George A. Hyman

Jaundice and intrahepatic cholestasis following high-dose megestrol acetate for breast cancer

High‐dose megestrol acetate, a synthetic progestin, has been advocated recently in treating patients with metastatic breast carcinoma; no significant increase in adverse effects has been reported. This report describes a patient with jaundice and intrahepatic cholestasis after high‐dose megestrol acetate therapy. This cholestatic lesion may have a pathogenesis similar to that observed with estrogens and oral contraceptives.

Disseminated carcinoma of the ovary treated by L‐phenylalanine mustard

Forty cases of widely disseminated ovarian cancer were treated with L‐phenylalanine mustard administered by mouth. The diagnosis in all cases was established by biopsy. There were 12 objective responses. A case was classified as showing an objective response if one or more of the following phenomena occurred: (1) 50 % or more decrease in the clinical size of the tumor mass; (2) 50% or more decrease in the size of the tumor on roentgenogram and (3) 50% decrease or complete disappearance of pelvic and pleural effusion. The response lasted 3 to 36 months or more. The authors found no evidence to suggest that the drug prolonged life. Complications from the drug were minimal and in most instances the patients were managed as out‐patients during a large part of their treatment. The effect of phenylalanine mustard on disseminated ovarian cancer was much the same as that of other alkylating agents.

Possible defect in rna metabolism in leukemic cells

Autoradiographic techniques were used to explore possible differences in RNA synthesis rates between leukemic and nonleukemic leukocytes. In the past, reports have dealt primarily with DNA synthesis employing tritiated thymidine. The present report deals primarily with differences in the quantities and distribution of labeled RNA in leukemic and normal leukocytes employing tritiated uridine and cytidine. One hundred adults were studied; 63 patients had acute or chronic lymphocytic, myelocytic or monocytic leukemia. Thirteen normal individuals also were studied. The results demonstrated the potential value of RNA‐labeling techniques in leukemia. The finding of increased intranuclear H3‐RNA and decreased cytoplasmic H3‐RNA is of particular interest and may be explained by an abnormality of RNA in leukemic cells.

Effect of Cortisone and Adrenocorticotropic Hormone (ACTH) on Experimental Scurvy in the Guinea Pig.

Summary 1. Cortisone and ACTH prolong life and reduce the hemorrhagic manifestations of scurvy in guinea pigs. The effects of the two hormones are similar. 2. The effect of these two hormones is also parallel in the direction of maintenance of glycogen storage in liver, adrenal, and muscle in the scorbutic guinea pig. 3. The moderating effect of ACTH on scurvy makes it seem probable that vitamin C is not needed for the production of the corticosteroids similar to cortisone. This idea receives further support from other observations, including the demonstration of increased adrenal activity induced by ACTH in the absence of demonstrable adrenal ascorbic acid. 4. The locus of action of adrenal corticosteroids in the amelioration of certain hemorrhagic phenomena is not clear, but may be on the blood vessels or perivascular tissues.

Efficacy of cyclophosphamide in the management of reticulum cell sarcoma

Because prior chemotherapy in patients with disseminated reticulum cell sarcoma had been unsatisfactory, cyclophosphamide (Cytoxan) therapy was evaluated. The 66 patients had documented disease so widespread that radiotherapy to symptomatic areas was no longer feasible; 42% had remissions with greater than 50% objective improvement for 2 to 22 months. If possible, an initial dose of 25 to 40 mg/kg was administered intravenously in divided daily doses over 4 to 5 days. Because second courses of therapy were ineffective, oral maintenance therapy was employed after initial response. Careful titration of dosage with particular attention to pretreatment therapy minimized toxicity. Only one death from hepatic insufficiency and one from gram‐negative sepsis and leukopenia were drug‐related. Patients less than 13 years old, with central nervous system involvement, or in the leukemic phase did not respond. Over‐all survival has not altered significantly in the past 20 years, with a 10 month, 50% survival from diagnosis. Nevertheless, cyclophosphamide, because of its effectiveness, minimal toxicity and ease of dosage control, is the treatment of choice at present for effective palliation of patients with disseminated reticulum cell sarcoma when radiotherapy is no longer possible.

Autoradiographic studies of oral lichen planus

3H cytidine autoradiographic labeling patterns have been categorized into those characteristic for neoplastic, preneoplastic, and normal cell types. Specific differences in the patterns of transcription (RNA synthesis) revealed that the histology of a particular lesion generally correlated with (1) the percentage of cells labeled with the isotope, (2) the number of grains per cell, and (3) their intracellular distribution. When these three criteria of labeling were applied to lesions of the oral mucosa, very interesting data were collected on cases of lichen planus. The benign histologic appearance of the oral lichen planus epithelium exhibited a preneoplastic-appearing autoradiogram, an observation which is of particular interest in view of the fact that a small number of patients with this disease develop intraoral squamous cell carcinoma.

The definition of erythrocyte osmotic fragility in normal and abnormal blood.

Summary The osmotic fragility of blood can be numerically defined by measuring the change in osmolarity (Δ mOsm) required to hemolyze 50% of the erythrocyte population when hemolysis is proceeding at the highest rate. In normal blood Δ mOsm = 11.8 ± 1.1 mOsm. In all blood dyscrasias which were studied this osmotic fragility index was significantly different from normal. It was abnormal in the bearers of sickle cell or thalassemia trait. It was also abnormal in Hodgkins disease and in cancer patients.

Treatment of Breast Cancer with Medroxyprogesterone.

Excerpt The observation that progestational agents alone or combined with estrogens might be useful in the management of cancer led to the treatment of 36 patients (34 women and 2 men) with dissemi...

The Medical Use of Marihuana and THC in Perspective

The curative properties attributed to marihuana for several thousand years have proved to be disappointing. The ancient oriental claims of marihuana as a pain soother and for the relief of muscle spasms, convulsions, rheumatism, epilepsy and migraine headaches were introduced into western medicine during the 19th century. The reason for the lack of success with marihuana remedies at that time was the same as the present observations encountered with THC and all of its novel applications: the variability and inconsistency of its effects associated with unwanted psychological and cardiovascular effects. The discovery of THC, the active ingredient of marihuana gave a new impetus for an intensive search for its potential therapeutic applications. THC and its psychoactive derivatives were proposed as analgesic, antidepressant, hypnotic tranquilizer, as a treatment for withdrawal symptoms, glaucoma, spasticity, nausea, vomiting, and to enhance the appetite. Marihuana smoke, in spite of its toxicity to the lung and immune system, was even advocated by some as a medically acceptable vehicle for THC. For many of these therapeutic applications, molecular pharmacologists have been able to tailor specific molecules targeted to receptor sites which control acute and inflammatory pain, nausea, vomiting, and glaucoma. These fundamental studies in molecular pharmacology have also provided for an explanation of the therapeutic inadequacy of THC. This cannabinoid deregulates the physiological signaling role of a receptor protein to which it binds and of the membrane bilipid layer which it permeates. This deregulation of membrane signaling will result in discordant and partial therapeutic effects coupled with unwanted side effects.

The 1997 Medical Controversy over the Legalization of Marihuana for Medicine

In November of 1997, following a well financed media campaign, two referenda in Arizona and California were approved, giving a legal status to marihuana for medicine. At that occasion, conflicting positions were formulated by two groups of physicians. One group supported the legal use of marihuana for medicine in smoked or orally administered form, the other objected to the use of smoked marihuana. Their detailed opinions follow: that of Dr. J.P. Kassirer, editor of the New England Journal of Medicine, and that of Gabriel Nahas, Kenneth Sutin, William Manger, and George Hyman who expressed their views in the Wall Street Journal.