Talk:The Johns Hopkins Medical Journal 8 (1897)

THE PRESENCE IN THE BLOOD OF FREE GRANULES DERIVED FROM LEUCOCYTES, AND THEIR

POSSIBLE RELATIONS TO IMMUNITY.*

By Wm. Royal Stokes, M. D., and Arthur Wegefarth, M. D.

[From the Bacteriological Laboratory of the Health Department of Baltimore.]

I. — Free Granular Bodies in the Blood.

H. F. Miiller,' an assistant in Nothnagel's clinic in Vienna, has recently described certain "small, generally round, colorless granules," which he finds constantly present in the freshly-drawn blood from healthy and diseased persons. These granules are readily distinguishable from blood plates.

We have been able to confirm Mtiller's observation by the examination of numerous specimens of blood taken from human beings and certain of the lower animals. Since some of our conclusions are different from those drawn by Miiller, we shall first present an abstract of his work and then the results of our own experiments.

Miiller always found the above-mentioned granules in fresh human blood, and by means of their small size he was able to differentiate them from red blood corpuscles, leucocytes and blood plates. He describes them as small, round, colorless bodies, about the size of the finest fat particles, and is quite sure that they are normal constituents of the blood and not foreign matter introduced through accident. His attention was first called to these granules by observing many small bodies resembling mici'ococci free in the plasma of a case of

• Read before the Johns Hopkins Hospital Medical Society,

October 18th, 1897.

Addison's disease. Upon examining healthy blood as a control, the presence of similar granules was demonstrated, and, as mentioned above, after many observations upon the blood of healthy and diseased individuals, Miiller came to the conclusion that these refractive bodies are regularly present in the blood. Their diameter is 1 ii or under, their size being somewhat variable. They are further described as highly refractive, round or dumb-bell shaped bodies, which show a dancing, molecular movement, but no independent motion. When the fresh blood is prevented from drying by surrounding the cover-slip with oil, these granules can still be seen after 24 hours, and the same may be said when the blood is mounted in 1 per cent, osmic acid. The reaction for fat does not occur with this acid, nor can they be dissolved by acetic acid or ether. They are not concerned in the formation of fibrin, since they remain outside of the fibrinous network or are only accidentally attached to it.

From these observations the author concludes that these granules are a normal constituent of the blood. His technique guarded against the introduction of foreign particles from the skin, etc. He does not consider them as Ehrlich's neutrophilic granules escaped from leucocytes. He states that the neutrophilic granules are dissolved by dilute acetic acid, while the bodies which he has studied are not dissolved by this acid.

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He does not believe that they are true particles of fat, since they do not give a reaction with osniic acid, but advances the opinion that they may be bodies resembling fat, but which fail to show the osmic acid stain. He leaves the question open as to their fatty or albuminous nature, and ends by calling them " Haemokonien," or "Blutstiiubcheu" (blood dust). No mention is made of any attempts at staining.

Briefly stated, therefore, Mtiller has observed a varying number of small refractive, spherical bodies, of undetermined origin and composition, in all of the specimens of human blood which he examined.

Other authors have also observed bodies resembling fat granules in the blood of normal human beings, Kolliker,^ Kanvier,^ Bizzozero,* and von Limbeck' all mention such bodies in the blood. Mtiller was unable to reconcile their description by these authors with the bodies which he observed, but he thinks that certain fat drops or granules described by Schiefferdecker and Kossel" are probably identical with his bodies. Hayem' also speaks of spherical granulations resembling fatty particles, which Miiller considers as identical with the granules described by himself.

The bodies which we have observed correspond in their general appearance to those described by Miiller. We especially wish to emphasize the fact already mentioned that the granules vary in size. Occasionally one meets with the larger round body about 1 //. in diameter, but by far the more frequent variety are the fine granules, almost diist-like in appearance. They exhibit molecular movement, but no independent motility.

We first began the study of the bodies by ordinary daylight, but we soon found that they can be brought out much more clearly by means of the artificial light of the Welsbach gasburner. We have been able to demonstrate the presence of these granules in the fresh specimens of blood taken from the lobes of the ears of about 500 persons. Most of the specimens were from dispensary patients, but about 100 were taken from normal individuals. Care was always taken to thoroughly cleanse the ear, and the first drop of blood was always wiped away with a clean towel. In perfectly fresh specimens the granules were not numerous, but they seemed somewhat increased in patients who had been taking tonics or the various alcoholic drinks. No attempt was made to determine their relative frequency in different diseases.

After having observed these granules in all of the specimens of human blood which we had examined, the question naturally arose as to their origin. It was first noted that these granules, when examined by artificial light, resembled those of the eosinophilic and neutrophilic leucocyte. These leucocytes, when observed at once in a perfectly fresh drop of blood, kept at the room temperature, are usually motionless, and the granulations show no activity. AVhen the blood specimen is surrounded by vaseline and is then exposed to a temperature of 35° C. for an hour or more, the picture becomes somewhat different. At times the granular leucocytes become actively amoeboid, and the granules within the ueutrophile exhibit a characteristic activity, which might be compared to the swarming of bees around a hive. The number of fine granules free in the plasma is perceptibly increased. The

eosinophilic granulations also show a less vigorous tremulous motion, and both varieties follow the changes in the direction of the pseudopodia, the protoplasm being thrown out first, and the granules slowly following. The characteristic dancing motion of the granules in the neutrophilic leucocyte can be brought out very plainly by simply mixing the drop of blood with an equal amount of distilled water containing 1 per cent, of alcohol. The granules soon become very active and present a characteristic picture.

And now a difficult question presents itself. Can these granules be actually seen to leave the leucocyte ? It is certainly not easy to be sure, even after continuous observation for an hour or more, that one has actually seen one of these granules leave an amceboid leucocyte. We think, however, that we have observed this phenomenon upon several occasions, both in fresh specimens of blood exposed to 35° C. and in blood to which 1 per cent, of alcohol had been added.

As already mentioned, Miiller does not think that his granular bodies can be derived from the neutrophilic leucocytes, since Ehrlich's granules are dissolved by dilute acetic acid, while the bodies which he describes are not dissolved by this fluid. According to our observation, dilute solutions of glacial acetic acid (c. p. 99.5 per cent.) cause a great increase in the number of granules free in the plasma when added in equal parts to fresh blood. Many granules can still be seen in the protoplasm of both varieties of granular leucocytes, however, and we cannot convince ourselves that any destruction of the granules has taken place. If a 0.5 per cent, solution of this acid be added to a drop of blood, the eosinophilic and neutrophilic leucocytes often become amceboid, and the granules of the eosinophile often show a slight tremulous motion. The neutrophilic granules exhibit a most characteristic movement, and soon flow into and fill the clear spaces present in the fresh pseudopodia of amoeboid leucocytes. Many fine granules can be seen in the clear plasma and around the neutrophile, and it would seem that occasionallv a granule leaves the active leucocyte and becomes free in the surrounding fluid. When 1 per cent, glacial acetic acid is employed the leucocytes are no longer amoeboid, nor the intracellular granules active. Many granules can still be made out, however, within the protoplasm of the leucocyte, and there are more granules present in the plasma than in the fluid portion of untreated blood. When 5 per cent., 10 per cent., and even stronger solutions are used, the protoplasm of the leucocyte becomes clear and practically free from granules.

Similar free granules can also be made out in the clear blood serum, and they are fairly numerous if the separation has taken place at 35° C. In specimens of blood heated in the usual way for microscopical study, extracellular granules can be stained by a deep red solution of aqueous eosin. This stains the eosinophilic and neutrophilic granulations, and at times a granule of both kinds can be seen immediately adjacent to the leucocyte. Of course such pictures may be due to the manipulation of spreading, and the most convincing phenomena are certainly to be obtained by studying specimens of fresh blood.

Our next series of investigations consisted in the observation of the blood of various animals. In the blood of the

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horse the eosinophile presents a remarkable appearance, the individual granules being often from five to ten times the size of the human variety. Even in perfectly fresh horse's blood a few large, round, refractive bodies can be seen free in the plasma, which entirely resemble the intracellular bodies in size and appearance. Another variety of leucocyte containing granules about the size of the human eosinophilic granules is also present, and a few granules of the same size can be made out in the surrounding fluid. When the specimens of horse's blood are exposed to 35° C. for an hour or more, both varieties become amoeboid, and the intracellular granules show a slow flowing motion. The number of the granules free in the plasma, resembling both varieties, is also perceptibly increased, and the conclusion seems almost irresistible that they have been extruded from the leucocytes. The serum which has separated from the clot also contains many granules I'esembling those described above, especially if the separation has taken place at 35° C.

The eosinophile is the only granular leucocyte present in rabbit's blood, and the granules are about the size of those of the human eosinophile. When the blood has been exposed to a temperature of 35° for an hour, a few round bodies can be seen free in the plasma which resemble the granules of the eosinophile in size and appearance. No smaller dust-like particles can be seen, and this can probably be explained by the fact that the rabbit possesses no finely granular leucocytes. In hardened specimens stained by aqueous eosin the intracellular granules can be easily seen, and at times similar bodies can be observed outside of the leucocyte.

The cat's blood contains about an equal number of eosinophiles and finely granular leucocytes, and the granules are about the size of those present in these respective leucocytes of the human being. Even in perfectly fresh specimens a few granules can be found corresponding exactly to both varieties mentioned above, and when the blood is exposed in the thermostat for an hour there is a great increase in the number of granules of both kinds.

In the guinea-pig the blood contains a few eosinophiles, and many more finely granular polymorphonuclear cells, and the granules of both varieties can be plainly made out in the leucocyte ; while if the blood is placed at an artificial temperature, similar granules can be seen dancing round the leucocytes, or free in the plasma. When stained by aqueous eosin the smaller granules are slightly smaller than the human neutrophile, while the larger granules about equal the human variety in size.

In the blood of the rat both eosinophilic and finely granular leucoytes are present. Many large and small granules, entirely resembling those inclosed in the protoplasm of both varieties, can be made out free in the plasma, especially after an hour at 35° C. In stained specimens the fine granules are as small as the human variety, and the rarer eosinophilic leucocytes contain perceptibly larger granules.

After exposure to a temperature of 35° 0. for an hour there are more free granules present in the blood of the cat and white rat than in the blood of the other animals which we have studied. There are also granules present in the blood of such animals as mice, frogs, fishes, land-terrapins, tadpoles.

and even oysters and clams. They are also present in hydrocele fluid, and the serum of such animals as the horse, hog, steer, rabbit, and dog. They present a striking appearance in the usual varieties of pus, and the intracellular granules are often active.

These observations simply strengthen the conclusion that the granules of the eosinophile and the neutrophile are present as free bodies in the plasma and serum.

II. — Bearing of the Foregoing Observations upon Immunity and Natural Kesistance.

Our observations indicate that granules derived from leucocytes appear free in the blood. It occurred to us that these granules may be concerned in the protective properties of the blood in immunity. A brief review of the two principal theories in regard to immunity, and the later work concerning this matter, will here be in place.

Metchnikoff, as is well known, believes that bacteria are destroyed in the body chiefly by means of the leucocytes. These amoeboid cells or phagocytes engulf the invading organisms and gradually destroy them, being attracted to certain bacteria by means of positive chemotaxis. If this attraction exists between the phagocytes and the bacteria, and the former are able to include and destroy the latter, the animal is saved. If, on the other hand, the bacteria repel the phagocytes by means of negative chemotaxis, or the phagocytes are incapable of completely destroying or preventing the development of the infectious organisms, the bacteria gain the upper hand and the animal suffers a fatal infection. This well known theory of phagocytosis is summarized by Metchnikoff as follows :

" We have the right to maintain that in the property of its amreboid cells to include and to destroy micro-organisms the animal body possesses a formidable means of resistance and defense against infectious agents."

The work of Buchner has certainly imposed some restrictions upon the unqualified acceptance of this theory, although his later investigations point towards the leucocyte as* the origin of the germicidal material. Buchner demonstrated that the bactericidal property of blood is not dependent upon the presence of leucocytes, inasmuch as the serum of the dog and rabbit, which had been freed from cellular elements by separation and centrifugalization, is still capable of destroying such bacteria as the typhoid and anthrax bacilli, and the spirillum of Asiatic cholera.

After freezing and thawing the blood serum he found that it still remained bactericidal while this treatment destroyed the leucocytes, and he excluded the action of these cells by filtration of the serum through double filter paper. From these results he concluded that the actual presence of the leucocyte is not necessary for the bactericidal power of the serum. He later modified his earlier views by admitting that the leucocytes probably furnish a bactericidal substance, although he does not believe that they actually as a rule consume and destroy the agents of infection.

He demonstrated this property of the leucocytes to furnish a germicidal substance in the following manner. He first injected a sterilized emulsion of wheat-flour paste into the

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pleural cavity of dogs and rabbits, thereby obtaining an exudate which had much more germicidal strength than the blood or serum of the injected auimals. Although this was referred to the greatly increased number of leucocytes present, he argued that it was not due to their phagocytic action, since by freezing the exudate the leucocytes were destroyed, and yet upon thawing out this material the bactericidal proijerties of this fluid were even slightly increased.

Other observers have also recently pointed out that the leucocytes seem to contain germicidal substances in a concentrated form. Hahn° has confirmed the work of Buchner in regard to the heightened bactericidal effect of pleural exudates containing a large number of leucocytes, and' he has also succeeded in partially extracting this material and imparting the power of destroying bacteria to other fluids than serum. He first introduced wads moistened with sterile chemotactic substances into the peritoneal cavity of rabbits. After 24 hours these wads were I'emoved and were found to contain countless leucocytes. The fluid from the sponges was then frozen and the leucocytes thereby destroyed. After thawing, this fluid was found to possess decided bactericidal effects. From his experiments he concludes that the germicidal material is not a j)roduct of the destruction of the leucocyte by the system, but that it is a secretion formed during the active existence of this cell.

Bordet" has also made a number of important communications bearing upon this subject. This investigator produced an cedematous fluid free from leucotypes in guinea-pigs immune from the cholera spirillum, by means of compression exerted by rubber bauds around the extremities. He then compared the bactericidal power of this cell-free fluid to that of the animal's serum containing leucocytes, by introducing into each equal numbers of cholera spirilla. He found that cultures made from the serum were always sterile in from one to one and a half hours, while similar cultures taken from the cedematous fluid showed a perceptible increase in the number of bacteria. Later cultures from the (Edematous fluid showed even greater increase. He also produced a hypoleucocytosis by means of carmine injections, and found that the power of such blood to destroy bacteria was greatly decreased when compared with its bactericidal properties before the artificial diminution of the leucocytes. Bordet concludes that the leucocyte is the seat of the bactericidal material, which under abnormal circumstances it gives up to the surrounding fluid.

Schattenfroh'" has made some exceedingly interesting observations in regard to the bactericidal properties of the leucocyte. He has found that the diluted inflammatory exudates from rabbits were much more bactericidal when he added many leucocytes than when the fluid was free from cellular elements. He also secured leucocytes by centrifugalizing these fluids, and by adding the sediment to salt solution he found that this fluid became capable of destroying bacteria. By drying this sediment of leucocytes in a vacuum over phosphorus pentoxide he secured a fine powder which rendered salt solution very destructive to bacteria. He thinks that the leucocytes furnish the bactericidal substance by a process of destruction. His promised detailed account should be a communication of great interest.

Bail" has made some tests which in his opinion prove that the leucocytes contain a bactericidal material. After injecting virulent stajjhylococci into the pleural cavity of rabbits he found that the leucocytes underwent a characteristic change. They formed round, empty bodies, containing several vacuoles in the nucleus. The granules generally disappeared. Upon destroying the staphylococci by adding ether, and diluting the centrifugalized sediment, the granules showed a dancing motion, and were seen to leave the periphery of the cell and enter the surrounding medium.

He also secured leucocytes by Buchuer's method, added sterile salt solution, and obtained a sediment of leucocytes by centrifugalization. By adding a diluted product of the staphylococcus pyogenes aureus called leukocidin to this sediment, he found that the leucocytes were destroyed, and that they then gave up their bactericidal material to the surrounding fluid. If the leukocidin was heated to 60° 0. it lost its property of destroying leucocytes. He found that nutrient fluids to which untreated leukocidin and leucocytes were added, became very destructive to bacteria. This he explained by the fact that the leukocidin destroyed the leucocytes, thus freeing the alexin. When the leukocidin was heated to 60° 0. its destructive powers were destroyed, and when this altered material was added to the fluid containing the sediment of leucocytes the fluid was not destructive to bacteria. This was because the inactive leukocidin could not free the bactericidal substance from the leucocytes. Such bacteria as the typhoid and colon bacillus, the spirillum of Asiatic cholera, and the staphylococcus pyogenes aureus were practically destroyed in 6 hours.

Bail concluded from these and other experiments that the white blood corpuscles of the rabbit contain a bactericidal material, which at times becomes free and appears in the surrounding medium.

We have also performed a series of experiments which seem to show that the leucocytes are directly concerned in furnishing a definite amount of bactericidal material, but the methods need a preliminary explanation.

Certain investigations were made for the purpose of determining whether there existed any difference in the bactericidal power of fresh blood serum before and after it had been filtered through new sterile Miincke filter-cylinders.

Dziergowski" has shown that such fluids as abrin solution, diphtheria toxin and tetanus toxin suffer a slight diminution in their toxic properties when filtered through porcelain cylinders, and Martini" has shown that the antitoxin of diphtheria is also weakened by this process.

Denys and Havet" consider that the leucocytes of the dog play the principal part in the destruction of bacteria, and they base their conclusions upon the results obtained from the following experiments.

They first proved that the blood of the dog was capable of destroying many more colon bacilli than the serum of this animal in a given space of time. Thinking that this increase in the bactericidal power of the blood, as compared to that of the serum, might be due to the greater number of leucocytes present in the former fluid, they next compared ihe relative destructive powers of filtered and unfiltered blood. The fluid

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was filtered through double filter paper, as this method was found to deprive the blood of its white blood corpuscles. They found an enormous difference between the bactericidal power of the blood possessing its leucocytes, and that which had been deprived of the same by filtration.

These observers were also able to greatly increase the bactericidal power of the serum by the addition of the sediment of leucocytes obtained from a sero-puruleut exudate in the pleural cavity of a dog. This was produced by the injection of dead fluid cultures of the staphylococcus pyogenes aureus. By the addition to filtered blood of the leucocytes obtained from the pleural fluid of a dog injected with dead spirilla of Asiatic cholera they were able to restore the lost bactericidal properties of the blood.

They conclude from the observations above mentioned that the blood of the dog when filtered loses its bactericidal power, but that this property can be restored by the addition of living leucocytes.

The blood from which we obtained our serum was secured from rabbits and dogs by means of a sterile cannula introduced into the carotid artery under aseptic precautions. The first few drops were allowed to escape and the rest of the blood was caught in sterile jars. These were stoppered with cotton and allowed to stand at 33° C. for from 13 to 34 hours, when one-half of the serum was filtered through porcelain, while the other half was siphoned off into sterile flasks, care being taken to prevent any admixture of red blood corpuscles. We never worked with serum over 48 hours old.

Our first series of experiments demonstrated a decided difference between the undiluted serum of dogs and rabbits before and after filtration through the unglazed porcelain filter.

When such motile bacteria as the spirillum of Asiatic cholera, the Finkler-Prior spirillum, and the typhoid bacillus were introduced into unfiltered dog serum, complete agglutination took place in from 15 to 30 minutes, together with cessation of motility; but when filtered serum was used no cessation of motility or agglutination took place, even after 3 hours. The rabbit's unfiltered serum caused agglutination and cessation of motility of the typhoid and cholera organism in 15 minutes, and affected the Pinkler-Prior spirillum and bacillus pyocyaneus similarly in about 30 minutes. This condition did not change during 34 hours. The specimens in filtered serum remained active and showed no signs of agglutination, even after 34 hours.

The specimens were all examined in hanging drop-slides, and allowed to remain at the room temperature. From the foregoing experiments we concluded that filtration of the undiluted serum of rabbits and dogs removes their normal property of causing the agglutination and cessation of motility of the organisms above mentioned.

Our next endeavor was to ascertain whether we could demonstrate any difference in the capacity of the filtered and unfiltered serum actually to destroy these bacteria, and for this purpose we adopted the following method :

Twenty-four hour cultures on slanted glycerine-agar of the various organisms to be mentioned below were prepared, and one loopfnl of the surface growth was transferred into 2

cubic centimeters of sterile salt solution. Two loopfuls of this fluid were then introduced into 1 cubic centimeter of the unfiltered serum of the rabbit, and a similar amount was used in 1 cubic centimeter of the filtered serum. The same loop was always used, and an agar plate culture was made from the filtered and unfiltered serum at once, in order to compare the number of germs originally introduced with those present in the serum at varying intervals of time. In all our experiments control plates made from the serum before using remained sterile.

Five loojifuls were planted at the end of 3 hours from both varieties of serum, and at the end of 17 hours 1 loop was planted from the different filtered serums, and 5 loops were planted from the unfiltered serums. With anthrax 1 loopful of the culture was directly introduced into the serums. All of the specimens were kept at a temperature of 35° C. during the experiments.

Table I. — Results with Rabbit's Serum.* Bacillus typhosus. Colonies.

At once. 2 hrs, 17 hrs.

Filtered serum. 1960 730 Great increase.

Unfiltered serun. 936 Sterile. Sterile.

Spirillum of Finkler-Prior. Filtered serum. Unfiltered serum.

Cholera spirillum. Filtered serum. Unfiltered serum.

Proteus mirabilis. Filtered serum. Unfiltered serum.

Anthrax bacillus. Filtered serum. Unfiltered serum.

Staph, pyog. aur. Filtered serum. Unfiltered serum.

1330 1010 Great increase.

959 Sterile. Sterile.

201 960 Great increase.

3 Sterile.

1740 1650 Great increase.

1934 1806 "

804 1530 Great increase.

643 163

743 383 Great increase.

1050 348 "

The foregoing table shows that while unfiltered serum will completely destroy such organisms as the typhoid bacillus and the spirilla of cholera and Finkler-Prior, these same bacteria will increase enormously in filtered serum. The growth of the anthrax bacillus was only temporarily restrained, while the remaining bacteria were not affected.

A similar series of experiments was carried on with the serum of a dog.

• AI1 serums from the same species of animal are not equally

bactericidal, and the results are affected by the amount of serum used and the number of bacteria introduced. Buchner says 1 cubic centimeter of serum will destroy 1000 typhoid bacilli. With a certain rabbit's unfiltered serum we obtained the following results : One cc. of serum. Typhoid bacillus ; at once, 734 ; 2 hrs., 4 colonies; 5 hrs., sterile; 20 hrs., great increase. — Anthrax ; at once, 9144 ; 2 hrs., 2394 ; 5 hrs., 354 ; 20 hrs., 28,800.

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Table II. — Results with Doq Serum Spirillum of cholera.

At once. 2 hrs. 20 hrs.

941 1334 Great increase. 876 Sterile. Sterile.

535

455

Great increase.

638

38

Sterile.

1308

1494

Great increase.

Sterile.

Sterile.

1800

1140 240

Great increase.

Filtered serum. Unfiltered serum.

Bacillus typhosus. Filtered serum. Unliltered serum.

Spirillum of Fiukler-Prior. Filtered serum. Uutiltered serum.

Bacillus pyocyaneus. Filtered serum. Unfiltered serum.

These tables show that the filtered serum cannot destroy the typhoid bacillus or the spirilla of cholera and of FinklerPrior, while the unfiltered serum can practically bring about this result in about two hours.

Having demonstrated that the filtered serum had lost its bactericidal property, our next endeavor was to ascertain whether we could restore this lost property by adding the leucocytes to the filtered serum. We found that the centrifugalization of clear serum will cause the precipitation of many leucocytes and red blood corpuscles. Many granules similar to those described before were also present in the sediment.

Our method of restoring the leucocytes to the serum was as follows :

Ten cubic centimeters of clear unfiltered dog serum were thoroughly centrifugalized in sterile tubes, and the supernatant fluid was then poured off, care being taken not to contaminate the sediment. The few remaining drops were removed from the sediment by means of sterilized swabs of absorbent paper, and a semi-fluid deposit was allowed to remain in the bottom of the tube. Under the microscope this consisted of leucocytes, free granules and red blood corpuscles. This we designated as the small sediment. In another instance 10 more cubic centimeters of serum were added to a tube already containing a sediment, and a second deposit was obtained from this fluid by means of centrifugalization, making the accumulated deposit from 30 cubic centimeters of unfiltered serum. This we called the large sediment.

Two cubic centimeters of filtered (non-bactericidal) serum were then added to tubes containing the large and small sediment, and as a control, filtered aud unfiltered serum was used. All of the serum tubes were then inoculated by means of the following method.

One loop of a 24-hour culture of the typhoid bacillus was added to 3 cubic centimeters of sterile bouillon, and 1 loop of this fluid was then added to the filtered serum, the filtered serums plus the sediments, and the unfiltered serum. Three loops from the inoculated serums were always used for the plates made for numerical comparison, and the serum was kept at 35° C. during the experiments. The plates were allowed to remain in the thermostat for 48 hours before counting. The typhoid bacillus was used for the experiments.

Table III. — Results with Bacillus Typhosus.

Colonies present. At once. 3 hrs. 6 hrs. 20 hrs.

Filtered serum plus

Small sediment. 383 367 690 Great increase.

Filtered serum plus

Large sediment. 463 318 596

Filtered serum. 334 900 29445

Unfiltered serum. 346 Sterile. Sterile. Sterile.

These figures show conclusively that the presence of the sediment consisting of granules, leucocytes and red blood corpuscles in the filtered serum rendered this fluid capable of inhibiting the growth of large numbers of bacteria, although it was incapable of preventing the subsequent development of bacteria in this fluid. This later development was probably due to the presence of the nutritive material in the red blood corpuscle, which property gradually neutralized the germicidal qualities of the serum. The abstraction of the red blood corpuscles by water robbed the sediment of its bactericidal qualities, so that so far we have been unable to eliminate its nutritive effect. This has been accomplished by the work of Schattenfroh and others, and the results, therefore, accord with our experiments. We have not been able to render the bactericidal power of filtered serum equal to that of the unfiltered fluid, but we mention our method at this time in order to propose a simple method of obtaining large quantities of fluid for further experimentation, and as a slight addition to the mass of evidence in favor of considering the leucocyte as the dispenser of the bactericidal material.

Conclusions.

In the blood plasma and serum of man and many of the lower animals there are present varying numbers of granules, which resemble the granules of the eosinophilic and neutrophilic leucocytes in size aud appearance.

After addition of dilute acids, dilute alcohol, etc., and subjection to body temperature, the granules of the leucocyte assume marked activity, and such treatment increases the number of granules present in these fluids. These free granules are almost certainly derived from the granular leucocytes.

The filtration of the serum of the dog and rabbit through new Miincke porcelain cylinders removes its normal property of causing the agglutination and cessation of motility of many motile pathogenic bacteria, and of destroying large numbers of these organisms. This property can be partially restored by adding a sediment consisting of leucocytes, free granules and red blood corpuscles. Siuce the red blood corpuscles are not germicidal (Buchner), it follows that the restoration of the bactericidal property is due to the addition of the leucocytes and free granules, aud that these cells can furnish a germicidal material.

The larger extracellular granules of man, and of the frog, horse and rabbit can be stained by eosin, or by means of Ehrlich's triple blood stain.

Theory of Immunity based upon these Observations. And now it being demonstrated that the leucocytes not only contain a bactericidal substance, but also under certain conditions can give up a portion of their protoplasm to the sur

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rounding medium, one naturally looks for some experimental proof showing that the germicidal substance and the material that leaves the leucocyte are identical. This jiroof, however, is extremely difficult to furnish, since filtration of a sediment even through double filter paj^er will allow leucocytes as well as granules to pass.

We have added the typhoid bacillus to various normal bloods and serums, but without demonstrating any distinct attraction of the bacilli for the free granules. We have succeeded in immunizing a guinea-pig from the typhoid bacillus by means of Pfeiffer's method, and upon adding 24-hour motile bacilli to the fresh blood of such an animal the results are slightly more suggestive.

The bacilli become immediately motionless and clumped, and after 15 minutes at 35° 0. fine granules can be seen around the periphery of the clumps, or even dancing about in the meshes of the massed organisms. This condition can be noticed even after several hours, but the granules are never vei'y uumerous. Often several can be seen about a single typhoid bacillus.

Novy and Vaughn" have extracted a germicidal nuclein from blood serum, and they think that it is derived from the leucocyte. Hankin" believes that the granules of the eosiuophile gradually dissolve in the serum, thereby furnishing the alexin.

The suggestive work of Kauthack and Hardy" should also be mentioned in this connection. These investigators made a number of painstaking observations concerning the effect of the introduction of a few anthrax bacilli into the lymph of the frog. They either injected the bacilli into the various lymph sacs and then withdrew the mixture of lymph and bacilli at varying intervals of time, or they mixed the lymph and bacteria, and then observed the specimen in the hanging drop for several hours.

They found that the destruction of the bacteria could be divided into two distinct stages. The first stage consisted in the approach of the oxyphilic or eosinophilic leucocyte to the chains of anthrax bacilli. These leucocytes were said to apply themselves to the surfaces of the chains of bacilli, and then discharge their granules by a quick streaming motion, when the bacilli would begin to show signs of degeneration.

The next stage in the phenomenon of destruction was the approach of a cell described by the writers as the hyaline cell, which was said to contain a round or kidney-shaped nucleus, but no granules. These cells were seen to approach the masses of eosinophiles and bacilli and gradually replace the eosinojihiles.

The hyaline cells would then include the bacteria within their protoplasm, and many cells could be found possessing vacuoles containing fragmented bacilli. The eosinophiles were thought to prepare the bacteria for ingestion by the hyaline cells, but they never were seen to include the bacteria themselves.

Although in a more limited series of observations on five frogs we have failed to observe any distinct clinging of the eosinophile to the chains of anthrax bacilli, we have noticed the fact that after an hour or more the eosinophile will frequently only contain a few granules. Many large eosino

philic granules can be made out free in the plasma, but these are accompanied by smaller dust-like granules. We believe that these smaller granules are derived from the leucocyte of the frog possessing fine granules and a nucleus of the polymorphous variety. These fine granules are at times active within the protoplasm of the cell, and upon one occasion we observed such a leucocyte with active granules which contained an anthrax bacillus in its protoplasm. When specimens taken from the subcutaneous sacs of the frog into which a few anthrax bacilli had been introduced, were stained with methylene blue, typical phagocytosis could be observed in cover-slij)S prepared half an hour after the injection of the bacilli. Often from one to three bacilli could be made out within the protoplasm of a cell containing a typical polymorphous nucleus, and resembling the ordinary pus cell.

In hardened specimens stained by Ehrlich's triple blood stain, or simple eosin and methylene blue, many large granules exactly resembling the large intracellular granules of the eosinophilic leucocyte could be made out as extracellular bodies, but bacilli were never found within the protoplasm of the eosinophile. The eosinophile seems to form the majority of the white blood corpuscles of the frog, the finely granular cell being more rarely seen.

It would seem, therefore, that the free granules, both from the eosinophilic and finely granular leucocyte, may weaken and destroy the anthrax bacilli by their presence in the plasma, and that then the finely granular leucocyte with the nucleus of the polymorphous variety, together with the hyaline cell of Kanthack and Hardy, complete the process of destruction by inchiding the bacteria within their protoplasm.

The many suggestive facts which we have just mentioned have induced us to advance the following theory :

The bactericidal power of the leucocyte of the blood, and of the serum of man and many animals, is due to the presence of specific granules, especially the eosinophilic and neutrophilic.

When called upon to resist the action of invading bacteria, the granular leucocytes can give up their granules to the surrounding fluids or tissues.

Not only does this enable us to understand how apparently cell-free fluids can destroy bacteria, but the production of the alexin by the leucocytes also affords a better explanation of the hyperleucocytosis of infection so strongly urged by Metchnikoff, and by no means disproves the supposition that the leucocytes can take up bacteria either while alive or after being destroyed by means of the germicidal granules.

References.

1. Miiller: Ceutralbl. f. allg. Path, und path. Anat., VIII, (1S9G).

2. Kolliker: Handbuch der Gewebelehre des Menschen. 5 Aufl., Leipzig, 1867, S. 630.

3. Kanvier: Traite technique d'histologie. Paris, Savy, 1875, p. 214.

4. Bizzozero: Handbuch der klin. Mik. 2 Aufl., Erlangen, Besold, 1887, S. 43 u. 74.

5. von Limbeck : Grundriss einer klinischen I'athologie des Blutes. 2 Aufl., Jena, G. Fischer, 1896, y. 131.

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6. SchiefferdeckerandKossel: Gewebelehre. Braunschweig, Brun, 1891, Bd. II, 1 Abth., S. 356.

7. Hayem : Du sang et de ses alterations anatomiques. Paris, Masson, 1889, p. 113.

8. Hahn: Archiv f. Hygiene, Bd. XXV, S. 105.

9. Bordet: Annales de I'lnstitui Pasteur, T. IX, No. 6.

10. Scliatteufroh : Miiuch. med. Woclienschr., April 20th, 1897, No. 16.

11. Dziergowski: Archiv d. sciences biologiques, IV, 43.

12. Martini : Centralbl. f. Bakt., XX, Nos. 23, 21.

13. Novyand Vaughn : Ptomaines and Leucomaines. 1896.

14. Hankin : Centralbl. f. Bakt., Bd. XII, Nos. 22, 23, 1892.

15. Deuys and Havet : La Cellule, T. X, 1894.

16. Kauthack and Hardy: Phil. Trans., Vol. CLXXXV, 1894, p. 279.

17. Bail: Berliner klin. Woehenschrift, Oct. 11th, 1897.

ON THE ANATOMICAL RELATIONS OF THE NUCLEI OF RECEPTION OF THE COCHLEAR

AND VESTIBULAR NERVES.

By Florence R. Sabin. [From the Anatomical Laboratory of the Johns Hopkins Unieersity.]

Since the investigations of Babiuski,' v. Bechterew,' Bumm,' Cramer,' Flechsig, Forel,' Kirilzew," v. Monakow,'" Ouufrowicz," and Roller,'* much light has been thrown on the central connections of the cochlear and vestibular nerves by Ramon y Cajal,' Held,' v. Kolliker,'" Martin" and Sala." The exact topographical relations of these nuclei have, however, so far been only imperfectly described.

The material used in the present study was human tissue and consisted of two superb sets of serial sections, transverse and horizontal, through the medulla of the new-born babe, prepared by Dr. John Hewetson at the Anatomical Laboratory of the University of Leipzig. Through the courtesy of Dr. Hewetson these preparations have been made accessible for study to research-workers in the Anatomical Laboratory of the Johns Hopkins University.

A flat reconstruction on millimetre paper has been made from the right-hand side of the sections of the transverse series which show the nuclei in question. Reference to the diagram (Fig. 1) will show the following points : At the lower end of the diagram the zero point on the scale represents the superior (anterior) limit of the decussation of the pyramids, and at the npper end the diagram extends nearly to the lower border of the inferior colliculus of the corpora quadrigemina. The lines drawn across the diagram represent approximately the planes of the sections having the corresponding numbers.* The areas occupied by the nuclei of the nervus hypoglossus and nervus abducens are given to help in orientation. The lines rt-re represent the lateral boundary of the fourth ventricle, which has been traced from the point at which the canalis centralis opens out into the floor of the ventricle, through the area of the recessus lateralis and forwards to the aqueductus cerebri. The line b-b represents the lateral boundary of the corpus restiforme. The entrance of the corpus restiforme into the cerebellum is not shown, but the line runs to its upper

• Tbe planes of the sections are in reality slightly different from

those represented by the lines on the diagram, which are drawn at right angles to the median line. The sections have been cut slightly obliquely, the right side being struck at a higher plane than the left. Theslightdiscrepanciesbetween the drawings of the sections and the diagrams are thus explained.

limit. The motor and sensory nuclei of the nervus trigeminus are shown with the exception of the nuclei minores (radicis descendentis). The tractus spinalis uervi trigemiui, together with the adjacent substantia gelatiuosa, is represented in outline from its beginning, at the entry zone of the nerve, downward as far as the decussation of the pyramids. Its course further spinalwards is not given. The entering root bundle of the nervus trigeminus is also not illustrated, but the lowest section which shows it corresponds to number 45 on the scale, and as the nuclei of the nerve are inferior to the point where it enters, the fibres can be traced farther upwards than the diagram goes. The lines dz and di represent the surface markings on the floor of the fourth ventricle corresponding to the ala cinerea. The complete length of the nucleus alffi cinerea3 is not shown, but it can be traced from the inferior end of the nucleus nervi hypoglossi to the point marked d\ on the diagram. The line rfi-rfs, in which the two sulci meet, corresponds to the portion of the ala cinerea which has been pushed into the depth by the spreading of the nucleus nervi vestibularis medialis dorsal to it over the floor of the ventricle.

The line e represents the continuation of the lateral sulcus over the area occujiied by the nucleus nervi abducentis. The sulcus is here further lateral, corresponding to the position of the nucleus nervi abducentis, which is further from the median line than the nucleus nervi hypoglossi.

Nervus vestibuU. The area of entrance of the root bundle of the vestibular nerve is shown in the diagram. The well known fact that the vestibular root bundle is farther forwards (cerebralwards) than the cochlear root bundle is well illustrated. The reconstruction shows clearly the generally recognized fact that the four principal vestibular nuclei are continuous with one another. (See J/., L., S., and R. d. n. ve. in the diagram.) These nuclei can be distinguished in part by position and in part by the character of the cells within them. The relation of the nucleus nervi vestibularis medialis to the nucleus of the descending tract of the vestibular nerve is very striking. Ramon y Cajal has already pointed out their close connection. The lowest sections in which descending vestibular fibres can be distinctly made out show cells between the fibres (sections between 15 and 17 on the scale). These cells higher up make an oval mass which lies.

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lateral to the ala cinerea and extends dorsal aud medial to the descending vestibular fibres. As the ala cinerea recedes into the depth, and the nucleus nervi hypoglossi disappears, these cells spread to very near the middle line. The large area M, together \vith the dark area Y, represents the nucleus nervi vestibularis medialis ; it can easily be seen that any division between this nucleus and the nucleus of the descending vestibular tract, throughout their whole extent, must be merely an arbitrary one. It is extremely difficult, too, to determine exactly the medial border of the nucleus nervi vestibuli medialis ; it goes over insensibly into the central gray matter surrounding the ventricle. In general the nucleus nervi vestibularis medialis begins from 2 J to 3 mm. below the superior end of the nucleus nervi hypoglossi and extends in the floor of the fourth ventricle as far forward as the nucleus nervi abducentis. Its anterior extremity (J' in the diagram) passes forward some distance further lateral to the nucleus of the sixth nerve. The descending tract of the nervus vestibuli begins at the entry zone of the vestibular root fibres in the region of the nucleus nervi vestibularis snperior (Bechterew), and of the nucleus nervi vestibularis lateralis (Deiters). It is made up of the descending branches of the root fibres and lies dorsal to the tnictus spinalis nervi trigemiui, at first at a distance of 1.3 mm. from the floor of the ventricle (Fig. 3). Farther posterior it approaches the floor, and the isolated bundles of fibres of which it is made up occupy a very characteristic oval area, the long diameter of which lies in the dorso-ventral direction (Fig. 3). A reference to the diagram will show that it extends downward from its origin in a straight line as far as the level of the superior (anterior) end of the nucleus nervi hypoglossi. From this point it curves medialwards, giving place to the nucleus funiculi cuueati. It can be traced downwards to a plane a little superior to the middle of the nucleus nervi hypoglossi. The ascending branches of the vestibular fibres are not represented in the diagram, but they are shown in figs. 3 and 4.*

At the extreme superior and lateral angle of the nucleus nervi vestibularis medialis is situated a.large group of cells, in part capping the descending tract of the vestibular nerve (Fig. 3, Nil. ij). It is oval in shape aud is distinctly visible in section just below the floor of the fourth ventricle. As will be seen in the diagram (Fig. 1, P), it lies adjacent to the nucleus nervi vestibularis lateralis, to the nucleus nervi vestibularis medialis, and to the nucleus nervi vestibularis spinalis (Kadix descendens). This nucleus, however, is worthy of a special description in that it is peculiar: (1) in the size of the cells, they being much larger than those of that part of the nucleus nervi vestibularis medialis marked M in the diagram, but smaller than those of the nucleus nervi vestibularis lateralis; (2) by the staining capacity of the mass, which on the whole stains in Weigert-Pal preparations of the new-born babe much darker than Deiters' nucleus of the

• The so-called cerebellar acoustic nucleus of Ramon y Cajal, the

cells of which accompany these fibres, is not representeil. No attempt was made to locate in the diagram the gray masses in the roof of the cerebellum, with which tlie ascending branches of the vestibular nerve undoubtedly come into relation.

same section ; (3) by the fact that the cells are closely packed together, which brings it into marked contrast with the more scattered cells of the nucleus nervi vestibularis lateralis ; (4) by its distinct outline in ruell stained preparations, which makes this group of cells easier to differentiate than any of the other vestibular nuclei. A reference to Figs. 3 and 4, and to the diagram, Fig. 1, will show the position of the nucleus. This nucleus evidently corresponds to a part of the ganglion dorsale acusHci of v. Kolliker (Hattptkern of Sch walbe.) It is continuous posteriorly with the nucleus of the descending root, and laterally (in its posterior part) with the rest of the nucleus nervi vestibuli medialis. It is not so easy t.o locate it definitely in series in which the gray masses are not particularly well differentiated, but even in such a series, after having defined it easily in Dr. Hewetsou's sections, its limits have been recognized without much difficulty. Until attention can be paid to the course of the axones of these cells and a comparison can be instituted between its constituent neurones and those of the other vestibular nuclei, I prefer to give the group a distinct place in the diagram and to refer to it as nucleus y.

It may further be seen in the diagram that the nucleus nervi vestibularis lateralis and the nucleus nervi vestibularis superior are in the region of the entry zone of the vestibular nerve. The lateral nucleus appears to be separated into two portions by the root fibres of the nerve. One part {Lt in Fig. 1, and Nu. n. v. I, in Fig. 3) is further inferior (posterior) and lateral, and it lies also further ventral than the other part (Z/ in Fig. 1, and Nu. n. v. I in Fig. 4). L\ lies between the entry zone of the vestibular root fibres and the corpus restiforme. Its cells are rather smaller than those of L. The part of Deiters' nucleus marked L lies in its upper part almost in the floor of the fourth ventricle and is continuous laterally with Bechterew's nucleus, from which it can be easily distinguished, however, by the size of the cells. In the longitudinal series these two parts of Deiters' nuclei Zand L\ are seen to be in reality continuous; a few scattered cells joining them can be seen between the fibres of the nerve. They are seen with the high power not to be such separate entities as the diagram would make them appear. In his articles on the medulla oblongata Ramon y Cajal describes the nucleus nervi vestibularis lateralis in the white mouse as a crescent-shaped mass, convex on its dorsal border, and showing two sorts of cells, the larger being further ventral, the smaller more dorsal and lateral. In human tissue I find that the nucleus is convex on the ventral border, and to be so inclined that on the whole the smaller cells are further ventral as well as lateral. Fig. 3 shows the lateral portion (Zi)ofthe nucleus nervi vestibularis lateralis, while Fig. 4, which represents a section .6 mm. further forward, shows the medial portion (Z).

The nucleus nervi vestibularis superior (Bechterew) lies in the floor and lateral wall of the fourth ventricle, occupying its lateral angle. In the diagram. Fig. 1, it is marked .5 and is given a heavy outline. It lies in a plane dorsal to that of the nucleus nervi vestibularis medialis, and its inferior (posterior) extremity corresponds about to the inferior (posterior) end of Deiters' nucleus. As seen in the diagram

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it extends even further laterally than does the nucleus nervi vestibularis lateralis of Deiters. A reference to Figs. 3 and 4 will show that it is bounded laterally in a part of its course by the corpus restiforme. As the nucleus extends upwards (cerebral wards) it lies more and more dorsally, so that it comes to lie between the lateral wall of the ventricle and the brachium conjunctivum. It is interesting to note how far it can be traced at its cephalic extremity into the region of the nuclei of the nervus trigeminus. It is traversed by the ascending branches of the root fibres of the vestibular nerve.

Thtre seems to be a general agreement that the root fibres of the vestibular nerve bifurcate. The descending limbs pass into the descending root, many of the ascending go up into the cerebellum. Keceut investigations make it probable that axones also run in the opposite direction from the cerebellum to the nucleus nervi vestibularis lateralis. Fig. 4 shows two distinct sets of fibres extending between the cerebellum and Deiters' nucleus; one running between the brachium conjunctivum and the corpus restiforme and lying in the plane of the transverse section for a considerable distance, the other being more medial and going actually through the nucleus nervi vestibularis superior and the brachium conjunctivum. The latter fibres are so inclined that they do not run far in the plane of any one section, but by following the series downward (caudalwards) from the region of Deiters' nucleus, scattered fibres show in the brachium conjunctivum, lying in a plane perpendicular to the fibres of the latter, and so contrasting strongly with them. These fibres are farther dorsal in each succeeding section downward as far as the nucleus fastigii, dorsal to which a well marked decussation is visible (Figs. 3 and 2).

Fig. 5 repi'esents a longitudinal section taken through the area of the vestibular nuclei. The lines 66 on the transverse sections represent approximately the plane of this section. All of the vestibular nuclei, the nucleus nervi vestibularis medialis (with the part of it which I have designated nucleus F), the nucleus of the descending vestibular root, the nucleus nervi vestibularis lateralis and nucleus nervi vestibularis superior, are shown.

Very little of the nucleus nervi vestibularis superior shows, however, inasmuch as this nucleus lies for the most part dorsal to the plane of this section. It will be seen that there is a well marked group of fibres /? running obliquely forwards from the region of the nucleus nervi vestibularis superior. These fibres have been traced on both series, and the area they occupy is represented in the general diagram (Fig. 1, z). They extend between the nuclei of the nervus trigeminus and the raphe. Toward the floor of the ventricle they pass through the nucleus nervi vestibularis superior, as is shown in the diagram. They decussate in the raphe dorsal to the fasciculus longitudinalis medialis. As to their further course it is impossible to say from these sections.

Nervus Cochlea. The areas corresponding to the nuclei of the nervus cochleae are illustrated in Fig. 1. It is interesting to note that the nucleus nervi cochlearis dorsalis is continuous with the nucleus nervi cochlearis ven trails and that the transition from the one to the other is very rapid. Figure 6 represents a reconstruction to show the relations of the

cochlear nuclei to the corpus trapezoideum and the complex of the nucleus olivaris superior. The nucleus nervi cochlearis dorsalis begins just above (anterior to) the nucleus nervi hypoglossi. It is in the dorso-ventral direction a long, narrow nucleus, the apparent breadth of the area represeniing it in the diagram being due to the fact that it curves somewhat around the corpus restifoi-me. Its size and general character are illustrated in Fig. 2. Both the section and the diagram show how far lateral it lies, though it by no means extends so far lateral as the nucleus nervi cochlearis ventralis, a point which is in disagreement with many of the figures in the textbooks. It has comparatively few medullated axones in it, and these run parallel to the long axis of the nucleus as seen in transverse section. The division into three zones, a mesial, middle and lateral, is clearly shown in Fig. 2. This division has already been described by von Kolliker and by Sala. The mesial and lateral zones are rich in medullated fibres.*

In Fig. 6 is represented a flat reconstruction of the mesial and lateral bundles of medullated fibres of the nucleus nervi cochlearis dorsalis. The mesial bundle is marked m, and the lateral I. It may be seen that the areas corresponding to both bundles run toward the middle line.

The fact that the root bundle of the cochlear nerve enters the nucleus nervi cochlearis ventralis has been observed by Held and Sala. It is interesting to note in Fig. 6 that the area of the entering root bundle of the nervus cochlese is considerably superior (anterior) to that of the nucleus nervi cochlene dorsalis. Both Held and von Kolliker have described the bifurcation of the cochlear root fibres. Eamon y Cajal has observed the bifurcation both in the new-born mouse and in the rabbit and says that it takes place in the nucleus nervi cochlearis ventralis.

The two branches are, he states, usually equal in calibre, but the ascending branches are short and end in the nucleus nervi cochlearis ventralis. On the other hand the descending branches are longer and can be traced in a definite bundle to the inferior part of the nucleus nervi cochlearis ventralis and the nucleus nervi cochlearis dorsalis. He says that jn the mouse these fibres, at first scattered, soon form a definite bundle, which can be traced to the inferior part of the nucleus nervi cochlearis dorsalis. A bundle of medullated fibres, apparently corresponding to the bundle of axones described by Ramon y Cajal, has been easily traced in the sections I have studied, and is shown in the figure (Fig. 6, /*). Near the entry zone of the cochlear nerve it consists of scattered fibres, but it soon forms a compact bundle on the mesial border of the ventral nucleus. The bundle runs spinalwards and at the same time so rapidly dorsalwards that in cross section its fibres are cut almost longitudinally. The reconstruction brings out the fact that it is connected with the mesial zone of the nucleus nervi cochlearis dorsalis corresponding to the area of medullated fibres m (Fig. 6).

The arrangement of the fibres of the nucleus nervi cochlearis dorsalis in parallel lines has already been mentioned (Fig. 2). In strong contrast to this is the appearance of the nucleus

• According to Sala the cells of the mesial layer and the middle

zone give rise to the striie acusticte.

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nervi cochlearia ventralis (Fig. 3). The arrangement of the cells and fibres of the ventral nucleus in the form of a basketwork has already been described by Held, von Kolliker and Ramon y Cajal. The latter divides the nucleus nervi cochlearis ventralis into two regions, an inferior (tail) and a superior (head). In the human tissue which I have studied it is the inferior part that is characterized by the basketwork. In the superior portion the cells are fewer and more scattered. Indeed, the cells are so scattered and there are so many fibres running to the corpus trapezoideum in this I'egion that it is very difficult to determine exactly in Weigert-Pal preparations the superior limit of the nucleus. The area C i. (Fig. 6) represents the corpus trapezoideum. It may be noticed that the lateral boundary of the corpus traiiezoideum is continuous with that of the lemniscus lateralis. In both series of sections a continuous line of cells can be traced from the nucleus olivaris superior to the nucleus of the lemniscus lateralis, so that it is impossible to say where the nucleus of the lemniscus lateralis begins. A description of the auditory neurones of the second order cannot be entered into at this time. The diagram shows vei-y clearly, however, the intimate connection of the nucleus nervi cochlearis ventralis with the corpus trapezoideum and superior olivary complex. An examination of Fig. 2 shows how few fibres are medullated at this period in the nucleus nervi cochlearis dorsalis. They are so scattered after leaving the nucleus that it is very difficult to follow them far. The long distance between the nucleus olivaris superior and the anterior extremity of the dorsal cochlear nucleus is another striking feature of the diagram.

This study was undertaken at the suggestion of Dr. Mall and Dr. Barker. I wish to thank them for constant advice and suggestion.

Bibliography.

1. Baginski : Ueber den Ursprung und den centraleu Verlauf des Nervus acusticus des Kaninchens. Virchow's Archiv, Bd. 105, H. 1, S. 28. — Ueber den Ursprung und den centraleu Verlauf des Nervus acusticus des Kaninchens und der Katze. Virchow's Archiv, Bd. 119, H. 1, S. 81.

2. Von Bechterew, W. : Ueber die inuere Abtheiluug des Strickkorpers und den achten Hirnnerven. Neurol. Centralbl., Bd. IV (1885), S. 145.— Zur Frage liber den Ursprung der Hornerven. Neurol. Centralbl., Bd. VI (1887), S. 193.— Zur Frage fiber die Striae medullares desverliingerten Markes. Neurol. Centralbl., Bd. XI, 1892, S. 297.— Der hintere Zweihiigel als Centrum fiir das Gehor, die Stimme und die Eeflexbewegungen. Neurol. Centralbl., Bd. XIV (1895), S. 706.

3. Bumm: Experimenteller Beitrag zur Kenutnissdes Hornerveuursprungs beim Kaninchen. Allgem. Zeitschrift f. Psych , Bd. 45, S. 568. — Experimentelle Untersuchungen fiber das Corpus trapezoides und den Hornerven der Katze. Festschr. zur 150 jithr. Stiftungsfeier der Univ. Erlangen, Wiesbaden, 1893 ; Abstract Neur. Centralbl., Bd. XIII (1894), S. 448.

4. Cajal, Eamon y S. : Beitrag zum Studium der Medulla oblongata des Kleinhirns und des Ursprungs der Gehirnnerven. Deut. Uebersetz. von Bresler. Leipzig, 1896.

5. Cramer, A.: Beitriige zur feineren Anatomic der Medulla oblongata und der Briicke mit besonderer Beriicksichtigung des 3.-12. Hirnnerven. Jena, 1894.

6. Flechsig, P. : Zur Lehre vom centraleu Verlauf der Sinuesnerven. Neurol. Centralbl., Bd. V (18S6), No. 23.— Weitere Mittheilungen fiber die Beziehungen des unteren Vierhfigels zum Hornerven. Neurol. Centralbl., Bd. IX, 1890, S. 98.

7. Forel: Vorlitufige Mittheilung iiber den Ursprung des Nervus acusticus. Neurol. Centralbl., Bd. IV, 1885, S. 101.

8. Held, H.: Die centraleu Bahnendes Nervus acusticus bei der Katze. Arch. f. Anat. und Phys., Anat. Abth., 1891. — Die Endigungsweise der sensiblen Nerven im Gehirn. Arch, f. Anat. u. Phys., Anat. Abth., 1892. — Die centrale Gehorleitung. Arch. f. Anat. u. Phys., Anat. Abth., 1893.— Ueber eine directe acustische Eindenbahu und den Ursprung des Vorderstrangrestes beim Menschen. Arch. f. Anat. u. Physiol., Anat. Abth., 1892.

9. Kirilzew: Zur Lehre vom Ursprung und centralen Verlauf der Gehornerven. Vorliiufige Mitth., Neurol. Centralbl., Bd. XI (1892), S. 669.

10. Von Kolliker : Der feinere Bau des verliingerten Markes. Anat. Anzeiger, Bd. VI (1891), S. 427-431 ; Handbuch der Gewebelehre des Menschen, 6 Aufl., II. Bd. 1893.

11. Martin, P. : Zur Endigung des Nervus acusticus im Gehirn der Katze. Anat. Anzeiger, Bd. IX (1894), S. 181.

12. Von Monakow: Ueber den Ursprung und den centralen Verlauf des Nervus acusticus. Correspondeuzblattf. Schweizer Aerzte, 1887, No. 5 ; Abstract in Neurolog. Centralblatt, Bd. VI, 1887, S. 201.— Striae acusticae und untere Schleife. Arch. f. Psych, u. Nervenkr., Bd. XXII, S. 1.

13. Onufrowicz, B. : Experimenteller Beitrag zur Kenntniss des Ursprungs des Nervus acusticus des Kaninchens. Arch, f. Psych, und Nervenkr., Bd. XVI, S. 711.

14. Eoller : Die cerebralen und cerebellaren Verbindungeu des 3.-12. Hirnnervenpaares. Die spinaleu Wurzeln der cerebralen Sinnesnerven. Allgem. Zeitsch. f. Psych., Bd. XXXVIII (1882), S. 228.

15. Sala, L. : Sur I'origine du nerf acoustique. Arch. ital. de biol., t. XVI, 1891, p. 196 ; also in Monitore zoologico italiano, Florence, Ann. II (1891), and in Neurol. Centralbl., Bd. XI, 1892, S. 200.

Legends for Figures. Fig. 1. Diagram representing flat reconstruction of the nuclei of reception of the cochlear and vestibular nerves. The line a, a represents the lateral wall of the ventricle; the line b corres2ionds to the lateral outline of the corpus restiforme ; the line d\ to (U, (h to rfa, and the line e, e, e correspond to sulci in the floor of the fourth ventricle ; C. d., nucleus nervi cochlearis dorsalis ; G. v., nucleus nervi cochlearis ventralis ; the graduated line corresponds to the middle line of the floor of the ventricle. Flor., flocculus ; K. VII, knee of nervus facialis; L., medial portion of nucleus nervi vestibuli lateralis (Deiters); L\, lateral portion of nucleus nervi vestibuli lateralis (Deiters) ; M together with y, nucleus uervi vestibuli medialis (Schwalbe); Nuc. XII, nucleus nervi hypoglossi; Nuc. VI, nucleus nervi abducentis ; F.f., pedunculus flocculi ; N.m.p. F., nucleus motorius princeps nervi trigemini ; N.o. s., nucleus olivaris superior ; A', s. V., nucleus uervi trigemini (sensory); TV. c, root bundle of nervus cochleie; N.vesi., root bundle of nervus vestibuli; Ii. d. n. re, radix descendens nervi

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vestibuli ; iS., nucleus uervi vestibuli sujjerior (Bechterew) (area enclosed iu the broad black Hue) ; Ti: s. n. t., tractus spinalis nervi tvigemini; F, nucleus ?/, antero-lateral portion of nucleus nervi vestibuli medialis ; z, decussatio nervi trigeniini.

JrConj, Cr

Fig. 3 (corresponds approximately to line 3 on the diagram, Fig. 1). G.r., corpus restifornie; F. (f., fasciculus ventro-lat

eralis (Gowersi); i^. ?.?»., fasciculus longitudinalis medialis; N. XII, root bundles of the nervus hypoglossus; Nu. d., nucleus dentatus cerebelli ; N^(. n. c. d., nucleus nervi cochlearis dorsalis ; N. o. i., nucleus olivaris inferior ; Nu. n. v. m., nucleus nervi vestibularis medialis ; Nu. t.s., nucleus tractus solitarius ; Py., pyramis ; R.d.n.i'esf.,Ym\\\ descendeus nervi vestibuli.

Fig. 3 (corresponds approximately to line 4 on the diag. Fig. 1). Br.Conj., brachium coujunctivum ; C. r., corpus restiforme; i. G'., fasciculus veutro-lateralis (Gowersi); F.J.m., fasciculus longitudinalis medialis; i\. c, nervus cochlese; N. IX and X, nervus glossopharyugeus et vagus ; JVJt. n. c. v., nucleus nervi cochlearis ventralis ; Nu. «. v. I., nucleus nervi vestibularis lateralis (Deiters) ; Nu. n. v. m., nucleus nervi vestibularis medialis (Schwalbe) ; N^i. n. v. s., nucleus nervi vestibularis superior (Bechterew) ; A^«. o. /., nucleus olivaris inferior ; Nu. y., nucleus y (anterior-lateral portion of nucleus nervi vestibularis medialis); P. /., peduneulus fiocculi ; Py., pyramis ; R. d. n. vest., radix descendeus nervi vestibuli ; (SV. )'. l, stratum interolivare lemnisci.

Fig. 4 (corresponds approximately to line 5 on the diagram, Fig. 1). jBr. Conj., brachium coujunctivum ; 0. r., corpus restifornie; F. I. in., fasciculus longitudinalis medialis; F. p., libra? pontis; iV.c, nervus cochlere; N. VI f, nervus facialis;

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JV.vesL, nervus vestibuli; Nu.n. VI, nucleus iiervi abduceutis ; JVu. n. VII, nucleus nervi facialis ; JVu. n. c. v., nucleus ner?i cochlearis ventralis; Nu.o.i., nucleus olivaris inferior; Pif., pyramis; S.g., substantia gelatinosa; St.i.l., stratum iuterolivare lemnisci; Tr.s.n.t., tractus spinalis nervi trigemini.

Fig. 5 (section 66, horizontal sei-ies). a, fibres extending between lateral lemniscus and brachium conjunctivum; Aq.c, aqueductus cerebri; /J, decussating fibres of nervus trigeminus; C. I., colliculus inferior; C r, corpus restiforme; C. s., colliculus superior; F. c, fasciculus cuneatus ; F. g., fasciculus gracilis ; L. I., lemniscus lateralis ; N. IV, root fibres of nervus trochlearis; iVJ«. «. c, nucleus alse cinerets; Nu.n.c.d., nucleus nervi cochlearis dorsalis ; Nu.f. c, nucleus funiculi cuneati; Nu.f.g., nucleus funiculi gracilis; Nu.n. v. I., nucleus nervi vestibularis lateralis (pars medialis) ; Nu. n. v. h, nucleus nervi vestibularis latei'alis (pars lateralis); Nu. n. v. m., nuc

leus nervi vestibularis medialis ; Nu. n. v. s., nucleus nervi vestibularis superior (Bechterew); Mi. n. XII, nucleus nervi hypoglossi; Nu.Vl, nucleus nervi abducentis ; Nu. Y, nucleus y (antero-lateral portion of nucleus nervi vestibularis medialis) ; R. d. n. t., radix descendens nervi trigemini ; R. d. n. vest., radix descendens nervi vestibuli ; TV. s., tractus solitarius. Fig. 6. Diagram representing flat reconstruction of nuclei nervi cochlearis and corpus trapezoideum. C. d , nucleus nervi cochlearis dorsalis ; C. f., corpus trapezoideum ; C. v., nucleus nervi cochlearis ventralis; h., portion of root bundle of cochlear nerve running past the ventral cochlear nucleus to the region of the dorsal cochlear nucleus ; I., area occupied by medullated fibres of lateral portion of dorsal cochlear nucleus ; ?«., area occupied by medullated fibres in the medial portion of the dorsal cochlear nucleus; L.I., region of lemniscus lateralis; N.c, nervus cochlea; Mo.s., complex of nucleus olivaris superior.

TYPHOID INFECTION WITHOUT INTESTINAL LESIONS.

By Simon Flexner, M. D., and Norman McL. Harris, M. B.

[From the Patliological Laboratory of the Johns Hopkins University and Hospital.']

The observation that the clinical symptoms of typhoid fever may co-exist with relatively very slight intestinal lesions indi_cative of the disease is not a new one, but it was not jiossible before the present era in bacteriological study, and especially before the isolation of the bacillus typhosus by Gaffky, to bring forward conclusive evidence of the occurrence of typhoid fever without any demonstrable intestinal lesions whatever. The studies of the last few years have shown the typhoid bacillus to be much more widely disseminated than would have been predicted, and to be associated with a considerable number of different pathological conditions. But thus far the number of instances in which the typhoid bacillus has been found in human cases which presented during life the symptoms of typhoid fever and in which there was an entire absence of intestinal lesions at autopsy, is limited to a very few authentic reports. Accepting the cases reported by Banti,f Karlinski,J and Guaruieri,!! which date from a period in which the difficulty in separating the bacillus typhosus from the colon group of organisms was less appreciated than now, there exist, in addition, in the literature available to us, the cases of Du Cazal,§ Kiihnau,^] Guinon andMeunier,** Pick,tfand especially those of Chiari and Kraus.|J

• A more complete report on this subject is reserved for the

Report on Typhoid Fever, No. 3, to be issued in the Johns Hopkins Hospital Reports, Vol. VII.

t Riforma medica, Ottobre 1887 ; Ref. Baumgarten's Jahresbericht, 1888, p. 148.

t Wiener med. Wochenachrift, 1891, No. 11 u. 12.

||Riv. gen. ital. di clin. med. 1892; Ref. Baumgarten's Jahresbericht, 1892, p. 234.

§Bull. et m^m. Soc. med. d. h6p. de Paris, 189,3, p. 243.

Tl Berliner klin. Wochenschrift, 1896, No. 30.

••Le Bull, med., 1897, p. 313.

ttWiener klin. Wochenschrift, 1897, No. 4.

XX Zeitschrift f . Heilkunde, 1897, Heft. V u. VI, p. 471.

Guarnieri as early as 1892 described a case of primary typhoid infection of the bile passages (angio-cholitis). Lesions of the intestine were absent; but cultures from the liver and spleen, as well as a culture made from the blood 12 days before death, gave growths of bacilli having the character of the bacillus typhosus. In the case reported by Du Cazal the symptoms during life were those of typhoid fever, but at the autopsy there could not be discovered, even upon the closest inspection, any lesion of the intestinal mucosa. However, the mesenteric glands, spleen and kidneys were in a swollen and congested condition, and cultures from the much enlarged spleen yielded a growth of bacilli morphologically and culturally agreeing with the bacillus typhosus.

The very recent case of Kiihnau occurred in a puerperal woman 32 years of age, who died in the eighth week of the disease. There was an absence of intestinal lesions at the autopsy. The mesenteric glands were swollen and showed areas of necroses or abscesses, the kidneys also contained abscesses, and the left internal spermatic vein contained a partially softened thrombus. Typhoid bacilli were isolated from the abscesses and from the spleen. The case of Guinon and Meunier is of much interest, as it indicates an unusual portal of entry of the typhoid bacillus. The patient, a boy 8 years of age, presented the symptoms of recent lung tuberculosis. Some days after his entrance to the hospital rose spots appeared and the temperature curve became typhoidal. The Widal reaction was positive. At the autopsy the lesions appeared to be those of acute miliary tuberculosis, small ulcers in the intestine being typically tubercular in character. Typhoid bacilli, however, wei'e cultivated from the spleen, pleural fluid and lungs. The peculiar lesions of typhoid fever were not present. Pick's case gave a marked positive serum reaction, but at autopsy no typhoid intestinal lesions and no swelling of the spleen were found; the bacteri

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ological examination gave typhoid bacilli, not, however, in the spleen.

The most important contribution to this subject has just been made by Chiari and Kraus. They had the remarkable experience of finding in 19 cases (autopsies from January to May, 1897) of typhoid fever, 7 in which the anatomical lesions of the disease were wanting. The negative eases from thepost mortem point of view had, however, given positive serum reactions. Chiari and Kraus divide the cases of typhoid fever into four anatomical groups. The first is the group of anatomically typhoid cases; the second, anatomically atypical cases in which, however, at the autopsy a diagnosis can still be made ; the third comprises cases in which an anatomical diagnosis of typhoid fever is not possible, but in which the bacteriological examination discloses infection with typhoid bacilli. Among these cases examples of typhoid septicaamia are met with. His fourth group contains instauces in which no anatomical typhoid lesions exist, the serum test during life being positive, but in which at autopsy the bacteriological examination is negative while the serum test may still be positive.

Of interest to us, in this connection, are groups II and III, especially the latter. In the three cases reported by Chiari and Kraus belonging to the second group the intestinal lesions consisted of slight swelling of follicles in the ileum or large intestine ; no necrosis. Mesenteric glands and spleen usually enlarged. The cultures from the mesenteric glands, spleen and bile were positive in one case only, so that the diagnosis of typhoid fever rests largely upon the serum reaction.

Chiari and Kraus describe in their third group five cases. These are regarded as anatomically non-diagnoscible. They represent, in their opinion, examples of typhoid septicajmia. We purposely refrain from discussing their views at this time, but will call attention only to the fact that iu three of the cases only were bacilli demonstrated in cultures. In their Case XIII, from the gall-bladder and mesenteric glands; spleen negative; Case XIV, bile immediately at autopsy negative, but from the bile after several days iu the thermostat pure culture of bacillus typhosus ; mesenteric glands and spleen negative ; Case XVII, gall-bladder, b. coli com.; spleen, staphylococcus aureus; urine, staphylococcus aureus and b. typhi; abscesses kidney, s. aureus; pneumonic lung, micrococcus lanceolatus. The remaining two cases (XV and XVI) showed upon histological examination clumps of bacilli in mesenteric glands, and in Case XV in the spleen as well; cultures negative.

• The case which we have encountered will be found to belong to the third group of the above classification. It, however, fulfills the conditions there laid down much more perfectly than any of the cases given. We are indebted to Dr. Osier for the privilege of abstracting the clinical notes.

Clinical Summary. W. G., male, aged 68, native of U. S., admitted to hospital, October 38th. On entrance complains of shortness of breath. Past history unimportant. Present illness dates back two months, since which time he has been losing weight and strength. Appetite poor. No chills or fever; no night sweats. Two weeks ago suffered from

severe pain in the back ; shortness of breath began at this time, as well as painful sensations in the abdomen. October 2Cth, while undressing, fell to the floor; very quiet next day, not having moved from the position in which he had been placed on the bed.

On admission (Oct. 38th) very dull and listless; seems in much pain ; groaning with each expiration. Kespirations -14 to minute. Thorax : somewhat barrel-shaped ; right side more prominent than left; jjercussion note in front hyper-resonant; in back more resonant than normal. Eespiration harsh; expiration prolonged; loud friction rub iu axilla. Heart: relative dullness at sternal margin 3d rib ; absolute dullness at 4th rib. Point of maximum impulse visible and palpable in 5th space 10 cm. from median line. Spleen : not palpable. Examination of blood negative for malarial organisms ; leucocytosis of 18,000. Patient gradually sank and died at 10 o'clock, October 30th.

Abstract of Protocol. — Anatomical Diagnosis. Typhoid fever without intestinal lesions ; typhoid septictemia. Thrombosis of main branch of pulmonary artery supplying lower lobe of right lung ; gangreue of lung ; perforation of pleura ; pyo-pneumo-thorax. Acute splenic tumor. Parenchymatous degeneration of liver and kidneys ; obliteration of lumen of appendix vermiformis.

Autopsy, one hour post mortem. Body of a large, stronglybuilt and moderately well-nourished man. Surface of the body presents a sallow hue. Patchy li vor mortis over posterior aspects of the trunk.

The right half of the thorax is more prominent than the left; on percussion hyper-resonant. Diaphragm at right side 7th rib ; left side 6th space. On puncturing the right pleural cavity under water free escape of gas.

The right lung is compressed, the upper and middle lobes are quite airless ; the lower lobe more voluminous ; this lobe is bound to the diaphragm by old adhesions. The parietal pleura is generally thickened and covered by a layer of shaggy fibrin. The fibrinous membrane is thickest over the visceral pleural membrane. The lower lobe is not only voluminous, but of very dark color and quite solid consistence. The pseudo-membrane covering this portion of the lung is also dark in color. On the removal of this membrane several defects in the pleura become evident ; but the whole pleural membrane is so friable that it easily breaks on handling the specimen. The main branch of the pulmonary artery supplying this lobe is occluded by a moderately firm, partially decolorized thrombus, from which more recent, usually red, thrombi extend into the communicating branches iu several directions. The section of this lobe of the lung presents a dark greyish appearance. The odor is moderately offensive.

Spleen weighs 160 grams; consistence diminished; cut surface dark iu color.

The gall-bladder moderately distended with thick, darkcolored bile. Contains a large number of small concretions (gall-stones).

The 03Sophagus, stomach and intestines, except the appendix vermiformis, which is converted into a fibrous cord, show nothing abnormal.

The mesenteric glands are not swollen.

December, 1897.]

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Bdderiological examination. Plate cultures upou agar-agar were made from the heart's blood, right lung (gangrenous portion), left lung, liver, kidneys and spleen, and a blood serum tube was inoculated from the cerebro-spinal fluid. After 48 hours in the thermostat at 37° C. the plate from the heart and the serum tube only remained sterile.

The results of the plate method were as follows : Plate from the consolidated right lung crowded with colonies, necessitating replating ; plate from left lung about 65 separate colonies ; from the spleen eleven colonies ; liver 80 to 90 colonies ; kidney a single colony only. With the exception of the single colony in the kidney, which proved to be a diplococcus forming at times short chains, a single bacillary form only was found in all the plates.

In morphology the organism isolated from the plates agreed with the bacillus typhosus. The tests employed to distinguish the colonies from each plate consisted of growths on agar-agar, potato, litmus-milk and 1 per cent, glucoseagar ; the absence of indol in Dunham's solution,* the demonstration of flagella with the arrangement seen in typhoid bacilli (peri-tricha), and finally the reaction with blood serum from a case of undoubted typhoid fever.

The bacilli isolated from the various sources were actively motile, grew characteristically upon agar-agar, slightly reddened but did not coagulate the litmus-milk, failed to ferment glucose-agar, but upou the potatoes gave vise to a slightly visible growth. Parallel cultures upon potato made with typhoid bacilli of known origin showed a similar growth in each. The agglutinating reaction was obtained in 30 minutes

with a serum dilution of 1 to 35, and in one hour with a dilution of 1 to 50.

The cover-slip preparations from the gangrenous lung and pleural exudate showed bacillary forms of several kinds, including large, coarse individuals not unlike certain putrefactive bacteria. It is interesting to note that upon the aerobic plates only the bacillus typhosus developed.

Histological examination. Study of sections of the liver, spleen and kidneys from the case stained by the ordinary histological methods, and especially for bacteria (carbolthionin, polychrome methylene-blue, alkaline niethyleneblue), failed to develop anything which especially supports the diagnosis of typhoid infection. The " lymphomata " so often found in the liver of ordinary cases of typhoid fever were absent, a single area of necrotic liver cells the size of a miliary tubercle alone being found in many sections; and the typical appearance of clumping of the bacilli in the spleen and liver was wanting, while, however, single bacilli were discovered in several sections. The spleen showed a moderate hyperplasia of lymph cells and considerable congestion; the liver cells were swollen and granular.

The tests employed for the identification of the organisms isolated from the several viscera leave no doubt as to their nature, and the case therefore is properly to be regarded as one of typhoid infection without intestinal lesions or glandular enlargement. Indeed it would have been impossible to diagnose the case as typhoid fever in the absence of the bacteriological examination.

APPARATUS FOR STERILIZINCx INSTRUMENTS WITH FORMALDEHYDE; EXPERIMENTAL TESTS.

By H. 0. Eeik, M. D., and AV. T. Watson, M. D.

At the recent meeting of the American Medical Association in Philadelphia, Dr. E. A. de Schweinitz, bacteriologist to the Bureau of Animal Industry, United States Department of Agriculture, presented to the Ophthalmological Section a paper treating of the sterilization of instruments by formaldehyde, both in solution and in the gaseous form.

Knives which had been used in dissecting were washed in water and placed in a 1 to 2000 formaldehyde solution. It was found that in thirty-five minutes they were completely sterilized.

In testing the effect of the gas, a small copper drying oven was used, and 25 cc. of 40 per cent, formaldehyde solution (the preparation known as formalin) was placed in a small dish in the bottom of the oven. The instruments used were proven sterile, then infected with staphylococcus pyogenes aureus, wiped with dry cotton, placed in the oven, and when tested after ten minutes showed growth on culture media. If knives infected in a similar manner were rinsed in hot water, wiped dry and placed in the oven, no growth was

•Planted in Peckham's alkali-peptone bouillon and incubated for 3 days, a faint but unmistakable indol reaction could be obtained. See Journal Experimental Medicine, No. 5, 1897.

noted after a teii minutes' exposure. Forceps treated in the same way required from fifteen to twenty minutes. The gas used was obtained by spontaneous evaporation of formalin, but it is important to note that "the solution of the gas was placed in the oven some hours before the instruments which were to be disinfected, in order that a sufficient volume of the gas might be present to act immediately upon the organisms adhering to the knives."

The length of time required to disinfect the knives by the formalin solution and the length of time required to generate the gas in the chamber previous to disinfection would materially interfere with the practicability of these methods, for if so much time is necessary to put them into operation they offer but little advantage over other methods.

Again, we would respectfully suggest that the tests were scarcely conclusive as to the value of the gas, for, may not some portion, at least, of the disinfection have been produced by the rinsing of the infected instruments in hot water and their subsequent wiping with dry cotton ?

We have seen no other report of work in the direction of disinfecting instruments with formaldehyde, although Dr. Valude, in the Revue Generale d'Ophthalmologie for July, 1893, recommended that, " as formalin does not attack metals,

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it is well adapted for antiseptic solutions in which to keep instruments before and during operations."

The report by Dr. de Schweinitz, however, in connection with the experiments of others to disinfect various objects and large areas, led us to expect that instruments could be more quickly sterilized by the gas if it could be conveniently and rapidly prepared in a small apparatus. We used in our experiments the box exhibited here, simply an air-tight tin oven with a capacity of 1} cubic feet. By the introduction of wooden blocks the capacity was reduced to 1 cubic foot. Two racks or trays for holding instruments are suspended in the upper half of the box and the gas is manufactured below. We first attempted to secure the gas by spontaneous evaporation. One hundred cc. of the 40 per cent, solution, formalin, was placed in an evaporating dish in the bottom of the box and presented a surface of about 16 sq. inches. The knives and probes here presented, and which were used in all our tests, were infected with a fresh culture of staphylococcus pyogenes aureus and placed on the racks over the formalin dish. The cover was then removed from this dish, the door of the apparatus quickly closed and evaporation allowed to proceed. At the end of 1 minute the door was opened, the knife removed, and the formalin dish re-covered. A culture was made from this knife upon agar and placed in the thermostat. Control cultures were also made from the aureus used, in order to be sure of its vitality.

This experiment was repeated with the exception that the time of exposure was lengthened to 2, 3, 4, 5, 10 and 15 minutes. Then a jump of large intervals was made, the tests being at half-hour intervals up to four hours. In every interval between the tests the door of the box was left open to permit escape of the gas, so that there might be no accumulation of it and we might thus be able to determine just how long au exposure to the spontaneous evaporation of the gas would be necessary. The time proved much longer than we had expected, and it was only after a 2i hour exposure that we could feel sure of sterilization. This would evidently not do for practical work and we were compelled to look for some more rapid means.

We did not use formalin for the generation of the formaldehyde gas by heat, for two reasons : 1st, we feared that the heat which would drive off the gas would at the same time vaporize the water which contained it and thus possibly cause a rusting of the instruments; 3nd, we found in paraform a much more convenient substance for the purpose.

Paraform is polymerized formaldehyde and occurs as a light white jjowder, which can by means of heat be entirely converted into formaldehyde. Commercially it can be obtained in the form of j)astilles weighing 1 gram each.

The next problem was how to get the gas in the chamber. Should it be generated outside and then introduced, or could we generate it inside the apparatus ? To generate it outside has many objections. Our next experiments were made to discover if it were possible to vaporize the tablets by means of a lamp inside the closed chamber. We feared that the oxygen contained in the chamber would not support combustion long enough to develop suflBcient heat to generate the amount of formaldehyde needed. Our fears in this regard

proved to be quite unfounded, but we found that the kind of alcohol lamp used was a very important factor. After using two ordinary alcohol lamps in our possession we abandoned them for the Sobering formalin lamp, which we found more efficacious, generating far more gas with the amount of oxygen at our disposal and beins: much more economical in the use of alcohol.

This lamp we find will burn in a closed chamber containing 1 cubic foot of air for about 14 minutes. In that time it will vaporize 35 grains of paraform. The temperature of the apparatus will be raised in this time to less than 30 degrees Centigrade, so that the element of heat does not affect our results.

This amount (35 grains) of paraform was found to be far in excess of the quantity necessary to disinfect this chamber. We then proceeded to find the minimum amount of paraform required to disinfect the chamber in a reasonable length of time. We vaporized quantities ranging from 3 grains up to 10 grains for different intervals of time. Even 2 grains will sterilize the chamber if given sufficient time. Three grains will do it in 15 minutes, 5 grains in 10 minutes, and 10 grains in 7 minutes. We could not proceed in this way indefinitely to use larger quantities and diminish the time because 10 grains in 7 minutes is the full vaporizing capacity of the lamp. Nor is it desirable to increase the amount of jiaraform, for when the chamber is opened there is an escape of gas into the room which, while not injurious or particularly objectionable, yet is not to be desired. For practical purposes 10 or 15 miniites is a short enough time for the sterilization of instruments, and this can be done with 5 or 3 grains of paraform.

The micro-organisms used in these experiments were the staphylococcus pyogenes aureus and the anthrax bacillus. The knives were sterilized by boiling and then infected from slant agar cultures. The germs could in every instance be seen en masse upon the instruments when put into the chamber. After exposure to the gas, cultures were made upon slant agar.

One feature of this disinfection by evaporation of the paraform needs a little further investigation. After performing numerous experiments during which large quantities of paraform were vaporized, there appeared upon the sides of the chamber a thin greasy deposit which afterwards became converted into a dry white powder. This, we are informed from the literature on the subject, is paraform which has become deposited again from the gaseous state. We did not in any instance find this deposit visible upon our instruments, still the possibility of its adhering we have in mind, and later will experiment to determine whether or not it is present, and if so, whether or not it would have a deleterious influence upon wounds. From the literature at our command we believe that there is but little danger from this source.

Another important matter to be considered is whether or not the cutting edge of the instruments is dulled by this method of disinfection. Upon this point we have the opinions of Drs. E. A. de Schweinitz and Swan M. Burnett of Washington, who state that from the use both of the gas and of the liquid formalin there has been no influence whatever upon the sharpness of the instruments.

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From these experiments we conclude that :

1st. A lamp will hum in any absolutely closed chamber long enough to generate more than sufficient formaldehyde for its disinfection.

2nd. In a chamber of 1 cubic foot space 3 grains of paraform in 15 minutes, or 5 grains in 10 minutes, will accomj)lish disinfection.

3rd. The expense of such disinfection, including the cost of paraform and alcohol, will not exceed 1 cent, and the labor involved is almost nil.

4th. For the disinfection of small instruments, such as those used by ophthalmologists, otologists, laryngologists and dentists, it is by far the most convenient and speedy method.

5th. This method, probably better than any other, for the work designed, carries out the principles of disinfection laid down by Koch, viz. " the absolutely certain destruction of all pathogenic organisms, in the shortest possible time, at the least expense and with a minimum of injury to the object of disinfection."

E. B. Meyrowitz, of New York, has in preparation an apparatus specially designed by us for the use of this method, and Sobering and Glatz will manufacture pastilles of 5 grains each for use in the apparatus.

In concluding we wish to thank Dr. McShane for permission to conduct these experiments in the City's Bacteriological Laboratory, and Dr. Stokes for advice and guidance in our work.

Discussion.

Dr. OuLLEN. — Dr. Hurdon is, at the suggestion of Dr. Kelly, now carrying on experiments in this line. The apparatus used contains about 6 cubic feet, and particular attention has been paid to the sterilization of dressings. Using four pastilles of paraform it was possible to render a piece of gauze that had been dipped in a jnire culture of anthrax, sterile in ten minutes, but if the piece of gauze was wrapped in seven or eight layers of gauze and this bundle enveloped in three thicknesses of foolscap paper, twenty minutes were required for sterilization. The only disadvantage noted was that on opening the box the escaping gas caused considerable irritation of the eyes of those in the room. With regard to the effect on instruments I was glad to hear what Dr. Keik said, because the ophthalmologist's instruments are so delicate, and, as Dr. Kinyoun, in a recent report on experiments with formaldehyde, states that gold and

silver are not affected, but that the effect on the iron is to cause oxidation.

Dr. Theobald. — I was very much interested in the report by Dr. Reik, and I think it would be a distinct advantage if we could have such a sure and easy method of disinfection of our instruments. It is very diflBcult to submit our instruments to boiling or even to dry heat without dulling the knives, and they also become tarnished when immersed only for a few moments. To sterilize them by this method would certainly seem to be a distinct gain.

Dr. Watson.— I would like to ask Dr. Cullen whether Dr. Hurdon found much deposit on the bandages. I read in a circular issued by the manufacturers of the pastilles that after vaporizing the paraform it was readily deposited upon woolen goods. We did not find it on the knives at all, and thought possibly this might be due to their smooth surfaces or to the nature of the metal.

Dr. Cullen. — The box used was six cubic feet, very large, and Dr. Hurdon has not noticed any deposit.

Dr. Stokes. — These experiments are of value when viewed from several different standpoints. It is a good thing to have proved that the spontaneous evaporation of the gas is not a very practical method for the sterilization of instruments, and again it is of value to have shown that the evaporation of such small quantities of the gas from the solid pastilles will cause the thorough surfiice disinfection of such a chamber.

This work seems to show that it is possible to render not only the instruments of the ophthalmologists sterile, but to destroy bacteria on the surfaces of even larger instruments, and so this method may be applied in general surgery.

I am also glad to learn from Dr. Cullen that several layers of gauze can be disinfected even when wrapped in paper, for that seems to show that the ordinary dressings used by the ophthalmologists, for instance, may be rendered sterile. I think the general experience with formaldehyde has shown that with finely woven textures, like cotton, penetration is a difficult thing to attain.

In regard to Kinyoun's experiments, they were performed in a large room and the gas was allowed to remain in contact with the iron lor some time. I hardly think that any harm could be done the instruments in just the few minutes they are exposed in this chamber, but this can be determined by further experimentation.

PROCEEDINGS OF SOCIETIES.

THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Meeting of October 4, 1897. Dr. Barker in the Chair.

Exhibition of Specimens.— Fibroid Lnng-Bronchiectasis—

Brain Abscess. — Dr. Livingood.

The first is a section of lung showing fibroid induration. The upper lobe is uniformly solid, grey and very firm. The middle lobe is not so firm. The lower lobe is congested and shows an area of fibrous induration in the lower part. Extend

ing through these solidified portions are tubular bronchiectatic cavities with blood-stained walls.

The other specimen is a section through the right hemisphere of the brain about the paracentral convolution, in the upper part of which is an abscess cavity the walls of which are irregular.

Both these specimens came from the same case and demonstrate an interesting association. Their color is partially preserved by the Kaiserling method, but is no longer as intense as at the time of autopsy.

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The case was that of a young colored man (F. C), 21 years old, who was brought here by strangers in a half-conscious condition, so that at the time of admission no history at all could be obtained, except that he had been working but half a day at North Point, when he was " taken with a fit," his condition later being the same as at the time of admission. It was learned later that he had been living a rough life, wandering about the country in search of work ; that he had had a cough for two years and was said by his friends to have had "consumption."

On admission he did not present the appearance of one who was suffering from chronic disease ; his frame was well formed and there was no evidence of emaciation. He died four days after admission. During this time his condition remained about the same, except that he became progressively weaker, and during the last two days had an apparent right-sided hemiplegia and athetoid movements of left arm. His greatest distress seemed to be a violent pain in the head. He was in profound stupor during this whole time ; was seized with paroxysms of coughing of a sharp, moist character, accompanied by very little expectoration owing to his weakness and stupor. The sputum which was obtained was of a dark reddish-brown color, containing necrotic material and of extremely foetid odor. Examination showed it to contain pus and epithelial cells and a great number of organisms, both cocci and bacilli, none of which showed the typical staining reaction of tubercle bacilli. He was extremely restless at times, and in the last two days showed athetoid movements of the left side. I will have to omit the other interesting nervous phenomena which were noted by Dr. Camac and Dr. Bardeen at different times. His temperature curve was very irregular, running up each evening ; once to 104.5° F.

Physical examination of his chest indicated complete consolidation of the upper lobe of the right lung, which was noted to be very intense ; signs of partial consolidation in the lower lobe. Associated with these signs were coarse, moist rdles. The left lung was apparently normal during the first three days, on the fourth day there developed signs of broncho-pneumonia.

At autopsy the right pleural cavity was found obliterated in the upper part. The middle lobe of the lung was slightly adherent. The lower lobe was very firmly attached to the diaphragm about the middle of its posterior margin. The fibrous adhesions about the upper lobe were very dense, and at two points the sub-pleural tissue seemed to be involved, so tliat on freeing the lung some of its substance remained adherent to the ribs at these points. In this way two cavities were exposed extending into the lung tissue.

The pleura covering the upper lobe was oedematous. The lobe was strikingly firm, voluminous, with little puckering and of grey color. The middle lobe was more resistant than normal, likewise grey, but more translucent than the upper lobe. The lower lobe was for the most part congested, but through its substance ran an area of fibrous consolidation, broadest in the lower part where the lung was adherent to the diaphragm.

On section through the lung, the upper lobe had a firm, glistening, almost cartilaginous appearance, with broad

strands of fibrous tissue radiating out from the thickened bronchi. Scattered over the surface were small translucent and opaque yellow points resembling miliary tubercles. The middle lobe was not so completely solidified, it appeared more translucent and elastic. The lower lobe had a salmon pink color; its density was generally increased, and through its centre extended downwards an area presenting the same condition as upper lobe.

Through the upper, middle and dense portion of lower lobe ran tubular cavities, the lumen about a centimeter in diameter. The walls were much thickened and the inner surface hsemorrhagic. These cavities communicated freely with the bronchi, and sections showed that they were directly continuous with them. They contained a fcetid, blood-stained muco-pus. The peribronchial glands were enlarged, but showed no tubercles. The left lung was congested and in the lower lobe showed patches of broncho-pneumonia.

Examination of the brain showed that the dura was adherent and thickened, especially on the right side. There was slight oedema of the pia at a point where the brain surface was discolored and depressed. This corresponded to a point at the upper end of the fissure of Eolando in the right hemisphere. On lifting up the pia an underlying cavity discharged a small amount of a greenish foetid pus. This cavity, measuring about 3 cm. in all diameters, was seen to occupy the paracentral convolution and to cause a bulging of this area into the longitudinal fissure. The ascending frontal convolution showed no involvement, but the area of softening extended down the ascending parietal convolution for a distance of 5 cm.

Microscopically the induration of the lung is seen to consist of broad strands of fibrous tissue which represent thickened inter- and intra-lobular connective tissue. These main strands have the appearance of old fibrous tissue, poor in cells. Encroaching still more upon the bronchioles and individual alveoli is a younger, much more cellular, fibrous tissue, which surrounds them and which has compressed the alveoli into the form of small racemose gland acini, the epithelium having reverted to its embryonic cubical form. Often the alveoli are filled with fatty epithelial ceils which, in the gross specimen, gave the appearance of caseous tubercles. The walls of the bronchi are very thick and are surrounded by cellular fibrous tissue, and are infiltrated withpolymorpho-nuclear leucocytes. The bronchi are filled with pus cells and desquamated epithelial cells. The induration in the middle lobe is of the same character but is not so complete. There is a slight deposit of coal pigment in the peribronchial tissue.

The type of fibroid lung here seen is not that which has been described by Ziegler, Von Kahlden and others, in which there is an organization of an alveolar exudate by an outgrowth from the connective tissue of the alveoli, nor of the type secondary to atelectasis described by Orth. It is rather a more common form due to a thickening of the interlobular connective tissue, but is of interest in its extensiveuess and in the distribution which seems to indicate its etiology. Structurally it has the appearance, described by Charcot, which follows subacute broncho-pneumonia.

By far the commonest cause of fibroid lung is tuberculosis,

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but I think that we have grounds to exclude this in the present case. There is no evidence of tuberculosis elsewhere, no appearance of tubercle or of tuberculous tissue in the lung itself, no areas of caseation, sections stained for tubercle bacilli after careful search failed to reveal the organism. There are a few giant cells, but they have the character found about foreign bodies, with centrally located nuclei and distinct, rounded peripheries.

Inhalation of dust and of irritating vapors is a frequent cause of induration. As in this case there is a distribution along the bronchi, but our specimen shows but little foreign substance, coal pigment, — not enough to give rise to the marked changes.

Syphilis, which has its distribution along the bronchi, is difficult to exclude, although its involvement is usually at the root of the lung and is sometimes associated with gummata. The distribution and histological picture in this case seem to indicate that it is one of those cases of induration subsequent to the absorption of toxic substances, bacterial in origin, by way of the bronchi : a subacute bronchitis and peri-bronchitis. The irritation is not intense enough at any time to produce an acute reaction throughout the lung, but sets up a slow formation of connective tissue. Subsequently, as frequently happens, there is the formation of bronchiectatic cavities at the points where the bronchial walls are weakened by the more intense effects of the toxic substances, and these cavities in turn offer opportunity for lodgment and activity of various kinds of bacteria. In this way a fresh inflammatory process is lit up and a vicious circle is established which in time causes complete induration of the lung tissue.

The association of brain abscess with bronchiectatic cavities has frequently been noted. Williamson has recently reported that out of 39 cases of brain abscess, 17 were associated with putrid bronchiectasis.

On cover-slips from the cavities there appeared a great variety of organisms, from which I succeeded in isolating but one, the pyogenic streptococcus. Cover-slips from the brain abscess showed likewise a great number of organisms, some of which I had recognized on cover-slips from the lung. None, however, grew out on my culture plates. If the streptococcus pyogenes was present, it failed to grow.

NOTES ON NEW BOOKS.

Burdett's Hospital and Charities, 1897, being the Year-Book of Philanthropy, containing a Review of the Position and Requirements, and Chapters on the Management, Revenue and Cost of the Charities, etc. By Henry C. Burdett, Editor of "The Hospital." [London: The Scientific Press, Limited, 1897.) We have had occasion in previous years to speak in the highest terms of this Year-Book which is now in the eighth year of publication. It presents a volume of statistics of the greatest utility to all who are engaged in any form of philanthropic work. It would be fortunate for all charitable boards, not only of hospitals, but of missionary societies, orphanages, nursing and convalescent homes, if copies could be placed in the hands of each member.

As might be anticipated in view of the fact that the Queen of England and the Prince of Wales have shown great interest in hospitals and nurses' training schools, two chapters of the present

volume are given up to the Queen's commemoration and the Prince of Wales' fund for the relief of distressed London hospitals.

The chapter on "Hospital Construction during 1896" is a new feature and one which is destined to become increasingly valuable. Il gives sensible and brief criticisms on the plans of infirmaries, general hospitals, nurses' homes, cottage hospitals and convalescent homes which have been erected in Great Britain during the year. If a similar chapter can become an annual affair it is altogether probable that many mistakes in future hospitals will be corrected. The editor in a previous volume recommended that all hospital plans be revised by competent experts prior to letting any contracts or commencing any building. It is to be hoped that the present attempt to criticise hospital plans may eventually lead to this.

We are much gratified to know that the editor still insists upon his former dictum in hospital expenditures, viz. that lavish expenditures do not necessarily imply efficient administration. The list of institutions for the insane in the United States is far from complete and should he revised before another edition of the book.

Lectures on the Malarial Fevers. By Wm. Sydney Thay'er, Associate Professor of Medicine in the Johns Hopkins University, pp. 1-326, with 19 illustrative charts and 3 lithographic plates. (New York: D. Appleton & Co., 1897.)

The publication of this book has occurred opportunely. The exhaustive studies which have been made during the past seventeen years have led to marked changes in the ideas of the medical profession concerning the nature of the malarial diseases. These researches, especially those dealing with the parasitology, have now attained to a degree of completeness which permits of a satisfactory collective treatment of the subject.

When Laveran in 1880, while studying the blood of fever patients in Algiers, discovered the malarial parasite, he could have had but little idea of the richness of the mine in which he was doing such successful prospecting. He knew he had made a valuable finding, for within a month after his first positive observation a preliminary paper concerning it was presented to the Academy of Paris. This was soon followed by other communications from the same investigator, who appeared to be well aware that where so valuable a nugget had been easily extracted, richer treasures might reasonably be supposed to exist.

Laveran was at once convinced, on seeing the organism, that he was dealing with a living parasite. He studied the various forms which it assumed, and the descriptions which he has given us of his early observations are interesting and accurate. His contributions, however, remained for some time without marked influence, a fact attributable largely to the wide acceptance met with by the ideas concerning the aetiology of malaria which had been advanced by Klebs and Tomassi Crudelli in 1879. The doctrine of the bacillary origin of malaria, fathered by these investigators, was advanced in the blooming period of the science of bacteriology at a time when protozoan diseases had scarcely been heard of. Notwithstanding its falsity it is perhaps but little wonder that it attained to such sudden general credence.

Although Richard, as a result of his own research, confirmed Laveran's statements, and the latter made personal demonstrations of the parasite to others, it was not until some five years later that general interest became aroused in the subject and investigators in different countries recognized the truth and significance of his reports. About this time a number of clinicians began investigating for themselves, and since 1885 a host of men have been at work at the subject in the most different parts of the world, perhaps most actively in Italy and America.

Three distinct varieties of the malarial parasite have been identified: (1) that of quartan fever; (2) that of tertian fever ; (3) that of the sestivo-autumnal fevers. Each of these varieties of the parasite undergoes a peculiar and characteristic developmental

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cycle, culminating in its multiplication by the process of segmentation. Coincident with the segmentation simultaneously of a large group of parasites a malarial paroxysm occurs.

The cycle of development of the parasite in quartan and tertian infections was first made out by Golgi ; that of the restivo-autumnal fevers was independently established by I\Iarcbiafava and Celli and Canalis.

The clinician has now at his ilisposal a mass of diagnostic and prognostic data with reference to the malarial diseases. Not only have the various stages in the developmental cycle of each variety of the parasite been accurately studied and described, but the time relations in the different cycles have been ascertained with astonishing exactness. The skilled hamatologist can now decide, from his study of the blood alone, not only that he is dealing with a case of malaria, but also as to the particular nature of the attack. He can tell the patient the periods of past paroxysms, and if the case be left untreated, can prophesy within tolerably narrow limits the time of occurrence of those to come. He is afforded many clues as to the gravity or benignancy of a given infection, and is able to draw valuable conclusions concerning the probable efficacy of quinine in a given case. He is further able to pass judgment as to whether urgency in the treatment is essential, and thus is ready to suggest the method of administration of the specific drug most suitable to the case.

The bibliography of the malarial fevers has by now assumed enormous proportions, for although many important veins remain to be followed up, the malarial mine has already been very thoroughly worked. In the process much pure metal has been extracted. A great deal of valuable material is still mixed, however, with baser mineral, and unfortunately the literature also is encumbered with quantities of spurious ore, consequent mainly upon investigation guided by the "divining rod" of preconceived idea.

To write a comprehensive and discriminative book on the malarial fevers correspondent to the needs of students and practitioners at the present time, one not only must be widely read in the bibliography of his subject, but he must also have had an extensive practical acquaintance with the microscopic characters of the blood of a large number of patients at various seasons of the year. To read and assimilate all the articles — and there are now many hundreds of them — dealing with malaria since 1880 is of itself no small task. To painstakingly analyze more than 1600 cases of malarial infection in which the type-diagnosis has been established by actually demonstrating the variety or varieties of the parasite present in the blood or in the juice removed from the spleen is a laborious undertaking. "It's dogged as does it," but it is thus that the author of the lectures before us has qualified himself for his work.

Dr. Thayer's book, which, very appropriately we think, he has dedicated to Dr. Osier, contains nine lectures. In these the essential facts concerning the parasitology of the disease, the clinical phenomena, the morbid anatomy, the pathogenesis, diagnosis, prognosis, treatment and prophylaxis are dealt with.

In the first lecture a brief history of the development of knowledge concerning the pathogenic agent of the malarial fevers is given. Copious references in the form of footnotes make it possible for the reader to consult the original articles in all languages. The different views which have been advanced concerning the classification of the parasites, their finer structure and manner of reproduction, are here briefly but clearly discussed. The author believes in the specificity of the three main types of malarial parasites —tertian, quartan, and restivoautumnal, and combats the idea still held by some that the organisms are all varieties of one parasite, and that the morphology varies simply according to the season of the year and the conditions to which it is subjected. To the viewformerly expressed in his monograph (in conjunction with Hewetson) entitled "The Malarial Fevers of Baltimore," concerning the parasites of the sestivo-autumnal fevers, namely, that they all rep

resent varieties of one specific type, and are not divisible into a quotidian and tertian variety as Marchiafava and Bignami assert, in the absence of inoculation experiments bearing on the question, the author still adheres.

The methods of examination of the blood and the appearances of the different varieties of the parasite in all stages of development in fresh blood and in dried and stained specimens, are described at length in the second and third lectures. We are glad to see italicized as the opening paragraph of this section of the book the following statement : — "It is impossible to make reliable examinations of the blood for malarial parasites without first being familiar with the ordinary appearances of normal blood and the more common pathological changes." How many unfortunate mistakes and lamentable exhibitions of ignorance would have been avoided had the appreciation of this fact been more general ! Non-acquaintance with thevacuolelike appearances so often met with in the red corpuscles, certain puzzling forms encountered in poikilocytic conditions, the blood platelets, the various kinds of white blood corpuscles which exist, or the artefacts which can arise from faulty preparation of the specimen and the like, has led many an observer into error, and has been responsible for more than one publication which should have, if it has not, made its author long for an obscurity in which, as Johnson put it, he could be " glad to be hid, and proud to be forgot." However excusable some of those may have been who have fallen into such traps in the past, there is no longer any justification for the repetition of these foolish and unnecessary errors, and it is a pity that articles containing them still occasionally creep into respectable medical journals.

All who have had practical experience will agree with the statement on page 35 that "the best method of studying the malarial parasite is in the fresh untreated blood at the bedside or in the consulting room." Dried and stained specimens are at best an unsatisfactory substitute for the fresh blood-slide. The directiors given in this section are detailed and might at first thought seem unnecessarily minute, but any one who has observed students fail over and over again simply from the non-observance of some trifling technical point will approve of the explicit directions. It would seem scarcely possible, with the clean-cut morphological description of tertian, quartan andrestivo-autumnal parasites given in these pages, that the careful student should fail to identify them, especially as the descriptions are accompanied by three admirable lithographic plates reproducing Max Broedel's drawings made directly from the parasites in the fresh blood. These plates include some 35 illustrations of the parasite of tertian fever, 17 of those of quartan, and 49 of those of £estivo-autumnal fever. In fact, all the forms likely to be met with in ordinary clinical examinations are faithfully delineated.

The various views which have been advanced concerning the nature of the flagellate bodies are outlined on page 78 and the following three pages. Since the writing of Dr. Thayer's book, much new light has been thrown upon these curious structures by the researches of Dr. W. G. MacCallum. When another edition of the book is called for, it will be the author's pleasant task to supplement the unsatisfactory hypotheses concerning the flagella referred to in the present volume with a description of the process of fertilization in the malarial parasite, as observed by the investigator referred to.

The general conditions under which the malarial fevers prevail are dealt with on pages 82 to 96. The geographical distribution ; the effect of climate, seasons, time of day ; the influence of moisture, soil, altitude, and winds; the effects of cultivation and drainage of malarious districts ; the relation of malaria to the drinking water, are among the topics which here receive atten^tion. There are short paragraphs also on the significance of race, sex, age and occupation in connection with malaria. The various modes of infection which have been suggested are discussed ; it is to be regretted that the author, concluding this section, is compelled to make the statement, " We are absolutely ignorant of the form in

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which the malarial parasite exists outside of the human body, and equally ignorant of the manner in which it enters."

The clinical description of the malarial fevers is given in Lectures IV and V. Each type of the fever is analyzed, and the various modifications met with fully illustrated. This portion of the book is liberally interleaved with charts showing the temperature-range in typical cases personally observed by the author. The description given of the pernicious fevers is worthy of especial mention, as are the paragraphs dealing with masked malarial infections, and the cases in which combined infections with dilferent varieties of the malarial parasite have been encountered.

The sequelaj and complications of the malarial fevers are next taken up. The eases in which simple insolation has been confused with pernicious malaria are among those referred to under this heading.

In his lectures on the morbid anatomy of the malarial diseases, Dr. Thayer follows closely the accurate ilescriptions of Bignami, the investigator who certainly has made more important contrilmtions in this field than any other single individual. The anatomical changes in both acute and chronic infections are clearly set forth, though not at greater length than is consonant with the nature of a clinical manual.

The only part of the book in which the writer has indulged in speculation is in Lecture YIII, the section on General Pathology. The hypotheses brought forward are, however, unmistakably designated as such, and nowhere are they confused with a statement of facts. Considering the extended first-hand knowledge which the author possesses, there will be scarcely any one, we believe, deeply interested in the problems discussed, who will not seek his opinion respectfully regarding disputed points, or who will not weigh carefully the conclusions to which he has arrived. Dr. Thayer thinks it highly probable that the febrile manifestations in malaria are excited by the presence of circulating toxic substances, and proceeds to enquire as to the nature and origin of the toxines. Considering the data at hand he says (p. 254) : " Despite the lack of absolute proof, we are inevitably led to the conclusion that the most important exciting cause of the malarial paroxysm is the liberation of some toxic substance by the specific parasites at the time of their sporulation. While, very possibly, toxic substances may arise as a result of the disintegration and destruction of red blood corpuscles which occur at this period, it is improbable that these play the primary part in exciting the paroxysm."

After brief paragraphs upon the pathogeny of the antcmia, the pain in the bones, the jaundice, the cerebral symptoms, and the phenomena referable to disturbance of the alimentary tract, two important topics are considered : (1) The Origin of Infections with Multiple Groups of Parasites, and (2) The Mechanisms of Defence in Malarial Infections. With regard to the former subject, the author thinks that the main difficulty lies in the explanation, not of the multiple seativo-autumnaH but rather of the double tertian, and of the double and triple quartan infections. The occurrence of the paroxysms so nearly at intervals of 24 hours, and the tendency to segmentation in the morning hours, are especially difficult things to explain, and it is admitted that the whole question still remains unsolved. The author believes that a number of the cases represent instances of multiple infection from the beginning, but thinks that there are examples in which a second group may be derived from one original generation, through anticipation or retardation of the ripening of certain of the parasites. Some ingenious suggestions are offered to explain this process, and especially to account for the fact that the anticipation or retardation usually amounts to almost exactly twenty-four hours.

As regards the mechanisms of defence involved in malarial infections, the author is of the opinion that too much stress has been laid by many upon the riMe played by phagocytes. He would rather assume that the more important factor in spontaneous cure is some parasiticidal substance or substances circulating in the

blood serum, admitting, however, that the latter may be of cellular origin. The dispute is an old one, and is not limited to malaria alone, but pertains to the whole group of infectious diseases, and is, moreover, one not likely to be settled to the entire satisfaction of all, at least in the very near future.

The last chapter of the book deals with diagnosis, prognosis, treatment, and prophylaxis. This chapter is eminently satisfactory. The disease is sharply differentiated from conditions likely to be confounded with it, and the diagnosis is helped out to a certain extent by the introduction of comparative tables in the text. Concerning the treatment, the writer seems to have rejoiced at the opportunity of dealing with a disease in which there can be no talk of therapeutic nihilism. The modes of administration of the specific drug best suited to the different kinds of malarial infection are treated of at some length. Sensible advice is also given as to the application of general measures, such as rest in bed, change of surroundings and diet.

The work of the publishers is, on the whole, excellent ; the type and paper are agreeable, and the binding neat. One finds rather more imperfect letters, however, than should appear in a first edition. We prefer the spelling defence rather than defense as employed throughout the book. The index is full, and as far as we have tested it, accurate. The introduction of an in<lex of authors' names is a pleasing feature. The book will not only be valuable to clinicians in the districts in which malaria prevails, but doubtless will, from the especial interest which the subject has excited, also appeal to many who practice in regions in which the disease is but rarely met with. L. F. B.

A Manual of the Practice of Medicine. By Geoege Roe LocKwoon, M. D., Professor of Practice in the Woman's College of the New York Infirmary, etc. With 75 illustrations in the text and 22 full-page colored plates. (Philadelphia: W. B. Saunders, 1890.) This admirable little book is a useful manual for students and medical men who desire to get terse and clear accounts of diseases and their treatment. Some of the sections are models of concise, orderly and systematic statements. Take for example the opening section on typhoid fever, the sections on nervous diseases and the section on malarial fever. Some of the remarks on treatment are less satisfactory, as for example, in the treatment of cholera infantum no mention is made of the desirability of withdrawing milk, which in the majority of cases is the essential thing to do. In delirium also bleeding and purging are recommended. The letterpress and illustrations are good, and the book is almost wholly free from annoying typographical errors. We notice, however, that cholera nostras appears as cholera nostra.

BOOKS RECEIVED.

A Pictorial Atlas of Skin Diseases and Syphilitic Affections, in Photolithochromes from Models in the Museum of the Saint Louis Hospital, Paris. By E. Besnier, A. Fournier et al. Edited and annotated by .T. J. Pringle, 1\LB., F. R. C. P. Fol. 1897. Part XII. AV. B. Saunders, Phila., Pa.

Constipation in Adults and Children. With especial reference to habitual constipation and its most successful treatment by the mechanical methods. By H. lUoway, M. D. Svo. 1897. 495 pages. The Macmillan Co., New York.

Twenty-eighth Annual Report of the State Board of Health of Massachusetts, 1896. Svo. 920 pages. 1897. Wright & Potter Printing Co., Boston.

Fiftieth Anniversary of the Hartford Medical Society. Founded September 15, 1846. Proceedings at the Celebration, October £G, 1896. 4to. 124 pages. Hartford, Connecticut.

Essentials of Bacteriology : being a Concise and Systematic Introduction to the Study of Micro-organisms. M. N. Ball, M. D. Third edition. 1897. 12mo. 218 pages. W. B. Saunders, Phila.

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Archives of the Roentgen Uai/. (Formerly Archives of Skiagraphy.

Edited by W. S. Hedley, M. D., and S. Rowland, M. A. Fol.

Vol. II, No. 1. July, 1897. The Rebman Publishing Co.,

Limited, London. W. B. Saunders, Philadelphia. Pathological Technique. A Practical Manual for the Pathological

Laboratory. By Frank Burr Mallory, A. M., M. D., and James

Homer Wright, A. M., M. D. 1897. 8vo. 397 pages. W. B.

Saunders, Phila. Transactions of the Chicago P.ithological Society from December, 1895,

to April, 1897. Vol. II. 1897. 12mo. 328 pages. American

Medical Association Press, Chicago.

Report of the Sewerage Commission of the City of Baltimore ; consisting of Mendes Cohen, F. H. Hambleton and E. L. Bartlett, appointed by joint resolution of the City Council, approved May 25th, 1893. 8vo. 1897. 231 pages. (Plates.) Baltimore, 1897.

An Epitome of the History of Medicine. By Roswell Park, A. M., M. D. Based upon a Course of Lectures delivered in the University of Buffalo. 1897. 8vo. 348 pages. The F. A. Davis Co., Phila.

A Te.vt-Book of the Practice of Medicine. By James M. Anders, M.D., Ph.D.,LL.D. 1898. 8vo. 1287 pages. W. B. Saunders, Phila.

INDEX TO VOLUME VIII. OF THE JOHNS HOPKINS HOSPITAL BULLETIN.

Abel, John J. On the blood-pressure-raising constituent of the suprarenal capsule, 151.

iEsthesiometer, 125.

Anatomical relations of the nuclei of reception of the cochlear and vestibular nerves, 253.

Apparatus tor sterilizing instruments with formaldehyde; experimental tests, 201.

Arch of aorta, anomaly of, with additional muscle in neck, 234.

Atkinson, A. Duval. Parotitis following visceral inflammation, 204.

Bacillus aerogenes capsulatus (Welch), cases of infection by, 68.

Bacillus aerogenes capsulatus, observations to determine motility of, under anaerobic conditions, 74.

Bacillus proteus Zenkeri in an ovarian abscess, 4.

Bad Nauheim, visit to, 101.

Bardeen, C. R. Certain visceral pathological alterations, the result of superficial burns, 81; — Edingeron "The Development of Brain Paths in the Animal Series," 120.

Barker, Lewellys F. A new sesthesiometer, 125 ; — Congenital facial diplegia, 131 ; — Demonstration of Florence's iodine test for seminal stains, 133 ; — Hsemocytozoa of birds, 52 ; — Phrenology of Gall and Flechsig's doctrine of association centres in the cerebrum, 7 ; — Trichinosis, remarks on, 81.

Berkley, Henry J. Lesions induced by action of certain poisons on nerve cell. Study VI. Diphtheria, 23; — Studies on the lesions induced by the action of certain poisons on the cortical nerve cell. Study VII. Poisoning with preparations of the thyroid gland, 137.

Block, E. Bates. Case of typhoid fever in which the typhoid bacillus was obtained twice from the blood during life, 119.

Bloodgood, Jos. C. Rarer cases of, and observation on streptococcus infection, 47 ; — Cure of hernia by implanting section of sterilized sponge, discussion of, 45.

Books received, 15, 83, 113, 135, 197, 287, 207.

Brain paths in the animal series, Edinger on development of, 120.

Brain tumor, demonstration of probable case of, 215.

Brooks, Wm. K. William Harvey as an embryologist, 167.

Brown, George S. Case of pneumo-cardial rupture, 33.

Brown, T. R. Studies on trichinosis, 79.

Calvert, Wm. J., and Elting, Arthur W. Experimental study of the treatment of perforative peritonitis in dogs by a new method of operation, 143.

Camac, C. N. B. Visit to Bad Nauheim, 101 ;— Importance of employing pure salts in Schott bath, 214.

Carter, Edward Perkins. Report of a case of polybacterial infection in typhoid fever, 115.

Cataract, second series of operations (one hundred and fifty-eight), 199.

Cavernous angioma of the tunica conjunctiva, case of, 236.

Chatard, Pierre, 185.

Clark, J. G. Function of the peritoneum under normal and pathological conditions, 60 ;— Postural method of draining dead spaces in the pelvis, 62 ; — Mechanism of absorption of fluids and solid

particles in the peritoneal cavity, 01 ; — Postural method of draining the peritoneal cavity after abdominal operations, .59 ; — Rare case of lithopedion, 221 ; — Report of cases where postural method of drainage was employed, 03.

Clendinen, William Alexander, 189.

Cohen, Joshua I., 190.

Cone, Claribel. Encysted dropsy of the peritoneum secondary to utero-tubal tuberculosis and associated with tubercular pleurisy, generalized tuberculosis and pyococcal infection, 91 ; — Tuberculosis of the cesophagus, 229.

Cone, S. M. Squamous epithelioma and epithelial hyperplasia in sinuses and bone following osteomyelitis, 140 ; — Squamous epithelioma in a dermoid of the jaw, 208.

Correspondence, 33.

Cullen, Thomas S. Rapid method of making permanent specimens from frozen sections by the use of formalin, 108 ; — Demonstration of specimens, 216.

Cushing, H. W. Hrematomyelia from gunshot wound of the cervical spine, 195.

Dermatitis, a case of, due to the X rays, 17.

Dermatitis, due to the X rays, additional cases of, 46.

Diphtheria, lesions induced by the action of certain poisons on the nerve cell, 23.

Discussion : Dr. Barker, Trichinosis, 81 ;— Dr. Bloodgood, Cure of hernia by implanting section of sterilized sponge, 45 ; — Dr. Flexner, Puerperal sepsis due to infection with bacillus aerogenes capsulatus, 28 ;— Dr. Halsted, Gall stones, 31 ; — Dr. Osier, Trichinosis, 80 ; Congenital facial diplegia, 131 ; — Dr. Piatt, Cure of hernia by implanting section of sterilized sponge, 46 ;^Dr.Reed, Malaria as a water-borne disease, 43 ;— Dr. Thayer, Malaria as a water-borne disease, 43 ; Trichinosis, 80 ;— Dr. Thomas, Congenital facial diplegia, 130 ; — Dr. Welch, Malaria as a water-borne disease, 42.

Dixon, W. T. Address at presentation of Thorwaldsen's statue of Christ, 1.

Dobbin, George W. Puerperal sepsis due to infection with bacillus aerogenes capsulatus, 24.

Dunham, Edward K. Cases of infection by the bacillus aerogenes capsulatus (Welch), 08 ; — Observations to determine mobility of bacillus aerogenes capsulatus under anaerobic conditions, 74.

Duval, Douglas F. Palpation of the foetal heart impulse in pregnancy, 207.

Elting, Arthur W., and Calvert, Wm. J. Experimental study of the treatment of perforative peritonitis in dogs by a new method of operation, 143.

Epithelioma, squamous, and epithelial hyperplasia in sinuses and bone following osteomyelitis, 146.

Epithelioma, squamous, in a dermoid of the jaw, 208.

Eyeballs, congenital motor defects of, discussion on, 129.

Finney, J. M. T. Five successful cases of general suppurative peritonitis treated by a new method, 141 ;— Typhoid perforation treated by surgical operation, 110.

December, 1897.]

JOHNS HOPKINS HOSPITAL BULLETIN.

269

Flexner, Simon. Discussion of puerperal sepsis, 28 ;— of agglutination of typhoid bacilli, etc., 54;— of pseudo-tuberculosis hominis streptotricha, preliminary note, 128.

Fle.xner, Simon, and Harris, Norman McL. Typhoid infection without intestinal lesions, 259.

Friedenwald, Harry. Early history of ophthalmology and otology in Baltimore, 184 ; — Joseph Friederich Piringer, his methods and investigations, 191.

Frick, George, 186.

Futcher, T. B. Association between so-called perinuclear basophilic granules and the elimination of the alloxuric bodies in the urine, 85.

Gall stones, surgical significance of, 31.

Ghriskey, Albert A., and Kobb, Hunter. Bacillus proteus Zenkeri in an ovarian abscess, 4.

Gibson, John Mason, 188.

Gibson, William, 185.

Gilchrist, T. Caspar. Additional cases of dermatitis due to the X rays, 46 ; — Case of dermatis due to the X rays, 17 ; — Case of porokeratosis, preliminary notice of, 107.

Gilman, D. C. Address at presentation of Thorwaldsen's statue of Christ, 2.

Gonococcus, cultivation of, in two cases of gonorrheal arthritis and one of tsenosynovitis, 121.

Gould, George M., and Pyle, Walter L. King Arthur's medicine, 239.

Hsematomyelia from gunshot wound of cervical spine, 195.

Hsematozoan infections of birds, 235.

Hjematozoan infections of birds, pathology of, 51.

Hsemocytozoa of birds, 52.

Hagner, Francis R. Successful cultivation of gonococcus in two cases of gonorrheal arthritis and one of tsenosynovitis, 121.

Hamilton, Alice. Multiple tuberculous ulcers of the stomach, with report of three cases, 75.

Harper, John, 189.

Harvey, William, as an embryologist, 167.

Hernia, radical cure of, by implanting section of sterilized sponge, 44.

Herrick, A. B. Rare anomaly of arch of aorta, with additional muscle in neck, 234.

Influence of Louis on American medicine, 161.

Is malaria a water borne disease? 35; — Discussion, 42.

Jameson, Horatio G., 188.

Johns Hopkins Hospital Medical Society Proceedings: Bilateral dacryo-adenitis. Dr. Randolph, Dr. Thayer, 132;— Case of acquired paralysis of both external recti muscles with unilateral facial paralysis, Dr. Theobald, Dr. Thomas, 131, 132 ;— Certain visceral pathological alterations, the result of superficial burns, C. R. Bardeen, 81 ; — Congenital facial diplegia. Dr. Barker, Dr. Osier, Dr. Thomas, 130, 131 ;— Discussion of "agglutination of typhoid bacilli," etc., Dr. Flexner, Dr. Reed, 54 ; Dr. Thayer, 55 ; —Discussion of congenital motor defects of the eyeballs, Dr. Baton, Dr. Theobald, 129, 130 ;— Discussion of surgical significance of gall stones, Dr. Halsted, 31 ;— Demonstration of a case of probable brain tumor. Dr. Thomas, 215 ;— Demonstration of Florence's iodine test for seminal stains, Dr. Barker, 133 ;— Demonstration of specimens. Dr. Cullen, 216; — Excision of a parovarian cyst without removal of its ovary or tube. Dr. Kelly, 50,51 ; Discussionof, Dr. Welch,51 ;— Fibroid lung-bronchiectasis — brain abscess. Dr. Livingood, 263 ; — Hsemocytozoa of birds. Dr. L. F. Barker, 52; E. L. Opie, 52, 53; Dr. Osier, 52, 53; Dr. Thayer, 53; Dr. Welch, 53 ;— Hsematomyelia from gunshot wound of cervical spine, Dr. Cushing, 195 ;— Operations for cataract, Dr. Randolph, 133 ;— Ophthalmoplegia externa. Dr. Woods, 48 ; — Pathology of hsematozoan infections in birds, W. G. MacCallum, 51 ; — Rarer cases of and observation on streptococcus infection, Dr. Bloodgood, 47 ;— Simple contrivance for effecting pneumatic massage of the tympanal membrane and ossicles. Dr.

Theobald, 49 ; — Surgical significance of gall stones, Dr. Lange, 29 ;— Typhoid perforation treated by surgical operation. Dr. Finney, 110 ; Discussion of. Dr. Osier, 113.

Johns Hopkins Medical Society, 29, 47, 81, 110, 129, 195, 215, 263.

Kelly, Howard A. Excision of a parovarian cyst without removal of ovary or tube, 50, 51.

King Arthur's medicine, 239.

Lange, F. Surgical significance of gall stones, 29.

Lesions induced by action of certain poisons on cortical nerve cell. Study VII : Poisoning with preparations of the thyroid gland, 137.

Lesions induced by action of certain poisons on the nerve cell — diphtheria, 23.

Lithopedion, rare case of, 221.

Livingood, Louis E. Fibroid lung-bronchiectasis — brain abscess, 263.

Long, the discoverer of ansesthesia ; presentation of his original documents, 174.

Norton, Rupert. Is malaria a water-borne disease? 35.

MacCallum, W. G. Hsematozoan infections of bird.s, 235 ;— Pathology of hsematozoan infections in birds, 51.

Notes on new books:— Annual report of the Supervising General of the Marine Hospital Service, 57, 83 ;— Baldy, J. M., and Gould, George M., American year-book of medicine and surgery, 82 ; — Bishop, S. F., Diseases of the ear, nose and throat, 158 ; — Burdett's Hospital and Charities, 1897, 265;— Butler, G. F., Textbook of materia medica, therapeutics and pharmacology, 158 ; — Canfield, W. B., Practical notes on urinary analysis, 14 ; — Corwin, Arthur M., Essentials of physical diagnosis of the thorax, 159 ;— Crandall, Floyd M., Transactions of the American Pediatric Society, 113 ;— De Schweinitz, G. E., Diseases of the eye, 14 ; — Dorland, W. A. Newman, Manual of obstetrics, 15 ;-Fuller, Wm., Architecture of the brain, 83; — Gant, S. G., Diseases of the rectum, anus and contiguous textures, 197 ;— Gould, George M., and Pyle, Walter L., Anomalies and curiosities of medicine, 158 ; — Hyde, James Nevins, Manual of syphilis and the venereal diseases, 56; — Lockwood, G. R., Manual of the practice of medicine, 267 ;— McCosh, Andrew J., and James, Walter B., Medical and surgical report of the Presbyterian Hospital, S3; — Meigs, Arthur v., Feeding in early infancy, 159 ;—Obersteiner, Heinrich, Arbeiten aus dem Institut fiir Anatomic und Physiologie desCentralnervensystems an der Wiener Universitiit, 135 ; — Palmer, C. F., Inebriety, 218 ; — Park, Roswell, Treatise on surgery, by American authors, 55 ; — Pathological Report of the Illinois Eastern Hospital for the Insane, 159;^ — Pollack, Dr. B., Die Fiirbetechnic des Nervensystems, 134;— Preston, George J., Hysteria and certain allied conditions, 219 ;— Proceedings of the American Medico-Psychological Association at the 52d Annual Meeting, 159; — Rowland, Sydney, Archives of clinical skiagraphy, 218;— Shattuck, George B., Councilman, W. T., and Burrell, Herbert L., Medical and surgical reports of the Boston City Hospital, 57 ; — Stoney, Emily A. M., Practical points in nursing, 14;— St. Thomas's Hospital Reports, 159 ;— Thayer, W. S., Lectures on the malarial fevers, 265; — Thrush, John C, Water and water supplies, 15 ; — Transactions of the American Gynecological Society, 57 ;— Transactions of the Chicago Pathological Society, 57j_Xyson, James, The practice of medicine, 133 ;— Wilson, J. C, and Eshner, Augustus A., An American text-book of applied therapeutics, 134 ;— Yearsley, Macleod, Injuries and diseases of the ear, 218.

Ophthalmology and otology in Baltimore, early history of, 181.

Ophthalmoplegia externa, 48.

Opie, Eugene L. Hsemocytozoa of birds, 52, 53.

Osier, William. Congenital facial diplegia, 131 ; — Hsemocytozoa of birds, 52, 53 ; — Influence of Louis on American medicine, 161 ; — Trichinosis, remarks on, 80; — Typhoid perforation treated by surgical operation, 113.

Otology, early history of, in Baltimore, 189.

270

JOHNS HOPKINS HOSPITAL BULLETIN.

[Xo. 81.

Owings, E. B. Infectiousness of chronic urethritis, 210.

Parotitis following visceral inflammation, 204.

Parovarian cyst, excision of, without removal of its ovary or tube, 50.

Pelvis, postural method of draining dead spaces in, G2.

Perinuclear bisopliilic granules, association between, and elimination of alloxuric bodies in the urine, 85.

Peritoneal cavity, mechanism of absorption of fluids and solid particles in, 61.

Peritoneum, encysted dropsy of, secondary to utero-tubal tuberculosis and associated with tubercular pleurisy, generalized tuberculosis and pyococcal infection, 91.

Peritoneum, function of under normal and pathological conditions, 60.

Peritonitis, general suppurative, cases of treated by new method, 141.

Peritonitis, perforative, in dogs, treated by new method of operation, 143.

Permanent specimens from frozen sections, rapid method of raaliing by formalin, 108.

Phrenology of Gall and Flechsig's doctrine of association centres in the cerebrum, 7.

Piringer, Joseph Friederich, his methods and investigations, 191.

Piatt, W. B. Cure of hernia by implanting section of sterilized sponge, 44.

Pneumo-cardial rupture, case of, 33.

Porokeratosis, case of, 107.

Pregnancy, palpation of fojtal heart impulse in, 207.

Presence in the blood of free granules derived from leucocytes, and their possible relations to immunity, 246.

Proceedings of societies, 29, 47, 81, 110, 129, 195, 215, 203.

Pseudo-tuberculosis bominis streptotricha, preliminary note, 128.

Puerperal sepsis due to infection with bacillus aerogenes capsulatus, 24.

Randolph, Robert L. Bilateral dacryo-adenitis, 132 ;— Operations for cataract, 133 ;— Second series of cataract operations (one hundred and fifty-eight), 199.

Recti muscles, case of acquired paralysis of, with unilateral facial paralysis, 131.

Reed, Walter. Discussion of malaria as a water-borne disease, 43 ;— Of agglutination of typhoid bacilli, etc., 54.

Reik, H. 0. Case of cavernous angioma of the tunica conjunctiva, 236.

Reik, H. O., and Watson, W. T. Apparatus for sterilizing instruments with formaldehyde; experimental tests, 261.

Robb, Hunter, and Ghriskey, Albert A. Bacillus proteus Zenkeri in an ovarian abscess, 4.

Sabin, Florence R. On the anatomical relations of the nuclei of reception of the cochlear and vestibular nerves, 253.

Schott bath, importance of employing pure salts in, 214.

Schott bath, rules for, 103.

Schott exercises, 104.

Schott treatment, bibliography of, 105.

Schott treatment, rules for operators, 104.

Seminal stains, Florence's iodine test for, demonstration of, 133.

Smith, Nathan Rhyno, 189.

Specimens, demonstration of, 216.

Spence, W. W. Address at presentation of Thorwaldsen's statue of Christ, 1.

Stokes, Wm. Royal, and Wegefarth, Arthur. The presence in the blood of free granules derived from leucocytes, and their possible relations to immunity, 246.

Stomach, tuberculous ulcers of, 75.

Streptococcus infection, rarer cases of and observation on, 47.

Suprarenal capsule: alkaloids, 154.

Suprarenal capsule, blood-pressure-raising constituent of, 151.

Thayer, William Sydney. Discussion of case of bilateral dacryoadenitis, 132 ;— Of agglutination of typhoid bacilli, etc., 55 ; — Of

hsemocytozoa of birds, 53;— Of malaria, a water-borne disease,

43 ;— Of trichinosis, 80.

Theobald, Samuel. Case of acquired paralysis of both external recti muscles with unilateral facial paralysis, 131, 132; — Contrivance for effecting pneumatic massage of the tympanal membrane and ossicles, 49; — Discussion of congenital motor defects of the eyeballs, 130.

Thomas, H. M. Discussion of case of acquired paralysis of both external recti muscles with unilateral facial paralysis, 132 ;— Of congenital facial diplegia, 130 ;— Demonstration of a case. Probable brain tumor, 215.

Thorwaldsen's statue of Christ, presentation of, 1.

Thyroid extract, insane patients treated with, histories of, 138.

Thyroid guinea-pigs, histories of, 140.

Thyroid mice, liistories of, 139.

Trichinosis, studies on, 79.

Tuberculosis of the oesophagus, 229.

Tympanal membrane and ossicles, pneumatic massage of, 49.

Typhoid fever, case of, in which typhoid bacillus was obtained twice from blood during life, 119; — Case of polybacterial infection in, 115.

Typhoid infection without intestinal lesions, 259.

Typhoid perforation treated by surgical operation, 110.

Urethritis, chronic, infectiousness of, 210.

Visceral pathological alterations, the result of superficial burns, 81.

Welch, William H. Discussion of excision of parovarian cyst without removal of ovary or tube, 51 ;— Of haemocytozoa of birds, 53 ; — Of malaria as a water-borne disease, 42.

Woods, H. Ophthalmoplegia externa, 48.

Young, Hugh H. Long, the discoverer of anaesthesia, presentation of his original documents, 174.

ILLUSTRATIONS.

Thorwaldsen's statue of Christ, 2.

Sagittal section through brain (Fig. 1), 11.

Horizontal section through brain (Fig. 2), 11.

Horizontal section of brain (Fig. 3), 11.

Sagittal section through brain (Fig. 4), 11.

External view of right cerebral hemisphere (Fig. 5), 11.

Internal view of left cerebral hemisphere (Fig. 6), 11.

Case of X-ray dermatitis (Figs. 1, 2, 3), 22.

Temperature charts of infection by bacillus aerogenes capsulatus (Cases 1, 2, 3, 4), 70.

Encysted dropsy of the peritoneum (Fig. 1), 94.

Bacillus typhosus (Figs. 1, 2, 3, 4), 119.

A new KSthesiometer (Figs. 1, 2), 125.

Tracings of blood-pressure-raising constituent of suprarenal capsule (Figs. 1, 2, 3), 156.

Portrait of Dr. Crawford W. Long, 177.

Portrait of Dr. George Frick, 187.

Longitudinal section of abdomen, 217.

A lithopedion, 223.

Section of oesophagus, 232.

Aortic arch and its branches (Figs. 1, 2), 234.

Supernumerary muscle in the neck (Fig. 3), 235.

Cavernous angioma (Figs. 1, 2), 236.

Diagram of reception nuclei of cochlear and vestibular nerves (Fig. 1), 257.

Section of nuclei of cochlear and vestibular nerves (Fig. 2), 257.

Section of nuclei of cochlear and vestibular nerves (Fig. 3), 257.

Section of nuclei of cochlear and vestibular nerves (Fig. 41, 268.

Section 66 horizontal series (Fig. 5), 258.

Diagram of nuclei of nervi cochlearis and corpus trapeioides (Fig. 6), 258.

December, 1897.]

JOHNS HOPKINS HOSPITAL BULLETIN.

271

PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.

THE JOHNS HOPKINS HOSPITAL REPORTS. Volume I. 423 pages, 99 plates.

Report in Pntbolosy.

The Vessels and Walls of the Dog's Stomach; A Study o( the Intestinal Contraction;

Healing of Intestinal Sutures; Reversal of the Intestine; The Contraction of the

Vena Portae and its Influence upon the Circulation. By F. P. Mall, M. D. A Contribution to the Pathology of the Gelatinous Type of Cerebellar Sclerosis

(Atrophy). By Henry J. Berkley, M. D. Reticulated Tissue and its Relation to the Connective Tissue Fibrils. By F. P.

Mall, 51. D.

Report in Dermatology. Two Cases of Protozoan (Coccidioidal) Infection of the Skin and other Organs. By

T. C. Gilchrist, M. D., and Emmet Rixford, M. D. A Case of Blastomycetic Dermatitis in Man; Comparisons of the Two Varieties of

Protozoa, and the Blastomyces found in the preceding Cases, with the so-called

Parasites found in Various Lesions of the Skin, etc. ; Two Cases of MoUuscum

Fibrosum; The Pathology of a Case of Dermatitis Herpetiformis (Duhring). By

T. C. Gilchrist, M. D.

Report in Patliology. An Experimental Study of the Thyroid Gland of Dogs, with especial consideration

of Hypertrophy of this Gland. By W. S. Halsted, M. D.

VoLUATE II. 570 pages, with 28 plates and figures.

Report in Medicine.

On Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with

Gallstonea. By William Osler, M. D. Some Remarks on Anomalies of the Uvula. By J0H» N. Maceenzie, M. D. On Pyrodin. By H. A. Lafleor, M. D. Cases of Post-febrile Insanity. By William Osler, M. D. Acute Tuberculosis in an Infant of Four Months. By Harry Toulmih, M. D. Rare Forms of Cardiac Thrombi. By William Osler, M. D. Notes on Endocarditis in Phthisis. By William Osler, M. D.

Report in Metlicine. Tubercular Peritonitis. By William Osler, M. D. A Case of RajTiaud's Disease. By H. M. Thomas, M. D. Acute Nephritis in Typhoid Fever. By William Osler, M. D.

Report in Gynecology. The Gynecological Operating Room. By Howard A. Eellt, M. D. The Laparotomies performed from October 16, 1889, to March 3, 1890. By Howard

A. Kelly, if. D., and Hunter Robb, M. D. The Report of the Autopsies in Two Cases Dying in the Gynecological Wards without Operation; Composite Temperature and Pulse Charts of Forty Cases of

Abdominal Section. By Howard A. Kelly, M. D. The Management of the Drainage Tube in Abdominal Section. By Hunter Robb,

M. D. Tlie Gonococcus in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Peritoneum;

Ovarian Tumor; General Gynecological Operations from October 15, 1889, to

March 4, 1890. By Howard A. Kelly, M. D. Report of the Urinary Examination of Ninety-one GjTiecological Cases. By Howard

A. Kelly, M. D., and Albert A. Ghriskey, M. D. Ligature of the Trunks of the Uterine and Ovarian Arteries as a Means of CHiecking

Hemorrhage from the Uterus, etc. By Howard A. Kelly, M. D. Carcinoma of the Cervix Uteri in the Negress. By J. W. Williams, M. D. Elephantiasis of the Clitoris. By Howard A. Kelly, M. D. Myxo-Sarcoma of the Clitoris. By Hunter Robb. M. D. Kolpo-Ureterotomy. Incision of the Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gjniecological Operations. By

Howard A. Kelly, M. D.

Report in Snrgery, 1. The Treatment of Wounds with Especial Reference to the Value of the Blood Clot

in the Management of Dead Spaces. By W. S. Halsted, M. D. Report in >enrology, I. A Case of Chorea Insaniens. By Henry J. Berkley, M. D. Acute Angio-Neurotic Oedema. By Charles E. Simon, M. D. Haematomyelia. By August Hoch, M. D. A Case of Cerebro-Spinal Syphilis, with an unusual Lesion in the Spinal Cord. By

Henry M. Thomas, M. D.

Report in Fatliologry, I. AmtBbic Dysentery. By William T. Councilman, M. D., and Henri A. Lafleub, M. D.

Volume III. 766 pages, with 69 plates and figures.

Report in Patliologry.

Papillomatous Tumors of the Ovary. By J. Whitridqe Williams, M. D.

Tuberculosis of the Female Generative Organs. By J. Whitridqe Williams, M. D. Report in Pathology.

Multiple Lympho-Sarcomata, with a report of Two Cases. By SIUON Flexner, M. D.

The Cerebellar Cortex of the Dog. By Henry J. Berkley, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman, M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Russell, Ph. D.

Heart Hypertrophy. By Wm. T. Howard, Jr., M. D.

Report in Gynecology.

Tlie Gynecological Operating Room; An External Direct Method of Measuring the Conjugata Vera; Prolapsus Uteri without Diverticulum and with Anterior Enterocele; Lipoma of the Labium Majus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Source of Error in Gynecological Diagnosis; Operation for the Suspension of the Retroflexed Uterus. By Howabd A. Kelly, M. D.

Potassium Permanganate and Oxalic Acid as Germicides against the Pyogenic Cocci. By Mary Sherwood, M. D.

Intestinal Worms as a Complication in Abdominal Surgery. By A. L. Stayelt, M. D.

Gynecological Operations not involving Coeliotomy. By Howard A. Kelly, M. D. Tabulated by A. L. Stavely, M. D.

The Employment of an Artificial Retropositlon of the Uterus in covering Extensive Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdominal Pelvic Operations. By Howard A. Kelly, M. D.

Photography applied to Surgerj*. By A. S. Murray.

Traumatic Atresia of the Vagina with Hsmatokolpos and Hxmatometra. By Howard A. Kelly, M. D.

Urinalysis in Gynecology. By W. W. Russell, M. D.

The Importance of employing Anesthesia in the Diagnosis of Intra-Pelvic Gynecological Conditions. By Hunter Robb, M. D.

Resuscitation in Chloroform Asphyxia. By Howard A. Kelly, M. D.

One Hundred Cases of Ovariotomy performed on Women over Seventy Years of Age. By Howard A. Kelly, M. D., and Mary Sherwood, M. D.

Abdominal Operations performed in the Gynecological Department, from March 5, 1890, to December 17, 1892. By Howard A. Kelly, M. D.

Record of Deaths occurring in the Gynecological Department from June 6, 1890, to May 4, 1892.

Volume IV. 504 pages, 33 charts and illustrations.

Report on Typhoid Fever,

By William Osler, M. D., with additional papers by W. S. Thayer, M. D., and J. Hewetson, M. D.

Report in Nenrology. Dementia Paralytica in the Negro Race; Studies in the Histology of the Liver; The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of the Submaxillary Gland of Mus musculus; The Intrinsic Nerves of the Thvroid Gland of the Dog; The Nerve Elements of the Pituitary Gland. By Henry J. Berkley, M. D.

Report in Surgery. The Results of Operations for the Cure of Cancer of the Breast, from June, 1889, to January, 1894. By W. S. Halsted, M. D.

Report in Gynecology, Hydrosalpinx, with a report of twenty-seven cases; Post-Operative Septic Peritonitts; Tuberculosis of the Endometrium. By T. S. Cullen, M. B. Report in Pathology. Deciduoma Malignum. By J. Whitridqe Williams, il. D.

Volume V. 480 pages, with 32 charts and illustrations.

CONTENTS: The Malarial Fevers of Baltimore. By W. S. Thayer, M. D., and J. Hewetson, M. D. A Study of seme Fatal Cases of Malaria. By Lewellys F. Barker, M. B.

Studies in Typhoid Fever. By William Osler, M. D., with additional papers by G. Blumer, M. D., Simo.v Flexner, M. D., Walter Reed, M. D., and H. C. Parsons, M. D.

Volume VI. 414 pages, with 79 plates and figures.

Report in Nenrology.

Studies on the Lesions produced by the Action of Certain Poisons on the Cortical Nerve Cell (Studies Nos. I to V). By Henry J. Berkley, M. D.

Introductory. — Recent Literature on the Pathology of Diseases of the Brain by the Chromate of Silver Methods; Part I. — Alcohol Poisoning. — Experimental Lesions produced by Chronic Alcoholic Poisoning (Ethyl Alcohol). 2. Experimental Lesions produced by Acute Alcoholic Poisoning (Ethyl Alcohol): Part Il.^^crum Poisoning. — Experimental Lesions induced by the Action of the Dog's Serum on the Cortical Nerve Cell; Part III. — Ricin Poisoning.— Experimental Lesions induced by Acute Ricin Poisoning. 2. Experimental Lesions induced by Chronic Ricin Poisoning: Part IV. — Hydrophobic Toxaemia. — Lesions of the Cortical Nerve Cell produced by the Toxine of Experimental Rabies; Part V. — Pathological Alterations in the Nuclei and Nucleoli of Nerve Cells from the Effects of Alcohol and Ricin Intoxication; Nerve Fibre Terminal Apparatus; Asthenic Buibar Paralysis. By Henry J. Berkley, M. D.

Report in Patliology.

Fatal Puerperal Sepsis due to the Introduction of an Elm Tent. By Thomas S. Cullen, M. B.

Pregnancy in a Rudimentary LTterine Horn. Rupture, Death, Probable Migration of 0\'um and Spermatozoa. By Thomas S. Cullen, M. B., and G. L. Wilkins, M. D.

Adeno-Myoma Uteri Diffusum Benignum. By Thomas S. Cullen, M. B.

A Bacteriological and Anatomical Study of the Summer Diarrhoeas of Infants. By William D. Booker, M. D.

The Pathology of Toxalbumin Intoxications. By Simon Flexn'ER, M. D.

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272

JOHNS HOPKINS HOSPITAL BULLETIN.

[No. 81.

THE JOHNS HOPKINS MEDICAL SCHOOL. SESSION 1897-1898.

FACULTY.

Daniel 0. Oilman, LL. D., President.

William H. Welch, M. D., LL. D., Dean and Professor of Pathology.

Ira Remsen, M. D., Ph. D., LL. D., Professor of Chemistry.

William Osler, M. D., LL. D., F, R. C. P., Professor of the Principles and Practice

of Medicine. Henry M. Hord, M. D., LL. D., Professor of Psychiatry. William S. Halsted, M. D., Professor of Surgery. Howard A. Kei.lt, M. D., Professor of Gynecology and Obstetrics. Franklin P. Mall, M. D., Professor of Anatomy. John J. Abel, M. D., Professor of Pharmacology. William H. Howell, Ph. D., M. D., Professor of Physiology.

William K. Brooks, Ph. D., LL. D., Professor of Comparative Anatomy and Zoology. John S. Billings, M. D., LL. D., Lecturer on the History and Literature of Medicine. Charles Wardell Stiles, Ph. D., M. S., Lecturer on Medical Zoology. Robert Fletcher, M. D., M. R. 0. S., Lect\u-er on Forensic Medicine. William D. Booker, M. D., Clinical Professor of Diseases of Children. John N. Mackenzie, M. D., Clinical Professor of Laryngology and Rhinology. Samuel Theobald, M. D., Clinical Professor of Ophthalmology and Otology. Henry M. 1'homas, M. D., Clinical Professor of Diseases of the Nervous System. Simon Flesner, M. D., Associate Professor of Pathology. J. Whitridge Williams, M. D., Associate Professor of Obstetrics. Lewellys F. Barker, M. B., Associate Professor of Anatomy. William S. Thayer, M. D., Associate Professor of Medicine. John M. T. Finney, M. D., Associate Professor of Surgery.

Georqe P. Deeyer, Ph. D., Associate in Physiology.

William W. Rdssell, M. D., Associate in Gynecology.

Henry J. Berkley, M. D., Associate in Neuro-Pathology.

J. Williams Lord, M. D,, Associate in Dermatology and Instructor in Anatomy.

T. Caspar Gilchrist, M. R. C. S., Associate in Dermatology.

Robert L. Randolph, M. D., Associate in Ophthalmology and Otology.

Thomas B. Aldrich, Ph. D., Associate in Physiological Chemistry.

Thomas B. Futcher, M. B., Associate in Medicine.

Joseph O. Bloodqood, M. D., Associate in Surgery.

Thomas S. Cullen, M. B., Associate in Gj-necology.

Ross G. Harrison, Ph. D., Associate in Anatomy.

Frank R. Smith, M. D., Instructor in Medicine.

George W. Dobbin, M. D., Assistant in Obstetrics.

Walter Jo.ves, Ph. D., Assistant in Physiological Chemistry.

Adolph G. Hoen, M. D., Instructor in Photo-Micrography.

Sydney M. Cone, M. D., Assistant in Surgical Patholc^y.

Louis E. Livinqood, M. D., Assistant in Pathology.

Henry Barton Jacobs, M. D., Instructor in Medicine,

Charles R. Bardeen, M. D., Assistant in Anatomy.

Stewart Patos". M. D., Assistant in Nervous Diseases.

Norman McL. Harris, M. B., Assistant in Pathology.

Haevey W. Gushing, M. D., Assistant in Surgery.

J. M. Lazear, M. D., Assistant in Clinical Microscopy.

J. L. Walz, Ph. G., Assistant in Pharmacy.

GENERAL STATEMENT.

The Medical Department of the Johns Hopkins University was opened for the instruction of students October, 1893. This School of Medicine is an integral and coordinate part of the Johns Hopkins University, and it also derives great advantages from Its close afiiliation with the Johns Hopkins Hospital.

The required period of study for the degree of Doctor of Medicine is four years. The academic year begins on the first of October and ends the middle of June, with short recesses at Christmas and Easter.

Men and women are admitted upon the same terms.

In the methods of instruction especial emphasis is laid upon practical work in the Laboratories and iu the Dispensary and Wards of the Hospital. While the aim of the School is primarily to train practitioners of medicine and surgery, it is recognized that the medical art should rest upon a suitable preliminary education and upon thorough training in the medical sciences. The first two years of the course are devoted mainly to practical work, combined with demonstrations, recitations and, when deemed necessary, lectures, in the Laboratories of Anatomy, Physiology, Physiological Chemistry, Pharmacology and Toxicology, Pathology and Bacteriology. During the last two years the student is given abundant opportunity for the personal study of cases of disease, his time being spent largely in the Hospital Wards and Dispensary and iu the Clinical Laboratories. Especially advantageous for thorough clinical training are the arrangements by which the students, divided into groups, engage in practical work in the Dispensary, and throughout the fourth year serve as clinical clerks and surgical dressers in the wards of the Hospital.

REQUIREMENTS FOR ADMISSION.

As candidates for the degree of Doctor of Medicine the school receives ;

1. Those who have satisfactorily completed the Chemical-Biological course which leads to the A. B. degree in this university.

3. Graduates of approved colleges or scientific schools who can furnish evidence: (a) That they have acquaintance with Latin and a good reading knowledge of French and German ; (6) That they have such knowledge of physics, chemistry, and biology as is imparted by the regular minor courses given in these subjects in this university.

The phrase "a minor course," as here employed^ means a course that requires a year for its completion. In physics, four class-room exercises and three hours a week in the laboratory are required; in chemistry and biology, four class-room eierclses and five hours a week In the laboratory in each subject.

3. Those who give evidence by examination that they possess the general education implied by a degree in arts or in science from an approved college or scientific school, and the knowledge of French, German, Latin, physics, chemistry, and biology above iAdicatcd.

Applicants for admission will receive blanks to be filled out relating to their previous courses of study.

They are required to furnish certificates from officers of the colleges or scientific schools where they have studied, as to the courses pursued in physics, chemistry, and biology. If such certificates are satisfactory, no examination in these subjects will be required from those who possess a degree in arts or science from an approved college or scientific school.

Candidates who have not received a degree in arts or in science from an approved college or scientific school, will be required (1) to pass, at the beginning of the session in October, the matriculation examination for admission to the collegiate department of the Johns Hopkins University, (2) then to pass examinations equivalent to those taken by students completing the Chemical-Biological course which leads to the A. B. degree in this University, and (3) to furnish satisfactory certificates that they have had the requisite laboratory training as specified above. It is expected that only in very rare instances will applicants who do not possess a degree in arts or science be able to meet these requirements for admission.

Hearers and special workers, not candidates for a degree, will be received at the discretion of the Faculty.

ADMISSION TO ADVANCED STANDING. Applicants for admission to advanced standlug must furnish evidence (1) that the foregoing terms of admission as regards prellmluary training have been fulflUed, (2) tliat courses equivalent iu kind aud amount to those giveu here, preceding that ye.ir of tho course for adtnisslon to which application is made, have been satisfactorily completed, and (3| must pass examiuatlons nt the beginning of the sosslon iu October in all tho subjects that have been already pursued by the class to which admission is sought. Certiflcates of standing elsewhere cannot be accepted iu place of these examiuations.

SPECIAL COURSES FOR GRADUATES IN MEDICINE.

Since the opening of the Johns Hopkins Hospital in 1889, courses of instruction have been ofl"ered to graduates in medicine. The attendance upon these courses has steadily increased with each sticceeding year and indicates gratifying appreciation of the special advantages here afforded. With the completed organization of the Medical School, it was found necessary to give the courses intended especially for physicians at a later period of the academic year than that hitherto selected. It is, however, believed that the period now chosen for this purpose is more convenient for the majority of those desiring to take the courses than the former one. The special courses of instruction for graduates in medicine ai'e now given annually during the months of May and June. During April there is a preliminary course in Normal Histology. These courses are in Pathology, Bacteriology, Clinical Microscopy, General Medicine, Surgery, Gynecology, Dermatology, Diseases of Children, Diseases of the Nervous System, Genito-Urinary Diseases, Laryngology and Rhinology, and Ophthalmology and Otology. The instruction is intended to meet the requirements of practitioners of medicine, and is almost wholly of a practical character. It includes laboratory courses, demonstrations, beside teaching, and clinical instruction in the wards, dispensary, amphitheatre, and operating rooms of the Hospital. These courses are open to those who have taken a medical degree and who give evidence satisfactory to the several instructors that they are prepared to profit by the opportunities here offered. The number of students who can be accommodated in some of the practical courses is necessarily limited. For these the places are assigned according to the date of application.

The Annual Announcement and Catalogue will be sent upon application. Inquiries should be addressed to the