Cisplatin-induced conditioned taste aversion: attenuation by dexamethasone but not zacopride or GR38032F.

The 5-HT3 receptor antagonists zacopride and GR38032F are highly effective inhibitors of emesis induced by ionizing radiation and chemotherapeutic drugs such as cisplatin. The present study evaluated zacopride and GR38032F for efficacy in inhibiting the formation of the conditioned taste aversion (CTA) induced by cisplatin or lithium chloride in rats. The glucocorticoid dexamethasone, which has been reported to be effective against both the emetic and CTA-inducing effects of cisplatin, was included as a reference compound. When administered alone by i.p. injection, zacopride (0.1-10 mg/kg), GR38032F (10 mg/kg) and cisplatin (0.32-1.8 mg/kg) induced a CTA to an 0.1% saccharin solution; lower doses of each compound were ineffective. When administered as a pretreatment, neither zacopride (0.001-0.1 mg/kg) nor GR38032F (0.01-10 mg/kg) attenuated the CTA induced by cisplatin (0.32 and 0.56 mg/kg) or lithium chloride (10 mg/kg). In contrast, dexamethasone (0.32 and 1.0 mg/kg) attenuated the CTA induced by 0.32 but not 0.56 mg/kg of cisplatin. In an attempt to evaluate higher doses of zacopride against cisplatin without the potentially confounding factor that these doses by themselves induce a CTA, rats were injected with zacopride on three separate days prior to the aversion conditioning session. This pre-exposure treatment blocked the formation of the zacopride-induced CTA, but did not improve the efficacy of zacopride in attenuating the cisplatin-induced CTA. These results suggest that neither the cisplatin- nor the lithium-induced CTA in rats are due to effects that are sensitive to 5-HT3 receptor blockade.

Mortality study of men employed at a large chemical plant, 1972 through 1982.

The mortality experience of a cohort of approximately 9,000 traced men employed at a Tennessee chemical plant was examined between 1972 and 1982. Statistically significant total mortality deficits of 41% to 46% and 14%, respectively, were observed compared with general population and occupational controls. Cancer deaths were 22% (significant) below expectation based on state and national vital statistics, whereas comparison with an employed group showed no difference. Significantly low mortality differentials were also reported for other major causes, including diseases of the circulatory, respiratory, and digestive systems. Analysis of the data by length of employment, payroll status, and chemical production division demonstrated no unusual patterns. The cohort's favorable mortality experience may be attributed to such factors as employee selectivity, health maintenance, accessibility to medical care, and less cigarette smoking.

Maximal cardiac output in angina patients before abd after coronary artery surgery.

Ten patients with angina pectoris underwent multistage maximal treadmill exercise with hemodynamic measurements before, and again 6 months following coronary artery surgery. Subjectively, 9 patients experienced a total and one patient partial relief from angina, and all patients noted improved exercise tolerance following surgery. Objectively, significant improvement was found in duration of exercise, maximal oxygen intake in maximal cardiac output, maximal heart rate, and maximal pressure-rate product. Surgery did not significantly affect systemic or pulmonary arterial pressures during exercise. Despite these improvements, maximal cardiac output did not return to normal levels following surgery, due to an unexpected but significant reduction in stroke volume.