probably from fatty degeneration. The organ elsewhere seems slightly pale in color, and granular in appearance. The lobules can be made out fairly well. The gall-bladder contains 25 cc. bile, no stones, ducts free.

The spleen is of ordinary size and general appearance. On section it is fairly firm. Its trabeculae are visible but not specially increased. The pulp is not softened. The capsule is not thickened nor adherent to the surrounding organs; there is no change in the vessels.

The kidneys are of the same size and general appearance; there is a small amount of perirenal fat. The organs are deep red in color. The capsule strips off readily. On section their consistency is rather decreased and the cut surface is rather bloody. The cortex is smaller and granular in appearance. The pyramids are deep red in color. On pressure blood exudes from numerous openings of vessels.

The uterus and ovaries are normal.

The skull is of ordinary thickness; there are no marks of disease or fracture of bone. The membranes are of normal thickness; the vessels are all injected over the surface of brain. On section the brain-substance is soft and is handled with difficulty; the puncta vasculosa are very bloody. There is no excess of fluid in the ventricles, but at the base of the brain there is a considerable amount of clear serous fluid.

Of the cord, nothing macroscopically can be made out.

INOCULATION EXPERIMENTS IN CASE OF IONE CARR

Two healthy young rabbits, A and B, were inoculated from a portion of the medulla of Ione Carr, made into an emulsion with bouillon. The skull was trephined with a small instrument at the sulcus between the cerebrum and cerebellum. The wounds healed nicely in about ten days. The animals remained healthy, feeding well and showing nothing abnormal until July 7. 17 days after the inoculation, when rabbit A was found in the morning to be lying on the left side, and was much frightened when approached and touched. It moved with great difficulty in the cage, and when placed on the floor would move in a circle nearly always to the right. There was marked impairment of the limbs, especially the hind ones which were left sticking straight backward. When left alone he ate freely. He was found dead the following morning. He manifested no tendency to bite.

The autopsy showed the wound to be healed nicely. There was a small discoloration of the cerebellum at the point of inoculation, the meninges were normal, the brain normal, the heart, lungs and kidneys were normal, the liver was of a reddish-brown color, of ordinary consistency.

Rabbit B remained perfectly normal until July 8, when he presented the same symptoms as A. He appeared to be restless, and when approached tried to get away, which he did not do in a healthy state as he was very tame. He moved in a circle when placed on the open floor, lying on his left side.

He could not be made to remain on his right side but immediately turned over when placed in that position. The movements were somewhat incoordinated, but there was no marked paralysis of any of the limbs. There was a slight diarrhea on the 17th and 18th days. The temperature was 39.6° C. in the rectum. The respiration was 240. There developed a marked inflammation of the left eye probably from traumatism from lying on the left side. There was no apparent increase in the amount of saliva secreted. He ate and drank well up to the last day.

These symptoms increased in severity, movement becoming more and more difficult and he died on the night of the 22nd day after inoculation. The food of both animals consisted of clover, grass, plantain, leaves, lettuce, cabbage, oats and water.

Autopsy of rabbit B:-There was marked inflammation of the left eye, the abdomen was free from fluid, the bowels large, distended with feces, and the bladder very much distended with urine. The liver was somewhat enlarged and of a deep dark-brown color, the spleen normal. Kidneys, striæ visible, cut surface rather opaque. The lower left lobe of the lung shows pneumonia. The brain, membranes and cord are normal macroscopically. One rabbit each was inoculated with portions of medulla of both rabbits A and B and by the same method as the original inoculations, and both animals remained healthy up to forty days after inoculation. At about the same time, June 21, an animal suspected of rabies was shot in front of Charity Hospital and a portion of the medulla having been secured a third rabbit, C, was inoculated in an identical manner with the first two. The wound healed nicely and the rabbit showed no signs of disease up to nine weeks after inoculation.

Referring to Bulletin No. 10, U. S. Department of Agriculture, in a valuable report upon Rabies in Cattle, by Dr. D. E. Salmon, Chief of Bureau of Animal Industry I find in a large number of inoculation experiments made on rabbits to corroborate the existence of an outbreak of rabies in cattle in Iowa, the symptoms developed by the rabbits and the post-mortem appearances, and even the time of development of symptoms correspond almost exactly to those manifested by the rabbits inoculated in our experiments with portions of the medulla of Ione Carr.

In summing up his report he says: "The results demonstrated the fact that these animals were affected with rabies or at least with a disease not distinguishable from that malady as determined by comparative inoculation experiments." And that is about all the conclusions I am able to draw from the facts in the case which I now report.

Dr. C. W. Dulles, in the Medical Record, June 26, 1897, says that paralytic rabies, that form resulting in these inoculation experiments, was unknown before the time of Pasteur's so-called prophylactic treatment, and in an extremely interesting article says that since a previous report made in 1895 he has investigated ninety-two cases of persons bitten by dogs sup

posed to be rabid, with five deaths, and every one of these five patients had been treated at the Pasteur Institute in New York; and again he reports the death of four children in Baltimore out of eight bitten by one dog and all treated at the New York Pasteur Institute, and states that he is strongly of the opinion that the boys died partly of laboratory rabies, partly of dread and mental impressions, and partly from the way in which they were treated. Dr. Dulles is not alone in his belief that paralytic rabies is a new disease and attributable to the Pasteur treatment. Dr. Dolan, editor of the Provincial Medical Journal says: "Not only does Pasteur not protect from the disease under the very conditions demanded by himself, but he has added a new terror to it by the introduction of paralytic rabies."

That hydrophobia has increased with wonderful rapidity in sections near the so-called Pasteur Institute, while it remains as infrequent as formerly in remote places is a fact that scarcely needs comment. How we are to determine a genuine case of rabies, I do not know. Symptoms identical with those of this disease have often developed in patients bitten by dogs which never themselves showed any signs of the disease. And yet, many distinguished members of our profession are firmly convinced of its existence as a distinct disease, and say that it can never be confounded with anything else after a case has once been seen. I am somewhat inclined to agree with Dr. Dulles in considering the term hydrophobia one to be used just as we use convulsion, without prejudice as to the cause of the phenomena.

T

OBSERVATIONS ON FROG-SKIN GRAFTING

BY GEORGE SEELEY SMITH, A. M., M. D.

HE restoration of the integrity of the skin through grafting will always prove of interest to the medical profession, restoring, as it does, the epithelium of the part, and thereby preventing the deformity and loss of function which would follow if the process of granulation were allowed

to mature.

The healing of a large granulating surface is a slow process, even under the most favorable circumstances, and the resulting cicatrix is often large, giving rise to contractions, and not infrequently becomes the seat of keloid and ulcerative processes.

Grafting is the recognized procedure when the skin has been destroyed over any considerable area, human epidermis being always the material of election, to be taken from the patient himself when practicable, and from others when the patient's condition makes it inadvisable to add this further tax upon his resources. But there are many times when it is difficult, or indeed impossible, to obtain human epithelium, and the situation confronts us of allowing nature to take its course, with the resulting formation of the slowly contracting fibrous tissue, or to use some substitute for the human

skin, in the hope of hastening convalescence, and preventing subsequent deformity.

During the past five years I have used the skin of the frog on a number of cases with varying degrees of success. I purpose this evening to give you the results of my limited observations, and shall endeavor to speak of the cases in which frog-skin is most likely to prove serviceable.

In order to better understand the method and theory of grafting with skin from frogs, let us make a few preliminary observations..

The theory of healing by granulation and of skin-grafting may be obtained by consulting any modern text-book on surgery, and would prove both needless and wearisome here. Suffice it to say that a granular surface undergoes contraction during its development into connective tissue, and thereby approximates the margins of the wound; and if any considerable area is involved the surface heals by the formation of fibrous tissue before a new epidermis can be developed from the edges of the wound.

Two layers of granulation-tissue are to be seen by the microscope, the more superficial presenting vertically disposed, and the deeper, horizontally placed capillaries. In cases in which the granulations become exuberant, this upper soft layer must be removed in order to assure success.

In frog-skin grafting the best results are attained when the granulations are from four to six weeks old and firm. This skin does not take in the ordinary sense of the word, but on the contrary it invariably sloughs. The term grafting, as applied in this connection, is therefore not strictly correct. Why the skin does not itself become identified with the granulating surface I cannot say. Perhaps a glance at its anatomy may assist in solving the problem.

As in man, the skin of the frog consists of a corium and an epidermis. The latter is possessed of several strata of epithelial cells, those of the most superficial layer being flattened, very transparent and horny. This horny section consists merely of one or two layers of flattened cells, and is for the most part very thin. In some situations, as on the back, it is much thicker and rough.

The corium is divided histologically into three layers, the most superficial of which is a much pigmented vascular layer, and forms a loose support for numerous glands; the middle layer is composed principally of connectivetissue fibers; the deepest layer forms an important lymph-space, is composed of delicate white and yellow elastic fibers and attaches the whole integument to the underlying organs. The glands of the skin are of two kinds-serous and mucous.

Why the skin sloughs in operations of grafting remains an unsolved problem. It may be owing to the fact that the epidermis cannot be detached from the corium, as is possible in human skin, therefore making it obligatory to use both layers; or perhaps it is due to the difference in its vascular or

ganization. However that may be, we are dealing with a condition and not a theory, and it is probably fortunate that the skin does not "take," for in that case it might assume more or less of its original appearance, whereas, as it is, it loses all of that, and assumes much the appearance of human epithelium. The corium of the frog-skin is richly supplied with leucocytes and embryonal tissue-cells, and these latter, being deposited upon the granulating surface, and remaining after the grafts have sloughed, are probably the active agents in the formation of the new epithelium. During this process the granular surface is capable of nourishing these tiny formative cells until the development of the new and elastic covering; not indeed possessing all of the functions of the human skin, but so vastly superior to a contracting fibrous tissue as to commend the method in cases in which human skin is not available.

The time required for healing is much longer than in the Thiersch method of grafting, as the skin has to advance from the embryonal state; but it is far shorter than it would be to allow the process of granulation to proceed uninterrupted. We are now better prepared to understand the clinical aspect of the subject as presented by the following cases. The first to be reported is the patient from whom I secured the specimens to be shown under the microscope.

CASE I. In August of 1893, before locating in Cleveland, I was called to see a case of very deep and extensive burn in a child five years of age. On July 18th, four weeks previous to my first visit, the boy's clothing caught fire, and before the flames could be extinguished the entire thickness of the skin had been destroyed over a large area of the trunk, face, neck and arm. The part involved may be traced by a line running from the thyroid cartilage down the median line of the body to within an inch of the umbilicus, and from here following the band of the trousers around to the left to the middle of the back; up to the external occipital protuberance; to the malar bone, on the left, including a portion of the ear; diagonally across the face to the right corner of the mouth, and completing the area by connecting this point with the thyroid cartilage. The axilla was also involved, and the upper arm was denuded over its entire circumference, and from two-thirds of the distance from the shoulder to the elbow.

I found the entire surface covered with healthy granulations that bled freely upon the slightest touch. In other respects, however, the case had received but little attention, a fact which was emphasized by the fold of the axilla being firmly adherent, through neglect to separate the parts in dressing.

As a consequence the arm was firmly bound down, and my first care was to break up these adhesions under ether. It being evident from the first that healing by granulation would not only require many months, but would eventually result in considerable deformity, it was decided to resort to grafting. Here the first difficulty presented itself, as the surface was so extensive,