Michael B. Shimkin

Study of tinea capitis in Philadelphia using case and control groups.

DERMATOPHYTOSIS of the scalp is well described in the medical literature in regard to its clinical manifestations and the identification of causative organisms (1). Surveys of population groups in the United States (2-8), Canada (9-11), and Europe and Africa (1) have also been reported. Such surveys contribute information on the occurrence and distribution of the infection, but provide a, limited basis for conclusions regarding etiologically related factors or the modes of transmission. Clinical opinions are available, too, (2-16), but they are not supported by statistical epidemiologic evidence. We undertook a study of tinea capitis in Philadelphia, using cases and controls, to explore the effects of economic status and hair care practices on the occurrence and transmission of the infection.

Acute Toxicities of Rotenone and Mixed Pyrethrins in Mammals

Rotenone and pyrethrum are proposed as harmless substitutes for inorganic insecticides, 1 and mixed pyrethrins are recommended as anthelmintics 2 and as scabicides. 3 The only critical report on the toxicity of rotenone in mammals is by Haag, 4 who indicates that there is little if any danger of acute intoxication following the ingestion of foodstuffs sprayed with rotenone. Chevalier 2 states that pyrethrum orally produces no untoward effects even when given to children. In order to ascertain the probable toxic range of rotenone∗ or mixed pyrethrins† after absorption into the body, these drugs were given intraperitoneally or orally to guinea pigs, rats, and mice in 0.1-14% dilutions in ethylene glycol or petroleum oil, respectively, Animals were observed for one month. Controls, given the solvents alone, were unaffected over the period of observation. 1. Rotenone injected intraperitoneally killed half or more of the animals in doses of 2 to 10 mg. per kg. (Table I). Death occurred within 30 minutes in 50% of the fatalities, and within 14 days in the remainder. Toxic symptoms noted were: respiratory depression, incoordination, clonic convulsions, muscle tremors, and death due to respiratory failure. At necropsy one-third of the dead animals showed pulmonary congestion; no peritonitis or ulceration at the site of the injection were encountered. Orally, the drug was given in powder form in gelatine capsules to guinea pigs, and in a 1% dilution in ethylene glycol by rubber tube to lightly anesthetized rats. The average minimal killing dose was 75 to 100 mg. per kg., and, as on intraperitoneal injection, was more toxic for rats than for guinea pigs (Table I). Thirty per cent of the fatalities occurred in 4 to 24 hours, 50% in 24 to 48 hours, and the rest in 3 to 10 days. Seventy per cent of the dead animals showed pulmonary congestion of varying degrees, and in 40% the mucosa of the stomach was reddened or sloughed. The animals surviving lost up to 10% of their initial weight in 3 days, but gradually regained it.

Experimental Chemotherapy of Neoplastic Diseases

It is intriguing to forecast the advances in cancer research that may be anticipated during the forthcoming decade. The exploration, by trained investigators with imagination, of such new fields as intermediary metabolism with the aid of radioactive and heavy isotopes, cytochemistry in conjunction with tissue culture, the isolation and identification of nucleo-proteins and other components of cells, and the measurement of biologic phenomena by sensitive electronic methods, will extend biologic research, including the study of cancer, beyond horizons which now can be envisioned. It is logical to anticipate that the eventual solution of the cancer problem will be achieved through fundamental investigations of carcinogenesis and of the nature of the cancer cell. Several large programs of research, however, are being devoted to a systematic examination of numerous chemical agents for their effect on neoplastic growth. This semi-empirical approach has already yielded a number of compounds having some action on...

Acute Toxicity of Mononitrobenzene in Mice

In a comprehensive review of nitrobenzene intoxication, cover. 265 papers, Schneider 1 states that “the minimal toxic dose in anima. experiments is nowhere noted.” The investigations on dogs, cats, rabbits, guinea pigs, rats 1 and frogs 2 are concerned primarily with the manifestations and effects of mononitrobenzene poisoning, and with the study of methemoglobinemia or, as in guinea pigs 3 and rabbits 4 some other non-oxygen-carrying derivative of hemoglobin formed with the agent. The minimal lethal dose of mononitrobenzene (oil of mirbane) was determined in mice in the course of experiments on its effect upon tumor growth. The report was stimulated because mice have not been generally used in the studies of this important industrial poison, and because the toxic manifestations in mice were practically identical with those described in man. 1 , 2 , 5 Experimental: Eighteen female mice of the C3 H strain, weighing 35-40 g, were shaved over the abdomen and were painted lightly with a brush soaked in mononitrobenzene over an area less than one-tenth of the body surface. In one hour, 15 mice were in partial collapse, but all recovered within 24 hours. The animals were painted again; next day, 3 were dead. The rest were painted a third time; within 48 hours, 9 died. Thus, after 3 applications, 24 hours apart, the mortality was 12 out of 18 animals. Ten male mice of strain A, about 30 g in weight, were painted vigorously over the unshaved abdomen for about 20 seconds. In 30 minutes, all were in partial collapse, and in one hour, 6 were motionless, cold and breathing forcibly; 2 were dead within 3 hours, and 4 within 20 hours. Two more mice, which apparently had recovered from collapse, died within 3 days; the total mortality, therefore, was 8 out of 10 animals.

Blood histamine in gastric cancer and peptic ulcer.

Summary Blood histamine is within normal limits in patients with gastric carcinoma and with peptic ulcer. There is no relationship between blood histamine and the presence or absence of free hydrochloric acid in the stomach. Blood histamine in man is carried chiefly by granulocytes, but is not directly related to the number of granulocytes in the blood.

Chymotrypsin in Cancer

Summary Parenteral injections of chymo-trypsin had no effect on the course of 101 cases of neoplastic disease in man.

Changing concepts concerning cancer.

THE UNITED STATES has manifested an unswerving dedication to the solution of the cancer problem. The National Cancer Institute Act of 1937 is a concrete demonstration of the conviction that the problem of cancer can and will be solved by scientific research. One manifestation of progress in cancer research is that our concepts regarding cancer have not remained static. A whole series of changed and changing ideas and approaches has occurred during the past few years. This, of course, is not surprising. All of medicine shares in the technological revolution of our times. Discoveries and opportunities are upon us at a rate that exceeds available resources of men, space, and time to exploit them. Cancer research certainly is not an exception. I have selected a few concepts concerning cancer that seem to me to reflect the main streams of progress. I shall deal with them under three general headings: (a) some biological aspects, (b) some clinical aspects, and (c) some social aspects of cancer.

Lack of effect of lactogenic hormone on mammary adenocarcinoma in mice.

Many clinical observations have indicated that the growth of mammary cancer in women is accelerated by pregnancy and lactation (1,2). The effect of lactation alone is not known, although Geschickter (3) believes that it does not influence the growth rate of in filtrating cancer of the breast. Pregnancy stimulation is usually ascribed to the high estrogen titre, a situation which does not apply during lactation(3). In mice, estrogens exert a carcinogenic effect on the mammary gland (4), but the estrogen preponderance of pregnancy apparently does not accelerate the tumor growth(5). The influence of lactation, with its high lactogenic titre, has not been established, although it has been shown that a crude prolactin preparation did not modify the growth rate of these tumors (6). With the recent availability of homogeneous pituitary lactogenic hormone, it was thought worth while to test this substance for its possible effect upon the growth of mammary adenocarcinoma in mice. Procedure. Virgin female mice of the C3H strain, 5 to 6 months old, were used. To obviate any ovarian influence half the group was oophorectomized. After a 7 week recovery period, uniform fragments of a transplantable C3H strain mammary adenocarcinoma were implanted by trocar in the dorsal subcutaneous tissues. Eight days later subcutaneous injections were begun. Half of each group, castrated and intact, received two 0.1 cc injections daily, each containing 1 mg of purified lactogenic hormone assaying 30 I.U. per mg(7). The control groups received equal volumes of normal saline. Periodic recordings were made of body weights and tumor diameters. Daily vaginal smears of the hormone-treated mice showed anestrous periods of 12 to 15 days occurred regularly throughout the experiment, thus demonstrating the continued potency of the hormone.