Because of the Evident Availability to Children Of
Total Page：16
File Type：pdf, Size：1020Kb
content of 290 mg. per 100 cc. and a carbon dioxide combining power of 14 vol. %. After we received this report, our impression was that we COUNCIL ON PHARMACY were dealing with some overwhelming infection and diabetic AND coma. In view of the report that the urine was normal prior to CHEMISTRY hospitalization, it was decided to withhold insulin therapy until further laboratory study. Intravenous administration of fluid in the form of 1/6 molar lactate and distilled water instead of REPORT TO THE COUNCIL glucose solution was Antibiotic was con- begun. therapy given, The Council has authorized sisting of one million units of penicillin intramuscularly every publication of the following report its Committee on Research. three hours and 100 mg. of oxytetracycline (Terramycin) in from 50 cc. of distilled water intravenously every four hours. Adrenal R. T. Stormont, M.D., Secretary. cortical extract was administered, with 10 cc. given initially and 5 cc. four hours. every The Committee on Research, through its Subcommittee on At 8:20 that evening the temperature rose to 106 F, and the Steroids and Cancer, is sponsoring a collaborative study on child began to have tonic and clonic convulsions. Phénobarbital steroids and mammary cancer. Reports summarizing this work was given intramuscularly to control the seizures. At 9:20 p. m. have been published (Estrogens and Androgens in Mammary the blood glucose level fell to 210 mg. per 100 cc, without Cancer: A Progress Report, report of the Council on Phar- insulin therapy; there was 3+ glucosuria, but the twitchings and macy and Chemistry, J. A. M. A. 140:1214 [Aug. 13] 1949. seizures still persisted and the temperature remained high. A Proceedings of the First Conference on Steroid Hormones and spinal tap done at this time revealed normal fluid content. After Mammary Cancer, American Medical Association, Chicago, continuous antipyretic and hydrotherapy, the temperature fell April 4-7, 1949. Current Status of Hormone Therapy of Ad- to 103 F at midnight and the glucosuria was 2+. The convul- vanced Mammary Cancer, report of the Council on Pharmacy sions were diminishing. At 6 a. m. the child called for its and Chemistry, J. A. M. A. 146:472 [June 2] 1951). In the mother and began taking fluids by mouth. At 10 a. m. the following report, the conclusions expressed are those of the temperature was 100.2 F, and the child sat up. The following authors, and final conclusions of the Subcommittee must await day, 48 hours after admission the child was afebrile, and all evaluation of the studies now in progress. the laboratory findings were within normal limits. The child Paul L. Wermer, M.D., Secretary. was discharged on the fifth day of hospitalization. One week after the child was discharged, we were EFFECTS OF INTENSIVE SEX STEROID HORMONE notified by the mother that the child confessed to having THERAPY IN ADVANCED BREAST CANCER eaten some berries off a bush in the picked park, just B. J. Kennedy, M.D. to the onset of the illness. A with some of the prior twig and berries was submitted to the Botanical Garden Brooklyn Ira T. Nathanson, M.D., Boston for identification and was subsequently shown to be Rhodotytos of the rosacea family, a bush imported from Intensive therapy with estrogens and androgens is employed Japan whose berries are called "jet beads." in the palliative treatment of advanced cancer of the breast.1 These berries contain the glycoside amygdalin, which, Since observations of the systemic effects and complications of this therapy may a clue to the when breaks down into acid. Dr. provide mode of action of the ingested, hydrocyanic sex steroids in breast cancer, they may be important. Many John C. Krantz, professor of physiology of the University effects of sex hormone therapy have been recorded, but addi- of Maryland Medical School, advanced a possible ex- tional manifestations not commonly recognized have become planation of the clinical condition found in our case. He prominent and more frequently noted at the higher dosages usually employed in breast cancer. The of this stated that "it was that this purpose report possible drug (hydrocyanic is to record these reactions and their relative frequency with acid) has a centric action in the region of the hypoth- intensive and prolonged hormone therapy. The alamus and that as one has here a glycémie center as duration of treatment varied from a few days to several well as a heat center, each of these may have been years. Deleterious reactions occurred early in some patients, necessitating discontinuance of effects that effected by the drug, a and therapy. Thus, might producing hyperthermia have occurred at later intervals could not be recorded. Most to the simultaneously contributing hyperglycemia." of the patients, however, were treated for a minimum of one and a received COMMENT month, large majority continuous therapy for considerably longer periods. The causes of the shorter periods It is difficult to estimate the actual number of acci- of observations were as follows: (1) development of later re- dental poisonings that occur in children, because as a rule only unusual or fatal cases are Aikman* con- This is publication no. 790 of the Cancer Commission of Harvard Uni- reported. versity and no. 165 of Pondville Hospital. siders that the fatal cases alone amount to about a 800 Because of lack of space, the bibliographic references have been year in the United States. Where the clinical is omitted from The Journal and will appear in the authors' reprints. picture work and and is the This was supported in part by an institutional grant to the Massa- irregular confusing poisoning suspected, chusetts General Hospital from the American Cancer Society and in part and other in close contact with the by a grant from the Damon Runyon Memorial Fund at the Massachusetts parents persons General must be Hospital. patient questioned closely. Although we did From the Medical Laboratories of the Collis P. Huntington Memorial not elicit such a history, our clue that this not be Hospital at the Massachusetts General Hospital; the Tumor Clinic of the might Massachusetts General Hospital; and Pondville a true diabetic coma was the Hospital (Massachusetts suggested by report of Department of Public Health) Walpole, Mass. Dr. Kennedy was formerly normal urine obtained several hours to admission. Public Health Service Research Fellow of the National Cancer Institute prior and Clinical Research Fellow of Harvard University at the Massachusetts A public health question is also posed by this incident General Hospital; he is now Assistant Professor of Medicine, University because of the evident to children of of Minnesota School of Medicine. availability poison- The following pharmaceutical firms supplied the hormones used in this ous berries in city parks. study: Ayerst, McKenna & Harrison Limited, conjugated estrogenic sub- stances (Premarin); Ciba Pharmaceutical Products 895 Eastern Incorporated, testos- Parkway (Dr. Rascoff). terone propionate (Perandren) and ethinyl estradiol (Eticylol); Schering testosterone 1. Corporation, propionate (Oreton) and ethinyl estradiol (Esti- Aikman, J., in Brenneman's Practice in Pediatrics, McQuarrie, I., nyl); E. R. Squibb & Sons, diethylstilbestrol and editor, W. dienestrol; Wallace & Hagerstown, Md., F. Prior Company, Inc., 1948, vol. 1, chap. Tiernan Products, Inc., mestilbol and 17, p. 3. (Monomestrol) dimethyl ether of diethylstilbestrol; and White Laboratories, Inc., dienestrol. Downloaded from www.jama.com at Wright State University on March 29, 2010 actions necessitating cessation of therapy; (2) discontinuance of Alopecia.—Partial loss of scalp hair, often associated with use of the hormone because of rapidly progressing disease; hypertrichosis elsewhere, was noted in 22% of the patients. (3) systematic interruption, a procedure in the therapy pro- The hair of the scalp became dry and coarse and fell out gram, whenever an excellent response was obtained;lk or (4) whenever it was combed. Recession at the temples was noted death of the patient. in some patients, and occasionally baldness of the vertex of It will be shown that the incidence and degree of effects the scalp resulted. When use of the hormone was stopped, continued to as was some increase therapy prolonged. Since hair reappeared in these areas. Although hair loss occurs in other debilitating diseases, these women generally felt well Table 1.—Minimal Incidence of Side-Effects of Testosterone and maintained satisfactory nutritional states. Occasionally, Propionate in Eighty-Two Patients with Advanced the hair of patients who received large doses of androgens Breast Carcinoma turned gray. It has been postulated that androgens produce No. Demon- alopecia primarily in persons who have a hereditary suscepti- No. of strating bility to baldness. This was strikingly demonstrated in eunu- Cases Side- Incidence, Side-Effects Analyzed ' Effects % choids who received androgen therapy.4 Queries of women in whom such revealed that their male Hoarseness . 77 47 61 changes developed Hirsutism . 75 40 52 predecessors had had a high incidence of spontaneous alopecia. 12 22 Hair loss. Dermatological Changes.—Aesthetically distressing was the Acne. 71 21 30 of acne. The lesions resembled those seen in Ruddy complexion. 64 28 44 appearance puberal children and varied from small milia and scattered 70 7 10 Drowsiness to extensive furuncles and over the 18 papules papules face, back, _ 71 13 Nausea and chest. Increased oiliness and of the skin also Vomiting 70 8 11 thickening were .. noted. Known effects of androgens have been suggested of 76 58 76 Feeling well-being. to the acne: an increase in sebaceous secretion and Weight increase. 76 54 71 explain Libido increase. 59 22 37 hyperplasia of the epithelial cells at the mouth of the hair follicle.5 With superimposed infection, papules and pustule Edema . 67 11 16 formation may follow. The measures for skin Hypercalcemia 73 7 10 customary 4 hygiene were of benefit in the treatment of the acne, although Uremia .