10 mm. has been described by Allen." He states that between 7 mm. and 8 mm. the Wolffian body is almost doubled in size, while at 10 mm. it is half as broad again, and has also increased dorso-ventrally. MacCallum has found at this same stage of 8 mm. well-formed glomeruli and tubules throughout the whole length of the organ.' The Wolffian duct is also fully developed and according to Minot is larger proportionately at this stage than at any time later.

The Wolffian bodies are elongated structures attached to the mesentery close to the dorsal wall. The anterior and posterior ends curve toward the median line, though the curve is more exaggerated in the case of the former. The anterior end tapers slightly when the gland is at its fullest development, and it is in this portion that atrophy begins. The Wolffian duct lies as a ridge on the flat dorso-lateral surface of the gland and extending from the anterior end empties into the urogenital part of the cloaca. During its course across the organ it sends out at regular intervals tubules which are very much contorted and almost encircle the periphery of the organ. The arteries supplying the gland penetrate the dorso-medial portion and form with the distal end of these tubules glomeruli similar in structure to those of the true kidney, though slightly larger.'

The venous system in this gland consists of branching capillaries which follow the periphery and anastomose profusely in the midst of the organ. Injections consequently resulted in almost solid masses of black with no definite structure. The relation of the arteries and veins is easily discerned by sections and shows a vascular arrangement similar to that of the kidney. The arteries and veins in the glomeruli are sur


A study of the foregoing tables shows comparatively little variation in the body lengths of the embryos in each uterus. In the cases of abnormal development of the kidney, it is interesting to note the corresponding size of the Wolffian body.


' Allen, B. M., Embryonic Development of Ovary and Testis of Mammals, American Journal of Anatomy, Vol. Ill, No. 2.

MacCallum, J. B., Notes .on the Wolffian bodies of Higher Mammals, American Journal of Anatomy, Vol. I, No. 3.

MacCallum, op. cit.


Febeuaet, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


63


rounded by an epithelial membrane similar in structure to Bowman's capsule of the kidney, and the histological structure of the tubules is also quite similar. Each tubide begins at the glomerulus as a somewhat constricted tube and widens in the middle, narrowing again before reaching the duct. The space between the tubules, according to Minot, is lined with epithelium and gives evidence of a sinusoidal circulation. Kidney. — The kidney, as has been long known, arises as a tubular diverticulum from the Wolffian duct near its entrance into the cloaca. This broadens at its distal end, forming the renal pelvis, while the tubular portion becomes the ureter. When the embryo is 12 mm. in length the pelvis of the renal


between the Wolffian body and kidneys is more easily illustrated.

In Figure 1 the kidney is moving in a cephalic direction toward its permanent position and has at this stage received no apparent blood supply. To ascertain that no injection had reached the organ it was completely mascerated and studied under high power. No suggestion of arterial supply was discovered and it is probable that the renal arteries in the pig embryo as in the human fetus do not penetrate the kidneys until they have reached their permanent position. It was supposed that these arteries might enter the kidneys earlier and grow i;p the aorta as the organ ascended, but injections
























/


















/

















/


















/

















/

















^


/

















y


















/













^


^




/










^


"^








/



->'•"


..v:::i




^


^











^^


~





j^


rll^-

-^^


->'^ ^(^^^>-'





^


--

^









^^


-^















)


10 —


IC —


iO —


to-.^


i^O^.^


to-^


IC —


»0


so —


100 —



IJO,

IW.


140__


tj-0


ito-.


Diagram showing tlie relative size of the Itidney and Wolffian body as compared with the length of the embryo. Averages were made of the measurements of the embryos in each ulterus except ia certain cases of abnormal development, when only the average of those normally developed was taken.


anlage is between the fifth lumbar and second sacral vertebrae, just below the division of the dorsal aorta into the right and left hypogastric arteries."

From this stage in the development of the kidney and WolSian body, which has already been so thoroughly worked out, the following figures trace the relative development of these glands and their blood supply.

It was found best in order to avoid confusion to omit from the drawing the adrenal glands, ureters and Wolffian ducts as well as the ovary or testis. In this way the comparison


'Lewis, F. T., The Gross Anatomy of a 12 mm. pig, Vol. VII, Americal Journal of Anatomy.


and examinations of sections show no vascularization until the kidney has reached its permanent position. That the absence of injection fluid in the kidney at this stage was not due to imperfect injection is evinced by the fact that the finest capillaries of the lower extremities and viscera are completely filled.

As in the htmian embryo, rotation of the kidney occurs before the entrance of the blood supply. According to Pohlman, this rotation takes place in the human embryo at 14 mm.° My study of sections of pig embryos places the rotation of the


° Pohlman, A. G., Concerning the embryology of Kidney Anomalies, American Medicine, Vol. VII, No. 25, pages 987-990.


64


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


kidneys in this genus between 12 and 15 mm. The vascularization of these glands in the human fetus, as has also been proved by Polilman, talces place during the time the embryo is increasing in length from 25 mm. to 30 mm. In the pig embryo, the first appearance of the renal artery which I have been able to demonstrate, occurs at 28 mm.

The Wolffian bodies at this stage are highly vascularized and the glomeruli are fully developed.

The number of arteries leading from the aorta to these glands during the early stages is approximately the same, while the increase in size is proportional to the body growth.

Figure 2 shows the entrance of the renal artery at the earliest stage, though only a very slight arterial supply to the glomeruli was discernible. The Wolffian body is more highly vascularized and has broadened and lengthened.

In Figure 3 the glomeruli of the kidney have received their arterial supply while the Wolffian arteries have increased considerably in diameter. The organ has also increased in size. The heavy injection shown in the dorso-medial region indicates as in the first two figures the region of the glomeruli. It is around these that the tubules end. The position of the organs relative to the vertebrae is but slightly changed. At this stage the development of these vertebrae and the kidneys and Wolffian bodies seems quite proportional.

Figure 4 shows the rapid increase in the vascularization of the kidney and its relative growth. A slight atrophying of the anterior portion of the Wolffian body has begun, and the arterial supply of the glomeruli of this part of the gland is less extensive than in the posterior end, where the blood supply still continues to increase.

In Figure 5 the four anteriorly situated arteries to the Wolffian body have decreased in diameter and the accompanying glomeruli show consequent lack of blood supply. The posterior glomeruli on the other hand are still well vascularized, and there is no atrophy of the gland itself in this portion. The kidney manifests a further development, both in the number of its glomeruli and in its uniform growth.

In Figure 6 it was found to be impossible to separate the two glands so that we find the Wolffian body closely attached to the lower ventral border of the kidney. The atrophy of the anterior portion of the Wolffian body has become most evident, though this degeneration is more manifest in width than in length. The glomeruli in this part of the gland have practically no blood supply and several of the arteries have entirely disappeared. By this time the cortex of the kidney has become so thickened that only the bhirred outlines of the arteries are discernible.'

Figure 7 shows the complete disappearance of the anterior Wolffian arteries and the absence of glomeruli in this portion of the gland. Three of the posterior arteries still persist


'Recent injections which were cleared in a saturated solution of sodium hydroxide instead of a 2% solution bring out quite distinctly the course and distribution of the renal arteries and the location of the glomeruli in the kidneys of pig embryos 68 mm. and 75 mm. in length. The general arrangement of these arteries and glomeruli is similar to that found in figure five.


and supply the glomeruli of this part of the organ, though one of these seems ready to atrophy. In the kidney development there is little more to be noticed except a general increase in size and blood supply.

Injection methods give no further information concerning the Wolffian body after this stage. It is well known, however, that the anterior portion continues to rapidly diminish in width and later in length, and that the remaining tubules are finally claimed by the testis or ovary.

In the male the Wolffian duct becomes the canal of the epididymis, the vas deferens and the common ejaculatory duct, and the remains of the gland itself become the vasa afferentia, ductuli aberrantes and the rudimentary paradidymis.

In the female, the duct becomes the longitudinal duct of the parovarium and the hydatids of Morgagni, while the tubules of the Wolffian body are transformed into the rudimentary tubules of the parovarium and of the paroophoron.

SUMMAEY.

A. The renal artery penetrates the kidney when the embryo

has attained a length of 28 mm. ; rotation of this gland having occurred between 12 mm. and 15 mm.

B. A balancing of function is suggested by a study of the

measurements of these glands.

C. As the blood supply to the kidney increases there is a

corresponding atrophying of the Wolffian arteries.

D. Atrophy of the Wolffian arteries is first evident when the

embryo is 45 mm. in length.

E. As atrophy of the Wolffian body itself continues, the sex

gland becomes more firmly attached to the posterior

portion, and the remaining tubules and duct are

claimed by the ovary or testis.

Before completing this article, I wish to thank Professor

Keibel, of the University of Freiburg, for the privileges of

his laboratory, in which a portion of this work was done.


INSTRUCTION IN PSYCHIATRY AND NEUROPATHOLOGY.

A limited number of graduates in medicine can have an opportunity for work in the laboratory of the Sheppard and Enoch Pratt Hospital.

Instruction in neuropathology will be given by the director of the laboratory, and those attending the course will be permitted to attend the clinical and other conferences of the medical staff. Clinical forms of insanity will be discussed, as well as the hospital and home care of the insane.

Physicians taking this course will also have an opportunity to attend the neurological clinics at the Johns Hopkins Hospital.

For particulars, apply by letter to Dr. E. N. Brush, Physicianin-Chief and Superintendent, Sheppard and Enoch Pratt Hospital, Station " A," Baltimore.


THE JOHNS HOPKINS HOSPITAL BULLETIN, FEBRUARY, 1905.


PLATE VIII.



Flo. 1. — The right Wolffian body and the left kidney of a pig embryo 20 millimeters long: injected through the hypogastric artery with India ink. The length of the Wolffian body is 7.3 mm., and the kidney is 1.2 mm. long. D. A., dorsal aorta. K., kidney. L. H. A., left hypogastric artery. W., Wolffian body. 12 T. R., twelfth thoracic rib. 1 S. V., first sacral vertebra.


Fig. 2. — The right Wolffian body and the left kidney of a pig embryo 28 mm. long; injected through the hypogastric artery with India ink. The entrance of the renal artery is first demonstrated at this stage. The length of the Wolffian body is 8.5 mm., and the length of the kidney is 2.6 mm. 12 T. V., twelfth thoracic vertebra. 1 S. V., first sacral vertebra.



Fig. 3. — The right Wolffian body and the left kidney of a pig embryo 33 mm. long; injected through the hypogastric artery with India ink. The length of the Wolffian body is 9.1 mm., and the kidney is 3.9 mm. long. K! T. V., thirteenth thoracic vertebra. 1 S. v., first sacral vertebra.


Fig. 4. — The right Wolffian body and the left kidney of a pig embryo 45 mm. long; injected through the hypogastric artery. The length of the Wolffian body is 10.6, and the length of the kidney is 6.3 mm. 14 T. V., fourteenth thoracic vertebra. G L. V., sixth lumbar vertebra.


THE JOHNS HOPKINS HOSPITAL BULLETIN, FEBRUARY, 1905.



Lh


Fid. 5.— The right Wolffian hody ami the left kidney of a pig emhryo .54 mm. in length; injected through the hypogastric artery. The length of the Wolffian body is 11.2 mm., and the length of the kidney is S mm. 14 T. V., fourteenth thoracic vertebra. L. V.. sixth lumbar vertebra.


m



TV. 14


LVt



Pi(i. fi.— The right Wolffian body and right kidney of a pig emljryo US mm. long; injected through the hypogastric artery with India ink. The length of the Wolffian body is 11.3 mm., and the length of the kidney is 11. .5 mm. 14 T. V.. fourteenth thoracic vertebra. 6 L. V., sixth lumbar vertebra.


Pro. 7.— The right Wolffian body and right kidney of a pig embryo 75 mm. long; injected through the hypogastric artery with India ink. The length of the Wolffian body is 10.9 mm., and the length of the kidney is 12.2 mm.


February, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


65


HIGH BIFURCATION OF THE BRACHIAL ARTERY WITH REUNION AT THE ELBOW.


By Minerva Herrinton.


The abnormality herewith reported is of interest because it blends three variations, which, taken alone, are not common in one specimen. The specimen is from the left arm of a white woman, 50 years old, whose death was caused by acute aneurysm (No. 1131). It was my good fortune to dissect this arm while a student of anatomy at the Johns Hopkins University, and with the permission of Dr. Mall I report it.

The axillary and brachial arteries are normal in arrangement until the middle third of the arm is reached. Then


ehial artery at the elbow and that if it bifurcates higher this same force has a tendency to reunite the branches as shown in these cases.

Without entering into the discussion of the arteries of the early embryo, it may be noted that in their later development those arteries which are more favored are preserved. Such branches pass to the ulnar and radial muscle masses and then are arranged on either side of the humerus and later slide down to the forearm. In case the brachial arterv bifurcates



Fig. 1. — Outline of the Brachial Artery and its Branches. Reduced. 1, brachial artery; 2, radial; 3, ulnar; 4, branch accompanying ulnar vein ; 5 and 6, branches anastomosing with the posterior ulnar recurrent and anastomotica magna ; 7, anastomotica ; 8, superior profunda; A, branch accompanying the musculospiral nerve; B, branches to muscles and the anastomoses around the elbow Joint.


between the middle and lower thirds of the arm the artery divides into the ulnar and radial arteries, which are about equal in size. These branches continued somewhat separated until they passed the elbow, when they came in apposition and anastomosed by an opening about as large as the lumen of either of the arteries. The accompanying figure, which is drawn at one-fourth scale, shows the dimensions, form and relation of the arteries. The anastomoses with the posterior ulnar recurrent and anastomotica magna are also shown.

A specimen in the Army Medical Museum at Washington, prepared by Dr. D. S. Lamb, shows a similar variation, high division of the brachial artery with partial reunion at the usual site of its bifurcation into the radial and ulnar. Similar cases are also reported by Quain,' Henle,' Tiedemann,' Power,* Green," Maestre ° and others, which together indicate that there must be some force which favors the bifurcation of the bra


while the muscle masses are high and obstacles are then placed between the two branches, the condition continues during life. If the bifurcation is low, say the lower third of the humerus, there is no marked obstacle, and by a process of union and shifting the two arteries may unite until they reach an obstacle, which is at the usual point of division. For this reason a bifurcation in the lower third of the upper arm is rare. In this case some obstacle prevented such a union all the way down, but since these arteries were again close together at the usual point of bifurcation, one of the many small branches which united them at this point in the embryo enlarged, for it was " put into use frequently," so to speak. From this time on there "was a balance which favored the circulation first through one of the channels of the bifurcation and then through the other, which of necessity caused blood to flow through the anastomosis. Had this not been so, one of the


66


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


two channels would have been obliterated or the anastomosis would have closed, as under similar conditions the foramen ovale, ductus arteriosus and other vessels become obliterated.

EEFEEENCES.

1. Quain, E. : Anatom}' of the Arteries of the Human Body. London, 1844; atlas.

Elements of Anatomy, Vol. II, Part II, London and

New York, 1892.

2. Henle, J. : Handbueh der Systematischen Anatomie des Menschen, Vol. Ill, Gefasslehre. Braunschweig, 1876.


3. Tiedemann, E. : Explicationes supplementorum ad tabulas arteriarum corporis humani. Heidelberg, 1846 ; atlas.

4. Power, J. H. Anatomy of the Arteries of the Human Body. Phila., 1863.

5. Green, P. H. : An Account of the Varieties in the Arterial System of the Human Body. Dublin, 1830.

6. Maestre, A. : Notable anomalio de la arteria humeral. La Espana Medica. Madrid, 1864, IX.

A preparation by D. S. Lamb, Act. Asst. Surg. U. S. A., in the Army Medical Museum is that of a dissected and injected right arm showing high division of the brachial artery with partial reunion at the usual site of bifurcation into the radial and ulnar.


FIXATION OF TISSUES BY INJECTION INTO THE ARTERIES.

By Burton D. Myers, M. D., Associate Professor of Anatomy, University of Indiana.


Diiring the past year, while preparing tissues for the course in histology at Johns Hopkins University, the injection method recommended by McFarland ' of Leland Stanford, Jr., University, was given a trial. The result was so excellent as to lead to its continued use.



The method as suggested by McFarland is very simple. Two bottles with an outlet near the bottom are fitted up with tubes and clamps. This system is to be run up by means of rope and pulley to such a height as will give the gravity pressure required. Simple as the method is, it is very effective. It has, however, the disadvantage of being somewhat inconvenient to handle, and of giving no satisfactory registration of the pressure used, for the pressure varies not alone


'Jour, of App. Microscopy, Vol. II, No. 10.


with the height of the injection flask, but with the specific gravity of the injection mass. Moreover, the method is such an excellent one that some of the more expensive fixing agents were experimented with, which would have been out of the question if one had to fill up an extensive injection apparatus, consisting of a flask and six or seven feet of rubber tubing, with so expensive a fixer as Hermann's fluid, for instance. Still further, it is entirely too difficult to keep so extensive a system as warm as is necessar}' for a fine injection of blood-vessels with carmine gelatin. Therefore connection was made, in the laboratory, with a very effective air-blast run by water pressure, and this in turn gave place to the inexpensive apparatus figured below. As will be seen readil}^, the figure illustrates a blast apparatus. The tube W, leading from a water tap, is attached to a glass tube B, a part of the apparatus. This glass tube B ends at x, a constricted portion of a chamber to which the air has free access through the tube A. Water passing through the system leaves the txihe B at X, drawing along with it a quantity of air into the tube C. The force of the water in this tube C is broken by the cap at its lower end, and the water and air escape through the openings D and D' into the chamber E, out of which there are but two ways of escape, one at F and the other at G. The escape of the water at G is regulated by a screw clamp according to the air pressure desired. In the chamber E, the air, of course, rises to escape at F through the rubber tubing connecting F with the T tube interposed at H, through one arm of which connection is established, J, with the injection flask M, and through the arm K connection is made with the mercury manometer L.

It is obvious that in the chamber E and in the tubes F J K and in the flask M the air pressure is the same, and will be registered on the millimeter scale placed back of the open leg of the manometer.

On this scale the reading is doubled, for the mercury falls


February, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


67


in the closed as much as it rises in the open arm, and the difference between the columns is the sum of the rise plus the fall, or double the rise.

Let us suppose our animal, preferably a young one, killed, the artery exposed, and the ligatures in place ready for tying in the glass canula N. Let us suppose the injection flask filled with 300 or 400 ce. of normal salt solution heated to 38 or 40° C, and the cork in place, through which, by means of a glass tube, connection between J and M is established. Now loosen the screw clamp at just enough to let the 13inch tube and the canula N fill with the injection mass and drive out all the air. Kow cut the artery, insert the canula and tie it in place. Then cut one of the large veins, say the inferior vena cava, to permit the washing out of the vessels, turn on the water at the tap and loosen the clamp at 0. If only a little water is turned on, the water and most of the air escape at G and the air pressure remains very low. Even if the full water pressure is turned on, if the escape at G is too free, considerable air escapes that way and the air pressure remains low. Therefore, when a good flow of water is established, gradually tighten the screw clamp at G, at the same time watching the manometer; the water begins to back up in the chamber E, escape for the air at G is cut off, and the air pressure rises. Thus a balance may be established between the water pressure used and the air pressure.

If the water in the chamber E rises much beyond the openings D D', the clamp at G must be loosened a bit, or the water will back up into the tubes F K J and then over into the flask M.

The limit of the pressure to be secured with this apparatus depends upon the water pressure, which, however, is usually much greater than should be used for injection. It is usually possible to get a pressure of 240 to 250 mm. mercury, i. e., a 5-pound pressure, and as a rule one-fourth of this is sufficient.

When the vascular system is well washed out by the normal salt solution, clamp off the flow at 0, turn off the water at the tap, pour out the remaining normal salt solution, fill the flask as full as desired with the fixing agent heated to 40° C, and again begin the injection.

With this method any rapid fixer may be made use of. It is not always necessary to wash out the blood-vessels with normal salt solution. Fixation is usually better, however, for having done so. With mercuric bichloride it does not so much matter. With formalin and Hermann's fluid, however, it is advantageous for fine fixation. The best fixers have proven to be mercuric bichloride, formalin, Hermann's fluid, and alcohol.

By this method the tissues, after a few minutes bath in warm normal salt solution, are instantly penetrated to the last cell by the fixing agent. The advantages are very great. The tissues, within a few minutes after ansesthetizing the animal (for anaesthetizing, illuminating gas is recommended as being cheap, and causing no salivation), are perfectly fixed in a normal position, at normal distention, and during normal activity. The possibility of post-mortem changes in the


central nervous system is practically eliminated. The processes of digestion and absorption are arrested and fixed in the act, and tissues may thus be secured in any desired stage of physiological activity. Engorged tissues are caught with the blood in them, giving a picture of rare beauty. Blood and bone marrow are perfectly fixed.

For studying bone marrow the ribs of a kitten or baby rabbit fixed with HgCL will decalcify over night in a solution of 3 per cent HNO^ made up with 67 per cent alcohol, and from such ribs, sections 3J^ may be secured easily, giving a picture of bone marrow with its connective-tissue framework normally distended and marrow elements in normal position. On sections so thin an oil immersion objective may be used, blood stains employed, and eosinophilic cells in great numbers may be demonstrated outside the blood-vessels of the bone marrow. Particularly are these marrow elements, together with nucleated red blood corpuscles, shown with great beauty in the ribs of a 10-cm. embryo pig. Bone marrow in this form is a decidedly different tissue from bone marrow studied as a smear.

The thoracic wall of a small white rat, fixed by injection of Hermann's fluid, may be cut at S^/jl without decalcification, and, stained with iron hematoxylin, shows not only marrow elements, but the intercostal muscles and nerves in normal position with the usual beauty of a Hermann's fiuid fixation. In short, we get a penetration with Hermann's fluid impossible by the ordinary method of using it.

There is scarcely a tissue that is not shown with new beauty by this method of fixation. Sections of lung fixed by HgCl^ injection and cut at 3^/i give a picture unequalled in beauty. The epithelial lining is intact and shows the more perfectly in that the tissue is at normal distention.

A brain fixed and hardened in situ presents a very different appearance from a brain supported on a sheet of cotton.

The method is invaluable not only in preparing tissues for classes in histology, but also as a research method.

In the use of HgCL as a fixer by the usual method, the crystalline deposits formed are very annoying and detract from the value of the fixer. This dilficulty is overcome in the simplest manner. At a pressure 130 mm. mercury, 400 cc. of a saturated aqueous solution of HgCL are injected in about 10 minutes into a small kitten or rabbit, the time depending somewhat on the freeness of the venous opening. If the venous opening is not sufficiently free an csdema is likely to be caused, which in some cases is no disadvantage. Follow the injection of the HgCU by an injection of 500 cc. of 67 per cent alcohol. This not merely washes out the HgCl^, but the HgCL is about 3 times as soluble in alcohol of this strength as in water, so the washing out is doubly effective and the hardening of the tissue is begun at the same time. After such a washing out, if properly done, one may cut out whatever tissues desired without blackening the knife or tissues. It is usually best to leave the tissues in 67 per cent alcohol for one day, though, if necessary, they may be transferred at once to 82 per cent alcohol after having been washed out with 67 per cent alcohol.


68


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


It is found best to inject only one-half an animal at once. The canula should be placed in the abdominal aorta with the mouth just above the cceliac axis when injecting the thoracic viscera and head and neck, and low down in the tlioracic aorta when injecting the abdominal viscera. In either case the vena cava should be opened either above or below the liver. It is best to place a block under the back of the animal to insure a free venous outflow.

If the animal is rare or valuable, a double canula may be placed in the abdominal aorta and the whole animal injected at once. After such an injection the whole animal, or the part injected may be left over night in 67 per cent alcohol and then removed to 83 per cent alcohol, which should be changed a few times. Thus a great deal of tissue, excellently prepared in a very short time, may be had on hand for any emergency.

The inner ear of a guinea pig fixed by HgCL injection gives a rarely fine picture on section. After decalcification the cochlea should be laid open by a section passing through the


modiolus. This permits better infiltration and imbedding, with the result that the delicate membranes are held in position by the celloidin when cut and do not present the appearance so often seen of having been dragged.

Tincture of iodine added to the 67 per cent alcohol used in washing out the HgCL showed no noticeable advantage.

A very valuable use of the method is in the preserving of brain tissue. A brain may be fixed in situ by formalin injection, and then removed, the brain stem cut out and placed in potassium dichromate solutions preparatory to sectioning and staining by the Weigert-Pal method. Those who have had the disappointment of having such post-mortem changes take ijlace in the inner capsule and pyramidal tracts, before the penetration of the fixer, as to render the tissue useless, will appreciate the value of this procedure.

Though many uses of the method have been noted they are but a part of the many ways in which the method was found very valuable in the Anatomical Laboratory of the Johns Hopkins University during the past year.


A CONVENIENT STILL TO MAKE ABSOLUTE ALCOHOL

By William J. Calvert, M. D.,

Assistant Professor of Internal Medicine, University of Missouri.


In 1895, while working in the Anatomical Laboratory of the Johns Hopkins University, it occurred to me that the home manufacture of absolute alcohol would be more economical and satisfactory than buying it in small quantities. With permission from Dr. F. P. Mall, a small still was made which for a time gave satisfactory results. This apparatus consisted of an ordinary tin can and an inverted Liebig's condenser for the first portion of the work. When ready for distillation the condenser was changed to the inclined position and the alcohol was caught in an ordinary receiver. While this apparatus gave satisfactory results, it required more care and knowledge for its operation than can ordinarily be placed in an average janitor, already busy with numberless small chores. Since then, an absolute alcohol still has been constructed by Dr. Mall, which requires practically no care or thought on the part of the operator, yields an excellent quality of alcohol, and is inexpensive. The apparatus is made of heavy copper, tinned on the inside, and a block-tin worm. It is composed of a gas-stove, an automatic water-bath, boiler, condenser, and receiver. (Figs. 1 and 5.)

The only especial requisite for the gas-stove is a stop-cock in the supply pipe by which the gas flow may be regulated, thus permitting the stop-cock in the gas main to be turned on full. A stove similar to No. 8157, Eimer and Amend's Catalogue, 1902, p. 211, is satisfactory.

Naturally the size of the still must depend on the amount of work to be done. For making an amount of absolute alcohol used in our universities the following dimensions are


sufficient : a water-bath, eleven inclies in diameter and eleven and one-half inches high, with a substantial support one and one-half inches above its bottom to support the boiler and still, will allow one and one-half inches of water about the sides and bottom of a boiler eight inches in diameter and ten inches high. The support for the boiler should be fastened to the sides and bottom of the bath, with a smaU depression on the upper surface or several small uprights to hold the boiler in one place. The automatic water supply now used on the ordinary water-bath in chemical laboratories is suificient. The connecting tube U should be three-fourths of an inch in diameter and not longer than one-fourth of an inch, placed four inches above the bottom of the bath. The tube V should be one inch in diameter, extend from a point level with top of bath to a point one inch below lower side of tube U, and be well anchored to side of water-bath, near the top. Supply tube X, Fig. 4; sufficiently large to take a one-half inch rubber tube, is inserted at a right angle into the posterior side of tube V two inches from top. One-fourth of an inch from tube V tube Z is bent downward at an angle of 15°; this is to prevent kinking of rubber tube connecting X with C. The height of the water in V is regulated by height of tube W, which is either fastened in V by penetrating a cork stopper or permanently Qxed in a cap to screw on V. Tube W should extend to one inch below top of V, and its lower end should accommodate a one-half inch rubber tube which carries waste water to a sink.

The boiler (Figs. 1 and 5) is eight inches in diameter


Pebkuaky, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


69


and ten inches high from bottom to side Q, which may slope inward and upward at any desired angle. The opening P to P' should be at least four inches; walls of neck N may be parallel or slightly flared at top and two inches high. At top of iV a heavy flange M three-fourths of an inch wide is firmly attached. The top is composed of wall which closely fits into neck N and extends about one-quarter of an inch below the point P and P', with the lower edge slightly flanged inward as shown in the figure, to prevent, as far as possible, capillary attraction between the walls and N. At the top of a flange L, corresponding to flange M, is firmly attached, a sufficient distance above M to admit a rubber or asbestos ring. The top may then be firmly fastened to the boiler by placing



Fig. 1. Median section tlirougli the still.

Fig. 2 shows relative position between tube H, D and C. If the still is placed near or against a wall, tube H should be a little in front of the plane through D so that the cock I may be more easily rsached.

Fig. 3 shows course of block-tin worm from bottom of condenser to J in Fig. 1, seen from below upward.

Fig. 4 is a side view of V, showing tube X.

several simple clamps on flanges. Beginning at top of 0, the wall K extends upward, cone shaped, to an apex J, through which passes the lower end of the block-tin worm A. This joint will be more secure if the tin tube extends about one inch below the apex and is braced as shown in Fig. 1. Immediately above the point J the tin tube bends at almost a right angle and runs in a spiral direction outward and upward to the bottom of the condenser B, the bottom of which should be about one and one-half inches above the point /. The spiral tube is shown in Figs. 2 and 3. In the middle third of tube


F, Fig. 3, is soldered a short piece of tin tubing, in which a stop-cock I is placed, in such a manner as to form a small trap in the bottom of tube F, which must be filled before the alcohol, returning from the condenser, can flow back to the boiler. Fig. 3. This trap is made by removing the bottom and spreading the sides of tube F to receive tube E. Tube H, in Fig. 3, contains a stop-cock, which, when closed, causes the return alcohol from the condenser to fill the trap and flow into the boiler and when open permits the return alcohol to flow through tube H to the absolute alcohol receiver. The lower end of tube H is to receive a three-eighths rubber tube, which in turn connects with a glass tube the lower end of which penetrates a cork in the absolute alcohol receiver, which is an ordinary large bottle.

The worm should be of one-half inch block-tin tubing, the coils of which- should be from one and one-half to two inches



Fig. 5. — Side view of still, one-fourth scale.

apart and three-fourths of an inch from the walls of condenser B. When the coil reaches the top of condenser Bj it should be deflected until the wall of the condenser is reached, here securely fastened and then extend perpendicularly upward four or five inches. Condenser B should be at least five inches in diameter and ten inches high, and firmly attached to top E by four supports, E, E', E". It is necessary to have condenser and top K one rigid piece to prevent straining the block-tin tube and disarranging the trap in tube F. Near the bottom of the condenser is a cold water intake 0, for threeeighths rubber tubing, with stop-cock. On the opposite side one inch from top of condenser is an outflow pipe, C, for a onehalf inch rubber tube. One-fourth of an inch from condenser, tubes C and D are deflected at 45° to prevent tubing from kinldng. Across the top of condenser run two bars at right angles for supporting a handle to which is attached a rope which runs over a small pulley flxed in a bracket a few inches above the condenser. By means of this rope and pulley the condenser is raised so that the wall of top clears wall N


70


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


of boiler and is then pushed to one side, so the boiler may be removed from the bath for cleaning and reiilling. If the condenser is thus handled there is no danger of injuring the joint between and N. The rubber tubing connecting the intake D with the water main and tube C with tube X must be sufficiently long to permit the condenser to swing free of the boiler.

The cheapest method of abstracting water from alcohol is by using fresh well burnt lime, quick lime according to the formula CaO + S^O = Ca{0H)2, which when expressed in atomic weight values is 55.85; 17.95 or 3.11 grams of quick lime for each gram of water. Ordinary commercial 95 per cent alcohol varies from 92 to 95 per cent alcohol, so contains from 5 to 8 grams of water per 100 cc. For safety it is best to calculate 5 grams of lime for each gram of water and allow for 10 cc. of water per 100 cc. of alcohol. On this basis it requires 500 grams of lime per liter or about four pounds of lime per gallon of alcohol.

Directions for operating the apparatus : The boiler is threefourths filled with lime and 95 per cent alcohol, placed in the water bath, tightly connected with the condenser and allowed to stand over night. On the following morning the bath is heated to, and kept at, about 90° to 93° C. During the first two or three trials the stove must be regulated by the stop-cock in the gas stove, keeping the valve at the gas main open full. When the gas supply has been regulated the valve in stove must remain untouched. The supply of water is regulated by the valve at D, keeping the valve on the water main open full. In this way when the apparatus is to be used instructions are to put — grams or pounds of lime and — quarts of 95 per cent alcohol in boiler, tightly connect boiler


and condenser, close valve /, allow to stand over night, in morning open water main valve and gas main valve full, light stove ; in afternoon, shut off gas and water ; next morning open water main and gas main valve full, light stove and open valve /. When alcohol ceases to flow into absolute alcohol receiver remove and tightly cork the absolute alcohol and immediately clean the boiler. If the lime is allowed to remain in boiler it may be difficult to remove.

Cost of absolute alcohol made in this way is about as follows. From 50 to 75 per cent of 95 per cent alcohol is recovered as absolute :

1 gallon absolute costs,

2 gallons of 95 per cent, at 50 cents . . . .$1.00

8 lbs. of lime at from 3 to 4 cents 24

About 100 ft. gas 15

Water, about 10

$1.49

The cost in 95 per cent alcohol depends on the care in operating. If too much heat is used the loss will be greater. During the first day the alcohol need not boil, as a temperature near the boiling point will complete the reaction.

This still may also be used for making extracts, etc., and can be made of any desired capacity.

If the trap pictured in Fig. 3 be blown in a glass tube which could be connected with an ordinary Liebig's condenser a very convenient chemical apparatus would be had.

A number of these stills have been manufactured by Vaile and Young, 210 N. Calvert street, Baltimore, at a cost of about $25 each.


ANNOUNCEMENT CONCERNING GRADUATE INSTRUCTION IN THE MEDICAL DEPARTMENT

OF THE JOHNS HOPKINS UNIVERSITY.

By W. H. Howell, M. D., Dean of the Medical Faculty.


The courses that have been offered to gi-aduates in medicine by the Johns Hopkins University, since the opening of the Hospital in 1889, consisted in the beginning of a combination of general courses, laboratory and clinical, so arranged as to give systematic instruction to large groups of students. In recent years these courses have been given only during the months of May and June, and it has been found desirable to supplant the general courses, to a large extent, by special courses confined to a limited number of students. Although designated as graduate courses, the instruction has been for the most part of an elementary character, especially in the laboratory work, as many of those who entered had not enjoyed the advantages of a training in modern scientific methods. Our experience during the last few years, however, leads us to believe that at present there is no great need on the part of


graduates for elementary courses of this character. The wide adoption of laboratory methods in all of our reputable medical colleges, and the general improvement in medical iastruction that has been going on for a niimber of years past, have produced a better trained body of graduates, and those who desire to take post-graduate work are, as a rule, prepared for more special and advanced instruction. The Medical Faculty of the Johns Hopkins University believe, therefore, that the time has come to make specific provision for a higher grade of instruction to medical graduates. They have decided to abandon for the most part those systematic courses heretofore given in May and June, of which the chief aim was to supplement deficiencies in previous training. As a substitute for these May and June courses they propose to offer opportunities of a wider character which, while still


Febeuaet, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


71


giving to those who so desire a chance to obtain elementary instruction, are especially intended to encourage the development of truly graduate work, such as can be accomplished most satisfactorily by individual study under competent direction. Specific regulations along these lines have been adopted and will be stated in full in the next annual announcement.

For the information of those who may desire to avail themselves of the facilities of the Medical School and the Hospital during the present session, it may be said that these regulations make possible the following opportunities :

1. In each department a limited number of graduates will be received during the whole or a part of the year, either to engage in advanced work of an individual character or to enter the regular courses given to undergraduates. Applications to enter upon such work should be made directly to the Head of the Department.

2. Each instructor in the Medical School may offer to graduates special courses in his subject at any time during the year. These courses may be similar to those heretofore offered during May and June only, that is, courses of a more or less elementary character, but limited to a small number of students so that personal supervision may be obtained from the instructor, or they may be arranged only for those who are prepared to do advanced work.

For the present the following courses may be announced. Those coming under the first group described are designated as University Courses, while those of shorter duration, coming under the second head, are designated as Special Courses. For further details, application may be made to the Dean of the Medical Department.

UNIVEKSITY COUESES.

These courses are of two kinds, elementary and advanced. The elementary courses will cover the subject as usually given to undergraduates in medicine and the work may be done with the medical classes. The advanced courses will be given only to those who are prepared to undertake special studies, and the work will be done under the personal supervision of the instructor in charge of the course.

Medicine, Elementary. A limited number of physicians will be admitted to the regular class exercises in this subject, including ward rounds, clinics and work in the clinical laboratory. Fee $100.00 for the entire year; $50.00 for a half year. Applications should be made to Professor Osier.

Medicine, Advanced. Physicians properly trained in the methods of clinical diagnosis will be given opportunities for experimental investigation in the clinical laboratory. Fee $50.00 for the year. Applications should be made to Dr. C. P. Emerson.

Gynecological PATJiOLOOT, Elementary. (Limited to three students.) Drs. Cullen and Hurdon.

The work in this course begins October 1 and extends to May 1. The class meets Tuesdays and Thursdays,


13 m. to 1 p. m. Fee $50.00. Applications for this course should be sent to Professor T. S. Cullen not later than September 15.

Obstetrics, Advanced. A limited number of physicians will be received for advanced instruction under Professor Williams during the Academic year — October to June. Those intending to enter upon this work should apply to Professor Williams stating the character of the work they desire and their qualifications for undertaking it. Fee $50.00

Pathology of the Heart and Circulatory System, Advanced. (Limited to five students.) Professor W. G. MacCallum. The course will begin October 9 and continue for fivt; weeks, with three exercises a week.

These exercises will consist of lectures, experiments on animals, and anatomical, chemical and microscopical demonstrations. The following topics will be considered : Diseases of the pericardium, diseases of the endocardium and myocardium, pathology of the pulmonary circulation, pathology of the systemic circulation, pathology of the lymphatic channels. Fee $30.00. Those desiring to take the course should correspond directly with Professor MacCallum.

Pathology, Elementary. A limited number of physicians will be received during the year in the courses in bacteriology and pathology. Fee for the entire year $50.00, fee for half year $25.00. Apply to Professor W. H. Welch.

Pharmacology and Toxicology, Elementary. January 1 to June.

A limited number of physicians will be received into the regular course as outlined in the catalogue of the Medical School. Fee $25.00. Apply to Professor J. J. Abel.

Pharmacology and Toxicology, Advanced. Professor Abel.

Those who have had the necessary preliminary training and who desire to do work of a special character will be received at any time during the Academic year. Fee $50.00 for the entire year.

Physiology, Elementary. (Limited to four.) Laboratory course in experimental physiology, October to December 25.

The work will consist in exercises in the various graphic methods used in physiology to study the properties of muscle and nerve and the circulatory and the respiratory organs. Fee $25.00. Apply to Professor W. H. Howell.

Physiology, Advanced. (Limited to two.) January to June 1. Professor Howell.

Individual instruction will be given in the methods used in physiological demonstrations and research. Especial attention will be paid to the methods employed in the study of the circulation. Fee $50.00.


72


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 167.


Anatomy, Advanced. Those who have had the necessary preliminary training and desire to undertalie the study of special problems, will be received at any time during the Academic year. Fee $25.00. Apply to Professor P. P. Mall.

Histology and Okganology, Elementary. Professor Harrison, Drs. Sabin and Knower, October 1 to February 15, Monday, Wednesday and Friday afternoons. (Limited to three.) Fee $50.00.

Neurology, Elementary. A systematic course in the gross and microscopic anatomy of the central nervous system, from February 1 to March 15. Lectures, Dr. Sabin, three hours a week; laboratory work. Dr. Sabin, Professor Harrison, Drs. Knower and Streeter, Monday, Wednesday and Friday afternoons. (Limited to five.) Fee $25.00.

Neurology, Advanced. (Limited to two.) Dr. Sabin, March 15 to June 1, forenoons.

The work will take up special topics in the development and structure of the central nervous system. Fee $25.00.

Neurological Technique, Advanced. (Limited to two.) Dr. Streeter, March 15 to June 1. A knowledge of general histological technique will be assumed. Fee $35.00.

Embryology, Elementary. (Limited to two.) Dr. Knower, March 15 to June 1.

A laboratory course in the development of the mammalian body as illustrated by pig and human embryos. Fee $25.00.

Human Embryology, Advanced. Professor P. P. Mall, October Ito June 1. (Limited to two.) Fee $25.00.

Experimental Embryology, Advanced and Research. Professor Harrison, March 15 to June 1. (Limited to two.) Fee $25.00.

Physiological Chemistry, Elementary. March 15 to June 1, every afternoon.

A limited number of physicians or others who have had the requisite preliminary training in chemistry will be received for the laboratory course and lectures given to the medical students. Fee $25.00. Apply to Professor Walter Jones. Physiological Chemistry, Advanced. Professors Abel and Jones.

Those who have the necessary preliminary training and who desire to do work of a special character will be received at any time during the Academic year. Fee $50.00, for the entire year.

SPECIAL COUESES.

Medicine. Drs. McCrae, Cole and Boggs, June 1 to July 1. (Limited to fifteen.) Fee $100.00. The course will not be given if less than eight register.


Api)lications for this course must be sent in not later

than May 10.

The whole material of the medical service will be

available for the class. Special attention will be given

to the study of the general methods used in the clinic. The course consists of:

I. Ward Rounds. Drs. McCrae and Cole, from 9 to 11 daily. Special attention will be given to diseases of the circulatory and digestive systems. II. Physical Diagnosis. Dr. McCrae, five hours a week. The general methods of diagnosis will be taken up and special attention given to diseases of the thoracic and abdominal organs. III. Clinical Microscopy and Medical Bacteriology. Dr. Boggs, three afternoons — 9 hours a week. This course consists of lectures, demonstrations and especially of practical work. All of the available specimens of blood, urine, sputum, gastric contents and stools are studied. The ordinary methods of clinical bacteriology will be demonstrated.

Pediatrics. Dr. S. Amberg, June 1 to August 1, daily from 11 to 13, Dispensary. (Limited to eight.) Fee $40.00. The participants are expected to examine patients personally under supervision.

Surgical Pathology. Professor Bloodgood. This course is given three times during the year, as follows: Course I, October 10 to December 30 ; Course II, January 10 to April 20; Course III, May 2 to June 30. (Each course will be limited to twelve.) Fee $50.00. The course consists of:

a. Systematic instruction in clinical and pathological

diagnosis, illustrated by pamphlets, photographs, museum specimens, and microscopic sections.

b. Demonstrations on all fresh material received in the

Surgical Pathological Laboratory.

Demonstrations, October to May, Tuesdays, 3 : 30 p. m. to 4:30 p. m. ; Wednesdays and Fridays, 1 : 30 to 3 : 30 p. m. Demonstrations in May and June, Tuesdays, Thursdays and Fridays, 8 to 9 a. m. Students taking this course should plan to give at least three hours a day to the work. Operative Surgery on Animals. Professor Gushing, April 39 to June 31, Wednesdays and Saturdays. Sixteen exercises of from four to five hours each, commencing at 8 : 30 a. m. (Limited to ten.) Fee $60.00.

The course will be limited to ten graduate students who will be divided into two groups of five, thus making up two complete operating staffs, an operator, first and second assistant, anaesthetist, and attendant. The members of the class rotate in these positions during the various exercises. An effort is made to carry out as closely as possible the same technique that is used in the general operating room of the Hospital. The graduates taking the course do all of the operative work themselves.


February, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


73


Emphasis will be laid upon methods of operating in general, rather than upon any particular operations. A schedule of the exercises showing the operations performed will be furnished on application.

Genito-Urinary Surgery. Professor Young. Fee $100.00. A limited number of graduates will be taken for special work in Genito-Urinar}' Surgery. The course will include clinical and laboratory work and the student is expected to give his entire time, or most of it, to the department, and to enter for six months or more. Eesearch studies will be encouraged.

Orthopedic Sdrgeet. Dr. Baer, May 15 to August 1, Monday, Wednesday, Thursday and Saturday, 10 to 12 m. (Limited to ten.) Fee $50.00.

A course will be given in the Orthopedic Dispensary from 10 to 12 m. on the days noted in which the students will be given practical work in the diagnosis and treatment of all orthopedic affections. Ward rounds covering this class of cases will be made from 9 to 12 on Monday mornings. Opportunities at this and other hospitals will be posted during the course so that one may be able to see practically all orthopedic operations.

X-Eay Diagnosis and Therapeutics. Dr. Baetjer. This course is given three times during the year as follows ; Course I, October 15 to December 15; Course II, January 15 to March 15; Course III, April 15 to June 15. (Limited to five in each course.) Fee for each course, $50.00.

Each course will consist of daily demonstrations from 11 a. m. to 12 :30 p. m., and the aim of the course is to give a practical Imowledge of the construction of the X-Ray apparatus, and its use in diagnosis and treatment.

Gynecological Pathology. Professor CuUen, during March and April, Tuesday and Thursday, 12 to 1 p. m. Pathological Laboratory. (Limited to ten.) Fee $50.00. A course in the diagnosis of uterine scrapings. All pathological conditions of the cervix and body of the uterus that could be mistaken for cancer are discussed, and special consideration is given to the early diagnosis


of cancer of the uterus. The methods of obtaining and examining pieces of uterine tissue are given in detail. Cystoscopic Examinations. Dr. Hunner, Monday and Friday, 2 to 4 p. m. May 12 to July 30, inclusive. (Limited to six.) Fee $50.00.

Fifteen clinics covering the entire subject of diseases of the urinary tract in woman. Demonstrations of the newer instruments used in urinary work.

This course is for beginners in cystoscopy.

Bacteriology, Elementary. Dr. Ford, May 1 to June 1. Three mornings a week. (Limited to ten.) The character of the work will be adapted to the needs of the class. The course will include instruction in: 1. Elementary Bacteriology. 2. Sanitary Bacteriology, including water and milk. 3. Technique of agglutination, hremolysis and immunization of smaller animals. Fee $50.00. Pathology, Elementary. Dr. Bunting, May 1 to July 1. (Limited to ten.) Three afternoons a week. Lecture and laboratory exercises in general pathological histology. The course will not be given if less than five register. Applications must be received before April 15. Fee $50.00. Ophthalmoscopy and Ophthalmology. Dr. Mills, June 1 to July 1, Monday, Wednesday and Friday, 3 to 4 p. m. (Limited to ten.) Fee $25.00. This course is intended for general practitioners. Gross Anatomy. Professor Lewis, October 1 to June 1, hours arranged with the instructor. Fee $25.00 per month.

Dissection, study of prepared specimens and of frozen sections.

REGISTRATION. Before entering upon any of these courses of graduate instruction the student must register at the Office of the Dean of the j\Iedical School. Upon payment of the requisite fees a card will be issued stating the courses which the holder is permitted to take. This card must be presented to the instructor in charge of each course at the beginning of the classwork in order that the holder may be duly recognized as a member of the class.


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


Vol. XVI.-No. 16 8.


BALTIMORE, MARCH, 1905.

CONTENTS - March

  • The Special Field of Neurological Surgery. M. D., Hakvet Gushing, 87
  • Tumor of the Parathyroid Gland. By W. G. MacCallcm, M.D.,
  • Bacillus Violaceus Manilae. By Paul G. Woolley, M. D., ... 89
  • A Report Upon the Agglutination Reactions of the Bacillus Dysenteriae (Shiga) with the Blood Serum of Patients Suffering with Summer Diarrhoea. By Charles K. Winne, Jk., M. D., . . 93
  • Repeated Copious Haemoptysis from an Aortic Aneurism, Extending into the Right Lung aud Finally Rupturing into the Pleura. By Thomas Wood Clarke, M. D., . . . , 98
  • A Case of Ciesarean Section Following Ventral Fixation. By Alfred Hull Clark, JI. D., and Robert Lee Bowley, M. D., ... 101
  • A Survey of Ovariotomy at Extremes of Life. Report of a Case in a Girl Aged 5. By Harry I. Wikl 102

Proceedings of Societies :

The Johns Hopkins Hospital Medical Society, 109

Loss of Entire Lower Lip. Repair by Flap from the Arm [Dk. Watts] ; — Report of Cases: Adeno-carcinoma of the Umbilicus; Cancer of Liver; Melanotic Sarcoma with Metastases [Dr. Collen] ; — Recurring Phlebitis of Obscure Origin |Dr. BriggsI ; — Demonstration of Pathological Specimens IDr. MacCallum]; — Biliary Cirrhosis of Family Type [Dr. OslerI; — Crossed Dissociated Sensory Paralysis with Lesion of Medulla IDr. Thomas]; — Situs Transversus and Atresia of the Pylorus [Dk. Little and Mr. Helmholz] ; — Experimental Streptococcus Arthritis [Dr. Cole] ; — Professor Smith on the Jersey Mosquito [Dr. Kellt];— Gastric Ulcer: Clinical Varieties and Symptoms [Dr. Howard]; — Gastric Ulcer: Diagnosis and Medical Treatment [Dr. McCrae] ; — Report of a Case of Ulcerative Endocarditis, with Embolism of the Aorta [Dk. OslerI; — Case of Typhoid Fever Showing Some Unusual Features [Dr. Cole]; — Puerperal Infection with Gas Bacillus [Dk. Little] ; — Report of a Case of Arteriovenous Aneurism of the Thigh IDr. Osler]; — Survey of Ovariotomy at Extremes of Life. Report of a Case in a Child aged Five [Mr. H. I. Wiel|.

Notes on New Books, 120


THE SPECIAL FIELD OF NEUROLOGICAL SURGERY

By Harvey Gushing, M. D., Associate Professor of Surgery, The Johns HopHns University.


Genilenieii : — In response to the friendly request of Dr. Crile, your presiding officer, I shall attempt to formulate some personal views concerning a branch of surgery, which, in this country at least, largely owing to the allurement of other and more immediately promising fields of operative endeavor, has hardly received the attention it deserves.

Through the generosity of Dr. Halsted, his junior associates have been given, in a measure, the privilege of directing the work in some of the subdivisions of his large surgical clinic, in order that they may concentrate their efforts toward advancement along particular lines. It has thus fallen to my lot, temporarily and under his guidance, to control the group of cases which present features chiefly of neurological interest; and it is upon the present possibilities and limitations, as well as upon the future outlook for this department of surgery, that I shall briefly dwell tonight.

To many of us as students, neurology was the pons asinorum of the medical curriculum. Nor can I recall any very earnest efforts to cross the bridge, particularly by those of us

' An Address delivered before the Academy of IMedlcine of Cleveland, November 18, 1904. Reprinted from the Cleveland Medical Journal, January, 1905.


whose ability to visualize lesions, that probably had never been seen under the microscope nor handled in the gross, was — to say the least — not abnormally developed; and who, for the stimulation of their interest, needed certainties of diagnosis and assurances of therapeutic results. Even for a student, whose inclinations from the beginning may tend in this direction, a steady prosecution of the subject is beset with great discouragements. Special training is necessary before one can obtain a working knowledge of the imderlying pathological processes, without which the clinical superstructure is built upon sand. The morbid anatomy of the lesions is greatly obscured by the imperfections of our methods of examination, but still more because they are but rarely seen except at the autopsy table and then only in their terminal stages. Furthermore, owing to the technical difficulties of our present laboratory methods, so long a time often elapses before the histological alterations in the tissues are demonstrable, that, in the interim, our recollection of the clinical picture has become dimmed and interest has fled elsewhere. That the morbid physiology of the subject — its experimental side — when compared with the researches that have been made in other directions, has hardly been touched, may be a matter of


78


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 168.


regret, but can hardly surprise us when we consider that the normal structure and function of many parts of the nervous system remain as yet unknown. Finally, the privilege of regarding as historic the days when there existed " a plague of drugs .... least mischievous when merely superfluous," and which a century ago evoked the well-known aphorism of Eenjatain Franklin — "He is the best physician who Icnows the worthlessness of the most medicines " — carries with it a satisfaction that is not without alloy. For what eager student of medicine can face without dismay the " poverty of therapy " that characterizes the present day, and which is emphasized more especially in the neurological clinic, which stands largely on the therapeutic tripod of iodine, bromine and electricity.

Will a more general application of surgical methods offer anything for this department in the way of diminishing the present number of the medicinally incurable, or of improving the condition of those whose maladies time alone, not medicine, restores to a certain degree? Certainly not, while the neurologist and surgeon maintain the same distant relations that have heretofore existed between them. Aware, so far as one who does not operate can be, of the possibilities of surgical therapy in a given condition, the neurologist spends days or weeks in working out the presumable location and nature of, let us say, a cerebral tumor. An operator is called in ; he has little knowledge of maladies of this nature and less interest in them, but is willing to undertake the exploration. The supposed site of the growth is marked out for him on the scalp by the neurologist; and he proceeds to trephine. The dura is opened hesitatingly ; the cortex is exposed, and too often no tumor is found. The operator's interest ceases with the exploration, and for the patient the common sequel is a hernia, a fungus cerebri, meningitis and death. But should this be a matter for surprise? Does the internist deem it his duty to instruct an operator in the mysteries of an abdominal tumor and show him where and how to make his exploration ? Does he not demand that the surgeon should be as familiar with the symptomatology and the underlying morbid factors of the disease as he is himself? Certainly the relationship between the internist and the general surgeon is far closer than it was in the days of the professional herniotomist, whose instruments were looked over and who was directed in the course of his operation by the physician.

I take it that we all are, or should be, branches gro^Ti from the common stem of Jledicine — in the broad Hippocratic meaning of the term — and nourished through the roots of General Pathology. And whether one chooses to follow lines of surgical therapy in his own subject, and another not, is purely a matter of personal inclination and manual training. Nor is it less true, I think, of any individual branch of this parent stem than of the tree itself, that, without flourishing surgical twigs, it will, like Dean Swift's noble elm, die at the top.^


' " The chief lesson of the Hippocratic period for us is that, in practice as in honor, medicine and surgery were then one; the Greek physician had no more scruple in using his hands in \he


But why this long preamble? Because it seems clear that in order to advance surgical measures, whether they are to deal with diseases of the nervous system, the deformities of children, the maladies peculiar to women, genito-urinary diseases, or those belonging to any other more or less limited branch, specialization, or better, concentration of thoughts and energies along given lines is necessary. Why are we so slow to understand that we cannot graft an independent twig of operative surgery on any of the branches of this huge medical tree and have it grow undeformed? Original growth from the main stem of general medicine and surgery is necessary, but some at least of those whose inclinations follow the branch of neui-ology, must do their own surgery, if it is to aid in the development of their therapy, and not depend on the help supplied by the lukewarm assistance of other departments.

To successfully cope with the many operative problems offered by the various disorders of the nervous system, a man, after a thorough training in pathology and medicine (in its broadest sense) must study, not only in the neurological clinic but also in the laboratory, the pathologv^ of these afflictions in their histological and — what is still more important — in their experimental aspects. Any one who like myself has passed from general surgery into this special branch without this preliminarj^ training, finds himself but ill prepared for his new work and must be satisfied to merely follow the lead of others, as I have largely had to do.

Though a surgeon possesses a natural tendency towards handicraft in matters therapeutic, I do not wish to be considered as one who distorts neurological problems by viewing them with an operative strabismus uncorrected by the proper spectacles. I wish merely, so far as my time allows, to point out some of the present possibilities of affording surgical relief in certain maladies for which the outlook is otherwise most forlorn, and at the same time to lay stress on certain points that give us hope for the future. I shall keep away, so far as possible, from beaten paths; for that a cerebral abscess should be evacuated, a ruptured meningeal vessel tied, the spinal cord relieved from pressure, and a severed nerve sutured, has long needed no comment.

The Buain axd its Envelopes.

At the outset something may be said relative to the surgery of cerebral tumors. A very natural reaction followed after it became generally known how unsatisfactory had been the results in the early series of cases, so enthusiastically undertaken when for the first time aseptic processes had permitted surgeons to perform craniotomies with a certain assurance — so


service of his brains than had Phidias or Archimedes; and it was by this co-operation in the fifth century that the advance was achieved which in our eyes is marvellous. As we pursue the history of medicine In later times we shall see the error, the blindness, and the vanity of physicians who neglected and despised a noble handicraft. The clear eyes of the ancient Greeks perceived that an art is not liberal or illiberal by its manipulations, but by its ends." — Clifford Allbutt. An Address on the Historical Relations between Surgery and Medicine. The Congress of Arts and Sciences, St. Louis, Sept. 27, 1904.


March, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


79


far as wound healing was concerned — of operative safety. In 1891, Agnew concluded an admirable paper on the subject with the words, " it is more than probable that, as our observations multiply, the sphere of the trephine, as a preliminary m.easure for the removal of brain tumors, will be lessened rather than amplified." And this from the city which, perhaps above all others, has since contributed the greatest number of successful cases ! Von Bergmann's discouraging views are too well known to repeat here, and I doubt not that his opinion has done more than any other single factor to keep the surgery of this particular group of cases at a standstill : just as the views of the physiologist Flourens — that all parts of the cortex have precisely the same signification — so long retarded the studies of cerebral localization. Happily for us things are far different today. Not only has the localization of the more approachable parts of the cortex — after a long series of researches culminating in Flechsig's anatomical observations " and in the experimental researches of Sherrington and his co-workers,* — been put on a working basis for us, but also through the enormous strides in operative technique, particularly through Wagner's osteoplastic method of resection, we are now able to bring under observation extensive portions of the cerebral surface. In the earlier days of cranial surgery, it must be remembered, lesions in the motor area of the cortex were about the only ones that were considered approachable, and when we realize how far afield the experimentalists had gone in delimiting the " motor cortex " and, guided solely by calculations of the Rolandic area made upon the scalp, through what small trephine openings operators attempted to disclose underlying growths, it is little wonder that failures were almost universal. Today the reports of successful extirpations ° are becoming more and more frequent.

Happily also a perfect functional restoration has taken place in many cases, for we now know that a considerable percentage of the growths originate in the meninges and, being by nature non-infiltrating, damage the cerebrum by a compressive invasion alone.

It is, however, upon another and less thoroughly ventilated aspect of the subject that I wish to dwell, namely upon the performance of palliative operations both for the supposedly inaccessible growths as well as for those which in the light of our present knowledge still remain non-localizable. In affording a measure of relief "to these distressing cases, one may fulfill the chief of his duties as a physician — to prolong life and at the same time alleviate suffering. For the mere


' Paul Flechsig, " Einige Bemerkungen iiber die Untersuchungsmethoden der Grosshirnrinde, insbesondere des Menschen." Berichten der matheniatisch-physischen Klasse der Konigl. Sachs. Gesellschaft der Wissenschaften zu Leipzig. Sitzung vom 11 Jan., 1904.

Grunbaum and Sherrington. The Cerebral Cortex of the Higher Apes. Proceedings of the Royal See, 1901.

° Even of growths from situations, which a few years ago were considered inaccessible; such as the " lateral-recess," tumors (cerebello-pontine), of which Sir Victor Horsley has had a considerable series. It is not impossible that a diseased pituitary body may some day be successfully attacked.


lengthening of a patient's months or years without rendering them more livable, is, as Dr. Fitz has so emphatically pointed out, no justification whatsoever of an operative procedure."

The triad of symptoms, the profound headache, the vomiting, and sooner or later the stasis papillse with ensuing loss of vision, are due to the increased tension and consequent disturbance of circulation within the closed box of the skull. Whatever and wherever be the lesion itself — whether there be a simple growth located in a hemisphere, another which obstructs in some way the outflow of cerebro-spinal fluid, a ventricular dilatation from inflammatory causes, or circulatory disturbances from a longitudinal sinus thrombosis — in all cases the tension phenomena are the same, varying only in degree and in their time of onset. The symptoms of a localizing nature whether motor, sensory, visual, psychic,' or what not, that may be superimposed on this triad, bear no necessary relation to the headache, vomiting and ocular symptoms, which, if unrelieved, cause perpetual suffering, lead to blindness, and finally are responsible for death itself, except in those rare instances of direct implication of some vital center in a spreading lesion. Complete relief to these symptoms may be brought about, and brought about promptly, in the vast majority of cases by the " decompression " of a palliative craniectomy as many neurologists ' and surgeons have emphasized, and patients may go on for months or possibly years, free from pain, and best of all, with their eyesight preserved.

I have at the present time several of these cases under observation, patients who before the operation were bed-ridden and suffering invalids. Two of them have been able to return to their occupations; some others, sad to relate, though comfortable, are practically blind owing to the long postponement of the decompression. And it is for the preservation of vision, particularly in these cases in which the intellectual faculties are in no way disturbed, that the operation should be resorted


° R. H. Fitz. Some Surgical Tendencies from a Medical Point of View. Boston Medical and Surgical Journal, Vol. 145, Dec. 19, 1901.

" Any operation which does not better the condition of the patient must be regarded as a therapeutic error, since the knowledge thus obtained shows that the operation should not have been performed."

' The cases with superimposed psychic symptoms, indicating as they do lesions of the frontal lobes, frequently end their days in asylums for the insane. The recent report by Blackburn (" Intracranial Tumors among the Insane," 1903, Gov. Printing Office, Washington) from the Government Hospital for the Insane, records the discovery, in their series of autopsies, of 28 true tumors, of which 17 were of the so-called " endothelial sarcoma " variety; that is, they were comparatively benign growths, originating from the meninges and many of them distinctly operable.

"Thus Alfred Sanger of Hamburg, in a paper (Ueber die Palliativ-operation des Schadels bei inoperablen Hirntumoren) read before the German Surgical Congress, says: " In short, palliative trepanation in case of cerebral tumor is an operation which even if not absolutely free from danger, is of extraordinary blessedness, and, in the hands of a practiced surgeon, one that I would like to recommend in every case, in consideration of the impotency of internal medicine and in view of the distressful (qualvollen) suffering, and above all of the menacing blindness."


80


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 168.


to promptly, that is, as early as possible after the diagnosis of probable brain tumor has been made.

The dread of the operating room, which many doctors share with their patients, together with the supposed uncertainties of an exploration, has led and still leads to one invariable course of treatment, large doses of the iodides being given with the vague hope that lues venerea may be at the bottom of the trouble. But even should there be definite grounds for this suspicion, the indications for an operation in many eases are none the less clear. In the first place, many, perhaps the largest proportion, of the gummata are superficial, accessible, and when exposed easily enucleated : they are, furthermore, very resistant to the usual antisyphilitic therapy, and, during the necessarily long term of treatment, the experience of watching a choked disc going on to a more or less complete optic atrophy, or of seeing other troubles supervene, is by no means uncommon. Some time ago I had under my care a patient, known to have had syphilis, and who presented symptoms of a cerebral growth, presumably an approachable one, since irritative motor phenomena of a Jacksonian character were superimposed. It was deemed advisable, on consultation, to prolong still further the use of mercury and potassium iodide, though these drugs had already been given a fair trial, with only a modicum of relief. The woman died suddenly one night in status epilepticus and at the autopsy a cortical gumma was found in the situation expected. Such experiences should teach us that, unless the intracranial symptoms, in cases of tliis sort, subside very rapidly under the treatment, a more prolonged trial of these drugs had better be reserved for the post-operative period. Moreover it must not be forgotten that symptoms occasioned by non-luetic processes, often for a time show a marked amelioration under these every-day measures, so that, unless we are on our guard, we may easily be led astray in our conclusions based upon these so-called therapeutic aids to diagnosis.

A palliative trepanation, although in itself not a very difficult operation, demands not a little forethought as well as manipulative skill. When there is no expectation of finding a growth and when the operation is to be carried out for decompressive purposes only, the site must be carefully chosen, for the hernia which necessarily results, and which is meant to act as a " safety valve " for the compressed brain, strangulates practically all function out of that portion of the cerebrum which protrudes. For this reason we must be careful lest, in relieving the patient of his pain, we substitute some serious form of paralysis. A more or less silent field of the cortex, therefore, should be selected. A relatively wide area of bone must be removed, its extent depending upon the degree of tension found at operation. The dura should be left open, after being slit up in a stellate fashion to the edge of the wound, or better still cut away entirely; otherwise there may be local pain resulting from pressure by the hernia which may crowd this sensitive membrane against the edge of the bone. Even to the painstaking final approximation of the scalp wound, every detail of the operation and of the local aftertreatment must be followed out with the greatest care, if one


wishes to avoid that most distressing of all complications, a fungus cerebri, which I am happy to say has occurred to me only twice in a long series of operations. In some cases of " silent " basilar tumors leading to an obstruction of the ventricular outflow the hernise have rapidly grown to be almost as large as the patient's head without any parting of the scar.'

The particular form of decompressive operation which has proved most serviceable in the majority of the recent cases of non-loealizable growths, is an inter-muscular one, sometimes conducted bilaterally, through the temporal region, with the removal of the squamous portion of the os temporale and closure of the muscle and its fascia over the denuded brain. But of the details of this procedure, more will be said in another paper.

I shall now pass on to the consideration of another large group of cases, those in which the symptoms are due to intracranial hemorrhage. Certain of these, more particularly the extradural forms of circumscribed effusion, which are usually due to the laceration of a branch of the meningeal artery, have long been recognized as distinctly and urgently operable. Interference with other varieties of hemorrhage is less commonly advocated. Nevertheless, we are coming to feel that the diffuse subdural hemorrhage associated with fracture ol the base of the skull, the hemorrhage which occurs in the newborn — both of which usually follow the rupture of veins alone — and also the arterial hemorrhages of the adult into the substance of the brain, in selected cases, are as properly and advisedly attacked surgically as are the more accessible, localizable, and easily treated effusions of the blood.

In the diffuse bleeding from traumatic basal fractures, which in most ciises can readily be differentiated from the extradural form by means of a lumbar puncture, there often is urgent need for decompression with the evacuation of clots, and drainage, if there is a continuance of the bleeding. In these eases also, the operation mentioned above has been found to be the most convenient means of approach. Of course it is not always possible to save these patients when the extravasation is large and especially when it is associated with a serious contusion of the brain. Nevertheless, trepanation will go a long way toward warding off the later compression effects produced by traumatic oedema, which, in the light of Cannon's experiments, is doubtless responsible for many of the fatalities.

Some months ago during a race, two young men were thrown from a tandem motor-cycle, and both sustained severe cranial injuries. They were brought to the hospital, unconscious. Bloody fluid was withdrawn from the lumbar subarachnoid space of each patient. One of them, apparently the more severely injured, was trephined low down in the skull, and bloody fluid with clots in considerable amount was evac


" Many of the technical details, found to be best adapted to my personal needs in performing cranial operations, and in avoiding local post-operative complications, have been described elsewhere. (Pneumatic Tourniquets, etc. The Medical News, March 26, 1904.)


March, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


81


uated; the other was left alone. The former patient was np in 48 hours, after the operation; he was entirely free from symptoms, left the hospital early, and would probably have been well, today, had he not a short time later died the almost inevitable traumatic death of a motor-cycle pace-maker. The other patient remained in the hospital for a month, during which time he complained of headache, dizziness and the usual familiar sequels of these injuries, from which he has never become entirely free.

To cite a second case : A young man was tilted out of the back seat of a wagon by the unexpected starting of the vehicle, and landed upon the back of his head on the hard road. After some hours of unconsciousness he was found to have a homonymous hemianopsia and aphasia. Instead of investigating the cause of these symptoms, presumably due to local hemorrhages in the right occipital lobe, and, by contrecoup, in the left inferior frontal region, his physician, owing to the fact that there was neither a scalp wound nor any external evidence of fracture, and because the patient was making a progressive though slow improvement, decided against operation. Two months later there occurred an epileptic attack with a peculiar uncontrollable motor-speech (jargon) aura. These attacks increased in frequency and severity. Finally, a year later, the lower frontal convolutions were exposed, disclosing an adherent dura and a depressed scar over Broca's convolution. The epileptic attacks have ceased, but the visual defect and aphasia remain as before.

In the following case a different course was followed : A college boy sustained a severe blow on the head during a football scrimmage, and soon became unconscious. There was no indication of any external lesion. Though his symptoms had in large part subsided by the following day, he remained somewhat stuporous, responding slowly and reluctantly to inquiries. The movements of the face, tongue and arm on the right side seemed somewhat less free than those of the corresponding parts on the opposite side, and when roused and questioned, the patient stated that his hand was " numb." Blood-stained iluid was found within the lumbar meninges. Through an intermuscular incision in the left temporal region a subdural clot, about a centimeter thick and covering the lower Eolandic area, was bluntly scraped and irrigated away. The patient came out of the anaesthetic with a perfectly clear and active sensorium, though with no memory of the events subsequent to the injury. His convalescence was rapid and he escaped the usual slow restoration to the normal — perhaps never quite to the normal — of these cases when left alone. Numerous other instances might be enumerated.

For the more severe, the more desperately injured cases, which present bulbar symptoms, owing to an implication of the vaso-motor, vagus and respiratory centers, a prompt craniotomy, perhaps bilateral and into the cerebellar fossa, with evacuation of clots and drainage, offers the only hope of life. In passing, I may remind you that it is clinically well recognized that when these intracranial hemorrhages are complicated by extensive fractures of the cranial vault, the


patients more frequently fail to show critical symptoms than do those who have escaped with an intact though fissured skull.

Much more important, it seems to me, are the intracranial hemorrhages which occur at birth. The problem is the same as in the cases just mentioned, there being a free escape of venous blood into the subarachnoid space, but with the additional element in favor of the child that the cranium is in a measure distensible. The conditions, therefore, are comparable to those hinted at above as occurring in the adult, namely a diffuse hemorrhage accompanied by some fragmentation of the vault. But given the distensibility of the cranium, the immediate consequences are not so likely to be serious even with an extensive effusion; and yet the late sequels are lamentable enough. The usual history is sadly familiar to all of us: A first-born child; a prolonged labor, often ending with instrumental delivery; some difficulty experienced in getting the child to breathe satisfactorily; a tense fontanelle; the child too weak to suckle and so fed by a dropper for several days; and after a time an apparent restoration to health. But too often, some months later, it is noticed that the child uses one side of the body, an arm or a leg, badly, or may be mentally deficient or blind. He eventually grows up, often with one or more spastic limbs, but worst of all, not uncommonly, he is subject to cortical fits. In this particular group of epileptics I have had a considerable experience in trephining and when the attacks were of a Jacksonian (motor) character, in extirpating areas of the precentral gyrus. And I can only say that the extraordinary variety of cortical lesions encountered defies description. Why should not these children at the time of the accident have been afforded the same chance of avoiding subsequent complications that is given an adult with intracranial hemorrhage? The reason is not far to seek. The author of one of our best text-books of neurology accredits most of the cases of spastic paraplegia to hemorrhages occurring at birth or in infancy, and while granting that it would be ideal if we could, at the time, treat them surgically, concludes that infants could not possibly survive the ordeal. A leading psdiatrist, also, whose knowledge of the pathology and symptomatology of these conditions is surpassed by none, has stated that these lesions cannot be attacked at the time of their occurrence because the coagulation time of the blood in the new-born is so slow that a fatal hemorrhage would necessarily follow any operation of this severity. This latter view would seem to have resulted from a misconception, unless our observations on coagulation are at fault ; and, so far as endurance of the operative procedure is concerned, when one considers what the child's head is fitted by nature to withstand during parturition, the far milder traumatism of an operative procedure should on a priori grounds certainly be as well borne.

Two years ago, while making some investigations on the cerebro-spinal space, I was privileged by the obstetrical de|iartment to autopsy a number of the children, who were stillborn or who had survived only a few hours or days. To my surprise I found that about half of them had died with, if not


82


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 168.


from, an intracranial hemorrhage." Shortly after this Dr. Dabney consulted me in regard to an infant, 48 hours old, the first born of twins, which evidently was dying with compression symptoms. Contrasted with its normal twin the child had a very tense fontanelle, a slow pulse, slow and irregular respiration and a dilated right pupil. We operated as soon as preparations could be made. The right parietal bone was turned down and on opening the tense, plum-colored dura there was found a large, thick clot, which spread over almost the entire hemisphere. This was easily broken up and irrigated away with warm salt solution and the wound was closed. The child survived only eight hours. Since that time, however, I have had two successful operations of a similar nature, the details of which need not be entered into here except to say that preservation of warmth and avoidance of loss of blood may be regarded as the prime essentials. The procedure itself, though delicate in performance, need not entail serious consequences. In the last case a bilateral operation was performed, in order to expose both hemispheres.

The third group of hemorrhages, of which a word will be said, is of a totally different variety, being arterial in origin and intracerebral in site. Nevertheless, I am convinced that in properly selected instances much may be accomplished for these cases also, by proper operative intervention. The lesion by nature is, of course, an immediately destructive one and cannot be obviated by an evacuation of the clot ; still it probably lies in our power to effectually ward off the fatality, which results from an exhaustion of the medullary centers, subjected, over a prolonged period, to an increased tension of high degree. The damage already done to the brain, however, particularly by a hemorrhage in the right hemisphere, is not necessarily incompatible with subsequent physical and mental activities of a high order.

None of the cases of apoplexy upon which I have operated, have recovered; improvement, however, after the trepanation was considerable in all of them in spite of the fact that only those patients were subjected to the operation, who, at the time, were profoundly unconscious and for whom death seemed imminent. For two or three days the condition of one of them was so much better that hopes of recovery were entertained; but he succumbed, apparently from an inhalation pneumonia. In view of the fact that no anaesthetic had been necessary, we can only suppose that the pulmonary complication had originated during the long period of snoring and irregular (Cheyne-Stokes) respiration, that had preceded the operation."

The exploration could be done much better today, I think, by employing the intermuscidar operation through tlie tem


" The lesion frequently found was a rupture of one of the delicate cerebral veins near its point of entry into the longitudinal sinus, the vessel having been torn, doubtless, by the strain put upon it from the overlapping of the parietal bones during labor.

" From a physiological point of view, reference has already been made to these cases in the American Journal of the Medical Sciences for .Tune, 1903. " The Blood-pressure Reaction of Acute Cerebral Compression," etc.


poral region to which reference has been made. Anyone who has had the experience of opening the skull and dura in a case of apoplexy and consequently is aware of the enormous degree of cerebral tension encountered, would hesitate to expose the brain in another, similar case, unless safeguarded by an intermuscular means of approach. Fortunately, the temporal region furnishes the nearest access to the usual large capsular clot; and according to my experience, when a sufficient opening has been made down to it, the clot will practically extrude itself.

The only case of actual intracerebral hemorrhage which I have seen recover after operation was in a patient from Dr. Thomas' clinic in whom the bleeding had followed a penetrating stab-wound of the left superior parietal region. This had produced an extensive contra-lateral hemianfesthesia, astereognosis, loss of muscle sense and word blindness. At the operation the cortex was incised in the track of the puncture and on reaching the hemorrhagic cavity, clots, amounting to about an ounce, extruded themselves with immediate subsidence of the increased tension. This patient still retains some blunting of stereognostic perception in the right hand; but all of the other sensory symptoms disappeared within a few days after the operation.

There are many other intracranial conditions that promise to have an essentially operative therapy when our knowledge of the underlying mechanical conditions has been increased. As one example may be mentioned internal hydrocephalus with its oft accompanying niaklevelopment of the spine — a condition which hitherto has successfully baffled all efforts to secure satisfactory remedial measures. In the series of cases (now six in all) observed during the past few years at the Johns Hopkins Hospital and in which drainage into the retroperitoneal space by trephining the vertebra, has been carried out, it seems that the nearest approach to a rational operation has been attempted, and the results in three of the cases have been most encouraging. But it is necessary before going any farther, to learn something more of the mechanical factors wliich lead to the condition, by further experimental study of the normal course of the circulation of the cerebro-spinal fluid, and if possible, by the experimental production of these anomalies in the lower animals.

Similarly, drainage of the meningeal spaces, when they are infected, is by no means a hopeless surgical problem, although much is to be learned by experience of ways and means to this end. One patient that was operated upon some j^ears ago, for a purulent (staphylococcus aureus) spinal lepto-meningitis, after irrigation and prolonged drainage, entirely recovered from the local infection. His death occurred six months later from the complications of a pyo-nephrosis and at the autopsy, beyond the slight scar in the dura, Dr. Flexner could oliserve no macroscopical evidence whatever of any preexisting infection." In the epidemic forms of meningitis, though a few cases presenting serious compression phenomena, have


'= This case, among others, was reported by Dr. Osier in the Cavendish Lecture, June 24, 1899.


Maech, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


83


been surgically drained and irrigated in one way or another, no permanent beneficial effects have been observed, though the symptoms frequently abate in great measure and life may seemingly be prolonged, much as by the use of frequent lumbar punctures. Similarly in one child with hemorrhagic encephalitis, the threatened terminal symptoms of the paralytic stage were warded off by a decompressive operation, but without anything more than a postponement of the eventual fatality. It is not impossible that in the slowly progressive infections of a tuberculous origin, the mere exposure of the meninges may exercise some beneficial effect, as seems to be the case in tuberculous peritonitis, by increasing the local resistance of the tissues to the spread of the disease.

Maladies, such, for example, as the major neuralgias of the trigeminus and the complications of suppurative otitis media have belonged too long to the field of surgery to need any detailed mention here. But before leaving the subject of operations upon the brain, however, I should like to say something in general of methods of procedure.

Chloroform narcosis has been advocated by the highest authority, for the reason that less bleeding accompanies operations under its administration than when ether is employed.

This is undoubtedly true, but this result is brought about through the lowering of blood pressure, the very condition that one would wish to avoid and one, which, were it desirable, could readily be assured by a certain amount of blood-letting. Ether is a much safer drug.*" The only annoying arterial hemorrhage comes from the scalp and in the majority of craniotomies (all but basal ones) this may be controlled by the proper use of a tourniquet. The venous hemorrhage, which at times may be profuse, from the diploe, sinuses or brain, must be controlled by special methods. Posture is oftentimes of great help in lessening this form of bleeding, but an upright position is attended by some hazard unless some means of supporting the general arterial pressure is employed. In this connection the inflatable suit, the result of the ingenious researches of Dr. Crile, can often be used to advantage. With our present knowledge the doctrine that in cranial operations rapidity is all-important would certainly appear to be based upon erroneous conceptions. I feel sure that experience will show that in cranial work, as in operations elsewhere, time, in the majority of cases, is vastly secondary in importance to careful heemostasis.

The Spinal Cord.

The surgical procedures, which we are called upon to carry out for spinal lesions, require no such delicacy of handicraftmanship, and present no such critical complications as those with which we have just been dealing. For purposes of


" The effect of the anaesthetic, together with other physiological reactions, reflex and otherwise, associated with operations upon the central nervous system, is best appreciated by keeping a blood-pressure chart. Such a record not only furnishes instructive and interesting general data, but often furnishes a means of properly interpreting the effects, beneficial or otherwise, of the various operative steps.


localization, however, a knowledge of neurological anatomy is no less essential for work here than on the brain, and the site of each segmental unit in relation to the skeletal landmarks must be familiarized, as well as the physiological part which each of them plays. There are no clinical puzzles more interesting to disentangle, none more confusing when left in a snarl, than those connected with the segmental localization of a cord lesion; the determination from disturbances of function of its transverse extent; a decision as to the recoverability of the injured tracts; and a knowledge of just where the intact arches of the spinal vertebra must be entered in order to expose the diseased focus. The small and removable spinal cord tumors especially put one's knowledge of localization to the test. The primary growths fortunately, are usually of a benign nature; they spring from the meninges, are enucleable, and if removed early allow of complete restoration of function in the cord. Probably these meningeal (intrathecal) tumors are by no means rare, and that so few successful extirpations have been recorded in this country, is possibly due to the fact that mistaken diagnoses have been frequent, explorations have been lamentably rare, and too often localizations have been incorrectly made. A single visit to the laboratory of the Queen's Square Hospital and a view of the tumors of this nature there preserved, enables one to realize how frequently in other parts of the world they must have been overlooked.

My personal experience with spinal tumors has been small. I have had one successful case of an enucleable tumor, with complete and early recovery from the compression paralyses. In another patient, who had been treated for 17 years for transverse myelitis, a fibroma was found, the size of a man's fist, which had caused a compression erosion of the overlying vertebra. At so late a date the cord had naturally been destroyed beyond repair. In a third patient, a child, the pressure of a mid-dorsal, inclusion (dermoid) cyst had caused symptoms of a total physiological transverse lesion ; a complete restoration of function has followed its removal. The other cases have been illustrations simply of invasion of the spinal canal from without, usually by malignant disease. One of these patients almost completely recovered from the compression symptoms after a laminectomy and the removal of as much of the growth as was accessible. Some months later the pressure symptoms returned with accompanying severe root pains and a second operation was undertaken and abandoned as hopeless. Had I appreciated the intensity of suffering which this patient was destined to undergo, purely as a palliative measure I would deliberately have divided the cord at a point a segment or two above the growth. I believe this to be a justifiable measure whenever disease of a hopeless character has seriously damaged the cord and when the radiating root pains are severe.

The indications for surgical intervention in cases of spinal traumatism when there is evidence of injury to the cord, have given rise to much discussion. On the Baconian principle that " it is easier to evolve truth from possible error than from certain confusion " and for the sake of having some tangible


84


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 168.


and definite rule for conduct, I have always divided these cases into three categories. (1) Those in which an operation is contraindicated because it can do no good and may increase the damage already done. To this group belongs the traumatic hsematomyelias, a not uncommon lesion, one easily recognized from its symptoms alone and without radiographic aid, and one which, up to a certain point is recoverable by natural processes of repair. Of these cases we have had twelve. (2) Cases of fracture-dislocation, which are relatively common and which, so far as we know, are beyond all hope of restoration, owing to the complete transverse nature of the lesion. In these, operation can do no harm, but it is an unjustifiable ordeal for both patient and operator. (3) Cases of partial injury to the cord with symptoms which are increased and perpetuated by pressure from a foreign body, such as a fragment of bone or a bullet, form a group in which an operation undoubtedly will do good, provided it is so conducted as not to aggravate by further traumatism the already existing symptoms. All of these conditions are commonly regarded as surgical, and I have mentioned them for the sake of emphasizing certain limitations which should be recognized. Not a few cases of hsmatomyelia have come under my notice in which the s3'mptoms were markedly aggravated by surgical meddling, and I have known many cases of total transverse lesion which have been needlessly subjected to laminectomy.

I do not hesitate to confess that elements of error may be present in this working division. For it is possible that certain cases of focal hemorrhage into the substance of the cord, like similar conditions in the brain, may come to be considered surgical disorders. Again we are not in a position to say with finality, that divided spinal tracts are incapable of regeneration; nor can we always be certain that a complete transverse destruction of a segment and not a partial injury with a physiological " block " of the remainder is indicated by the disturbances of function caudad to a lesion. Undoubtedly either of these conditions might give rise to an immediate total flaccid paralj'sis, an absolute anjesthesia up to its segmental level, a total and permanent loss of the deep, and a progressive diminution and final loss of the superficial reflexes. Collier's recent studies " offer sti-ong evidence in favor of some regenerative power of the conducting paths, and they show furthermore, that the supposed symptoms of an anatomically total lesion are not unequivocal. If this assumption proves to be true, even the cases falling into my second group become as urgently operable as any, inasmuch as " the onset of the flaccid state in compression paraplegia is a sign which indicates that operative interference for the relief of pressure must be undertaken at once, if it is to be of any avail; for the total physiological abrogation from compression signifies the presence of serious evasciilarization, and the inevitable sequel of such ischaemia — irreparable degeneration — cannot long be delayed."

Only in the long-standing cases, therefore, which present


" Collier, The Effects of Total Transverse Lesion of the spinal cord in Man. Brain, 1904, Vol. 27, p. 38.


when seen undoubted evidences of transverse destruction — no matter whether the lesion in its transverse extent originally was or was not complete — is an operation to be considered utterly futile. But though a laminectomy may avail nothing, much may be done in a palliative way even for these hopeles? cases. Most important is the care of the bladder and in view of the functional isolation of the lower sacral segments, it is a wise routine practice to institute permanent drainage by a perineal or a suprapubic cystostomy. The procedure is a simple one, indeed not even requiring a local anaesthetic, for in low level lesions the perineal operation may be carried out, and, providing the cord injury be above the twelfth thoracic segment, the suprapubic route may be chosen. Prom either the gain to the patient in comfort and tidiness, and to the attendant in freedom from responsibility is immeasurable. Nothing is so provocative of pressure decubitus as the maceration of the skin from a dribbling bladder, and nothing so inevitably follows frequent catheterization as a terminal infection.

Did the scope of this address permit, many other problems connected with the surgery of the spine might be considered, for example : Under what circumstances should the pressure palsies following a tuberculous spondylitis be treated by the open method ? What may we expect from sensory root division or excision of the dorsal root ganglia in the intractable neuralgias which may follow amputations or herpes zoster? What diagnostic value is to be attached to the measurement of tension as well as to the cellular content and chemical composition of the cerebro-spinal fluid obtained by lumbar puncture? What of the administration of medicaments by this route and for what physiological reason has spinal anoesthetization by cocaine faUen into disgrace? The discussion of these questions must be left for another occasion.

The Peripheral Nerves.

Of the many comparatively new discoveries that have a practical bearing upon the surgery of the peripheral nervous system, both somatic and splanchnic, much could be said, both in regard to the successes as well as in explanation of the failures in this more familiar field of neurological surgery. At present I must content myself with the brief presentation of some few of them.

The process of repair, that precedes the restoration of function in injured and degenerated nerves, represents the key to the situation. This must be found before the last word on nerve suture and nerve anastomosis can be said. Some of the most important and suggestive pieces of scientific investigation of recent years have been directed toward the solution of this problem, and, although the question is not yet ended, many of the facts, which have been brought to light during its course, have proven of clinical importance through their practical applicability. The doctrine, commonly accredited to His, tliat each nerve fiber is an outgrowth of a single cell, the two making a nerve unit, for a long time met with almost universal acceptance. More recently, however, strong opposition against this view has developed owing to the studies of Bethe, Nissl,


March, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


85


Dohrn, Schultze and others, who claim that the fibers do not grow out from the central nerve cells, but arise independently in the periphery from chains of cells which ultimately represent the sheath of Schwann and which only secondarily become united with the central cell. If this view proves to be correct, and if the histological and functional changes, which Huber and Howell, Bethe, Ballance and Stewart, and many others, have observed to take place in the peripheral end of a divided nerve, without any discoverable reunion with its central end, prove actually to be regenerative processes of the nerve, the possibilities of future work on the peripheral nerves promise to be enormous. If, for example, in anterior poliomyelitis, though the central cell is destroyed, there is some tendency toward restoration on the part of the Schwann cells of the fiber itself, there will be at least, a preparedness of the fiber, if subsequently given an opportunity, to make functional connections with other cells.

It must be confessed that the unequivocal acceptation of these views of peripheral autogenetic regeneration has received something of a check through the more recent publications of Langley and Anderson," who have indicated some of the possibilities of error, particularly in Bethe's investigations. Again, the recent discoveries made by Dr. Harrison " can hardly be brought into harmony with Bethe's views. This investigator has shown that, if, in a frog embryo, the ganglionic crest, destined to give rise not only to the dorsal root ganglia but also to the cells of Schwann, be removed, naked motor axis-cylinder processes will grow from the remaining intact ventral portion of the rudimentary cord, and make their normal functionating connections with the muscle plates. Further, in studying the outgrowth of the fibers from the cells he has observed that there is a definite wandering or amoeboid property of the axis-cylinder process — a discovery which, if correct, completely disproves the postulate of Hensen, that there is some original connection with the periphery which serves during growth to draw the nerve out to its ultimate terminus. Harrison's observations, on the other hand, would indicate the existence of an active outgrowth, influenced by some chemical affinity for its field of destination. In some such way it would seem, the central ends of divided fibers of the adult actively tend to regain their peripheral connections and succeed in doing so unless there be some mechanical interference in the tissue to prevent this. Whether or not there io an autogenetic process of repair in the isolated end of the fiber, or whether the central cell plays the entire part, or, what is not improbable, whether both factors are together concerned," must for our purposes be looked upon as a secondary


" Autogenetic Regeneration in the Nerves of the Limbs. Journal of Physiolog}', 1904, Vol. 31, p. 418.

"Neue Versuche und Beobachtungen uber die Entwicklung der peripheren Nerven der Wirbeltiere. Bonn, 1904.

" It does not seem at all improbable that it may be some chemical affinity, exerted by the proliferating cells of Schwann at the periphery upon the amceboid-like downgrowth of the axiscylinder processes, that leads them to their proper destination. Both factors may, on such an explanation, be actively Influential in the regenerative process and not one of them alone.


consideration; it is this normal active chemotactic tendency to unite which chiefly concerns us. In their laboratory experiences, investigators into the problems connected with autogenetic regeneration, have found that the greatest difBculty arises from the fact that it is almost impossible to prevent some reunion of the divided nerve fibers, with their original central ends, or with the central ends of fibers from other sources, which have been unavoidably cut through during the operation. This fact is worthy of mention, because we have long been taught that such a reunion is not to be expected, unless the fibers of a severed trunk are encouraged to find their proper connection by a surgical approximation of the stumps with suture or other means. It seems probable on the other hand, that, unless there has been some gross error in technique — as from the accidental interposition of some other tissue, or a loss or necessary extirpation of a large portion of a nerve, the ends will reunite of their own accord. In the case of the smaller, peripheral nerves, divided during an approach toward deeper parts, we know this to be the usual result, and the more dry and skillful and careful the dissection, and the more painstaking and accurate the apposition of the parts during the closure of the wound, the more complete and rapid will be these reunions. Perhaps these changes can be best appreciated by making a careful study of the post-operative areas of cutaneous anaesthesia and motor palsies after extensive dissections such, for example, as are necessitated during a complete excision of the glands of the neck. In these cases an examination will show that, when the wound has been carefully closed, the anterior cutaneous branches of the cervical plexus and the spinal accessory, which are almost always injured, invariably reunite, even when no attempt has been made to suture them, whereas after a rough operation and a hurried and careless closure of the wound, they will not. The same thing is true after operations over the parotid region in which the N. facialis is so liable to injury. We have always been taught that incisions in this region should be made parallel to the facial fibers, but the text-books in general contain no such warning in regard to operations elsewhere on the body (except in regard to the musculospiral, external popliteal nerve and a few others), because the resultant disturbance, whether motor or sensory or both, being unobtrusive and unlocked for, escapes observation. But to take these points into account even in the case of the smaller and less significant nerves should not be regarded as finicky surgery. Avoidance of injury to nerves, large or small, must always be a desideratum in operations. Here, however, I would only emphasize the fact that after such divisions as are often unavoidable, a careful approximation of the tissues, the avoidance of blood clots and points of necrosis — the organization of which increases the density of the resulting cicatrix — will serve to bring the severed ends of the nerves sufficiently near together, so that the chemotactic influence, whatever it may be, will suffice to bring about reunion. The same is true of the larger nerve trunks, and I doubt not that the suture material used in apposing the stumps of divided nerves.


86


JOHNS HOPKINS HOSPITAI. BULLETIN.


[No. 168.


by increasing sear-formation, frequently serves to defeat the very ends for which it has been employed.

Langley in the course of his investigations was the first, or among the first, to put to experimental test the possibility of nerve crossing, through which has been opened up such a promising field for peripheral nerve operations. During the process of reunion of a divided nerve it is hardly conceivable that each fiber will make connection with its own original fiber in the peripheral stump and thus find its way to its original end organ. If this is so, why should it not be possible to graft the peripheral end of one severed nerve, whose central connections have been destroyed, with the central end of another nerve of like nature, which has not suffered injury? It has been shown that not only is this possible, but that, at least for the extremities, a reeducation of the central activities takes place, particularly in young individuals, to such a degree that practically the normal function is resumed, one group of cells sufficing to preside over its owa, as well as over the territory of the nerve originally injured, proving itself capable, as it were, of driving a team as well as a single horse. More simple even than in the case of mixed nerves would seem to be possibilities of anastomosis between two purely somatic efferent nerves, and the idea of grafting a neighboring intact motor nerve into a paralyzed facial branch, in the hope of overcoming the seriously obtrusive deformity, occurred a few years ago almost simultaneously, to surgeons in England, France, Germany and this country, and was acted upon with results which doubtless are known to you."

In three of my own cases I decided upon the spino-facial form of anastomosis; and though the hypoglossal, from what would appear to be merely conjectural reasons, is favored by others, the functional results after the latter operation seem in no instance to have been comparable with those after the spino-facial grafts. But no matter by what method they may be performed, anything short of an absolutely perfect result in these cases will show itself plainly by some asymmetry during the finer expressional movements. This would not be the case after anastomoses between the limb nerves and it is here, in dealing with the paralyses of anterior poliomyelitis, that we may expect to find the field of greatest promise for the application of these principles. Let us take a simple illustration. Terminal paralyses or palsies of certain groups of muscles characterize the residual features of an anterior poliomyelitis. The destruction of the ventral-horn cells is most intense in certain spinal segments ;'° the cells of the adjoining ones, having suffered less severely, ultimately resume their normal activity and so, up to a certain point, the early wide-spread paraly


" The bibliography of the subject will be found In Ballance and Stewart's article in the London Lancet, May, 1902; and at the end of the writer's paper in the Annals of Surgery of the same date.

" Segmental In much the same way as is the best known of the diseases of the dorsal-root ganglion cells (herpes zoster) for which Head has suggested the name posterior poliomyelitis. The toxic agent, whatever it may be, in each disease has an especial affinity for one or the other variety of these cells. There is usually a rapidly acquired immunity which spares the remaining cells, and which usually persists for life.


ses disappear. Thus, let us suppose that the ventral-horn cells, which give rise to the fibers of the peroneal nerve and wliich are clustered largely (?) in the first sacral segment, have been for the most part destroyed. A paralysis of the peronei and of the extensors (dorsal flexors) of the toes and ankle results, leaving the foot and ankle unbalanced and often useless, owing to the lack of opposition to the pull of the sound flexors and supinators. If done at the proper time, an intentional section of the degenerated peroneal nerve and an implantation of its peripheral stump into an incision made into the functionally intact internal popliteal, should restore the balance as no tendon transplantation could possibly do; for, unless there is some flaw in the entire argument, the divided central ends of the internal popliteal fibers should, without discriminating between them, grow dovra and make connections with the originally degenerated fibers of the peroneal and also with the newly degenerated ones that lead to the nerve's natural field of peripheral distribution. Many of these operations have already been done and it remains only to determine the time most advantageous for the anastomosis. It is probable that after it has become evident what the extent and what the seat of the residual palsy are likely to be, the earlier the operation is carried out the greater will be the probability of success. Possibly just when the peripheral changes in the degenerated nerve, supposed to be reparative in nature, are at their most active stage, may be the most desirable time. Certainly after these changes — whatever be their nature — have retrogressed and the muscle spindles and end-organs have atrophied, the chances for restoration of control are much diminished.

More complex problems arise when the paralyses are diffuse and scattered; as, for example, when the movements at the knee and hip are affected or the upper arm is palsied. On one child from Dr. Thomas' clinic, that presented this extreme type of paralysis with an involvement of all four extremities, I have done several operations. In the upper part of the cord the fifth cervical segment was particularly the seat of injury, the deltoids being absolutely, and the biceps and supinator muscles in large measure paralyzed. The spinal accessory has been sacrificed and transplanted into the upper radicle of the brachial plexus. Anastomoses have likewise been made on each of the lower extremities. On the side most seriously crippled, the N. femoralis being the only nerve that had remained in large part intact, it was anastomosed in tlie pelvic fossa with the obturator and first radicle of the sacral plexus with the hope of restoring power, in the thigh, sufficient to let the child stand and possibly walk. Of course, in cases of this kind, no tendon transplantation could be of service.

It is quite possible that there are other maladies which may be greatly benefited by measures conducted along these same lines. Kennedy, it will be remembered, cured a patient, who was suffering from an extremely trying facial (motor) tic, by deliberate division of the N". facialis and an immediate spinofacial anastomosis. I have recently had a similar case. After reading some of Bethe's experiments, I have vainly looked for a proper case in which to anastomose central end to central end


March, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


87


of the nerves of an amputation stump, when there existed an intractable neuralgia originating in the so-called amputation neuromata. Unions of this nature, the " polarity " of the opposed ends being the same, are of course, unaccompanied by any functional transmissibility in the nerve, but they probably would suffice to prevent the formation of the terminal and painful tangle of outgrowing axones.

The possibilities of nerve anastomosis do not end here with the grafting of like upon like, for Langley has demonstrated the surprising fact that nerves, normally subserving a different function, may, under favorable circumstances, be interposed. Thus he and Anderson " found that certain somatic efferent nerve fibers, such as are contained in the fifth cervical nerve, are capable of maldng a functional union with the preganglionic fibers of the cervical sympathetic, and vice versa. For example, the preganglionic fibers of the sympathetic may unite with the peripheral ends of the recurrent laryngeal, phrenic, or spinal acessory. It is quite within the realm of probabilities that this principle may be applied to a great number of neurological conditions, to cases of bulbar palsy for example, or to restore tone in the muscles of a paralyzed larynx, however it may have been produced.

With these crude generalizations I must close this section of my paper on the peripheral nerves, leaving much unsaid of the particular operations such as those for torticollis, for paralyzing lesions of the brachial plexus — whether from injuries at birth or in adult life, of neurectomy for Bernhardt's paresthetic meralgia, of the operations for tetanus suggested by the discoveries of Meyer and Eansome," of cervical sym


™ Langley and Anderson, The Union of Different Kinds of Nerve Fibers. Journal of Physiology, 1904, Vol. 31, p. 365. This, their more recent publication, contains a summary of the earlier work which has appeared under various titles.

=> Archiv f. Exper. Pathol, u. Pharm., 1903, Vol. XLIX. They have shown that the neurones are protected with remarkable efficiency against circulating tetanus toxin, and that the central cells are reached only by way of the long paths of their axiscylinder processes, which must first suffer injury before the poison can effectually enter them. The long incubation period is taken up with this slow process of attack through the muscle " Endorganen." The toxin travels cellulipetally after entering the nerve fiber and thus it is possible by an early exposure of the nerves, central to the point of lesion, and by the local (intra-neural) injection of antitetanotoxin to effectively combat the progress of the intoxication.


pathectomy for glaucoma and exophthalmos, and, indeed of the entire surgery of the sympathetic, a large subject of itself. The particular disorders of many individual nerves — the trigeminus, for example, in its relation to congenital naevi, herpes, morphcea, neuralgia and other phenomena of disease — would alone be enough to write a book upon.

And now that all has been said, which may justly be crowded upon the pages of a single address, may I, for a moment, in closing, return again to my introductory theme? In talking the matter over with my surgical friends, many of them have expressed themselves emphatically against any form of operative specialization. But, granting the wisdom and necessity of a general surgical training beforehand, I do not see how such particularization of wor£ can be avoided, if we wish more surely and progressively to advance our manipulative therapy. Are practice of hand and concentration of thought to go for nothing ? Whether as the result of individual fitness, or opportunity, or training, certain things must be better understood, and, from purely a handicraftman's point of view, better done by one man than by another. Gowers has said that " the separation of medicine from surgery is itself specialization.^ In this sense everyone specializes, and the misfortune to medicine of its long divorcement from surgery, its only inductive branch, has been recently emphasized by Clifford Allbutt. We all are, or should be primarily internists, but although all build on the same foundation, some by inclination or fitness prefer the mechanical side of therapy. The same principle applies to the sub-departments of medicine, and in this particular field of neurology some of those who finally focus their studies in this direction, must, in aid of their scant therapeutic resources, do their own operating.

What Billroth, in the early days of abdominal surgery, said of the future of medicine in general, is just as applicable to this smaller field: " Die innere Medizin miisse mehr chirurgisch werden."


^ I wish to quote, in this connection, a paragraph of some historical interest from John Morgan's " Discourse upon the Institution of Medical Schools in America," Phila., 1765.

" First, I propose to confine myself, in practice, to those cases which belong most immediately to the office of a Physician, that I may prescribe for and attend such cases to greater advantage. I shall therefore avoid, all I can, interfering in the proper business of surgery, viz., manual operation."


TUMOR OF THE PARATHYROID GLAND.

By W. G. MacCalldm, M. D., Associate Professor of Pathology, The Johns HopJcins University, Baltimore.


Two tumors arising from the parathyroid gland have been described, the first by Benjamins ' and the second by Erdheim." In Benjamins' case a tumor the size of a child's head developed rapidly in the thyroid region and was extirpated. It


^Benjamins, Zieglers Beitrage, Bd. 31, 1902, p. 143. = Erdheim, Ibid., Bd. 33, 1903, p. 158.


was surrounded by a capsule in which at one point a normal parathyroid was found. Its substance was made up of broad strands and masses of epithelial cells resembling those of the normal parathyroid, with very slightly tinged protoplasm and vesicular nucleus. Toward the connective-tissue stroma there was almost everywhere a palisade row of cells taller and with


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 168.


deeper staining nucleus than the rest. Occasional colloid droplets were seen.

Erdheim describes a nodule 2i x li em. in size, found at an autopsy in an 18-year-old person, at the lower pole of the thyroid, without being more directly connected with that organ. No other parathyroid glands could be found. Microscopically this tumor consisted of strands and irregular masses of cells with relatively sparse vascular suppl}' in the delicate stroma. The cells corresponded with those of the normal gland, even the oxyphile cell groups being found. Colloid droplets were observed between the cells although there were no definite follicles. In one section a cyst was found, lined with one layer of cells and containing degenerated fatty cells. Erdheim. suggests the possibility that since the other parathyroid glands were not to be found this may have begun as the result of a work hypertrophy, which gave the impulse tc tumor formation.

At an autopsy in the case of a young man ast. 26, who had suffered for several years from symptoms of a chronic nephritis and on whom two 3'ears ago the operation of decapsulation of the kidney had been performed in the Johns Hopkins Hospital, there was found on the right side just below the lower pole of the thyroid and quite separate from it a round smooth mass enclosed in a delicate capsule and lying in the loose connective tissue. This mass measured about 3 cm. in diameter was almost spherical, being somewhat flattened. Externally and on section it was of a uniform opaque whitishyellow color and in consistence was rather soft. On section the cut surface of the homogeneous slightly granular substance of the mass bulged outward. In the center was a small cavity with smooth walls containing a clear fluid. The mass was not richly supplied with blood-vessels.

Two well formed parathyroid glands were found which both macroscopically and microscopically were normal. The thyroid was normal throughout. Otherwise the chief lesion to be noted was an advanced chronic diffuse nephritis. The patient died in urasmia.

The mass was fixed in Zenker's fluid. Microscopically it proved to be composed of a tissue which, as in the cases of Benjamins and Erdheim, most closely resembles that of the parathyroid. There are strands and very large anastomosing branched masses of cells which are separated by a relatively delicate stroma which bears the blood-vessels. Compared with the normal parathyroid, the blood supply is extremely meager. The columns of cells are usually solid, the cells being packed together and pressing one another into polygonal forms. Sometimes there are as many as 24 cells abreast in such columns, but most of the strands are not so bullsy and may be so small as to contain only two or three cells abreast. Some of the larger solid-looking masses are found to be permeated by a network of filaments of the stroma, bearing blood-vessels. The cells are quite as they are in the normal parathyroid showing vesicular nuclei and protoplasm which may be faintly granular or perfectly clear and free from any stainable granules. Solid masses of these latter cells occur and there is one especially


large wedge-shaped area composed of them alone. Large and small groups of cells corresponding precisely with the normal oxyphilic cells of the parathyroid are scattered here and there among the other cells. Their protoplasm has the appearance of ground glass and takes a deep eosin stain. Their nuclei vary somewhat in size, but stain more deeply than those of the other cells. Mitotic figures of great beauty occur in all these cell forms.

The palisade arrangement of the peripheral cells is not especially striking in the great mass of this tissue, nor does it seem so to me in the normal parathyroid. There are certain of the masses of cells, however, in which a central cavity is found about which the cells are often arranged as a palisade. This is less marked when the cavity is surrounded by many rows of cells than when its wall is formed, as it frequently is, of a single row in which the cells then become high and cohimnar with the nucleus peripherally placed. These cells sometimes appear to possess cilia, but of that I cannot be sure as they are very imperfect. Not only the ordinary cells but the very clear variety and the oxyphilic cells may take part in forming the walls of these follicle-like cavities. The cavities are sometimes rounded and small, sometimes quite large and elongated or branched. They contain sometimes a finely granular coagulum, as if a thin watery albuminous fluid had been coagulated there by the fixing fluid. Oftener they are filled with bubblelike vesicles of about the size of red corpuscles and somewhat resembling shadows of those cells. The variation in their size, however, makes it seem that they are really analogous to those vesicle-like structures, so frequently seen in the renal tubules. Desquamated epithelial cells also occur there and occasionally red corpuscles. In one or two alveoli there are masses of red corpuscles, some well preserved, some broken down, together with particles of blood pigment, indicating that a haemorrhage had occurred some time before death.

Of colloid-like material there is practically no trace either among the cells or in the alveolar spaces.

The larger cavity which was opened in cutting through the mass is found to be lined with one layer of flattened epithelial cells, which have been in large part desquamated. It contains a fluid a little of which has adhered to the lining wall and is coagulated into a finely granular almost colloid-like pink staining material.

The capsule is delicate and consists of fibrous tissue into which the epithelial cells do not extend.

It is evident that except in bulk, in the size of the cell masses and in the formation of such definite cavities this growth differs in no way from the normal parathyroid unless it be in that there is no adipose tissue between the cell strands. The question therefore arises as it did in Erdheim's case as to whether we should regard it as a tumor or as the result of a compensatory hypertrophy. Erdheim was moved to the suggestion of the possibility of a vicarious hypertrophy by the absence of the other parathyroid glands. In this case, however, two other normal parathyroids were present. On reviewing the anatomical conditions elsewhere in the body, the only


Maech, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


89


other suggestion that arises is the possibility that in the state of extreme renal insufiSciency, which had existed for so long, extra demands might have been made upon the parathyroid.

Two other cases of advanced chronic nephritis in young persons were stiidied and in the parathyroids in one abundant mitoses were foimd, while none were to be seen in the parathyroids of the other.


No evidence of invasive growth is to be found, and in the ahsence of any convincing explanation for a compensatory h3'pertrophy it seems that we shall have to speak of this as an adenomatous new growth, while recognising the fact that many so-called adenomata in glandular organs have turned out to be evidences of compensatory or regenerative hyperplasia.


BACILLUS VIOLACEUS MANILA.

(a pathogenic micro-organism.)

By Paul G. Woollet, M. D.,

Assistant Director, Serum Laboratory, Manila, P. I.

(From the Government Biological and Serum Laboratories.)


I can find no account, in literature, of a pathogenic organism similar to the one of which a description follows, but there are one or two bacilli, which resemble it so closely in morphologic and cultural characteristics, that it seems wisest to consider the present germ as simply a variety of certain well-known but, at least usually, non-pathogenic forms.


CARABAO 431


BACILLUS 431



MONKEY 609



(70» C.-45 MIN ) DOG 614 ISUBCUTJ


CALF 498 iSUBCUTj

A Scheme to Show the Couese of the Inoculation Expeeiments.


The group, to which reference is made, is the one the individual members of which are discussed collectively by Migula (System der Bak-terien, 1900, II, 939), under the title of Pseudomonas violacea, and which are separately described by other authors as B. violaceus, B. violaceus Berolinensis, B. violaceus Lutetiensis, B. violaceus Laurentius. etc.

The organisms are described by these authors as bacilli.


which are short or of medium length, sometimes somewhat bent, and with rounded ends. The measurements are about Ix 0.6-3 m, although some individuals may attain a length of 3 /x. In cultures on agar and potato, formations much resembling spores, but which are like these reproductive bodies in appearance only, are seen within the individual rods. These pseudo spores are considered to be either plasma globules, or vacuoles, and true spores have not been demonstrated. The rods are motile; sometimes, as in cultures kept at body temperature, quite actively so. They possess a single polar flagellum. Deep colonies in gelatine have an irregular rounded appearance, with projecting filaments. On the surface the colonies form small depressions, in which blue-gray masses of bacilli are seen. The color gradually becomes more intense, and the straggling filaments grow out into the surrounding medium. On agar the growth is blackish-violet. Blood serum is liquefied — peptonized. On potato the growth spreads over the surface of the medium, and forms a rich pigment, which does not stain the whole fragment of the vegetable, but only that portion immediately beneath the growth. Broth is clouded, and a dirty white sediment falls to the bottom of the tube, and takes on a pale violet color. No pellicle is formed on the surface. The organisms grow fast at room temperature, but more slowly than most water bacteria, and they do not grow beneath the isinglass. They are most readily stained with hot carbol-fuchsin, and are decolorized by Gram's method.

B. Violaceus Manilce corresponds with the above descriptions in some details, but in some it does not. This organism is a short rod, measuring approximately 0.5 x 1.0 to l.o^u. Occasional rods are even longer. It stains with the usual aniline dyes, best perhaps with carbol-thionin, or with carbolfuchsin or gentian-violet diluted five times with water. It is not stained by Gram's method, and is not " acid-fast." When well stained by any of the above mentioned solutions, it appears as a short, thin bacillus, very frequently slightly bent, and with rounded ends. It does not, as a rule, stain uniformly, and may show one or more clear spaces which are not tinted, and which appear remarkably like spores. These clear spaces cannot be stained by the usual methods used in


90


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 168.


coloring spores. The organisms are generally single, sometimes in pairs, occasionally arranged in short chains of 3 or 4 individuals. They are motile, usually sluggishly turning and twisting, but frequently single rods may be seen to cross the field of the microscope with a more rapid, wriggling motion. Each organism possesses one polar flagellum. In rare instances two flagella may be distinguished springing from the same pole of the bacillus.

On agar plates, within 24 hours at 37 degrees C, colonies appear as small, round, violet-gray spots. These slowly enlarge and become deeper in color. The maximum depth of color is attained in from 48 to 72 hours. As the colonies grow, their margins become slightly irregular, and with a rather indefinite concentric arrangement of layers, which are somewhat thicker towards their peripheries, with the result that the centers of the colonies have a less intense blue color than the edges. These masses of organisms are slightly tenacious, but after removal from the medium are readily dissociated in water. The growth on agar slants is similar to that on plates ; extension being slow, but rather even, resulting in a very slight crenation. The water of condensation is clouded and bluish, with a blue sediment. In stab-cultures in agar the growth is scant, and no pigment is formed below the surface.

Gelatine is liquefied slowly at the temperature of the icebox, the growth forming a funnel-shaped area with a cupshaped upper portion. The sediment is bluish.

Bouillon is diffusely clouded. A delicate pellicle is formed, which, upon 1 per cent alkaline material, is but slightly pigmented, but which is better developed and bluer on a 1 per cent acid liquid. The sediment in 1 per cent acid bouillon is pale violet-blue, and rather viscid.

Dunham's peptone solution is also clouded, and a thin pigmented pellicle is produced. A sediment is deposited in this medium, which resembles that in broth, but in which more pigment is present. The whole medium becomes diffusely bluish within 48 hours.

On potato the growth extends over the whole surface of the medium, and to the water of condensation. The pigment production is luxuriant. The superficial layers of all the solid medium are stained by the soluble blue pigment. In sugarcontaining media — glucose and lactose — no gas is formed.

The reaction of milk, after seven days, is slightly acid, but there is no coagulation. However, the casein is peptonized, and the upper third of the tube becomes almost clear, being faintly violet.

The organism thrives better and produces pigment somewhat more freely at 37 degrees C, than at lower temperatures; it does not grow at all well, and does not produce any pigment, below the surface of a solid medium. It is almost an obligatory aerob. It is killed by boiling for one minute; by a temperature of 67 degrees C, after an exposure of 5 minutes; and by a temperature of 57 degrees C. after one hour. It does not form spores.

The pigment is soluble in alcohol, giving a deep, rich, violet


solution. It is slightly soluble in water, barely dissolved in ether, and insoluble in chloroform.

The organism described above has been isolated from three carabaos, which died suddenly with such noticeable absence of clinical symptoms, that acute hemorrhagic septicaemia was suspected. In two of these cases. Dr. Jobling obtained cultures of this organism from the lymph-glands and lungs, and in the third case the writer found it predominating in cultures from the same organs. Later on, in the press of work, the cultures from the first cases were lost, and only those from the third were used in the following investigation. However, Dr. Jobling had injected his organisms into guineapigs, producing the same kind of lesions which I shall describe. The details of the first autopsies are meager. Little can be said, except that the prescapular glands resembled those to be described in connection with the third case.

Like the first ones, the third animal died suddenly. It had had no rise in temperature, as far as the records of the corral show, and symptoms of rinderpest were absent. On removing the hide, none of the gross lesions of hemorrhagic septiCEemia or surra were encountered — neither hemorrhages nor cedemas. The prescapular glands were enlarged and intensely injected, but neither showed true hemorrhages nor necrotic areas. There were a few small petechia under the visceral pericardium, and under the endocardium of the left ventricle. 1'he lungs were not collapsed, but were for the most part crepitant. The surfaces of these organs were dotted with small pale areas varying in size from that of a pinhead to a small hazel-nut. These areas were firm and projected slightly above the surface of the pleura. They were not round, but irregularly stellate, and each was surrounded by an appreciable zone of congestion. On section they appeared granular and gray, and with no indication of caseation or suppuration. Other non-crepitant areas, which occurred chiefly along the anterior margins of th£ lungs, had much the appearance of red infarcts. They were dark red, and raised above the general surface of the organ in which they occurred. On section they were dark and moist, simulating the stage of red hepatization in pneumonia. The lungs on section were generally pale and oedematous, and in their substance contained large numbers of the small miliary nodules, similar to those seen upon their surface. The spleen appeared to be normal. The liver showed no macroscopic changes. The gall-bladder was somewhat larger than normal, but the stomach showed no pathologic lesions visible to the naked eye, nor were any found in the trachea, pharynx or tonsils. The kidneys were perhaps a trifle pale. The intestinal tract was normal.

Smears from the prescapular glands showed a few very small organisms, which appeared as diplococci or polar-stained bacilli, and a large number of somewhat larger rods; some of these irregularly stained, and others curved. Cover-glass preparations, made from the nodules of the lungs, showed almost nothing but small bacilli, which stained unevenly. Smears from the heart showed no organisms.

Cultures from the blood gave no growth after some days, and those from the lung lesions produced a few colonies of


Mabch, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


91


a large thick bacillus, resembling B. subtilis, and other colonies in very much larger nimibers, (in one plate, these latter only), which developed a blue color after 34 hours at 37 degrees C, and which were composed of the organisms which have been described. In cultures from the prescapular glands two organisms were demonstrated. One was identical with the chromogenic one isolated from the lungs, the other was a small coccus arranged mostly in clumps, which, after several days, produced a very faint yellow color. Both of these organisms, the coccus and the chromogenic bacillus, were studied carefully. One was in all probability a modified staphylococcus aureus, which produced a minimum of pigment, coagulated milk very slowly with coincident reduction of the litmus, and which did not kill guinea-pigs in reasonable doses, either when injected into the peritoneal cavity, or under the skin. The other has been described in its cidtured and morphological character, and corresponds quite closely with Bacillus violaceus (Schroter), or Pseudomonas violacea (Migula). In none of the books, to which we have access, have I been able to find any reference to the pathogenicity of Bacillus violaceus. This makes the following experimental study of some interest:

One cubic centimeter of a 48-hour-old culture from the lung of the carabao (No. 431), was injected under the skin of a guinea-pig (No. 329). The animal became quite ill within the next 24 hours, and a large semi-fluctuating mass appeared at the site of the inoculation. Coincidently, the temperature, which previously had been running between 36.5 degrees and 38.4 degrees C, rose to 39.8 degrees C, and then dropped gradually until the animal died. Death occurred on the fifth day after infection.

At autopsy a large area of necrosis was found under the skin about the point of inoculation. This was surrounded by tissue in a state of coagulation necrosis, in which were occasional lacunae filled with a dark gelatinous material. There was no true pus, and no hemorrhages appeared, although the adjacent tissues showed extensive congestion. The peritoneal cavity contained a small amount of a clear fluid. The kings were the seat of large and small hemorrhagic infarcts, the lower lobes of both sides being almost completely infarcted. The spleen was markedly enlarged, was very dark, soft and mottled with miliary gray spots, resembling focal necroses. The liver was also thickly studded with similar areas. There were no macroscopic lesions in the heart or kidneys, though the latter were pale. The adrenals were markedly enlarged, their medullffi congested and with small areas of necrosis in the cortices. The lymph glands of the axillae and groins were enlarged and injected. Nothing abnormal was remarked in the intestines, stomach or bladder.

Smears were made from the subcutaneous tissues at the site of the primary lesions, from the lungs, spleen, liver, lymph glands and heart. All save those from the heart showed numbers of rods morphologically identical with those which had been injected, the "organism was recovered in pure cultures from the liver, peritoneal cavity, lungs, the primary lesions and the heart.


A second guinea-pig (No. 458), was inoculated intraperitoneally with one-half of a cubic centimeter of a bouillon culture obtained from the carabao. It survived the operation.

From the cultures obtained from the first guinea-pig, a second (No. 327), was inoculated with | cc. of an emulsion made with three loopfuls of a 24-hour-old agar culture in 5 cc. of a normal salt solution. The animal died on the third day after inoculation. The anatomical picture was the same as that in the first guinea-pig, except that in the lungs small miliary necroses were present in place of the infarcts noticed before. Pure cultures of the experimental organisms were obtained from the heart, liver and the subcutaneous lesions.

With 1 cc. of an emulsion, made with 3 loopfuls of the organisms, obtained from this last animal, and 5 cc. of salt solution, a rabbit (No. 474) was inoculated subdermally. It died within 36 hours. Autopsy showed a bloody fluid in the peritoneal cavity, a wide-spread hemorrhagic lesion at the site of inoculation with no suppuration, but with necroses in the liver. The organisms were recovered in pure culture from the }.:eritoneal cavity, liver and heart. At the same time, a guinea-pig inocidated with an equal amount of the same material, died within 20 hours. The only macroscopic lesions were miliary abscesses of the liver. Cultures were obtained from the heart, liver and peritoneal cavity.

A cat (No. 366), was inoculated under the skin of the belly with 1 cc. of an agar suspension of a culture obtained from guinea-pig No. 327. The succeeding day a large semifluctuant mass surrounded the point of inoculation. The second day after infection, this abscess was discharging externally by a sinus, the edges of which were ragged, and about ^i-liich the skin was semi-necrotic. Eventually, all the skin about this first sinus sloughed, leaving an ulcer measuring 5x5 cm., whose base was on the subjacent muscles, and whose edges were regular, indurated and undermined. This ulcer gradually healed, and the animal showed a complete skin on the 30th day after inoculation. When recovery had been established, M second dose of a suspension of the organism from No. 474 was introduced hypodermically. No lesion was produced. The serum from this animal taken at this time agglutinated the specific organisms in a dilution of 1-60 after about 40 minutes; in dilution of 1-200, after about 1 hour and 15 minutes.

Five rabbits were inoculated with different amounts of the organisms to show what variations occurred in the lesions, if possible. The first (No. 454), received i a loopful, the second (No. 455), one, the third (No. 436), two, the fourth (No. 435), three, and the fifth (No. 433), four, of a culture obtained from rabbit No. 474. All of these animals died; Nos. 454, 455 and 436 in three days, No. 435 in four days and No. 433 in five days after inoculation. From all, the organism was recovered from the tissues and heart's blood, except in two cases (No. 435 and 436), in which the cultures from the heart were negative.

The progressive changes in the organs of these animals was noticeable and interesting. In animal No. 454 the subcutaneous Jelly-like oedema was present; there were miliary ab


92


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 168.


scesses in the liver, none in the spleen, none in the lungs, which were simply injected. In animal No. 455 there were a few nodules in the lungs and in the liver; the other organs appeared like those in animal No. 454. In animal No. 436 there were large abscesses in the lungs, and but a few small ones in the liver. Animal No. 435 showed similar lesions. In No. 433 there were a few very small abscesses in the liver and spleen, while the lungs were generally consolidated, showing comparatively large areas composed of collections of miliary abscesses. In other words, the lesions varied as the dose of the organisms, and while with small doses the liver was more prone to be affected, with large ones the lungs were more prominently diseased. This may, or may not, be true for other animal species. At any rate, the principal feature of the pathogenic action of the bacillus is its necrotizing power.

A dog (No. 515) was inoculated subcutaneously with 1 cc. of an agar suspension of a culture from No. 474. Several days later a local lesion appeared, which resembled that produced in the cat, but which was less extensive and healed more rapidly. About three weeks afterwards, this dog received 1 cc. of similar material in the femoral vein. Following this injection the animal was irritable, eating but little for a few days. On the third day, and continuing for four days, tremors were noticed in the head and limbs, the animal lying quietly without seeming to suffer. He subsequently became entirely well.

In the case of another dog (No. 516), in which the organisms were introduced into the trachea, no illness followed.

A calf was inoculated in the dew-lap with 2 cc. of the same material which was used with the dogs. The day following inoculation there was a large, painful oedematous mass visible in the region of infection. This enlarged until it reached the size of a large fist, and then gradually disappeared.

Inoculation into the peritoneal cavity of 1 cc. of a 48hour-old agar culture suspended in salt solution, caused the death of a rabbit (No. 492), within 12 hours. At autopsy there was nothing to be seen, except evidence of an acute peritonitis. Cultures from heart and peritoneal cavit}' were positive and pure.

Intravenous inoculation of ^ cc. of a 48-hour-old agar suspension killed a rabbit (No. 490), within 10 hours. No lesions were visible to the naked eye. Cultures made from the heart, peritoneal cavity, and pleura showed the organisms in uncontaminated growths.

Feeding experiments were negative. Large quantities of virulent agar cultures were fed to two monkeys (No. 488 and 489) with no ill effects.

Experiments upon serum reactions were begun with a monkey (No. 468), which had received a dose of one cubic centimeter of an emulsion made from a 24-hour-old agar culture of the organisms isolated from the carabao. The monkey did not succumb to this first subcutaneous injection, and four days later a second one was made with li cc. of an emulsion made with a 24-hour-old culture of the organisms isolated from the second guinea-pig (No. 327). The day following this second injection, a small quantity of blood was witlulrawn


and its agglutinative powers tested. In dilutions of 1-20 a complete agglutination was present at the end of 15 minutes. In 1-40, a complete reaction was given in half an hour. In a dilution of 1-200, the result was positive and complete in one hour.

Later this animal was inoculated subcutaneously with 1^ cc. of an agar suspension made with a culture of the organisms recovered from animal No. 474. Two days afterwards a large slough appeared on the abdomen about the point of inoculation, and the animal was very ill. It was killed and the blood drained off into a sterile tube. The serum obtained from this blood was tested for its agglutinative and bactericidal powers. In a dilution of 1-200 agglutination was complete in 20 minutes; 1-400 in 30 minutes; 1-600 in 45 minutes; 1-1000 in 50 minutes; 1-2000 incomplete after 1 hour; 1-4000 was negative.

This experiment was repeated in small tubes, so that the reaction could be watched with the naked eye. The tubes vrere allowed to stand over night. The next day all the organisms were contained in a precipitate, except in the control tube, in which the liquid was still cloudy. Cultures made from all these tubes gave luxuriant growths. No appreciable bactericidal action was present.

To determine whether or not a soluble toxin was produced, a four-day-old culture in peptone was filtered through a Pasteur-Chamberland bougie F. The filtrate was kept at 37 degrees C. over night and no growth occurred. The next day 5 cc. of the material was injected under the skin of a monkey (No. 509). Following this there was no sign of toxaemia, no rise of temperature, nor any sign of altered health in the animal.

After it had been proved that even very small amounts of the living organisms would cause death of small animals, and at the same time produce the specific lesions without the appearance of any appreciable immunity, cultures were heated to 57 degrees C. for one hour and these dead cultures, suspended in normal salt solution, were used for injection.

This material was used subcutaneously in a guinea-pig ( No. 486), and a monlcey (No. 411). In the case of the monkey, 1 cc. of an agar suspension was used for the first injection. There was no appearance of a reaction until the fifth day, when the temperature rose one degree above the normal one lor the animal. The day following this reaction, a second injection of the same amount of the same material was given. On the fourth day following, the blood was tested for its agglutinating powers. Complete agglutination was accomplished in dilutions of 1-400 in 15 minutes. A third inoculation was then made with 0.75 cc. (intraperitoneal) and 0.75 cc. (subcutaneous), of the same material which had been used for the other inoculations, and four da3's later a fourth inoculation was made with 2i cc. subcutaneously. Two days after the last inoculation, the monkey was found dead. At autopsy there were no macroscopic lesions at the site of the last inoculation, where there was a small pocket of a bluish material. Cultures from this lesion, from the heart, liver and spleen were entirely negative, and the media was perfectly


March, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


93


sterile after five days. Tlie serum talcen from tlie heart at autopsy gave a perfect agglutination in a dilution of 1-1000 in 40 minutes. The guinea-pig suffered no harm from the inoculations.

Later, iising cultures of the organisms from animal No. 474, and which had been killed by heating to 70 degrees C, for •J6 minutes, a dog was inoculated with a series of injections. He remained well throughout the time. However, after the third inoculation his blood agglutinated in a dilution of 1-30 only, after one hour.

The essential lesions produced in experimental animals are found at the site of inoculation, in the lungs, liver, lymph glands and spleen.

At the site of inoculation, when infection has been caused subcutaneously, there is a wide area of necrosis with local and circumambient cedema resembling the lesions produced by the diphtheria bacillus. The whole area may undergo necrosis, become gangrenous and slough away.


In the rabbits, the cedema has been more marked than the necrosis. In the cat, the necrosis occurred with but little oedema. The monkeys showed cedema as well as necrotic and gangrenous processes, as did the guinea-pigs.

The lesions in the parenchymatous organs are miliary abscesses, which may show a suppuration stage. In the lungs and liver the surface of these abscesses may be covered with a fibrinous exudate. The bacilli are found in all the lesions.

The losses in stock due to infection with B. violaceus Manila, are not extensive, and there seems to be little danger of an epidemic. In all our work we have seen but these three cases. Each was in a different herd, and these herds were widely separated from each other.

So far as treatment is concerned, there is little to be said. All the animals have died so suddenly and unexpectedly, that there was no time either for experiment or speculation on this subject.


A REPORT UPON THE AGGLUTINATION REACTIONS OF THE BACILLUS DYSENTERIC]

(SHIGA) WITH THE BLOOD SERUM OF PATIENTS SUFFERING WITH

SUMMER DIARRHCEA/

By Charles K. Winne, Jr., M. D., Late Assistant Resident Physician, The Thomas Wilson Sanitarium. (From the Laboratory of the Thomas Wilson Sanitatium for Sick Children.)


The accompanying table (Table I) is the summary of what is by no means intended as an exhaustive study of the problem of the agglutination reactions of B. dysenterice, but simply of the work done during the summer of 1903, at the Thomas Wilson Sanitarium as a matter of routine upon the blood reactions of the cases of dyspeptic diarrhoea. Unfortunately it does not include all patients treated at the Sanitarium during that time, for in the rush of the clinical work of midsinnmer many cases were of necessity allowed to pass unexamined.

The report is based upon examinations of the blood of one hundred patients (patients with two admissions with blood examinations on each admission being counted twice), in a few instances upon two or more occasions; of these 45 gave positive (including No. 287), and 55 negative results. No result is reported as positive unless the reaction occurred at a minimal dilution of 1-100, though every case was tried 1-20 and 1-50, and in the table a few such cases are recorded (136, 146, 147, 151, 161). When possible all dilutions were carried up to 1-1000, and in a few cases to 1-1500.


REPEATED COPIOUS HJIMOPTYSIS FROM AN AORTIC ANEURISM, EXTENDING INTO THE RIGHT LUNG AND FINALLY RUPTURING INTO THE PLEURA

By Thomas Wood Clarke, M. D.,

Late Medical House-Ofiicer, Johns Hopkins Hospital, Baltimore.

Resident Physician, Lakeside Hospital, Cleveland, Ohio.


The case I wish to report is that of J. McD., an Irishman, 39 years of age, who was admitted to the Lakeside Hospital, Medical Number 4303, in the service of Dr. Edward F. Gushing, on July 13, 1904, comf)laining of pain in the right upper chest, cough, and expectoration of blood. His father had died of consumption. Beyond this the family history was negative. The patient had always been a healthy, strong man, by occupation a laborer, and had done hard work all his life. He had rheumatism twelve years ago, and slight attacks of the same disease ever since then. As to specific history, the patient admitted having gonorrhoea three times, the last attack eight years before, and a soft chancre eighteen years ago. No history of a primary sore or secondary syphilitic lesions could be obtained. Except for the minor diseases of childhood, the patient had had no further illnesses. He used alcohol to excess.

The patient dated his present trouble from a year Ijefore admission to the Hospital, when he began to have discomfort in his chest, especially the right front, shortness of breath.


'Read before the Clinical and Pathological section of the Cleveland Academy of Medicine, on Nov. 4, 1904.


dizziness, ringing in the ears, and attacks of weakness. His general condition grew worse until two weeks before admission to the Hospital, when he began to cough and expectorate small amounts of blood. At this time, the pain in the chest grew much more severe, and on admission it extended to the right shoulder and down the right arm to the elbow. On the day he came into the hospital, he had had an especially profuse hffimorrhage, but was quite indefinite as to the exact amount. During the past year, he had lost twenty pounds in weight.


A CASE OF CESAREAN SECTION FOLLOWING VENTRAL FIXATION.

By Alfred Hull Glare, M. D., and Egbert Lee Bowley, M. D., Hartford Hospital, Hartford, Conn.


In a recent number of the Bulletin, Dr. Lynch published an analysis of a series of cases of Cffisarean section necessitated by ventral fixation of the uterus. To this the following case treated at the Hartford Hospital may be added.

J. I. (No. 36,541), white, aet. 39, was admitted May 3, 1904. She began to menstruate when she was fourteen and her periods had always been regular and the flow moderate in amount diiring the three days it generally lasted. She was married at twenty, but had no children. In July of 1901, she entered the Hartford Hospital with a history of painful defecation during the previous four or five years. A diag


nosis of a malignant tumor pressing on the rectum had been made before her entrance, but on examination the trouble was found due to a retroverted uterus. This was fixed firmly to the anterior abdominal wall and her symptoms were relieved.

In the spring of 1903, she was married again. She became pregnant, her last sickness dating from July 15, 1903, and had a comfortable, normal pregnancy with no oedema, headache, 01 morning-sickness. She re-entered this Hospital, May 3, 1904. She had expected her confinement April 22. At the time of her entrance she was in no pain.

A physical examination showed a slender, rather poorly


102


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 168.


nourished woman. Head, heart and lungs were negative. The abdomen was fairly symmetrically enlarged, the umbilicus was flat and the lineiB strise were not numerous. The position of the child could not be made out by external palpation, the palpable parts being very confusing and the abdominal walls tense. The foetal heart was heard 5 cm. above the navel in the median line. The cervix could not be reached per vaginam until a small hand was introduced when it was felt above the promontory of the sacrum and well back toward the spinal column.

Pelvic measurements : Between anterior-superior spines, 37 cm. ; between iliac crests, 28 cm. ; Baudelocque's diameter, 18 cm.

Upon May 4, the head of the child was thought to be in the left upper quadrant of the abdomen. With the patient under chloroform version was tried, one physician manipulating the foetus externally and a second with his hand in the vagina. The child could not be turned. After the manipulations there was slight bleeding from the vagina which continued until she was delivered two days later. The night was passed comfortably, but during the night of May 5, she was very uncomfortable and restless though there were no typical labor pains.

May 6, at 1 p. m. the os was found dilated about 2.5 cm. and at 4 p. m. it was almost fully dilated. The patient had constant pain in back and groins. Late in the afternoon internal version was decided upon and attempted, but on introducing the hand into the uterus to grasp a foot a shelf of tissue was found on its anterior wall which much impeded any search for parts though the position of the head was recognized. Upon further examination the bowel was found prolapsed into


the uterus. The diagnosis of a ruptured uterus led to her hasty transfer to the operating room.

On opening the abdomen the uterus was found ruptured in its very much thinned posterior wall and a dead, hydrocephalic foetus was found lying half in the uterus and half in the peritoneal cavity. The uterus was amputated from the cervix, freed from its attachment to the anterior abdominal wall and removed together with its appendages. The peritoneum was sutured over the stump and the abdominal wall was closed in layers.

The patient was comfortable the next morning, but in the afternoon complained of pain in the abdomen and about 6 jj. m. developed a maniacal excitement that necessitated restraint by a sheet. The mania was of extreme violence and once she caught her tongue between her teeth and bit it until it was cyanotic. This disturbed condition lasted until the morning of May 8, when she gradually regained her normal mental status and from that time made an uneventful recovery except for a slight stitch abscess and a profuse, purulent, vaginal discharge Irhich, however, soon cleared up under bichloride douches.

The fundus of the uterus was found firmly fastened to the anterior abdominal wall by a broad area of adhesions which allowed no motion whatever. The anterior wall and fundus of the uterus were very much thickened and the anterior wall so sharply bent upon itself that its upper segment formed with its lower an acute angle which made the shelf of tissue felt per vaginam. The posterior wall was very much stretched and thinned out and was ruptured enough to allow part of the foetus to prolapse into the abdominal cavity and bowels into the litems. The rupture probably occurred at the time of the attempted external version.


A SURVEY OF OVARIOTOMY AT EXTREMES OF LIFE. GIRL AGED 5.

By Hakey I. WiEL.


REPORT OF A CASE IN A


The occurrence in the service of Dr. Howard A. Kelly at the Johns Hopkins Hospital, of an ovariotomy in a girl 5 years old, has afforded the raison d'etre of a survey of the cases reported in literature suggesting not only a consideration of the subject in relation to the very young, but by wa}' of contrast, also in the aged. It is not the purpose of this article to go into the pathological and clinical aspects of the subject in detail, as the writings of Hennig, Homans, Kelly, and Bland Sutton consider in full that side of the question. Here is meant rather to emphasize by statistics the frequency of occurrence of the various tumors of the ovary and the results of ovariotomy.

That all of us realize the plasticity of statistics, is true.


' Presented before the Johns Hopkins Hospital Medical Society, December 19. 1904.


The Germans put it very aptly when they say " Papier ist geduldig," and that note of warning should be sounded in the interpretation of these. We have taken the statistics as we found them, and when the percentage of recoveries is noted it must be borne in mind that many of the cases were reported solely because there was recovery, while it may be assumed that some cases with unfavorable issue are unrecorded. Furthermore,many of the reporters mean by recovery, merely immediate recovery, though death (as happened in some cases) occurred from metastasis of the tumor. These remarks apply more particularly to the cases in the young than those in the old, for the reason that the after histories of the latter have been followed more extensively, and that when death did occur, circumstances of age determined the cause to be something entirely foreign to the ovarian condition.

Under the term " extremes of life " we have arl)itrarilv fixed

the limits of 10 years of age and under, and TO years of age and over. The story of ovariotomy at these ages has been told before, and those who have told it have come to definite conclusions.

Garrigues speaks thus : " The age of the patient need not he taken into consideration; ovariotomy has been performed with success in young children and in old women over 80 years of age." Baginsky, though less enthusiastic, says: " Ovariotomies in young children are frequently performed, even with cures. Prognosis becomes better every day as technique of operations in this region progresses." Kelly expresses himself that " The age of the patient does not, as one would suppose, contribute any valid reason for refusing to operate. . . . On account of the large percentage of malignant tumors (in children) and the consequent dangers of delay the operation should be performed as soon as the patient can be suitably prepared for it. The best tonic relief is afforded by the removal of the growth." Even Hennig whose article appeared in 1878, recognized the advantage of early operation in children.

The story in old age does not differ. There seems to be a consensus of opinion among those who have had to deal with the matter, that the extreme age of the patient offers no contraindication whatever. Kelly and Sherwood came to the conclusion that the indications and contraindications in old age are the same as in general operations. They quote Skene Keith, whose emphasis and enthusiasm can best be appreciated in his personal communication, "We like old women to operate on; they always do well." Homans, who from his wide experience gave a large list of ovariotomies, was extremely impressed with the good result in this class of cases, and Bland Sutton, though pessimistic on many subjects, gives a list of 11 ovariotomies in women over 80, all recovering, a result truly remarkable.

It is Bland Sutton, however, who speaks unfavorably of ovariotomy in young children. In the cases he collected (these included 15 years of age and under), dermoids and cysts did well, but in operations for sarcomata of the ovary the results were disastrous. Of his 21 cases of ovarian sarcomata, 11 were dead one year after the operation, a percentage of 52.3 per cent.

Kelly expresses the state of affairs best, viz. : that operation on children under 4 years of age is attended by a mortality of more than one-half of the cases; but on the other hand the


results obtained in the older children are remarkably favorable. One would think that the cause of this might be the increased frequency of malignant tumors in the younger years, and Dr. Kelly was of that opinion, but as will be seen by the tabulations below, such is not the case, the malignant tumors being hardly in higher percentage under 5 years of age than between 5 and 10 years.

Dr. Kelly's results were in some degree similar to those of Bland Sutton, and for the sake of comparison, their findings are here given in tabulated form.

Cysts^ Dermoids Solid Tumors

cases mortality oases mortality cases mortality

Kelly 43.67c. 7.2% 37.2% 21.2% 19% 33.37o

Sutton 41 7.3 38 13.1 21 52.3

These figures, as well as those to follow, are based only upon operated cases. There can be found in the literature, frequent mention of tumors of the ovary, in autopsy cases, and among these one can find instances occurring even in foetal life. Von Franque reports such a case. Olshausen reports an autopsy case of carcinoma of the ovary in a girl 8 years old, and another is reported by Amann, where merely an exploratory incision, and not an ovariotomy was done.

The youngest operated case is that of Chiene's, the patient being 3 months old. The result in this case is not known, as the after history is not reported. The child left the hospital however, with the wound healed. The oldest case is that of Thornton's, the patient being of the extreme age of 94. Here there was recovery. More remarkable, however, is the case cited by Owen. He operated on the patient in her 79th year for a parovarian cyst with successful result. In her 8Gth year she submitted to a second operation for an ovarian cyst of the same side. This was so successful that when seen ^4 months after, the patient looked, to quote Owens, " as though she would live to be 100.

The Johns Hopkins Hospital has had some experience in cases of this character, and the results are gratifying. Six ovariotomies in women over 70 are on record, the mortality being nil. All of the tumors were cystic, 3 multilocular and 3 unilocular, 1 of the latter being carcinomatous. Of this number, 5 are reported by Dr. Kelly, the other by Dr. Schenck.

A statistical study of the cases on record here follows :


^ Under the heading cysts, Sutton includes " cysts and adenomata." In the mortality of Sutton's cases of solid tumors, which were sarcomata, 4 of the cases counted here as deaths, recovered from the operation, but died later of metastasis.


CASES 5 YRS. OF AGE AND UNDER.


BKPORTEE.


AGE.



Chlene


3 mos.



1% yrs.



1%

2

2

2H 2% 2% 2% 2%



Pf an



Busch-Olshausen

Glbb







Neville





TDMOn.


Cyst.

Cyst. Teratoma. Sarcoma. Dermoid. Dermoid. Cystic Sarcoma. Sarcoma. Dermoid. Dermoid. Sarcoma.


Recovery. Recovery. Recovery. Recovery. Death.


Death. Death. Death.


BEFBBENCI}.


Edinburgh Med. Journal, June, 1884. Brit. Med. Journal, March 5, 1895. Deutsche Med. Woch., Dec, 1883. .\merican Journal of Obstetrics, Oct., 1904. Clin. Chir., 1887-8. Pitha-Bill.

Glasgow Med. Journal, Ix, No. 1, p. 33. St. Louis Courier of Med., Aug., 1884. Amer. Jour, of Obstetrics, xlx, 1022. Obstetrical Journal of Great Britain, vlii. Amer. Jour, of Obstetrics, xxxvi.


104


JOHNS HOPKINS HOSPITAI. BULLETIN.


[No. 168.


CASES 3 TRS. OF AGE AND UNDER.— Continued.


BEFDRENCE.


Alcock

Cameron

Kalb

Boiat

Schwartz

Thornton

Foerster

Bj-ford

Bangs

Simons

Johnson

Syme

Pten

Page

Lucas

McKee

Hamaker

Dandois

Barker

Croom

Owens

Thornton

Chenoweth

Cupples

Black

Stolypinsky

Dawson

Spencer Wells . . . Omori and Ikeda .

Chenoweth

Gussenbauer . . . .

McKenzie

Duchamp

Parkes

Deletrez

Routier

Polotebnow

Malins

Forbes

Leopold

Pton

Vincent

Omorl and Ikeda

McBurney

Wagner

Meigs

Fenomenow

Karcewski

Baldy

Romans

Bomans

Kaltenbach

Keith (Skene) ...

Hall

Hennig

Homans

Eastman

Edwards

Fehling

Freund

Frommel

Davis

Eastman

Cluness

Croom

Croom

Bantock

Barnes

Van der Veer . . . .


3% 3%


4% 4% 4% 4%


Multilocular Cyst.

Sarcoma.

Dermoid.

Cyst.

Adeno-Cystoma.

Dermoid.

Sarcoma.

Sarcoma.

Multiloc. Cyst.

Papillomatous Cyst

Cyst.

Cyst.

Dermoid.


Death.

Death.

Death.

Death. Recovery. Recovery.

Death. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery.


Lancet, 1871, vol. ii.

Glasgow Med. Journ., 1SS9.

Medical Sentinel, March, 1S97.

Proc. Path. Soc. of N. Y., ISSS.

ArchiT fiir Gynec, xiii, 4.

Med.-Chir. Trans., viii, 4.

Amer. Jour. Obst., xxxi.

Chicago Med. Record, 1891-2, ii.

Amer. Gynec. and Obst. Journ., 1896.

Virginia Medical Semi-Monthly, Mar. 22, 1901.

Lancet. 1897, i, p. 1093.

Australian Med. Journ., xv, 442.

Clin. Chir., 1887-1888.


CASES 6-10 TRS. OP AGE.


Sarcoma. Mult. Cystoma.

Dermoid.

Mult. Cystoma.

Dermoid.

Dermoid.

Sarcoma.

Dermoid.

Dermoid.

Mult. Cystoma.

Dermoid.

Dermoid.

Carcinoma.

Papillomatous Cyst.

Dermoid.

Dermoid.

Sarcoma.

Carcinoma.

Dermoid.

Cyst.

Cyst.

Dermoid.

Dermoid.

Dermoid.

Cysto-Sarcoma.

Myxo-Sarcoma.

Carcinoma. Mult. Cystoma. Cyst. Dermoid. Sarcoma. Sarcoma.

Cyst.

Sarcoma.

Dermoid.

Papillomatous Cyst.


Recovery. Recovery.

1 Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. ?

Death. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery.

Death. 7

Death. Recovery.

Death. Recovery.

Death. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery.

Death. Recovery. Recovery.


Lancet, Dec, 1895.

Trans. Clin. Soc, London, xxi, 224.

Univ. Med. Magazine, Phil., 1900.

N. Y. Med. Jour., Sept., 1889.

" Pediatrics," Dec, 1896, p. 520.

Phil. Med. Times., Nov.. 1874.

Edinburgh Med. and Surg. Journal, 1893, p. 689.

Sutton : Surg. Diseases of Fall. Tubes and Ovaries.

Brit. Med. Jour., 1881, vol. ii.

Amer. Journ. Obstetrics, xv.

Richmond and Louisville Med. and Surg. Jour., Dec, 1879.

British Med. Jour., 1874, vol. i.

Revue de Gynecologic et de Chir. Abdom., viii, 708.

Virginia Medical Seml-Monthly, March, 1901, p. 680.

British Med. Jour., 1874, vol. i.

Berl. Klin. Woch.. 1S90, No. 7.

Amer. Jour, of Obstetrics, vol. xv.

Wiener Med. Wochenschrift, 1894, No. 47.

Dublin Jour, of Medical Science, 1888, Ixxxvi.

Arch, de Tocol., 1884, p. 23.

Amer. Jour, of the Med. Sciences, 1890, p. 258.

Annales de I'Inst. Chir. de Brux.

Rev. Gen. de Clin, et de Ther., 1895.

Centralblatt f. Gyn., 1887, i.

Lancet, 1S90, i, 1174.

Australian Medical Journ., Melbourne, 1894, xvi.

Centralblatt f. Gynekologie, 1894, xvili.

Arch, de Toe et de Gyn., 1893, p. 580.

Lyon M^d., Ixxiii.

Central, f. Gyn., xvi.

Ann. of Surgery, Phil., 1895, xxi, 706.

Ann. f. Klin. Chir., xxx, 704.

Boston Med. and Surg. Jour., cxii, p. 316.

Rev. de Gyn. et de Chir. Abdominale, 1904, vol. viii, p. 708.

Centralblatt f. Gyn.. 1904, No. 17.

Amer. Gyn. and Obst. Journ., 1899, xiv, 184-186.


CASES 70 YRS. OF AGE AND OVER.


Mult. Cyst.


Recovery


Mult. Cyst.


Recovery


Mult. Cyst.


Recovery


Cyst.


Recovery


Solid Tumor.


Recovery


Mult. Cyst.


Recovery.


Mult. Cyst.


Recovery.


Mult. Cyst.


Recovery


Mult. Cyst.


Recovery.


Mult. Cyst.


Recovery.


Cyst. (Cancerous?).


Death.


Mult. Cyst.


Recovery.


2 Colloid Tumors.


Death.


Mult. Cyst.


Recovery.


Cyst.


Death.


Mult. Cyst.


Death.


Parovarian Cyst.


Death.


" Tumor."


Recovery.


Cyst.


Recovery.


Multiloc Cyst.


Kelly and Sherwood, Johns Hop. Hosp. Reports, lii, 532.

Ibid.

Ibid., p. 530.

British Med. Journ., 1887, i, 271.

Cincinnati Lancet-Clinic, 1887, xix, 1-4.

Inaugural Dissertation, Leipzig.

Kelly and Sherwood, Johns Hop. Hosp. Reports, iii, 528.

Ibid., p. 524.

Ibid.

Ibid.

Records of Frauenklinik der Universitiit, Strassburg.

Kelly and Sherwood, Johns Hop. Hosp. Reports, iii.

Ibid., p. 542.

Ibid., p. 524.

Trans. Med. Soc of California, 1872-73, p. 48.

Trans. Edinburgh Obstetrical Society.

" Analysis of 100 Cases of Abdominal Section," Edin. Med.

Journ., May, 1889. Brit. Gynec. Journ., May, 1892, p. 17. " Ovariotomy in Aged People," Provincial Med. Journ., Apr.,

1SS8. Transactions of Med. Soc State of New York, 1888 ; Annals

of Surgery, May, 1888.


Maech, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


105


CASES 70 YES. OF AGE AND OVEn.-Continued.


REPORTER.

Wells

Werth

Werth

Tait

Thornton

Thornton

Sims

Sims

Reamy

Hoberts

Meredith

Morison

Lohleln

liomer

Martin

Van der Veer

Werth

Thornton

Savage

Srhroeder

Sims

Peugnet

Martin

Kelly

Homans

Bantock

Wilson

Sims

Rhelnstadter

Sanger

Mundg

Morison

Martin

Kelly

Uomans

Homans

Gerster

Frommel

Cutler

Barnes

Zweifel

Werth

Werth

Btaude

Soderbaum

Maury

Kelly

Lltzmann

Homans

McCann

Keith

Homans

Homans

Homans

Crooker

Brennecke

Balls-Headley

Peterson

Martin

Spiegelberg

Noble

Morison

Kelly

Kaltenbach

HoCfmeler

Boldt

Croom

Carmichael

Martin

Kelly

Davies

Croom

•Bennett, E. and C. .

Wilson

Josephson


73

73

73

73%

73

73

73

73


TUMOR.


RESULT.


" Tumor."


Recovery.


Mult. Cyst.


Recovery.


Mult. Cyst.


Recovery.


Cyst, (both ovaries).


Recovery.


'• Tumor."


Recovery.


Carcinoma (both ovaries).


Death.


Cyst.


Recovery.


Mult. Cyst.


Recovery.


Mult. Cyst.


Recovery.


" Tumor."


Recovery.


Mult. Cyst, (papillomatous).


Recovery.


Fibroma.


Recovery.


Mult. Cyst.


Recovery.


Mult. Cyst.


Death.


Mult. Cyst.


Recovery.


Mult. Cyst.


Recovery.


Papilloma (both ovaries).


Recovery.


Mult. Cyst.


Recovery.


Dermoid.


Recovery.


Cyst.


Recovery.


Cyst.


Recovery.


Cyst.


Recovery.


Sarcoma.


Death.


" Tumor."


Recovery.


Cyst.


Death.


Mult. Cyst.


Death.


Cancerous Cyst.


Death.


Mult. Cyst.


Recovery.


Mult. Cyst.


Recovery.


( Mult. Cyst. R. ovary. j Fibroma, L. ovary.


Recovery.



Mult. Cyst.


Recovery.


Mult. Cyst.


Recovery.


Mult. Cyst.


Death.


Mult. Cyst.


Recovery.


Mult. Cyst.


Recovery.


Papillary Cyst.


Recovery.


Mult. Pap. Cyst.


Recovery.


Cyst.


Recovery.



Recovery.



Cyst.


Recovery.


Mult. Cyst.


Recovery.


Cyst, (both ovaries).


Recovery.


Mult. Cyst.


Recovery.


Cyst.


Recovery.


Carcinomatous Cyst.


Recovery.


Cyst.


Recovery.


Solid Tumor.


Recovery.


Fibroma.


Recovery.


" Tumor."


Recovery.


Mult. Cyst.


Recovery.


Cyst.


Recovery.


Mult. Cyst.


Death.


Mult. Cyst.


Recovery.


Mult. Cyst.


Recovery.


Dermoid.


Recovery.


Cyst


Recovery.


Cyst.


Recovery.




Mult. Cyst.


Recovery.


Mult. Cyst.


Recovery.


Parovarian Cyst.


Death.


Mult. Cyst.


Recovery.


Mult. Cyst.


Recovery.


Cyst.


Recovery.


Mult. Cyst.


Recovery.


Tuberculosis.


Recovery.


Mult. Cyst.


Recovery.


Cyst.


Recovery.


Mult. Cyst.


Recovery.


Mult. Cyst.


Recovery.


Papilloma.


Recovery.


Glandular Cyst.


Recovery.


REFERENCE.


Qicle, Manchester, Oct., 1892. 104 Ovariotomies," Med.-Chir. Transactions,


Kelly and Sherwood, Johns Hop. Hosp. Reports, vol. ill, p. 540. Ibid. Ibid.

British Med. Journal, 1886, i, 923. Med.-Chir. Trans., Ixxi, 1887, 57. Ibid.

Kelly and Sherwood, Johns Hop. Hosp. Reports, vol. Ill, p. 536. Ibid.

Ibid., p. 542.

Medical Chro;

Report of

Ixxii, 50. Lancet, Jan. 21, 1893.

Kelly and Sherwood, Johns Hop. Hosp. Reports, ill, 530. Ibid.

Ibid., p. 532.

Kelly and Sherwood, Johns Hop. Hosp. Reports, vol. ill. p. 540. Ibid.

Med.-Chir. Transactions, Ixx, 1887, p. 64. Records of Women's Hospital, Birmingham. Berl. Klin. Woch., 1879, i, p. 2.

ICelly and Sherwood, Johns Hop. Hosp. Reports, vol. ill, p. 530. New York Med. Jour., xxiv, p. 191. Kelly and Sherwood, Johns Hop. Hosp. Reports, ill, p. 336.

er. Jour, of Obst., xxxiv. No. 2, 1896. Kelly and Sherwood, Johns Hop. Hosp. Reports, iil, 532. On Hyperpyrexia after Listerian Ovariotomy," Med.-Chir.

Trans., Ixiv. Kelly and Sherwood, Johns Hop. Hosp. Reports, ill, 540. Ibid., p. 536. Ibid. Ibid.

Ibid., p. 534. Lancet, 1893, Jan. 21.


Kelly and Sherwood, Johns Hop. Hosp. Reports, ill, p. 532.

Amer. Jour. Obst., xxxiv. No. 2.

Kelly and Sherwood, Johns Hop. Hosp. Reports, ill, p. 528.

" Laparotomies."

Results of Aseptic and Antiseptic Surgery, 1st Edition, 1888,

p. 141. Kelly and Sherwood, Johns Hop. Hosp. Reports, ill. Hospital Records, Waltham, Mass. British Gynec. Jour., Aug., 1892, p. 159. Kelly and Sherwood, Johns Hop. Hosp. Reports, iil, p. 540. Ibid. Ibid. Ibid.

Eira, Goteborg, 1882, vi, p. 69. Mississippi Valley Medical Monthly, 1885, 5. Kelly and Sherwood, Johns Hop. Hosp. Reports, iii. Ibid. Ibid.

Brit. Med. Journal, 1903, i, 127. Ibid., 1887, ii, 592. " Laparotomies." Ibid. Ibid.

Kelly and Sherwood, Johns Hop. Hosp. Reports, iil, p. 522. Ibid., p. 520. Ibid.

Ibid., p. 540. Ibid., p. 532. Olshausen, p. 394.

Monthly Homoeopathic Review, London, 1903. Lancet, Jan. 21, 1893. Amer. Jour. Obst., xxxiv. No. 2.

Kelly and Sherwood, Johns Hop. Hosp. Reports, iil, 530. Ibid. Ibid.

Trans. Edinburgh Obst. Society. New England Med. Gazette, Apr., 1888, p. 119. Kelly and Sherwood, Johns Hop. Hosp. Reports, iii. Ibid.

Brit. Gynec. Journal, 1887, iii, 414. Kelly and Sherwood. Johns Hop. Hosp. Reports, iii. American Medical Times, N. Y., Aug., 1861, iii, 86. Kelly and Sherwood, Johns Hop. Hosp. Reports, iii. Fohr-Svenska, 1889, Kelly and Sherwood.


' First case reported.


106


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 168.


CASES 70 YES. OF AGE AND OVER. -Continued.


r.EpoKTEn.


Holland

Croom

Croom

Umkel

Wilcke

Wells

Terrier

Morison

Mann

Lomer

Samvrin

Itorsini

Staude

Heywood Smith Freund

Keith

Tuttle

Schroeder ....

North

Keith

Romans

Schroeder .... Richardson . . . Pippingskold

Owens

Heywood Smith

Edis

Cartledge

Spencer

Homans

Remfrey

Kraft

Bush

tOwens

tThornton


78 or 80 79% 79


Mult. Cyst.

Papilloma.

Mult. Cyst.

Cyst. H. ovary.

Mult. Cyst. L. ovary.


" Tumor." Fihroma (both ovaries). JIuIt. Cyst. Mult. Cyst. Mult. Cyst. Cyst.

Mult. Cyst.

Mult. Cyst.

Mult. Cyst.

Parovarian Cyst.


Mulf. Papill. Cyst.


Mult. Cyst.

Mult. Cyst.

Mult. Cyst.

Parovarian Cyst.

Cyst. Mult. Cyst. Mult. Cyst. Mult. Cyst. Mult. Cyst.

Cyst.


Recovery. Recovery. Recoverj'. Recovery.

Recovery.

Death.

Recovery.

Recovery ( ?).

Recovery ( ?).

Death.

Recovery.

Recovery. Recovery. Recovery. Recovery.

Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery. Recovery.


IlErEHENXE.


Brit. Gynec. Jour., vii, 179.

Records of Edinburgh Royal Inf.

Ibid.

Kelly and Sherwood, Johns Hop. Hosp. Reports, ill.

Olshausen, p. 394.

Med.-Chir. Transactions, Ix.

Progrfs-Medical, 1888, p. 466.

Lancet, Jan. 21, 1893.

Med. Record, Sept. 1, 1883.

Kelly and Sherwood, Johns Hop. Hosp. Reports, ill.

Amer. Journ. of Obst. and Diseases of Women and Children,

Feb., 1884. Rev. Ital. di terap. ed. ig., Piacenzia, 1881, i, 367. Kelly and Sherwood, Johns Hopkins Hosp. Reports, iii. Lancet, 1892, ii. " Ovariotomie bei Greisinnen " Inaugural Dissertation, Strass burg, 1890. Kelly and Sherwood, Johns Hopkins Hosp. Reports, iii. Roosevelt Hosp. Records, N. Y., 1891. Krankbeiten d. Weibl. Geschl. Brit. Med. Journ., 1903, ii, 1590.

Kelly and Sherwood, Johns Hopkins Ilosp. Reports, iii. Ibid.

Krankbeiten d. Weibl. Geschl. Brit. Med. Journ., 1894.

Finska Liikare Handlinger, 1884, Helsingfors. Brit. Gynec. Journ.. iv, SS. Lancet, 1894, i, 1618. Brit. Gynec. Journ., Aug., 1892, p. 162. Trans. Southern Surg. & Gynec. Ass'n, x, 153. Brit- Med. Journ., 1893, ii, 1271. Boston Med. & Surg. Jorn., 1888, cxvii, 454. Trans. Obst. Soc, Lond.. xxxvii, 152. Hospitalsridende, Copenhagen.

Kelly and Sherwood, Johns Hopkins Hosp. Reports, iii. Lancet, 1895, i, 542. Trans. Obst. Soc, Lond., xxxvii, 152.


t Second operation, first performed in 80th year. t Oldest case.


TABLE I.

GENER.U:, Resuxts.

70 YES. AND OVER. 10 TBS. AND UNDER.

130 Total number of cases. 60

16 cases. 12.3% Mortality. 14 cases. 22.4%

4 " 3.07% Result not ascertained. 5 " 8.3%

TABLE n.

Results in the Various Tumors.

70 yrs. and over. 10 yrs. and under.

cases s( occurrence mortal. cases. S occur, mortal.

2 1.5% 0. % Dermoids 22 35.2% 22.7%

65 50. % 11. % Mult. Cysts 6 9.6% 16.6%

.1 0.7% 100. % Sarcoma 14 22.4% 35.7%

24 IS. % 8.7% Uniloc. Cysts 13 20.8% 23. %

9 6.9% 0. % Papillomatous 3 4.87o 33.3%

4 3. % 75. % Carcinoma 3 4.8% 33.3%

4 3. % 0. % Fibroma

4 3. % 50. % Parovarian

1 0.7% 0. % Tuberculosis

Teratoma 1 1.6% 0. %

22 16.5% i.5% Unclassified

TABLE IlL Cases 80 Years of Age and Over.

Number of cases 14

Nature of Tumor as far as ascertainable, all benign cysts.

Mortality 0%.


TABLE IV.

Cases 5 Years of Age and Under.

Total number 24

Deaths 8 Proportion of 33.3%

Results not given 2 " " 8.3%

TU.MOR. number OF CASES. PROPORTION. MORTALITY.

Dermoid 7 29.1% 65.1%

Sarcoma 7 29.1% 42.8%

Mult. Cyst 2 8.3% 50. %

Uniloc. Cyst 6 24.9% 16.6%

Papilloma 1 4.1% 0. %

Teratoma 1 4.1% 0. %


TABLE V.

Cases 5-10 Ye.irs of Age.

Total number of cases ... 36

Mortality 6 Proportion of . .

Results not given 3 " " . .

TUMOR. number OF CASES. PROPORTION.

Dermoid 14 42.7%

Sarcoma 8 24.4%

Cyst 6 16.3%

Mult. Cyst 5 15.2%

Carcinoma 3 8.2%

Papilloma 2 6.1%


16.37^ 8.3%


MORTA 7.8

25. 33 0. 33. 50.


3%



TABLE VI. Cases Arba>"Ged Accobding to Yeab of Life.


Under 1 year. 1 2 3 4 5 6 7 S 9 10


NUMBER OF CASES. 2 2

7


AGE.


NUMBER OF CASES


70


35


71


11


72


14


73


17


74


11


75


5


76


5


77


9


78


4


79


5


80


4


81


3


82


2


83


1


84


2


87


1


94


1


History of the C.\se.

Elizabeth T., a girl aged 5, was admitted to the Johns Hopkins Genitourinary Dispensary on October 8. 1904.

Her complaint was that she was suffering from a vaginal discharge.

There was nothing of any importance in the family history, and except for two things her own past history was not interesting. The one was an attack of typhoid (?) in the first year of her life, and the other was a trauma, viz., a fall from a second-story window when she was 1% years old.

The present illness on close questioning really dated from that fall. The child was apparently unhurt immediately after and went on with her playing as usual. Soon, however, she complained of pain which was so severe as to prevent sleep, and at times she would roll on the floor on her stomach trying to get relief. Her mother thought for a while that the child was shamming and acting as so many children do, for she could find nothing on feeling and looking at the child's abdomen which suggested to her anything wrong. This pain continued for a long time, about IVz years, the mother thinks, and then subsided, except for occasional appearance. The next symptom was stcelUng, and this appeared only two months before visit to the dispensary. Following this there came vaginal discharge, for which the patient was brought here for relief.

On examination at the dispensary an offensive, white discharge was noted which the patient said was irritating. Other than some excoriation of the labia, there was no abnormality seen about the external genitalia.

Her second visit to the dispensary, on October 23, 1904, showed a change. The patient complained that the discharge which was formerly white had become pinkish, and the mother expressed some alarm. The genitalia were examined, and though no discharge was found there, in the garment there was every evidence of a bloody discharge. This led to further examination, and then there was found the tumor, which on the dispensary card is described as follows: "Above the pubic region there is a hard, rounded mass extending to the umbilicus, in shape, position as well as consistency resembling the uterus." Axillary and cervical glands were enlarged as well as the inguinal, and both mamms were very large for a child of that age.

Having in mind the possibility of tumors in that region being distended bladder. Dr. Pollack and myself catheterized the patient but only 20 cc. of dark, clear straw-colored urine were obtained, and the tumor remained as before. Ether examination was not made then owing to lack of facilities for anaesthesia.


The patient was sent into the hospital where she was admitted on October 28, 1904. The results of examination there are these:

" Patient well nourished, no glands felt. Chest well formed. Breasts large for the age. Respiratory sounds well heard. A few fine rales in right axilla heard regularly at the end of inspiration, otherwise lungs clear. Heart P. M. L in 4th interspace inside the mammary line. Sounds normal at apex and base. Pulse regular, 27 to %, of good volume.

" Hepatic dulness extends to costal margin. Edge of liver not felt. Abdomen looks rather full, especially just below the level of and at the side of the umbilicus. Appears symmetrical. On palpation the most prominent area of the abdomen is occupied by a more or less rounded, solid feeling mass, sharply circumscribed. Upper border of the tumor mass is about at the level of the umbilicus, but seems to pass a little higher up on the left side than on the right. Lower border crosses the median line about 2 fingers' breadths above the symphisis. More of the mass seems to be on the left side of the navel than on the right. Tumor the size of a large cocoanut, fairly freely movable and apparently not adherent to the pelvic organs of either side. Over the mass percussion is dull except along the left border where there is slight tympani. Neither kidneys nor spleen palpable. Pubic hairs well developed."

Measurements of Abdomen.

Girth at umbilicus 51.5 cm.

Greatest circumference 52.5 "

Distance from symphisis to umbilicus 13.5 "

umbilicus to xiphoid 13.5 "

to right ant. sup. spine . . 10.5 •• left ' 11.

Under chloroform anjesthesia, a combined vaginal and rectal examination showed a small uterus In anteflexion and that the mass was probably ovarian. A diagnosis of multilocular ovarian cyst was made by Dr. Kelly.

Before proceeding to tell of the operation and results, I should like to emphasize the sequence of the cardinal symptoms in this case. It is this :

Trauma, 3^ years before admission.

Pain, 3^ years before admission and not so severe recently.

Swelling, 2 months before admission.

White discharge, 3 to 4 weeks before admission.

Bloody discharge, 8 days before admission to hospital.

The operation performed by Dr. Kelly was a left Salpingooophorectomy. A median incision was made and through this there was delivered a tumor of the left ovary about the size of a large cocoanut and freely movable. With it the left tube was removed, all of which was accompanied by no haemorrhage. The right ovary which was seen, was small and apparently normal. The uterus was infantile, but rather larger than would be expected for 5 years. No evidence of metastasis of the tumor to the peritoneum or elsewhere. Catgut was alone employed, and the abdomen was closed in layers.

The patient stood the chloroform well and was removed to the ward in good condition, where she made an uneventful recovery and left the hospital, well, November 19.

Gross Appearance of the Tumor. — This tumor of the left ovary is ovoid in shape, and represents the whole organ tumified. It is 12.5 cm. long, 8.5 cm. broad, 7 cm. thick. Immediately after operation it had a somewhat boggy feel, something like that a soft solid tumor would give, but more suggesting a cyst with thick walls. It was mostly of a bluish-green tinge and shimmering, but in places could be seen beefy, brownish-looking areas showing through the glistening surface.


108


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 168.


The tube Is entirely attached to the tumor by a fold of peritoneum and this peritoneum extends along the tumor as far as ascertainable, about 5 cm., where it seems to affect a junction with a capsule about % mm. thick. Radiating from the attachment of the tube are beefy-looking nodular yellowish-brown areas, extending all the way from 3 to 8 cm. On the surface these show a rich vascular supply.

Cutting the tumor in its long axis we find a capsule, % mm. thick, from which extend bands of connective tissue which in some places more than others separate the underlying tissue into distinct alveoli, grayish in appearance and granular. The tissue underneath the capsule is found nothing other than the thick walls of a large cyst, the long axis of which corresponds with that of the tumifled ovary. This wall varies from 2 to 4.5 cm. in thickness, and is for the most part alveoloid in arrangement, as heretofore described, though in some places there are more homogeneous white areas. The vascularity seems fair.

The large cyst is 7 cm. long, 4 cm. wide, 5 cm. through. It has


new growth was highly suggestive of sarcoma and under a high magnification there was nothing to contraindicate that diagnosis. No alveolar arrangement was to be seen and the cells themselves were so aberrant as to suggest either the connective tissue or the epithelial tumor. At the advancing edges of the growth, however, a definite alveoloid and glandular arrangement was tobe distinguished, and here the cells resembled much more suggestively the epithelial type.

Vascularity was good throughout and only in few places were there to be seen areas of slight degeneration and necrosis. Scattered throughout the sections were smaller cysts, the walls of which were plainly made out to be composed of many layered actively proliferating epithelium. Some of the cysts seemed to have as their content epithelial debris, others mucinous matter, and still others blood.

Trabeculse of fibrous tissue were seen extending in from the capsule, but on the whole, stroma was present in not great proportion.



Gross Appearance of Longitodinal Section of the Tdmefied Ovary with Adherent Tube.


a distinct lining membrane, thicker than the external capsule. This membrane is in some places perfectly smooth and arranged like a dome; in others it is thrown into rugie and folds. The membrane is protruded in three distinct places by small underlying cysts, and at the external inferior angle of the cyst there protrudes a tumor 2x1 cm., apparently another cyst with a thick wall. Alongside of one of the cysts underneath the membrane of the large cyst, runs a good-sized vessel about V2 mm. in diameter. In the walls of the large cyst, these walls making up most of the tumor, are 5 to 6 other cysts of less dimension, about 1.5 cm. in diameter, which contain a white gelatinous substance. Throughout the tumor are numerous small cysts of various sizes, each lined by a definite membrane.

Microscopic. — The diagnosis of adeno-carcinoma of the ovary was definitely made by Drs. Cullen and Hurdon. This was not done, however, until a very careful examination of many sections was undertaken. In some places the cellular arrangement of the


This is the type of adeno-carcinoma of the ovary which Dr. Cullen describes as being extremely deceptive unless we examine many sections from various regions of the growth. It will usually be found, however, that at the advancing edges the carcinomatous arrangement will be quite typical and establish the diagnosis.

It is quite possible that some of the cases in literature diagnosed as sarcoma were rather tumors of this type.

As to the prognosis, it is certainly difficult to be of a definite frame of mind. Carcinoma occurs rarely in young children, at least in the ovary, and this is but the fourth case which has been operated on for removal of the growth. In the other three, Stolypinski's case is reported without giving the result, Gussenbauer's was well 6 months after the operation, and Leopold's died in 6 months from metastasis.


March, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


109


This tumor, though malignant, was extremely localized and even encapsulated. There were absolutely no signs of involvement of anything but the ovary and tube, and the operation was most successful in removing all of the morbid process. At the date of this writing, 3 months after the operation, the child is entirely well and active and shows no signs of any ailment.

From a consideration of the statistical study the following conclusions seemed Justified :

First, and most important. — Age is no contraindication to operation in these cases.

Second. — Prognosis is extremely favorable in the aged, even in the most aged. In the young it is not so favorable, but nevertheless good.

Third. — Malignant ovarian tumors are rare in the aged but more common in the young, this greater frequency accounting for the greater mortality. The most frequent ovarian tumors in the aged are the benign cysts, particularly the multilocular variety, these tumors being comparatively rare in the young. Ovarian dermoids and sarcomata are the most frequent ovarian tumors in the young and the rarest in the aged.

In conclusion I must express my most sincere thanks to Dr. Kelly for the privilege of undertaking and reporting this work, and to Drs. CuUen, Hurdon and Holden for many points in pathology.

Bibliography.

The bibliography here appended includes only references to general considerations of the subject. The bibliography of the cases is fotmd in the tables.

Ashby and Wright : " Diseases of Children," p. 6.35. Baginsky : " Lehrbuch der Kinderkrankheiten." p. 10.37. Bland Sutton : " Surgical Diseases of the Ovaries and Fallopian Tubes."

Bland Sutton : " Tumors, Innocent and Malignant." Garrigues : " Diseases of Women." Gebhard : " Path. Anat. Weib. Sex. Organe," p. 648. Hennig: Gerhardt's Handbuch der Kinderkrankheiten. Holt: "Diseases of Infancy and Childhood."


Homans : '" Laparotomies."

Jacobson and Steward : " The Operations of Surgery," vol. ii, p. 527.

Kelly and Sherwood: Johns Hopkins Hospital Reports, vol. iii.

Kelly: Keating's Cyclopedia of Diseases of Children.

Kelly : " Operative Gynecology."

Von Franque: Zeitschrift f. Gebiirtsh. u. Gyuak., 1900, xliii, 257.

D1SCUS.SION.

Dr. Kelly. — This subject is most interesting on account of the tender age of the patients. Enough attention has not been paid to the examination of children gynaeeologically, for we find practically nothing relating to this important subject in the average text-book and but little in the literature.

It is so easy to use a little chloroform in the child and the danger is so much less in children than with adults that we ought to make more frequent use of anajsthesia in examining them.

An important point is the relatively greater length of the examining finger. If the child's pelvis is half the size of the adult's, the finger is then twice as long in proportion.- It reaches further into tlie abdomen and we can examine a much wider territory.

Another important point in the vaginal examination of children is that instead of using the finger, which produces trauma and is painful and always repulsive, you can use a little cylindrical speculum, from 10 to 15 mm. in diameter; put the child in the knee-chest position and place a pledget of cotton saturated with 10 per cent cocaine within the hymen and then after about 7 minutes introduce the speculum, and with the head-light you can investigate all parts of the vagina, which is distended, and the cervix, and you can at the same time take some of the secretions for microscopical examination. You can also better treat these patients in this way, making strong applications, if need be, to diflierent areas. It does not hurt the child. They get used to the position and submit readily to treatment in this way.


PROCEEDINGS OF SOCIETIES.


THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Monday Evening, October 17, 190 Ji.

The meeting was called to order at 8 o'clock by the President, Dr. Thomas B. Futcher.

Election of officers. — The Society elected Dr. J. C. Bloodgood, President and Dr. C. H. Bunting, Secretary for tlie ensuing year.

Loss of Entire Lower Lip. Repair by Flap from the Arm. Dr. Watts.

This boy, who is 15 years of age, was admitted to the service of Dr. Halsted on July 6, 1904, with the history of having


had his lower lip bitten off two days before by a circus pony with which he was playing.

On examination, the entire lower lip was found to be absent, even the periosteum of the lower Jaw having been stripped oif in places. The wound was clean and free from infection.

Considering the great extent of the wound, it was thought best to cover the defect with a flap from the arm, rather than to attempt to obtain a flap from the face or neck. Accordingly a large flap was dissected from the right upper arm. This flap which included skin and subcutaneous fat was about 12 cm. in width and 18 cm. in length. Its under surface and the raw surface of the arm, from which it was taken, were covered with grafts removed from the thighs. All of these


110


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 168.


grafts took well and at the end of ten days we had a flap with skin upon both sides. Some of the skin upon its under surface was intended to form a substitute for mucous membrane upon the unattached portion of the lip, and to some extent prevent subsequent contracture.

The patient had a bad bronchitis for some time, following this operation, and further operative procedure was thus postponed more than a month. During this delay, the flap, which had already become considerably shortened by the sloughing of its distal extremity due to imperfect circulation, contracted to a wonderful extent.

On August 18, we dissected up the flap somewhat farther, in order to lengthen it as much as possible, and then sutured its free extremity to the left side of the wound in the lip. A small portion of the vermilion border which had been preserved on this side, was sutured along the upper edge of the flap.

The arm was held in place by means of a plaster cast for a period of about three weeks. The flap was then severed from the arm. This was done under local anaesthesia in several stages to allow the circulation to become more perfectly established.

The patient seemed very comfortable in the cast, the strained position of the arm causing almost no pain. At two subsequent operations, at intervals of two or three weeks, the lower and right borders of the flap were trimmed up and sutured in position. A very good functional and cosmetic result was thus obtained.

The photographs show very clearly the various stages of the operation.

Report of Cases. Dr. Cullen.

Adeno-carcinoma of the Umbilicus.

Dr. Cullen exhibited a growth which he had recently removed from the region of the umbilicus. The inguinal glands had become enlarged in consequence of metastases from the original tumor. A pathological examination showed the growth to be an adeno-carcinoma with the typical glandular arrangement. There was no evidence of any malignant process in the peritoneum or in any of the abdominal organs.

Cancer of Liver.

About a year ago Dr. Cullen presented to the Society a specimen of carcinoma of the kidney which had been removed by an operation in January, 1903. The patient remained well until June, 1904, a period of 17 months, when she developed a tumor which increased rapidly in size. As her temperature was 102|° and she was losing weight rapidly, she was removed to a hospital and an immediate exploratory operation was advised, notwithstanding the fact that she had but a single cystic kidney. Upon the abdomen being opened a large cancerous nodule the size of a eocoanut was found in the liver. It was thought not to be a metastasis from the original tumor, as the stump had been found free from thickening or secondary nodules. At first an attempt was made to remove the nodule by means of the cautery, and although it was possible to roll


the liver out of the abdomen, it was found impracticable to use it. Long blunt needles were accordingly forced through the liver substance and mattress sutures were introduced and the tissue afterwards was carefully separated by the knife, the tumor being kept constantly in a state of tension. Two or three sutures were introduced at a time and the dissection was progressively done. If a large vessel was encountered it was picked up and tied. By proceeding in this manner the operation was completed without the loss of more than two drams of blood and the patient was removed from the table with a pulse of 104. The upper and under surfaces of the liver were drained and the patient was able to leave the hospital in about four weeks. In September she was seen again and definite nodules had appeared on the left side. Of course any further operation is not to be thought of.

A certain Eussian who has worked with Mikulicz has shown that operations upon the liver are feasible if suitable suture material and needles are employed. The needles are to be carefully forced throiigh the liver, shoving the vessels aside in their passage, and as many sutures can be inserted as are needed. Sections of the carcinoma of the liver and also of the kidney show that the two growths are identical and lead to the conviction that the liver growth is secondary' to that of the liver.

IVIelanotic Sarcoma with IVletastases.

He also reported a case of a patient who had a pigmented mole of the neck which was associated with a similar condition in the peritoneal cavity.

Discussion.

De. Fdtchee. — I think the first of Dr. Cullen's cases should be emphasized, as showing the important part played by pigmented moles of the skin. Here was a patient who had a pigmented mole on the neck with metastases in the peritoneal cavity. The importance of these apparently benign tumors of the skin has recently been emphasized by Dr. Keen in a paper read before the Surgical Section of the American Medical Association, at Atlantic City, in which he recommends the removal of all pigmented moles, owing to their liability to become malignant and to cause the development of metastases in various parts of the body. Some of the members of the present house staff will probably recall a case shown in the dispensary clinic, two years ago, of a colored man who had a pigmented mole over the right scapular region, with enlarged glands in the right axilla. We happened to discover the existence of this mole and mentioned its probable association with the enlarged glands. The patient went to another hospital later, was operated upon, and the enlarged glands in the axilla proved to be a melanotic sarcoma, from which the patient eventually died.

The umbilical nodule which was present in Dr. Cullen's second case is also of interest, because one has to remember that metastases not infrequently occur in this sitiiation in association with malignant disease of the liver and stomach.


March, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


Ill


Clinically, it is not so very uncommon to find these metastatic nodules at the umbilicus in malignant diseases of the deeper structures.

Recurring Phlebitis of Obscure Origin. Dr. Bkiggs.

(To appear later.)

Discussion.

Dr. B. B. Browne, Jr. — I should like to ask Dr. Briggs if there was any tendency to urticaria in his cases. He has investigated carefully the histories as to rheumatism and gout, but does not mention urticaria. We know that urticaria is most frequently met with in rheumatic and gouty subjects and it may possibly be at times a factor of considerable importance in inaugurating changes in the arteries and veins. That a sub-endothelial infiltration can occur in the arteries in urticaria, similar to the infiltration of serum under the rete of the skin forming the " wheels," I feel sure of, from a case of urticaria which I recently observed, in which a distinct systolic murmur and thrill were noted over the aortic area and the thrill could be felt in some of the larger vessels, indicating a temporary narrowing of the vessels. If this condition should occur in veins where the vis a tergo is slight we would have a factor for the condition Dr. Briggs speaks of. I think all cases of arterio-sclerosis and phlebitis should be investigated as to a previous history of urticaria, and a trial made to ascertain the presence or absence of " factitious urticaria."

Dr. Briggs. — I should perhaps like to add something in regard to the frequency with which the diagnosis of gout is made in these conditions. Tuckwell, who with Paget, has his name associated with the subject, laid it down as a law that every apparently spontaneous phlebitis was due to gout. He made spontaneous phlebitis as diagnostic of gout as Dr. Osier makes the recognition of tophi. To those who follow Tuckwell this present paper would have no justification, as all these cases would be characterized as gouty, but I have had unusually good opportunities of studying the first case and can exclude anything in the nature of gout. In the one other case that I have seen myself there was at the time I saw it Raynaud's Disease, and that has been put down in the list of ills which go with uric-acidasmia.

I should like to hear from Dr. MacCallura as to whether the pathological anlage is a condition of sclerosis or not. My idea was that a thrombus beginning at a sclerotic patch might extend beyond it itself, increase the sclerotic change, and so go on step by step up the vein. That is very tentative, of course, but there have been no studies at all made as to the pathology.

In regard to Dr. Browne's question, I would say again, with Dr. MacCallum, that my own views of the possible pathology were very theoretical and I have not studied the question as Dr. Browne has brought it up. There was no urticaria in the cases I saw, and in none of the other histories was it noted. There has been no mention made of that or of any other skin lesion.


Demonstration of Pathological Specimens. Dr. MacCallum.

The first case illustrates a condition seldom so clearly shown as in the present instance, the embolic occlusion of the coronary artery of the heart. The case was that of a man past middle age who had long shown evidences of the presence of a ventral endocarditis. The final illness which led to his death was remarkable for its duration, as the intense symptoms began in February and lasted until October without, however, being characterized by the sweats which are so frequent in the cases of ulcerative endocarditis of shorter duration. Death occurred quite suddenly and at the autopsy which was performed next day the following condition was found : The heart is somewhat enlarged. The right side of the heart is unaffected except for the presence of two or three fresh vegetations on the edges of the tricuspid valves. The left auricle, however, shows a rough nodular mass of fresh vegetations upon its posterior wall. The mitral valves are thickly covered with large soft vegetations which have apparently developed upon valves already the seat of old lesions. These vegetations extend over the chordee tendineae many of which are ruptured and their ends rounded off by the masses of vegetations. So extensive has this rupture of the chordse tendinese been that the valve flaps freely through the auriculo-ventricular orifice and at the autopsy its two leaflets were found projecting upward into the auricle. It seems probable that the vegetations upon the auricular wall may have resulted from the implantation of bacteria from these flapping valves. The aortic valves bear upon the central point of each segment buUcy vegetations. Of special interest however, is the condition of the coronary arteries. The right one is open throughout, and its walls are smooth. The left is plugged at its orifice as with a cork by a thrombus mass which projects less than 1 cm. into its lumen and which hangs free in the sinus of Valsalva. This mass is fairly tightly wedged into the orifice but can be easily pulled out showing that it has no attachment to the vessel wall which is quite smooth at its points of lodgment. Further along in the course of the vessel which contained only fluid blood, there are some yellow patches, but the degree of sclerosis is nowhere very marked. From the position and relations of the plug and especially from the fact that it projects free into the sinus of Valsalva without any attachment to the adjacent valve or to the aortic wall and is not surrounded by clot, it seems certain that it is an embolic phig and the immediate cause of the man's death. The heart muscle shows no special alteration. There were numerous infarctions of varying age in spleen and kidneys. The case is chiefly of interest because of those reported in the literature there are so few in which the occlusion of the artery can be so certainly described as due to embolism and not to local thrombosis of the sclerotic vessel. Chiari, Oestreich, Barth and Hektoen report such cases while Marie denies the existence of coronary embolism.

To illustrate this case other specimens may be shown in which the coronary occlusion was shown and death did not result instantaneously. In these we cannot say definitely that the plugging was of embolic nature. In the first three


112


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 168.


in which the sclerotic coronary arteries are occluded by thrombus masses throughout a considerable part of their course, definite sharply outlined anaemic infarctions of the heart wall have occurred, in one instance leading to such softening of the tissue that a sort of aneurysm of the heart wall has been produced. The pericardial surface of such infarctions is covered with a fibrinous deposit. Another specimen shows a practically complete occlusion of the coronary by arteriosclerotic patches in its walls with the result that not an infarct, but a gradual disintegration and disappearance of the heart muscle fibers has occurred throughout the area supplied by that artery leaving a thin fibrous scar-like wall over a considerable portion of the ventricle upon the inner surface of which large globular thrombi have formed.

The second case which I wish to bring before you is that of a man who had suffered for years from dysentery. Toward the termination of his life, perforation of the intestine had occurred in the neighborhood of the urinary bladder and an abscess formed which had eventually ruptured into the bladder — other abscess cavities or sinuses had extended from this point far through the pelvic tissues encircling and isolating even the symphysis pubis and the neck of the left femur.

At autopsy the bladder wall was found to present numerous papilliform projections over almost its whole surface, but especially large and abundant immediately about the orifice through which the intestinal contents could filter into the bladder. These seem quite superficial and microscopically prove to consist of a much inflamed fibrous stroma covered by a somewhat thickened and folded layer of epithelium.

The condition found in the large intestine is especially interesting in affording the obvious explanation of many cases of polyposis of the intestine, resulting from longstanding inflammatory processes. There are extensive ulcers which have destroyed the mucosa and part of the submucosa leaving only islands and bridges of mucosa. In the upper part of the intestine these are overgrown by fresh epithelium, in the lower part especially in the rectum they are still uncovered and the undermining is relatively recent. So that the islands and bridges of mucosa retain practically the appearance of normal mucosa. Higher up, however, the islands have been elevated and rounded off by the contraction of scar tissue about them — a similar rounding ofp of the bridges of mucosa has occurred and frequently they have been broken through at one end so as to hang free by the other end in the cavity of the intestine. The proliferation of the mucosa which remains in these tags soon converts them into bulkier masses which are the polypoid structures so frequently seen after ulceration processes from whatever cause. Naturally this cannot be offered as the explanation for the other and more regular forms of pol3npoid growths in the intestine which are of quite different nature.

November 7, 1904.

The meeting was called to order at 8 :30 p. m., by the President, Dr. Joseph C. Bloodgood.


Biliary CirrHiosis of Family Type. Da. Osleb.

Cirrhosis of the liver is not an easy disease for students to understand, as the multiplicity of forms is confusing and the striking differences between the descriptions in the text-books and the clinical pictures in the ward upset the equanimity even of the third year student.

A very easy thing to remember, and perhaps the best practical division of the forms, is according to the tissues in which the disease begins, namely: portal cirrhosis, biliary cirrhosis and capsular cirrhosis. The portal form starts in the portal vessels, perilobular and sublobular; the biliary form begins in the small biliary vessels, the canaliculi inside the lobules ; and the capsular form starts about the capsule of the liver. There is a great deal of dispute about the biliary type. Many English authorities refuse to recognize such a form. Yet I think there can be no doubt that such does exist, characterized by; first, a protracted course, extending over a period of from five to ten, or twelve years; secondly, a persistent jaundice, often of great intensity, always chronic (not as in the ordinary types of cirrhosis appearing and disappearing, but remaining as a prominent feature of the disease) and being generally very intense; thirdly, pains, which are often of a mild character, chiefly in the hepatic region ; fourthly, its occurrence in comparatively young persons not subjects of alcoholism but coming in the third decade, or even earlier ; it is the type met with in children ; fifthly, the absence of all signs of portal obstruction, no ascites, no distended veins, no hsmorrhoids, or vomiting of blood; and lastly the frequency with which these patients have hemorrhages, particularly from the skin and mucous membranes. There are some other minor points, but those are the most important. It differs most markedly from the ordinary alcoholic form in the occurrence in young persons, without an alcoholic history and the persistence of the jaundice over a period of years. On examination you find an enlarged and hard liver, usually too, enlargement of the spleen. Now I find that students, as soon as they find an enlarged liver regard it at once as a type of biliary cirrhosis. That is an error. All forms of hypertrophic cirrhosis are not this type. It may be an alcoholic; in the early stages of portal cirrhosis there is enlargement. There may also be enlargement due to the presence of fat. It is probably a special form of alcoholic cirrhosis with hypertrophy, in which the increase in bulk is due to the presence of large amounts of fat. It is possible in some cases that a remarkable regenerative process may produce hjipertrophy ; the great enlargement that we sometimes see in the left lobe of the liver in cirrhosis may be due to active regenerative changes.

We have had a few cases of the genuine type of biliary cirrhosis in the Hospital; only six or seven. Recently a case has brought to mind two remarkable instances of the disease that we studied in the session of 1898. They were brothers called W., one thirty-two, the other twenty-four years of age. They came of a healthy family; no alcoholic history. One had had jaundice for nearly eight years; the other for four years. As some of you will recall they were very much alike. Both came at intervals to the dispensary and the one who


Makch, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


113


subsequently came into the Hospital was watched by many of us with great interest. He had in addition to the jjersistent jaundice an enlarged liver, pains in the hepatic region, which recurred at intervals for many years, and the fourth especial feature was hajmorrhage. He had recurring attacks of bleeding from the nose and subsequently from the gums; he bled continuously from the gums during the last five years of his life, being almost never without a slight oozing from the gums. He died, as nearly all these cases do, of a terminal infection. He had an increase of the jaundice, high fever and delirium and in fact all the features of an acute toxeemia. Blood cultures were made and the staphylococcus and streptococcus isolated. He had a greatly enlarged liver and a moderately enlarged spleen.

The brother had jaundice for four years and was intensely yellow. He too had pains on the right side in the region of the liver and had hasmorrhages, chiefly epistaxis. He also died of an acute terminal infection with high fever. There M'as no autopsy in his case.

Recently there has been in the wards a case that comes under this family variety or form of cirrhosis. A man, twenty-three years of age, a farmer from Virginia. He was admitted ten days or two weeks ago and had a good family history, so far as his father and mother and grand parents were concerned. He had had measles at ten and diphtheria and pneumonia six or seven years ago. He had had no malaria, no lues, and had no alcoholic history. He had had a chronic otitis media for several years. He had had an attack of jaundice at the iifth year from which he recovered. In October, '99, five years ago, he first noticed this yellow color, which has never cleared up, though it became lighter at times. He has lost in weight nearly twenty pounds in the past few months. He has occasionally had epistaxis and several times has vomited a small quantity of blood. He has had no pain and no fever. The coagulation time was three minutes. The liver was felt below the costal border and did not seem greatly enlarged; but the post mortem showed it to be much larger than we supposed from our palpation. There was no leucocytosis. The man's life was very miserable; he was in a wretched condition, and was anxious for operation. He was brought down one day for operation, but his blood coagulation time had gone up to ten or twelve minutes and he was sent back. On the day he was operated upon his coagulation time was one minute and forty-five seconds. At operation the bile passages were foimd clear, there was no obstruction. He had a few gall stones in the gall-bladder, but there was nothing in the bile passages themselves. He bled as these cases so often do following operation and died directly of the haemorrhage. The post mortem Dr. MacCallum will speak of. We found out from a brother after the death, that this jaundice from which he had suffered was a family condition. He had two brothers with jaundice and two sisters. One brother had been operated upon in Washington Territory and the brother who came had jaundice and had had it for five years. Two sisters also have jaundice, so that it is quite possible that this I'epresents another illustration of the family form of this


type of cirrhosis. The condition of the liver is interesting and it is quite possible that it is an early stage of this capillary angio-cholitis which is supposed to be the essential anatomical feature in the biliary or true hypertrophic cirrhosis.

Discussion.

De. MacCallum. — At the autopsy it was found that the gall-bladder had been opened and drained — its wall was somewhat scarred, but especially thickened by the hsemorrhage which had occurred since the operation. The liver was very dark green in color, but the lobulation was not distorted, there were no evident bands of fibrous tissue throughout its substance and its consistence was not increased. The cystic duct, common duct, and hepatic ducts as far as they could be traced into the liver were delicate and normal in appearance. They showed no evidence of the presence of obstructions of any kind.

Microscopically it is seen that there is a very slight increase in the connective tissue about the portal spaces and in some instances about the central veins, but this is so slight as to be hardly distinguishable except by the aid of some special stain.

The liver cells in each lobule show a very marked degenerative change, especially in the more central portion of the lobule about the central vein. Many of them are actually necrotic and disintegrated. Leucocytes frequently crowd the capillaries and lie about among the broken cells in these areas. Where the bile capillaries are preserved they are frequently distended with green bile pigment.

There is no satisfactory explanation of the jaundice to be derived from this microscopical picture, although possibly the explanation recently offered by Eppingor for the development of icterus might apply here.

The process suggests a toxic origin, but it is difiicult to decide as to the source of such a toxic substance.

Dn. OsLEE. — One interesting thing about these cases is that though intensely jaundiced, and perhaps in some of them a deeper jaundice than we see in any cases except those of malignant disease, it is not an obstructive jaundice because bile is present in the stools, though in small quantities. Even these cases of most intense jaundice still have bile in the stools. The whole essence of the process is apparently a capillary angio-cholitis. Of course in this case it may be an early stage of a process which may last for ten or more j'ears.

Crossed Dissociated Sensory Paralysis with Lesion of Medulla. Dr. Tiiojias.

Situs Transversus and Atresia of tlie Pylorus. Clinical Notes, De. Little. Pathological Notes, Mb. H. F. Helmholz.

(To appear later.)

November 21, 1904 The meeting was called to order at 8 P. M., by the President, Dr. Joseph C. Bloodgood.


114


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 168.


Experimental Streptococcus Arthritis. De. Cole.

I wish to speak briefly tonight of some work we have been doing in regard to arthritis induced by the action of streptoccccij with especial reference to the etiology of acute articular rheumatism. At present acute articular rheumatism is regarded by most authorities as an acute infectious disease. Those who consider that it is due to bacteria hold various theories. These are that it is due to :

1. A specific micro-organism, as yet undiscovered.

2. Various pyogenetic cocci, mainly the ordinary streptococci; that it is a mild form of pyemia.

3. A specific streptococcus or diplococcus.

4. A specific bacillus — BaciHus of Achalme. ^

At present the second and third views have the most supporters and it is mainly these that we propose to consider.

The reason why this disease is thought to be due to a streptococcus or diplococcus is that in a number of cases clinically resembling acute articular rheumatism streptococci or diplococci have been isolated from the joints, from the heart's blood or from inflammatory exudates. Also Meyer, recognizing the frequent association of angina and rheumatism, made cultures from the throats of rheumatic patients suffering from angina and isolated from a number of them a streptococcus, which, when injected into animals, produced characteristic lesions or lesions resembling those of acute articular rheumatism. In 1903, Menzer reviewed the whole question and he concluded :

The cause of acute articular rheumatism is not a specific bacterium, but the ordinary parasites of the mouth, which under certain conditions . have become pathogenic. Almost exclusively are streptococci the organisms concerned. These streptoccocci are by far the most common cause of the different forms of angina, and also of the so-called angina rheumatica.

Notwithstanding these conclusions regarding the specificity of these cocci, several English observers, namely, Poynton and Paine, Ainley Walker, Beaton and Walker, Shaw and Beattie, have continued to report the isolation of streptococci or diplococci from rheumatism cases, going so far as to name these Micrococcus or Diplococcus rheumaticus.

The claims of these observers as to the specificity of these organisms are based on cultural and morphological peculiarities and on experimental results obtained by the injection of these organisms into animals. As regards morphology, these observers are not unanimous, some of them considering the organism a streptococcus, others a diplococcus. Most agree, however, that they may appear either as streptococci or as diplococci, depending upon their environment. In fact. Walker, who has made the most extensive studies of the morphology and ciiltural characteristics of these organisms says:

We have no hesitation in saying that without animal experiments it would almost certainly he diagnosed as an ordinary streptococcus by anyone to whom cultures and stained preparations were submitted without comment. ,

Culturally this organism resembles a streptococcus, but that it is specifically different from the ordinary streptococci is


rendered probable by our results on the application of the test of Marmorek.

Since, however, the value of this test for determining specificity has had so much doubt thrown upon it by the work of Meyer, and Aronson, and others, and especially since Walker's observations were so few and reported with such slight detail, this evidence at present, at least, cannot be considered very valuable.

The same may be said for the specific reaction claimed for it by Shaw, namely, the property of causing blood agar to change in color to a dull brown or rusty tint when this organism is grown upon it, while in the case of the common streptococcus this does not occur. Schottmiiller, however, has shown that this property is common to a large number of streptococci from widely differing sources.

From all this it is evident that the claims for specificity of this organism must rest not on morphological or cultural grounds but on the peculiar lesions produced when inoculated into animals.

Practically all of the observers who have been mentioned as describing a coccus associated with rheumatic fever, have been able, by the inoculation into rabbits of quite large amounts of this streptococcus, to induce multiple arthritis of variable grades of intensity, in some cases endocarditis and pericarditis, and in a few experiments a condition said by the writers to resemble chorea.

My own work began with the study of a streptococcus isolated from the circulating blood of a man with endocarditis and septicemia. For a year or more he had been troubled with " rheumatic pains in his joints," though no definite history of acute rheumatic fever could be obtained.

However, thinking it possible that the streptococcus might be the one described by Poynton and Payne, and others, we began inoculating rabbits, and rather to our surprise found that arthritis was produced with marked regularity, almost every rabbit showing some grade of arthritis. As, however, the cultures of this organism did not differ essentially from those of ordinary streptococci, we thought it better to proceed with streptococci from other sources. We made cultures and inoculations from six races of streptococci. The sources of these various races were : peritonitis following carcinoma of the stomach; puerperal fever-autopsy; blood during life in terminal septicemia following myocarditis; empyema; blood during life in septicaemia following appendicitis; scarlet fever adenitis.

The diversity in the sources of these races renders it impossible that they could all have had any association with rheumatism, so that we could not have been working always with the so-called " Micrococcus rheumaticus."

The technique of inoculation was practically that of the English observers. The cocci were grown on solid media, an emulsion was then made and this was inoculated into the ear vein of a rabbit. With all seven races studied intravenous inoculation of amounts insufficient to cause death of the animals within six or seven days led to the production of mild grades of arthritis.


Maech, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


115


On about the fourth or fifth day after inoculation the rabbit usually appeared ill, remained quietly in a corner of its cage and only when it was put upon the floor and urged to move about would one see that it was quite lame. The lameness would sometimes appear in one leg and then in a day or two other joints would become involved. Usually recovery from the lameness occurred in a few days but in some death occurred. Other rabbits we killed while they were still lame. Still others we allowed to recover and then reinoculated when they would again show signs of arthritis. One we kept reinoculating in this way over a period of several months.

When the rabbits died or were killed, the joints were all carefully examined and certain of the joints were always found to contain a thick, sticlry, tenacious exudate, very different from that found in the normal joints. In these affected joints the surface of the cartilage was smooth, but the capsular lining was usually injected and red and covered with the thick turbid exudate. There was also usually considerable oedema 'about the joint. Microscopical sections were made from most of the joints and the lesions carefully studied. Smears made from the exudate showed numerous polymorphonuclear leucocji:es and a few mononuclear cells. Almost invariably diplocoeci were found in these smears; occasionally chains of three or four pairs were found. The cocci were usually flattened on one side, the flat sides approximated, so that one seeing them for the first time would certainly call them diplocoeci and not streptococci. Cultures were always made from the affected joints, however, and a typical growth of streptococci occurred in most cases.

In two of the rabbits a typical endocarditis occurred. The hearts of these rabbits have been preserved and I pass them around so that you can see the small vegetations present on the mitral valves.

Two of the animals on the day before death showed tj^ical twitchings and incoordinate movements. They threw themselves about in the cage and when placed on the floor would run around and dash their heads into the wall, a condition which might be considered choreiform, but not at all analagous to the chorea we see in children.

The only reason we have to offer why this arthritis has not previously been noted by all observers who have done experimental work with streptococci is that usually such work is done with the idea of testing the pathogenicity of organisms, usually determined by the amount and time necessary to produce a fatal result, and when post-mortem examinations were made the joints have not been carefully studied as a routine procedure. During life a rabbit having arthritis will usually remain quiet in one corner of the cage, and it is only when the rabbit is placed on the open floor and urged to move about that the lameness is detected. So, too, in most cases the swelling of the joint, unless extreme, is rather diSicult to detect through the thick skin and fur. Often a considerable distension of the joint and oedema of the surrounding tissues has been found after dissecting away the skin, when previously it could not with certainty be detected. In many cases the joint affection is mild, and unless one were especially in


terested in looking for it, it might be overlooked. It is only by making a routine examination of all joints that the lesions are discovered.

It may be stated that, while slight morphological and cultural differences existed between the various races of streptococci studied, none of these were constant enough to speak of a distinct variety. Each one differed slightly from the other in its manner of growth in bouillon, its growth in milk, etc. To make such comparative studies of any value, they should be repeated at intervals over a considerable length of time, to make certain that the characteristics have at least a fair degree of constancy. This has not yet been done with the organisms studied.

There was considerable variation in the pathogenicity as measured by the lethal dose of the races studied. Thus, while with certain of the organisms an emulsion made from the growth on six to eight tubes could be safely inoculated, in the case of the streptococcus obtained from the cervical adenitis in scarlet fever, one fourth of a tube caused death in five days when so inoculated.

As a result of this work we may say that arthritis and endocarditis may be produced by the intravenous inoculation of rabbits with streptococci from widely varying sources and that the results are similar to those described as produced by the inoculation with the so-called Micrococcus rheumaticus. I have seen the joints resulting from the inoculation of the organism isolated by Wassermann and also those produced by the organism isolated by Longcope and they do not differ from those produced here by these various streptococci.

Whether or not rheumatism is a form of streptococcus infection, I think we must still consider as undecided.

Discussion.

Dr. Cole. — During the past three years, in practically all cases of acute articular rheumatism treated in this Hospital, routine cultures have been made from the blood, and from the joints whenever any effusion was present in the latter. So far all our cultures from cases of acute articular rheumatism have been negative.

Similar results are reported by Philipp in the Deutsche Archiv fiir klinische Medicin, Band 76. He made cultures twenty-one times from the blood and six times from the joints in twenty-four eases of acute articular rheumatism. The cultures were made in a great variety of both solid and liquid media, and were cultivated both aerobically and anaerobically. Inoculations directly from patients were also made into guinea-pigs, rabbits, dogs, monkeys, and calves. But from none of these cases could any bacteria be cultivated.

Dr. Thayer. — That was the result obtained by Singer some years ago.

Professor Smith on the Jersey Mosquito. Db. Kelly.

Prof. J. C. Smith, of Eutgers College, President of the Entomological Institute, who has written an admirable hand book on the mosquitoes of New Jersey, giving the


116


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 168.


life habits of the more important species and an analytical key of some thirty species, presented me about a year ago with this handsome collection of eggs, embryos, larvae and adult forms. Notliing like it, I believe, has ever been prepared before. There are as you see a great variety of culices, the anopheles punctipennis, and the psophora or giant mosquito. In each upper row, on the most delicate entomological pins, are the males, and on the lower, the females, while the bottles contain the larval forms.

I desire to present this to the Hospital, to be placed where it can be seen and studied by our students.

I would ask if there is any evidence that the anopheles punctipennis carries the malarial parasite ? This whole question of mosquito distribution is so important that I will, with Dr. Osier's permission, ofEer to any member of the third year class, who presents next year a satisfactory thesis upon this subject, discussing the distribution of mosquitoes and presenting a map showing where they breed about the city, with suggestions as to the best methods of getting rid of them, a prize of fifty dollars.

Decemler 5, WOJ).

Gastric Ulcer: Clinical Varieties and Symptoms. De. Howard.

Dr. Howard gave the results of a careful study of ulcer of the stomach and duodenum based upon a series of eighty-two eases, with the following conclusions :

1. Gastric ulcer is rare in the Johns Hopkins Hospital as compared with cancer, the respective incidences being 1 to 225 and 1 to 56 general admissions.

2. Gastric ulcer in our series was as common in the male as in the female. In the male the percentage of greatest frequency was between the ages of forty and fifty — a decade later than usual.

3. Ulcer was in our cases relatively more frequent in the colored race and among Germans.

4. Vomiting occurred in 85.3 per cent; pain in 83.9 per cent, and hsematemesis in 75.6 per cent.

5. Great loss of weight may be present; thus, in 36 cases there was a loss of more than ten pounds, and in 9 of forty pounds or more.

6. Our statistics would indicate that hyperchlorhydria is not so constant as usually maintained ; it was present in only 17.6 per cent of our cases.

7. The blood picture is one of chloransemia as seen from the average count (haemoglobin, 58 per cent; red blood corpuscles, 4,071,000; white blood corpuscles, 7500 per c. mm.

8. Haemorrhage was the cause of death in 8.5 per cent of the total number of cases, and in 29.5 per cent of the fatal cases.

9. Perforation is rare (3 cases, or 3.6 per cent of our series). General peritonitis occurred in but one instance (1.2 per cent).

10. Ulcus carcinomatosum is rare — at least 4.8 per cent of our series.


11. Operation is indicated in all cases with perforation or perigastric adhesions, and in eases of copious or recurring hemorrhage, when medical means have failed after a fair trial.

12. The mortality of the series was 29.3 per cent; in the cases, however, who received treatment there was a mortality of only 18.8 per cent; in those receiving medical treatment alone, 8.6 per cent.

Gastric Ulcer: Diagnosis and Medical Treatment. Db. McCeae.

In common with the majority of diseases one must recognise that the diagnosis of gastric ulcer in tjrpical cases is usually very easy, in atypical cases very difiScult. We have to keep in mind that a large number of cases are latent and that it is sometimes impossible to make a diagnosis. The experience of the post mortem table proves that. Perforation or hemorrhage may occur without any previous history. Concerning ordinary typical cases very little requires to be said. The pain with its characteristics, the presence of blood and especially of blood microscopically are important. In a large percentage of cases blood is vomited, but it is important in cases in which there is no vomiting of blood to make a careful microscopical examination. One has to exclude cases where the presence of blood follows excessive straining. Hyperacidity is not regarded by us in this country as so frequent as by the German authorities. Coming to the more atypical cases one has to distinguish certain other conditions from ulcer, the most frequent ,of which are the various gastric neuroses. That is in many cases difficult to do and in many instances one has to leave the matter open. Fortunately the medical treatment may be the same whether the case be one of neurosis or ulcer. The pain is not so constant in the neuroses and repeated gastric analysis usually aids the diagnosis. Next probably comes the diagnosis from gall-stones. The character of the gall-stone attacks with their very severe character, the rapid onset and rapid recovery, generally help us, and the symptoms are not so constant. The gastric crises of locomotor ataxia rarely give much difficulty. Practically all the acute abdominal conditions may give trouble at times. In the chronic ulcer the most important point in diagnosis is that to be made between ulcer and neoplasm, and in many cases this is very difficult. In the majority of cases the finding of a large mass and free hydrochloric acid speaks for ulcer, but we have to remember the possibility of a neoplasm having developed in a former ulcer, in which the free hydrochloric acid is retained. In such a case if one is in doubt there should be no hesitancy in turning the case over for surgical exploration, especially as the procedure for diagnosis and treatment is the same.

Turning to the question of treatment I think it is well to discuss this in three groups of cases ; first, the doubtful caseSj largely composed of those where the diagnosis is between gastric neurosis and ulcer. The treatment of this doubtful group may come under the same heading as in the second group, the ordinary acute ulcer, the third group being the chronic ulcer.

As to the treatment of the ordinary acute gastric ulcer, in


Maech, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


iir


which one may also put the doubtful cases, the first essential is absolute rest in bed for a period of at least four weeks in the average cases. The rest is important in itself because by keeping the patient in bed you can control the question of feeding. In the majority of cases if the necessity of rest is properly explained, stress being laid upon the danger of the ulcer becoming chronic and the complications that may arise, the majority of patients will submit. In the treatment of the ulcer itself the essentials are rest, absence of irritation and the securing of the best blood supply. Eest is best secured in the majority of cases by the withdrawal of food by the mouth for a few days. That depends a little on the severity of the case and an average of four to six days is generally enough, during which time the patient is to be fed by the bowel. A small amount of water by the mouth may be allowed. As a rule at the end of four days of starvation it is well to begin with small amounts of liquid nourishment. Of foods milk stands first, probably given best peptonized or in the form of whey. One should begin with small quantities and gradually increase the amount. As a rule it is best for the first ten to fourteen days not to give anything else but milk. Probably a quart is enough in the majority of patients, though some writers advise two quarts a day. As a rule it should be given well diluted and with an alkali, either with an alkaline water or with a small amount of bicarbonate of soda. At the end of ten days or two weeks one may increase the diet gradually and more milk may be given, then the gruels, beef juice, jelly, etc., until at the end of four weeks one has the the patient back on soft food again. It pays to be conservative, to go slowly, increasing very little from day to day, and if any signs of irritation arise put the patient back on liquid diet at once.

To reduce the gastric secretions atropin may be given in 1/150 or 1/100 grain doses before food. Large quantities of alkalies should be given, sodium bicarbonate and magnesium carbonate in large doses. This probably in the majority of cases will be enough but there are a few other drugs which we usually employ, not perhaps in every case, with the idea of assisting the process of healing. Perhaps the most useful are bismuth, silver nitrate and olive oil. In giving bismuth in gastric ulcer one should give large doses, if by the mouth, dram doses at least four to six times in the twentyfour hours. An ounce may be given at one time through the stomach tube. Many writers advise washing out the stomach and then putting in an ounce of bismuth with water. Silver nitrate may be given in capsule, followed by half a glass of water, or dissolved and taken through the tube, the essential thing being to have it fresh. Of olive oil an ounce may be given at a time, perhaps four times in the twenty-four hours. A doubtful question is that of washing out the stomach. I think in the majority of cases one may wash out the stomach if the patient is having pain, lavage with an alkaline water often giving relief. In the majority of cases, however, the tube is not required. There is little danger if it is done with caution. An important point to keep in mind is that your treatment must not stop when the patient, so to speak, is well.


The gastric ulcer is very prone to recur and one should certainly keep track of these patients for a year, watching the diet and keeping up the use of the alkalies. If this were done there would be fewer cases of relapse. The use of alkaline salines is always helpful, for instance, Carlsbad salts. If there be ansmia iron should be given.

In the chronic cases we have quite a different condition. The ordinary acute case if taken early and treated systematically does extremely well; in the chronic ulcer it is different. But in the majority of these cases, unless there is indication for operation, I think it is well to give the same treatment as in the acute cases, remembering that it must be for a much longer time. If they do not improve under the ordinary treatment which we have gone over it is well to consider the advisability of surgical measures, and I think they are certainly demanded in three conditions: one for diagnosis, where there is doubt as to malignancy. The second is in cases of repeated haemorrhages. If you wait until the patient is exhausted and his hsemoglobin is low from repeated hasmorrhages you greatly handicap his chances. The third is the occurrence of pyloric stenosis due to ulcer.

With care in the diet and the use of the drugs mentioned pain is usually not troublesome, but in many cases certain of the sedatives are required. Small doses of the bromides with codein is enough sometimes but in some cases morphia must be given. It is best to give it by mouth and accompanied by bismuth. Morphia hypodermically is to be advised against in ulcer cases. There is only one treatment for perforation and that is immediate operation, but in order to be able to do that you must have made preparation beforehand. Just as the prognosis in operation for perforation in typhoid fever depends upon quick diagnosis, so it is in perforation of gastric ulcer. Those looking after the case should report at once any sudden abdominal pain or any sudden change in the patient's condition. The treatment of hfemorrhage in the acute case is largely that of rest; I am speaking of the ordinary hsemorrhage which we see and which is generally not alarming. Practically all we have to do is to cut off the food by mouth and give morphia hypodermically. The value of styptic drugs by the mouth is doubtful. There are certain of these cases in which haemorrhage is the direct cause of death, and in such cases operative procedures may be justified. If there are repeated haemorrhages it will be well to have the patient operated on. In the great majority of cases, as in cases of pulmonary haemorrhages, if the patient does not die at once there is very little danger. In the chronic cases the repeated haemorrhages are a strong indication for operation.

The patient with gastric ulcer has the right to demand two things : first, from the surgeon, that his technique be as good as possible so that there is no risk more than that incident to his condition in having operative procedures carried out, and I think the surgeons have fulfilled this ; second, he has a right to ask the physician that he recognise when the necessity for surgical interference has come.


118


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 168.


Discussion.

Dr. Panooast. — I should like to report two or three unusual features in a case of perforation. The first is that although the perforation occurred forty-eight hours before operation the patient is alive at the end of three weeks. He had a high grade of peritonitis throughout the greater peritoneal cavity and so far as the general peritoneal cavity is concerned the peritoneum is taking care of itself. A second point of interest to me is that the patient was distinctly jaundiced and had bile in the urine, and in his general peritoneal cavity. There was a large amount of bile in the general peritoneal cavity, so much that the contents were •dark green. A third point of interest is that he has developed since the first operation two secondary abscesses. One in the pelvis was easily drained through an incision on the other side of the abdomen. The other abscess was drained last night through the 9th intercostal space on the left side. 1600 ee. of pus were removed. It was probably a subphrenic abscess. The patient is very ill and probably will not recover.

December 19, 190^.

The President, Dr. Joseph C. Bloodgood, in the chair.

Report of a Case of Ulcerative Endocarditis, with Embolism of the Aorta. Db. Osleb.

The patient, aged 13 years, a factory girl, was admitted November 3, 1904. Past history negative. No history of genito-urinary infection. Onset of present illness October 24, with chill, fever, headache and some abdominal pain. Chill came on while at work and was followed by a chill every day afterward. She vomited daily and was thought to have iyphoid fever. She was admitted to Ward' G on November 3. Physical examination was practically negative, except for a rather rough systolic murmur at the apex transmitted outward to anterior axillary line, but not heard in the axilla. The second pulmonic sound was not accentuated. Edge of spleen could be felt. There was active knee-jerk and ankle clonus present. Koenig's sign absent. Leucocytes were 28,000. Temperature high, irregular, and there was a daily chill. Sweating slight. The systolic murmur increased in intensity .and was transmitted into axilla. Petechias appeared over the face, chest and arms. On November 8, lumbar puncture gave 70 CO. very clear fluid. Pressure 280 mm. Culture negative. There was a slight vaginal discharge but no intracellular diplococci. On December 4, for the first time there was a presystolic thrill and rumble. She also cried out with pain in the lower limbs and there was apparently anaesthesia below the Imees. Stools and urine were passed involuntarily. No pulsation could be felt in the dorsalis pedis or popliteal. On De•cember 5, feet were not cold or discolored. Knee-jerks were present, but diminished. On December 7, pulsation felt faintly in popliteal. Widal was repeatedly negative. Blood cultures were made on November 4, November 11 and Decem


ber 4. Urine cultures on December 15, and November 22. The patient died December 16.

The illness was of six weeks, with high and irregular fever, and with no special embolic features until two weeks before death ; there was a great deal of doubt at first whether it was typhoid fever or endocarditis. The diagnosis was reached by exclusion, and it was not until the murmur increased in intensity and changed in character and the cardiac symptoms became more positive that a definite diagnosis was made of ulcerative endocarditis. A point of special interest is that a week before death she had paralysis of her legs with slight change in sensation and complete absence of pulsation in the arteries. Of course we suspected a plugging of the vessels, probably of the aorta, but strange to say, instead of the usual sequence, namely, change in color of the feet, at first bluish, then black, and almost certainly followed by gangrene, in this case the legs remained cold, sensation was reduced ; there was no pulsation in the vessels, but no gangrene followed, and there was not even change in the color, a most unusual thing.

The specimen, which is a most remarkable one, shows typical ulcerative endocarditis of the mitral valve with a large thrombus occupying the lower part of the aorta and blocking it completely. There was a small embolus in the spleen and one in one kidney.

We had another illustration of plugging of the aorta by thrombus in a case of chronic mitral disease and I show the specimen.

Case of Typhoid Fever showing some Unusual Features. Db.

Cole.

Dr. Osier has asked me to speak of a case of typhoid fever in a young colored girl, showing some unusual features. The child, aged 10 years, was admitted on December 8. The onset of the illness occurred on December 1 with a violent attack of vomiting. Following this there was fever and some pain in the right side of the abdomen. There was no delirium. The child remained in bed, but on December 8 walked to the hospital and did not seem very ill. While waiting to be sent to the ward, however, there suddenly developed active, talkative delirium. This continued almost constantly, and slight stiffness of the neck and extremities developed. On December 12, a lumbar puncture was performed and 25 cc. of fluid obtained under normal pressure. No growth occurred in the cultures from this fluid and microscopical examination was negative. The Widal test performed on December 10 was also negative. The fever continued high, between 102° and 105°. The signs of meningitis became more definite, there was retraction of the head, the knee-jerks were active, and a fairly definite Kernig's sign was obtained.

Notwithstanding this, a second lumbar puncture performed on December 16 gave negative results as before. On the same day, however, the Widal test was positive, and in cultures made from the blood a pure growth of B. typhosus developed. The abdominal pain continued ; she grew gradually worse and died on December 18.

This case was interesting, first, from the standpoint of diag


March, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


119


nosis. The marked meningeal features and absence of an)' definite signs of typhoid fever made the diagnosis difficult. The first definite evidence that we were dealing with a case of typhoid fever was given by the blood cultures and Widal reaction. Second, this case well illustrates the not infrequent occurrence of marked meningeal features during typhoid fever. As I have previously stated, these cases may be divided into three groups : first, those in which there is no direct association of the bacilli with the cerebral manifestations, and no lesions are to be found in the brain to account for the symptoms; second, those in which the bacilli are present in the spinal fluid, but no marked inflammation of the meninges is present; and third, the cases of true suppurative typhoid meningitis.

This case is a good e.xample of the first group, and of those cases to which certain of the French writers have applied the term meningisme. In this case lumbar pimcture was performed on two occasions with negative results, and at autopsy absolutely no lesions could be demonstrated in the brain or meninges. Typical typhoidal lesions were found in the intestines and there was very marked enlargement of the lymphatic glands, the mesenteric glands and Peyer's patches being of enormous size, as you can see in these specimens which I exliibit.

Discussion.

Dr. Osler. — Tt is difficult in these cases to determine whether a true meningitis is present or not. I would refer you to Stokes' well-known dictum that the acute congestion of the cerebro-spinal centers in fever may give rise to all of the symptoms of a meningitis ; there may be no single symptom absent in cases where there is only this extreme engorgement. We have had several instances where the meningeal symptoms were very marked without the existence of actual meningitis.

Puerperal Infection with Gas Bacillus. Dr. Little. (To appear in April Bulletin.)

Report of a Case of Arteriovenous Aneurism of the Thigh. Dr.

OsLEli.

ilany of you may recall that about three weeks ago I showed at the clinic three remarkable cases of aneurism, one of them an arteriovenous aneurism of the femoral artery in a man aged twenty-nine years, who was shot 15 years ago. The tumor has gradually grown to about half tlie size of a pineapple. The leg was greatly enlarged, blue to the foot, and on palpation over the tumor there was a remarkable vibratory thrill which could be felt up the thigh over the entire anterior and posterior portion of the leg. On listening with the stethoscope one could hear a murmur of great intensity, a humming-top murmur, intensified with each systole. I called your attention at that time to the original description of the disease by William Hunter, which pass around again, as it is the first account of this form of aneurism. Yesterday this man died suddenly, and Djs. Cole and MacCallum secured the specimen.


Discussion.

Dr. MacC.\llum. — Orth divides the traumatic aneurisms in which communication between artery and vein is estaljlished into three groups: (1) the arteriovenous aneurism in which an ordinary aneurism has ruptured into a vein; (3) the aneurisma varicosum in which a sac lying between the two vessels forms the communication between them; and (3) the varicoaneurismaticus in which the artery and vein are intimately united and communicate through openings in their walls. The sac whieli forms in the second variety is the result of the encapsulation of a hsematoma through which the blood still circulates.

Bramann (Arch. f. klin. Chir., XXXIII), has collected 141 cases, of which the greater number resulted from venesection, but there were also 35 cases of communication between the femoral artery and vein. The condition is usually produced by such an injury as a stab or gunshot wound. The present case does not correspond precisely with any of Orth's classes. The femoral artery is greatly dilated and at about the beginning of the lower third of the thigh it shows two perforations separated by a bridge of tissue. The femoral vein lying close beside it shows one perforation at the same level. A probe can be passed from the artery into the vein through these apertures; in so doing it passes the orifice or mouth of a sac about 12 cm. in diameter which lies to the inner side and somewhat in front of the artery and vein. The sac thus does not form the communication between the vessels, although the probe passes readily from either into it ; nor are they directly united, but rather by way of a small space or vestibule which lies in front of the orifice of the sac. This sac is formed of dense fibrous tissue and is lined by a granular, deeply pigmented clot. The veins were enormously distended both below and above the level of the communication. The stagnation was such that the man suffered for many years from a persistent leg ulcer.

Operative interference is seldom advisable in such cases on account of the risk of gangrene.

Dr. Osler. — The question of operation is a very interesting one. You may remember that by a curious coincidence the other day upon which I showed this patient at the clinic I received a letter from an old friend, a patient of mine, who had had for many years an arteriovenous aneurism in the axilla. He was a man of 43, who when 15 years of age was running down a steep grade with a lead pencil in his pocket and it penetrated his axilla. He had a sudden redness and then blackness of the hand with the gradual growth of an aneurism, and he has had that aneurism ever since. He is a strong, vigorous man. He has had the day fixed for operation, but I think wisely, deferred it. The gi'eat danger of operating is in the gangrene which is apt to follow. A very interesting ease was reported a short time ago by a Spanish surgeon, who in a case of this kind opened the artery, stitched the orifice and closed it up again and the man made a complete recovery.

Survey of Ovariotomy at Extremes of Life. Report of a Case in a Child aged Five. Mr. H. I. Wikl, (See this Bulletin, page 102.)


NOTES ON NEW BOOKS.


Vol. XVI. - No. 16 9.


BALTIMORE, APRIL, I905.

CONTENTS - April

  • The Surgery of the Posterior Mediastinum ; its Past and its Future. By J. D. Faure, M. D., 135
  • Aplastic Anaemia Associated with Lymphoid Hyperplasia of the Bone-Marrow. Hy George Blomeb, M. D., 127
  • Preliminary Communication Regarding an Immune Body Capable of Inhibiting the Development of Cancer in Mice (Adenocarcinoma, Jensen). By G. H. A. Clowes, Ph. D., .... 130
  • A Multiplex Slide-Holding Device. By Edward F. Miller, . . 132
  • Dr. Heinrich or Henry Keerl, of Baltimore, tlie "Hessian Surgeon." By Eugene F. CoRDELL, M.D., 133
  • The Bacillus Aerogenes Capsnlatus in Puerperal Infection. By Herbert M. Little, M. D.

Proceedings of Societies :

The .Johns Hopkins Hospital Medical Society, 146

A Case of Arterio Venous Aneurism IDr. Osler] ; — The Immunization of Mice to Cancer [Dr. G. H. A. Clowes] ; — Pathological Changes [Dr. Welch] ; — Apparatus for the Treatment of Fracture of the Femur; Treatment of Esophageal Stricture [Dr. Theodore DnsHAM] ; — Peri Pancreatic Abscess (Dr. Thater; Surgical Treatment, Dr. Finney] ; — Gastric Tetany [Dr. Howard); — The Pathology of Tetany [Dr. MacCallum; — Synsesthesia [Dr. H. L. Smith]; — Hanging Block Cultivation of Bacteria; The Ultraviolet Rays; Thermophilic Bacteria [Dr. Ford]; — The Cure of Uterine Cancer [Dr. John G. Clark); — Pathology of Cervical Cancer |Dr. Sampson].

Notes on New Books, 150


THE SURGERY OF THE POSTERIOR MEDIASTINUM ; ITS PAST AND ITS FUTURE.^

By J. D. Faure, M. D., of Paris, France.


The revolution which gave to surgery a scope previously unknown and far beyond the dreams of our predecessors, has as yet failed to supply efficient means for the treatment of affections of the posterior mediastinum.

The fact that this region is situated in the depth of the chest between the lungs, before the vertebral column, and behind the bronchia and the superior part of the heart, has, until very recently made it unattainable, and protected it from invasion on the part of even the most daring surgeons.

When abdominal surgery was achieving all conceivable operations upon the uterus and its adnexa, the liver and the bile ducts, the spleen, the stomach, and the intestine; when the surgery of the chest ventured to incise the lungs in order to reach abcesses, or even to extirpate fragments of lung tissue; when the cranium and the vertebral column were opened in order to explore the nerve centers, and evacuate cerebral abscesses, or to extirpate tumors of the spinal cord or of the encephalon; when the anterior mediastinum was entered for the purpose of suturing wounds of the heart, the posterior mediastinum alone still remained inaccessible.

^Address deUvered at the Jolins Hopkins Hospital, April, 1904.


There were, it is true, many bold attempts at its surgery, all or nearly all of which attacked the esophagus either for cancer or for occlusion occasioned by a foreign body. I do not here take into account the few operations performed upon scrofulous abscess, which led surgeons as far as the anterior part of the vertebral column, because although they were actually operations on the posterior mediastinum, they achieved nothing more than the cleansing of a tuberculous abscess, and cannot be considered in the same light as the deliberate opening of that region for the purpose of operating upon the organs which it contains.

Operations of the latter kind have been very rare, and although, in 1888, Wassalow showed for the first time that it was possible to reach the esophagus by resecting a few ribs and separating the pleura from the costo-vertebral groove, the most important publications made since that date have been entirely anatomical. Quenu and Hartmann, and Potarea have investigated the connections between the esophagus and the thorax and demonstrated that in order to reach the former it is necessary to pass either by the left of the vertebral column (Quenu and Hartmann) or by the right (Potarea).


126


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 169.


Schwartz has made some interesting researches on the means of reaching the bronchia in order to extract foreign bodies. Lery experimented in resections of the esophagus upon dogs, and Jowet utilizing the same animal, succeeded in affecting the trans-diaphragmatic anastomosis of the esophagus with the cardiac end of the stomach.

Operations upon the posterior mediastinum in human beings, undertaken with a therapeutic purpose, have been very rare. Eelm attempted to extirpate cancer, but only succeeded in incising the esophagus. Slobet and Tuffier, the latter operating through the pleura, have also incised this organ, to relieve cicratricial stricture, and Forgue made an effort to extract a foreign body from it, but was obliged to abandon his attempt without opening the esophagus, succeeding only in exploring it with the finger tip. Curtis, in 1886, opened the right bronchus through the posterior wall in order to extract a foreign body, which, after all, he could not reach. Such, unless I am mistaken, are all the operations hitherto performed on the posterior mediastinum. They have all, as you see, been tentative and have ended in failure, or at least terminated in simple incision of the esophagus or the bronchi. However bold and skilful the surgeons who made these attempts may have been no other result was possible, at least in the case of operations upon the esophagus; bronchotomy, performed for the extraction of a foreign body might be successful, but operations upon the esophagus such as those just cited, were foredoomed to failure.

According to Wassalow's method, which all operators are now bent upon following, any extensive operations upon the esophagus are utterly impracticable. It is true that it is possible to reach it after the third, fourth, fifth, and sixth ribs have been resected and the pleura pushed aside, and after it is recognized and grasped with a pair of forceps, a foreign body, impacted at this level, can be extracted. It may also be possible to incise a stricture, but there is not suiBcient space for extirpation of the esophagus. In fact, if extirpation is to be attempted, it is best to adopt the transpleural route with liberal opening of the chest, as indicated by Tuffier, though it is a great inconvenience to operate through the pleura and the risks of accident are multiplied by doing so. This method supplies more room, however, and although like those of Wassalow, Potarea, Quenu, and Hartmann it is perilous and difficult, it does not, at any rate, present impossibilities. It is insufficient, it is dangerous, and it is bad, but it is practicable.

For some time I have been strongly convinced that some better method might be devised, for I believed that it was not only possible but easy to open a clear wide pathway to the posterior mediastinum, afEording sufficient space to permit the execution of any operation.

It seemed to me that I could best demonstrate this fact by performing the most difficult operation possible, and therefore I undertook the extirpation of a cancerous esophagus situated in what is held to be the most inaccessible region.


that is the center of the posterior mediastinum, behind the bifurcation of the bronchia and the pedicle of the lung.

I succeeded in performing this operation without accident, and even without difficulty, and although both my patients died in consequence of unforeseen accidents I believe that I have, nevertheless, demonstrated the possibility' of operating successfully on the only part of the human body from which surgeons have heretofore been withheld by a consciousness of impotency.

I do not insist that such operations must be performed exactly as they are described in the Bulletin de la Societe de chirurgie de Paris for January 25, 1903, I only wish to insist upon the conditions which are essential to success. One of these is a means of access to the posterior mediastinum sufficiently wide to permit ease of movement and enable the operator to execute all the numerous delicate manipulations and explorations demanded in such an important operation. All surgeons have hitherto obstinately limited the extent of their original opening to the resection of three or four middle ribs, but this is too narrow a means of access and fails to give sufficient space and light. To enable the surgeon to see clearly and fully it is necessary to include the first rib in the costal resection, although this, for some inexplicable reason has heretofore been respected. It is the section of these ribs and particularly of the first one," however, that governs the conditions of the operation. So long as the first rib is intact it is impossible to make any extensive manipulation in the posterior mediastinum, and even if all the other ribs from the second to the eighth, or even the ninth be removed, the first rib still fixes the shoulder and all the adjacent parts of the chest immovably to the vertebral column; if, on the contrary, the first rib is resected or even simply divided, the corresponding half of the chest is immediately loosened from the backbone, while the shoulder is pushed aside to such an extent that it becomes necessary to hold it to avoid wrenching the roots of the brachial plexus. The posterior mediastinum then opens like a book, and nothing is easier, after detaching the pleura and the apex of the lung, than to reach its depths and execute all possible manoeuvres. In my operations, conducted after this method, I have been able to explore the posterior part of the trachea and bronchia, to dissect the pneumogastric nerve behind the pedicle of the lung, and to make, in short, all the manipulations necessary to success in a complicated operation such as the extirpation of a part of the thoracic esophagus.

This new technic has brought the most difficult operations on the posterior mediastinum within the range of possibility. Only experience can show what a future is in store for them, but we are at liberty to speculate in regard to it.

It is, of course, evident that this class of operations must always be of a serious character, since the life of the patient is at stake, and they are indicated only in cases where all other means of treatment have been tried in vain and where life is in immediate danger, such as cancer, foreign bodies iu the esophagus, or suppurative mediastinitis. In extracting foreign bodies retained in the bronchia, it seems to me that the


April, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


127


usual methods are best, using the Williams bronchoscope for the purpose, or if such means absolutely fail, a simple bronchotomy may suffice. But should the latter operation, which is somewhat obscure, prove unsuccessful, it is obvious that the " enlargement of the restricted path afforded by resection of three or four ribs into a wide exploration by section of five or six ribs such as I practice and advise would be indicated as a last resource.

Suppurative mediastinitis, does not often, in my opinion, afford a suitable opportunity to trv' this final expedient. The signs of the condition are generally too obscure and its evolution too rapid, to render such intervention possible. Under certain conditions, however, it may be necessary to employ it.

The results obtainable in cancer of the esophagus is a question of importance. I do not entertain, with certainty, any hope that cancerous patients can often survive the extirpation of the esophagus many years. But I do not see why the operation should not sometimes be followed by a lasting success.

It is true that my two patients died, both succumbing in the same way after twenty-four hours, without hemorrhage and without fever, but with symptoms which may, I think, be ascribed to slow suffocation. I had thought it necessary to leave a large drain in the posterior mediastinum, and through this, as I could plainly see, a large quantity of air penetrated the mediastinum at each inspiration, producing a genuine extra-pleural pneumothorax, and so lessening, by just so much, the quantity of air entering the lungs. I have had no further opportunity to perform the operation, and to ascertain, as I intend to do, if the suppression of the drain will obviate the symptoms just described. If, as I think possible, this cause of death can be removed, I see no reason why the operation, although undoubtedly a serious one, should not yield results m.ore successful than these to which I have as yet attained, thanks to the technical improvements which new operations always introduce.

Sauerbach (Mickulicz' assistant) has just developed upon animals a method which may, to a certain degree, avoid the accidents I have described as well as those which may result from pneumothorax. He operates in a hermetically sealed box, where a certain amount of vacuum is created. The head


of the animal is kept outside. The surgeon and his assistants are inside the box, operating upon the body of the animal, the neck of which is set in a hermetically sealed rubber collar, which prevents communication with the outside air. The excess of pressure inside the lungs communicating with the outer air, on the pressure outside the lungs exercised by the rarified air of the box prevents accidental pneumothorax and allows, so its author claims, the execution of the most complicated operations within the thorax without any danger of opening the pleura. I earnestly wish this method may be successful, but I fear it is very difficult of application to man and I hardly expect to see it in use among surgeons. The point of present importance, in my opinion, is to guard against the danger of extra-pleural pneumothorax, occurring, as I have just described, and to prevent it by suppressing the use of drains.

It is, however, in the extraction of foreign bodies impacted in the thoracic part of the esophagus that posterior thoracotomy will, I hope, give its best results. Under these circumstances, when attempts to extract foreign bodies by the natural channels have failed, this form of thoracotomy should be the operation of choice. In spite of the best guiding marks, the simple resection of the middle ribs may not suffice for the discovery of a foreign body in the thoracic esophagus, and still more is it likely to fail in its extraction. This new technic will permit extraction without difficulty and with every prospect of success.

I should never advise this operation in the case of strictures of the esophagus due to cicatricial tissue. This condition can be relieved by means which are fully as efficacious and less dangerous. A patient whose esophagus has been removed can be perfectly well fed by the more harmless and perfectly sufficient gastrotomy.

The gravity and difficulty of the operation just described are such that it must be reserved, as I have said, for patients whose lives are in immediate danger from cancer or from the presence of a foreign body in the esophagus. I shall consider myself well repaid for my trouble if only one life is saved by means of it. Allow me to add that nothing could please me more than to see one of you perform the first successful operation of this kind.


APLASTIC ANiEMIA ASSOCIATED WITH LYMPHOID HYPERPLASIA OF THE BONE-MARROW.

By George Blumer, M. D.,

Associate Professor of Pathology, Cooper Medical College, San Francisco.

[From the Pathological Laboratory of Cooper Medical College, San Francisco, Cal.'\


Since Ehrlich * described the first case of so-called "aplastic" anjemia in 1888, a number of cases have been placed on record. Up to the time that Senator^ reported


' Charlte-Annalen, 1888.

' Zeitschrift fiir klinische Medicin.


Bd. LIV. Hft. 1 and 2.


his recent case many writers seem to have regarded the lesions underlying this condition as essentially imiform, thougli there has been a good deal of discussion as to whether these lesions were to be regarded as a specific pathological entity or merely as a subform of ordinary pernicious anaemia. There is certainly a striking difference between the narrow lesions in


128


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 169.


Muir's case/ in which the marrow was aplastic and fatt}' throughout, and those in Senator's case, in which it was hyperplastic and lymphadenoid throughout. These cases again differ from those with the ordinary lesions of pernicious anaemia plus aplasia of the bone-marrow. The examination of the 1ione-marrow in many of the reported cases is comparatively imperfect, and it is therefore difficult to say, positively, under which type many of them are to be placed. As atypical cases are often of value in clearing up doubtful points, we venture to record a case which was observed in the service of Dr. J. 0. Hirschfelder in the City and County Hospital. We are indebted to Dr. Hirschfelder for the opportunity to study the case. The following is a simimary of the important points in the clinical and pathological history of the case :

P. D., male, a laborer by occupation, was admitted to the Hospital November 4, 1904, complaining of general weakness and shortness of breath.

His family history was negative. Aside from a definite history of an attack of lues thirty years ago his past history was unimportant. His present illness began one year and ten months prior to admission. He dated it from the passage of a considerable quantity of blood from the bowel as a result of hemorrhoids. Since then he has had occasional passages of blood, but only when constipated. As far as can be judged the quantity of blood lost In this way has not been great. Aside from his rectal trouble he has had no symptoms of note until eight months ago when he began to have gastric disturbances. Since that time he has vomited a good deal, at times as often as thrice daily. At no time has he vomited blood. At the same time he has suffered from a progressively increasing wealsness and shortness of breath. He has lost ten or twelve pounds in weight since the beginning of the illness.

Examination shows a well developed and moderately well nourished individual with a distinctly yellowish pallor. The chest is fairy well formed. Aside from the usual physical signs of emphysema the lungs are negative. The area of cardiac dullness is not enlarged, and the heart sounds are clear. The second pulmonic sound is accentuated. The liver dullness measures 12 cm. in the mammillary line, the edge of the organ is palpable. The spleen is not palpable. The lymph nodes throughout the body are slightly enlarged. There is a projecting external hemorrhoid, and rectal examination shows a number of internal hemorrhoids and a sloughing ulcer on the right wall of the rectum.

Smears from the blood show slight variations from normal in the size of the red corpuscles. There are a very few macrocytes most of which show polychromasia. A moderate number of microcytes are seen. Poikilocytosis is present but not marked. An occasional red corpuscle shows granular degeneration. There Is very evident leucopenia. The predominating type of leucocyte is the small mononuclear form, and 80% of these are typical small lymphocytes. The remainder differ from them only in slight irregularities of the nucleus, and in the possession of a greater amount of protoplasm containing an occasional basophile granule. Hardly any blood plates are to be made out. The following table shows the result of the blood counts:

Reds. Leuc. Hb. Poly. L. Mono. 8. Mono. Eos. Has.

5th 6.0% 4.5% 89.5%

7th 1,516,000 4,600 20% 10.3% 1.3% 88.3%

8th 1,304,000 20% 8.0% 1.5% 90.0% 0.5%

9th 7.5% 2.0% 90.5%

10th 1,100,000 2,450 . . 7.5% 2.0% 90.5%

14th 1,204,000 4,200 22% 7.5% 2.25% 90.25%

= British Medical Journal, 1900, Vol. II, page 909.


An average of one nucleated red to each differential count was observed. The cells were all of the normoblast type, or but slightly aberrant. No definite megaloblasts were seen.

The stomach analysis shows an absence of free hydrochloric acid, a trace of lactic acid, and microscopically a few large bacilli.

The urine contains no albumen or sugar, microscopically a few leucocytes and a few granular casts are present.

The feces contain no parasites or ova.

During the time the patient was under observation there was an irregular temperature ranging between F. 100 and P. 103.5. The patient died thirteen days after admission with signs of bronchopneumonia.

The autopsy was made by Dr. Wm. Ophiils. three hours after death. The following notes are abstracted from the protocol:

Heart. — The pericardium contains 70 cc. of clear fluid. The heart muscle is dark brown and firm. The valves are normal.

Lungs. — There is marked diffuse emphysema. There are easily torn adhesions at the apex of the left lung, and a small scar in the lung beneath them. The upper part of the left lung shows localized oedema and hypersemia. There is a small scar at the right apex. On the right side there are larger areas of oedema and hyperaemia. and some consolidated spots. There is an encapsulated caseous area a little below the right apex.

Liver. — The organ measures 16 x 27 x 6 cm. It is dark brown in color. Over the anterior part of the right lobe there is a circumscribed thickening of the capsule with a small scar in the liver tissue beneath. The gall-bladder is large, and filled with clear, light yellow bile containing a few dark flakes.

Spleen. — The organ measures 10.5 x 2.5 x 2.5 cm. The markings are very definite. There are some barely visible brown spots in the pulp.

Kidneys. — The left measures 11 x 5.5 x 3 cm. The capsule is firmly attached. The tissue is pale and slightly brown. Right kidney same as left.

Adrenals. — Both are small and dark brown In color.

Genitalia. — Marked atrophy is present in the external genitals. There are large white scars in both testes.

Stomach. — The organ contains thin yellow fluid. The mucous membrane shows slight atrophy.

Intestines. — The duodenum contains bright yellow contents. The jejunum is normal. There is marked atrophy of the ileum and colon. The upper end of the rectum is contracted. At the anus there are several external hemorrhoids, the largest 2.5 X 1.5 cm. Extending 5 cm. up the rectum is a large irregular ulcer with partly brown, partly yellow necrotic masses at the bottom. At one place the ulcer has perforated into the peri-rectal fat.

Aorta. — There are a few yellow spots in the intima.

Lymph Nodes. — There are some moderately enlarged, reddishgray lymph nodes in the supra-clavicular space. The peribronchial lymph nodes contain calcified areas. The retroperitoneal hsemolymph glands are slightly enlarged, and dark red in color.

Bone-marrow. — The bone-marrow in the upper part of the right tibia is yellow and fatty. There is partly red and partly yellow marrow in the upper end of the left humerus and the lower end of the left femur. The vertebral marrow shows no marked change to the naked eye.

Bacteriologic. — The cultures from the lung show the diplococcus lanceolatus associated with the bacillus of Friedlander and the bacillus pyocyaneus. The cultures from the liver, spleen, and kidney show the bacillus pyocyaneus with the colon bacillus.

The following were the important points brought out by the histologic examination:

Heart. — The right ventricle shows a moderate degree of fatty infiltration. The left ventricle shows well-marked brown atrophy.


April, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


129


Lungs. — The usual appearances of emphysema, csdema, and hyperjemia are present. In the consolidated areas the lesions of broncho-pneumonia are found, the predominating cells in the exudate being polynuclear leucocytes.

Liver. — Marked brown atrophy is present. The pigment, which is present in considerable amount, follows the course of the bile capillaries. It does not give the iron reaction.

SpJeen. — There is periarteritis of most of the splenic vessels. The lesions of chronic passive congestion associated with an early chronic interstitial splenitis are present. There is a little brown pigment in the pulp which does not give the iron reaction.

Kidneys. — Both kidneys show a few patches of atrophy in the cortex. There is a moderate degree of cloudy swelling.

Testicles. — There is atrophy of the glandular tissue associated with patches of dense scar tissue.

Stomach. — There is a moderate degree of atrophy of the mucosa.

Intestines. — The mucous membrane of the ileum shows a moderate degree of atrophy. The ulcer of the rectum shows a base made up of granulation tissue; this is capped by a necrotic layer in which a few polynuclear leucocytes are present.

Lymph Nodes. — There is slight hyperplasia. The hcemolymph glands do not show any evidence of increased blood destruction.

Bone-marrow. — Smears from the tibia showed only blood having the same characteristics as that from the peripheral circulation. Smears from the vertebral marrow show a marked hyperplasia of the lymphoid elements, and almost complete absence of nucleated reds. The predominating cell is a mononuclear element about the size of the small mononuclear cell of the circulating blood. This cell has a large, pale-staining, centrally-situated nucleus, with a narrow rim of protoplasm which stains but little darker than the nucleus, and is at times scarcely distinguishable from it. Granular cells are almost absent, those most numerous being mononuclear cells with small, thicklyclustered, basophilic granules. Nucleated reds are very scarce, only 15 being seen in a count of 3200 cells. These were all of the normoblastic type. A count of 3200 cells gives the following:

Small Mononuclear cells 98.52%

Large Mononuclear cells 28%

Polynuclear leucocytes 03%

Polynuclear eosinophiles 03%

Neutrophile myelocytes 18%

Basophile myelocytes 21%

Atypical forms 75%

The sections of the bone-marrow confirm these findings. The marrow from the tibia consists entirely of fat; that from the lower end of the femur, and from the vertebra shows marked lymphoid hyperplasia, most marked in the vertebral marrow. In both of the last named sections the almost complete absence of nucleated reds and granular leucocytes is apparent.

From a clinical standpoint this case presents all of the leading characteristics of progressive pernicious anEemia: the yellow anffimia without much emaciation, the gastro-intestinal symptoms, the progressive weakness and dyspnoea, and the lack of physical findings. Yet neither the blood picture nor the pathological findings correspond to those of ordinary pernicious anaemia. The blood, in fact, shows none of the changes which are ordinarily found in pernicious anaemia except the progressive character of this anjemia, and the leucopenia with the relative increase in the mononuclear leucocytes. The great variation in the size of the red cells, the presence of megalocytes and megaloblasts, and the high color-index are lacking. The picture presented corresponds to that originally


described by Ehrlich in 1888 as " aplastic " anaemia. As the name indicates there is, in such cases, a lack of evidence in the blood of any attempt on the part of the bone-marrow to compensate for the loss of blood corpuscles. The picture presented by the peripheral blood is that of a progressive loss of red corpuscles without any marked variation in the size or shape of the cells, and without the presence of nucleated reds. The leucocytes are usually diminished in number, and there is a relative increase in the mononuclear forms with almost complete absence of cells with granular protoplasm. The pathological lesions in our ease do not correspond to those found in cases of the Ehrlich type, in fact, instead of a simple aplasia the bone-marrow showed in places a hyperplasia of the mononuclear elements.

Since Ehrlich's case was reported a number of cases have been recorded in which the blood picture was similar. A study of these cases from the pathological side shows that the essential lesions are not in all instances alike. Three main groxips may be recognized: (1) Those cases in which the lesions are those of progressive pernicious anasmia. (2) Those cases in which the bone-marrow shows primary (?) aplasia. (3) Those cases in which there is a hyperplasia of the mononuclear elements of the bone-marrow. There is also evidence to show that in one condition which is usually followed by recovery, Barlow's Disease, a blood picture essentially similar to that of aplastic anaemia may be present, and autopsy may show aplastic marrow. This simply indicates that the condition which we clinically term aplastic anaemia is not a pathological entity, but may be due to a variety of causes.

In cases in which the bone-marrow is aplastic throughout there is little difficulty in explaining the blood picture. The same is true of eases of pernicious anaemia with aplasia of the bone-marrow. The actual cause of the aplasia is still obscure. Possibly it is due to conditions similar to those seen in severe infections without leucocytosis, i. e., the causative irritant is of exceptional intensity or the individual power of regeneration is excessively low.

In cases of the character of the one here reported, and the cases of Senator and Wolff* seem to be the only similar ones, the blood picture is more difficult of explanation, and the exact nature of the bone-marrow changes is open to discussion.

The explanation of the blood picture in Senatoi^s case does not seem so difficult as in our own, as in his case the bone-marrow was hyperplastic throughout. In this case it might be supposed that the anaemia was due to a crowding out and replacement of the erythroblastic elements such as occurs, according to Dock and Warthin," in chloroma, and presumably in other forms of leukaemia. In our case, however, the shafts of the long bones showed no lymphoid hyperplasia, and it is necessary to assume either that two distinct processes, lymphoid hyperplasia and aplasia, were going on at the same time, or that the hyperplasia, though only partial, caused all the


Wolff: Berliner klinische Wochenschrift. Jahr. 42, No. 2, 1905. ° Trans, of the Association of American Physicians, 1904.


130


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 169.


changes. The latter seems to us the more probable. One hypothesis which Senator advances seems to explain both the hyperplasia and the anasmia much more satisfactorily than does a mechanical replacement and crowding out. This explanation is, that the lymphoid cells which have undergone hyperplasia represent the parent cells from which should arise both the red corpuscles and the granular leucocytes. It is easily seen that if these cells fail to go through their normal cycle of existence, and instead undergo proliferation unchanged, neither red cells nor granular leucocytes could be produced. Why in our case there should be no regenerative changes in the marrow of the long bones is more difficult to explain unless we assume that when this marrow regenerates the regeneration takes place by the emigration of leucocytes from pre-existing red marrow. Perhaps the same cause which produces tlie loss of differentiating power in the parent cells also leads to a loss of power to emigrate, though Senator's case does not support this view.

Query as to the exact nature of the bone-marrow hyperplasia in these cases brings up the whole subject of the pathology of leukemia and allied conditions. Senator regards his case as a pure myelogenous pseudoleuljffimia and our case closely resembles his. The relation of such cases to lymphatic leukae


mia is still doubtful. There are cases on record in which the blood picture is said to have changed from that of pseudoleukemia to that of leukfemia, and there are cases of lymphatic leukjemia in which the leucocj'tes have dropped to normal, or even below normal, before death. Inasmuch as the ordinary lesions of leuksemia were wanting in the internal organs in this case it might seem improper to class it with this disease, though the bone-marrow changes correspond closely to those found in cases of lymphatic leukaemia without enlargement of the lymph nodes. If we follow Warthin's ' recent classification of the leukffimias, based on the theory that the essential lesion is a neoplasm of the leueoblasts, the case would be classed as a nonchloromatous aleukemic leucoblastoma, and such we believe to be the most rational interpretation of it. After all the classification of this group of diseases must rest upon the pathological findings, and not upon the clinical picture and the changes in the blood in the peripheral circulation. The mere fact that in one case the proliferated cells gain access to the circulation while in another they do not, may serve as a basis for clinical classification, but does not alter the fact that the underlying pathological condition in both classes of cases is essentially the same.


' Trans, of the AssociatioE of American Physicians, 1904.


PRELIMINARY COMMUNICATION REGARDING AN IMMUNE BODY CAPABLE OF INHIBITING THE DEVELOPMENT OF CANCER IN MICE (ADENOCARCINOMA, JENSEN)/

By G. H. A. Clowes, Ph. D., Qratwick Research Lahomtonj.


This communication deals with one phase of an investigation which is being carried out at the present time by Dr. H. E. Gaylord and myself, assisted by Mr. F. W. Baeslack.

A considerable number of authentic cases of recovery from cancer in human beings are recorded in the literature but no attempt has apparently been made to test the effect exerted by the serum of such recovered cases upon tumors of like nature in other individuals. We have not up to the present been able to procure human cases of a type suitable for experiments of this nature, but the possession of a series of readily transplanted mice tumors, some of which recovered spontaneously has afforded us an opportunity of making some preliminary investigations regarding the influence exerted by the seriim of those mice which have recovered upon rapidly developing tumors in other mice.

In the spring of 1904 Dr. Gaylord visited Copenhagen and received through the courtesy of Professor Jensen of the Veterinarian High School in Copenhagen a couple of white mice inoculated with tumors described by Jensen as adenocarcinoma (Centralblat f. Bakt. Vol. 34). These mice died shortly before reaching Buffalo but transplantations from one of them were successful, twelve out of twenty-four mice de


' Presented to the Jonhs Hopkins Medical Society of Baltimore, January 16, 1905.


veloping tumors in the course of three or four weeks, thus affording ample material for the subsequent inoculation of a large number of normal mice.

We did not in the course of these early experiments observe any marked hereditary tendencies. In some cases an exceptionally large percentage of tumors were obtained on inoculation of the offspring of mice that had themselves exhibited a considerable resistance to inoculation. Great difficulty was at first experienced in transplanting this material to gray mice but in the course of the autumn the inoculation of a batch of sixteen young gray mice (the offspring of non-susceptible parents) resulted in the production of ten rapidly and excessively virulent tumors which, as will be seen later, were of great value in maintaining the tumor series.

Early in July a series of experiments made with a view to determining certain physical and chemical constants was commenced, but received a serious check a couple of months later when the discovery was made that a considerable number of unused small tumors had imdergone spontaneous retrogression, the mice having recovered entirely and showing no tendency to fresh development of cancer. At the time at which this incident occurred the number of actively growing tumors was too small to permit of any of them being employed to test the efficiency of the serum of the spontaneously recovered mice immediately after the disappearance of the tumors, but a


April, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


131


month later, the series having been once more established through the successful inoculation of the young gray mice referred to above and of certain other white mice, it was possible to commence work of this nature. A series of experiments was then undertaken making use of both gray and white mice having tumors varying from the size of a pea to that of a large cherry. In every case two mice derived from the same source, inoculated at the same time and having tumors of about the same size, were used for comparison, one receiving a dose of the blood obtained by killing one of the spontaneously recovered mice, the other receiving an equivalent dose of normal mouse blood. A marked effect was exerted by the immune serum on small tumors, three of which about the size of peas disappeared in four or five days, residues consisting almost entirely of connective tissue being all that was to be found on subsequent operation. A larger tumor about the size of a cherry treated in the same manner diminished considerably in size, became harder and remained stationary in its development, was removed successfully by operation and has not recurred in the course of the last month. A microscopic examination of the tumor in question showed a marked increase in connective tissue with destruction of the greater portion of the cancerous epithelium. A still larger tumor was retarded in its development, reduced slightly in size and eventually one-half removed by operation, tlie remainder being left for further developments. (A considerable amount of blood was lost at the operation, the animal was subsequently bled for other purposes and eventually, the treatment with immune serum having been suspended, the tumor once more developed and formed local metastases.)

Tumors weighing more than three or four grams were not appreciably affected by the serum, but the cachexia from which the mice suffer in the last stages was in all cases noticeably alleviated. The tumors in the control mice referred to above which had received the normal serum were unaffected and developed in the usual manner leading eventually to the death of the animals. The serum of the mice cured of their tumors by the above treatment was found to possess a certain degree of activity, in one case causing the disappearance of a tumor as large as a buckshot in less than two days, but it can scarcely be said to have exhibited as great a degree of activity as did that which was obtained from certain spontaneously recovered mice. The activity of the serum of spontaneously recovered mice varies apparently within very wide limits. Whilst in two cases .2 ec. prodiiced a marked effect on tumors weighing from two to three grams in two or three da3'S, in the majority of cases only smaller tumors were influenced and in four or five of the spontaneously recovered mice no serum activity whatever was to be noted.

Up to the present (January 15) experiments have been carried out on twenty mice. Of those treated with repeated doses of the so-called immune serum one only has failed to sliow some effect which may be attributed to the serum and all are still living. Of those treated with equivalent doses of normal serum, five are already dead and the remaining mice have


tumors exceeding in size those of the mice for which they served as controls.

It must of course be borne in mind that these mice tumors are very irregular in their development some appearing within a fortnight and others as late as five months after inoculation ; some developing so rapidly as to reach dimensions almost equal to those of the mice themselves and causing the deatli of the animal in a fortnight's time, whilst others develop much more slowly not producing a fatal result in less than ten or twelve weeks. With such variations under normal circumstances the greatest precautions must necessarily be observed in drawing conclusions from the above experiments but it must be remembered that at the time at which they were carried out, the tendency to spontaneous recovery was far less than in the previous generation; also that only in one case has a tumor larger than a buckshot been known to recover spontaneously.

Apolant in a communication from Ehrlieh's laboratorj' regarding the influence of radium on mice tumors makes no mention of having tested the serum of cases which had been cured. (Deutsche med. Woehenschr. 24 March, 1904.) Not having radium of sufficient activity at our disposal we have exposed a series of tumor mice to the x-rays and in three cases in which fair sized tumors were cured by this treatment the serum when tested was found to produce no appreciable effect upon other tumors.

A series of test tube experiments carried out to determine the nature of this serum make it appear extremely improbable that it can be classed in the category of cytolysins. In any case it does not exert a more marked haemolytic effect than does normal serum or the serum of a mouse dying of cancer.

Sections of tumors which have undergone partial spontaneous retrogression show changes in the epithelium closely allied to simple atrophy. The connective tissue stroma of the tumor is greatly increased in amount and if the tumor is not removed for a few days nothing is found but a connective tissue nodule containing isolated masses of degenerating coalescing epithelial cells. The tumors inhibited in growth show about the periphery a marked increase in connective tissue stroma with extensive round-celled infiltration, characteristics which are not to be found to the same extent in the growing tumors. Disintegration of cancer nests associated with atrophy of the epithelium and the formation of coalescent masses of the latter cells characterize those tumors which have been successfully treated as well as those which have recovered spontaneously. Minute masses of connective tissiie presenting the characteristics of ordinary organizing connective tissue are frequently all that is to be found a few days after treatment of a small tunior. In general, it may be said that the changes found in the spontaneously cured tumors and in those inhibited or cured with the immune serum, correspond fairly closely to the changes already described by several authors as indications of partial spontaneous recovery from human cancers.

Whilst it is to be hoped that work of a similar nature may eventually lead to the discovery of a means of treating human cancer, it must be borne in mind that the proportion of spontaneous recoveries in mice, which amounted in the course


132


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 169.


of our work to 15 or 20 per cent is so far as we know, infinitely greater than the percentage of such recoveries in human beings. Also, whilst the microscopic appearance of the tumor has remained unchanged, it is impossible with the limited data at our disposal to estimate at present the effect which may have been exerted by repeated transplantations of the tumor material from one mouse to another, amounting to at least thirty generations from the first Jensen mouse. In any case it appears probable that a combination of circum


stances has in the course of our experiments, led to such a modification of the original conditions as to render it possible for a relatively slight immunizing factor to exert sufficient influence to turn the scale in favor of the normal protective forces of the animal.

The point upon which we would lay special stress is the evidence afforded by the above experiments of the existence of immune forces antagonistic to the development of cancer.


A MULTIPLEX SLIDE-HOLDING DEVICE.

By Edward F. Miller.

(From the Hearst Anatomical Laboratory, Unmnity of California.)


Anyone who has had much experience in staining a large number of paraffin sections for class use or research work has been impressed with the enormous waste of time and energy in preparing these specimens. Not only is the process expensive from the view-point of the labor involved, but also on account of the waste of re-agents and alcohols. Of the various mechanisms that have been devised to obviate these difficulties, perhaps the most successful hitherto have been special dishes so constructed as to prevent the slides from rubbing against each other and designed as well to be economical in the quantity of fluid used. While these dishes have solved the problem to some extent, the technician has never been able thus far to handle more than a single slide at once. It has seemed, desirable, therefore, to place on the market a simple device, which I have designed to make it possible to treat a large number of slides bearing parafiine sections at one time and to keep them as well in such a small compass as to minimize the waste of stains, re-agents and alcohols in the process of mounting.

The Multiplex Slide-holding Device consists of a series of perforated vulcanized-rubber plates placed in a holder so that they may be clamped against a metal plate by means of a thumbscrew. The device is exceedingly simple, is not acted upon by any of the re-agents used either in the simple or complex methods of staining, is easily cleaned, and, when ordinary precautions are taken, is practically indestructible. From an inspection of the illustration, the method of using the apparatus is at once self-evident, although there are worth noting one or two points concerning its use which may save the technician some time and trouble. The holder has a carrying capacity of 26 slides, which should be placed between the vulcanized-rubber plates and then clamped securely by means of the thumbscrew. Care should be taken to place the side of the slide bearing the sections towards the part of the holder marked " Front," for not infrequently after the preparation is complete it is difficult to determine which side of the slide the sections are on. This simple precaution prevents the possibility of sections being rubbed or injured. It is, of course, obvious that this point is of the utmost importance


in the preparation of serial sections, where the loss of a single one may destroy the value of the entire series. It is not advisable to clamp the slides between the vulcanized plates back to back in order to increase the capacity from 26 to 52, for capillary attraction draws the fluid between the slides whence it is difficult to extract it by the ordinary processes of diffusion and consequently stains or water are carried to the higher alcohols or even to xylol, thus preventing the subsequent clearing of the sections. If it is necessary to handle more than 26 sections at once, it is advisable to use two



or more holders. In the ordinary methods of preparation, that is to say, with the commoner nuclear stains and contrasts, the holder with 26 slides may be taken directly through the stains as an ordinary section without any precautions being taken; but in the more complex special methods of staining, the time element, particularly in tissues fixed by different methods, is often of importance. Under these circumstances it is advisable to carry a test slide through the stain in order to determine the exact time required to get the desired result. After this is done the holder with the large number of slides is treated exactly like the control. In this way 27 slides may be stained in the time ordinarily consumed in preparing two.


April, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


133


The results, furthermore, are absolutely equal, as the unequal intensity of stain that is sometimes embarrassing in careful work is thereby obviated. In my experience, it is not necessary to leave the slide-holder laden to its maximum capacity in the re-agents longer than one would leave a single slide. This is particularly true if it is moved about in order to bring fresh fluid in contact with the sections. Care should be taken not to allow either stains or the lower alcohols to come in contact with the slide-holder. This is easily done if the level of the fluid in the baths is adjusted so as to keep it 4 or 5 mm. below the slide-holder. When the staining and subsequent dehydration is almost complete, the slide-holder is inverted in absolute alcohol in order to remove any possible water that may have come in contact with the holder. After removal from the absolute alcohol tlie thumbscrew is loosened and again inverted in the xylol bath. As soon as the clearing is complete, the slides may be removed directly from the bath one by one and mounted ; the portion of the holder marked " front " determining, of course, the side of the slide to which the sections adhere. As the slide-holder is taken from one bath and placed in another, it is always better to drain the slides by touching the free ends to filter-paper, blotter or some other absorbent medium. This precaution, of course, prevents the waste of re-agents. It may be mentioned that the prolonged action of xylol softens the vulcanized rubber; but the entire holder can be immersed in xylol repeatedly for a time sufiicient to clear any set of sections without injuring it in the slightest. The construction is so simple that it can be very easily taken apart for the purpose of cleaning and drying, a precaution which will naturally prolong the life of the instrument.

Two types of jars have been found serviceable in our ex


perience to hold the stains and re-agents, one a battery jar with a glass lid and the other a round dish with a metallic screw-top. The battery jar has the advantage of using a small amount of fluid, which is particularly desirable when the more expensive stains are used. It is, indeed, possible to economize still more by immersing the slides in a deep Stender dish, which will hold a dozen or more of the slides. Although the round jars with screw-tops take a greater volume of liquid, I have found that owing to the tight screw-tops, in the end, they are quite as economical as the square dishes owing to the prevention of evaporation. The same bath consequently may be used for a greater length of time than in the case of the battery jar.

The instrument is manufactured by the Spencer Lens Company of Buflialo, New York, and is sold by them. In case the vulcanized rubber deteriorates it may be purchased separately. To sum up the advantages of this apparatus, we may say that :

First: 26 slides bearing paraffine sections may be stained and mounted with but a slightly greater expenditure of time than is consumed in staining and mounting a single section.

Second: There is a great saving in the quantity of reagents used when the slide-holder is employed.

Third : There is no danger of injuring the sections. The entire series can be mounted without the loss of a single section.

Fourth: The staining of the entire set is absolutely uniform, a result impossible to obtain by the old method.

Fifth : The apparatus is so constructed as to be, with ordinary care, almost indestructible.

Sixth : By the use of this holder it may be possible to give to classes in microscopic anatomy sections stained by the more complex methods owing to the economy of time and re-agents.


DR. HEINRICH OR HENRY KEERL, OF BALTIMORE, THE "HESSIAN SURGEON."

By Eugene F. Cordell, M. D.


We have all read of the famous Hessian troops who fought against us in the Revolutionary War. The name has always had a very bad odor among us, for why should these Germans leave their own homes to fight the battles of a nation and a war in which they had not the least interest. We forget that those were the days of absolutism, when men, as Frederick the Great said, were esteemed little more than cattle. There is ample evidence that many of these men sympathised with patriots who were fighting for their freedom from foreign oppression and would have exchanged sides if they had dared.

It is not generally known perhaps, that one of these Hessians, a distinguished surgeon, settled in this city, and after a long, honorable and successful career died, leaving many prominent and influential descendants here.

Dr. Keerl was descended from a Bavarian family, of the higher class, which could trace its lineage back to the beginning of the sixteenth century. He was born in the town of


Mainbernheim, thirteen miles from Wiirzburg, in the year 1755. He was the only child of his parents who survived, two brothers having died in infancy. Early losing his parents, he was educated by a wealthy uncle, a widower without children, whose wealth according to expectation he was to inherit. He adopted the profession of medicine, completing his studies at the University of Gottingen, then sharing with Halle the supremacy of the German universities. Meanwhile his uncle married again, thus dissipating his prospects of affluence. About this time the American war broke out and the British Government hired tlie soldiers of some of the petty German princes to aid them in subduing their rebellious colonies. By his uncle's influence. Dr. Keerl obtained a commission as surgeon in one of these " Hessian Regiments " (as they were called), commanded by Colonel von Rail. He left Germany with his command more in a spirit of adventure than from any definite purpose of life, and expecting to re


134


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 169.


turn at the end of his term of service. But "Der Menseh denkt's, Gott lenkt's," and it was destined that he should not see his native land again.

The employment of the troops of the Ehenish principalities by George III is an episode of the American war of great interest and I have already alluded to it at length in a paper read before the German Historical Society entitled, " A Memoir of John Peter Ahl, Surgeon's Mate in the Continental Army." Dr. Ahl also probably came over with the Hessians, at any rate he was in the British service. Early in the war he espoused the cause of the patriots, served them faithfully and was severely wounded while defending some of their sick and wounded from an attack of Tarleton's dragoons at White Plains on the Hudson. After the war he settled in Baltimore and died here in the same year as Dr. Keerl.

The treaty between George III and the Landgrave of Hesse Cassel, dated January 15, 1776, calls for 12,000 men of the troops of Hesse to be employd in the former's service, consisting of four battalions of grenadiers of four companies each, fifteen battalions of infantry of five companies each, and two companies of chasseurs. Part of this force was to be ready to march February 15, 1776, and the remainder four weeks later, if possible. These troops formed a part of the army of General Howe operating against Washington from New York and were under General Heister, who was recalled after the Trenton affair. Over 4000 Brunswickers under General Eiedesel were assigned to the army operating from the direction of Canada under Burgoyne and surrendered with that general at Saratoga. The exact number of German troops hired by Great Britain was 16,900.

The brigade of von Eall, consisting of his own, von Knyphausen's and von Losberg's regiments, had covered itself with glory in the campaign of 1776, taking conspicuous part in the battle of White Plains and in the storming of Port Washington on the Hudson. As a reward for this distinguished gallantry, to it was assigned the post of honor at the close of the campaign by being stationed on the farthest outpost— that directly in front of Washington's army. It occupied the best winter quarters at Trenton.

It is well known how von Eall, elated by his successes, and sharing the opinion, general throughout the British army, that Washington was crushed and the war virtually at an end, neglected the commonest dictates of prudence. Although within but a few miles of a hostile force and although warned, he refused to believe that he was in any danger or that precautions against attack were called for. Well, suffice it to say, that after a Christmas spent in drinking and festivity, von Eall and his men retired to their heavy slumbers to be aroused early the following morning by Washington and his men who had crossed the Delaware and surprised them. Von Eall, hearing the firing, rushed from his quarters and bravely attempted to form his command, but was wounded at the beginning of the action. It is said that he fell into the arms of Dr. Keerl and expired shortly after, entrusting to his surgeon for his wife his watch and sword. The Germans en


deavored to retreat but were cut off and captured, suffering a loss of 17 killed, 78 wounded, and 868 prisoners.

So depressed had become the spirits of the Americans that they would not believe that the Hessians had been beaten, and Washington had to march his prisoners through the streets of Philadelphia in order to convince his countrymen. The prisoners were marched to the interior of Pennsylvania for safety. The oflicers petitioned to go with them but were not allowed to do so; they were sent on the 6th of January, 1777, to Baltimore, where they were paroled. Dr. Keerl spent some time traveling through the country, no doubt with a view to permanent location. At one time he and a friend visited the Carolinas and, according to family tradition, " were solicited to remain and marry among the rich widows whose husbands had been killed in the war." But having formed agreeable acquaintances and finding a favorable opening in Baltimore, he settled finally here about the year 1782, and devoted himself with industry to his profession, meeting with the success which his assiduity and professional acquirements entitled him to. His residence was at 17 West German Street. His experience in the service and the reputation he had acquired as a surgeon were of great advantage to him and brought him forward especially in the line of surgery. He rapidly acquired practice and friends among the best people in the town. In connection with his profession he had a drug store, which was situated on Baltimore Street near Sharp. In the Maryland Journal of August, 1789, he advertises the sale of medicines and instruments at the " Sign of the Golden Swan, upper end of Market Street, near Congress Hall." He also kept for sale glassware of all kinds.

From the time of his settlement in Baltimore, Dr. Keerl seems to have had an uneventful life, moving as Horace says,

" With soul serene amid the nooks And silent by-ways of a blameless life."

He early became a member of the Medical and Chirurgical Faculty of Maryland. That he was a Lutheran seems probable from the name " Heinrich Keerl," appearing in the list of contributors to the building of the Gay Street Church, finished in 1808. [See Dr. Scheib's article on the Early Lutheran Church in Baltimore, Transactions of the German Historical Society, Vol. I.] He invested his earnings in real estate, and at his death, which occurred on the 6th of July, 1827, he left to his family a very considerable fortune, which was divided equitably by will among his heirs.

He was twice married; first in early life to Anna Maria, daughter of Jacob Myers, a prominent merchant of Baltimore and one of the founders of the German Presbyterian Church which stood for many years at the corner of Baltimore and Front Streets. His second wife was Margaret Kandel, of Frederick, Md. By his first marriage he left four sons, viz. : John C, Samuel, George H., and Joshua. The first-named was educated in Germany, receiving from his professors there the highest testimonials to his character and attainments. He began life as a merchant, took part in the battles of Bladensburg and North Point, and retired from business in middle


Apkil, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


135


life. Samuel was a director in the Firemen's Insurance Company and for a long period president of the first Baltimore Hose Company, composed entirely of leading j'oung men of Baltimore, and especiall}' of representatives of the principal Quaker families. He also participated in the War of 1813. Gorge H. was of the firm of Henry Keerl & Sons, wholesale druggists, Baltimore Street near Howard, and carried on this business iip to his death; he left six children. George H. and Joshua were partners and also married sisters, but the latter died early and left no issue ; the other two brothers never married. One of the daughters of George H. married Dr. Eobert Atkinson, of Baltimore.

By his second marriage, Dr. Keerl left three children, of whom William pursued medical study in Paris, married Ellen Douglass, of Maryland, a daughter of Colonel Douglass, of the Eevolution, and moved to Charlestown, W. Va., where his descendants now reside. One of his sons was killed in the Confederate Army. Charles, the second son, settled in Hagerstown, and Amelia married Dr. Eobert Fulton, of Baltimore, and left two sons, one of them. Dr. Henry Keerl Pulton, a graduate of the University of Maryland, who lived in Washington. Dr. Keerl's second wife died in 1866.

Of the German branch of Dr. Keerl's family, a distinguished representative recently resided at Schloss Liebersteen, near Augsberg, Germany, and other descendants and members were not many years ago residing at Nuremberg, and heartily welcomed their American relatives who visited them there. Before his death Dr. Keerl had a very beautiful monument erected over the grave of his mother.

The descendants of Dr. Keerl in Baltimore have in their possession an oil painting of him said to be by one of the Peales; also an old German bible, his sword and letters and pictures of Mainbernheim and of the University of Gottingen, where he was educated. At one time they also had his pair of pistols, but they have been lost. The portrait represents a robust, vigorous man of forty-five or fifty years, with full, ckan-shaven, oval face and ruddy complexion; a handsome face, full of intelligence and character.

The following obituary notice of Dr. Keerl appeared in the Baltimore papers at the time of his death : " On Monday evening, 16th inst.. Dr. Henry Keerl, in the 73d year of his age. Dr. Keerl was one of the oldest inhabitants of Baltimore, and the respect due to his memory may be safely left


to the decision of his fellow-citizens. Plain and unoffending in manners, conscientious and just in his dealings, benevolent and liberal on all proper occasions of public or private charity, he enjoyed and deserved the entire confidence, esteem and good will of all to whom he was known. At that solemn crisis when the world was fast fading from his view, he contemplated the close of his earthly career with calmness and resignation. To him who can look back on a long life spent in the habitual practice of piety and virtue, death is disarmed of all its terrors." [Baltimore Gazette and Daily Advertiser, July 18, 1827.]

Dr. Keerl's will is dated November 8, 1823. He leaves his wife, Margaret Keerl, $1200 per annum for life out of the rents of his two warehouses or stores on the south side of Baltimore Street, one occupied by George H. and Joshua S. Keerl, druggists; the other by Samuel Keerl, as a dry goods store ; if these rents be not sufScient, the amount is to be made up from his ground rents. He also gives her his house and lot in German Street, as long as she remains a widow. To his sons William and Charles he gives $10,000 each. To his daughter Amelia Henrietta he leaves the interest arising from 66 shares of stock in the Bank of the United States and 12 shares of stock in the Bank of Baltimore, the said shares to go to her in trust at the age of 18. Also to this same daughter a negro girl who is to have her freedom at the age of 44, his piano-forte and one-half of his household and kitchen furniture. He also leaves to his wife one-half of his household and kitchen furniture and two negroes who are to be free at the age of 44. He authorizes his executors to lease his unimproved ground for 99 years, renewable forever. After the above dispositions, the rest of the estate is to be divided into seven equal parts, one of which is to go to each of his sons, viz. : John C, John Samuel, George H., Joshua S., William, Charles F., and to his daughter Amelia Henrietta. He explains that he has already previously given to each of his four oldest sons $10,000, and has also allowed to his son George H. $4000 in addition for his conduct of the business theretofore pursued by him. Finally, he appoints his friend Charles Bohn and his son George H. as his executors.

We learn from this will that Dr. Keerl had accumulated what was a large fortune for his times, and it seems to have been due entirely to his industry, good judgment and business capacity.


STUDIES IN TYPHOID FEVER.

SERIES I-II-III.


The papers on Typhoid Fever, edited by Professor William Osier, M. D., and printed in Volumes IV, V and VIII of the Johns Hopkins Hospital Reports, have been brought together and bound in cloth.

The volume includes thirty-five papers by Doctors Osier, Thayer, Hewetson, Blumer, Flexner, Reed, Parsons, Finney, Gushing, Lyon, Mitchell, Hamburger, Dobbin, Camac, Gwyn, Emerson and Young. It contains 776 pages, large octavo, with illustrations.

The price is $5.00 per copy. Address The Johns Hopkins Press, Baltimore, Maryland.


136


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 1G9.


THE BACILLUS AEROGENES CAPSULATUS IN PUERPERAL INFECTION.

By Herbert M. Little, M. D.

Besident Obstetrician, The Johns Hophins Hospital.

(From the Obstetrical Department of the Johns Hopkins Hospital and University.)


In 1897, Dobbin reported from this clinic the isolation of B. aerogenes capsnlatus from a case of pliysometra, and suggested that this organism was the true etiological factor concerned in its production. This observation has since been abundantly confirmed by other investigators, though the role of the gas bacillus as an infecting agent has received much more attention from pathologists than from obstetricians.

Apart from Dobbin's original case and one which he observed subsequently, no one in America or England has recorded the isolation of this bacillus during the course of puerperal fever. Such observations, however, have been made both in Prance and Germany, and as in both countries the organism is described under varying names, it may be well to consider briefly the various bacteria which have been described as original but which are nevertheless imdoubtedly identical with the bacillus of Welch and Nuttall.

B. aerogenes capsnlatus (Bacterium Welchii, Migula, 1900), better known in America as the "gas bacillus," was first described by Welch and Nuttall in 1892. Dr. Welch has briefly given its characteristics as follows : " A rather coarse, non-motile, anaerobic bacillus; stains by Gram; grows on all of the ordinary culture media under anaerobic conditions, Ijest at body temjierature but also at room temperature; liquefies gelatine slowly; forms spores constantly according to the race and culture medium; and is capable of generating gas, not only by fermentation of sugars but also from proteids."

Capsules are usually readily demonstrable with the usual stains, particularly when the bacilli are grown in milk or obtained directly from the tissues of an inoculated animal.

Milk is probably the most satisfactory culture medium as the reaction is very striking. The milk becomes acidified and coagulated, then partially digested, giving a " worm-eaten " appearance to the clot. For absolute identification, this reaction may be supplemented by the other characteristic test suggested by Welch ; namely, the production of gas in the tissues of a rabbit killed within a few moments after the injection of an emulsion of the organism into its ear vein. This last test, which Dr. Welch considers the most important of all for the identification of the bacillus, we have applied in every instance with positive results, and we were also able to obtain the organism from the heart's blood of the animal.

The Vibrion Septique. — This organism, or complex of organisms, was discovered by Pasteur in a class of puerperal cases which appeared to him to have a peculiarly fatal course. Unfortunately, he was never able to cultivate it alone, but of recent years it has been generally believed that the bacillus of malignant oedema, isolated bv Koch, represents it in pure


culture. There is, however, reasonable ground for doubting whether this view is really correct, since Pasteur's vibrion was frequently present in cases of puerperal infection and was widely distributed in nature, being invariably present in the intestinal canal and in cases of putrid gangrene. It was motile in the absence of oxygen but lost its power of motion when exposed to the air. The bacillus of malignant oedema, on the other hand, is far less widely distributed, is rarely isolated from the human intestine, and, so far as I have been able to ascertain, plays a very limited part in the production of puerperal infection. Moreover, it differs from the gas bacillus in being motile and decolorizing when stained by Gram's method ; but this latter test was unknown to Pasteur. In short, B. aerogenes capsulatus seems to conform very closely to the descriptisn of the vibrion septique, and the isolation of an identical organism from a large number of cases of criminal abortion — the only class of cases now exposed to the same danger of infection as all cases in Pasteur's time — renders it highly probable that the organism in question represented an impure culture of the gas bacillus.

In 1880, Doleris, who was a pupil of Pasteur, divided the bacteria giving rise to puerperal fever, into micrococci and " Bacteries Cylindriques Septiques,"- — the latter a new name for the vibrion septique. Eighteen years later, in reporting the autopsy findings in a case of infection following the removal of the placenta by a midwife, he noted that the body was distended with gas and that three organisms were present, streptococcus and colon bacillus, which were obtained in pure culture, and also the vibrion septique, which he could not isolate.

Meuereul, likewise, reported a case of crepitating gangrene which he ascribed to infection with the vibrion septique, although the results of his cultures and inoculations make it reasonably certain that he had to deal with the gas bacillus. Indeed, a study of the French literature upon the subject, from 1880 until the present time, gives a practically unbroken chain of evidence in favor of the identity of Pasteur's organism and B. aerogenes capsitlatus.

Bacillus Phlegmones Emphysematosa;. — In 1893, Fraenkel described as the cause of gaseous phlegmons, the organism to which he gave the above name. The same year Ernst isolated a similar organism at an autopsy upon a case of infected abortion, but both bacteria were believed to differ in some degree from the original gas bacillus. Goebel in 1895 insisted upon the identity of the three; and although as far back as 1899 Fraenkel admitted this to be true, his organism is the only one widely known in Germany.


April, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


137


Bacillus Perfringens. — This bacillus was isolated from cases of otitis, mastoiditis, pulmonary gangrene, appendicitis. Bartholinitis and pelvic abscess, and was described by Veillon and Zubert in 1897. One year later the same investigators admitted that it was identical with Fraenkel's bacillus, but in France, it nevertheless retains the name given by them.

Bacillus Emphysematis Vagince. — Lindenthal in 1897 described this organism as the cause of gas cysts of the vagina and isolated it in two of six cases examined during pregnancy. In 1899, working with Hitschmann, he admitted its identity with B. aerogenes capsulatus as well as with Fraenkel's ba"cillus. His original communication is of interest as an evidence of the peculiar distribution of the gas bacillus.

The (xranuloha-cUhis Saccharohutyricus Immohilis Liqirefacien^. — This bacterium was isolated by Schattenfroh and Grassberger from a great many samples of milk, ground water, etc. ; and there would appear to be but little doubt as to its identity with the various bacilli noted above.

Bacillus Aerogenes Aerophilis Agilis. — In 190"3, ITffenheimer isolated this bacillus at an autopsy upon a case of puerperal infection ; and his note, " Exemplare ihre Beweglichkeit verloren," together with the admitted mixed character of the infection, would, apart from some imperfections of his technique, as pointed out by Westenhoffer, suggest that he was dealing with an impure culture of the gas bacillus.

Only one other organism is perhaps worthy of mention in tliis connection — the B. scptique aerobic of Legros and Lecene. This seems to be identical with what Dr. Welch calls the aerobic form of the gas bacillus, and is practically interesting from the fact that it was so named to accentuate its points of similarity with, and dissimilarity from, the vibrion septique.

The cultural characteristics and pathological properties of B. aerogenes capsulatus are well known ; but many are not aware of the extent of its distribution. It has been found regularly in the faeces of human beings, as well as of dogs, cats, and swine, also in those of rabbits, rats, guinea-pigs, mice, chickens, and cows, and likewise in the excreta of flies found hovering about dead bodies. It is frequently found in garden earth, but rarely in street dust; occasionally it may be isolated from the dust of hospital wards and from scrapings of the human skin. Its presence in the uterus in eases of infection is not surprising.

According to Dr. Welch its introduction into the pregnant or puerperal uterus may give rise to one or more of the following conditions :

I. Emphysema of the foetus. II. Puerperal endometritis.

III. Physometra.

IV. Emphysema of uterine wall. V. Gas sepsis.

Being chiefly concerned, in this article, with puerperal endometritis, we shall slightly alter this order and consider the second subdivision last.

Emphysema of the Fcetus. — Knowledge of the pathology of


the condition dates from Dobbin's observations in 1897. In his case, infection of the fcetus occurred by way of the placental circulation. Kronig and Menge have shown that the liquor amnii may become infected prior to the rupture of the membranes (1. c, p. 90), and in three cases reported by them (p. 167) the infection of the fcetus was undoubtedly due to tlie swallowing of infected amniotic fluid.

Physometra or Tympania Uteri. — Formerly it was held that this condition could be produced by the aspiration of ordinary air into the uterus, but it is now universally recognized as being bacterial in origin. Gebhard in 1893 analyzed six cases and found in all a bacillus which he identified as Bacillus eoli. In four cases it occurred in pure culture, while in two others it was associated with the streptococcus.

Chiari, Hitschmann, and Lindenthal have shown that Bacillus coli is capable of producing gas only in the tissues of diabetics. Moreover, the clinical and experimental work of the latter observers, supplemented by that of Halban, has shown that even this is very exceptional, and has served to confirm Dobbin's suggestion that the gas bacillus is the usual cause.

Emphysema of the uterine wall is usually associated with tympania uteri and has a like causation. It is of interest, as the condition frequently found at autopsies on cases dying as a result of puerperal infection, and was the lesion present in the case from which Ernsf s bacillus was obtained.

Gas sepsis is probably the most important of the five subdivisions. Though cases showing evidence of general infection with the gas bacillus are not infrequently seen at autopsy, it is often difficult to decide whether the infection occurred during life or postmortem. Thus, in thirteen cases collected by Dr. Welch the evidence of ante-mortem invasion of the tissues seemed conclusive in but seven, including those of Dobbin, Ernst, Halban, and Kronig and Menge above referred to, and two others reported by Wood, and Graham, Steward and Baldwin, respectively. In none of these cases was the bacillus isolated from the blood during life; and but five cases have been reported in which this has been accomplished, all of which terminated fatally. Thus, Gwynn repeatedly cultivated the bacillus from the blood in a case of chorea, and Cole, and Norris from cases of infection following trauma ; while the two remaining instances occurred in connection with puerperal infection, and are recorded by Fraenkel and Lenharz. Fraenkel's case was reported with practically no detail, while in Lenharz's the patient died from a general infection following an abortion at the second month. The vagiua had been tamponed. There were marked pyrexia, jaundice, and airhunger ; later the patient became irrational. At autopsy, gas was present in the heart, and bacilli were found in sections from all the organs. There was no note of general emphysema. i In Case 9, which is reported in detail in the latter part of Ibis article, the infection of the rabbit, the presence of bacilli in the smear preparations, and the distribution of the organisms in the microscopical sections of the tissues, leave little


138


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 169.


or no room for doubt that the bacillus was present in the blood some days prior to death.

Puerperal endometritis is second in importance only to gas sepsis, and must be considered as a possible forerunner of that condition. Apart from cases ascribed to Bacillus perf ring ens by MoTichotte and Jeannin, no examples of such infection have been reported since Dobbin's paper.

Mouchotte, examining the uterine lochia from eighteen cases of abortion occurring between the second and the fifth months, isolated Bacillus perf ring ens in thirteen cases or 72%. In no instance was it present alone, being usually associated with streptococci, staphylococci, or Bacillus coli. Three of the thirteen patients died and one came to autopsy, at which there was no note of the presence of gas in the organs. Jeannin, likewise, made cultures from the foetal surface of the placenta in five cases of delayed labor and obtained Bacillus perf ring ens in four. In his cases there was high fever (103°104° F.) lasting from four to eleven days after delivery. The same observer has recorded the bacteriological findings in twenty-one cases of puerperal infection, Bacillus coli being noted in eighteen and Bacillus perfringens in twelve (57%).

The clinical character of the latter group of cases is interesting. In four, premature rupture of the membranes occurred, and in six, portions of the placenta or membranes were retained after delivery. The fever was noted as early as the first and as late as the eighth day, and invariably reached 103°-104°. Two cases died on the twenty-fifth and the fortyfifth days, respectively. There was no note of the condition found at autopsy.

In addition, Jeannin examined eighteen cases of incomplete abortion with subsequent infection, and isolated Bacillus perfringens twelve times. Streptococci were equally frequent and the Bacillus coli was present in fifteen cases. Two of the patients died, but there was no autopsy. Clinically, this group of cases is also of interest. In one instance there was no fever; in three the temperature dropped from 104° to normal immediately after cleaning out the uterus; while in two others a sudden drop to normal was noted after slight preliminary rise, and none of the six had fever subsequently. A seventh case had a slight temperature on the second day, and two other rises on the fourth and sixth days, respectively; though the cultures taken with these rises suggest infection at the time of operation. Thus, in all his cases, the tendency was for the fever to fall abruptly upon cleansing the uterus. Jeannin has also reported three cases of physometra in which Bacillus perfringens was isolated. Two of these cases died and came to autopsy but there is no note of general infection, nor of the presence of gas in the tissues.

Finally, Eist and Mouchotte reported three cases of infection following abortion, in two of which they were able to obtain Bacillus perfringens from the uterine cavity. Streptococci and staphylococci were also present, and, in one instance, other anaerobes. The fever was alarmingly high in both cases, but recovery followed in each. These observers


suggest the identity of Bacillus perfringens with Fraenkel's bacillus and the vibrion septique.

Our experience with the gas bacillus comprises some fifteen cases in the Obstetrical Department of the Johns Hopkins Hospital, in only ten of which was the bacillus identified with absolute certainty. These, including Dobbin's two cases, are given in detail below.

Bacillus aerogcnes capsulatus may gain access to tlie uterine cavity in one of two ways. The first, and by far the more usual, is its introduction by means of the examining finger or by instruments. By reason of its almost invariable presence in the faeces of human beings,, this is particularly liable to occur in spontaneous labor when the perineal and vulvar regions are insufficiently cleansed, as well as in operative cases even in spite of this care. In the second place, the organisms may occasionally be present in the circulating blood, by which they are carried to the uterus, and then be cultivated from the lochial discharge. It is noteworthy in this connection, that in both of our cases which terminated fatally, intestinal ulcers were found at autopsy.

The passage of the gas bacillus into the circulation by way of typhoid ulcers is not merely a hypothetical supposition, as Hitschmann and Lindenthal have reported the case of a boy, ffit. 8, in whom a general infection could apparently be traced directly to such lesions.

The presence of bacteria similar to or identical with B. aero genes capsulatus has not as yet been noted by any of the investigators of the organisms present in the normal vagina, and the two cases in which they were found by Lindenthal in gas cysts must be considered quite exceptional.

It is worthy of note, that of our ten cases of infection, seven followed operative procedures, and an eighth, a self-induced abortion. All of these had been repeatedly examined. In one case, however, which entered the hospital profoundly infected, the patient stated that she had not been examined vaginally. The organisms cultivated from this patient were obligate anaerobes, and this was one of the cases in which intestinal ulcers were found at autopsy.

Once within the uterus, the character of the reaction produced will probably vary with the facilities for growth and development afforded by circumstances. Kronig has stated that anaerobes cannot develop in the uterus in the presence of oxj'gen, and it would seem that the anaerobic growth is favored by such procedures as packing the vagina. In cases where the infection is mixed, it is doubtful whether free drainage would preclude the growth of anaerobes; since, as Kedrowski has shown, aerobes in their development not only absorb a certain amount of oxygen, but also give off some substance favoring the growth of anaerobes. We, ourselves, have noted that, even with free access of air, the gas bacillus developed fairly profusely in milk when associated with the staphylococcus aureus.

Symbiosis, moreover, would not only appear to favor the growth, but also to enhance the virulence of the organism. Thus, Achalme, as early as 1880, increased the virulence of streptococci by associating anaerobes with them. Eoger, Novy


April, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


139


and Penzo have also shown that the association of B. proteiis or B. prodigiosus will markedly increase the virulence of the bacillus of malignant cedema; while Besson has noted the same in reference to the vibrion septique. The last-named observer even goes so far as to say that the vibrion septique is harmless in healthy tissues unless in association with other bacteria.

On the other hand, the work of Dr. Welch, confirmed by Fraenkel, and more recently by Kamen, leaves no doubt as to the ability of the gas baciUus to induce by itself a typical inflammatory- reaction ; but it is interesting to note that in only two of our eases (one of which was a case of mastitis) was the organism found alone. In a third case (B. L., Case 7), the cultures take after the febrile rise showed only the gas bacillus, but a previous culture had shown in' addition the presence of streptococci.

It is the custom in the Obstetrical Department of the Johns Hopkins Hospital to examine the uterine contents bacteriologically in every case in which the temperature reaches 102° during the puerperium, and to take cultures after the conclusion of the third stage of labor whenever the patient enters with a temperature, or has been subjected to attempts at delivery by persons not connected with the department. Likewise in all cases of incomplete abortion, especially if of a criminal character, cultures are taken before the patient is examined vaginally.

In every instance 2-4 cc. of the uterine contents are secured by means of a lochial tube, and from this inoculations are made upon various culture media, — plain agar, hydrocele agar, blood serum, milk, and bouillon. Eoutine anaerobic inoculations are made by mixing the lochia with glucose agar which has been freshly sterilized or boiled, then cooled rapidly to 40°. After inoculation, the agar is allowed to solidify and its free surface is then covered with a layer of parafifin or agar. In the majority of cases, however, two sets of tubes are inoculated, one of which is incubated in an atmosphere of hydrogen.

Should the gas bacillus be present, there is usually no difficulty in recognizing it in coverslip preparations made directly from the uterine contents, particularly when stained by Gram's method. When associated with other organisms, its isolation in pure culture may offer some difficulty. Fraenkel suggested that this could be effected by killing off the other microorganisms, taking advantage of the fact that the bacillus in question offers Considerable resistance to heat — Pasteurization. For this purpose the inoculated tubes are placed in a water bath and heated to 65° C. for three to five minutes, after which they are removed and cooled. It has been repeatedly demonstrated that the gas bacillus will survive this treatment, (according to Fraenkel it will withstand 70° C. for three minutes), while its more usual associates will for the most part be destroyed.

When the organism has been isolated in pure culture, we have, as noted above, invariably proven its identitj' by ob


taining a characteristic reaction after its inoculation into a rabbit.

If for no other reason, the recognition of the presence of the gas bacillus is important in relation to that large group of cases known as " Saprsemia ; " " to produce which," according to one American authorit}-, " germs of putrefaction — saprophytes — must gain access to the uterus after labor." The diagnosis in this class of fevers is usually not based upon bacteriological examination, but merely upon the benign clinical course of the case, and the fallacy of this method is shown by the fact that Bumm was able to demonstrate streptococci in a number of cases presenting the supposedly characteristic clinical features. Moreover, the observations of Jeanntn as well as the bacteriological findings in our cases (Cases 4 and 6) bear out the contention of Bumm and Williams, that no case should be diagnosed as Saprsemia without a bacteriological examination.

Doleris says that all organisms found in saprophytic infections have been found in the vagina. As B. aerogenas capsulatits is not an inhabitant of the vagina, and as it would appear neither advisable nor justifiable to classify it with the ordinary putrefactive bacteria, the possibility of its giving rise to autoinfection or Sapnemia is very remote. This being the ease, it is probably always introduced from without, and just as in streptococcic infection, the physician should be held responsible for its introduction, unless satisfactory proof to the contrary can be adduced.

The ideal treatment in these cases of infection is, of course, prophylactic, and this can best be attained by careful aseptic technique during labor. In the Johns Hopkins Hospital the routine is as follows: A rectal enema is given during the first stage of labor, and the patient is prepared for vaginal examination by first clipping close the vulvar hair, then scrubbing with green soap and water, followed by sponging with 95% alcohol; finally, a towel soaked in a 1-2000 bichloride solution is applied, and left in position until the examination — a minimum of three minutes. In all operative cases the vulva and perineum are shaved and cleansed by the permanganate-oxalic-acid method in addition to the above. The hands are disinfected as for major operations. No douches of any kind are given. If no details of this technique are omitted, the results will be good. Unfortunately, in emergency cases it is often necessary to operate without the preliminary enema, and the introduction of the hand during operations such as version may unavoidably carry up intestinal bacteria into the vagina and uterus. But even if this occurs the bacteria may cause no trouble, provided the third stage be carefully conducted and no portions of the placenta or membranes be retained.

Should fever ensue, the first requisite is an accurate diagnosis. This is important more from the standpoint of prognosis than of treatment, as the latter, no matter what the infecting agent, will, in general, be along three lines: (1) removal of necrotic material offering a medium for growth of organisms, (3) establishment of free drainage from


140


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 169.


the uterus, and (3) stimulation of the natural resistance of the patient. The finger should be used in removing debris, as the curette, however carefully manipulated, will undoubtedly interfere with the attempt at local reaction on the part of maternal tissues and may open up sinuses and dislodge thrombi. A large douche (4 liters) of hot salt solution (110° F.) will also aid in cleansing the cavity. So-called antiseptic douches will accomplish little that the salt solution will not, while the danger of poisoning from absorption should not be overlooked. If the cervix is sufficiently patulous to admit two fingers, as good drainage will be obtained by leaving it alone as by introducing gauze. To aid resistance, the patients are well fed and when necessary strychnia and alcohol are given ; but the greatest emphasis is placed on the necessity for large quantities of fluids either taken by mouth or injected into the rectum.

The greatest danger to be feared is the passage of the organisms from the uterus into the circulating blood. While patients with streptococcus septicaamia not infrequently recover, all known instances of gas sepsis have ended fatally. If the infection be grave and definitely localized in the uterus, hysterectomy is Justifiable, but theoretically, only when the infection is on the point of becoming generalized. The difficulty in establishing this definite moment is obvious, and the operation, as in our Case 9, may completely fail in accomplishing its purpose.

Following is a synopsis of the cases in which we have demonstrated the presence of the gas bacillus. Two of them had been noted previously in the articles of Drs. Welch and Dobbin, but are here incorporated for the sake of completeness.

It is not contended, nor is it intended to imply that B. aerogenes capsulatus was, in each instance, the determining factor in the causation of the fever. The varying -effects of such infection have been shown above, and even when typical gas production is absent, the possibility of the organism in question in influencing the virulence of others with which it may be associated, must be continually borne in mind.

Case I. — Generally contracted pelvis; dystocia; frequent examinations by midwife; gas noted in vaginal discharge; basiotripsy; death.

P. A., (0. O. S. No. 56.) (Dobbin's first case.) " A Bohemian woman with a generally contracted pelvis had been in labor some three to four days under the care of a midwife. When she came into our hands, the head of a macerated child was found firmly engaged in the superior strait, the uterus being in a state of tetanic contraction. A fcetid, dark-colored discharge, which contained many gas bubbles, was escaping from the vagina with a crackling sound. Delivery was effected by means of Tarnier's basiotribe. The mother was profoundly infected and died next day. Within a few hours after death her body had nearly doubled its original size, as a result of development of gas in the subcutaneous tissues. Similar changes were observed in the foetus and placenta, and we were able to demonstrate the presence of the gas bacillus in the tissues of both, as well as in the uterine lochia. No autopsy was allowed."

Case II. — Generally contracted rachitic pelvis; dystocia; frequent examinations and attempts to deliver; rise of temperature during labor; prolapse of cord; perforation and extraction of child; recovery.


M S., (H. No. 316.) l-para, white, was admitted to the hospital in labor. An outside physician had made several vaginal examinations and had attempted delivery with forceps. The following are extracts from the note on admission: — " Small, slightlybuilt woman, facies expressive of suffering, pinched and drawn; superficial examination suggests rachitis; breasts large, nipples prominent, colostrum; heart and lungs negative; abdomen enlarged to size of full term pregnancy, fundus two fingers' breadth below ensiform; there is no contraction ring, though the uterus Is apparently tetanically contracted; the round ligaments converge upwards. An accurate diagnosis of the presentation and position is impossible, though the occiput is directed downward and to the left side. No foetal heart heard. The pelvic measurements are Sp. 23.5, Cr. 23.5, Tr. 28, D. B. 16.5 cm."

The results of vaginal examination were as follows: "Marked oedema of soft parts; forceps abrasions; cervix fully dilated, cord prolapsed, not pulsating. The head is movable at the superior strait in L. O. I. T., the sagittal suture being only about 1.5 cm. from the symphysis pubis; there is a marked caput succedaneuni. The diagonal conjugate measures 9.5 cm. and the anteroposterior and transverse diameters of the outlet are 8 cm. and 7.5 cm., respectively. At this time, the patient's temperature was 101°, her pulse 108 and her respiration 22 per minute."

The head was perforated and the child extracted with the cranioclast. It was 46 cm. long and weighed 1850 gms. without the brain. There were no macroscopic evidences of infection, but a uterine culture was taken immediately after the completion of the third stage of labor. The day after delivery the patient's temperature reached 103°, and the following day a second culture was taken and a douche given. The fever persisted for seven days but the woman left the hospital in excellent condition.

Bacteriological Report, M. S., Fever Case 64. Culture I.

Smears show a few cocci and a number of large bacilli with

rounded ends. Cultures show: — Streptococcus pyogenes, Staphylococcus albus.

Culture II. Smears show bacilli similar to those previously seen. Capsules

can be demonstrated. Cultures show: — Streptococcus pyogenes, Staphylococcus albus, Bacillus coli, Bacillus aerogenes capsulatus.

Case III. — Generally contracted pelvis; dystocia; frequent vaginal examinations; rise of temperature during labor; craniotomy; recovery.

A. T., (O. 0. S. No. 762), a black primipara, was seen in consultation outside the hospital. She had been in labor for two days and had been repeatedly examined. She was dull and listless. Temperature 101°, pulse 120. Her uterus was tetanically contracted upon a large child; no foetal heart heard. The pelvis measured Sp. 22.5, Cr. 24, Tr. 28, D. B. 18. Vaginal examination: Outlet relaxed, vagina hot and dry, cervix fully dilated, membranes ruptured; head at brim, in L. 0. I. A., not engaged; diagonal conjugate 10 cm. A marked caput succedaneum had formed and palpation of this elicited gaseous crepitation. Tho forceps was applied ineffectually and craniotomy was resorted to, the placenta being subsequently removed manually. Cultures were made from the liquor amnii, and from the lochia on the first day of the puerperium.

At autopsy upon the child there was abundant evidence of general infection with the gas bacillus.

Bacteriological Report, A. T., Fever Case 102. Source of cultures: — (a) Liquor amnii, (b) Uterine lochia. Smears show micrococci and bacilli.

Cultures show: — Streptococcus pyogenes, Bacillus coli, B. aerogenes capsulatus.


April, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


141


This patient's temperature chart is unusual in that but slight rises in temperature are noted, in no instance above 100°. This may possibly be explained by the fact that the temperature was taken but twice daily, and at irregular intervals.

Case IV. — Inevitable abortion; vaginal pack; marked rise in temperature subsequent to labor. Saprarmia {f).

M. W., (H. No. 1145), a white multipara, entered the hospital April 10, 1902, with a history of irregular bleeding for two weeks, which became alarmingly free two days previous to entry. She had menstruated last October 21, 1901.

The fundus uteri was one finger's breadth above the umbilicus, the child lying in L. S. I. A. No foetal heart heard. Temporizing measures were employed, but the bleeding continued, and as there was no evidence of life on the part of the fffitus, it was decided to induce labor. The vagina was accordingly packed with sterile gauze which stimulated the uterus to contract, and at 5 a. m., April 12, the patient spontaneously expelled a dead foBtus (6mos.). The same day about 6 p. m., subsequent to the expulsion of some large clots covered with decidua, the temperature rose to 103°, and the pulse to lOS. There were no subjective symptoms and the temperature became normal within 48 hours.

Bacteriological Report, M. W., Fever Case 184. Source of cultures: — Uterine lochia.

Smears show coarse bacilli staining by Gram's method.

Cultures show: — B. aerogenes capsulatus.

Case V. — Precipitate labor; ha;morrhage; collapse; submammary infusion; mastitis.

E. W., (O. O. S. No. 619), a white primipara, had a precipitate labor resulting in a bad perineal laceration. The placenta was retained, but as it was desired to repair the perineal tear at once, Crede's method of expression was employed. The patient subsequently collapsed, and was infused with 2000 cc. of sterilized normal salt solution prepared from tap water. The following day her temperature rose to 102°, but almost immediately fell tc normal. On the fifth day it again rose, reaching 103.4°, with evidence of local inflammation in one breast. This was incised and drained, after which the puerperium was uneventful.

Bacteriological Report, E. W., Fever Case 84. Source of Culture: — Pus from breast abscess.

Smears Cultures


show B. aerogenes capsulatus.


This case has been included with a view of showing the great danger of infection in all procedures such as douches and irrigations where the asepsis is not absolute, and as evidence of the fact recently insisted upon by Kamen, that the gas bacillus may operate alone in producing local inflammation, particularly it superimposed upon an injury.

Case VI. — Normal pelvis and pregnancy ; self-induced abortion; infection; removal of infected ovum; recovery.

0. H., (H. No. 1738), a white multipara, was admitted to the hospital March 30, 1904. She had menstruated last in December, 1903, and one week previous to admission (i. e., March 22, 1904), knowing herself to be pregnant, had introduced a bougie into her cervix for the purpose of inducing an abortion. This was attended by slight bleeding, which persisted until entry into the hospital. The night prior to her admission (March 29) she had had a slight chill and vomited a good deal. The day of admission she had five slight chills, and entered with a temperature of 102.7° and a pulse of 136.

From external examination little could be made out except slight tenderness above the symphysis pubis, but as there was a foul-smelling discharge from the vagina, preparations were made to remove the infected ovum. The patient was anaesthetized and prepared for operation in the usual manner. A culture was taken


from thhe uterine cavity, after which the cervix was dilated to admit the finger. A considerable amount of foul-smelling tissue was removed, and the uterine cavity was thoroughly washed out with normal salt solution. Within twelve hours the temperature fell to normal, where it remained till the 13th day, when it rose following a vaginal examination, but fell to normal again almost immediately.

The tissue removed from the uterus was preserved and examined microscopically.

0. H., Current work No. 689. Microscopic examination.

The specimen apparently consists of the entire ovum. The amnion and chorionic membrane are completely necrotic, as well as the villi immediately surrounding the latter. The decidua is well-marked, and shows but slight development of Nitabuch's layer; between it and the amnion are chorionic villi in all stages of degeneration, some perfectly normal, others completely degenerate. There are no blood-vessels; most of the intervillous spaces are filled with blood, though here and there it is distinctly coagulated. Sections stained by the Gram-Weigert method show myriads of thick bacilli of varying lengths, and also cocci. Diagnosis: Infected abortion. •

Bacteriological Report, 0. H., Case 249. Source of Culture: — Uterine cavity before operation.

Smears show chiefly large coarse bacilli, often in pairs and frequently intracellular. They retain Gram's stain. Culture shows: — Micrococcus aureus. Micrococcus albus, B. aerogenes capsulatus. It is noteworthy that in addition to its development in all the cultures grown anaerobically, the gas bacillus was also demonstrable in the milk grown aerobically probably owing to its association with staphylococci.

Case VII. — Normal pelvis and pregnancy ; prolonged labor; dystocia; Champetier de Ribes Balloon; version and extraction: post partum haemorrhage; vaginal pack; puerperal infection: recovery.

B. L., H. No. 1597, a white multipara aet. 41, was admitted to the hospital on October 31, 1903. She had been pregnant ten times before, five of her children being still-born and three others living for only a few minutes after birth. One child had presented by the breech, but apart from this and one forceps operation, her labors had been normal. She invariably lost much blood after the labor, particularly after the last, when " the after-birth came before the child." Following this confinement she was in bed four weeks with fever, and since that time menstruation has been painful. Last menstruation February 1^, 1903. Examination showed the presence of a cystic goitre, a rapid pulse, and slight oedema of the lower limbs; apart from this her condition was normal.

Pains began 10 p. m., November 29, but in spite of the fact that they became hard and frequent, the cervix failed to dilate. On December 2, at 8.30 p. m., a Champetier de Ribes bag was introduced into the cervix, and was expelled four hours later, when the cervix was found three-fourths dilated. During the night the patient's temperature rose to 101.6°, but almost immediately fell to normal. After the expulsion of the bag the pains gradually ceased and the patient slept till morning, when, in the complete absence of pains, it was decided to complete the dilatation of the cervix manually and deliver the child by version. The version was readily accomplished, but owing to the large size of the child's head, great difiiculty was experienced in extraction, and though the fcetal heart continued to beat for several minutes after delivery, the child could not be resuscitated.

The patient lost 1000 cc. of blood during the third stage, and examination showed a slight i)erineal tear and also a bilateral laceration of the cervix. The former was repaired immediately,.


142


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 169.


but as the uterus contracted firmly after the expulsion of the placenta and the bleeding abated, suturing the cervix was considered inadvisable. A uterine culture was taken immediately after the third stage. Four hours after the completion of the operation the bleeding still continued and as it was evidently from the cervix, it was thought that it might be controlled by a vaginal pack, which was accordingly carefully introduced. The patient's pulse had risen to 156 per minute, but following the introduction of the pack and the administration of stimulants, marked improvement occurred. The pack was removed some eighteen hours later (9 a. m., December 4).

On the morning of the third day (the day following the removal of the pack), a second uterine culture was taken. The cervix was far back, its lumen practically occluded. When its anterior lip was drawn forward with a tenaculum, a large amount of foulsmelling brown fluid escaped from the uterus, but there was no evidence of the presence of gas. Following the culture, the temperature rose to 101.4° but fell again to normal, rising to 104° the next day at 4 p. m., falling during the night to 97°, but reaching 103.6° at 8 a. m. With both these rises there were chills, but the patient's general condition remained good and the physical examination was negative save that the fundus uteri was soft and high, and the lochia rather foul.

The day of the first rise (4th day) the haemoglobin was 45%; the leucocyte count, 20,200.

After the second rise (5th day, 8 a. m.) a third uterine culture was taken and a douche of 2 litres of salt solution was given. A blood culture was also taken.

The fever continued till the 9th day, varying from 100° to 103°, but the patient gradually improved, and left the hospital the 22d day in excellent condition.

Bacteriological Report, B. L., Fever Case 235. Source of culture: — Uterine lochia.

(a) Immediately after labor. Smears, negative.

Cultures, negative.

(b) Morning of third day.

Smears show numerous thick bacilli with rounded ends, stained

by Gram's method; no cocci seen. Cultures show: — Streptococcus pyogenes, B. aerogenes capsula tus.

(c) Morning of 5th day. Smears show as in "(b)."

Cultures: — Aerobic, iiegative. Anaerobic, B. aerogenes capsular tus. Blood culture, 5th day, negative.

The streptococci were evidently few in number, and accordingly narrowly escaped being overlooked. lx)w has pointed out that in large numbers of cases where colon bacilli alone are demonstrable, the primary invader is the streptococcus, which later outgrown, cannot be obtained in cultures.

Case VIII. — Incomplete abortion; curettage; septicwmia with anaerobic organism; thrombosis; death.

M. F., (H. No. 1702), a colored multipara, entered the hospital February 20, 1904. She had been perfectly well up to February 12, having menstruated last in November, 1903. On the day noted above she began to bleed, without any apparent cause, and during the night passed a mass of some sort per vaginam. Since then she had bled at irregular intervals. She denied any internal examinations or manipulations. She was a sparely-built colored woman, eyes sunken, mucous membranes pale, tongue coated, temperature 102.7°, pulse 130, respiration 30. No other abnormality was noted on physical examination. She was prepared for operation in the usual manner and a uterine culture was taken before an internal examination was made. The uterus was then curetted and douched with a large quantity of salt solution. After the operation the temperature rose to 104.3° and remained


above 101.7° till the morning of the third day, when it became subnormal, rapidly rising again to 106°. This same day thrombosis of the left saphenous vein was noted, though there was practically no oedema of the extremity. The leucocyte count was 28,000. From this time on, the temperature remained persistently elevated, frequently reaching 105° and occasionally 107°.

Blood cultures taken on the 8th and 11th days were positive, as well as a urine culture the 15th day. Jaundice was noted on the 6th day, but never became marked. Patient died the 18th day.

Anatomical diagnosis, M. F., Autopsy 2260: "Abortion, clean uterine cavity; thrombosis of vena cava, left common iliac, femoral and saphenous veins, partial thrombosis of right iliac vein. Embolic abscesses in the lung. Cloudy swelling of liver and kidney. General ansmia. Hemorrhagic ulcers of rectum. Acute splenic tumor. Infarct of spleen. Jaundice. Oidio-mycosis of oesophagus. No formation of gas in the organs.

Examination of material removed from the uterus by curettage 11 days post abortum. (Current work No. 677.)

" The stroma is much denser than usual, and is infiltrated with round cells and a few leucocytes. Scattered through the tissue are a few areas which stain brightly with eosin, some of which are apparently fibrinous in character, while in others distinct remnants of decidual cells can be found. Examination with the high power shows at the margins of portions of the endometrium, but particularly in the blood surrounding, numerous cocci, and occasionally large thick bacilli. The cocci are usually in groups, but short chains are also to be seen. The bacilli occur in an isolated manner and in no case can more than two be found in the same field."

Bacteriological Report, M. F., Fever Case 239.

A. Source of culture: — Uterine cavity.

Smears show micrococci in chains, also coarse bacilli, occasionally in chains. Both forms retain Gram's stain. The bacilli are occasionally seen within leucocytes.

Culture: — Aerobic plates and tubes absolutely negative.

Anaerobic tubes show: — (I) B. aerogenes capsulatus, (II) a streptococcus.

B. Blood.

Source of culture: — Blood from med.-basilic vein.

Culture I, made on the 8th day.

Ten tubes of various forms of agar were inoculated for the purpose of making plate cultures, but as by accident there were but 9 plates, 9 tubes were poured, and in one the agar was allowed to solidify. After incubation there was absolutely no growth on any of the plates but in the bottom of the solid tube, several colonies were seen. These proved to be a micrococcus growing in chains and similar to the one isolated from the uterus.

Blood culture No. II, made on 11th day.

Bearing in mind the previous result, ten tubes were inoculated as before and when pouring them into Petri dishes, about 2 cc. of the medium was retained in the tubes, which were rolled and cooled in the manner described by Esmarch. Five plates and the same number of tubes, selected indiscriminately, were incubated in the usual manner, and the others, in an atmosphere of hydrogen. None of the former showed any growth after 5 days, whilfc numerous colonies developed upon those incubated anaerobically. These consisted of micrococci growing in chains, apparently identical with those previously obtained.

C. Urine.

Source of culture: — Catheterized urine.

No. I: — Made on the 15th day (contaminated).

No. 11:- — Second culture obtained within five minutes after death of patient showed in all media streptococci and an unidentified bacillus. The cocci were noted in both aerobic and anaerobic


April, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


143


tubes, possibly developing in the former as a result of the symbiosis.

In all instances the organism was apparently identical with that first obtained from the uterine cavity, and had the following characteristics: • Micrococcus, invariably paired, more frequently in chains of ten to twelve elements. Retains Gram's stain (1.2. .5 min.). Grown on agar mixed with blood frequently shows a distinct hEemolytic ring. Capsules not demonstrated. No spores, no motility.

Anaerobic growth was as follows:

Milk. — Acidity, no coagulation.

Glucose-bouillon. — Slight sediment.

Glucose-agar. — Fine pin-point raised pale gray colonies.

Blood serum. — Similar growth.

Hydrocele agar. — Similar growth, more profuse.

Transfers were made to various media in attempt to obtain aerobic growth. There was a slight growth on one hydrocele agar tube and one or two colonies on blood serum. The remaining tubes showed no growth and transfers could not be obtained from the two noted as positive.

At autopsy the same organism was obtained from the thrombus and by gradually reducing the percentage of hydrogen in which it was grown, aerobic cultures were finally obtained. These, however, died out in two or three days. The presence of a capsule w-as also suggested. So far as I am able to learn, this is the first instance recorded in which an anaerobic organism other than the gas bacillus has been obtained from the blood during life. The case is also of interest from the fact that in spite of the almost complete occlusion of the veins of the extremity there was practically no oedema and the swelling was only appreciated after more careful comparative measurements.

Case IX. — Fehricula during pregnancy ; normal labor; puerperal fever. Isolation of Bacillus aerogenes capsulatus from the uterus; blood culture negative; hysterectomy ; isolation of Bacillus aerogenes capsulatus (?) and Bacillus typhosus from the circulating blood; death; lesions of typhoid fever; gas bacilli and typhoid bacilli in cultures at autopsy, and in sections from organs.

L. S.. (H. No. 1597), aet. 19, black, 1-para, married. Was first seen in the dispensary January 9, 1903. Her previous pregnancy and labor had been normal and her condition at that time was excellent. The pelvis measured Sp. 24.5, Cr. 26, Troch. 30, D. B. 18, D. C. 11.75.

She was admitted to the hospital January IS. Her condition then, apart from pregnancy, was quite normal: Temperature 97.6°, pulse 92, respiration 24. On the third day following her admission (January 20) she complained of some headache, and had a temperature of 100.4°. For nine days the temperature ran an irregular course, elevated in the afternoon, normal in the morning, only once reaching 102°. In the afternoons, she occasionally complained of headache and pain in the back of the neck, but these invariably disappeared by the following morning. Typhoid fever was thought of, but there was complete absence of definite symptoms and physical signs; moreover, as she had a doubtful history of syphilitic infection, she was put upon antisyphilitic treatment and apparently improved under it, the fever gradually subsiding, so that she appeared perfectly well on January 30.

Labor pains began early in the morning of February 2, and she was delivered spontaneously at 5 p. m. The child and placenta were normal. On account of the fever before labor, a uterine culture was taken immediately after the completion of the third stage.

On February 4 (third day post partum) there was no visible growth in the tubes and a second culture was taken, in the smears from which, long chains of Gram-staining bacilli were found Two hours after this culture, the patient's temperature rose to


104°. A blood culture was taken on February 5, and on February 6 (fifth day) a third culture from the uterus, followed by a douche of salt solution. Part of the material obtained was inoculated into a rabbit which was shortly afterwards killed and incubated.

On February 7 (sixth day post partum) as the temperature was still markedly elevated, the rabbit having shown the definite lesions induced by Bacillus aerogenes capsulatus and the inoculations of various media with uterine lochia confirming this test, while no growth had occurred in the blood culture, supra-vaginal hysterectomy was done by Dr. Williams.

Following the operation the temperature fell almost immediately to 100.5°, but rose the following morning to 105.6° and ranged between 102° and 106° until death, 16 days later. The pulse was very rapid, never below 130 per minute, sometimes reaching 180. The patient was frequently irrational, and passed fseces and urine involuntarily; she could, however, answer intelligently till within 24 hours of her death. She complained of no pain, but towards the end dyspnoea became marked.

Treatment consisted in general stimulation with strychnia and digitalin, aided by infusions of large amounts of normal salt solution.

Clinical Bacteriology. Uterine culture " A " at completion of labor, February 2.

Smears negative.

Aerobic and anaerobic inoculations upon various media. Examination of same, four days later.

Aerobic cultures: — Negative.

Anaerobic cultures; — No growth in bouillon or milk; abundant growth of long, coarse bacilli retaining Gram's stain, in the condensation water of the blood serum tubes: Capsule stain positive, and spore-bearing forms seen. This organism inoculated into a rabbit produced lesions typical of those caused by Bacillus aerogenes capsulatus, the organism being cultivated from the heart's blood.

Uterine culture " B," third day after labor, February 4. Smears showed Gram-staining thick bacilli, singly and in chains. Aerobic and anaerobic inoculations: — Negative.

Uterine culture " C," fifth day after labor, February 6. ' Smears show many thick bacilli. May occur singly and in chains, retain Gram's stain and resemble Bacillus aerogenes capsulatus. Aerobic and anaerobic inoculations were made as before, and at the same time 2 cc. of the lochia was diluted with an equal volume of sterile bouillon and the mixture injected into the ear vein of a rabbit, which was killed five minutes later, and placed in the incubator for eight hours.

At autopsy typical gas bacillus lesions were present and the organisms were obtained on smears and cultures from the heart's blood.

Blood culture " A," February 4.

Aerobic and anaerobic inoculations negative after four days in thermostat.

Blood culture " B," February 10.

Owing to the poor quality of the circulation and the smallness of the superficial veins, only about 2 cc. of blood was obtained. The entire quantity was immediately injected into the ear vein of a rabbit, which was subsequently killed, and placed in incubator. The following morning the animal was markedly distended and Bacillus aerogenes capsulatus was obtained from its heart's blood in cover slip preparation and cultures.

On the advice of Dr. Welch, the above result was not considered absolutely conclusive, as the organism had not been grown In artificial media, and therefore the possibility of contamination from the intestine of the rabbit had to be considered.


144


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 1G9.


Blood culture " C," February 15.

Blood obtained from right-median cephalic vein and a large number of inoculations made. At the same time 15 cc. of blood was collected under weak bichloride solution, but no gas bubbles were observed. Upon centrifugalization with weak acetic acid, a number of bacilli, similar to those previously described, were found in the sediment, as well as a few others, differing slightly In morphology.

After 48 hours there was no growth except in the milk, and in one hydrocele agar tube, the former appeared slightly acidified, while a few non-Gram-staining bacilli were found in the condensation water of the latter. The tubes were re-incubated anaerobically, but no change was noted.

February 23 secondary inoculations were made from the milk flasks and showed an aerobic bacillus, which by its cultural and agglutinative reaction was proved to be Bacillus typhosus.

At the autopsy upon the patient (No. 2252, February 23, 1904), Dr. Bunting made the following anatomical diagnosis: — Typhoid fever; operation (amputation of uterus), infected abdominal wound; oedema and atalectasls of lungs; cloudy swelling of liver and kidneys; oedema and swelling of the pancreas; multiple abscesses of the kidney; acute splenic tumor; early arteriosclerosis; healing ulcers in small intestine.

Bacteriological examination by Dr. W. W. Ford gave the following results:

Bacillus typhosus in heart, blood, and spleen.

Bacillus aerogenes capsulatus in abdominal wound, spleen, kidney, and ureteral abscess.

Micrococcus aureus in ureteral abscess.

Microscopic examination of heart, lungs, liver, pancreas, and spleen were without special interest, as far as our case is concerned. On the other hand bacteria were demonstrated in the kidneys, mesenteric lymph glands, intestine, and appendix, as follows :

Kidney. — Capsular surface is regular, convoluted tubules dilated; epithelium is low, granular, and ragged; the lumina show the granular precipitate of the so-called " colloid-droplets." A few hyaline casts are found. The glomeruli are congested, their capsular spaces dilated and show granular precipitates. The interstitial tissue is oedematous, but is apparently not increased in amount. In one portion of the section there are several distinct abscesses which show cellular detritus and pus cells, chiefly of the polymorphonuclear type. In the periphery of the abscess, however, there are mononuclear cells which are actively phagocytic for other nucleated elements. There are groups of short, coarse hacilli, occurring in pairs, found in the abscess; also much coarser bacilli occurring chiefly at one focus.

Mesenteric Lymph Glands. — Show the sinuses crowded with large mononuclear cells, many of which are phagocytic for lymphocytes. The glands also show oedema and scattered areas in which the cells are necrotic. There is apparently also hyperplasia of the lymphoid elements. The glands themselves and especially their capsules, with the intervening connective tissue, show very many coarse, long bacilli, often in pairs or short chains.

Intestine. — Peyer's patches show Increase in the epithelioid elements and small mononuclear cells, with superficial necrosis, and also scattered areas of necrosis in the depth of the swollen patches. In these areas there is fragmentation of nuclei, degeneration of the cells and infiltration. The epithelioid cells are phagocytic.

The Appendix. — Shows in the lumen a necrotic slough. Necrosis also extends into the wall of the appendix to the muscularis at one point; the wall is here infiltrated with leucocytes. In the slough are a few coarse bacilli, similar to those already described, also smaller bacilli.


Examination of the puerperal uterus removed by supra-vaginal hysterectomy: — The organ weighs 515 grammes and measures 13 X 13 X 6.5 cm. Externally there is no abnormality. On opening its cavity, which measures 9 x 5.5 cm., a dark tenacious clot is disclosed 5x4x2 cm. On removing this, the'placental site is found in the upper left quadrant of the posterior wall, it measuring 6 x 4.5 cm. and covered with black protruding thrombi.

Microscopic examination on the greater part of the clot consists of fibrin, though included in it here and there are areas of degenerated tissue containing spaces with apparently hyaline walls. Large numbers of bacilli are readily demonstrable, both in the fibrin and the degenerated tissue.

Sections from the placental site show internally a thick layer of fibrin with very few cells in its meshes. Between this and the muscularis is a thin layer of degenerated tissue, more or less infiltrated with blood, and richly supplied with blood-vessels, chiefiy venous in character. Where the tissue is well preserved, it is made up of spindle-shaped cells with fusiform nuclei; scattered through it are large numbers of irregu,larly shaped cells with deeply staining nuclei. There is no trace of inflammatory reaction. Protruding into this tissue, but chiefly in the innermost layers of the muscularis, are numerous thrombosed vessels. The muscularis itself presents a normal appearance.

In some of the veins, but particularly in the necrotic tissue corresponding to the endometrium, many large tolerably thick bacilli can be seen. These stain by Gram's method, but can be seen even in specimens stained with hmmatoxylin and eosin.

Case No. X. Rise in temperature during labor; manual dilatation of cervix and extraction of child; puerperal infection; parotitis; recovery.

B. R., (O. O. S. No. 2170), set. 25, 2 para. Pelvis normal. Was first seen by Out-patient Department, 8 p. m., April 20. At that time her cervix readily admitted two fingers, but at midnight, in spite of good pains, there was little further dilatation. Patient slept until morning. At 2 p. m., April 21, there had been little advance, but as the patient's temperature was 100.4°, her pulse 105, and the foetal heart between 160 and 170 per minute, the cervix was dilated by Harris' method and the child extracted. The field of operation had been contaminated by fseces and a douche of hot normal salt solution was given after the completion of the labor. The temperature after labor was 100.6°. and the following day it rose to 102.2°. Its maximum, 103.5°, was reached on the fifth day; but from 103° on the sixth day, it fell to normal on the seventh day, and remained around 100° until the thirteenth day.

Swelling of the parotids was noted the day after operation, but was thought to be due to holding up of the lower jaw during the administration of the anaesthetic. Later, it was learned that a next-door neighbor had mumps, and that a member of the patient's family had had the same disease two weeks previously. A uterine culture was taken and a douche given on the third day, and on the fourth day a blood culture was taken.

Wliile it is quite possible that the primary trouble may have been the parotitis, the presence of marked subinvolution of the uterus noted at examination on the tenth day, makes the bacteriological findings at least of interest.

Fever Records No. 241, B. R., O. O. S. No. 2170, April 23, 1904.

Smears show diplococci and two forms of bacilli, one short, the other large and coarse. All of the bacilli and some of the cocci retain Gram's stain.

Culture. — Gonococcus (1). Diplococcus retaining Gram's stain. Strepto-bacillus aerogenes capsulatus.

Blood cultures taken on the fourth day were negative.

Since the completion of the article two more cases have come under our observation.


April, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


145


I. R. S., H. No. 1886, set. 41, white, married, aborted on August 17, 1904, when 3Vz months pregnant. For seven days her condition was excellent, but on August 24 she had a severe haemorrhage, to control which an outside physician packed the uterus with iodoform gauze. She was advised to enter the hospital, which she did on August 25.

On admission her temperature was 100° and her pulse 120. Large iodoform gauze packs were removed from the vagina and uterine cavity. A uterine culture was taken, some small fragments of the ovum removed with the finger, and a large douche of hot salt solution was given.

B. coH and B. aerogenes capsulatus were grown from the lochia thus obtained, but the patient made an uninterrupted recovery.

II. M. S., a white multipara, entered the hospital July 29, 1904, with a history of having had chills and fever during the day, accompanied by slight bleeding from the uterus. She denied having attempted to induce abortion, but her statement was later proven to be false.

On admission a purulent discharge was noted escaping from the cervix uteri. A uterine culture was taken and the infected ovum removed manually.

She developed pysemia with panophthalmitis of the right eye and abscesses in the left arm, the abdominal wall, and in the left broad ligament. The eye was removed, the abscesses opened and drained, and the patient made a good recovery.

B. aerogenes capsulatus was associated with streptococci in the original culture, and streptococci were obtained from the patient's blood and from the pus in each of the abscesses.

Literature.

Achalme: Considerations pathogeniques et anatomo-patliologiques sur I'erysipele, ses formes et ses complications. Essais stir la virulence du streptocoque. These de Paris, 1892.

Bumm: TJeber die Aufgaben weiterer Forschungen auf dem Grebiete der puerperalen Infection. Archiv fiir Gyn., 1889, XXXIV, 325.

Histologische Untersuchungen iiber die puerperale

Endometritis. Archiv fiir Gyn., 1891, XL, 398.

Beson: Contribution a I'etude du vibrion septique. Annales de I'lnstitut Pasteur, 1895, IX, p. 179.

Chiari : Zur Bakteriologie des septischen Emphysems. Prager med. Wochenschr., 1893, XVIII, 1, p. 1.

Cole: Note on a Case of Infection by Bacillus Aerogenes Capsulatus, in which the organism was demonstrated in the circulating blood during life. Johns Hopkins Hospital Bulletin, 1902, XIII, 234.

Dobbin: Puerperal Sepsis due to Infection with the Bacillus Aerogenes Capsulatus. Bull. Johns Hopkins Hospital, 1897, VIII, p. 24.

Doleris: Essai sur la pathogenic et la therapeutique des accidents inl'ectieux des suites de couches. These de Paris, 1880.

Septicemic gaseuse d'origine puerperale. Se maine Med., 1899, p. 289.

Discussion. 13^ Congres des Sciences Medicates

de Paris, Annates de Gyn., 1900, LIV, p. 1.

Ernst: Ueber einen gasbildenden Anaeroben im menschlichen Korper und seine Beziehung zur Schaumleber. Virchow's Archiv, 1893, CXXXII, H. 2, p. 308.


Fraenkel : Ueber die Aetiologie der Gasphlegmonen. Centralbl. f. Bakt. und Parisitenk., 1893, XII, 1, p. 13.

Ueber den Erreger der Gasphlegmonen. Miinch.

med. Wochenschr., 1899, XLVI, Nr. 43, p. 1369 ; Nr. 43, p. 1420.

Ueber die Aetiologie und Genese der Gasphlegmonen, Gascysten und der Schaumorgane des menschlichen Korpers. Ergebnisse d. allg. Path, und path. Anatomic, Wiesbaden, 1904, VIII, pp. 403-471.

Gebhard : Klinische Betrachtitngen und bakteriologische Untersuchungen iiber Tympania uteri. Zeitschr. f. Geb. u. Gyn., 1893, XXVI, 480.'

Goebel: Ueber den Bacillus der Schaumorgane. Centralbl. f. allgm. Path, und path. Anat., 1895, VI, 12, 13, p. 465.

Graham, Steward, and Baldwin : The Bacillus Aerogenes Capsulatus — case, diagnosis, autopsy, bacteriological study. Columbus Med. Journal, 1893, XII, p. 55.

Gwyun: A Case in which the Bacillus Aerogenes Capsulatus was Eepeatedly Isolated from the Circulation During Life. Bull. Johns Hopkins Hospital, 1899, X, p. 134.

Halban: Uterusemphysem und Gassepsis. Monatsschr. fiir Geb. u. Gyn., 1900, XI, p. 90.

Hirst : Text-Book of Obstetrics, 1903, p. 753.

Hitschmann and Lindenthal: Ueber die Schaumorgane und die bakteriellen Schleimhautsemphyseme. Sitzungsberichte der kaiserlichen Akademie der Wissenschaften, 1901, CX, 3 abt. H. VI, p. 93.

— Ueber die Gangrene foudroyante. Sitzungsbe richte der kaiserlichen Akademie der Wissenschaften (Wien), ]898, CVIII, 3 abt. H. Ill, p. 67.

Jeannin : Etiologie et pathogenic des infections puerperales putrides. These de Paris, 1902.

Kamen: Zur Aetiologie der Gasphlegmone. Centralbl. f. Parasiten- n. Infectionskrankheiten, 1904, XXXV, 6, p. 686.

Kedrowski : Ueber die Bedingungen unter welchen anaerobe Bakterien auch bei Gegenwart von SauerstofE existiren konnen. Zeitschr. fiir Hygiene, 1895, XX, p. 358.

Koch : Zur Aetiologie des Milzbrandes. Mitth. aus dem kaiserl. Gesundheitsamt, Berlin, 1881, 1, 1-31.

Kronig: Discussion, Congres de Paris, 1900. Annates de gyn. et d'obst, 1900, LIV, 11, p. 35, et seq.

Kronig und Menge. Bakteriologie des Grenitalkanales der schwangeren kreissenden und puerperalen Frau. Leipzig, 1897.

Legros; G. : Eecherches bacteriologiques sur les gangrenes gaseuses aigues. These de Paris, 1902.

Legros and Lecene : Comptes rendus. Soc. de Biol., Paris, June 22, 1901.

Lenharz: Die septische Erkrankrmgen. Nothnagel. Specielle Pathologic u. Therapie, 1904, Bd. Ill, Hft. 1, p. 320;

Lindenthal: Beitrag zur Aetiologie der Tympania uteri. Monatschr. f. Geb. u. Gyn., 1898, VII, 269.

Ueber die Aetiologie der sogenannten Kolpohy perplasia cystica. Wien. med. Woehenschrift., 1897, p. 3, 35.


146


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 169.


Menereul : Gangrene gaseuse produit par le vibrion septique. Annales de I'lnstitut Pasteur, 1895, IX, 7, p. 529.

Mouchotte: Documents pour servir a 1' etude de I'hysterectomie dans I'infection puerperale post abortum. These de Paris, 1903.

'Nory : Ein neuer anaerober Bacillus des malignen Oedems. Zeitschr. f. Hygiene, 1894, XVII, p. 309.

Norris: A Eeport of Six Cases in which the Bacillus Aerogenes Capsulatus was Isolated. Amer. Jour. Med. Sciences, 1899, CXVII, p. 172.

Pasteur: Septicemic puerperale. Bull. Acad, de Med., 1879, 256, 488. See also Comptes rendus des seances de I'Acad. des Sciences, (a) Pasteur et Joubert, 1877, LXXXIV, p. 900; (b) Pasteur et Joubert, 1S77, LXXXV, p. 101; (c) Pasteur et Joubert et Chamberland, 1878, LXXXVI, p. 103; (d) Pasteur, 1879, LXXXVIII, p. 1216.

Pasteur et Joubert : Comptes rendus des seances de I'Academie des Sciences, 1877, LXXXV, p. 113.

Penzo : Beitrag zur Studium der biologisehen Verhaltnisse der Baeillen des malignen Oedems. Centralbl. f. Bakt., 1891, X, p. 822.

Eist et Mouchotte: Note sur trois cas d'infection uterine apres avortement. Comptes rendus Soc. de Biol., 1902, LIV, 303.

Eoger: Quelques efEets des associations microbiennes. Comptes rendus de la Soeiete de Biologie, 1889, p. 35.


Schattenf roh and Grassberger : Ueber Buttessauregahrung. Archiv f. Hygiene, 1900, XXXVII, p. 54.

Uffenheimer : Ein neuer gaserregender Bacillus. Beitrage zur path. Anat. und Pathologic, 1902, XXXI, p. 383.

Vallery-Eadot : Life of Pasteur (Trans. Devonshire), 1902, II, p. 176.

A'eillon et Zuber: Soeiete de Biologie, Mar. G, 1897; Semaine Med., 1897, p. 85.

Kecherches sur quelques microbes strictement

anaerobies. Archiv de med. experimentale, 1898, X, p. 517.

Welch : The Distribution of the Bacillus Aerogenes Capsulatus. Journ. of the Boston Society of Med. Sciences, 1901, V, 7, p. 369.

Morbid Conditions Caused by Bacillus Aerogenes

Capsulatus. Johns Hopkins Hospital Bulletin, 1900, XI, 185.

Welch and Nuttall : A Gas-producing Bacillus Capable of Eapid Development in the Blood-vessels after death. Johns Hopkins Hospital Bulletin, 1892, III, p. 81.

Westenhoffer : Ueber Schaumorgane und Gangrene foudroyante. Virchow's Archiv, 1902, CLXVIII, Hft. 2, p. 185.

Williams : The Bacteria of the Vagina and their Practical Significance. Trans. Am. Gyn. Society, 1898, XXIII, p. 141.

Text-book of Obstetrics, 1903, 759-60.

Wood: Puerperal Infection with the Bacillus Aerogenes Capsulatus. Med. Eecord (N. 4), 1899. LX. 535.


PROCEEDINGS OF SOCIETIES.


THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

January 16, lOOJf.

A Case of Arterlo Venous Aneurism. Db. Osleb.

Dr. Osier showed a patient exhibiting this condition. The man — now 31 years of age — had, in his eleventh year, received a knife-wound Just above the right knee. This was soon followed by swelling of the calf of the leg and a little later pulsation was noticed along the femoral artery with the development of a swelling in that region. The patient's health had remained good and he was exceptionally vigorous except for some disability in the right lower limb and for attacks of hemorrhage from varicose veins in the lower leg. Along the outer thigh reaching from the lower ribs to the foot, ran huge, tortuous varicose veins, and the whole right leg was enlarged. Thrombi were palpable in the veins, some of them organized and a few probably calcified. There was a pulsating swelling in Scarpa's space and along the femoral artery. Over this a thrill was felt most intensely about the middle of the thigh. In the abdomen was another pulsating tumor 8 inches across and occupying most of the hypogastrium and right iliac fossa. The pulsation here, too, was expansible in character and over it a thrill could be feebly felt. The abdominal tumor was thought by Dr. Osier to be


a large venous sinus associated with the enormous venous dilatation above a traumatic arterio-venous aneurism. Its origin was, however, not perfectly clear, and, so far as he knew, there were no other eases like this one in the literature.

The Immunization of Mice to Cancer. De. G. H. A. Clowes.

Dr. Clowes made a preliminary report of recent work on this subject done by him at the Gratwick Laboratory, at Buffalo, in conjunction with Dr. Gay lord. The work started from the study of two mice infected with cancer brought to tliis country from Professor Jensen of Copenhagen. These animals — which were suffering from subcutaneous carcinoma simplex — died before reaching Buffalo; but inoculations from their tumors, though unsuccessful in the first and second experimental series, finally " took " in a large percentage of the descendants of these inoculated animals (hereditary predisposition?) and the investigators then had cancer experimentally produced on which to work. For the inoculations the tumor material was macerated in twice its weight of sodium chloride and injected subcutaneously. A tumor appeared locally (on the average in about 40% of selected cases), the animal grew cachectic, the blood count fell and the growth became, in a few months, nearly as large as the experimental animal. During the course of the work the


April, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


147


cancer material became attenuated and a certain number of animals with small tumors recovered spontaneously. It was from these recovered mice that immunizing serum was obtained for subsequent experimentation. A series of mice were inoculated with the cancer; half of this number then received a dose (.3 ccm.) of immunizing serum and the other half were kept as controls. This experiment was tried on animals with small, vrith medium, and with large tumors. In almost every case the difference between the history of the immunized mice and the " controls " was quite marked. In the former small tumors disappeared in about five days, larger tumors diminished to 1/2 their original size; in the latter, the disease took its usual progress. All the control animals are now dead; all the immunized animals (with the exception of one, dead from infection) are still alive. Later corroboratory experiments, while not quite so satisfactory as the earlier ones, gave in a general way always the same results. Tumors larger than a small cherry were never cured but treatment reduced their size, and rendered them more easily operable. Mice cured by serum immunization had sera capable of further curing, or at least counteracting, the disease. The sera of animals whose tumors had been improved by X-ray treatment were studied but they proved not to be protective. The protecting body of this immunizing serum was not a cytolysin, possessed no particular hemolytic activity and preeipitive tests all gave negative results. Its protecting activity was not great and a large dose was necessary. The hope for the application of these results to human cancer lay, of ceurse, in obtaining a case of spontaneously cured (or possibly even improving) cancer and then testing the serum of this patient for protective or curative powers.

Pathological Changes. Dr. Welch.

Dr. Welch discussed the microscopical features of the specimens showed by Dr. Clowes. The tumor produced in the mice was, he said, of the solid or simplex type, without acini and made up of polymorphous cells. The stroma was well developed and the connective tissue quite celhilar. In the immunized animals the microscopical picture showed a striking change. In the larger tumors retrogressive metamorphosis was shown by necrosis of many cells at the center by diminution in size of both protoplasm and nuclei of cells still preserved at the edge. In the smaller tumors it was almost impossible to tell that a carcinoma had ever been present, the picture being almost that of an inflammatory granuloma with multinuclear giant cells, necrotic center and vascular connective tissue shell. The observation of Drs. Clowes and Gaylord was, he said, a new and most important one. It offered at least a ray of hope for the treatment of human carcinoma; and while there was, as Dr. Clowes had said, a mathematical possibility that in the mice subsequently treated with serum, the cancer inoculation had led only to the development of an inflammatory new growth while in all the other cases it had produced true cancer and that tlie results had, therefore, been purely accidental he felt this chance to be almost infinitesimal and the experiments practically con


clusive within their own limits. It was extremely improbable that the serum of any animal would have the slightest effect on any human being; a spontaneously cured human being would have to provide the seram.

Apparatus for the Treatment of Fracture of the Femur. Dr. TnEODORE Dunham.

This apparatus was described by Dr. Dunham who devised it 10 years ago and has been using it successfully ever since. It consisted of a plaster spica of the hip, connected with a plaster bandage of the lower leg by two long metal plates incorporated in the two plaster dressings and fastened together by seizing. In applying the apparatus the plaster bandages were first put on and the metal plates incorporated. Extension was then made in the required direction and the two metal plates lashed together. Coaptation splints might be added for older children but were not indicated for young infants in whom the thigh might be put up at right angles, giving the natural position for nursing. The apparatus gave a constant extension, was simple and easily applied, did not necessitate keeping the patient in bed, did not interfere with the routine of life, allowed the thigh to be frequently examined without removing the dressing and had given excellent results. It was necessary to reapply the seizing at intervals in order to take up slack and keep extension perfect. Size and muscularity made the treatment unsatisfactory in adults.

Treatment of Esophageal Stricture.

Dr. Dunham also demonstrated a method of treatment of " impassable " stricture. A silk thread was passed into an ordinary drinking tube and its loose end allowed to float in a glass of water. The water was then sucked from the glass by the patient tlirough the tube and the silk thread was in this washed down the esophagus. Its lower end could then be caught through a gastrostomy wound and the stricture sawed by the method of Abbe. If regurgitation occurred or the patient resisted with his tongue, the thread could be passed through a rubber tube, inserted into the nostril, and could then be washed down by pouring water into an attached funnel. The lower end of the thread could then be caught through a gastrostomy and the upper end fished out from the pharynx. An instrument for cutting strictures was also shown consisting of a guide bougie on which was locked an olivary-tipped dilator. Through the olive ran a cord, the two ends of which were brought out through the patient's mouth. The filiform guided the dilator, the stricture being thus put on the stretch by the olive and sawed by the string. This allowed further dilation and was followed by further sawing.

A wire and spindle dilator was also shown provided with rubber-protecting tubes for portions of the esophagus both above and below the stricture ; and demonstrations of the use of the thread method were given on an apparatus constructed to represent esophageal stricture. Dr. Finney said that the great difficulty in these cases was in once getting something through and that Dr. Dunham had made an important con


148


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 169.


tribution to the solution of this problem. He himself had

modified Abbe's metliod by simjily tying knots in the cord and after passing these through fastening larger and larger bits of gauze for the purpose of dilatation.

Peri Pancreatic Abscess. Dr. Thayer.

The case reported by Dr. Thayer was of a woman, aged 51, who had been taken, in June, with epigastric pain and Jaundice. From this she recovered but shortly afterward had an attack of very severe abdominal pain accompanied by Jaundice, fever, nausea, and vomiting. Fever was intermittent in character and there were night sweats. She complained of a " sore pain " in the left abdomen where there was a slight prominence, especially above the iliac crest. A deep mass could be felt which did not reach to the perinephric region. Two weeks later, however, it had reached the loin and the kidney. Operation was performed by Dr. Finney, a peripancreatic abscess with fat necrosis being found and drained. Four similar cases had been seen at the Johns Hopkins Hospital characterized by abdominal pain (the onset being, in some cases, exceedingly severe), usually Jaundice, fever, sweats, sometimes chills and, on palpation, a deep mass. This might be felt in the pancreas region but in some cases extended much beyond it, even going well over to the right side. The clinical symptoms were fairly characteristic and the diagnosis could usually be made without urine, and stool examinations, which, to be of value, would be quite complex chemical procedures. Possibly the test for a fat-splitting ferment in the urine might be of use.

Surgical Treatment.

In peripancreatic abscess Dr. Finney said the surgeon could either do nothing or accomplish much by doing little. Opening and drainage were the essential features. If the case was seen early it was better to do this in two stages — the tumor being isolated by gauze in the first and opened in the second after peritoneal adhesions had formed.

February 6, 1905.

Gastric Tetany. Dr. Howabd.

Dr. Howard gave the clinical report of a- patient who died in the Johns Hopkins Hospital with this condition. The man was 58 years of age and had sufl'ered for years with attacks of indigestion characterized by gastric pain relieved by vomiting. There had never been blood in the vomitus. For three years before admission attacks of vomiting were frequent, large amounts of sour stomach contents being brought up. They were, however, much improved by the regular use of the stomach tube. Previous to this regular lavage there had also been several typical attacks of tetany, but they too disappeared with the use of the stomach tube. The patient, however, began to lose weight and strength and consulted Dr. Osier in November, 1904. A dilated stomach was found, peristalsis was visible and a surgical operation was advised. This was, however, postponed and the patient returned to the


hospital in January, 1905, much improved. During his stay in the ward he was one day suddenly seized with epigastric pain (following a dietary indiscretion), and some pain and cramps in the extremities accompanied it. Eelief followed the use of a stomach tube; but an attack of tetany supervened. Every muscle of the body went into tetanic contraction, the typical contracture of the hands being present as well as carpopedal spasm. Pain was agonizing, the face became purple and sweating was profuse. Trousseau's symptom was present. For twenty-four hours there was almost complete suppression of urine, and death occurred in forty hours, the patient being in a state of semicoma for the last twelve hours, during which time tetanic attacks were provoked by merely touching the patient's bed. There had been, Dr. Howard said, seven other cases of tetany in the Johns Hopkins Hospital. One was associated with repeated pregnancies, one came on after a severe fright, another was accompanied by a severe diarrhoea, and a fourth by tuberculous meningitis. The remaining three had been gastric cases associated with dilatation, hyperacidity, and hypersecretion. In adults the following forms of tetany were usually recognized: the epidemic, the gastrointestinal, the toxic (chloroform, etc.), and the forms accompanying pregnancy, acute infectious diseases, nephritis, nervous diseases, and thjrroid extirpation. The cause of gastric tetany has been much discussed. Kussmall thought that dehydration was the essential feature, others noting the frequent occurrence of attacks of tetany after the use of the stomach tube in patients with the disease, explained the phenomenon as a reflex. Toxines from decomposing stomach contents had also been suggested as an hypothesis to account for the condition and a certain peptotoxin had been isolated by the French. The condition was said to be rare, was usually associated with gastric dilatation, hypersecretion and pyloric stenosis. The disease is very fatal — sixteen deaths occurring in a series of twenty-seven cases collected by Eiegel.

The Pathology of Tetany. De. MacCallum.

It was to be noticed. Dr. MacCallum said, that the disease occurred in conditions associated with the elaboration of toxines; and there were certain experimental findings which added support to the toxine theory. If, for instance, tetany were artificially produced by extirpation of the parathyroid {not, as the books said, of the thyroid) the tetany could then be relieved by removing the animal's blood and replacing it with salt solution. Cure, at least temporary, could also be effected by the use of parathyroid emulsion. The tetany following extirpation of the parathyroids was, in brief, a specific form. The patient reported hy Dr. Howard had proven at autopsy to have five pairs of parathyroids instead of the usual four, and these had shown on section numerous mitotic figures (a rare finding in normal parathyroids) as though the parathyroids had become hypertrophied to neutralize large absorption of toxine from the stomach. Dilatation of the stomach was enormous, the capacity being 4f liters, and the organ reaching to the right iliac fossa. There was great contraction of the pyloric orifice which measured 5x2 mm. Micro


April, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


149


scopically the tissue at this point did not show the typical picture of a healed gastric ulcer, but Dr. ilacCallum was inclined to think that such had been the origin of the pyloric stenosis. The sudden death which occurred so often during the early history of thyroid surgery had been due, he said, to extirpation of the parathyroids. It had ceased to occur when complete thyroid removal ceased to be done, and the reason for this had been that the parathyroids were left in. Sudden death, however, associated with features of intoxication and occurring in goitre patients, was difficult to explain. It had been thought to be due to a leakage of colloid material, but experimental work had shown this to be not the case.

Synaesthesia. Dk. H. L. Smith.

Dr. Smith read a paper on this subject reporting several cases. The word was used, he said, to mean the occurrence of constant and involuntary association of irrelevant subjective symptoms in response to certain stimuli. " Soundfeelings " for example occurred in many normal individuals, the disagreeable shiver when glass is scraped being a familiar instance. " Sight-feelings " were also quite common ; and the statement had been made that 12.8% of all persons were normally sj'najsthetic. The association of letters and musical tones with colors was not infrequently seen and some musicians were said to tune their instruments by color sensations. Number sjnEesthesia was one of the commoner forms — numbers being conceived of as occupying definite positions in space, usually on a geometrical figure. Statements as to the phj'siological or pathological nature of this condition varied, but there seemed little doubt that heredity was an important factor in the etiology. The cases reported were all members of the same family, the father, four sons, and two daughters being affected. The sj-nssthesia took various forms in the different members, the association of colors with letters, of space position with numbers, of ideas (independent of their meaning) with words being prominent forms in the family. Transmission was plainly from the father, and all the members of the family were of a high grade of mental development. In each case the synaesthesia was most intense in youth and faded with the advance of age. Dr. Hurd reported a similar case, the patient being a person of fine intellect and unusual musical talent, but of a nervous temperament. Dr. Thayer reported a case of number synaesthesia in which the calendar was always thought of as being a definite geometrical form (an octogon), each date having its own position thereon. In this patient the alphabet was always thought of as a spiral and there was a definite geometrical scheme for the numbers. Xo color synaesthesia, however, existed.

Hanging Block Cultivation of Bacteria. Dr. Ford.

Dr. Ford described Hill's method of growing organisms and observing their morphology during their growth. The early discussion as to the nature and classification of bacteria had, he said, obscured their relation to disease and Koch had been led to propound his famous dictum that the biological nature of organisms was immaterial so long as they were con


stantly found in association with the same disease process. The recent work of Westbrook and of Hill had, however, thrown a good deal of light on the morphology of bacteria. An organism was sliown which had been thought to be one of the simple pigmented bacteria but which, in hanging block showed definite mycelial growth.

The Ultraviolet Rays.

Dr. Ford also reported some experiments he had made on the effect of the ultraviolet rays on bacterial growth. A quartz prism, a cadmium spark, and an agar plate of B. prodigiosus were used. Within the ultraviolet rays and reaching to the limit of the violet rays (i. e., including all wave lengths from .00034-.0002175) bactericidal action was evident. Bej'ond these limits there was none.

Thermophilic Bacteria.

During the sterilization of some blood-serum tubes in Dr. Ford's laboratory at 57° C. a growth was found to have occurred on the tubes. The organisms were plated and were found to grow only slightly below 40° C. and rapidly at higher temperatures. They were long, spore-bearing bacilli. Similar organisms have been described by Xovy, by the Italians, and by Eabinovitch, who isolated several forms from decomposing manure. The various forms are all much alike, all bear spores and do not grow on ordinary media. They cannot be differentiated except by the fact that some do and others do not liquefy gelatin.

Fehruanj 20, 1905.

The Cure of Uterine Cancer. Dr. John G. Clark.

Dr. Clark reviewed the recent literature on this subject, drawing conclusions as to operative treatment from the statistical studies which had been published. Radical and complete operation had aroused, Dr. Clark said, bright hopes as to the solution of the problem of the treatment of cervical carcinoma. The ultimate results had, however, been disappointing and led the speaker to take a pessimistic view as to the value of the complete operation. Up to the time of the publication by Dr. Clark in 1896 of a review of the experience of the Johns Hopkins Hospital with uterine cancer vaginal hysterectomy had been the operation done there; and the results of a series of forty-eight cases, though as good as in any hospital, were distressingly bad. It was then suggested that carcinoma of the uterus ought to be treated as carcinoma of the breast had been and an attempt was made to adopt the Halsted procedure for breast and axilla to the uterus and pelvis. Experience with this operation had, however, not given the results hoped for, and Dr. Clark did not think that complete dissection of the pelvis offered inuch for the future. Absolutely complete removal of all the glands was impossible; the prognosis might still be bad even if all the glands were removed; a large proportion of patients are quite inoperable when seen at the clinic; and death has usually been from local recurrence. These facts do not warrant one in expecting results in uterine cancer simi


150


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 169.


lar to those which have been obtained in breast cancer. The composite experience of various operators has also offered nothing to show that the complete operation accomplishes enough to offset its very much greater primary mortality. Reis, among the early writers, thought metastasis an early phenomenon and advocated complete glandular removal. Cullen and others said that metastasis to the glands did not take place early; but Wertheim, studying serial sections, found the glands involved in 31.7% of all cases and claimed that many metastases had been overlooked by others. Schauta, who advocates radical removal of the growth and not a prolonged search for metastases, divides the pelvic glands into six groups — the sacral, the iliac, the aortic, the eoeliac, and the deep and superficial inguinal. Groups 1 and 2 are operable ; groups 3 and 4 inoperable; while groups 5 and 6 did not usually enter into the question. Schauta reported sixty cases with eleven deaths, the prognosis varying notably with the site of the glandular metastasis. He found also that the extent of the disease was no criterion at all of the extent of the metastasis; and that the size of glands was of no clinical value in deciding on whether or not they were involved. No one has yet explained why some early uterine carcinomata metastasize while other late ones do not; nor why certain glands may be skipped by the metastasis ; nor why large glands may be free from cancer while small neighboring ones are involved. It is probable that not the glands alone but also the lymph vessels, veins, and surrounding tissues offer routes for the growth. Kundrath has shown that the growth may take place in several ways; first, by mass growth from the cervix, usually circumscribed, but in some cases with finger-like processes; second, association of circumscribed growth with metastases; and third, combinations of 1 and 2. Wertheim, in his 1901 report, said that unless the glands were enlarged they need not be removed. This is now known to be incorrect; but removal of glands, at any rate, is of prognostic and not of curative value. Dr. Clark's own opinion is that more is lost than gained by an attempt at complete glandular removal — a prolonged procedure with high mortality. While he thought the complete operation ought to be given a good trial by careful and competent men he did not expect much from it and personally never did the complete operation — removing all the growth and as much neighboring tissue as possible by means of the cautery (abdominal incision), but making no attempt to get out the glands. Olshausen, who uses vaginal hysterectomy, has reported a series of over six hundred cases, 31% of which were operable, and 18% remained well after five years. As to the future, something might be hoped for from the work being done to develop treatment other than surgical. From the operative standpoint the outlook was not bright. It was absolutely necessary to have the diagnosis made early when the cases could be saved by surgery — and physicians and laity should be educated (as they have been in Germany by the efforts of Winter) to watch all symptoms at the time of the menopause and always to report promptly uterine hemorrhage.


Pathology of Cervical Cancer. Dr. Sampson.

Dr. Sampson reviewed the pathology of this condition as illustrated by the cases seen at the Johns Hopkins Hospital. In the cervix cancer is more frequent than in the fundus, spreads more rapidly, is attended by a higher mortality and a lower percentage of cures. It is the most frequent form of primary cancer, is a disease of midlife and is frequent in those who are bearing children. It thus takes away valuable members of society when they can least afford to be missed. At the present very little is being done by way of surgical cure. Seventy-five per cent of the cases that come to the clinics are inoperable; recurrence occurs in three-fourths of the cases operated upon; and in practically 93% of all cases there has been simply no cure. Early diagnosis and complete removal of the growth — but not of the glands which are, when removed, of prognostic value only — offer the only hope of cure, the cases being curable early and operability increasing the earlier the disease is seen. Sixteen of the cases at the Johns Hopkins Hospital were living five years after the operation and four ten years after. Dr. Cullen said that he used Wertheim's operation, and did not dissect out the glands. Dr. Bloodgood said that the problem in uterine cancer was like the problem in cancer elsewhere; and that an extensive local operation should always be done. In the stomach complete glandular removal was attended by so great a mortality and the chance of recurrence was so great as not to justify the operation. In the breast the problem was simpler. There was practically no mortality from the operation ; and, in the cases at the Johns Hopkins Hospital over 45% have remained cured for three years. In cancer of the lip glands were easy to remove, the tumor was usually noticed early, and the mortality of the operation was small.


N^0TES Ol^ NEW BOOKS. The Practical Application of the Rontgen Rays in Therapeutics and Diagnosis. By William Allex Pcset, A. M., M. D., Professor of Dermatology In the University of Illinois; and Eugene W. Caldwell, B. S., Director of the Edward N. Gibbs Memorial X-Ray Laboratory of the University and Bellevue Hospital Medical College, New York. Second edition, thoroughly revised, and enlarged. 690 pages, with 195 illustrations, including four colored plates. (Philadelphia, New York, London: W. B. Saunders £ Co., 1904.)

The fact that this excellent work has attained the distinction of two large editions in one year is proof of its value.

A practical feature of the work is that nearly all the cases and illustrations are based upon the author's own experience. This edition contains a review of all the literature of X-ray therapeutics to date, and, as the author points out, but little new has been added to our knowledge, yet it is of the utmost value in confirming the earlier claims as to the value of the X-ray from a therapeutic standpoint.

The important feature in the work is the sane judgment of the author upon the therapeutic value of the Rontgen rays in deep-seated neoplasms. His view upon the subject is as follows: " The extravagant hopes of enthusiasts as to the cure of the gravest malignant neoplasms has not been realized, but if this


April, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


151


excessive demand upon it is eliminated, it has more than fulfilled the prospects of usefulness which it at first seemed to offer."

Part I of the work is devoted to apparatus and the technique of radiography. Part II, the larger section, deals with the therapeutic effects. The treatment of the various diseases is taken up in detail and supplemented with reports of a great number of cases. Each chapter has an excellent bibliography attached.

The work is a most excellent one, not only from its usefulness, but also as a book of reference.

Eye, Ear, Nose and Throat Nursing. By A. Edwabd Davis, M. D., and Beaman Douglas, M. D. With 32 illustrations. {Philadelphia: F. A. Davis Co., Publishers, 1905.)

Any nurse who expects to care for cases in the Eye, Bar, Nose and Throat can read with profit the pages of this book. It not only describes in detail the nurse's duties in these cases, but also gives a short account, in simple language, of the diseases themselves, and of the operative procedures undertaken, and thus puts the nurse in a position of cooperating more intelligently with the physician. The book contains a number of valuable suggestive points, which will be found of interest, not only to the nurse, but to the general practitioner as well, into whose hands a large number of these cases fall at first. It is well printed, in the main well arranged, and contains an excellent index.

Appendicitis. By Bayard Holmes, M. D., Professor of Surgery in the University of Illinois, Attending Surgeon Chicago Baptist Hospitals. (New York: D. Appleton & Co., 190^.)

While the greater part of this book is devoted to the subject of appendicitis, certain other diseases of the abdomen are discussed, namely, peritonitis, intussusception, perforating typhoid uJcer, and carcinoma of the intestinal tract.

Appendicitis is discussed thoroughly and in a most interesting manner. There is a short account of the history of the disease and then the anatomy of the appendix and the pathology, symptomatology, diagnosis, complications and treatment of appendicitis are considered.

The author discusses briefly the origin of pain in appendicitis and calls attention to the fact, now generally known, that the visceral peritoneum is practically insensitive to pain, whereas the parietal peritoneum is exquisitely sensitive. He says, " the origin of pain in appendicitis is hard to explain and no absolute demonstration of it has yet been given."

He gives a good, but perhaps somewhat exaggerated account of those cases of chronic appendicitis giving rise to indefinite and varied symptoms, the cases sometimes known as " grumbling appendices."

In the chapter on the complications of appendicitis the author mentions the cases with abscess involving the iliacus muscle, causing flexion of leg, etc., cases with subphrenic abscess and those with gangrene of ileum or caecum. Among the complications and sequelae, he does not mention post-operative intestinal obstruction, which is not a rare occurrence in most hospitals.

He condemns those who recommend the so-called expectant method of treatment in certain acute cases of more than 24 hours duration.

The author allows many of his cases to get up on the second day and to leave the hospital In four to five days. It seems to us that this is unnecessary haste.

An Introduction to Vertebrate Embryology, Based on the Study of the Frog and the Chick. By Albert Moorb Reese, Ph. D. (Johns Hopkins), Associate Professor of Histology, Syracuse University. (New York: G. P. Putnam's Sons, 190 Jf.)

This little book is designed to give in a brief and convenient


form an outline of the development of the common frog and the chick. As the author has stated, it is largely a compilation from larger and more expensive books such as Marshall's or Minot's Embryology. It gives an outline of the main stages in the embryological development and will be of service to those who wish a general survey of the subject without going deeply into it. The medical student will find that histology and pathology are only to be grasped clearly from the point of view of development and hence he will do well to gain as clear an idea of embryology as possible. The book is well illustrated, there being 84 figures selected wisely from various sources.

Atlas and Epitome of General Pathologic Histology. By Dr. H.

DiJRCK, of Munich. Edited, with additions, by Ludvig

Hektoen, M. D., Professor of Pathology, Rush Medical

College, in affiliation with the University of Chicago. With

176 colored figures on SO lithographic plates, 36 text-cuts,

many In colors, and 371 pages of text. (Philadelphia, New

York, London: W. B. Saunders d Co., 1904.)

This volume, which treats of various general processes in

pathology such as degenerations, inflammation, repairs, etc., and

of tumors, is part of the work on Pathology by H. Durck, of which

the portion devoted to special pathological anatomy has already

been reviewed. It is the translation from the German edition,

edited with many notes by Prof. Hektoen. The text reveals

Prof. Diirck's broad knowledge of pathology and of literature on

the subject toward which he maintains a critical attitude. It is

strikingly clear, logical and sane throughout, and Prof. Hektoen

has secured for it a pleasing English style.

The illustrations, though, are incomparable, both on the judicious selection of the preparations for which they were drawn, and from the wonderful perfection of their execution. The drawings of the tumors are not all so good as those in the first part of the book, but even so they are approached only by those of Borst's book on tumors. Finer illustrations have rarely been seen in any medical publication.

These plates together with the excellent text make the book extremely valuable to students, and should give it a place among the best works on pathology that have been printed in English.

International Clinics. A quarterly of illustrated clinical lectures. Edited by A. O. J. Kelly, M. D. Fourteenth series. Vol. III. (Philadelphia: J. B. Lippincott Co., 1904.)

The first part of this volume is devoted to discussion of certain phases of syphilis and Its treatment, the most notable being a thorough review of the hypodermatic methods of treatment by Fournier.

Of more general interest is Lawrason Brown's contribution on the digestive disturbances in tuberculosis. This is a close and detailed study of a subject of much importance and full of practical information, preventive, dietary, and therapeutic, which Dr. Brown has drawn from his experience at Saranac and from the literature. T. R. B.

A Text-book of Pathology for Practitioners and Students. By Joseph McFaeland, M. D., Professor of Pathology and Bacteriology in the Medico-Chirurgical College, Philadelphia. With 350 illustrations. (Philadelphia, Netv York, London: W. B. Saunders <£ Co., 190^.)

A volume of about 800 pages with numerous illustrations, of which part are original, is added to our list of text-books of Pathology. Ten chapters are devoted to general pathology and ten to the special pathology of various organs. On the whole the book is good as far as it goes. Mention is made of nearly everything that one might expect to find described in a text-book of


152


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 169.


pathology, and with a few exceptions the statements are correct. The hook is characterized, however, by an extraordinary conciseness, such that the least advanced student must remain dissatisfied with what he finds on any particular subject. While the brief statements correspond well with the current opinion, this seems to be rather the result of success in consulting the best author upon the subject than of a wide consideration of the | literature. More recent discoveries and the newer publications j are very summarily dismissed. The original illustrations are not i very good and there is practically nothing new in the book, either in text or method of arrangement. It is very doubtful whether such a summary, much of which consists essentially of definitions, is what is needed by students of the present day who have the intelligence and the will to read such living descriptions as are found in Orth's text-book and are not merely anxious to prepare for examinations.

Diseases of the Ear, for Practitioners and Studeiits of Medicine. By James Keer Love, M. D., Aural Surgeon, Glasgow Royal Infirmary; Lecturer in Aural Surgery, St. Mungo's College, Glasgow; etc., etc. With 54 Stereographic Photographs, 2 colored plates and many illustrations. (Published by John Wright if- Co., Bristol; and Simpkin, Marshall, Hamilton, Kent d Co., Ltd., London.)

A very excellent work and one that is sure to meet the approval of the otologists. The concise, practical manner in which the really important subjects of otology are treated will appeal not alone to the student but to the busy physician. It is a book that one can really read with sustained interest for there is not a word too much said of any subject. It is, altogether, a strong presentation of practical otology.

It is the first time I have seen stereographic photography used in a text-book, and I am not sure it will prove a complete success. The pictures are excellent and I have long expected that some one would use just this method of illustrating the temporal bone, which is so difficult to show by ordinary photography or by drawing, but it is not easy to examine them as bound in the book. I hope the plan will meet with general favor. H. O. R.

Modern Ophthalmology, A Practical Treatise on the Anatomy, Physiology and Diseases of the Eye. By James Moores Baix. M. D., Professor of Ophthalmology in the St. Louis College of Physicians and Surgeons. With 417 illustrations in the text and 21 colored plates. (Published by the F. A. Davis Co., Philadelphia.)

The title of this book is certainly well chosen for the author has evidently tried to give us a book befitting the period. I know of no other single volume text-book of Ophthalmology that approaches this one in completeness of subjects considered; every conceivable affection of the eyes has been mentioned and, in most instances, the very latest knowledge concerning each topic is given.

The publishers, too, deserve commendation; the paper, the print and the illustrations are of the best. H. 0. R.

First Report of the Anti-Malarial Operations at MiarirMir, 19011903. By Capt. S. P. James, M. B. (Lond.), I. M. S. (on special duty). (Office of the Supt. of Government Printing, Calcxilta, 1903.)

This report, which is issued under the authority of the Government of India, contains a detailed account of the investigations initiated by the Royal Society's Malaria Commission with the intention of demonstrating experimentally that malarial fevers can be prevented by practical measures based on the discovery that a particular species of mosquito is the definitive host of the


malarial parasite. It is Impossible to do justice to this interesting piece of work in the space available here, but the most important conclusions are these:

There appears to be no doubt that anopheles culicifacies is the chief, if not the only carrier of malaria! organisms in Mian-Mir, which is one of the most unhealthy cantonments in India. The source of infection in the Royal Artillery Lines, where the Investigation was carried on, was, beyond doubt, the children in the various Bazaars and followers lines. The results of the research show conclusively that the destruction of this species of mosquito, if carried out successfully, will effectually banish malaria, but such destruction is materially hindered by its difficulty and expense. In this connection, however, great importance is attached to the second set of experiments, namely, the attempt to lessen the effects arising from the obvious sources of infection in cantonments. It has been shown that this can be done by treating large numbers of native children regularly with quinine, and as this is a measure requiring no special knowledge and involving no great expense, it Is applicable to every place where large numbers of native children are gathered in the vicinity of European troops.

The report is well worth reading by anyone interested in the subject, for it contains a great deal of interesting matter which cannot be condensed.

Traite d'Hygiene Procedes rapides de Recherche des Falsifications et Alterations. Par Dr. P. Smolensky, de St. Petersbourg; translated from the Russian by S. Bboido and A. Zaqitelmann. Two volumes. (O. Steinhal, Paris, 1904)

The early part of this work is devoted to the description of methods for analyzing the food-stuffs in ordinary use. and of a character sufficiently simple and inexpensive to permit their being used in boarding-houses, asylums, hospitals, and even in private houses. The latter part deals with the hygienic questions associated with light, heat, clothing, the choice of dwelling houses, and other kindred subjects. The work contains much useful information and is well adapted for its purpose.

A Hand-book of Surgery. For Students and Practitioners. By Frederic R. Griffith, M. D., Surgeon to Bellevue Dispensary, etc. (Philadelphia, New York, London: W. B. Saunders <& Co., 1901)

This work can hardly be considered more than a compend. It shares with so many works of this kind the advantage of being pocket-size, and has for its recommendation the fact that it is neatly bound in flexible cover; the paper used is of good quality and the type is large and clear.

The whole field of Surgery, Including the specialties, is briefly outlined and there are brief chapters on Medico-Legal Surgery, Surgical Pathology and Technique.

The 417 illustrations, diagrammatic for the most part, supplement the text fairly well.

To the Practitioner its value will necessarily be very limited; to the Student preparing for quizzes and examinations it can be recommended as one of many.

The Channels of Infection in Tuberculosis. Being the WeberParkes Prize Essay, 1903. By Hugh Walsham, M. A., M. D. Cantab., F. R. C. P. (London: John Bale, Sons £ Danielsson, Ltd., 1901)

The Weber-Parkes Prize is given triennially by the College of Physicians in London for the best essay on some subject connected with tuberculosis, especially with reference to pulmonary tuberculosis in man. This prize was awarded to Dr. Walsham, in 1903. and this volume contains the essay.


April, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


153


The greater part of the work is taken up with discussion of the channels of infection. The work impresses one as rather a discussion of some of the questions coming under the head of infection, than a broad, comprehensive survey of the subject. Dr. Walsham is led into the discussion of side issues, which, however, are most important and of great interest. Thus he discusses the relationship of scrofula and tubercle. He has studied a number of cases at autopsy and comes to the conclusion that the so-called scrofulous gland is really a tuberculous one.

The channels of infection are considered under five headings:

1. Heredity.

2. Lymphatic vessels.

3. The blood-vessels.

4. Epithelial channels.

5. Inoculation.

Perhaps the most interesting section is the discussion of the question as to the frequency with which tubercle bacilli are absorbed by the tonsil or adenoid tissue. Out of thirty-four consecutive post-mortem examinations the tonsils were found to he more or less tuberculous in twenty. In some of these cases the tonsillar infection was perhaps secondary to the lung, but in others the primary source of infection seemed to be undoubtedly in the pharynx. The examination of tonsils and adenoid vegetations removed from the living patient was entirely negative. From his studies Dr. Walsham has come to the conclusion that the tonsils are very frequently affected. There is considerable space given to the question of renal infection.

The second part of the book takes up the conditions which render the tissues vulnerable; the relationship of alcohol, diabetes, cardiac disease, cancer, etc., to tuberculosis are dealt with.

Mention should be made of the illustrations, which are •numerous and satisfactory.

Diseases of the Liver, Gall-bladder and Bile-ducts. By H. D. RoLLESTON, M. A., M. D. (Cantab.), F. R. C. P., Physician to St. George's Hospital, London. {Philadelphia, New York, London: W. B. Saunders <£ Co., 1905.)

To write a good book on any subject is difBcult, but to write a good book on diseases of the liver would seem especially so. Those who have known Dr. Rolleston's work in the past have looked forward with much interest to the publication of this book, a work more ambitious than any he has yet done. Dr. RoUeston "has had the advantage of a thorough training in pathology, the usefulness of which in clinical medicine cannot be over-estimated. The present volume is a model of what such a work should be. It discusses subjects in a broad way, and at the same time contains a perfect mass of details, well arranged and easy of reference. There does not seem any doubt that this is the best work we have on the diseases of the liver. Murchison's work is, of course, well-known but since its publication there have been many advances along various lines.

Dr. RoUeston, very wisely we think, omitted any description of the anatomy and physiology of the liver. The book opens with a short section on some anatomical abnormalities, some common post-mortem appearances and acquired deformities. Following this is a section on displaced and movable liver. After this is a chapter on functional disease. When we consider the important place which this takes in the popular mind (and we fancy to a greater extent in this country, especially the South, than in England) we realize its importance. Dr. RoUeston believes that many symptoms often attributed to the liver are really due to gastric and intestinal conditions. He emphasizes the importance of the treatment of these other conditions. The various disturbances of the portal circulation are discussed and the various morbid conditions of the lymphatic vessels. Changes in the liver secondary to cardiac conditions are described and there is an


interesting section on pericarditic pseudo-cirrhosis. Acute congestion and acute hepatitis are also discussed.

The section on abscess of the liver is an interesting one. Dr. RoUeston points out the many difficulties of accounting satisfactorily for the etiological factors of some cases. There can be no question that amcebic abscess of the liver occurs without any dysentery, but it is only after the most careful examination of the bowel that the absence of intestinal lesions should be considered as proved. In a recent case one very small, almost healed ulcer, in the colon, was recognized only after most careful search. This should be kept in mind, as probably cases have been reported as having a normal colon in which a very slight ulceration had been overlooked.

The section to which one turns with the greatest interest is that dealing with cirrhosis. Various classifications are quoted but the author concludes that for practical work it is best to make a division into two probable types, (a) ordinary or common cirrhosis (portal), (b) biliary cirrhosis. A good comparison is made with some forms of kidney disease, portal cirrhosis being compared to a granular kidney and hypertrophic biliary cirrhosis to chronic parenchymatous nephritis. The terminal production of multilobular cirrhosis in a long-standing hypertrophic biliary cirrhosis corresponds to the contracting kidney following the large white kidney. There are so many interesting points which might be discussed in this connection that it is diflBcult to choose. For example, the cause of splenic enlargement in cirrhosis. Dr. RoUeston inclines to the toxemic theory. There is a great amount of detailed information regarding the various conditions, as for example haematemesis, the discussion of which is exceedingly good. A point of great interest is as to the relationship of ascites to chronic peritonitis. Hale White considers that cases of cirrhosis with ascites but without chronic peritonitis never survive to be tapped more than once. It would be well if this point could be definitely settled. The subject of hsemochromatosis receives adequate notice. Biliary cirrhosis is taken up at some length and a very clear description given. It is impossible to do justice in a review to this section on cirrhosis. It seems one of the best descriptions of the subject which we have in English.

Tuberculous and syphilitic diseases of the liver follow. We should agree with Dr. RoUeston in thinking that hepatic syphilis is very often overlooked, and he does well in emphasizing the importance of bearing in mind the possibility of syphilis in obscure enlargements of the liver. There is a section on hydatid cyst and on fatty and lardaceous diseases of the liver.

Malignant disease of the liver is taken up under the headings of primary and secondary and many statistics are quoted. Very many doubtful points associated with jaundice are well discussed. The cases are divided into two classes, (a) the extra-hepatic or obstructive, (b) the toxemic or intra-hepatic. The many causes which may give rise to jaundice are taken up at considerable length. If we ventured to make one suggestion it would be that Dr. RoUeston might have laid greater emphasis on the dangers of hjemorrhage from operations done on patients with jaundice. Preliminary treatment with calcium salts may greatly diminish the risk of bleeding at operation.

The second part of the book deals with diseases of the gallbladder and bile-ducts. Acute cholecystitis and tumors of the gall-bladder are taken up first. The section on cholelithiasis is an excellent one. The diagnosis is fully discussed. The author takes perhaps the moderate view as to surgical treatment. During an attack of colic an operation is justified only If there be a special complication which might prove fatal, such as a rupture of the gall-bladder, etc.

In reference to operation after repeated attacks Dr. RoUeston takes a rather non-committal attitude, which is perhaps the safer


154


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 169.


course, but the general tendency in the profession would seem to be to advise operation more frequently. The section on the general treatment of patients with gall-stones is a very excellent one.

The sections on morbid anatomy and histology are clear and satisfactory. In the discussion of the clinical material there is an excellent arrangement. The heads under which the various features are described are well separated and the reader has a clear idea of the whole subject as presented. Although many cases are quoted, they have been judiciously extracted and only the essential features are given. The material from St. George's Hospital has been extensively used. There are many references and it is pleasing to see how carefully the American literature has been extracted. The illustrations are good and there are a number of colored plates. Altogether we regard this as a most satisfactory work, and extend our congratulations to Dr. Rolleston on its success.

An Introduction to Phannacognosy. By Sjiith Ely JEixirrE, M. D., Ph. D., Profassor of Pharmacognosy in Columbia University. (PiiiladelpMa, 'Keic York. London: W. B. Saunders & Co., 1904-)

This book is published with the intention of giving a work in compressed form dealing with the general anatomical characters of drugs. Dr. Jelliffe has described both their macroscopical appearances and microscopical characteristics. As the author points out, pharmacognosy may be approached from several sides, for example from the botanical point of view, the histological aspect or the special study of the constituents of the plant.

The book opens with a description of animal drugs, under which the leech and cantharis are described. Naturally the greater part of the work deals with vegetable drugs. The method pursued is to describe first the gross characters of the structure and then the histology, with a note regarding the chemistry. The descriptions are clear and the illustrations are satisfactory and helpful. The work seems to be admirably adapted for the purpose kept in mind and should be very useful to students of the subject.

Adolescence: Its Psychology, and its Relation to Physiology, Anthropology, Sociology. Sex, Crime, Religion, and Education. By G. Stajjlet Hall, Ph. D., LL. D., President of Clark University and Professor of Psychology and Pedagogj-. Two Volumes. (New York: D. Appleton <f Co., lOO-i-)

Two methods suggest themselves for the accomplishment of the task the author of these notable volumes sets for himself. One consists of a simple statement of the facts of adolescence in their various relations; and the other, a most difficult, Herculean feat, the organization of these facts and their relation into a systematic philosophical study. The reader need hardly be told that to the latter Stanley Hall has addressed his energies. Many will recall the incident, made the subject of a newspaper story a few years ago, of the ambitious American student, who was given, as an initial task by his German, professor, the study of a frog's muscle. Few know that Stanley Hall was the student. In his words, " The mild dissipation of a somewhat too prolonged general culture and a little taste for easy, breezy philosophical speculation caused at first a strong sense of repugnance from so small and mean a theme. When it was well under way, however, and with the daily and personal guidance of this master in devising methods of experiment, planning new instruments for record and stimulus, suggesting fertile possibilities, showing the details of all the technique, suggesting and placing in my hands new reading, etc., I found that I must know in a more accurate way than before certain definite points in electricity, which was the


agent of stimulation; in mechanics, for the apparatus was complex, and there were possibilities of improvement and invention that might open up a new field of myological investigation; in the anatomy and physiology of other tissues for comparison; in chemistry, in order to judge something of the effects of the artificial blood for constancy; and in mathematics in order to compute and analyze the contraction curve into its components and to construct and interpret the records and tables. ... As the work went on, I felt that the mysteries not only of motor education and morality, but of energy and the universe, centered in this theme, from the persistent study of which, although in the end I made but an infinitesimal contribution to the vast body of certain scientific knowledge in the world, I learned several great lessons, viz.: that any object, however unattractive, may be a key to the greatest themes; that narrow specilization is now hardly possible."

This reveals the author's method. The reason lies not only in the large number of adolescents, " one-third of the inhabitants of America and all so-called heathen people," but in the vast importance of this period of life, in which individual character is developed, formed and completed, and in the light of which all subsequent personal history is but a repetition or a demonstration of the destiny nurtured in adolescence, the " most fascinating of all themes, more worthy perhaps, than anything else in the world of reverence, most inviting study, and in most crying need of a service we do not yet understand how to render aright. . . . Here the young appeal to and listen to each other as they do not to adults, and in a way the latter have failed to appreciate. Again, no biography, and especially no autobiography, should henceforth be complete if it does not describe this period of transformation, so all-determining for future life, to which it alone can often give the key. To rightly draw the lessons of this age not only saves us from waste ineffable of this rich but crude area of experience, but makes maturity saner and more complete."

The work consists of two royal octavo volumes of, respectively, six hundred and seven hundred and fifty pages. In a general way the division into volumes represents a distinction between the physical and the mental or spiritual aspects of the subject. The eight chapters of Volume One are entitled Growth in Height and Weight; Growth of Parts and Organs during Adolescence; Growtli of Motor Power and Function; Diseases of Body and Mind; Juvenile Faults, Immoralities, and Crimes; Sexual Development: Its Dangers and Hygiene in Boys; Periodicity; Adolescence in Literature, Biography and History.

It is not possible, even with generous allotment of space, to outline fairly in a review the scope of these topics. True to his own adolescent discipline in the investigation of the ranal gastrocnemius, the author describes the growth and function of the human body, not only by compilation of all available statistics, but by careful analogies with the life histories of all human and feral races and types. Thus the infantile movements of swimming are correlated with the stage of embryonic existence in which ichthyic evolution is represented; and the later phases of extra-uterine growth are shown to be represented, first in feral, later in savage ancestry.

From the category of diseases the author passes to juvenile faults, immoralities and crimes. Monstrosities, idiots, vagrants, itinerants, vagabonds, gadabouts, hoboes and tramps, their tendencies, sentiments and acts, make a most absorbing chapter. We may say, as Longfellow said of Dickens, "' He is prodigal and ample, but what a crowd of villains he contrives to introduce us to." The reader who takes up the volume casually for pleasure and profit finds in the later chapters compensation for the tedious mustering of dry facts with which it opens. As in fiction, the initial chapters delineate the characters, who later display their passions, ambitions, purposes and ends. Here these culminate in


April, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


155


the eloquent chapter entitled Periodicity, the apotheosis of the feminine adolescent, revealing the deep pedagogical insight and affectionate instincts of the author's ideals. There exists, perhaps, no better analysis of the characteristics of sex, and his pleas, not only here but elsewhere, for the preservation of the complementary attributes of men and women, and his protests against their destruction, by whatever means; — the virilization of the one, and the feminization of the other, must stand as the strongest thesis of the many he attempts. In education, religion, mental training of whatsoever sort, this deplorable tendency is condemned. He strikes a forcible blow in a practical way at one source of feminine depreciation: "There are now, happily, signs of a reaction against the recent excessively surgical tendency, which has been too dominant, toward a larger view of the whole life of woman. Specialists are beginning to realize that they must broaden their view from the pathology of her organs, till lately so often doomed, if she once consulted them, to the entire problem of regimen, and know at least as much about woman as about her pelvic diseases. Indeed, not a few experts are beginning to recognize that this larger field is relatively unknown to them, and that they must begin the study of the new or higher gynecology with something like a Socratic confession of ignorance. As long as they hold any exclusive theory which consigns to either ovaries, tubes, or central nervous system, the exclusive dominance, or assume that either the psyche or soma is always primal or causal, little progress can be made. Each of the modern views is partially correct and must always be considered as a possible aspect of each case."

Volume Two consists of Chapters Nine to Eighteen inclusive, entitled: Changes in the Senses and the Voice; Evolution and the Feelings and Instincts Characteristic of Normal Adolescence; Adolescent Love; Adolescent Feelings toward Nature and a New Education in Science; Savage Public Initiations, Classical Ideals and Customs, and Church Confirmation; The Adolescent Psychology of Conversion; Social Instincts and Institutions; Intellectual Development and Education; Adolescent Girls and their Education; Ethnic Psychology and Pedagogy, or Adolescent Races and their Treatment.

The second volume to greater extent than the first is liberally illustrated by what in medical language would be termed a casuistry. The author's text is thus elaborated by sketches of Social Instincts and Institutions, including the student's organization of all countries, and associations of youth. The customs and histories of the races in " relation of greater or less subjection to a few civilized nations," the " Adolescent Races," are quite fully extracted from authoritative sources. The author's purpose in this coaptation of civilized youth and barbaric manhood is two-fold; first, the ethnic establishment of the adolescent in nature; and, second, as a plea for the uplifting of inferior humanity, for " every vigorous race, however rude and undeveloped, is, like childhood, worthy of the maximum of reverence and care and study, and may become the chosen organ of a new dispensation of culture and civilization. Some of them now obscure may be the heirs of all we possess, and wield the everincreasing resources of the world for good or evil, somewhat perhaps according as we now influence their early plastic stages, for they are the world's children and adolescents."

In this closing sentence the author again, and finally, reveals his great sympathy as a teacher and leader of youth. Upon the apprehension of this sentiment by his readers will rest the success or failure of his book. From the enormous mass of material at his hand this professional instinct stands boldly forth, and beside It, the ventures into other fields sink into comparative insignificance. Thus arises question of his denial of the modern conception of " Narrow specialization." He has " tried to bring the subject-matter of each chapter within the reach of any intelligent


reader." There are few " intelligent readers " qualified to exercise discriminating judgment upon such variant philosophies as those of religion, art, education, medicine, psychology, sociology and evolution. And a reasonable doubt may be expressed of the author's fitness to treat from the pedagogue's chair of the most disputed questions of conversion or of mental medicine. Surely the discussion of " dementia praecox " has not yet reached the stage when it may be easily handled by a layman. And in no medical treatise would such rhetorical blunders as " plexi " and the " Island of Kiel " escape the proof-readers of one of the most famous publishing bouses of the world. The need of " narrow specialization " is still apparent. The phraseologj- of the author may be also open to question. It is difficult to comprehend very many of his statements without laborious analysis of his sentences. Students of medicine who are acquainted with the verbal simplicity of the German masters, who always reduce the most difficult problems to the simplest expression, so that all science becomes at once practical, will be surprised that stilted language should parade, even indirectly, under the pegis of Professor Ludwig, the hero of the frog's muscle. And the genial and plain-spoken Autocrat would writhe under the appellation given his " ophidian medicated novel, Elsie Venner."

Books inevitably assume one of two forms. They either contain the ideas of the author in the language developed in his processes of thought, which may prove ambiguous; or they set forth in plain, easily comprehended phrases, the crystallized results of thought, which carry a distinct meaning or conviction to the simplest reader. Stanley Hall's book may be placed in the first category, and must lose largely in effectiveness. It appears rather meristic and somewhat banausic In its treatment of the ephebic problems. In his psychonomic recapitulatory impulses the author reveals a trace of solipsism, which is thus found characteristic not of adolescence alone.

In spite of these defects the work is epochal. It centers attention upon the period of life in which character is developed. It reveals a marvellous amount of research and a most acute and analytical observation. The hope may be expressed that in abridged form, in simple diction, the author's knowledge of the training of youth, freed of compilations from philosophical fields in which he is but an observer, may be made available to all thinkers, the world over, who value the force in civilization of strong men and pure women.

J. M. Mosher.


SEPARATE MONOGRAPHS REPRINTED PROM THE JOHNS HOPKINS HOSPITAL REPORTS.


Vol. XVI.-No. 17 0.


BALTIMORE, MAY, 1905.

CONTENTS - MAY

  • Hyperplasia of the Chromophile Cells of the Hypophysis as the Cause of Acromegaly, with Report of a Case. By Dean D. Lewis, M. D., 157
  • The History of the Circulation of the Blood — Contributions of the Italian Anatomists and Physiologists — their Bearing upon the Discovery by Harvey. By John C. Hemmetek, Phil. D., M.;D., etc., 16.5
  • Comparative Surgery ; with Illustrative Cases, by C. M. Faris, H. C. Thacher, J. F. Ortschild, and F. C. Beall; and an Introduction by Harvey Coshino, 179

Correspondence, 199

Proceedings of Societies:

The Johns Hopkins Hospital Medical Society, 200

Resume of History of Blood Platelets [Dr. Osler]; — The Scope and Problems of Surgical Physiology [Dr. Crile] ; — Partial Occlusion of the Aorta [Dr. HalstedI ; — The Blood Pressure in Different Parts of the Arterial Tree [Dr. Dawson] ; — Heart Block in Mammals [Dr. Erlanger].

Notes on New Books, 303

Books Received, 204


HYPERPLASIA OF THE CHROMOPHILE CELLS OF THE HYPOPHYSIS AS THE CAUSE OF

ACROMEGALY, WITH REPORT OF A CASE.

By Dean D. Lewis, M. D. {From Vie Pathological Laboratory of Cook County Hospital and the Anatomical Laboratory of the University of Chicago.]


Observations of the clinical and anatomic changes in acromegalj' have been reported v/\\h increasing frequency during recent j'ears. In all but two of the forty-nine cases collected by Furnivall ' in 1898, the hypophysis was larger than normal. Pour additional cases in which the necropsy revealed no enlargement of the gland have been reported by other investigators : Virchow's ' case Mennig, the brothers Hagner observed by Friedreich' and Erb,' and the case reported by Sarbo." The Jjrothers Hagner should be classified as doubtful cases, as

'Furnivall, P.: Pathological Report on a case of Acromegaly, with the Analysis of the Results of 49 Post-Mortem Examinations on Cases of Acromegaly. Tr. Path. Soc, Lond., 1898, XLIX, 204217.

' Virchow, R.: Ein Fall und ein Skelet von Akromegalie. Berl. klin. Wchnschr. 1889, XXV, 81-85.

'Friedreich, N.: Hyperostose des gesammten Skelets. Virchow's Arch., 1868, XLIII, 83-87.

'Erb, W.: tjber Akromegalie (Krankhaften Riesenwuchs). Deiitsches Arch. f. klin. Med., 1888, LXII, 296.

"Sarbo. (Abstract by Joseph Collins.) J. Nerv. and Ment. Dis., 1893, VIII, 57.


Marie was inclined to believe that the changes presented by them were not typical of the disease ; in all probability the case reported by Sarbo is to be regarded as an hypertrophic osteoarthropathy of pulmonary origin.

A great variety of pathologic conditions have been described in the hypophysis in those cases of acromegaly in which it has been enlarged and obviously diseased, e. g., simple hypertrophy, twice; adenoma, seven times; sarcoma (variety not specified), five times; large-cell sarcoma, six times; cystic tumors, twice ; hypertrophy and colloid degeneration ; marked colloid degeneration and hemorrhage; sarcoma or glioma, spindle-cell sarcoma; cylindroma; round-cell sarcoma, glioma, adenoma with enlargement, one each."

The variety of lesions of the hypophysis described in cases of acromegaly is almost equalled by the divers pathologic conditions in the gland, with no symptoms of the disease, as


"Mitchell, L. J., and Le Count, E. R.: Report of a Necropsy in a Case of Acromegaly with a Critical Review of the Recorded Pathologic Anatomy. N. Y. M, J., 1899, LXIX, 517, 556, 595.


158


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


Erdheim's' and Breitner's ' cases of adenoma; Ponfick's ° of tumor (variety not specified); Packard's'" of hypertrophy; Cagnetto's " of telangiectatic sarcoma; Benda's '^ cases of sarcoma of the periosteum or dura of the sella turcica compressing the hypophysis and teratoma of tiie infundibuluin ; Woollcombe's " case of psammoma; Beadles' " and Hektoen's " cases of gumma; Beadles' of tuberculosis and Hinsdale's'" of sarcoma and finally Bassoe's " case in which the hypophysis weighed 5.9 g. and another in which a small calcareous nodule was found in the gland, both without symptoms of acromegaly.

The gland may be comi^letely destroyed without any symptoms of acromegaly intervening. One of the most notable examples of this is the case observed by Weir Mitchell " in which destruction of the gland was caused by an aneurysm, arising from an anomalous branch of the circle of Willis. The patient experienced no symptoms, except those directly referable to the aneurysm.

The results following experimental removal of the gland have been indefinite and contradictory. Horsley " has extirpated tlie gland and reports no physical or mental changes. Gley," after experimental removal of the thyroid gland and spleen, extirpated the hypophysis, and found that the symptoms following this extensive operation did not differ from those following removal of the thyroid alone. Vassale and


' Erdheim, J.: Zur normalen unci pathologischen Histologie der Glandula thyreoidea, parathyreoidea und Hypophysis. Beitrage z. path. Anat. u. allg. Pathol., 1903, XXXIII, 158-232.

"Breitner, E. : Zur Casuistik der Hypophysistumoren. Virch. Arch., 1883, XCIII, 367.

"Ponfick, E.: Uber Myxoedema u. Akromegalie, Munch, med. Wchnschr., 1899, XLVI, 1358.

" Packard, F. A. : A case of Acromegaly and illustrations of two allied conditions. Amer. J. M. Sc, 1892, GUI, 657-669.

"Cagnetto, G. : tjber die Anatomische Beziehung zwischen Akromegalie und Hypophysisgeschwulst. 2 Riun. Soc. Ital. di Patol., Abstracted in Ziegler's Centralbl., 1904, XV, Nos. 16 and 17, 688.

" Benda, C. : Uber den normalen Bau und einige pathologische Veranderungen der menschlichen Hypophysis Cerebri. Arch. f. Anat. u. Physiol., Physiol. Abth., 1900, 373-380.

"Woollcombe, W. L. : A case of Virchow's Psammoma of the Pituitary Body with remarks as to the function of that structure. Brit. M. J., Lond., 1894, I, 1351-1353.

"Beadles, C.: Gummatous Enlargement of the Pituitary Body. Brit. M. J., Lend., 1896, II, 1775.

"Hektoen, L.: Gumma of the Hypophysis. Trans. Chicago Path. Soc, 1896, II, 129.

"Hinsdale, G.: Akromegaly. Medicine, 1898, IV, 441-637.

" Bassoe, P.: Gigantism and Leontifisis Ossea, with Report of the case of the Giant Wilkins. Jour, of Nerv. and Ment. Diseases, 1903, XXX, 513-595.

"Mitchell S. Weir: Aneurysm of an Anomalous Artery causing antero-posterior division of the chiasma of the optic nerves and producing bi-temporal Hemianopsia. J. Nerv. Ment. Dis., 1889, XVI, 44-62.

"Horsley, V.: Functional nervous disorders due to loss of thyroid gland and pituitary body. Lancet, Lond., 1886, I, 3-6.

^Gley. E.: Recherches sur la fonction de la glande thyroide Arch, de Physiol., 1892, t. XL, 311-326.


Sacchi " noted that after extirpation of the gland animals suffered from dyspnoea, anorexia, depression of temperature, emaciation, tonic and clonic spasms and fibrillary twitchings. One animal survived the operation one year. No conclusions concerning the effects of complete removal of the gland can be drawn from reports which are so wanting in uniformity.

The apparent lack of similarity in the pituitary changes described in cases of acromegaly, the absence of evidences of acromegaly in instances of marked disease of the hypophysis from syphilitic or other chronic inflammations of the granulomatous type, the contradictory results following complete destruction or experimental removal of the gland, and finally the occasional observation of cases of acromegaly in wliicli the gland is of normal size and apparently not diseased, have inclined many investigators to discredit Marie's theory that disease of the hypophysis is to be regarded as the causative factor in acromegaly. It has been suggested that the enlargement of the gland is secondary to enlargement of the sella turcica.

Other theories have been advanced to explain the symptomcomplex, chief among which are the following :

1. Nervous theory (Magendi and von Recklinghausen). The disease is supposed to be dependent upon changes in the nervous system.

2. Theory of growth anomaly (atavistic, Freund and Campbell). Acromegaly is not to be regarded as a disease proper, but as an anomaly of growth, the whole appearance suggests a reversion to the anthropoid ape type.

3. Thymus theory (Klebs). This theory suggests that an increase in the vascular canals of a large and persistent thymus is the etiological factor.

1. Genital theory. Acromegaly is accompanied in the majority of females by an early menopause, and in males by impotence; hence the assumption that by the loss of function of the organs of generation an excess of blood is diverted to the extremities, resulting in their hypertrophy.

.5. Thyroid theory. Diseased conditions of the thyroid gland, which are occasionally found in acromegaly, are regarded as the causative factor.

All of the foregoing theories have met with serious objections and it has been found impossible to bring the contradictory observations into accord by means of any one of them. The refinements in histologic technic and consequent increase in our knowledge of the minute structure of the hypophysis have succeeded however in lending support to the theory that acromegaly is caused by an excessive function of the cellular elements of the anterior lobe of the hypophysis.

Benda" in a recent article, in which he reports the histological changes in the hypoj)hy.ses of four cases of acromegaly, comes to the conclusion that the hypertrophy and hyperplasia


^Vassale and Sacchi: Sulla distruzione della ghiandola pltuitaria. Riv. Sperim. di Freniat., 1892.

" Prankel, Stadelmann A., Benda, C: Klinische und anatomische Beitrage zur Lehre von der Akromegalie. Deutsche med. Wchnschr., 1901, 513, 536, 564.


May, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


159


of the chroraophile cells, probably indicating an excessive activity of the gland, are the important factors in the production of the disease; he also considers that mistakes in anatomic diagnosis accounts for the lack of uniformity in the descriptions of the lesions of the hypophysis associated with the disease. This conclusion merely confirms the statement I)reviously made by Le Count and Brooks, that many of the cases reported as sarcoma, angiosarcoma, lymphadenoma, etc., of tlie hypophysis are simply instances of hyperplasia or adenoma.

In the case about to be reported, the histologic changes found in the hypophysis, which was apparently unchanged upon gross examination are striking and confirmatory of the view advanced by Benda, that an increase in the chromophile cells is the distinctive anatomic lesion of the disease.

Clinical History.

C. H., aged 46, an unmarried German laborer, was admitted to the Cook County Hospital, in the service of Dr. J. B. Herrick, on the 6th of February. 1903. He complained of swelling of the feet, which he had first noticed two weeks before; dyspncea upon exertion: a cough, dry and hacking in character; frequent headaches and pains in the lumbar region and extremities. The pains he described as pinching in character. Three weeks before entrance to the hospital he suddenly lost consciousness and asserted that he did not regain it for twenty-four hours. He had been subject to frequent attacks of vertigo. During the previous six years there had been a gradual but constant enlargement of the head and feet. No measurements had ever been taken, but the patient stated that six years ago he wore a 7% hat, and a number 9 shoe; whereas at this time he required a number 8 hat, and upwards of an 11 shoe. He had not worn gloves, and could not give any information concerning the increase in the size of his hands, but judged from appearances, that they also had become enlarged. The patient could give no history of mental changes, and relatives could not be found to supply such information.

Post and Personal History. — He had typhus fever when twenty years of age; malaria ten years ago. All venereal diseases were denied. He was moderately addicted to alcohol and tobacco.

Family History. — The father is dead, but the mother, two brothers and one sister are living and well. No member of the family, so far as the patient knew, ever suffered from a similar illness. There is no history of any giantism or disease resembling acromegaly in the family.

As the patient improved sufficiently to leave the hospital frequently, returning after a two or three weeks' absence, and the physical examinations in all the histories are the same, with the exception that they indicate a progress in the disease, the following account of his illness dealing with the significant symptoms only, has been abstracted from the numerous history sheets.

Physical Examination. — The patient is a well developed and well nourished, middle-aged man. His speech is thick and slow, skin dry and warm, facial expression sleepy and dull. The head is fairly well proportioned, but the lower portion of the face appears larger than the upper. The pupils react to light and accommodation, there is a lateral deviation of the left eye. The ophthalmoscopic examination was unsatisfactory, but as far as could be determined there were no changes in the fundus. Vision


is slightly defective, and the patient experiences some diplopia. The pinna of each ear is increased in size; there is no defect in hearing. The nose is broad and flattened; the lips thickened and cyanotic; the teeth are well preserved, and there is no abnormal separation. The tongue is thick and tremulous, the palate high and arched. The chest is well formed, but there is to be noted an expansion of the lower thoracic zone, greater upon the left side. Relative dulness is noted over the sternum, corresponding to the sign described by Erb as indicating a persistent and large thymus.== Physical examination of the lungs elicits nothing abnormal. The right border of the heart extends 2 cm. to the right of the sternal line; the apex beat is found in the fifth intercostal space in the nipple line, and is diffuse; no thrills are palpable; a faint systolic murmur is heard over the mitral area, which is not transmitted into the axillary fossa. Over both the aortic and tricuspid areas systolic murmurs are heard, which are indistinct; that heard over the aortic area is not transmitted into the vessels of the neck. The second pulmonic tone is not accentuated.

The abdomen is large and flattened, and is prominent in the epigastric and hypochondriac regions. Hepatic dulness begins in the 4th intercostal space on the right side, flatness in the sixth. The anterior margin of the liver extends to the costal margin, but is not palpable; splenic dulness begins at the eighth rib in the mammillary line, and extends three fingers' breadth below the costal arch in the parasternal line; the organ is easily palpable and the crenations of the anterior margin are distinct; the kidneys are not palpable. Examination of a twenty-four hours specimen of urine: quantity 2200 cc; alkaline reaction; sp. gr. 1013; no albumen or sugar; urea 1.157o; the sediment contains triple phosphates but no casts. Genitalia negative. The fingers of both hands are enlarged and spatulous, due to a diffuse thickening of all the tissues. The feet are likewise enlarged, especially the great toes. The markings of both the hands and the feet are exaggerated. Unfortunately, no measurements were made of the enlarged extremities, but the accompanying illustrations from X-ray pictures (Fig. 1 and Fig. 2) reveal the increase in the size of the bones. The increase in the size of the head and of the feet is indicated by the statements concerning the larger sizes of hats and shoes, which he now requires. The skin over the anteromedial surface of the right leg is pigmented; there is also a pigmented scar on the left leg. The osseous system presents no changes except those noted in the hands and feet, in which the bones are symmetrically enlarged. The lower jaw is apparently somewhat larger than normal, but does not protrude much beyond the upper. The spinal column shows no deformity. There are no exostoses about the joints.

While the physical condition of the patient improved some during his stay in the hospital, his mental condition grew progressively worse. He was often found in a stupor, from which he could be aroused only with difficulty. At other times he was delirious, and would talk wildly and incoherently. These stuporous and delirious states alternated. He was also the subject of attacks in which he lost consciousness, resembling the one previously described. During the night of April 19, 1903, he lost consciousness, and when examined the following morning its return was only partial and he was restless and groaning continually.

From the seventeenth to the twenty-fourth of January 1904, he had involuntary passages of urine and f»ces. An examination of a twenty-four hours specimen of urine revealed, 550 cc; amber color; acid reaction; sp. gr. 1020; a trace of albumen; no sugar; urea, 3%; the sediment contained erythrocytes, leucocytes and calcium oxalate crystals.


'This sign may be produced by a thickened sternum.


160


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


The patient improved slightly, and at his request left the hospital on the fourth of April 1904, to return two weeks later. No significant changes were noted during the subsequent stay of five weeks in the hospital. Following his discharge on May 23, 1904, he returned eight days later, in a semi-comatose condition, and although he could be aroused, he could give no history of himself, and seemed to be entirely unconscious of his surroundings. His pulse was strong and regular; the respiration CheyneStokes in character. The results of the physical examination were the same as on previous occasions. Examinations of the blood by the usual methods revealed no important alterations. On the second of June, two days after admission to the hospital, a hemiplegia involving the right half of the face and body was noted. The course of the case from this time on was progressively downward. Defsecation and urination became involuntary; icterus developed, and the patient died at 5 a. m. on the eighth of June. Examination of the urine made on the day preceding death showed a sp. gr. of 1029, a small amount of albumen, no sugar or casts but some biliary pigments.

Autopsy.

At the post-mortem e.xamination made by Dr. A. M. Stober, Resident Pathologist, tlie anatomic diagnosis was as follows: Cerebral embolism with softening and secondary hemorrhage; chronic fibrous endocarditis of the mitral, tricuspid and aortic valves; hypertrophy of the heart; fibrous pleuritis of the right side; oedema of both lungs and hemorrhagic infarction (left lower lobe); cirrhosis of the liver; passive congestion of the kidneys and spleen; tuberculosis of the peribronchial lymph nodes and acromegalic osseous hypertrophy.

The following descriptions from tlie record are of interest.

" The thyroid gland weighs 30 g.. and is of normal shape and consistency. Upon section, the gland appears normal.

" The heart weighs 500 g., and has no abnormal external markings. The tricuspid orifice easily admits five fingers, and the mitral four. Sclerotic plaques are found upon both valves. The aortic and pulmonic valves are competent to the water test. The root of the aorta presents some areas of sclerosis, the right ventricular wall measures 7 mm. in thickness and the left 22 mm. The coronary vessels show no changes. The foramen ovale is closed, and the thoracic and abdominal aorta appear normal. The left lung weighs 1240 g. It floats low in the water, and has a middle lobe. The upper lobe is crepitant throughout with the exception of a small area near the apex, where there is an old scar. Crepitation can be elicited in the lower lobe anteriorly, but below and posteriorly crepitation is diminished, and in some places absent. Upon section a frothy, bloody fluid escapes, and in the region where crepitation is diminished is found a large hemorrhagic area. The middle lobe of the left side is normal, and the pleural cavity is free. The right pleural cavity is obliterated by heavy fibrous adhesions. The right lung presents nothing abnormal.

" The liver weighs 1080 g. Its external surface is irregular, and upon section the surface appears broken up into islands of liver tissue separated from each other by shining bands of connective tissue. The bile ducts are patent and normal.

" The spleen weighs 1169 g., its capsule is thickened. Upon section considerable bloody fluid exudes. The Malpighian bodies show distinctly, and an increase in the amount of connective tissue is evident.

" Together, the kidneys weigh 540 g. The right kidney measures 15 by 6.5 by 5.5 cm. Externally it is smooth and the capsule strips easily. The cortical markings are distinct. The cortex measuring 1 cm., the pyramids 1.5 cm.; considerable bloody


fluid escapes from the kidney tissue. A similar description answers for the left kidney, with the exception that it is larger and paler. The pelvis of each kidney is unchanged. The bladder is full of urine, and the mucous membrane covering the trigone contains numerous engorged capillaries. The seminal vesicles and testicles appear normal.

" Except for a slight diffuse thickening, the bones of the skull show no changes. On removal of the calvarium considerable blood stained fluid escapes; the dura appears normal. On removing the dura the left half of the cerebrum appears smaller than the right and there is considerable blood over its upper surface; an incision into the left ventricle parallel to the median fissure and 2 cm. on the left, from the occipital lobe behind to the frontal lobe in front, extends through an area of hemorrhage and considerable blood is present in the ventricle."

Since the brain was soft it was placed in 10 per cent formalin without further examination ; after hardening, frontal sections were made at intervals of from 3 to 3 cm., and the following record made.

" When the brain is viewed as a whole after placing the sections together, two striking changes are noticed; (1) a narrowing of the left occipital lobe: 6 cm. from the occipital pole its circumference is 12.5 cm., whereas the right at a similar point measures 23 cm. in circumference. This reduction in size is mainly in the vertical dimension, but also slightly in the lateral. (2) The upper surface of the left hemisphere except in the anterior part of the frontal lobe, shows a marked diminution in the size of the gyri which are sunken and separated by abnormally wide sulci and these are filled with clotted blood. These changes are perhaps most marked in the post-central and superior parietal gyri.

" In the hemisphere 1 cm., from the median line there is a rent which slopes outward to the roof of the lateral ventricle so that where it opens into the ventricle it is 2 cm. from the median line. This tear connecting the ventricle with the meningeal cavity is lined by dark necrotic brain tissue; its walls are the seat of many minute hemorrhages; the necrosis is superficial extending only from the surface of the tear 3 mm., on an average.

" On examining the sections of the brain there are no changes found in the first two, each made 3 cm. from the frontal pole. In the section 6 cm. from the frontal pole a small amount of clotted blood is found in the right lateral ventricle. Examination of the section 2.5 cm., posterior to the previous, shows a lessening, amounting approximately to 1 mm. in the thickness of the cortex of the left hemisphere from the mesial to the Sylvian fissures, when this half is compared with the right side. The pia dipping into the fissure of Rolando is ecchymotic, and in this section there is no blood in the right ventricle. In the next section (see Fig. 3) 3 cm. behind, the narrowing of the gyri is very marked and the sulci between the mesial and Sylvian fissures are both deep and wide. The tear found on the external surface extends 3 cm. forward from this section and in this plane the white substance of the superior and inferior parietal lobes is destroyed and partially replaced by blood.

" In the next plane of sectioning, 7 cm. in front of the occipital pole, the left occipital lobe appears very much smaller than the right and the right posterior horn is filled with blood clot; these changes, a small left occipital lobe and filling of the right posterior horn with clotted blood to its termination are the only changes revealed in the remaining sections. The right hemisphere weighs 550 g., the left 515 g. Posterior to the section 7 cm., from the occipital pole, the left hemisphere weighs 70 g. and the right 110 g."

The anatomic changes in the remaining organs do not demand a detailed description.


Mat, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


161


Histologic Examination.

The acini of the thyroid gland are filled with colloid material, and the interacinar connective tissue seems to be slightly increased, but otherwise the gland may be said to show no pathologic changes.

In the heart muscle the interstitial tissue is not increased in amount. There is some yellowish pigmentation of the poles of the muscle cells.

In a section through the hemorrhagic area in. the lower lobe of the left lung, the alveoli are seen to be so filled with blood that the appearance of alveolar structure is lost. In the alveoli bordering upon this area a granular material (coagulated albumen?) is seen; the respiratory epithelium is loosened in places, and the interstitial tissue appears swollen. Similar granular material is found in the alveoli of the right lung. The external surface of this lung is covered by a recently organized layer of connective tissue measuring about 1 mm. in thickness; immediately adjacent to the lung, round cells are found in abundance, also newly formed capillaries.

Liver. — The liver lobules are surrounded by a newly-formed connective tissue, which extends some distance into the lobule. There is no increase in the number of bile capillaries. The liver cells appear to be compressed, but for the greater part they appear to be quite normal.

Kidneys. — The glomeruli do not fill their capsules, the vessels of the capillary loops are filled with blood; the lining of the capsule is unchanged. The cells lining the secreting tubules appear swollen, but stain well. The lumina of the tubules are free; the interstitial tissue is not increased.

Spleen. — The capsule of this organ and its trabeculae are greatly thickened. The organ is congested, red blood corpuscles being diffused throughout the splenic tissue. No other pathological changes are to be noted.

Before describing the histologic changes in the hypophysis in this case, a brief consideration of the various theories concerning the nature and significance of the different kind of cells found in the anterior lobe of the normal gland would .seem to be appropriate.

But little space is devoted in text books on histology to the pituitary body. Bohm and Davidoff" describe its anterior lobe as being surrounded by a connective tissue capsule, within which are found variously shaped alveoli or follicles, or again, columns and trabeculse of cells, which are separated by connective tissue, supporting blood vessels. Mention is made of two kinds of cells, which can be differentiated by their staining reactions, size and structure. One variety, round or oval in shape, with a nucleus centrally placed, has a protoplasm which contains coarse granules, possessing an affinity for acid dyes; these are the chromophile cells. The other variety is cubic or columnar in shape, with a nucleus placed near the base of the cell ; their protoplasm is faintly granular, and has an affinity for basic dyes ; these are the chief cells.

Szymonowicz ^ describes two kinds of cells, and states that some authors regard the difference in appearance as due to post-mortem or to functional changes.


"Bohm and Davidoff: Text-book of Histology (edited and transl. by Huber). 1904.

^Szymonowicz: A Text-book of Histology and Microscopic Anatomy of the human body. 1902.


Flesch * and Dostojewsky " were the first to describe in the glandular lobe of the hypophysis two kinds of cells which they called chromophile and chromophobe cells. According to these observers the cells of the first variety are coarsely granular, measuring from 15 to 25/t in diameter. They stain readily with eosin, osmic acid and indigo-carmin; and in fresh unstained preparations appear darker than the chromophobe cells.

Subsequently Schonemann '^ divided these chromophile cells according to their reactions to hematoxylin and eosin, into the cyanophile and eosinophile cells. The former stain a light blue with hematoxylin, whereas the latter take the ordinary eosin stain. The chromophobe cells are smaller than the chromopliile ; do not stain with eosin and osmic acid; but present, after the use of these stains, a light yellowish tint.

In addition to these two kinds of cells Eogowitch " described groups of nuclei surrounded by a scanty protoplasm, which he regarded as embryonal or undifferentiated tissue.

Saint-Kemy '° in 1893, from results obtained by the use of the Altmann granule technic, suggested that all these types of cells are merely functional stages of one another, and his conclusions have been supported by Claus and van der Stricht" and Benda. Benda" using special fixing and stainir^g methods, was able to follow satisfactorily the transitional stages from the empty chromophobe to the loaded eosinophile cell and described the following types of cells. A small cell with irregular clear protoplasmic body containing few granules; a larger round cell, the body of which is so filled with granules that only a small zone about the nucleus and a light area "heller Tlof" containing the centrosome remain free; and, finally, a large irregular cell, containing isolated masses of stainable granules. In this last variety vacuoles are found which have been regarded by many investigators as secretion vacuoles, but Benda has demonstrated by the examination of fresh specimens and the use of Sudan III and osmic acid that tliey contain fat. His conclusions concerning the significance of these different types of cells are stated as follows : " I may conclude from the characteristics of these cells, that the small cells with few granules represent the indifferent embryonal forms capable of multiplying, that the accumulation of granules in the dark cells indicates the highest point of functional


=" Flesch, M.: Versamml. deutscher Naturforscher und Arzte in Magdeburg, 18S4, 195-196.

•'Dostojewsky: tJber den Bau der Vorderlappen des Hirnanhanges. Arch. f. Mikr. Anat, Bonn, 188f., XXVI, 592-598.

^Schonemann, A.: Hypophysis und Thyroidea. Virch. Arch., Berl., 1892, CXXIX, 310-336.

™Rogowitch, N.: Die Verandeiungen der Hypophyse nach Entfernung der Schilddriise. Ziegler's Beitrage, 1889, IV, 455-469.

™ Saint-Rfimy, G. : Contribution k I'histologie de I'hypophyse. Arch, de Biologie, 1892, XII, 425.

"Claus, A., and van der Stricht, O.: Contribution k I'etude anatomique et clinique de Tacrornggalie. Ann. et Bull, de la Soo. de M^d. de Gand., 1893, 71.

'^ Benda, C: Beitrage zur normalen und pathologischen Histologie der menschlichen Hypophysis cerebri. Berl. klin. Wchnschr., 1900, XXXVII, 1205-1210.


163


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


activity, and that, finally, the large cells with few granules result from a temporary or permanent cessation of function."

This theory that these different varieties of cells are merely functional stages of one another passed unchallenged for twelve years. Scaffidi" in a recent article, takes an opposite view. He has described two distinct and functionally independent types of cells. In his study he used acid hematoxylin as a nuclear stain, and a mixture consisting of two parts of a 2% watery solution of orange G., and three parts of a 1% solution of acid fuchsin, as a cytoplasmic stain; the two varieties of cells we may refer to conveniently as the " orange Gr. cell " and the " fuchsin cell." The former, measuring about 12/t in diameter, has a cytoplasm, which contains small round granules and stains readily with orange G. ; its violetdyed nucleus sharply differentiated from the yellowish cytoplasm is small, oval and fairly rich in chromatin granules. On the other hand, the " fuchsin cell " contains large, coarse, granules, which are irregular in form and unequal in size. Its nucleus is large and vesicular, and the chromatin network is loose enclosing large spaces. There are found almost constantly within the meshes of the chromatin network granular masses which stain with fuchsin. No similar granules are ever found in the nucleus of the orange G. cell.

According to Scatfidi, then, there are within the anterior lobe of the hypophysis two functionally distinct varieties of cells, each producing a specific substance ; the products of both together form the secretion of the gland. The cyanophile cell of Schonemann is to be regarded as a fuchsin cell in the advanced stages of elimination, and the groups of nuclei surrounded by a scanty protoplasm, as the end phase of secretion. Further, cells of the orange G. type are found, which differ in their histologic picture, according to the stage of secretion encountered. Scaffidi's work is apparently confirmed by the studies of Schafer and Vincent" who have isolated from extracts of the glandular lobe of the hypophysis, two distinct substances, one of which depresses the nervous system, whereas the other stimulates, and at the same time raises bloodpressure.

At the present time it is impossible to state which view concerning the nature of the cells of the hypophysis is correct. The theory advanced by Saint-Eemy and supported by Clans, van der Stricht and Benda, that they are merely functional stages of one another, demands as much consideration as the theory of Scaffidi, who regards them as independent forms of cells. Further investigation is needed to determine these questions.

Pathologically, it makes little difference which view we accept, for in either case the presence of an unusually large number of cells heavily loaded with granules indicates a gland which is functionally more active than normal.


" Scaffldi, v.: Uber den feineren Bau und die Punktion der Hypophysis des Menschen. Arch. f. Mikr. Anat., Bonn., 1904, LXIV, 235-257.

"Schafer and Vincent: The physiological Effects of Extracts of the Pituitary Body. J. Physiol., Lond. and Cambridge, 1899, XXV, 87-97.


The relative proportion of the chromophobe to the chromophile cells varies with the age of the individual. Erdheim has called attention to the predominance of the chromophobe cells in the foetus, only isolated chromophile cells being formd."'

The chromophile cells increase gradually, but constantly, up to the middle age, at this time, being equal in number to the chromophobe cells; after middle age the chromophile cells gradually decrease, so that in old age the relation between the two elements approaches more nearly that found in the foetus. In both varieties of chromophile cells fat is found. The fatty deposits increase with age, reaching their maximum in old age. Virchow states that a greater number of the cells of tlie glandular lobe undergo a fatty metamorphosis with advancing age, and that the fat gives to the extracts of the gland the appearance of the " milky fluid," described by Santorini. Occasionally, a tumor of the hypophysis is described as resembling softened brain tissue. This appearance probably depends upon post-mortem changes in the gland, with the expression of this " milky fluid."

Returning now to the case of acromegaly which forms the basis of this article, the hypophysis appeared normal macroscopically. Sections were taken from different parts of the gland, fixed in Zenker's fluid, and 5% formalin, imbedded in paraffin following the ordinary technic, cut and mounted serially. Different stains were used, the most satisfactory being hematoxylin with eosin or Congo-red, iron-hematoxylin and hematoxylin according to Bensley's formula.

The histological changes correspond in many ways to ihe description given by Shattock, Brooks, Benda, Mitchell and Le Count, and others, of tumors of the hypophysis, associated with acromegaly; they concern the character, number, and arrangement of the cellular elements. The stroma is reduced in amount. In the normal hypophysis there is a connective tissue supporting blood vessels, which surround the follicles and forms a basement membrane for the cells. In this hypophysis there is very little stroma, and the cells rest directly upon the endothelial walls of the capillaries, being irregularly grouped together In the intercapillary spaces.

Very few of the chromophobe and cyanophile cells can be found, and where present, they are grouped about the boundary zone between the nervous and glandular lobes. Two kinds of cells are easily distinguishable, a small round cell, with a small compact nucleus, and a large polyhedral cell, with a large vesicular nucleus and loose chromatin network. The former corresponds probably to the orange G. cell of Scaflidi, and the latter to the so-called fuchsin cell. It is impossible with the Congo-red and eosln stains to differentiate the granules in the cells, for the cytoplasm takes a homogeneous stain; but with the ironhematoxylin stain the granules may be seen in the cells which are not too heavily loaded. The granules are small and regular In outline. Many of the cells, however, are so full of granules, that these granules appear to be coalescent forming such a mass in the cytoplasm, that single granules cannot be differentiated. In Fig. 4 a number of the large polyhedral cells may be seen. Some contain two or three nuclei, but these multinuclear cells cannot be regarded as pathological, as they are often found in the normal hypophysis. No karyokinetic figures occur in these cells. Some also are vacuolated, but the vacuolation is not in excess of the normal. These chromophile cells have an atypical arrangement

The latter must be differentiated early, however, for I have found eosinophlle cells in the hypophysis of 4.5 cm. fcetal pig.


Mat, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


163


in that the follicles seem to have fused, and the cells are irregularly grouped.

All the changes in the gland, the great excess of the highly functionating chromophile elements, their irregular disposition, and the lessened amount of stroma, are indicative of excessive function. I have had the opportunity of examining sections of the hypophyses of other cases of acromegaly, and the histologic change, an hyperplasia or increase of glandular cells of a particular type, corresponds closely to the one under consideration.

The hypophyses from several post-mortem examinations taken at random were used as controls, and a brief description of these will suflice to indicate the peculiar and distinctive diiferences presented by the hypophysis in acromegaly.

Female, aged 50; clinical diagnosis: Exophthalmic goitre. The stroma is increased in amount; the alveoli are reduced in size, and although the chromophile elements are normal in number, they are smaller and more vacuolated than in the normal gland. No abnormal pigment is present. I think that one would be justified in saying that this gland was not functioning normally.

The vicarious relation supposed to exist between the thyroid gland and the glandular lobe of the hypophysis, make the examination of the latter important in Graves' disease. Benda has examined the pituitary glands of three eases in which death was due to exophthalmic goitre; in two the hypophyses were small and indurated, in the third it was macroscopically normal. The alveoli in the former were found, upon microscopical examination, to be small and to contain few chromophile elements; the cells were atrophic, vacuolated and contained a dark brown pigment. Some sections from the gland which showed no gross changes, presented a normal histologic picture, and in others the same changes occurred as in the atrophic glands.

The changes in these glands are of interest in connection with the alterations in shape of the fingers in acromegaly and in patients suffering from Graves' disease. In the latter the delicately pointed fingers which have been compared by Eevilliod to the fingers of the Madonnas of Raphael and Perugino, are in marked contrast to the blunt fingers of acromegaly.

Male, aged 28. Anatomic diagnosis: Syphilitic endarteritis, cerebral thrombosis and softening. The chromophile cells predominate in the central part of the gland and peripherally the chromophobe are found in excess, only isolated chromophile elements being found here. The eosinophile cells are of normal size, but are not vacuolated, as in the preceding case. The capillaries are filled with erythrocytes, but this hyperemia cannot be regarded as pathological.

Male, aged 44. Clinical diagnosis: Pernicious amaemia. The chromophobe and chromophile cells are about equally divided. The eosinophile cells take a lighter .stain than usual, and the granules are grouped together. The cells are vacuolated, but not to the extent one might expect in pernicious anaemia. The stroma is normal and the capillaries are empty.

Male, aged (io. Clinical diagnosis: Tabes dorsalis and cystitis. The alveoli are small; the chromophobe and chromophile elements are equally distributed and no other changes are found.

Male, aged 42. Anatomic diagnosis: Tuberculous meningitis. Several large colloid cysts occur near the nervous lobe;


these cannot be considered pathological, for they are often present in the normal gland. The chromophobe and chromophile elements are about equal in number, and show no changes.

Still-born infant. The glandular lobe of the hypophysis consists of well-formed columns of cells separated from each other by a scanty stroma. The chromophobe elements greatly exceed in number the chromophile, only isolated groups of the latter being found." Occasionally cells are found, the protoplasm of which takes a light stain with Congo-red. These cells are probably transitional stages from the chromophobe to the chromophile.

Male, aged 85. Clinical diagnosis: Senile dementia. This gland resembles the preceding. The chromphobe elements are in excess of the chromophile. It is well-known that in old age the latter cells decrease in number. The gland resembles somewhat that of the new-born, with the exception that the cells are larger, and contain more fat. The stroma is more developed than in the still-born infant.

In none of these hypophyses, therefore, was there any indication of the hyperplastic process, which, apparently is the fundamental and characteristic change in acromegaly, and which is so distinctive that the pathologist may make an anatomic diagnosis of acromegaly in cases which are doubtful from their clinical features, and thus differentiate acromegaly from other closely allied conditions. We might properly assume that if the disease in this case had pursued its usual clinical course and had not been interrupted by death from cerebral embolism and a terminal hemorrhage, the gland would have become enlarged; perhaps, incidentally, the seat of a tumor-like hyperplasia of cells which are found normally in the hypophysis.

Sarcoma of the hypophysis is the lesion most frequently described as being associated with acromegaly. Sternberg" states that adenomas have been described seven times, largecell sarcoma six times, and other forms of sarcoma five times. Among the forty-seven cases collected by Furnivall, in which the hypophysis was enlarged, some variety of sarcoma was noted in fifteen. However, all of these cases ran a longer clinical course thau is usual with sarcoma developing in other parts of the body, and no metastatic growths were reported although occasionally direct extension of the so-called tumor cells to adjacent structures was observed.

According to Sternberg : " In all cases of acute progress — and only these- — a true sarcoma of the liypophysis is present." These acute cases, few of which are reported, terminate fatally in three or four years. Although they resemble in length the clinical course of sarcoma of other organs, they differ essentially in some particulars. Eolleston,'" who has observed and reported one of the acute cases, thus expresses his belief that there are certain differences between the so-called sarcoma of the hypophysis and the ordinary sarcoma encountered elsewhere: "The cour.se of the disease (three years), which


" Mention has already been made of Erdheim's work, in which he finds that few chromophile elements are present at birth, but I hat they increase gradually, but constantly up to middle age.

"'Sternberg, M. : Die Akromegalie, Nothnagel's Specielle Pathologic und Therapie, 1903, VII. 30.

Rolleston. H. D.: A case of acute Acromegaly due to Sarcoma of the pituitary body. Tr. Path. Soc, Lond., 1898, XLIX, 237-242.


164


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


is comparatively long for malignant tumors, suggests either that some change has taken place in the nature of the pituitary tumor, such as supervention of a more malignant and rapid type of growth in the later stages of the disease, or that pituitary sarcoma is less malignant than sarcoma in general." It is hard to conceive why sarcoma of the hypophysis should be less malignant than sarcoma of other organs. Although, in Rolleston's case, the tumor had extended into the third ventricle, the optic nerve and the petrous portion of the temporal bone, no metastic growths were reported in distant viscera. In such a gland as the hypophysis, with large and numerous capillaries it would seem that abundant opportunity would be afforded for transportation of tumor cells, and that secondary growths in distant parts would result.

Relative to the nature of many of these reported cases of sarcoma, Le Count" makes the following pertinent observation : " If these growths were examples of a tumor as malignant as we know round-cell sarcoma to be, why do we not have cases of metastasis? Certainly not from lack of adjacent blood vessels. And why are the phenomena of cell division so common to sarcoma entirely lacking in the histologic descriptions? It miist be conceded that hyperplasia and not true tumor is the condition of the hypophysis in instances where large solid growths have been found." That mistakes in diagnosis of the lesions of the hypophysis in cases of acromegaly might arise, is readily understood when the atypical structure of the gland is considered. Benda has already emphasized this point. In examining sections of an adenoma of the hypophysis he found that the histologic changes varied; in some fields resembling a typical adenoma; in others a carcinoma, and in still others an angio-sarcoma. Brooks also mentions the possibility of such errors in diagnosis and in one case temporarily mistook a simple hyperplasia for a round-cell sarcoma. For these reasons, the long clinical course of acromegaly, the absence of metastatic growths, and the fact that errors may occur in a failure to recognize the process, we are justified in believing that the reported tumors of the hypophysis, in this disease, are instances of hyperplasia.


"Mitchell, L. J., and Le Count, E. R.: Report of a Necropsy in a Case of Acromegaly with a critical Review of the recorded Pathologic Anatomy. N. Y. M. J., 1899, LXIX, 517, 556, 595.


In this connection Tamburini's " suggestions that acromegaly is dependent upon excessive function of the gland is highly important. As yet no cases of undoubted acromegaly have been reported in which changes in the gland were absent upon both gross and microscopic examination; and in those instances where necrosis and softening (probably postmortem), sclerosis, colloid degeneration, etc., have been found no mention is made of the relation between chromophile and chromophobe elements. Experimental removal of this gland, its destruction by neoplasm, infectious granulomata, and aneurysm as previously stated do not produce the disease, so that it seems proper to assume that acromegaly is not dependent upon an abolished or lessened function of the hypophysis.

On the contrary, all the facts seem to point to an increased function of the gland as the essential etiological factor, and henceforth no report should be considered complete which does not take into consideration the character, number and disposition of the chromophile elements, for, as Brooks" aptly states, " An overgrowth of the hypophyseal cells mainly composed of the chromophile cells might not be accompanied with the grosser degrees of enlargement, and still be of great significance in acromegalia."

This case is noteworthy in that: 1. It came to autopsy at an unusually early stage of acromegaly, the usual clinical course of a benign or chronic case having been interrupted by death due to cerebral embolism and secondary liemorrhage. 2. The hypophysis appeared normal upon gross examination, but microscopic examination revealed a hyperplasia, especially of the chromophile cells, which is confirmatory of the theory that acromegaly is caused by excessive function of the glandular elements of the anterior lobe of the hypophysis.

I wish to express my thanks to Dr. E. R. Le Count for the material and valuable advice, to Dr. L. F. Barker for valuable suggestions and to Mr. L. H. Wilder for the accompanying drawing of a section of the hypophysis.


" Tamburini : Quoted by Mitchell and Le Count.

' Brooks, Harlow : Acromegalia. Archiv of Neur. and Psychopath., 1898, I, 485-652.


STUDIES IN TYPHOID FEVER.

SERIES I-II-IIl.


The papers on Typhoid Fever, edited by Professor William Oaler, M. D., and printed in Volumes IV, V and VIII of the Johns Hopkins Hospital Reports, have been brought together and bound in cloth.

The volume includes thirty-five papers by Doctors Osier, Thayer, Hewetson, Blumer, Flexner, Reed, Parsons, Finney, Gushing, Lyon, Mitchell, Hambura;er, Dobbin, Camac, Owyn, Emerson and Young. It contains 776 pages, large octavo, with illustrations.

The price is $.5.00 per copy. Address The Johns Hopkins fress, Baltimore, Maryland.


THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY, 1905.



o _^ ^

^ o 5 -^ ^ P*

O S ffl

O) b£ ce


^ a -a S


a> o ^ 13

^ C p. _ „

1 2 13 ,S S


THE JOHNS HOPKINS HOSPITAL BULLETIN, MAY, 1905.



Fig. 3. — Posterior view of the cerebruin in a frontal section 7 cms. from the occipital pole. The gyri on the left side are greatly reduced in width and the sulci are wide. At A rupture occurred.



Fig. 4. — Section of the hypophysis: The stroma is reduced In amount, the cells resting directly upon the endothelial walls of the capillaries. The cells are of the chromophile type and are grouped in the inter-capillary spaces, the follicles having fused. In some cells two nuclei are found, but these cannot be regarded as pathological, for in the normal gland cells containing two nuclei are frequently found. Stained with iron-hiematoxylin. (Leitz, Obj. 12. Ocular, No. 4.)


May, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


165


THE HISTORY OF THE CIRCULATION OF THE BLOOD-CONTRIBUTIONS OF THE ITALIAN

ANATOMISTS AND PHYSIOLOGISTS-THEIR BEARING UPON THE

DISCOVERY BY HARVEY.

By John C. Hemmeter, Phil. D., M. D., etc. Frofcssor of Physiology and Clinical Medicine, University of Maryland, Baltimore.


A very curious impression is made upon the objective investigator to see the scientific judgment obscured by illguided patriotism. No less than four monuments have been erected in three diilerent countries to perpetuate the memory of four different discoverers of the circulation of the blood. The Spaniards regard Michael Servetus, born in Villanueva in 1511, as the discoverer of the circulation, and have erected a monument in the Museo Anthropologico at Madrid. The Italians have three men to whom the title to this discovery is accredited with moi-e or less historic and scientific correctness, namely: Matheus Realdus Colombus, born at Cremona in 1516; Carlo Ruini, of Bologna;' Andreas Cesalpinus, born at Arrago in 1519. Monuments have been erected to Carlo Ruini at Bologna and to Andreas Cesalpinus at Pisa and Rome. William Harvey has been honored by a monument in London erected by the Sydenham Society, a second at Hempstead, and a third at Folkstone. This makes five discoverers in all, but there is one more. The French have claimed the discovery of the circulation of the blood, and tlieir discoverer is that incomparable satyric Frangois Rabelais, and this assertion is made by no less than Paquelin.^ But a critical study of the passages from Rabelais, which Paquelin cites, proves that the alleged French discoverer brings nothing new, nothing which was not already stated by Galen, that he novvliere mentions dissections or vivisections as basis for his claims.

The department of physiology which was most fatally retarded in its progress by a defective knowledge of the ancients is that concerning the circulation of the blood. In the Lane lectures, delivered at Cooper Medical College, San Francisco, in 1900, Sir Michael Foster has given us an admirable review of the history of the circulation of the blood. These lectures constitute a most scholarly and inspiring addition to our knowledge of the subject. The first and second chapters of this book treat of the circulation, especially the second chapter. 'J'he first chapter does not treat of the circulation directly, but of Vesalius, his forerunners and followers. In narrating the contrilnitions of the Italian physiologists and anatomists, there is tliis difference between the tenor and spirit of presentation by Foster, and that by Spanish and Italian medical historians. Foster leaves us under the impression that the Italian physiologists and anatomists made no contributions or


discoveries of enduring excellence or genuine scientific merit, whereas the Italian historians " make every effort to convince us that the work of their fellow-countrymen constituted solid building blocks in the architecture of physiology; that their conclusions were based upon precise and accurate observations and experiment, as far as such were possible in those days. In order to judge with what justification the claims of the Italian authors are made, and also to judge of the critical conservatism and broad experience of Sir Michael Foster, a brief and critical review of the main contributions of the more renowned Italian workers in physiology and anatomy, and of Harve}', becomes indispensable.

In the " Deutsche Rundschau," Helmholtz * credits poeticgenius with the power of reviving long-past historic personages and transactions, and clothing historic characters not only with flesh and bone and garments, but with exactly portraying their psychic individuality and real personality. At the same time there is also an exact probing of tlie plausibility of the existence of certain characters. We can see this in the Thalmud connoisseurs, some of whom, of Jewish creed, have denied that Job and Jonah ever existed, and upheld other characters of the Old Testament as real personages. One has to be a very thorough, patient, persistent, and judicial student of any great historic character in order to successfully think oneself into the life and work and individuality of the person.

This is true in the study of the lives of Michael Servetus, Vesalius, Harvey, and others; it is not sufficient to read their history, — one must repeatedly sink one's psychic self into the life and period of the personage to be studied. Medical history writing, unless the writer and student has sunk his soul into the soul of the character to be studied, unless he has become part and parcel of the life and work, individuality, and even the social, scientific, religious, and political condi


' Book on Anatomy and Diseases of the Horse, published in 1598, in which Ruini gives the unmistal^able evidence that he had grasped the action of the cardiac valves.

' Revue de Liter mgdic, 1878, p. 499.


' See Luigi Luciani, Physiology of Man, at present being translated into German by Baglioni and Winterstein: § G. Ceradini. Ricerche storico-critiche intorno alia scopprta della circolazione del sangue, Milano, Pratelli Rechiedei, editori, 1870. Difesa della mia Memoria intorno alia scoperta della circolazione, contro I'assalto dei signori H. Toll in teologo in Magdeburg, e W. Preyer fisiologo in Jena. Con qualche nuovo appunto circa la storia della scoperta Medesima. Genova, tip del R. Ifistituto Sordo-muti. 1876.

For further literature on this subject see list at end of this article: " Literature on the History of the Discovery of the Circulation of the Blood."

•Goethe's Wissenschaftliche Thatigkeit.


166


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


tion under wliich that character developed and produced his results, has little value for an analytical mind.

In order to present a medical character justly and as correctly as possible, it is necessary to become a connoisseur of that character, and all the conditions influencing and surrounding him. We thus are even now able to recognize specialists on Galen, Vesalius, Servetus, Harvey, just as there are music lovers who are specialists of the compositions of Rameau, Paganini, Bach, Mozart, Beethoven, C'liopin. Musical notes as printed are only the skeleton of music. Notereading and mechanical technique will never make an artistic player. " He is not a correct interpreter of a composer until he puts his soul into it."



problems in hand, — reading the literature in its original sources, and not from abstracts or quotations second-hand, and eventually, if possible, to combine the facts and data from all sources of information into an organic life-like whole, making the character and his times comprehensible to our modern methods of thinking.

The history of the discovery of the circulation of the blood begins with Galen (125-201 a. d.), who by his vivisections exposed the error of the Alexandrine school under Erasitratus (300 b. c). who held that the left portion of the heart and the arteries were empty and that they, communicating by means of the small bronchi with the arteria aspera (trachea) served to convey the spirit of life (pneuma) to the


GuiiXAi'ME Harvfv. 157S-1657 A. D.



Michael Skrvktus, 1511-1553 A. D.


This identification of the subjective powers of an artist with the work and musical nature of the composer, resurrects the composer before the mind's ear and eye of the performing artist. He begins to realize the subjective and objective peculiarities and becomes familiar with the train of thought and musical feeling that prompted the composition.

Similarly the mere reading of biographies and personal histories of distinguished anatomists and physiologists, without a calm, self-possessed and patient analysis of all the collateral sources of information, will not give a picture of life-like distinctness. It is like playing the notes of a composer mechanically in the absence of a wide reach of innate musical gifts. What is needed in medical biography as well as in the reproduction of classical music is the focusing of the entire mental energy of the writer upon the historic or musical


various parts of the body, to animate them and that the veins alone contained blood with which to nourish the entire body.

Galen showed that one need only to prick any artery or the left portion of the heart of a living mammal, in order to see blood gushing forth, which, in contrast with venous blood, was vaporous, thin, and " genuine," and which therefore consisted of a mixture of blood with the air inhaled in the lungs: " mixtum quid ex ambobus."

According to Galen the left side of the heart is the center of the arteries, which through systole drives the air-containing (sBrated?) blood (sanguis spirituosus) into all the organs, to animate them. The center of the veins on the other hand is-: the liver, from which the nourishing blood (sanguis nutritivus) is carried to all parts of the body by a kind of attractive and selective force. The blood from the right side of the


May, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


167


heart, from the cava inferior, goes for the most part into the left ventricle, through the pores of the septum (whicli Galen assumes, although he declares them to be invisible). In the left ventricle it becomes " spirituous " through mixture with pneuma, and through the aorta it is distributed over the entire body. However, a small portion of the blood contained in the riglit ventricle passes through the vena arteriosa (arteria pulmonaris) and then by way of the arteria venosa (venfe pulmonales) reaches the left ventricle.

Galen therefore had a notion, although imperfect, of the circulation of the blood through the lungs, and he knew that the venous vessels anastomose with the arterial ones, since he also had observed, that an animal might bleed to death from a single artery. One point, however, in Galen's theory might lead some critics astray in the explanation of the text. Galen assumed that the blood of the arteria venosa (vense pulmonales) flowed back into the lungs at each systole (through a sort of physiological insuiSeiency of the bicuspid or mitral valve), in order to exhale here the "soot" formed in the blood. Thus he assigned to the arteria venosa a double, and that an opposite, function, that is to say, first of conveying the reanimated blood from the limgs to the heart, and then again of conveying a portion of the same with the " soot " ° from the heart to the lungs. Similarly Galen assigned to the vena portae a double function, in that he assumed that during digestion it conveyed the chyle to the liver, and when the intestinal canal is empty, it conveys the blood from the liver to the intestinal canal.

Certainly the two errors of the permeability of the septum and the systolic reflux dim, not a little, the splendor of Galen's theory of the lesser circulation; nevertheless it cannot be denied that Galen was the first to have a conception of the same, a fact which was recognized (long before G. Ceradini again drew the attention of investigators to it) by representative interpreters such as Harvey, Haller, Douglas, Maurocordato, and Senae, who referred especially to a passage in the 10th chapter of Book VI, " De usu partium," in crediting Galen with a conception of the respiratory circulation.

Let us now see who first corrected and completed the theory of Galen, by the rejection of the assumption of the permeability of the cardiac septum, and by the determination of the fact that not only a part, but all the blood driven out from the right ventricle reaches the left ventricle by anastomoses of the pulmonary vessels.

In the year 1553 the Spanish physician and theologian Michele Eeves (better known by the anagram of Serveto or Servetus) published his book entitled, " Christianismi restitutio," which at the instance of Calvin resulted in the author's condemnation and death at the stake, in October of the same


• It is absurd to believe with some interpreters of Galen that he really meant " soot." We are dealing here with one of those orthologic diflBculties in that the Greek word which now means " soot " originally meant something entirely different and probably more in harmony with the opinions concerning the nature of venous blood of to-day.


year, at Geneva. In this book about a theological matter (there are only two copies extant, since the greater number were burned, first at Vienne (Dauphine) together with the eflBgy of the author, and then in Geneva simultaneously with the author'), there is a passage in which Serveto describes the lesser circulation, at the same time denying the communication of the two ventricles through the septum, and assuming that the blood from the right ventricle goes to the lungs where "flavus efficitur, et a vena arteriosa (arteria pulmonaris) in arteriam venosam (venae pulmonales) transfunditur" (it is made brighter (yellow) and is transfused from the vena arteriosa (arteria pulmonis) into the arteriam venosam (vense pulmonales)).

In the year 1559, that is to say six years later, Eealdo Colombo, of Cremona, who for fifteen years had been prosector and then successor of Vesalius in the chair of anatomy at Padua, published at Venice his work entitled, " De re anato- mica, libri XV," in which, on page 177, there is a description of the lesser circulation and a confirmation of the impermeability of the cardiac septum. The author lays great stress upon this discovery and claims the priority of it : " Nam sanguis per arteriosam venam ad pulmonem fertur, ibique attenuatur; deinde cum sere una per arteriam venalem ad sinistrtim cordis ventriculum defertur; quod nemo hactenus aut animadvertit, aut scriptum reliquit." (For the blood is carried through the " arteriosam venam " to the lungs, and there it is attenuated, thence (mixed) with air, it is carried through the " arteriam venalem " to the left ventricle of the heart; which no one up to this time has either observed, or left it in writing.)

It cannot be denied, that, if we consider solely the dates of the two publications the priority of the discovery belongs to Servetus, and if one could prove (as Tollin and Preyer in Germany and Willis in England have attempted to do) that Colombo had read the " Christianismi restitutio " of Servetus, then the Cremona anatomist would have to be declared guilty of plagiarism. But this is refuted by a number of incontrovertible facts, which G. Ceradini (1876-77) arranged with' great acumen.

Ceradini emphasized that Valverde, a Spanish pupil of Colombo, in a text-book on anatomy published at Eome in the year 1556, ascribed the theory of the impermeability of the septum to his teacher. The book is preceded by an introduction dated 1554, in which the author states that he had already caused to be made numerous plates for the embellishment of his book, which must have taken at least a year. Thus we reach the year 155S, in which Servetus published the book which cost him his life. The assumption seems justified, therefore, that Colombo had already for some yeajs


• Henri Tollin, I. c, presents convincing reasons for believing that numerous additional copies must have been in existence during Harvey's time of Servetus ' " Christianismi restitutio " and that it would be incredible to assume that such an omnivorous reader like Harvey was not familiar with the physiologic contents of this book.


168


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


taught his theory in his lectures before he published it in his text-book.

It has been demonstrated that the passage in the " Christianismi restitutio" treating of ph3'siology was only discovered towards the end of the seventeenth century. Ceradini further calls attention to the fact that in the year 1571 G. Giinther, who, as professor of anatomy at Paris, had been the teacher of Servetus and Vesalius, in describing the lesser circulation in the words of Colombo, lauded the latter, without mentioning his own pupil Servetus, a proof that he did not know the " Christianismi restitutio." It is also probable that it was unknown in Italy, since it was not on the " Index librorum prohibitorum " edited by the Council of Trent and published at Eome under Pius IV in the year 156-i, whereas this does contain two other heretical works of Servetus, " De trinitatis erroribus."

Finally Ceradini brought forward a splendid proof of the fact that Colombo had not plagiarized Servetus, in the comparison of the two theories.

Colombo denied the permeability of the cardiac septum completely and unconditionally; he emphasized the fact that not only the vena arteriosa, but also the arteria venosa was of considerable size; he further denied — even if incorrectly — the Galenian function of breathing, that is to say the formation of " soot " in the blood and the expulsion of the same by exhalation. Servetus on the other hand denied to be sure the existence of openings in the septum, but admitted that through it " aliquid resudare possit " (something could be expelled), and upheld the Galenian theory by the assumption that the blood " in ipsa arteria venosa inspirato asre miscetur, et exspiratione a fuligine expurgatur" (in the arteria venosa itself is. mixed with inspired air, and is cleansed by expiration from the " soot ") .

This question is a family quarrel among the Italian find Spanish anatomists and physiologists themselves, hence the sentiment due to national bias cannot be excluded in the conclusion of Luciani (professor of physiology at Rome), who says : " We will not go so far as to consider the hypothesis of Ceradini proved, that Servetus took the theory of the lesser circulation from Colombo, and tried to harmonize it with the old theory of Galen; but there can hardly be any doubt that the Cremona anatomist (Colombo) taught his theory for some time before it was published by the Spanish physician and theologian (Servetus)."

It is also of interest to determine to what extent Vesalius of Brussels was concerned in this theory, the great founder of modern anatomy, to whom Flourens (1857) ascribed the priority of the theory of the impermeability of the septum, while Henri Tollin (1884) accused him of plagiarizing Servetus, in which opinion Tigerstedt (1893) concurred.

In a recent publication' von Tackschath asserts that Vesalius is guilty of " plagiarism " and to have taken his anatomy — the " Fabrica" (1543) from Leonardo da Vincis.'


'Wien. med. Blatter, No. 46, 1902.

' See also Miinchener med. Wochenschr., Mai 3, 1904, p. 821.


In the first edition of his great work, " De humani corporis fabrica" (1543), Vesalius says that he is forced to admire the art of the master, who through invisible pores caused the blood to penetrate from the right into the left ventricle. In the second edition of the same work, which appeared in 1555, this expression of admiration for the creator is lacking, and the author declares that he cannot understand how " per septi illius substantiam ex dextro ventriculo in sinistrum vel minimum quid sanguinis assumi possit " (he could assume any substance even any blood to pass through the septum out of the right ventricle into the left)."

This more correct point of view, according to Tollin, was obtained by Vesalius from the " Christianismi restitutio " which Servetus had published two years previously, in 1553. It seems likely that Vesalius was using irony or sarcasm in the above expression, for he later on admitted that " he accommodated his statements to the dogmas of Galen."

But Ceradini proved convincingly, through a long series of quotations from the above work of Vesalius and also from some of his smaller publications, that Vesalius had become acquainted with the impermeability of the septum at Padua in the year 1543 through his prosector Colombo, and that he had defended it at Pisa in the year 1543, without however expressly emphasizing the necessary physiological consequence of this, that is to say the theory of the lesser circulation and the necessity, already recognized by Galen, of anastomoses between the arteria venosa and the vena arteriosa; he wished to avoid giving possible glory to Colombo, against whom he always had a grudge, because the latter had apparently sought to incite the students at Padua against him.'"

In the " Ergehnisse der Physiologie," Jahrgang II (1903), Biophysik, R. Tigerstedt presents an article on the lesser circulation (p. 533) which begins with a chapter "Zur Geschichte des kleinen Kreislaufs." Tigerstedt here accepts the opinion of M. Roth (" Andreas Vesalius Bruxelliensis, 1514-1564, Berlin") that the lesser circulation was discovered by Colombo. The doubt which is thrown upon the anatomical knowledge of Servetus in this article is by no means substantiated by the contemporary literature, nor by the impressions gained from the writings of Servetus themselves. Tigerstedt, following M. Roth, asserts that Servetus does not present real but speculative anatomy — that his main desire is to bring about an accordance between the Bible and anatomy by compilation from preexisting books, not from actual dissections. He denies that the recognition of the impermeability of the septum was original with Servetus, but ascribes this to Vesalius, a credit, which, as can be demonstrated from Vesalius' own " Fabrica," etc., stands on very feeble evidence. For it is on this point, " the impermeability of the septum," on which every student of anatomy must re


" For fuller English translation, see Sir Michael Foster, Lect. Hist. Physiol., p. 14.

" See Michael Foster, 1. c, and Henri Tollin, Colombo's Antheil an der Entdeckung d. Blutkreislaufs. Virch. Arch., Bd. 91, 1883.


May, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


169


gret the uncertain language of Vesalius. Servetus, who had been prosector for Giinter (Guiuterius), professor of anatomy at Paris (Tollin), cannot be accused of having learnt his anatomy from books alone.

Without tlierefore trying to belittle the great services of Vesalius in the reformation of anatomy, one can nevertheless regard it as an established fact that he had no direct share in tbe discovery of the circulation of the blood. Indirectly, however, he aided in this by his refutation of numerous errors of Galen, especially the tlieory of the formation of blood by the liver. The fact that the lumen of the vena cava in the neighborhood of tlie heart is greater than at the liver, was for him a suiHcient reason to return to Aristotle's theory of the formation of the blood by the heart, and to assume that not only the arteries but also the veins are offshoots from the heart.

In 1543 Vesalius was called by Cosimo I of Medici to become a professor at Pisa, where he determined to give a course in " amministrationes anatomica; " on the errors of Galen. It is probable that among his auditors was numbered Andrea Cesalpino of Arezzo, at that time scarcely nineteen years of age, to whom belongs the fame of being the first to have recognized and demonstrated the general circulation of the blood.

In the year 1571 the physician and philosopher of Arezzo published his " Peripateticarum questionum libri quinque," in which he assumes, that in all parts of the body there is physiologically a constant transition of blood from the arteries to the veins by means of anastomoses, which he defines as " vasa in capillamenta resoluta " ; the con,stant motion of the blood from the veins to tlie riglit side of the heart, from this to the lungs, from the lungs to the left side of the heart, and thence into the arteries ho defines as " Circulatio." He was the first to recognize tlic arterial structure of the pulsating vessel which arises at the right ventricle, and which Galen had designated as " vena arteriosa," and tbe venous structure of the non-pulsating vein which was formerly designated as arteria venosa. He recognized further that the blood in the arteries is under a much higlier pressure than in the veins, and that at its transition from the former to the latter the capillary anastomoses offer a greater or less resistance according to the degree of their contraction or expansion.

Twelve years after the " Quffistiones peripatetieas " appeared his books " De plantis " which alone would suffice to win for him imperishable renown as the forerunner of Linnaeus. In this work also he confirms that " sanguinem pervenas duci ad cor, et per arterias in universum corpus distribui " (that the blood is led through the veins to the heart, and is distributed by the arteries to the entire body).

In the year 1593 appeared Cesalpinus' work " Qua?stionuni medicarum libri II," in which he gave the experimental proofs of his theory. He observed that if in a living animal a vein is exposed and tied, and if soon thereafter an incision into the vein is made in the direction of the capillary, that the blood first appearing has a darker color, and that which flows out subsequently is lighter in appearance. From this obser


vation he, with great acumen, deduced the physiological purpose of the anastomoses found in all organs between arteries and veins, in that he assumed : " venas cum arteriis adeo copulari osculis ut, vena secta, primum exeat sanguis venalis nigrior, deinde succedat arterialis flavior, ut plerumque contingit " (that the veins are so connected with the arterial mouths that the vein being divided, first exudes a darker venous blood, then succeeds the brighter arterial, so for the most part it happens).

A second experimental proof of the circulation he founded upon the fact that in any part of the body the tied veins swell between the ligature and the capillary origin, and not between the heart and the ligature, as ought to be the case according to Galen's conception : " intercepto enim meatu, non ultra datur progressus; tumor igitur venarum citra vinculum debuisset fieri" (for the course being blocked, no longer a flow is permitted; therefore the swelling of the veins ought to be made on this side of the ligatures) (t. e. between vein and capillaries)).

In spite of these brilliant experimental proofs of the theory of circulation, which Cesalpinus was the first to offer, the view was held by some, and among them the famous Haller, that he had indeed known the circulation of the blood but had only assumed it for the state of sleep, not during the awake state ; they based their view upon a quite erroneous construction of a passage in which Cesalpinus assumes a certain reflux of the blood from the arteries towards the heart during the state of being awake. No one has better, and with more cogent logic, reduced ad ahsurduM the assertion of Haller than has Ceradini. It is a pity that Ch. Kichet in his " Dictionnaire de Physiologic," which is now in progress, repeats the erroneous opinions of Haller concerning Cesalpinus, which had already been refuted through the historical-critical studies of Ceradini; which Ch. Richet certainly cannot have taken into account. (Luciani, 1. c.)

H. Tollin, in a very thorough study of the life and work of Cesalpinus, concedes that this philosopher knew the greater circulation ("hat den grossen Kreislauf gekannt") but did not comprehend it.

A further very convincing proof of the circidation of the blood is found in the presence of the little valves, which are found in great number in the course of the veins, and which are so arranged that they only permit a centripetal flow of the blood and prevent a centrifugal flow. These valves Aquapendente knew and described, but did not comprehend their object.

This proof Cesalpinus did not take into account, with which fact Sprengel, a historian of medicine, reproaches him. It is a fact, however, that although Cannano of Ferrara as early as 1517 described a few of the valves of the vena azygos, and determined that their concave side was turned toward the heart, and although a few years later Fabricius of Aquapendente had found analogous valves in the entire venous system, and had demonstrated them to his pupils, he published his discovery " De venarum ostiolis " only in 1603, that is ten


170


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


years after the appearance of Cesalpinus' " Quaastiones peripateticse."

On the other liand it must be statetl tliat Fabriciiis, tlic describer of the valves in the entire venous system, did not recognize at all the function of the same, which consists in preventing the reflux of the blood in a centrifugal direction and to aid the centripetal flow during muscular activity; he thought on the contrary, that they were intended to retard the flow of the blood from the heart to the periphery of the veins. Who then was the first to base the theory of the circulation of the blood upon the function of the venous valves?

To Ceradini is due the credit of having brought to light a series of important documents which lead to the conclusion that the first to recognize the function of the venous valves was the famous theologian and canonist of the republic of Venice, Paolo Sarpi, the friend and pupil of Fabricius. It is a fact that some contemporary authors ascribed to Sarpi the discovery of the circulation of the blood. Brother Micanzio, Bartholin, Vesling, Gassendi, and Walaeus name him as the discoverer. Voss (1G85) wrote that the discovery made in Italy by Cesalpinus of the circulation of the blood " Paulo Sarpi veneto in primis placuit." Vesling wrote to Bartholin that he had seen in the possession of Brother Micanzio after the death of Sarpi an autograph of the latter, m which the circulation of the Mood was described. The famous Dutch physician Walaeus wrote in the year 1640 : " Paulus Servita Venetus valvularum in venis fabricam observavit accuratius .... ex valvularum constitutione aliisque experimentis, sanguinis motum deduxit egregioque scripto asseruit" (observed more accurately the device of the valves in the veins .... from experiments on the construction of the valves he deduced the movement of the blood, and defended it in an illustrious writing (thesis) ). Unfortunately, however, the manuscripts of Sarpi which were preserved in the library of the Servitians at Venice were destroyed, together with a large portion of the monastery, by a fire in September, 1769, and there was preserved only a passage cited from a letter, in Griselini's book entitled, "Del genio di fra Paolo Sarpi" (Venice, 1783), in which letter Sarpi makes allusion to that which he " had observed and written down concerning the circulation of the blood in the vessels of the animal body and the structure and function of the venous valves."

What credit then belongs to William Harvey, the British discoverer of the circulation of the blood, after Servetus and Colombo, after Cesalpinus, and Sarjn? Certainly he was not the first to correct the error of Galen relative to the permeability of the septum and to assume that all the blood passes from the right side of the heart through the pulmonary vessels into the left side: this was the discovery of Colombo and Servetus. It was not he who first recognized the presence of arterio-venous anastomoses, the passage of the blood through the same and the centripetal direction of the course of the blood in the veins : this was the great discovery of Cesalpinus. It was not he, who first described the venous valves, for already Cannano knew of them and his teacher Fabricius d'Acqua


pendente described them in detail — it was not he who discovered the physiological importance of the same for the circulation; this was probably the discovery of Paolo Sarpi. And yet great credit is due to Harvey, for the reason that he more clearly defined the theories of his predecessors, and firmly established them by numerous vivisections and ingenious experiments. The modern Italian physiologists (Luciani," 1. c.) accuse him of having committed a great wrong by trying to claim the glory of the discovery, not mentioning the names of Cesalpinus and Servetus, and making it appear that he did not know of their works.

After the historical-critical studies of Ceradini and also those of Tollin (which agree in this point) it would be absurd to assume that Harvey was not fully acquainted with the works of Cesalpinus, which appeared at Venice in the year 1.593, that is, five years before Harvey took up his abode at Padua, where lie remained four years (1598-1602) as the pupil of Fabricius d'Acquapendente. If he remained silent in the face of the charges of his contemporaries Micanzio, Vesling, Walaeus, Riolan, Bartholin, and others, who accused him of plagiarism, it was evidently because he wisely wished to refrain from entering into a discussion in which he had much to lose and nothing to gain.

In spite of all this his pamphlet of 72 pages, which appeared at Frankfurt in the year 1628, " Exercitatio anatomica de motu cordis et sanguinis in animalibus " is without doubt the masterpiece of a man of genius.

Even at the present day, after the lapse of more than two and one-half centuries of scientific investigation, this " oposculum aureum," as Haller called it, calls forth admiration of the reader, by the clearness of his ideas, and the logical arrangement of the observations, all of which were based on vivisection. With the exception of a few inaccuracies and errors, everything in the book is well observed and well conceived, and it can still at the present day serve as an introduction into a more detailed study of this interesting subject.

Upon laying bare the cardiac region of living animals, he observed that the heart is alternately in motion and at rest. During systole it rises, and with its apex moves the parietes of the chest; it contracts in its entirety, and especially in its lateral portions; it becomes hard, like the muscles of the arm when they contract, and in the case of the cold-blooded animals it grows pale, because all the blood is sent out from its cavity. Pulse of the arteries is synchronous with systole of the heart. When the heart is at rest, the arteries also cease pulsating. If one open an artery, the blood gushes forth violently at each systole. Accordingly, at the moment of systole the blood is driven into the arteries, and cannot flow back, because the cardiac valves prevent reflux.

Like the ventricles, so also the auricles contract and relax, but earlier than the ventricles. The motion seems to start from the atria, proceeding thence to the ventricles. When the


" See Lulgi Luciani, Physiologia, Vol. I, p. 125, translated into German from the Italian by Silvestro Baglioni, Winterstein, 1904.


Mat, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


171


heart dies, the left ventricle is the first to stop, then follows the left auricle, then the right ventricle, and the " ultimum moriens " as already Galen had observed, is the right auricle. If one cut through the apex of the heart at a moment when only the right auricle continues to contract, one sees blood coming forth at each contraction. Therefore the blood is driven into the ventricles by the contraction of the auricles, and not through the suction produced by the expansion of the ventricles.

The function of the motion of the heart is to force the blood coming from the veins into the arteries and thus distribute it over the entire body. Since the interventricular septum is impermeable, all of the blood, as has been recognized by Colombo, must go by way of the vena arteriosa and the arteria venosa through the lungs in order to pass from the right into the left ventricle. In all of this there is nothing essentially new, only the correction of some errors of Galen relative to the motion of the heart.

The conception of the general circulation is clearly expressed by Harvey in the following words: " . . . . patet sanguinem in quodcumque membrum per arterias ingredi, et per venas remeare ; et arterias vasa esse deferentia sanguinem a corde, et venas vasa et vias esse regrediendi sanguinis ad cor ipsuni; et in membris et extremitatibus sanguinem (vel per anostomosin immediatem vel mediate per earnis porositates, vel utroque modo) transire ab arteriis in venas; sicut ante in corde et thorace a venis in arterias : unde in circuituni moveri, illinc hue et hinc illuc, e centro in extrema scilicet, et ab extremis I'ursus ad centrum, menifestum fit" (it is evident, that the blood enters every portion of the body through the arteries, and returns through the veins; and that the az'teries are the vessels carrying the blood from the heart and the veins are the vessels and ways of returning the blood to the heart again ; and that in the members and extremities the blood passes from the arteries into the veins (either by immediate anastomosiSj or mediately through porosities of the flesh, or by some other way?) ; as before was made manifest, in the heart and thorax from the veins into the arteries; thence to move in a circuit, now in one direction, now in the reverse, manifestly from the center to the extremities, and from the extremities back to the center.) From his own words we recognize that Harvey evidently was ignorant of the capillaries.

To prove his assertions, he furnished experimental proof of the three following theses:

1. The blood propelled by the contraction of the heart passes incessantly from the vena cava into the arteries, in such quantities, " ut ab assumptis suppeditari non possit, et adeo ut tota massa brevi tempore illinc pertranseat " (that it could not be furnished by the food consumed, and in a measure that the entire mass will flow through thence in a brief time).

2. The blood propelled by the pulsations of the arteries penetrates incessantly into every member or every part of the body, " majori copia multo, quam nutritioni necessarium sit, vel tota massa suppeditari possit" (in far greater abundance


than is necessary for nutrition, even if the whole mass (of the body) could be supplied).

3. Ab uno quoque membro ipsas venas hunc sanguinem perpetuo retroducere ad cordis locum " (from any member its veins perpetually carry back the blood to the heart).

The demonstration of the first thesis is the most substantial portion of Harvey's work. Starting with the capacity of the right ventricle in human corpses (which is slightly more than three ounces of blood), he emphasizes the fact that a considerable quantity of blood must be driven into the arteries at each systole, in consequence of the size of the orifices (?) and the force of the contraction. However large this quantity be, it must be in proportion to the difference between the capacity of the contracted and the dilated ventricle. If the heart of man or of other animals convey only a single dram of blood at each contraction, and if in half an hour it perform a thousand contractions, the result is, that the heart in this short space has driven ten pounds and five ounces of blood into the arteries, a quantity which is much too large to be supplied by tlie food taken into the body, unless the blood return in the same way. One need not open the aorta, but merely any small artery, in order to cause all the blood of the body to gush forth in less than half an hour, as Galen already observed.

The demonstration of the second thesis is only an expansion of the experiments and ideas of Cesalpinus. If one apply a tight ligature to an arm, as in the case of amputations, pulsation of the arteries ceases in the periphery, while the arteries toward the center beat more violently and swell. The hand and arm cool after some time. If the ligature be only loose, as in the case of blood-letting, then the arm swells below the ligature, and tlie expanded veins appear prominently. Above the ligature on the contrary they become invisible. By the tight ligature the passage of the blood through the arteries is prevented, while the loose ligature prevents the course of the blood in the veins. Therefore the blood passes from the arteries into the veins. Here Harvey, with only slight changes, repeats the final deduction of Cesalpinus: " . . . . apparet qua de causa in plilebotomia .... supra sectionem ligamus, non infra" ("from which cause it is manifest tiiat in phlebotomy we bandage above the cut and not below ").

Also the conclusion drawn from this, that the blood flows toward the various organs in much larger quantities, " quam nutritioni suSieiens sit" ("than is sufficient for nutrition"), is taken from Cesalpinus, who designated as " alimentum nutritivum " that which the blood carries along for the nourishment of the organs, and as " alimentum auctivum " (growing) the part which returns to the right side of the heart, after passing from the arteries through the capillaries into the veins.

The proof of the third thesis is founded entirely upon the physiological function of the venous valves. Harvey treats this point with great acuteness, since it is best adapted to convince the incredulous, and he adds four illustrations of ligatured arms (one of them being simply a reproduction of " Figura I, Tabulm II, brachii vivi ad sanguinis missionem


172


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


ligati" (living arms ligated to hinder the flow of the blood) from the treatise of his teacher Fabrizio (Fabricius ab Aquapendente), " De venaruvi ostiolis," which exhibit the veins swelled varicosely at the place of the valves. The venous valves do not serve the purpose of preventing a superfluity oC blood in the lower portions of the body, for they occur also in the venffi jugulares, which go from above down, similarly in the venffi emulgentes, mesentericse, etc. They serve rather to prevent a rushing of the blood from the larger into the smaller veins, so that the latter may not tear and become varicose, they prove that the blood in the veins does not flow from the center to the extremities, but from the latter to the center. Injections through the larger into the smaller veins are often arrested by the resistance of the valves, while in the case of injections through the small into the large veins there is no obstacle.



Pig. 1 is a reproduction (Photozinkography) of the two first figures of Harvey's work, edition 1639, ex oflScizna Joannis Maire, Lugduni Batavorum.

Pig. 1 is an exact imitation of tlie illustration in Fabrizio's writing " De venarum ostiolis." At AA the arm is ligated as is customary in venesection. One sees the swollen veins, which show enlargements at the points B, C, D, E, F, which proceed from the valves. These are not only found at the bifurcations (E, F), but also at (C, D).

Fig. 2 shows the same arm in which the blood has been forced from to H, by drawing the finger forcibly along it from H to 0. The portion of vein ij to appears to be obliterated, because a valve exists at 0, which prevents the blood from flowing hack to H, and the finger pressing upon the vein at H prevents the blood from flowing in from the peripheral veins.

If on the ligatured arm one press the blood out of a vein with the finger, one sees that when the blood arrives above a nodule (which shows the position of a valve) (nodule) it cannot flow back again, and the portion of the vein between the nodule and the finger appears obliterated." Accordingly the function of the venous valves is the same as that of the semi


" See Pigs. 1 and 2, above.


lunar valves of the aorta and the vena arteriosa (arteria pulmonaris), which close the orifice and prevent a reflux of the blood.

One would think that tlie theory of the circulation of the blood, which had already been demonstrated by Gesalpinus, would, through its perfection at the hands of Harvey, haveimmediately been accorded scientific citizenship, and be recognized by all. But opponents were not lacking, and among the most important and at the same time most persistent of them was Jean Kiolau (Riolanus) , a famous Parisian anatomist, and Kaspar Holi'mann, a leader of German science of that period, who had been, like Harvey, a pupil of Fabricius d'Aquapendente at Padua. They recognized, indeed, that the new doctrine would result in the total collapse of the system of medicine of the period, and every means seemed justified in preventing this, which in their eyes at least seemed a deep disgrace. It is scarcely necessary to say that this opposition (although it disclosed some mistakes and errors of Harvey's work) only aided in propagating and advancing tlie new theory. And thus the remark of Ceradini seems very apt, that " Harvey owed liis success to the opposition of the Parisian anatomist, wlio, upon Fabricius' death was considered the greatest authority in Europe; and the error of the partisans of the Englishman arises from the parallel which they drew from the impression which his writings made in the scientific world, as compared with those of Gesalpinus. . . . Had Gesalpinus during his life met with a Riolan, to accuse him of plagiarism, absurdity, and of heresj', the very slow development of his ideas concerning the circulation, in lectures covering a period of more than thirty years (first at Pisa then at Rome), would have been impossible witliout discovering the possible results and appplications of the same, no one could have taken from him the great renown of his discovery." " Furthermore, Harvey himself was at the beginning so far from having any idea of the far-reaching consequences of the doctrine of the circulation of the blood, which he had learned from Andrea Gesalpinus, that he only thought of printing it after he had for nine years treated of it in his lectures; he was only impelled to do so by the fact that this doctrine had made both friends and enemies for him, and that the latter made a great stir about it. And even after the appearance of his book, in the year 1C49, the physiological importance of the theory seemed to him so problematical, that in his answer to Riolan, who declined to accept the theory, because he could see " neque efficientem, neque finalem causam " (neither the influence, nor the final effect) he had no better reply to make than to say : " Prius in confesso esse debet quod sit, antequam propter quid inquirendum. . . . Quot sunt in physiologia pathologia et therapeia recepta, quorum causas non novimus, esse tamen nullus dubitat?" (first it ought to be conceded what may exist, before inquiring what it means or wherefor. . . . How


" Ceradini here means that the complete comprehension of a discovery is often not made by the discoverer himself, but he may be brought to a wider comprehension of his contributions to science by the opposition of men of authority.


Mat, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


173


many things there are received in physiology, pathology and therapeutics, whose causes we know not, yet no one doubts their existence?)

As long as the theory of Aristotle flourished, which had been rehabilitated by Cesalpinus and Harvey, that the function of the lungs consisted in refreshing the blood, and that this organ, in which the blood was again made spirituous and thin was nourished by the thick blood flowing back from all the organs; as long as especially the place of blood-formation remained unknown, and also the channels through which the products of digestion reached the circulatory system; just so long did the theory of the circulation of the blood remain without its true significance, and it could only be regarded as a physiological curiosity.

'To judge from certain passages in Galen, it seems as if Herophilus and Erasistratus, the heads of the Alexandrian school (300 B. C) had seen the chyliferous vessels in the mesentery of the sheep. Towards the end of the 18th century Portal remarked, as in fact also Fracassatus had done more than a century earlier, that the celebrated Koman anatomist Eustachius," in studying the course of the vena azygos in the horse, had observed the thoracic duct and even some of , the valves of the same. But it is certain that every trace of these accidental and isolated observations had vanished to a vague tradition, when Gaspare Aselli of Cremona, professor of anatomy at Pavia, found, in 1G22, the chyliferous vessels in the mesentery of the dog, designating them by the name of lactiferous vessels. So happy was he at having found what lie had been seeking, that, as he relates, " conversus ad cos qui aderant: eu/irjxd, inquam cum Archimede " ("I turned to those who were present: I exclaim with Archimedes, Eureka"). But as yet he liad no idea of the true function and physiological importance of these vessels.

In the year 1C48 Pecqet, a young physician of Dieppe, who was studying in Montpellier, found that the lactiferous vessels do not send their contents to the liver, as Aselli had believed, but to a large vessel, the thoracic duct (re-discovered by him after Eustachius) which empties into the subclavian vein. Two years later Rudbeck, a Swede, discovered the lymphatic vessels of the liver, and recognized that they also send their contents to the thoracic duct. Finally, in the year 1G53, the famous Danish anatomist, Thomas Bartholin, discovered the same vessels in all parts of the body, and found that all of them, together with the chyliferous vessels, flow into the thoracic duct. In order to give further scope to the theory of the circulation of the blood, ascribed by him to Harvey, he published a new edition of his anatomy " ad sanguinis circulationem reformata," being correctly convinced that he had furnished a new argument in favor of it, indirect to be sure, but nevertheless valuable.

According to Ceradiui, Eiolan himself, the upholder of every old doctrine, and tlie opponent of everything new, in this case withheld the sharp arrows of his criticism, in order not to see them rebound harmlessly from tlie strength of


" Opuscula anatomica, Venetiis, 15G4.


facts. Harvey, however, denied the existence of the cuYLiFEROus and lymphatic vessels, and even the function OF the thoracic duct, and died without being converted, in the year 1058, six years after the deatli of Bartholin. Luciani (professor of physiology in Rome), in his elaborate liaudbook on liuman physiology, expresses surprise and regret that Sprengel, the famous historian of medicine, scarcely mentions this " ugly trait in the character of the Englishman, th w contempt for every discovery which was not hisvwn, a blemish irhich would be inexcusable, even if Cesalpinus had not demonstrated the circulation of the blood before him."

In order to complete the new theory, and to bring it to a state of absolute certainty, there was now only lacking the last decisive step, the discovery of the capillaries of the blood and the direct observation of the circulation of the blood tlirough these capillaries from the arteries to the veins. " Supererat" (it remains), as Haller said, " ut ipsis oculis circuitus sanguinis subjiceretur " (that the circulation of tlie blood be subjected to the eyes (be actually seen)).

Galen, who, as already mentioned, was the first to assume direct communication of arterial and venous vessels in tlie organs, thought of a kind of direct anastomoses or a simple meeting of the two kinds of vessels. This was not in accord with the idea which Cesalpinus had formed; the latter conceived tliat the junction was made " per vasa non desinentia, ulterius transmeantia " (by vessels not stopping, but passing through), or "per vasa in capillamenta resoluta " (by vessels broken up into hairs (threads)) (which Harvey changed to "per caruis porositates ") (through porosities of the flesh), and Cesalpinus tlius guessed the existence of a new kind of vessels, which unite the arteries witli the veins and which then were called capillaries.

Marcello Malpighi, with the aid of the microscope, was the first to observe the motion of the blood in the capillaries of the lungs of the frog. This was in 1661. With just pride he exclaimed : " Talia mihi videre contigit, ut non immerito illud Homeri usurpare possira ad rem praesentem melius; magnum certum opus oculis video" (it has happened to me to see such things, that not undeserving I might in the present instance use the saying of Homer : I see with my eyes a sure great work)."

After Malpighi, vain attempts were made by Lcouwenhoek, Cooper, and Haller to extend these observations also to the warm-blooded animals. The first to succeed in this was Lazzaro Spallanzani, who hit upon the idea of making use of the lien's egg during the process of development of the chick. The enthusiastic words with which the great physiologist reports his discovery cannot but provoke a smile. " For a long time I had been burning with the desire to discover the circulation of the blood also in the ease of the warm-blooded animals, to observe it in the same degree in which I had noticed it in cold-blooded animals, and thus these vessels (the vasa umbilica of the chick) attracted my attention more than


' Cf. Fig. 48.


174


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


anything else, because they belonged to that species of animal. Since the room in which I was, did not have sufficient liglit and I was determined in some way to satisfy my curiosity, I resolved to examine the egg in the open air, by direct sunliglit. After I had fastened it to the small Lyonet apparatus (a small microscope, used by Spallanzani) I immediately focused the lens upon it, and in spite of the flood of light which surrounded me, I could, by partly closing my eyes, distinctly see the blood circulate through the entire complex of the arterial and venous umbilical vessels. Overcome by this unexpected pleasure, I felt at liberty also now to cry out : ' I have found it, I liave found it ! ' I made the discovery in May, 1771, and in the summer vacation of that year I took pains to develop it suitably."

These observations of Malpighi and Spallanzani, separated by a century, constitute two of the chief events in the history of medicine. The glory of the first direct observation of the circulation of the blood belongs undoubtedly to the Italian pliysieians. Modern scientists, with moi-e perfect microscopes and more advanced technical skill, have only been able to perfect the description of the circulation of the blood as seen under the microscojie.

In speaking of Servetus, Sir Michael Foster does not concede to him any marked influence on the development of anatomic thought of his day, and declines to regard him as a real link in the chain which leads from Galen to Harvey." He would concede to the writings of Servetus only isolated bits of truth, floating along the stream of human thought, by the side of other truths, the outcome of the labors of other men. But though Sir Michael Foster speaks in the diminutive concerning the work of Servetus, he makes use of this very author's work to minimize the merit of another contributor to the history of the circulation, namely, Matheo Kealdo Colombo; for he suggests that Colombo might have taken the idea of pulmonary circulation from Servetus, and his reason is that in 1546 Servetus sent to Curio in Padua a manuscript copy of his " Eestitutio." " This Columbus may have seen. Again, when the edition of the published ' Eestitutio ' was burnt in 1553, some few copies escaped. One of these may have found its way to Rome before Columbus liad sent his work to the press." ToUin and Preyer " have arranged the quotations from Colombo and Servetus concerning the lesser circulation side by side, suggesting that Columbus learned what he knew from Servetus.

Sir Michael Foster furthermore attempts to support liis charge of the plagiarism of Columbus from Servetus by what he calls an " unabashed attempt to assert ownership of the discovery of the third ossicle of tlie ear, the stapes." According to Fallopius, the stapes was first described by Ingrassius of Palermo, a Sicilian, in 1548. This may be, as Foster states, a theft, but it is not absolutely proven, because at the present day, two physiologists or anatomist'!, in different coun


" Lectures on the History of Physiology, p. 24. "Virchow's Archiv., Bd. 91, 1883. " Samml. physiolog. Abhdl., 1876.


tries, have been known to make and claim an identical discovery simultaneously.

The character of Colombo is represented as having been that of a " vain and ungrateful successor of Vesalius," " and his standing, it is indicated, suffered by his fulsome adulation of Pope Pius IV, a pope whose character has met with mucli criticism.

From the standpoint of critical conservatism we cannot conceive that tlie charges of plagiarism and theft against Colombo have been satisfactorily proven. At least they would not be accepted as proven by a judicial mind. I have already given the proofs in the preceding on the authority of G. Ceradini,'" which are incontrovertible facts, that Colombo could not possibly have plagiarized Servetus. His accurate descriptions of the pulmonary circulation may be the results of his own research and subjective analysis. Some doubt is thrown on Ceradini's conclusion by the incomparably precise historic researches by H. Tollin,"' who does not consider that Colombo is original, but simply has confirmed what Servetus described before him.

Concerning the merits of Andreas Cesalpinus,^ Foster "' suggests that " they were not the outcome of patient researcli, or real study of the phenomena themselves, but may have been flung out in the spirit of controversy, as effective assaults upon the accepted doctrine of the times." In the preceding, however, I have given the evidence that we have no riglit to question, that tlie theories as announced by Cesalpinus were not the outcome of real study of the phenomena themselves.

A personal and systematic study of Cesalpinus' works undeniably gives the impression that he was a man of most vacillating character, of insufficient force of conviction even where there was every probability that his views were correct. But even his greatest opponent, Tauriel (of Montbeliard), has much to say in praise of his versatility and the inventive power as displayed in the " QuEestiones peripateticae," and that these talents when coupled with " love of truth and piety " would justify us in expecting great and useful things of Cesalpinus." (" Qua sua singulari facilitate poterat prodesse plurimum — res magnas et humanae societati utilisimas prsestare possunt.")

It cannot lead to a just opinion of Cesalpinus, to merely glean here and there in his works ; isolated patches of his writings must inevitably present a disconnected, illogical character, whereas in truth his argument is as liomogeneous and consequential as that of Colombo — whom Harvey honors and quotes to the total exclusion of Cesalpinus.

It is very regrettable that tlie great Haller made an erroneous construction of a passage from Cesalpinus, in which a reversal of the present idea of tlie circulation was assumed to take place during the waking state (a certain amount of reflux


" Puschmann Handb. d. Geschichte d. Medicin, Bd. 11, p. S31.

^ Loc. cit.

°' Loc. cit.

'^ See preceding.

'" Loc. cit., p. 35.


Mat, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


IT'S


of blood from the arteries to the heart during the waking state) .°* The forcible logic of Tollin"" and of Ceradini have set the views of Cesalpinus in the right light, and proven that he was a physiologic experimenter of ability. He had not only grasped clearly the pulmonary circulation, but also thr systemic circulation. There is no doubt whatever that he Icnew that the flow of blood to the tissues took place by the arteries, and that the "return of the blood from the tissues took place by the veins and not by the arteries. The published works of Colombo and Servetus to my mind represent independent and individual conceptions. The charges of plagiarism of one from the other, are ingenious speculations.

It cannot possibly deduct from the brilliancy of Harvey's genius to have the work of his predecessors set in the right light. His admirable combination of anatomical features with physiologic function, liis conception of experiments, both original and conclusive, testing the validity of his explanations, all combine to complete the picture of a physiologic thinker of colossal ingenuity. If other workers preceding Harvey fell short of his results, it may of course have been due to a lesser intellectual endowment, but it may also have been due to the fact that they were working in countries in which scientific research was under the ban of Church and State. Furtliermore, path-hewing is more difficult than path-widening. The older and preceding workers in any department of science do not, as a rule, grasp the entire truth concerning the relation of things. Scientific exploration takes place, as a rule, bit by bit, sometimes by strenuous and painful endeavor. The mental or subjective conceptions preceding the experiment being often more laborious than the actual devising of experiments to test the validity of the conception. All this in the discovery of the circulation of the blood took centuries.

As grateful recipients of the labors of the historic apostles of physiology, it behooves lis to maintain a Judicial mental attitude and interpret the contributions of each physiologic worker from the aspect of tlie condition and influences — political, religious, scientific, and otherwise, — that were predominating at his time, and in that light it is astounding to observe how near to the truth Servetus, Matheo Colombo, and Cesalpinus came with their crude methods of subjective and objective analysis, and we will have to sum iip in one abstract sentence with Professor L. Landois that " William Harvey, a pupil of Fabricius (until 1604) finally constructed, between the years 1616 and 1619, partly from his own investigations and partly from the results of former observers already mentioned, the picture of the circulation of the blood, tlie greatest physiologic achievement, which was published in 1628 and marks a new epoch in physiology."

A Eesdme of What We Have Learned from the Literature Quoted in the Preceding about Harvey and His Eelation to His Predecessors.

We gather from Harvey's own writings and the scholarly


' See preced'ug. ' Loc. cit.


studies of Henri Tollin,"* that, seven years before his death, Harvey plainly teaches that before him there was a knowledge of the circulation of the blood. In " De Motu Cordis " and in liis writings to Eiolan he teaches tliat Eealdo Colombo has shown that the blood does not pass from one ventricle into the other through the middle wall of the heart, but through a long circuit througli the lungs. Harvey imparts to his friend Koyle that he got his first suggestion of a circulation of the lilood from his Paduan teacher, Hieronymus Fabricius ab .Vquapendente, led to the idea by meditation over the function of the valves in veins, and to his friend But, that Fra Paolo Sarpi (1623) had left a writing on the uninterrupted return of the blood (to the heart) five years before Harvey publislicd his. Harvey declares it the duty of the scientific anatomist to learn the experiences of his predecessors, to prove and to use tliem. He abundantly makes use of this right and therefore walks in the foot-prints of Galen and Hippocrates, of I'liny and Aristotle, of Fernel and Vesalius, of Colombo and Aldrovandus, and of many, many other authorities. Harvey regards the moving blood as inseparable from the spirit, which first gives it movement, warmth, feeling, power of nutrition, even something heavenly, corresponding to "tlie element of tlie stars." Harvey makes this probable to us by many relative thoughts, which he has drawn from not only Eealdo Colombo, whom he cites several times, but also from Michael Servetus, Sarpi, and Andreas Cesalpinus. But tlirough the jiroud, independent, indomitable peculiarity of liis character, Harvey makes plain to us why, where the renown of a discoverer was at stake, he could not bring himself to say : " I am not the discoverer, but yonder Aristotle and Aquapendente, there AselJi, Pequet, Eudbeck, and Bartholin, there again Caspar Hoffmann, here finally Sarpi, Cesalpinus, Colombo, and already before them Michael Servetus."

I am well aware that Tollin's " conclusion may vary from the current, traditional jubilation over the great Harvey, the demonstrator of the entire circulation of the blood. But Tollin, if abused for this variation, will answer witli the words of his teacher, William Harvey : " Trust in your own experiences, not in those of others " (propria experientia nitendum est, non aliena (0pp. 172)).

The completion of the discovery of the circulation of tlie lilnod by Malpighi and Leeuwenhoeck, Iiy Eustachius, Aselli, Pequet, Eudbeck, and Bartliolin, by the injections of Swainmerdam. Home, and Euysch, the observation of invertebrate animals on the part of Willis and Milne-Edwards, by the discovery of graphic methods, by the observations of the vasomotor nerves on the part of Bernard, Brown-Scquard, Ijudwig, lead Chapman "* to the conclusion that " the spiritual develOPJtENT of humanity is also a growth that is governed by lifelaws, and that a discovery, although if it was not made by him, to whose name it is wont to be attached, yet at the appointed lime would have seen the light of the world." All circum


^ Loc. cit.

^ Henri Tollin, Arcii. f. Pathol. Anat., Bd. XXXI, 81, Heft I.

™ Loc. cit.


1?6


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


stances show that towards the end of the sixteentli century intellectual Europe was ripe for the acceptance of the discovery of the circulation of the blood. If it had come a few centuries sooner, it would have died at its birth. Italy and particularly Padua were alive with speculations, hypotheses, and theories concerning the course of the blood through the body. One who will compare the Latin original of Harvey's writing upon the circulation with the writings of the great Italian anatomists and pliysiologists of the sixteenth century, will be astonished at the similarity of thought and expression. (The same mode of thought and expression pervade both.)" In the method of his investigation, observation, and conclusions, Harvey is essentially Italian. An Englishman by birth, an Italian in thought, Harvey lived and died as a student of Padua. Thus Chapman returns to where he started out. Between Galen and Servetus, the second and third epochs of the discovery, Chapman establishes an interval of 1718 years; between Servetus and Cesalpinus 40 years; between Cesalpinus and Harvey 35 years. When Servetus stood forth, he risked that his discovery might be burned with himself. When Harvey stood forth, all had been prepared. He came, considered, and gained the victory.

Tollin pointed out what an advance in the investigation of tlie history of tlie discovery of the circulation of the blood, even in Harvey's fatherland, since 1878 (the 300th anniversary of Harvey's birth), we have to record. Before 1878 it was not only the dogma of tlie profane crowd of the educated but also of the professionally educated in England, that as Minerva from the head of Jupiter, even so fully and entire, the discovery of the circulation of the blood sprang from the head of Harvey. Now even in England it is said: When Harvey came, everything was fully ripe. If he had not harvested, then at that time another would have come and gathered in the harvest. The seed sowing was the work of the Spaniards, especially of Michael Servetus; the watering, the care, the pruning the work of the Italians, especially of Colombo, Cesalpinus, Fabriciiis de Aquapendcnte. To Harvey remained the honorable, remunerative, although always troublesome work of the harvest. But what we possess to-day, we possess through him who harvested it for us. And for this Tollin designates the gifted Harvey, " the great Briton, the pattern of all harvesters and classifiers."

William Harvey, armed only with a magnifying glass, accomplished such great things that one cannot express what this genius would have accomplished had he, like Malpighi, been furnished with a microscope. But the discoverer of the blood circulation is not Harvey, however much, misled by the favor of two kings and the almost idolatrous reverence of his nation, he sought to convince liimsclf that he was such. And he did convince himself and finally did believe in it, because this belief only too soon had become the dogma of his nation. But, in the moments when he is candid, he acknowledges that several persons before him, induced by Galen's authority and


™ Tollin: Log. cit.


that of Colombo and Servetus, beside other reasons, had taught the truth about the blood-vessels and had expressed the opinion which he now claimed as his own; yes, that many, long before him, had known of a blood circulation, by means of which continually the blood passed from the arteries into the veins and from the veins returned to the heart; that he himself had gladly and diligently read the books of those who had borne the torch of truth before us, that he willingly paid due respect to those old authorities and only had not mentioned particvlarly all of the modern ones in order not to give occasion for disputes; and that it was he who had erected upon firm and necessary foundations, more distinctly, more orderly, and fully corresponding to the actuality, the blood circulation discovered before him.

We once more affirm Harvey, the author of " De motu cordis et sanguinis," 1628, did not discover the lesser circulation. This Servetus discovered in 1546. Harvey did not discover the greater circulation. This Cesalpinus discovered in 1569. Harvey did not discover the venal valves. These Jacob Silvius, Sarpi, and most accurately Aquapendcnte discovered in 1574. Harvey did not furnish the clear-sighted proofs of the circulation. These were given by Servetus, Colombo, Valvcrde, Aranzi, Ruini, Rudio, Sarpi, Cesalpinus, and Aquapendcnte. Harvey never saw the circulation of the blond. Malpighi saw it several years after Harvey's death (1661).

Strictly speaking, Harvey did not even describe the circulation, but a double half circulation. Whether in the lungs and in the extremities the arterial endings were in communication with the commencement of the veins by anastomosis, or by infiltration of blood into the pores of the tissues, he never dared to decide, because the magnifying glass here failed to tell him. And so, since two half circulations suddenly end without a demonstrable continuation, there is no actual, no completed circulation.

Nevertheless, even then Harvey still remains an incompai'able genius. For " hy the accuracy and thoroughness of hix deductions, by the skillfulness, hy the industry and the abundance of his experiments, hy the carefulness and the delicacy of his observations, by the keenness and shrmvdness of the proofs, by the clearness and truth of the conclusions drawn, by the novelty and importance of the interposed reflexions, above all by the harmonious connection of the whole," William Harvey, the great regius predemonstrator of the blood circulation, the movements of the heart and of the blood, has lifted these from a hypothesis of the darkest possibility to the clearest probability, from the recesses of single obscure studies to the shield of public opinion, from the individual views of a few favored ones to a dogma everywhere sanctioned. And in this sense one can indeed say with Tollin: "Without the school of Padua, yes without Erasistratus, Aristotle, Galen, Servetus, Vesalius, Colombo, Cesalpinus, Aquapendcnte, we would have had no Harvey, but without Harvey no discovery of the blood circulation."

Harvey quotes among the authorities known at and previous to his time Aristotle, Galen, Erasistratus, Vesalius, Realdo


May, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


177


Colombo, and Fabricius de Aquapendente. He does not cite Michael Servetus nor Cesalpinus, and yet he must have been acquainted with their works, for his methods of thinking show manj resemblances to that of these writers. It is absurd to assujne that such an omniverous reader as Harvey, who studied four years at Padua, where the works of these two men were widely known, was not acquainted with tkeir writings. The omniverous reader, Harvey, who is described as accompanying King Charles I, and taking care of the princes, and during the battle of Edgehill (Oct. 23, 16-12), as sitting at the outskirts of the fight under the hedge reading a book (Aubrey)." Furthermore, Eobert Willis," the greatest Harvey connoisseur in England, actually asserts that Harvey was a free-thinker like Servetus and Cesalpinus, and even an Antitrinitarian, so that he must have been in religious sympathy with these two men, and for this reason again he probably sought and was familiar with their works. And yet we will have to excuse him for not quoting these two early discoverers for the following reason :

Because of his heretic work " De Trinitatis Erroribus," Michael Servetus was burned at the stake at Geneva, in 1553.

Cesalpinus, free-thinker like Servetus, friend of Trismegistus and precursor of Spinoza, could only save his life by retracting.

Matteo Eealdo Colombo was a diplomat, clerically inclined, friend of several cardinals and flatterer of the inquisitoriallyminded pope Paul IV, his memory was held in high esteem at the English Court, whose queen was a devout Catholic, and whose king was secretly her ally. A hater of the Protestants, an enemy of aU Puritans, and still more of the freethinkers, a systematic adherent of a strict bishopric regime, the royal patron of Harvey was the man who sent the members of Parliament into prison, who made the method of punishment severe to the utmost to Anabaptists and Antitrinitarians, and applauded the massacre caused by Ireland's Catholics among the Protestants. As is well known, the king was beheaded in 1649.

The Protestant England, with its independent spirit of inquiry, to whose free manner the Harvey jubilants attributed Harvey's great discoveries, did not exist at his time, and not for a long time after it. Harvey died the 3d of June, 1658. And still King Charles II, son of the executed Charles the first, forced on Bartholomew's Day, by his Acts of Uniformity, two thousand English clergymen to resign their positions because they refused to subscribe to the thirty-nine articles of the King's faith. Even quiet prayer-meetings in the attics were


"Foster: Loc. cit., p. 42.

" Loc. cit.

'^ A court physician, under such a tyrannical prince, who would have dared to confess himself to Cesalpinus or even to Michael Servetus, would have certainly been executed, like Harvey's contemporary, the Saxon Chancellor Nicholaus Crell, who was beheaded for heresy at Dresden, the 23d of October, 1591, after ten years of imprisonment in a fortress. And Crell was not even a free-thinker, but a Protestant, v.'ho had the courage to prefer to be called a Christian, instead of a Lutheran or a Calvinlst.


considered treasonable. The heretics were banished. None of the exiles were allowed ever to come again within five English miles of their villages or any English cities.

Twelve years after Harvey's death the nonconformist act was rendered still more severe. Indeed twenty years after his death nobody could venture to adhere publicly to Cesalpinus and Michael Servetus. Up to 1838 the Acts of Uniformity of Charles II governed, which excluded all nonconformists from Parliament and civil service, also from the ofBce of a royal court physician, which meant so much for Harvey. Under the son of Harvey's patron, 80,000 Englishmen had to suffer all kinds of persecution because they refused to take oath to the faith of the State. Eight thousand alone had to go to prison for their faith.

James II, successor of Charles II, declared himself openly a Catholic, to destroy the last remains of the free faith by strict government without Parliament.

But his son-in-law, William of Orange, thirty years after Harvey's death, set up the famous Acts of Toleration in 1689. But free-thinkers, like Peter Bayle, were dismissed from their offices (1693) and those who sided with Servetus, called the Socioians, were expressly excluded from every public tolerance.

There are some who lauded Harvey's character up to the skies, just as they called (according to the legend) Harvey's mother the best of all women, probably because one knows nothing of her. But has nobody discovered a predestination as a martyr in a man who always kept his faith as secret as possible, and who deserted his royal benefactor as soon as the luck left the king's banners. No wonder, therefore, that Harvey does not mention Cesalpinus and Michael Servetus, even had he known them by heart.

The fruit of an intellectual deed is frequently more evidenced in the incentive which that deed gives to investigation than in the actual contribution to science made therein. An immense industry was developed by the exact proofs of the circulation furnished by Harvey, diseases were conceived of in a new light, efforts at transfusion were made, and of injection of remedies into the circulation.

The discovery of the circulation of the blood was the work of almost a millennium from Aristotle and Galen to Harvey, but the one who first logically drew true consequences out of hundreds of years of preceding work, and upon whose broad intellectual shoulders all subsequent investigations rested, was William Harvey; and to-day, 328 years after his birth, we may side without reservation with the words of Bartholin: " At Harveyo omnes applaudunt circulationis auctori ! "

Literature on the Histoet of the Discovery of the Circulation of the Blood.

Tollin, Henri : Harvey und seine Vorgiinger. Biologische Centralblatt, Bd. Ill, October 1, 1883, p. 461; also October 15, 1883, p. 481 ; also November 1, 1883, p. 513.

Die Entdeekung des Blutkreislaufs durch Michael

Servet. Jena, 1876.


178


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


Tollin, Henri: Matteo Realdo Colombo's Sektionen und Vivisektionen. Pfliiger's Archiv, 1880, S. 349-360.

Matteo Realdo Colombo — Ein Beitrag zu seinem

Leben aus seinem L. XV d-e re anatomica. Pfliiger's Archiv f. Physiol., Bd. XXII, S. 262-290.

Ueber Colombo's Antheil an der Entdeckung des

Blutkreislaufs. Virchow's Archiv, Bd. 91, 1883, S. 39-66.

Andreas Csesalpin. Pfliiger's Archiv, Bd. XXXV,

S. 395-390.

Ein italienisehes Urtheil iiber den ersten Ent decker des Blutkreislaufs. Pfliiger's Archiv, 1884, S. 482493.

Die Italiener und die Entdeckung des Blutkreislaufs. Virchow's Archiv f. Pathol. Anat., Bd. XCIII, Hft. 1, S. 64-99.

Die Franzosen und die Entdeckung des Blutkreislaufs. Virchow's Archiv f. Pathol. Anat., Bd. XCIV, Hft. 1, S. 86-135.

William Harvey. Virchow's Archiv f. Pathol.

Anat, Bd. LXXXI, Hft. 1, S. 114-157.

Die Englander und die Entdeckung des Blutkreislaufs. Virchow's Archiv, ,Bd. XCVII, Hft. Z', S. 431-482.

Ibid. Virchow's Archiv, Bd. XCVIII, Hft. 2,

S. 193-230.

Robert Willis' neuer William Harvey. Pfliiger's

Archiv f. Physiol., Bd. XXXIV, S. 1-21.

Wie Michael Servet Mediciner wurde. Deutsche

Klinik, von Dr. Alex. Goschen, 1875, S. 57.

Michael Servet's Brevissima Apologia pro Sym phoriano Campegio in Leonardum Fuchsium. Archiv f. Geschichte d. Medicin u. med. Geographic, Bd. VII, S. 409442.

Des Arztes Michael Servet Lehrer in Lyon, Dr.

Symphorien Champier. Virchow's Archiv, Bd. 61.

Anleitung zum Studium der Medicin aus den

Jahren 1533 und 1340. Virchow's Archiv, Bd. LXXX, Hft. 1, S. 47-78.

Zu Thibault's Process. Archiv f. Geschichte d.

Medicin u. med. Geographic, Bd. Ill, S. 332-347.

Michael Servet in Charlieu. Archiv f. Geschichte

d. Medicin u. med. Geographic, Bd. VIII, S. 76-96.

Der konigliche Leibarzt und Hofastrologe Johann

Thibault, Michael Servef s Pariser Freund. Virchow's Archiv, Bd. LXXVIII, S. 302-318.

Saint Vertunien Delavau. Virchow's Archiv,

Bd. CI, Hft. 1, S. 44-70.

Kirchner, Martin: Die Entdeckung des Blutkreislaufs. Berlin, 1878.

Coxe, John Redman : An Inquiry- into the Claims of Dr. W. Harvey. Phila., 1834.

Poster, Sir Michael : History of Physiology. Cambridge, 1901.

Luciani, Luigi : Physiology of Man, translated into German by Baglioni and Winterstein.


Ceradini, G : Ricerche storico-critiche intorno alia scoperta della circolazione del sangue, Milano, Fratelli Rechiedei, editori, 1876. Difesa della mia Memoria intorno alia scoperta della circolazione, contro I'assalto dei signori H. Toll in teologo in Magdeburg, e W. Preyer fisiologo in Jena. Con qualche nuovo appunto circa la storia della scoperta Medesima. Genova, tip del R. Istituto Sordo-muti, 1876.

Preyer: Sammlung Physiolog. Abhandlung, 1876.

Chapman, Henry C : History of the Discovery of the Circulation of the blood. Phila., 1884. P. Blakiston Son & Co. An excellent American contribution and side piece to the article by J. M. DaCosta.

Harvey, William : De Motu Cordis et Sanguinis in animalibus anatomica exercitatio, cum refutationibus Aemylii Parisani et Jacobi Primirosii Lugd. Bat. J. Maive, 1639. For other editions of this work and other publications by and concerning Harvey, see Index Catalogue of the Library of the Surgeon-General's Office of the United States Army. 2d ser. Vol. VI. pp. 782 and 783.

DaCosta, J. M : Harvey and his Discovery. Philadelphia, 1879. A vivid and scholarly American presentation.

Farre, Guy A. (1871), Rolleston (1873), West, C. (1874), Ogle, John W: Harveian Orations. Brit. Med. Jouru., July 3, 1880.

Paget, James: St. Bartholomew's Hospital, 1846.

Reports III and VI of the Royal British Commission on Historical Manuscripts, 1877.

Huxley, Thos. : On Harvey. Fortnightly Review, Feb., 1878, and Edinburgh Review, Jan., 1878.

Bridges, J. H : Harvey and Vivisection. Fortnightly Review. New Ser. No. CXV. July, 1876.

Willis, Robt: Sydenham Edition of Harvey's Works.

Gamgee, Sampson : Harvey and Cesalpinus. Lancet, London, 1876. See also his polemic with Ceradini. Qualche appunto storico-critico, etc., etc., della Circulazione del Sangue. Geneva, 1875.

Roth, M. (Andreas Vesalius, Bruxelliensis, 1514-1564, Berlin) : Tigerstedt, R., in Ergebnisse d. Physiologic, Jahrgang II, 1903, p. 533.

For further literature on the history of the circulation of the blood, see Index Catalogue of the Library of the SurgeonGeneral's Oflice, second series. Vol. II, " Blood — Circulation of " ; also " History of the Discover}' of the Circulation of the Blood," pp. 440 to 445. Here one can find the works of Eiolanus, Spallanzani, twelve various editions of William Harvey, Walaeus, Ceradini, H. C. Chapman, J. C. Dalton, P. Flourens, several Harveian Orations and the Defence of Harvey, by D. Johnson, Puschmann (Geschichte der Entdeckung des Blutkreislauf), numerous of the articles by Tollin, already cited ; the writings of Tollin are, however, not completely represented.


Mat, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


179


COMPARATIVE SURGERY:

WITH ILLUSTRATIVE CASES, By C. M. Faris, H. C. Thacher, J. F. Ortschild, and F. C. Beall,

AXD AN INTRODUCTION, By Harvey Cdshing.


It is the purpose of this communication to report some of the cases which indicate, it is hoped, a new development in our present plan of teacliing operative surgery; for latterly as the work has been conducted, it has necessarily subjected vagrant animals to the risks and discomforts attending more or less serious surgical procedures carried out for the relief of merely hypothetical maladies.

Four years ago an effort was made in our medical school — and so far as I know for the first time in any school — ^to change in a radical way those methods of conducting an operative course, which, for the past generation, have been widely adopted and generally regarded as most practicable by tlie surgical teachers in the leading medical institutions.

Heretofore it has been the universal custom, I believe, wlienever anatomical material has been sufficiently abundant to justify its being shared by the clinical departments, to employ the human cadaver for the practical teaching of operative handicraft. And though the opportunities tlius offered are admirable in many respects the method is open to serious objections. If I may judge from my own experience not only as a participant but subsequently as an onlooker at these exercises, the students are usually coached in the performance of the more or less stereotyped operations principally on the head and extremities, — the various time-honored amputations, e.xcisions of bones and joints, set ligations of vessels, etc., etc., — and thus it is the perfected operation rather than the method of operating upon which chief emphasis is laid.

A course of this kind, in which students are called upon to play an active part, may be not only an excellent surgical supplement to the study of human topographical anatomy but is useful, too, as an introduction to the handling of the surgeon's tools, — still it seems to me that the one great essential of modem surgery is conspicuously wanting. The paramount call upon the instructor, in this Listerian era, is that he shall emphasize and drill into his students, not as mere onlookers or hearers but as actual performers, the significance of that much-abused term surgical " technique," of which to-day the all-important element is asepsis — the first and the everlasting

thing to be indelibly stamped on the make-up of everyone who proposes to undertake operative work whether as a surgeon or investigator. Surgical cleanliness, which must become a reflex matter — an operator's second nature — and which, like all other reflexes, must be learned early, is necessarily disregarded in the time-honored methods of teaching this branch in the most unsnrgical surroundincrs of a dissecting room.


Next in importance to the acquirement of this reflex habit of cleanliness is the ability to dissect and to gently manipulate living tissues without so damaging them as to interfere with perfect reactionless healing ; and a third great requisite, which cannot be learned upon the cadaver, is an acquirement of skill in the proper control of hsemorrhage from the large as well as small vessels, for the old-fashioned rough methods of haemostasis happily are still followed by few. Nor, finally, can facility in the particular technique of visceral surgery, whether abdominal, thoracic, or intracranial, be properly obtained through practice on the lifeless body, a fact which almost all of those who have been pioneers in these fields of work have emphasized.

With these ideas in mind, our present course of operative instruction was first started upon living animals, stray dogs being used for the purpose, and so far as our opportunities permitted, all of the formalities, that would be observed in regard to a patient admitted for treatment to the surgical wards of the hospital, have been followed. Clinical histories, of which examples will be shown you, have been kept on regular hospital history sheets ; the effect of the anaestliesia on the pulse and respiration has regularly been recorded ; the detail of the operative preparation both for the staff and patient has been followed; pathological and post-operative notes made; and in case of a fatality, a formal autopsy performed and its results added to the record.

The work has proved so interesting to the instructor and seemingly so acceptable to the groups of undergraduates and graduate students, to whom it has been possible to extend it, that it is gratifying to learn of the,establishment, in several other institutions, of courses modeled on similar lines. Our aim has not been to turn out a multitude of operating surgeons, any more than the aim of the manual training departments in some of our modern schools is to turn out finished cabinetmakers or iron-workers, but rather to teach the proper use of the hands and respect for the materials on which they work, tlirough simple actual problems, so that not only may all understand the way work is done and appreciate good work wlien it is done, but also the few, who are by nature best fitted, may learn of their special aptitude for this particular form of handicraft and be encouraged to continue with it.

After a course of training of this sort and with an acquirement of proper surgical reflexes, a student, when his turn comes, should be found a safe and valuable helper in the hospital operating room where blunders in technique must not


180


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


occur; and furthermore he may with profit to himself be an understanding onlooker at the surgical work of others, an occupation, which, for those who have never taken part in or conducted operations themselves, must be granted to be a comparatively fruitless expenditure of time.

For the carrying out of our plan of work, it has been necessary to assume lesions, for the relief of which operative therapy was appropriate — a stricture of the oesophagus, for example, which called for a gastrostomy of one form or another. And it has been our custom, in order that the students, just entering upon their first year of clinical instruction, might become familiar with actual cases rather than tiieir text-book presentation, for them to select from the hospital records cases that were supposed to represent the clinical condition of the animals presented for operation.

We have endeavored to combine this instruction in operative work with the necessary experimentation of the various laboratories, so that, for example, when a gastric fistula was needed in the physiological department, for the study or demonstration of the gastric secretion, the gastrostomy patient mentioned above would suffice, and thus a double purpose be served, with a possible sparing of animal life. The surgical share, also, in many experimental investigations has been undertaken at the same time that the students are learning how to operate — how to handle the tissues and to work with gloved fingers, how to tie and to sponge, how gauze should be used in " walling off " the peritoneal cavity, how incisions should be made and how closed, and a multitude of other things, not the least of which is the proper feeling of responsibility for the general welfare of the anaesthetized patient.

Though satisfactory enough in its ends the benefits arising from such a course are confined to the class and the preceptor and are entirely at the expense of the animal. There is naturally a feeling of regret in the minds of many — of none greater than our own — that animals, particularly dogs, should thus be subjected to operations, even though the object be a most desirable one and accomplished without the infliction of pain, and did expense permit, we would gladly have used animals with which there is an association of less acute sentiment on the part of all. This feeling in the past few months has been somewhat mitigated by me fact that, learning of our work, the owners of animals actually suffering from maladies of a surgical nature, and maladies which most veterinarians are loth to operate upon, have begun to bring these animals to us for treatment, so that there is promise of a clinic, which may furnish us with enough material to obviate in large measure the need of using normal animals.

The surgical report of some of these cases will be made by Messrs. Beall, Faris, Ortschild, and Thacher and it can be seen why the title of Comparative Surgery has been chosen for this report. In the past the work has been conducted at a great disadvantage owing to oht cramped quarters, and though every effort has been made for the comfort of the animals before and after the operations, not until the completion of the building, now being erected, will it be possible to give


tliem the real hospital care and accommodation which they deserve.


TWO CASES OF H.EMORRHAGIC CYST OF THE THYROID GLAND.

By C. M. F.\Eis.

Case I. — Large tumor of the right thyroid glaiifl.

The patient, a valuable and well-bred, Irish-setter dog, actively used every season for field work, was brought to us for operation by Dr. Cox in March, 1899. On the right side of the neck, in the region of the thyroid, was a tumor measuring on its surface about 8 by 12 cm. (Fig. 1). The time of its first appearance was not ascertainable. The growth has progressively increased in size and of late has greatly interfered with respiration. The mass was very hard to the feel, roundish in outline, with a smooth surface, and so tense as not to impart to the fingers any sense of fluctuation. It was quite movable from side to side, though not



FiQ. 1. — Profile view of cervical tumor in Case I.

in an up and down direction. Pressure against the tumor made the animal breathe with a marked inspiratory effort; but without such pressure and when the animal was quiet, there was no evidence of dyspnoea. The right pupil was contracted.

Operation. — March C, 1899. Ether aufesthesia. Extirpation o\ gland and cyst.

The usual transverse incision (Kocher), with its convexity downward, was made over the tumor. The outer capsule was exposed after division of the platysma and anterior thyroid muscles. The tumor was found to be very adherent, vascular, and its enucleation proved most difficult. It was necessary to divide the right sterno-mastoid muscle and even with this exposure, in the efforts to separate the cyst from the surrounding tissues, it ruptured and several ounces of dark grumous bloodclot escaped. The tissues became so stained that a clean dissection and individual ligation of the groups of thyroid vessels were precluded. Before the mass was finally freed there had been hfeniorrhage from several large vessels that had been divided before they could be recognized and secured with clamps. The enucleation was finally accomplished; the divided muscles were reunited with fine silk and the skin closed with a subcuticular silver suture. No drainage was used. An intravenous saline infusion was given.


Mat, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


181


The animal made an uneventful recovery. The wound healed per primam.

Subsequent History. — The animal lived until the autumn of 1904, four and one-half years after the operation. Death was said to be from old age. His shortness of breath had disappeared after the operation, and for several seasons he proved as useful as ever before as a field dog.

Patliological Repnri. — The specimen is a large roundish thick walled (1 to 2 cm.) cyst, containing a pasty, grumous, brownishred material. Its outer surface shows a somewhat shredded fibrous capsule dver which lie a number of very large bloodvessels. The inner surface of the cyst wall is divided into irregular spaces by numerous trabeculse. On section, the walls are found to be made up of several concentric more or less distinct layers, some of which are fibrous and tough, others more friable, having in places the color and appearance of normal parenchyma. Scrapings from the latter show epithelial cells with large vesicular nuclei. Examination of the contents of the cysts showed cholesterin crystals and degenerated blood-cells.



smooth, almost spherical in outline (Figs. 2 and 3). It gives no sense of fluctuation nor is there any bruit or pulsation.

Considerable interest was aroused as to the diagnosis in this case. The tumor, prominence of the eyes, irregularity of the pulse, nervousness and irritability were suggestive of exophthalmic goitre. Myxopdema was suggested by the change in the nutrition of the skin, the loss of hair, the increase in weight as well as the mental and physical inactivity. The animal however had been spayed and was reaching an age when dogs are liable to show such changes of coat and form.

Operation. — March 12, 1904. Ether anaesthesia. Enucleation of right thyroid and cyst. The operation was conducted as in the former case and almost the same difiiculties were encountered owing to the vascularity of the tumor and the adhesions about the capsule. In spite of all care, the cyst, as in Case I, ruptured during the manipulations of the tumor. Enucleation was finally accomplished. The left lobe of the thyroid was inspected and seemed normal in size. The wound was closed with silver as in the case above. Healing was absolutely without inflammatory reaction and recovery was uninterrupted.

The animal lived for about a year after the operation, when at



Fig. 2. — Anterior view of cervical tumor in Case II.

The microscopical findings will be described below.

Case II. — Large tumor of the right thyroid gland.

A large, thoroughbred, Russian-greyhound bitch, nine years of age, was admitted in March, 1904, with the following history:

She was a house pet and, having been spayed when four years of age, had grown very stout. Her health had been good until the past year when the present tumor started to develop. For several months she has been dull, inactive and irritable. She occasionally snaps when at play with the children, a thing which never occurred before. There has been some muscular twitching. She has grown very fleshy, has lost most of her hair, and the skin has become dry and scaly. There has been considerable distress for breath, with sighing and wheezing sounds particularly noticeable during her sleep, which is very restless.

Examination.— The pulse rate is fiO; the beats irregular in rhythm and quality. No definite exophthalmus is present though the eyes have the visual prominence characteristic of the hound. The right pupil is much larger than the left : both react normally to light. Her skin is rough and scaly though there is no eruption suggesting a cutaneous disease. She has lost most of her coat. She is very fat, and must weigh nearly 100 pounds.

On the right side of the neck, in the region of the thyroid gland, is a swelling about the size of a base-ball; its surface is


Fig. 3. — Profile of neck in Case II. Owing to the extended position of the neck the tumor is less prominent than it otherwise appeared.


her owner's request and owing to her poor physical condition, she was chloroformed. Though for a time after the operation her respiration had seemed to improve and her tremors to be less, the general nutritional state was not altered. The condition of the skin became worse; a cataract developed in the right eye. There were distressing attacks of paroxysmal dyspnoea with an extraordinary depression of the intercostal spaces during the inspiratory act. Thyroid extract was administered for some time before her death without bettering her condition.

Pathological Note. — The gross appearances of the tumor removed at the operation differed but slightly from those of the tissues described under Case I. There is the same thick walled cyst, which, when collapsed and after hardening, measures 8 by 6 by 4 cm., and which contains the same dark reddish, friable, grumous material. The surface of the cyst wall on section presents a laminated appearance, with superimposed fibrous layers between which can be made out, in some areas, narrow strips of thyroid parenchyma. Several small cysts, the larger of which measures VA cm. in diameter are to be seen in the surface of the section. No parathyroids can be found.

Microscopic Examii ation of the Hardened Tissue.— The wall of


182


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


the cyst is for the most part made up of dense fibrous layers, between which, in places are zones of glandular substance. The cyst content is made up of a granular, faintly staining mass in which the shadows of blood corpuscles and cholesterin crystals are to be made out. Organization of this clot has begun to take place in some areas along the inner wall of the cyst, where new formed granulation tissue is more or less abundant. Such of the parenchyma of the gland as is still preserved, is altered from the normal. The vesicles, which are still recognizable as such, by their structure and colloid content, are much deformed, most of them being compressed into flattened figures that lie concentric with the curved layers of the cyst wall. Others of them have a crenated outline from the irregular incurving of the epithelial lining. Some of them are partly filled with blood and contain crystals as well as desquamated epithelial cells. The epithelium which remains, is for the most part fairly typical in appearance, though the cells seem less high and contain less protoplasm than normal. In some areas the parenchymal cells are so massed as to have lost all resemblance to their proper glandular arrangement. There is no colloid in these areas, and they are traversed by blood-vessels having extremely delicate walls.



Fig. 4. — Slightly magnified photographs of three cross-sections of the hardened left thyroid gland removed at autopsy from Case II.

The letter A is placed near a hsemorrhagic cyst filled with recent clot; B is near a large intramural parathyroid body; C near a partially absorbed clot, the thick wall of which consists of compact parenchymal cells.


Autopsy. — February 10, 1905. On opening the body the musculature was found to be pale, the panniculus abundant. The abdominal and thoracic viscera were for the most part normal. The lower intestine was injected and on opening the bowel, a haemorrhagic enteritis extending from duodenum to anus was found. The ovaries were absent; the uterus much atrophied. A large cyst was present in the lower half of the left kidney. These organs, as were the adrenals, spleen, liver, pancreas, and stomach, were otherwise normal on section. There was no glandular enlargement. The heart and lungs were normal except for the presence of a few calcareous nodules scattered throughout the latter. There was no thickening or sclerosis of the aorta. The brain and cord were normal aside from the thickened and adherent membranes characteristic of an old animal.

A careful dissection of the neck was made. No remnant of the thyroid was found on the side (right) of the old operation; nor


were there any parathyroids to be found. No accessory thyroids were found in the mediastinal spaces.

The remaining thyroid gland, on the left, was found to be much larger than normal. It measured nearly 6 cm, in its long axis, and its transverse diameters on section were 2 by IM: cm. The section showed numerous small cysts, the largest measuring about 5 mm. across, and containing a small blood-clot (Fig, i, A). One large parathyroid was present on the surface, equatorial in position, and the section subsequently showed another buried in the substance of the gland (Pig, 4, B). There were no polar parathyroids to be found. Microscopical examination of the liver, spleen, kidney, adrenal, and intestine added nothing to the knowledge gained by the gross appearances.

Sections of the thyroid showed alterations varying all the way from the normal, or nearly normal, to the profound changes that had been found in the cyst wall of the gland extirpated the year before. The various compartments of the gland were fairly well



Fig. 5. — Microphotograph of section on the edge of a small organizing hfemorrhagic cyst (left upper corner). Showing compression of neighboring vesicles and hypertrophy in adjoining part of gland.


outlined by delicate fibrous trabeculae. In some of these compartments the colloid containing vesicles were quite well preserved and lined by a single layer of low epithelium. More commonly, however, the epithelium was infolded and the cells higher in form, while between the vesicles there was a marked cellular proliferation (Fig. 5).' This process had gone on in some places to such an extent that in some fields the infolding was so extreme and the multiplication of cells so great, that with the absence of colloid almost all trace of glandular arrangement was lost (Fig, 6), The appearances were closely akin to those seen in experimental thyroid hypertrophy or in advanced stages of exophthalmic goitre.

In some of the compartments of the gland (there were four or five of them), hemorrhages had occurred (Fig, 4, A) so that it

' This, as well as the following microphotographs, has kindly been taken for us by Mr. T. M. Wright, Jr., a simple microscope and ordinary camera being used for the purpose.


Mat, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


183


was possible to see in miniature just what had talien place on a large scale in the haemorrhagic cyst removed at operation. The extravasation seemed to have occurred in the central part of the lobule. This had distended and led to a thickening of the lobular fibrous capsule within which the parenchymal cells were massed and crowded together as a lining zone. Occasionally a flattened vesicle was to be seen containing colloid but for the most part the glandular structure in the zone lining the clot was completely lost. In two of the cysts, apparently those of longest standing, granulation tissue was growing out into the clot and large epithelioid cells filled with pigment were interspersed among the inner layer of parenchymal cells. In two of the cysts no effort at repair had taken place, the clot being sharply defined against the compressed glandular acini of the lobule and less evidence of the neighboring hypertrophic change had taken place in these instances.

A large parathyroid was found embedded in the substance of the gland near its middle. (Fig. 4, B). This, as was the case



-Edge of cyst shown in gross in Fig. 4, C. of compact parenchymal cells.


Showing zone


with the surface parathyroid, showed no apparent alteration from the normal.

Discussion.

Pathological changes in the thyroid gland of dogs are closely analogous to those occurring in man which are better known since they have been subjected to more careful study.

Aristotle, Pliny, Galen, and Aetius are said ^ to have mentioned swellings, which appear to have been goitres, in the necks of animals. Pliny even suggested that the animal's water supply might be responsible for the condition; an hypothesis supported by more recent writers, some of whom without success, have essayed to produce the malady in normal animals by administering in abundance the salts cantained in the water from those localities where the disease is most eom


'A. T. Sloan, Goitre in Animals. The Lancet, Lond., 1887, Vol. I, p. 1802.


mon. Particularly in certain parts of Europe, goitre is of as common occurrence in the lower animals, more especially horses and dogs, as it is in man himself. It is known in nondomesticated animals, as well. One writer is said to have described a new species of antelope, the distinguishing feature of which was a prominence of the neck which appeared with striking constancy.

The prevalence of goitre is especially noticeable in certain localities, whether from hereditary or geographical influences. Adami ' has called particular attention to this in describing tlie so-called goitre regions of Canada and the continent of Europe.

As the pathological and setiological factors seem to be so closely akin in man and animals, and as the veterinary literature on the subject is difficult of access, we will not limit ourselves to a consideration of the comparative pathology alone.

Simple cysts, as is well known, are of common occurrence in parenchymatous enlargements of the thyroids. The hemorrhagic variety however is comparatively infrequent. Cysts, apparently of hEemorrhagie origin, have been found by Dr. Bloodgood among the thyroids from the surgical department. But no instance of a large encysted clot such as occurred in our two cases has been met with. They are, however, not unknown. Thus, Bradley ' has described cases from Dr. Shepard's service in the Montreal General Hospital, some of them the e.xact clinical and pathological counterpart of our canine cases.

Many conjectures have been advanced in explanation of the way in which these hsemorrhagic cysts are produced. Though trauma may play a part, the predisposing elements are undoubtedly attributable to vascular changes. Thus, Witzel, noticing the ease with which the vessels of the thyroid were torn during operations, suggested that some structural alteration in the vessel wall, possibly a degenerative change, might be responsible for the haemorrhage. Earner noticed that the ruptured vessels sometimes tore longitudinally. Budde observed that, in cystic thyroids, the smaller arteries showed a connective tissue increase in the sub-endothelial layer without an increase in the intima; also that a degenerative process was demonstrable in the elastica, expressing itself as a separation of the internal membrane of Henle. This was often associated with deposits of calcium salts and as the process occurred in subjects too young for sclerosis, it was considered a3tiologically significant in explaining the fragility of tlie vessels described by Witzel and Earner.

Konig, in speaking of the heeraorrhagic cysts, calls attention to the extreme dilatation that may occur in the vessels of the thyroid — the so-called Struma aneurysmatica, — in which the vessels may form cirsoid aneurysms in the parenchyma, the veins themselves forming small cysts. Owing to an increase in the size of the vesicles, the supporting connective tissue


" Adami, On etiology and Symptomatology of Goitre. Montreal Medical Journal, 1900, Vol. 29, p. 1.

' W. I. Bradley, On Haemorrhagic Cysts of the Thyroid Gland. Journal of Experimental Medicine, 1896, Vol. I, p. 401.


184


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


network, in wliich the blood-vessels run, is pressed upon with resultant nutritive changes. The walls of the vesicles become weakened, coalescence takes place between them, and in this way colloid cysts result and may increase to almost any size. Secondary hemorrhage, occurring through the weakened and perhaps varicose vessels, would give the type of cyst and cystic content that characterizes these cases. The cysts, however, may not always be lined with thyroid epithelium, as might be expected if this were their method of formation, and Wolfner has on this ground been led to reject this theory in consequence. An extensive hagmorrhage, however, might easily spread to the capsule of the gland and only leave a trace of the original parenchyma as a shell on one side of the cyst the walls of which become gradually thickened by new formed tissue. This was the condition found in the two large cysts of our dogs, but in the small haemorrhagic cysts in the left lobe of the last case, the clots were entirely surrounded by the compressed interlobular parenchyma. It is noteworthy too that in this gland there were no non-haemorrhagic cysts whatever. We are inclined to agree with Bradley in the view that the cysts originate from the rupture of the intralobular blood-vessels primarily, and that the hsemorrhage may break into or separate and compress the interlobular vesicles.

The contents of these cysts may vary from pure blood mixed with thyroid secretion to dark grumous material, such as we have observed, containing pigment, cholesterin crystals, fat globules, and coagulated necrotic material. Papilloma have been described as occurring within the cysts, but Bradley thinks they are due to irregular infoldings of the walls rather than to neoplastic formation. The great increase in size that takes place in some cases is probably due to repeated hasmoi-rhages. Doubtless the epithelium lining the cyst ceases to secrete, is soon replaced by granulation tissue and plays no part in the tumor growth.

These cysts, when small, may become cicatrized through organization of the extravasated blood or the clot may remain in an inspissated condition for many years, as in our two cases, with a possible increment from time to time through fresh bleeding. In long standing cases the walls may become calcified or, according to some reports, even ossified. Suppuration of the contents may follow an infection. They may he found in either lobe and, indeed, there are reports of their occurrence in the accessory lobes of the thyroid. In one case of this sort, the writer, Pollard, thought the cyst had occurred secondary to a papillomatous growth.

The interesting complex of symptoms, in our Case II, had it not been for the animals old age, might have been mistaken for the clinical manifestations of myxoedema, for they closely resembled the symptoms shown by an animal after an experimental extirpation of both thyroids, a physiological sufficiency of parathyroid tissue having been left intact. The inefiBcacy of the treatment with thyroid extract, however, made this improbable and the post-mortem findings showed that the remaining gland possessed an abundance of actively functionating parenchyma. The changes in this remaining


lobe, aside from those secondary to the cystic processes, were closely akin to those brought about by physiological hypertrophy, such as Dr. Halsted " has described, and wliich takes ])lace in the portion of gland remaining after partial extirpation.


A REPORT OF TWO CASES OF UTERO-VAGINAL PROLAPSE.

By H. C. Thacher.

Case I. — Acute descensus of uterus, bladder, and vagina during parturition.

The patient, a large animal, of mongrel fox-hound type, was operated upon as an emergency case, November 1, 1904. She had received, three weeks previously, when early in her pregnancy, cancer transplantations in both inguinal breasts from the first of Mr. Ortschild's series of tumor cases. The wounds healed per primam and she had since been well and running free in the yard.

Present Illness. — So far as can be told, the animal reached her full term of pregnancy three days ago (October 29), when by her actions she was supposed to be in labor. She did not, however, succeed in delivering her pups and, seemingly as the result of the frequent efforts at expulsion, an cedematous mass began to protrude from the vagina. This prolapse has increased greatly in size and has apparently implicated the bladder, judging from the frequent efforts to micturate.

Examination. — The patient is a full grown, well-nourished animal with a greatly distended abdomen and lactating breasts. She looks sick, shivers almost constantly, and crouches frequently in a straining posture. Her pulse and respiration are rapid.

Protruding from between the labia majora is a large, pendent, rounded mass, measuring about 12 by 6 by 8 cm. Its surface is smooth, moist, cold to the touch; and the fundus of the protrusion is purplish red in color, suggesting almost complete strangulation. On the dorsal surface of the tumor appears the ringlike external os of the uterus. The tumor fluctuates on palpation. It does not sjem to be painful or tender.

The animal was prepared for immediate operation as it was conjectured that one of the pups had become fixedly engaged in the superior strait.

Operation. — November 1, 1904. Ether. Reduction of prolapse: total hysterectomy.

On opening the abdomen, an enormous pregnant uterus was exposed. This was drawn out of the wound; the broad ligaments were divided and the two horns liberated. The lower part of the right horn was found to be softened and gangrenous. It was torn during the manipulations, disclosing a macerated, foulsmelling foetus whose head was engaged in the pelvic inlet. The uterus contained eight other living, full-term puppies. By exerting traction upon the body of the uterus, aided by pressure against the prolapse externally, the latter was gradually reduced. Not until this was accomplished did the bladder become visible within the abdomen.

The uterus was then amputated as near the vagina as possible and the stump, after inversion and suture, was ventrally fixed in the parietal wound during its closure.

The animal survived the operation only twenty-four hours. The chart of pulse and respiration, kept during the anresthetization, shows that the operative procedure was badly borne.


° An Experimental Study of the Thyroid Glands of Dogs, with Especial Consideration of Hypertrophy of this Gland. The Johns Hopkins Hospital Reports, 1896, Vol. I, p. 373.


May, 1905.]


JOHNS HOPKINS HOSPITAI. BULLETIN.


185


Autopsy. — November 2, 1904. Nothing was found at the examination to account for death, beyond a slight localized peritonitia about the stump of the uterus and a considerable degree of hydronephrosis. The ureters and pelves of the kidneys were all dilated. There was no deformity of the pelvis. No cultures were taken.

Case II. — Recurrent vaginal prolapse, unassociated with pregnancy.

An animal of Irish-setter type, two years of age, was admitted for treatment January 5, 1905. with the complaint that an irreducible mass was projecting from the vulva.

Past History. — She has been a pet dog; has always been well and had the best of care. Owing, possibly to lack of regular exercise, she has grown very heavy. She has never been pregnant. In July, 1904, she was lined for the first time and subsequently suffered from a prolapse of the vagina. The protrusion was successfully replaced by her owner and did not reappear for six months.

Present Attack. — About three weeks ago, without assignable



Fm. 7. — Recurrent vaginal prolapse; condition before second operation.

cause — other than that she was at the time in heat — the prolapse recurred. The protrusion has resisted several forcible attempts at replacement and has gradually increased in size. It is a constant annoyance to the patient though it has seemingly in no way interfered with her health or activity.

Status Prusens. — The patient is a large well nourished bitch, weighing between 15 and 20 kilograms. Her general condition is excellent and aside from the local trouble, the examination proves negative.

Projecting from between the enlarged labia majora is a smooth, tense-looking, rounded mass, about 25 cm. in circumference and 7 cm. in length (Fig. 7). Upon the upper and posterior aspect of the protrusion lies the opening of the inverted vagina. The cervix uteri cannot be reached by the finger introduced within this opening. The greater part of the protrusion is covered with a somewhat congested, granular and thickened mucous membrane. On the lower aspect of the mass — that which comes in contact with the ground when squatting — there is a large superficial ulceration covered with a greyish slough. The tumor has a tough, boggy, (Edematous feel and is cold to the touch though its circulation seems good. The orifice of the urethra is drawn down into view on the anterior aspect of the neck of the tumor.

Diagnosis. — Prolapsus vagina' et vesica;.


Operation /.— Jsmuary 6, 1905. Preliminary morphia; ether anaesthesia. Reduction of prolapse. Abdominal hysterectomy. Ventral fixation of stump.

While the animal was being cleaned up for operation, an effort was made to reduce the prolapse; this was unavailing even with complete muscular relaxation under the anaesthetic and with the hind-quarters elevated. The abdomen was opened by an 11 cm. intermuscular incision, through the inner margin of the right rectus. After exposure of the uterus, a long, steady traction upon its body brought about a partial reduction of the prolapse, the manipulations succeeding in drawing into the abdominal cavity the bladder whose walls were very much congested. Complete reduction, however, was only attained after combining pressure from without with the traction upon the uterus. After the reduction the uterus was drawn well into the wound, was amputated close to the external os and its stump was amputated and inverted with mattress sutures. The broad ligaments were then divided, the uterine horns freed from their ovarian attachments and the entire uterus removed.

The abdominal wound was closed in layers, the stump of the vagina being drawn up and securely fastened to the posterior sheath of the rectus in the hope that this would suffice to prevent a recurrence of the prolapse. The relaxed vaginal canal was packed with iodoform gauze.

Post-operative Note. — On the following day the prolapse was found to have recurred iu its original form and was, if anything, even larger than before. There were otherwise no complications following the operation. With the exception of a single slight stitch abscess, the abdominal wound healed per primam.

Four weeks later a second and successful operation was conducted, as follows:

Operation //.—February 3, 1905. Preliminary morphia; ether anaesthesia. Combined abdomino-vaginal operation. Amputation of prolapse by Whitehead's method for rectal prolapse.

The abdomen was reopened in the line of the original incision. The stump of the vagina was (reed from its attachments to the abdominal wall; the bladder was, this time, found in place in the abdominal cavity. On catheterizing the urethra, it was ascertained that a loop of this canal was drawn down with the prolapsed tissues into the neck of the tumor. By introducing a straight catheter into the bladder it was possible to place the urethra in a position where it was unlikely to be injured in the proposed operation.

An incision was then made encircling the neck of the prolapse about at the junction of the vulvovaginal mucous membrane and just so as to escape the urethral orifice. While the tumor was grasped and drawn away from the body, this circular incision was gradually deepened with the knife and by blunt dissection— the large vessels being secured as they were encountered — until the sub-mucous coat of the non-inverted portion of the vaginal canal was reached. The vagina, at this situation was then amputated section by section, as its edges were sutured securely to those of the vulval side of original incision. The abdominal wound was then closed as before with fixation of the vaginal stump in the parietal wound.

Convalescence was without incident. As after the first operation the ventral wound healed with a single stitch abscess. There has been no recurrence of the prolapse.

Pathological Report. — The specimen consists of a piece of tissue, 10 by 7 by 4 cm., roughly ovoid in shape and obliquely traversed by a lumen about 2 cm. in diameter. The tissue is firm and elastic in consistency. The outer surface is, for the most part, covered with mucous membrane which passes into the lumen above described. The surface is brownish red in color, somewhat granular and at one point slightly ulcerated. Within the lumen the mucous membrane is pink and smooth. On section the tissue


186


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


is found to be very cedematous and somewhat vascular. It consists of a meshwork of grayish, semi-translucent bands and fibers, the majority of which seem to radiate from the lumen. The sub-mucosa is dense and thickened. The mass weighs 125 grams in its present shrunken state.

Discussion.

Obstetrical complications, as illustrated by the first of these cases, are very conmion in cloinestic animals. Upon their occurrence in cattle and horses there is a large literature." It is quite common for animals to die in labor without delivery. This is especially true of dogs.

The acute prolapses, which occur before and during parturition, are more frequently reported in the veterinary literature dealing with cattle — more attention being paid to this animal owing to its greater commercial value. According to Vennerholm,' it is of common occurrence in stall-fed and milch cows, particularly in animals standing in stalls with a floor sloping backwards for drainage. In pasture free animals it is comparatively rare. Relaxation of the pelvic floor and an extra large sized pelvic outlet" are predisposing factors. An unusually heavy uterus is also recognized as a causal factor and may have played a part in producing the lesion in the first of our canine cases.

As a rule, the prolapse in cattle appears only when the animal is recumbent and reduces spontaneously when the animal takes a standing posture. Rarely does the condition seem to offer any serious obstruction to labor. The usual veterinary treatment is an operative one in case the prolapse does not spontaneously disappear after labor. The procedure consists of the use of rnetal clamps to close the labia and prevent the descent of the tumor.

Kitt ' mentions the fact that prolapse is common — especially in animals dying from anthrax or black-leg — as an agonal occurrence.

Case II illustrates a condition much more rare. Some cases of prolapse unassociated with pregnancy, have been reported in young animals — colts — suffering with " colic." '" Reports of cases in which the bladder has formed part of the prolapse are still more uncommon. Franck recognizes two main types — one with simple inversion of the bladder, the other with its extrusion through the torn vagina. Very little attention seems to have been paid to complications of this nature which have arisen in dogs and the literature upon the subject is scant and inaccessible."


' Franck, Thierarzliche Geburtshilfe. Berlin, 1901. DeBruin, Geburtshilfe beim Rind. Wien u. Leipsig, 1897.

'Vennerholm in Bayer, and Prohner's Handbuch der thierarzliche Chirurgie und Geburtshilfe. Wien und Leipsig, 1897.

" Streble, Journal of Comparative Pathology. 1901.

•Kitt, Pathologische Anatomie der Hausthiere. Miinchen, 1901.

"Koepke, Berliner thierarzliche Wochenschrift. 1892.

" Since writing the above report a third case of prolapse of the nature of this supposedly more rare type, has come under our observation.


A REPORT OF EIGHT CASES OP CANINE NEOPLASM.

By J. P. Ortschild.

Case I. — Adeno-carcinoma of breast with glandular metastases.

A small, longhaired, yellow, Skye-terrier bitch, sixteen years of age, a nullipara and a house-pet, was admitted to the clinic in September, 1904.

History. — For the past six years the patient has been kept for the most part within doors and under close observation. Not until two months ago, was a small hard mass noticed in one of the breasts. It has been rapidly increasing in size and has become ulcerated. There is no history of traumatism.

Examination shows a very old, feeble, emaciated and inactive dog. The mucous membranes are pale; only a few loose teeth remain.

In the right, most posterior, inguinal breast, there is an ulcerating, f ungated growth, the size of a hickory nut (Fig. 8). The ulcerated surface has, upon one side, an overhanging edge, but



Fig. 8. — Tumor of right inguinal breast of Case I.

there is nowhere any definite undermining of the epithelial margin. The surrounding skin is darkly pigmented. On palpation the tumor is firm and has an irregular, nodular outline. The moist ulcerated surface is reddish in color, with some gray streaks made by superficial sloughs. The nipple does not seem to be involved in the growth, though it is somewhat retracted.

In the subcutaneous tissue to one side of the tumor are three or four hard, freely movable, discrete nodules, presumably involved glands.

Operation. — October 7, 1904. Morphia; ether. Amputation of breast.

The breast, the tumor, the glands and the neighboring fat of the inguinal region were removed in one piece, and though the surface of the tumor had been ulcerated, an effort was made to secure primary union and the wound was closed without drainage.

Subsequent history. — The wound broke down in large part and closed slowly by granulation. Soon after the operation an ulcer appeared at the angle of the mouth. This ulcer proved phagedenic, spread rapidly and assumed the clinical appearance of a cancrum oris (noma), finally involving the gums and the adjoining cheek. The patient died from this infection two weeks later.


May, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


187


Autopsy." — October 21. There were no visceral metastases; the abdominal and thoracic organs were practically normal. The eroding ulcer of the mouth had eaten its way into the nasal cavities, which were filled with pus. No cultures were taken.

Pathological Note upon the Tumor. — The mass on section shows a rather homogenous surface, which is slightly moist, of a pinkish gray color, and is flecked with yellowish points, which can easily be scraped off with the blunt edge of the scalpel. The glands are quite deeply pigmented; the deposition of pigment being most marked in the centre. Their appearance led to an operative diagnosis of melanotic sarcoma.

Histologically, the primary growth is found to be in reality a carcinoma. Its most striking feature (Fig. 9), is that of a malignant adenoma, with a stroma infiltrated by glandular elements. The stroma, however, is very cellular, containing large ovoid cells full of brown pigment granules. There are many cysts lined by high epithelium, some of them containing papillomatous growths.

The large metastatic nodule has similar characteristics, the



Fig. 9. — Low-power magnification. Showing character of adenomatous growth in primary tumor.

cystic and adenomatous elements predominating (Fig. 10). In the lymph glands containing early metastases, the adenomatous structure is not apparent, the cells making up the area of newformed tissue, being for the most part similar to the pigmented (mesoblastic?) cells of the primary growth (Fig. 11). Diagnosis: Adeno-cysto-carcinoma.

Transplantations from the tumor, immediately after its removal on October 7, were made into three dogs, one of which was practically of the same strain as the original host. Pieces of tissue were transplanted in one animal into the liver and between the transversalis fascia and peritoneum; in another case into the two inguinal breasts, both of which were supposed to be hypertrophied (in reality, as subsequent observations showed us, the prominence of the mammae was due to underlying inguinal herniae — compare Mr. Beall's report) ; in the third, a pregnant


"Owing to the length of Mr. Ortschild's report, the postmortem notes, as well as the histories of the animals that were used for experimental transplantation, must necessarily be greatly abbreviated. It is hoped that his interesting observations may be given more in detail in a later communication. (Gushing.)


animal, a sub-peritoneal as well as a mammary inoculation was made. A portion of the original tumor, as well as a fragment of an involved gland, was used for transplantation in each animal.



Fig. 10.— .Metastatic


uodule; field showing characteristics.


glandular and cystic


The subsequent history of these animals cannot be entered into here, other than to say, that the third of them is Case I, of Mr. Thacher's series, and that the second was found dead, six months



Fig. 11.- — Lymph node with very early marginal metastasis.


later, with an increase in size of the piece of tissue transplanted from the tumor into the right breast, and with enlarged and pigmented lymphatic glands in the inguinal region of the opposite side, namely, that into which the fragment of glandular metastasis had been transplanted.


188


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


Case II. — Mixed (teratomatous) tumor of the breast icith multiple metastases.



Pig. 12 (Case II). — Showing situation of primary growth and the palpable metastases. Site of nipples indicated by solid black dots.

A small, gray-haired, Skye-terrier bitch, was admitted January 16, 1905. She had been a vagrant animal and no history was



Fio. 13. — Photograph after patient was shaven in preparation for operation.

obtainable. She was an old dog, though seemingly in good condition; not cachetic nor anaemic. She was evidently a multipara from the appearance of the nipples.


Special Examination. — Scattered about the ventral surface of the thorax and abdomen, are numerous hard subcutaneous nodules, varying greatly in size (Pig. 12). The largest, evidently the primary growth, occupies the second left thoracic breast, on a level with the costal margin. It is made up, seemingly, of a conglomerate mass of separate tumors, forming in all an irregular growth about 5 by 4 cm. in length and breadth, and 3 cm. in thickness. It is freely movable on the underlying tissues; is covered by thin, freely movable skin, under which run considerably dilated vessels. The nipple is not adherent nor retracted. The growth is not sensitive on pressure and is very hard to the feel. From this main growth, a chain of nodules, varying in size from a buckshot to a large pea. spreads across the mid-line onto the right side. Though some of these nodules are fused, they, for the most part, are individually movable. The chief collection



14. — Same as Fig. 13. To show prominence of primary tumor and projecting nipple.


of them is clustered into a prominent tumor, almost as large as the primary growth (Figs. 13 and 14). A chain of these nodules, extending up toward the right axilla, can be palpated through the skin of the thorax. Higher up on the left side, above the axillary nipple, can be felt a similar chain. Two other large clusters are present, one over the left pectoral region, and another over the left inguinal breast, which was supposed to be hypertrophied (in reality overlying an inguinal hernia). There are a number of other individual nodules all of which are firm, but without the stony hardness possessed by the primary growth. No masses are palpable within the abdomen.

Operation. — January 16, 1905. Morphia; ether.

Through three separate incisions, the main tumor, together with the second left breast and the surrounding tissue, the mass of discrete nodules, together with the adjoining second right breast, and the larger one of the individual tumors, were removed. The wounds were closed without drainage.

Pathological Note. — The primary tumor presents, in gross, an irregular, nodular surface like that of a compact bunch of grapes. The surface is of a pinkish white color with some few points of haemorrhage. The rounded nodular projections are smooth and


May, 1905.]


JOHNS HOPKINS HOSPITAL BULLETIN.


189


glistening. The mass is firm and rock-like in consistency. On section, bony resistance is met with, the knife penetrating only with the exertion of considerable force. The .surface of the section shows an outer shell consisting of a layer of cancellous bone, varying in thickness from 1 to 2 cm. Radiating from this shell, into the substance of the tumor, are delicate bony trabeculae, visible to the naked eye. In the central portion are irregular islands of non-calcified tissue. These islands are tor the most part, whitish-gray, more or less translucent, and made up of soft tissue. Cartilaginous areas are to be made out.

The metastatic mass and the discrete nodule that were removed, resemble one another on cross section, very closely. They present a very cellular and granular appearance, with a more translucent cortical zone and a dark, pigmented center or medulla. No bony trabecuUe or cartilage can be detected. Some of the nodules are evidently lymph glands containing macroscopical areas of new growth.

Microscopically, the tumor shows, in addition to the bony trabeculae and cartilaginous areas, that are discernible with the naked eye, that the cellular areas are most diverse in structure



Fig. 15. — Field from primary tumor of Case II; showing bony trabeculip, separated by a strip of fibrous tissue from an adenomatous area with cyst formation.


(Pig. 15). Some of them are of a pure adenomatous type; others resemble carcinoma simplex. There are fields of closely packed, large, and small round epithelial cells, and in places the loose meshwork resembles embryonic connective tissue. In other places the tumor shows true osteoid tissue. The lamellae of the bone are uniform, have no Haversian systems, and are lined by numerous osteoblasts. The spaces between these lamellae are filled with a meshwork of spindle cells in which are also found large cells resembling epithelial cells. Several areas show squamous epithelium. In many places there is no sharp demarkation between stroma and epithelial cells, one being invaded by the other. In the metastases, the neoplastic elements are mainly adenocarcinoma (Fig. 16), with no cartilage or bone. Were it not for the cartilage and bone, the tumor could be correctly called an adeno-carcinoma.

Transplantations and Injections. — An emulsion of the original tumor was made immediately after the operation by grinding fragments of it in a mortar with sterile salt solution. The pulp thus obtained was used for injections. Portions from the metastatic nodules were similarly treated. This method was fol


lowed, owing to the success that has attended it in the transplantation from mouse to mouse of a malignant carcinoma simplex through many generations by Drs. Clones and Gaylord at the Gratwick Laboratory.

Inasmuch as it was surgically impossible to remove all of the involved nodules from the original host, it was considered justifiable to use this dog for control inoculations from her own tumor. Before she came out of the anajsthetic, therefore, a small portion of the original bony tumor was aseptically inserted under the skin in the right axillary region. A small piece from one of the involved glands was similarly implanted on the left. In addition, 2 cc. of the emulsion from the gland were injected under the skin at the suprasternal notch and a similar quantity of the primary tumor emulsion into the subcutaneous tissue between tlie scapulfe. Corresponding implantations and injections were made into four other animals. One of these animals, a very old dog, died of an intercurrent infection two weeks later and before any macroscopical growth could have occurred; but in the subcutaneous tissues of this animal, at the site of the inoculations of the glandular emulsion, there were found, microscopically, numerous clusters of viable epithelial cells. The other four of the series



-Metastasis from Case II. Field showing pure adenoma with cyst formation.


were killed about five weeks later by a vicious bull dog that was inadvertently let into the yard. The bodies were too much mutilated to be of any pathological value, though a fresh series of transplants was made from the remaining tumors of the original host.

C.\sE III. — Cysto-adenoma of the breast with metastases.

A small, short-haired, very stout, almost toothless, decrepit and inactive, old, black-and-tan bitch was admitted for operation, January 1(1, 1905. She was a vagrant dog without a history. The condition of her nipples evidenced previous pregnancies.

Examination. — In the second left breast, there is a firm, oval nodule, about the size of a pea. There is no retraction of the nipple nor any discharge from it. A chain of three distinct nodules, similar to the above, is present in the second right breast. The nipple is not retracted but discharges a thin, yellowish fluid on pressure. In the third left breast, there is an indistinct mass of very firm tissue, suggesting matted glands. In the third right breast, there is a large oval mass, evidently the primary growth, 2 cm. in length by 1% cm. in breadth and 1 cm, in thickness. This is firm, though not of bony hardness, freely


190


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 170.


movable, not adherent, circumscribed and irregularly nodular. The inguinal breasts are free from nodules but prominent owing to small underlying inguinal hernice.

Before the patient was subjected to operation, she died from a phagedenic buccal infection that seemed to originate in the gums about her few remaining and diseased teeth.

Autopsy. — January 29, 1905. The largest tumor, upon removal, is found to be irregularly nodular, smooth, encapsulated, and somewhat elastic in consistency. It is generally light in color, mottled with white and dark iirown areas. The surface, upon section, is granular and shows the same mottled appearance seen on the outer surface. The metastases have the same general aspect as this primary tumor.

The examination was otherwise negative, except for the presence of calculi in the bladder and urethra and the extensive ulceration of the mouth.

Microscopic examination shows the tumor to be divided into compartments by fibrous bands radiating through it from the capsule. Except th.it there are no bony or cartilaginous ele


PiG. 17. — Section of tumor of Case III. Showing the more cystic portion of an adenomatous field.

ments discernible, the general structure of the growth is not unlike that found in Case II. The predominating type of tissue is adenomatous. This is cystic in places (Fig. 17). The cysts, some of them very large, are lined by high columnar epithelium and in many cases contain papilliform ingrowths. Many of the cysts — and these have a lower form of lining epithelium — eontain a homogenous mass of waxy looking secretion. Some of the areas are densely cellular, having the character of spindle-cell connective tissue. But even in these densely packed fields there are to be made out structures resembling epithelial glands.


Case IV. — Mixed (teratomatous) tumor of the breast with metastases. Lipoma.

A valuable, black and brown, Gordon-setter bitch, 8 years of age, was brought in by her owner, February 3, 1905.

History. — Until the present trouble developed, she had been a strong and healthy dog, used for active field work. She has had five litters of pups. The last litter was whelped nine months ago. When the pups were a month old, one of them bit the patient in the most posterior right inguinal breast. The breast became sore and a short time afterwards she developed, what her owner calls, " a milk breast." The mass remained small and did not


become particularly noticeable until four months ago, but since then it has been enlarging rapidly.

Examination. — The animal has a glossy coat and seems in excellent general condition. In the posterior inguinal region of the right side, between the last two breasts, there is a large irregularly oval mass (Fig. 18), measuring 10 by 7 by 8 cm. The tumor hangs pendent from the abdomen and is freely movable over the underlying structures. The overlying skin, though not adherent, is somewhat thinned out and injected; and at the most dependent part has become abraded leaving a superficial area of ulceration about 4 cm. in diameter. The mass is irregularly, coarsely nodular, for the most part very resistant to pressure, though having several areas which are less firm and suggest the elasticity of tense cysts. The nipples are not retracted nor is



Fro. 18.— Right insuiual Uiinoi- in Case IV.

there any discharge from them. The inguinal glands are palpably enlarged on this side.

In addition, there is a small mass under the skin of the left pectoral region, oval in shape and about 3 cm. in diameter. It is lobulated, firm, freely movable under the skin, and not adherent to the tissu