Part 7

The ease with which wild rats are obtained and the readiness with which they adapt themselves to the conditions of life in captivity are factors which should make them more extensively used for laboratory purposes than is the case at present. We have described (New York Medical Journal, Feb. 6, 1909) the methods that have been found useful in keeping and handling these rodents. Without going into details here we may say that if rats of approximately the same size are kept together in a cage there will be practically no mortality from fighting. Of course, there should be no overcrowding. Rats should be fed meat or cheese and plenty of green food such as carrots or cabbage. In our experience in San Francisco it has been found practicable to keep for a year one series of ten inoculated wild rats without any loss. Judging from my experience I have no hesitancy in saying that the natural mortality in the laboratory is higher among both guinea pigs and white rats than it is among wild rats.

It is almost certain that some of the lesions described below are due to animal parasites, or to bacteria, but no such causative agent has been identified.

CIRCULATORY APPARATUS.

We have seen no lesion of the circulatory system with the exception of a few cases of pericardial effusion. The most extreme example was one in which the pericardial sac was dilated to such an extent that it filled almost the entire cavity of the thorax. The fluid in the sac was blood stained and there were a number of recent adhesions between the visceral and the parietal surfaces of the pericardium.

PULMONARY APPARATUS.

Pleural effusion, as is stated in another place, is an important sign of plague infection. A clear, watery effusion has been found in a few cases in rats that were not plague infected.

One example has come under observation of a large _Mus norvegicus_ that had both pleural cavities almost entirely filled with a milky fluid. The lungs were compressed and congested. Microscopical examination for animal parasites and for bacteria was negative.

A condition of consolidation of the lungs which closely resembles the stage of gray hepatization in lobar pneumonia in man is seen occasionally. The area may involve half of a lung. Upon microscopical examination one finds the air spaces and the small bronchi filled with leucocytes. There was no cavity formation in any of the cases that have come under observation.

Two relatively common purulent conditions of the lungs are encountered. In the first of these, large and more or less distinctly loculated sacs are found, which are filled with yellow semifluid caseous matter; in the second, the lesion is of much the same nature, but the material in the sac has the consistency of tough, ropy mucus. Aside from the main focus of this sort, numerous smaller areas of the same nature are seen scattered through the otherwise normal parts of the lungs. The extent of some of these purulent processes is remarkable. We have seen cases in which the chest cavity was almost filled by the lesions described.

DIGESTIVE TRACT.

CIRRHOSIS OF THE LIVER.

It was a matter of surprise to find well-marked cases of hepatic cirrhosis in rats, as this disease in man has been pretty generally regarded as very largely due to intemperance in the use of alcoholic beverages. Such an etiology hardly accounts for the condition in the rat. The lesion is by no means rare; well-marked cases are encountered probably as often as once in a thousand rats. We have never seen it in a young rat, probably because the condition develops slowly and the rat reaches adult life before the process is complete. The organ is usually somewhat yellowish, very firm, often, but not always, somewhat shrunken in size. The surface of the whole organ is covered with small, rounded elevations; a typical “hobnail-liver” in miniature.

Microscopically we find various degrees of increase of connective tissue. In a well-marked case the capsule is much thickened, and heavy bands of connective tissue run through the organ in every direction. This increase of connective tissue is most marked in the vicinity of the portal vein and its companion vessels. The microscope will show that in some fields over half of the structure is made up of fibrous tissue. The liver cells that remain appear to be normal. The presence of animal parasites in the liver is frequently associated with a considerable hypertrophy of the connective tissue of the organ. In a majority of cases of hepatic cirrhosis, however, no parasites are to be found. One case has come under observation in which the surface of the liver was covered with a number of flattened, wart-like elevations. Upon section nothing was to be found to account for this except an enormous overgrowth of connective tissue.

FATTY DEGENERATION OF THE LIVER.

A considerable number of cases of well-marked fatty degeneration of the liver have been seen. At times the fatty change is so extensive that the organ floats when placed in water. Microscopically the liver cells are found to be extensively infiltrated with fat granules.

HERNIÆ.

A few ventral herniæ have been observed. In the majority of the cases the sac contained intestine only and this was easily reduced. On two occasions other viscera have been found in the sac; the spleen on one occasion and in another case along with several loops of intestine which were easily reduced there was found the upper extremity of the right division of the uterus which carried a cyst about 1 centimeter in diameter. The cyst was partly adherent to the sac of the hernia. The other division of the uterus was dilated and full of pus. The hernial sac is rarely situated in the median line. One inguinal hernia has been seen.

GENITO-URINARY TRACT.

NEPHRITIS.

Nephritis is a rather common condition in rats. Among the large (old) ones it will be found probably once in every fifteen or twenty examined. It has been found to be especially frequent in rats that are suffering from the leprosy-like disease, as probably two-thirds of those having that interesting infection will show marked evidence of nephritis. The kidney is usually brownish or grayish, mottled, friable and often shows cysts upon the surface and in the substance of the organ. Some of these cysts may be as large as a pea, or indeed even much larger. The capsule strips very readily.

Microscopically the lesions are found to be due partly to epithelial and partly to interstitial change. There is a marked increase of connective tissue rather irregularly distributed throughout the organ. The epithelial cells show various degrees of degeneration; the nuclei are stained very lightly, or not at all; granular change of the protoplasm is well marked. Some tubules are encountered in which the epithelial cells are entirely wanting.

Cyst formation is a conspicuous feature in many of the cases. These cysts vary considerably in size, are often filled with granular débris, and are more or less completely lined with epithelial cells which are sometimes flattened. At times the epithelial lining is entirely wanting. The glomeruli, on the whole, appear to be better preserved than are the tubules. Occasionally areas are found in which there is a very marked round cell infiltration between the epithelial structure. One of the most marked cases of nephritis we have observed was in a large female _Mus alexandrinus_, in which both kidneys were almost entirely replaced by cystic formation, the largest cyst being perhaps 3 centimeters in diameter by 4 centimeters in length, and full of a clear, watery fluid. So extensive was the cystic formation that only a few remnants of kidney tissue remained. Microscopical examination showed a marked increase in the capsular and interstitial connective tissue, a shrinking of the glomeruli, which were surrounded by well-marked fibrous capsules, and extensive cyst formations. The lining of some of these cysts was made up of epithelial cells. Others were quite bare. This rat had, in addition, a large, rough calculus in the urinary bladder.

ABSCESS OF THE KIDNEY.

A female _Mus norvegicus_ had on one side of the neck a large cavity full of caseous matter. In each kidney there were five or six circumscribed collections of pus, the largest of which was about the size of a pea. Microscopical sections through these abscesses showed that they were walled off from the kidney structure proper by beginning connective tissue formation. The abscess cavity was filled with polynuclear leucocytes, some of them very markedly disintegrated. The epithelial structure of the kidney proper showed some parenchymatous degeneration.

ATROPHY OF A KIDNEY.

On one occasion we have seen a kidney represented by a very small flattened mass of tissue, the nature of which was not quite clear until microscopical examination showed a few fairly well-defined glomeruli and a few cell groupings suggestive of tubules. Whether the condition was congenital or acquired is not known. The other kidney appeared to be normal in every respect. There was no evidence of compensatory hypertrophy.

VESICAL CALCULI.

The bladder of rats very frequently contains very irregularly shaped, rough, somewhat branching concretions. These concretions are rather soft and tough and are dirty white in color.

In addition to these concretions we have seen several cases of well-marked vesical calculi. In one case 21 smooth round stones which completely filled the bladder were found. The total weight of the stones was 3.8 grams. In another case 6 calculi were found, the total weight of which was 7.8; the largest one weighing 5 grams. In a third case 8 smooth, round stones weighing 1.7 grams were found, the largest of which weighed 0.6 gram. The last two cases were female rats; the sex of the first was not recorded.

In each of these cases the bladder showed to the naked eye very marked evidence of inflammation. The mucous membrane was reddened, villous, and covered with tenacious mucus. In one case in which microscopical examination was made the mucous membrane was found to be covered with pus cells, the surface layers of which were undergoing degeneration.

Diseases of the genital tract in the human race analogous to those mentioned below are so generally regarded as due for the most part to infections from impure sexual relations that it was a distinct surprise to find such lesions in rodents.

In the male abscesses are occasionally met with in connection with the seminal vesicles. We have seen them varying in size from a pea to a sac whose contents would have measured 3 or 4 cubic centimeters. In the female purulent collections in the horns of the bifid uterus are encountered, but they are rare. We have seen cases that were anatomically exactly like the purulent lesions so commonly found in the fallopian tubes of women. In one case one horn of the uterus was closed at both ends and distended by a thin, watery pus into a large sausage-shaped mass about the size of an index finger. The opposite horn of the uterus contained six fœtuses. A very curious case was one in which four fœtuses, each one a little less than an inch in length, were found lying in the midst of a large, yellowish, puttylike mass that distended one horn of the uterus into a balloon-shaped mass about 3 centimeters in diameter. The fœtuses were partly dried, and had evidently been dead for a long time.

TUMORS.

Tumors among rats and mice are not infrequent when these animals are kept in captivity, and the tumors of mice especially have been made the subject of very extensive experiments for the purpose of determining the mode of transmission, the question of immunity, and other subjects that might throw light upon malignant growths in the human family. White or tame rats have been much less used than mice. However, it is interesting to note that the earliest observations on the successful transplantation of a malignant growth from one animal to another was that of Hanau[101], who reported a carcinoma of the external genitals of a white rat and he succeeded in transplanting this tumor into other white rats.

I shall not make any attempt to review the enormous literature on tumors in tame rats and mice, but shall merely mention some of the more important points that have been learned in an experimental way in regard to this subject. The histological nature of the tumors found in white rats was of particular interest, as we wished to compare them with the tumors that have come under observation among the wild rats in San Francisco.

In addition to Hanau’s case of carcinoma cited above the following tumors of white rats are mentioned. Herzog[102] observed a cystic sarcoma of the neck of a white rat. Loeb[103] mentions three tumors of white rats; an adenoma in the mammary gland, an adenocarcinoma of the pancreas, and a carcinoma of the thyroid. Flexner and Jobling[104] report a mixed cell sarcoma of the seminal vesicles of a white rat. This tumor upon transplantation showed a marked tendency to produce metastases. Gaylord and Clowes[105] report cases of fibrocarcinoma of white rats arising apparently from infected cages, and they present evidence that in certain breeding establishments carcinoma is endemic among the white mice. Spontaneous tumors are much more frequently met with in mice than in rats, and a number of epidemics of malignant growths have been observed among mice in captivity.

Tyzzer[106] found in a mouse a primary adenocarcinoma of the lung and an adenoma of the kidney. Loeb[107] found that upon the transplantation of a pure gland-like tumor (carcinoma) which originated in the submaxillary gland of a Japanese mouse both carcinoma and spindle cell sarcoma were developed, and this observation, that transplanted tumors may give rise to a different histological growth from that which was transplanted, has been made by others. Tyzzer[108] reports 20 spontaneous tumors in mice. Of these tumors 12 were papillary cyst-adenomas of the lung and were mostly very minute, some of them microscopic; 2 were cyst-adenomas of the kidney; 2 lymphosarcoma, 1 of the groin and 1 of the mediastinum, and 4 were adenocarcinoma. These 20 spontaneous tumors occurred in 16 mice, 4 of them having tumors of 2 different types. Ehrlich and Apolant[109] record the occurrence in a white mouse of a mixed tumor (carcinoma sarcomatodes). Saul[110] mentions spontaneous papillary adenocarcinoma and teleangiectatic carcinoma both in the mammary glands of mice.

Saul showed that by planting the common liver worm of the rat (_Cysticercus fasciolaris_) subcutaneously in a mouse he was able to develop a tumor which partook of the nature of a malignant (carcinomatous) growth. It will be seen by an examination of the data presented below relating to spontaneous tumors in wild rats that a considerable number of them have been associated with the presence of the parasite Saul used in his experiments. He also states[111] that Borrel found worms or their remnants in malignant tumors of mice.

When metastases occur in mouse tumors the most usual seat of the secondary growths is in the lungs, thus Tyzzer[112] observed metastases in 4 cases out of 73 mice inoculated with the Jensen tumor. He demonstrated that the metastases took place by the blood vessels, not by the lymphatic channels, although the tumors were of a carcinomatous nature.

Simon[113], who reviews the subject of mouse tumors with special reference to the subject of immunity, remarks that mouse carcinomata, although found most frequently in old females, when transplanted grows equally well in males, and better in young than in old animals. It has been found by some observers that a rat or a mouse unsuccessfully inoculated with a strain is thereafter immune, to even the most virulent strain.

Haaland[114] and other writers have found a marked variation in the susceptibility of different races of mice to mouse carcinoma.

Ehrlich[115] and his co-workers Apolant and Haaland have recorded many experiments in transplantation of tumors of mice. They have demonstrated that moderate heating of a mouse tumor lengthens the incubation period, diminishes the number of successful transplantations, and brings about certain changes in the histology of the tumors reproduced.

Gay[116] found a difference in the susceptibility of white rats from different sources. In his work with carcinoma in rats he found metastases regularly in the lungs and rarely in the lymph nodes. He was able to raise the virulence of the tumor by transplantation of the lung metastases. This increase of virulence was shown by increase in the rapidity in growth, increase in metastases, and the increase of the epithelial elements over the stroma.

Brooks[117] in considering the subject of tumors in animals concludes that true neoplasms are very rare in wild animals living under natural conditions. It should be stated, however, that Brooks refers especially to higher mammals such as are found in zoological collections.

TUMORS OF WILD RATS.

A new growth is found approximately once in every thousand rats examined in San Francisco. Ninety-two tumors have been examined microscopically. Time has been available for the study of but one or at the most two sections from each tumor and while in some cases the diagnosis was easily made in others there was room for considerable difference of opinion as to the nature of the growth. It is obvious that it is hardly fair to expect to make a final diagnosis in every case from one or two sections taken from one part of the growth, and it is possible that further study will throw more light upon the histological nature of some of them.

_Location._—The largest number of the tumors have been found in the subcutaneous tissue of either the thorax or of the abdomen, and as the majority of these have been found in female rats we have assumed that they were probably of mammary origin. The growths were occasionally located directly under the nipple, but in such cases the nipple was not retracted, and it was exceptional to find any ulceration. The tumors were very rarely adherent to the surrounding tissue. After the subcutaneous tissue tumors were found most frequently in the liver. Histologically, the most of these growths were sarcomas and the majority of them had a parasite, the _Cysticercus fasciolaris_, in some part of the tumor. This parasite, as is well known, is the larval stage of a tapeworm found in the cat. These tumors of the liver were frequently associated with an enormous number of secondary growths varying in size from a millet seed to 1 centimeter in diameter scattered through the omentum, mesentery, and other abdominal structures.

Several growths have been found in the kidney, mostly of an epithelial nature, one being a particularly well-marked example of a cystic papilloma. A few have been found in connection with other parts of the genito-urinary tract. A large bloody tumor, which upon microscopical examination was found to be an angiosarcoma, replaced a testicle. A large growth, apparently an endothelioma, was found near the end of one horn of the bicornuate uterus.

METASTASES.

Metastases have been found in a number of cases of sarcoma and a smaller number of cases of the epithelial growths. Most frequently the secondary tumors were in the liver, the mesentery or the kidney.

_Size._—In proportion to the size of the rat the tumors were quite large, scarcely any under 1 centimeter in diameter having been observed, and they varied from this to a growth several centimeters in diameter.

HISTOLOGICAL STRUCTURE.

The following tumors may be regarded as of the connective tissue type:

LIPOMATA.

One typical lipoma has been found. It was located in the subcutaneous tissue of the thorax and was similar in gross and microscopical appearance to the tumors of the same nature in man.

FIBROMATA.

A considerable number of subcutaneous tumors have been typical hard fibromas, others were fibromas in which there were a few cell nests that led to the suspicion that perhaps a malignant change was taking place in the tumor, or that a malignant growth was being converted into one of a benign nature.

SARCOMATA.

Typical spindle cell sarcomas have been encountered a number of times. A few round cell sarcomas were found in which there were usually a number of giant cells, but hardly enough to justify one in designating the growths as giant cell sarcomas. Several other growths have been seen which gave the impression of being sarcomas but left one in some doubt as to whether the tissue might not be of the nature of a granuloma.

Many tumors of the epithelial type were encountered which may be classed together.

ADENOMATA AND CARCINOMATA.

Several very typical adenomas and cystic adenomas have been found. A few tumors were observed that presented the appearance of carcinomas. A large number of growths were observed that apparently stood between the adenoma and the carcinoma and there was room for legitimate difference of opinion about any one of these, and in fact, different pathologists who have examined sections of these tumors have expressed different opinions as to the nature of the growths.

REFERENCES.

Endnote 101:

Hanau (Fortsch. der Med., vol. 7, 1889, May 1, p. 321).

Endnote 102:

Herzog (Journal Med. Research, 1902, vol. 8, old series, p. 74).

Endnote 103:

Loeb (Journal Med. Research, 1901, vol. 6, p. 28; also vol. 3, p. 44, and vol. 17, p. 299).

Endnote 104:

Flexner and Jobling (Journal Am. Med. Assn., 1907, vol. 48, p. 420).

Endnote 105:

Gaylord and Clowes (Journal Am. Med. Assn., 1907, vol. 48, p. 15).

Endnote 106:

Tyzzer (Journal Am. Med. Assn., 1906, vol. 47, p. 1237).

Endnote 107:

Loeb (Univ. of Pa. Med. Bull., 1907, vol. 19, No. 5).

Endnote 108:

Tyzzer (Journal Med. Research, vol. 17, No. 2, p. 155).

Endnote 109:

Ehrlich and Apolant (Berl. klin. Woch., 1907, vol. 44, pp. 399 and 1401).

Endnote 110:

Saul (Centralblatt für Bact., etc., Aug. 27, 1907, vol. 47).

Endnote 111:

Saul (Centralblatt für Bact., etc., 1909, vol. 49, p. 4).

Endnote 112:

Tyzzer (Journal Med. Research, vol. 17, No. 2, p. 137).

Endnote 113:

Simon (International Clinic, vol. 2, 18th series).

Endnote 114:

Haaland (Berlin, klin. Woch., 1907, vol. 44, p. 73).

Endnote 115:

Ehrlich, Apolant and Haaland (1906, Berlin, klin. Woch., vol. 43, No. 2).

Endnote 116:

Gay (1909, Journal Med. Research, Vol. XX, No. 2).

Endnote 117:

Brooks (1907, Am. Jour. of Med. Sciences, Vol. CXXXIII).

THE ECTOPARASITES OF THE RAT.

By NATHAN BANKS,

_Assistant Entomologist, Bureau of Entomology_.

The ectoparasites of the rat fall naturally into three groups, the fleas, the lice, and the mites. These three groups are widely separated from each other, the mites belonging to the class Arachnida, having four pairs of legs, no segmentation to the body, no antennæ, and no compound eyes. The fleas and lice belong to the class Insecta. The lice are near the order Hemiptera, sucking insects without a complete metamorphosis, while the fleas are related to the Diptera and pass through a complete metamorphosis. All of these three groups, however, agree in one character—they are wingless. The mites and lice have flattened or depressed bodies, while the fleas have compressed bodies. All three groups have many other species which infest various other animals. Few, if any, of these parasites confine themselves to the rat, and all can walk or jump in the adult condition, so that they can easily transfer their attentions from one rat to another or to some other host. The majority of them are known to occur on mice, and several of the fleas and mites will readily attack man.

FLEAS—SIPHONAPTERA.