Platelet activation in patients after an acute coronary syndrome: results from the TIMI-12 trial. Thrombolysis in Myocardial Infarction.

UNLABELLED: This study was designed to determine the magnitude and time course of platelet activation during therapy of acute coronary syndromes with an oral platelet antagonist. BACKGROUND: Platelet activation and aggregation are central to the pathogenesis of the acute coronary syndromes (ACS). However, few data are available on levels of platelet activation over time in patients with ACS, especially in the setting of chronic glycoprotein (GP) IIb/IIIa inhibition. METHODS: The Thrombolysis in Myocardial Infarction (TIMI) 12 trial was a phase II, double-blind trial evaluating the effects of sibrafiban, an oral, selective antagonist of the platelet glycoprotein IIb/IIIa receptor in patients stabilized after an ACS. A subset of 90 of the 329 patients in the study had measurement of platelet activation as assessed by the expression of platelet associated P-Selectin on days 0, 7 and 28. Platelet activation was measured in blood samples that were fixed either immediately (spontaneous activation) or after 5 minute incubation with 0, 1 microM or 5 microM ADP in order to assess platelet responsiveness to very low or moderate stimulation. RESULTS: At baseline there was a significant elevation of spontaneous platelet activation as compared to samples obtained from normal donors or from patients who did not have acute coronary syndromes (ACS patients 27.6+/-18.7%, Normal controls 8.5+/-4.4%, Patient controls 10.9+/-7.1%, p < 0.005 for both). In addition, there was a significant decrease in the levels of platelet activation with time during the 28 days of treatment with sibrafiban. Nevertheless, even on day 28, the TIMI-12 patients continued to show elevated platelet activation in comparison to the control groups (p < 0.05 for both). CONCLUSIONS: These results suggest that platelets remain activated long after clinical stabilization post ACS. Although platelet activation decreased after one month of oral GPIIb/IIIa inhibition, levels remained higher than normal, suggesting the need for long-term antiplatelet therapy following ACS.

Assessing the first eight years of an optional five-year medical curriculum.

Experience with the initial eight years (1980-1987) of a voluntary five-year medical degree program at the Boston University School of Medicine is examined. The program, called the Alternative Curriculum, permits medical students to "decompress" the first year of their medical school curriculum. The program was designed to be a parallel curricular pathway and not a remedial program. Some students in academic difficulty, however, have been enrolled in this program. The students' records and their responses to a questionnaire form the basis for this report. The students who entered the Alternative Curriculum before the start of classes or who, upon entering, were in good academic standing generally did well academically and were uniformly pleased with the time that was available to pursue other interests. Several of these students were subsequently permitted to decompress other curricular years, with uniform success. Of the students for whom the Alternative Curriculum was used as a remedial program, nearly half had left or been dismissed from school at the time of this report.

An assessment of the clinical skills of fourth-year students at four New England medical schools.

This paper describes a collaborative effort among five New England medical schools to assess important clinical skills of fourth-year medical students graduating in the class of 1988; results are presented from the four schools that provided sufficient data. Faculty from each school developed 36 patient cases representing a variety of common ambulatory-care problems. Over the course of a day, each student, on average, interacted with 16 different standardized patients, who were nonphysicians trained to accurately and consistently portray a patient in a simulated clinical setting. The students obtained focused histories, performed relevant physical examinations, and provided the patients with education and counseling. At each school, the performance of a small number of the students fell below standards set by the faculty. These deficiencies were not detected with the evaluation strategies currently being used. Although the use of standardized patients should not substitute for the process of faculty observing students as they interact with real patients, it appears that standardized patients can provide faculty with important information, not readily available from other sources, about students' performances of essential clinical activities and the levels of their clinical skills.

Teaching and funding of primary care education in third-year clerkships.

The authors in this article describe a 12-week primary care elective for third-year medical students. The administrative and teaching resources of the Boston University School of Medicine, clinical sites at three Boston community health centers, and federal/state and private foundation funding are coordinated to provide a longitudinal, integrated experience in ambulatory pediatrics and medicine. A literature review revealed no prior medical student programs combining psychiatric, pediatric, and internal medicine teaching in a community setting. Case vignettes and questionnaire results indicate that the program has been a success at introducing students to primary care and the biopsychosocial model. The implications of bridging disciplines as well as academic and community health centers and providing funding resources are discussed. The authors recommend this integrative model for enhancing the development of future primary care physicians.

Eosinophilic gastroenteritis with malabsorption, extensive villous atrophy, recurrent hemorrhage and chronic pulmonary fibrosis.

A patient with diffuse eosinophilic gastroenteritis, associated with progressive chronic interstitial pulmonary fibrosis, was followed for 29 years. His major symptoms were recurrent gastrointestinal bleeding, anemia, diarrhea, malabsorption, and increasing respiratory insufficiency. Multiple jejunal biopsies revealed eosinophilic infiltration and extensive villous atrophy. Results of a lung biopsy and pulmonary function tests were consistent with chronic interstitial pulmonary fibrosis. His gastrointestinal symptoms responded to steroid therapy, but he died of progressive respiratory insufficiency. At autopsy, villous atrophy was noted to extend throughout the whole extent of the small intestine in association with multiple "pseudopolypoidal" inflammatory lesions.