Faculty Bibliography

During blood coagulation human polymorphonuclear leukocytes release elastase in amounts that can exceed 100 nmol/liter. We therefore studied the effect of elastase on platelet structure and function. Physiologic concentrations of elastase specifically inhibited thrombin-induced platelet aggregation and ristocetin-induced agglutination of washed platelets in a time- and dose-dependent manner. This was associated with a decrease in the number of high affinity thrombin binding sites on the platelet surface (analysis by "Ligand" program) from 31 per platelet to 12 per platelet (P less than 0.05). As analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, treatment of 3H-labeled platelets with elastase resulted in a decrease in the percent glycoprotein at 130,000-150,000 Mr = and an increase in the percent protein at Mr = 102,000. The supernatant from elastase-treated platelets contained a Mr = 88,000 glycoprotein not found in the supernatant from untreated platelets. Immunoprecipitation studies with monoclonal antiglycoprotein Ib demonstrated that treatment of whole platelets with physiologic concentrations of elastase resulted in proteolytic cleavage of glycoprotein Ib. Elastase treatment of glycoprotein immunoisolated with monoclonal antiglycoprotein Ib antibody resulted in formation of a glycopeptide with the same electrophoretic mobility as the Mr = 102,000 membrane-related glycopeptide. In contrast, analysis by Western blot technique using antiglycoprotein IIb and IIIa antibodies demonstrated that elastase did not degrade glycoproteins IIb or IIIa. We conclude that elastase inhibition of thrombin-induced platelet stimulation is accompanied by (a) a reduction in the number of thrombin binding sites per platelet and (b) proteolysis of glycoprotein Ib.

Uncertainty about optimal treatment for many diseases results in heterogeneous management by definition. It was hypothesized that identifiable characteristics in a physician's background would influence the management of any such condition and thereby explain some of this heterogeneity. A vignette describing a patient with new-onset angina and a questionnaire ascertaining individual physician characteristics and management preferences were sent to attending physicians and house staff in the Department of Medicine at New York University School of Medicine. Although physicians believed very strongly that the patient had angina on the basis of the history, there was no consensus about managing the hypothetic patient. The age of the physician was the single most important predictor of management, with the younger half of the sample more likely to hospitalize (p less than 0.001), less likely to prescribe nitroglycerin as a sole therapy (p less than 0.005), and more likely to prescribe beta blockers (p less than 0.005). The era in which a physician trains may determine practices that persist for a lifetime. These findings may have important implications for medical education and the quality and cost of medical care