Atypical multicentric reticulohistiocytosis with paraproteinemia

Two women had multiple subcutaneous nodules that showed features of multicentric reticulohistiocytosis (MR). Neither had joint symptoms. Both had a raised erythrocyte sedimentation rate, an immunoglobulin G paraproteinemia, and raised levels of nonhepatic serum alkaline phosphatase. The skin lesions have been followed up, using light and electron microscopy, immunoperoxidase, and histochemical methods. The material in the giant cells stained positively for gamma heavy chain determinants: the light chain type in each case was that of the paraprotein. An attempt to reproduce the skin lesions in one patient by intradermal injection of her paraprotein failed.     

Hpertrophic subaortic stenosis is not rare in the eighth decade

During a five year period, idiopathic hypertrophic subaortic stenosis was diagnosed in nine patients 70 to 79 years of age and in 26 patients 20 to 66 years of age who were referred to the cardiology division of the Long Island Jewish-Hillside Medical Center because of symptomatic heart disease. Only one of the older patients, compared with 19 of the younger ones, was referred with the correct diagnosis. Coronary artery disease with papillary muscle dysfunction was incorrectly diagnosed in four of the older patients. Cardiac catheterization confirmed the diagnosis of idiopathic hypertrophic subaortic stenosis in all of the 26 younger patients and in five of the nine older ones; diagnosis was based on typical echocardiographic features in the other four patients. Symptoms, physical findings, and electrocardiographic observations were similar in both groups. Aortic valve calcification was found in one younger patient and three older ones. The ratio of women to men was higher in the older group (7:2) than in the younger group (12:14). Coronary artery disease was more frequent in the older patients (three of five, compared with six of 26). Our experience indicates that idiopathic hypertrophic subaortic stenosis is not rare during the eighth decade. The diagnosis should be considered in any patient with an unexplained appropriate heart murmur, and definitive studies, such as echocardiography, should be done. As with any condition, proper management depends on accurate diagnosis.     

Aminoglutethimide in the treatment of Cushing's syndrome

The efficacy and tolerability of aminoglutethimide for the treatment of Cushing's syndrome was assessed in 66 cases three of which are described in the present paper. Aminoglutethimide provided palliation from the signs and symptoms of hypercorticism in 13 of 21 patients with metastatic adrenocortical carcinoma and four of six patients with ectopic ACTH production due to metastatic carcinomas. All six of the patients with adrenal adenomas showed clinical and biochemical improvement, while 14 of the 33 patients with bilateral adrenal hyperplasia of pituitary origin improved. Adverse reactions attributed to aminoglutethimide such as drowsiness, rash, and nausea occurred in 58 per cent of cases. These data suggest that aminoglutethimide has a place in controlling the signs and symptoms of adrenocorticoid excess in patients with Cushing's syndrome due to malignancy and is effective preoperative therapy for patients with adrenal adenomas and bilateral hyperplasia.     

Impairment of diazepam metabolism by low-dose estrogen-containing oral-contraceptive steroids

The longterm use of low-dose estrogen containing oral contraceptives (OCs) and its impairment of diazepam clearance is reported. 8 healthy women, ranging in age from 52 to 72 years, participated in the study. All of the women had been taking low-dose estrogen containing OCs for more than 3 months. 1 of the subjects was a cigarette smoker. 8 healthy controls (all nonsmokers) who were not using OCs also participated. They ranged in age from 27-31 years. Diazepam (10 mg) was given by intravenous infusion over 15-30 seconds. Venous blood samples were drawn into heparinized tubes before the infusion, at the end of the infusion, at 5, 15, 30, and 45 minutes, at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours, and daily for 7 days after the infusion. Plasma concentrations of diazepam after intravenous infusion were analyzed by weighted iterative nonlinear least-squares regression techniques. The volume of distribution of diazepam was not significantly different between the groups, but the apparent elimination half-life of diazepam was significantly longer and the total metabolic clearance significantly less in the OC users than in the control group. The differences were not confounded by variations in protein binding. The mean diazepam free fraction was identical in the 2 groups. The clinical result of the decrease in diazepam clearance reported here would be increased steady-state plasma diazepam concentration after longterm use at a given daily dose, with the potential for increasing the clinical effects of diazepam in this population.