Comparing research activities of women and men faculty in departments of internal medicine.

The findings from a questionnaire prepared by the Association of Professors of Medicine and the Association of American Medical Colleges were published in two reports in 1986 and 1987. These reports assessed the research activities of full-time members of departments of internal medicine in 1982 and 1983. The purpose of the present study was to analyze the data of the earlier reports in order to compare the research activities of women and men who were full-time faculty in departments of medicine during the time period originally surveyed. More than half of the faculty women who responded (52%) were less than 40 years old, compared with 23% of the faculty men. Sixty-seven percent of the women held the rank of instructor or assistant professor, in contrast to 40% of the men holding these ranks. Although the faculty of both genders reported generally the same proportions of time devoted to research, the women researchers with M.D. degrees had significantly less National Institutes of Health (NIH) grant support than did their counterparts who were men. Since this difference may have been a function of age, the authors compared NIH grant support of the faculty men and women with M.D. degrees who were 40-59 years old. Even in this older group, significantly fewer of the faculty women had NIH grant support than did the men (16% versus 30%). Furthermore, the percentage of designated laboratory space was significantly lower among the faculty women, regardless of degree (M.D., M.D./Ph.D., or Ph.D.). Further investigation is warranted to monitor the progress of women attempting to develop their research careers and to assess their overall clinical teaching and administrative roles in departments of medicine.

Combined treatment with minoxidil and captopril in refractory hypertension.

The BP of four patients with severe hypertension could not be controlled by treatment with a variety of drugs including minoxidil and captopril. Satisfactory responses were obtained only when minoxidil and captopril were given in combination (along with diuretic and beta-adrenergic blocking agents). The doses of minoxidil could be reduced by the addition of captopril and adverse effects were thus minimized. The state of the renin-angiotensin system prior to therapy was not a reliable predictor of the hypotensive response of the combination.

Inhibition of cardiac guanylate cyclase by doxorubicin and some of its analogs.

Doxorubicin, an anthracycline antibiotic and antitumor agent, has cardiotoxic side-effects that limit its therapeutic usefulness. We have demonstrated that the drug inhibits cardiac guanylate cyclase activity in vitro. The biochemical changes following anthracycline treatment are described, and the various hypotheses attempting to account for cardiotoxicity in terms of a molecular mechanism are reviewed. It is suggested that inhibition of cardiac guanylate cyclase activity may be a consequence of the increase in free radicals and oxidative damage following treatment with doxorubicin or related compounds.

Inhibition of cardiac guanylate cyclase by doxorubicin and some of its analogs: possible relationship to cardiotoxicity.

The anthracycline antibiotic doxorubicin induces a variety of cardiotoxic effects. We have recently demonstrated that this drug also causes a selective inhibition of rat and human cardiac guanylate cyclase activity in vitro. In the present study, we examined the effect of 30 analogs of doxorubicin on cardiac guanylate cyclase activity. Structural modifications of these anthracycline antibiotics were found to alter their effect on rat cardiac guanylate cyclase activity, N-Substitutions on the sugar moiety eliminated the inhibitory action observed with the parent compound. Long-chain hydrocarbon substitutions in place of the methylketone side chain had a similar effect. Removal or substitution of the C-4 methoxy group had little or no effect on the ability of these compounds to modify guanylate cyclase activity. Substitutions of the C-9 side chain by a hydrazone derivative resulted in compounds that stimulated the enzyme. All of the anthracenedione derivatives were inhibitory. A comparison of the inhibitory effect of some of these anthracycline derivatives on in vitro cardiac guanylate cyclase activity with their cardiotoxic potency suggests a possible relationship between these two parameters.

Evaluation of guanabenz added to hydrochlorothiazide therapy in hypertension.

Guanabenz, a centrally acting alpha-adrenergic antihypertensive agent, produces neither the sodium retention seen with other centrally acting agents nor the metabolic abnormalities characteristic of diuretics. In this study, which involved 204 hypertensive out-patients, the additive effects of guanabenz and hydrochlorothiazide were compared with the effects of hydrochlorothiazide therapy alone. Before randomization to the 6-month blinded addition of either guanabenz or placebo, hydrochlorothiazide (50 or 100 mg/day; mean, 70 mg/day) was administered as sole therapy for 6 weeks. During this time, mean supine diastolic blood pressure (SDBP) decreased from 102 to 94 mm Hg (p less than 0.01), with a satisfactory clinical response rate of 62% and a mean weight loss of 2 lbs (p less than 0.01). No further change in mean SDBP occurred during the next 6 months of diuretic therapy, whereas the addition of guanabenz (mean dose, 24 mg/day) caused a further decrease in mean SDBP to 88 mm Hg (p less than 0.01), an increase in the response rate to 86%, and no weight change. Pulse rates in both groups were unchanged. The principal side-effects in both groups were dry mouth, drowsiness, weakness, and dizziness, with a greater incidence of each during the combination therapy. The usual laboratory abnormalities were associated with hydrochlorothiazide. Guanabenz was found to enhance the antihypertensive efficacy of hydrochlorothiazide without compromising its natriuretic properties or producing additional metabolic abnormalities.

Latex test for serodiagnosis of infectious mononucleosis.

A glycoprotein was isolated from bovine erythrocytes which has 20% carbohydrate and migrates on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a single band. This glycoprotein carries the reactivity of bovine erythrocytes with Paul-Bunnell heterophile antibody of infectious mononucleosis. This bovine glycoprotein was coupled to carboxyl-modified latex particles with water-soluble carbodiimide. The resulting reagent was then used to develop a new test for the detection of infectious mononucleosis antibody. The bovine erythrocyte glycoprotein-latex reagent is more stable than sheep or horse erythrocytes, the traditional reagents for detection of infectious mononucleosis antibody. This new reagent is used in a direct slide test; no preabsorption of the sera is necessary. In the present study the glycoprotein-latex reagent compared favorably in terms of sensitivity and specificity with two standard tests for infectious mononucleosis antibody. Ninety-nine serum samples were tested. Agreement of the latex test with a stabilized horse erythrocyte spot test was 90%. Ten samples were weakly positive with the latex test and negative with the horse cell test. Only one of these was also positive with an enzyme-treated sheep cell test. This latter test was somewhate more sensitive than the latex test.

Immunochemical studies of infectious mononucleosis. VI. a radioimmunoassay for the detection of infectious mononucleosis heterophile antibody and antigen.

The coated-tube method of solid-phase radioimmunoassay has been adapted to the detection of heterophile antibodies and antigens of infectious mononucleosis. Disposable plastic hemagglutination trays were coated with purified glycoprotein from horse erythrocytes and the subsequent uptake of antibody from test sera was detected by radio-iodinated horse erythrocyte glycoprotein. In a preliminary survey of sera from patients with infectious mononucleosis and sera from controls, the assay proved highly sensitive and specific. The test system was also useful in a competitive binding assay for immunochemical studies of glycoproteins from other heterophile antigen-positive species.