The New England journal of medicine
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When aspirin is administered by mouth in low doses, poor systemic bioavailability may contribute to its apparent dose-related "selective inhibition" of thromboxane A2 formation. Systemic bioavailability of orally administered aspirin is necessary to inhibit prostacyclin synthesis by systemic vascular endothelium, whereas cumulative inhibition of thromboxane A2 formation by platelets may occur in the presystemic (portal) circulation. We simultaneously administered unlabeled aspirin orally and deuterium-labeled aspirin intravenously in five healthy volunteers. ⋯ Thromboxane B2 formation in serum ex vivo after oral administration of 20 mg of unlabeled aspirin was reduced 39 per cent before aspirin was detected in the systemic circulation. Furthermore, incubation of simulated peak plasma aspirin concentrations in whole blood in vitro underestimated the inhibition of thromboxane B2 ex vivo after oral administration of 20 or 40 mg of unlabeled aspirin. These data are consistent with presystemic inhibition of platelets by aspirin and suggest that biochemical "selectivity" might be enhanced by slow administration of very low doses of aspirin, thereby optimizing conditions for cumulative, presystemic acetylation of platelet cyclooxygenase and inhibition of thromboxane formation.
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Randomized Controlled Trial Comparative Study Clinical Trial
The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study.
To determine whether corticosteroids are efficacious in severe septic shock, we conducted a prospective study of 59 patients randomly assigned to a methylprednisolone, dexamethasone, or control group. Patients were treated 17.5 +/- 5.4 hours (mean +/- S. E. ⋯ However, these differences in reversal of shock and survival disappeared later in the course. Overall, 16 (76 per cent) of 21 patients receiving methylprednisolone, 17 (77 per cent) of 22 patients receiving dexamethasone, and 11 (69 per cent) of 16 controls in the hospital died. We conclude that corticosteroids do not improve the overall survival of patients with severe, late septic shock but may be helpful early in the course and in certain subgroups of patients.