Biomedical subjects

Stuart Rich

Publications and source records attributed to Stuart Rich.

21 records · Page 2Linked to original sources

PubMed2002

Detection of subclinical cardiovascular disease: the emerging role of electron beam computed tomography.

BACKGROUND: Although extraordinary advances have been made in the management of advanced coronary artery disease, little progress has been made in its prevention. Traditional screening methods utilizing risk factor profiles and exercise treadmill tests have failed to identify populations who will subsequently have coronary events with a high degree of predictive accuracy. METHODS: We review the pathobiologic basis and clinical utility of electron beam computed tomography (EBCT) to detect coronary artery calcium as a screening tool for subclinical coronary artery disease. Because EBCT is able to perform subsecond imaging of the heart, it can detect and quantitate coronary artery calcium with a high degree of precision. Coronary artery calcium is a marker of complex atherosclerosis. RESULTS: Over 4,000 asymptomatic patients in several series have been studied with EBCT and followed prospectively for an average of 42 months (range 37-72 months). A positive scan is associated with a risk ratio for future coronary events of 8.7 (95% confidence interval 2.67 to 28.13). These data indicate that EBCT has the ability to detect subclinical coronary artery disease and predict future coronary events better than any previous existing method or technology. CONCLUSION: EBCT coronary artery screening may prove to be a valuable adjunct to the traditional methods for the detection of subclinical coronary artery disease and to identify those who would benefit from focused preventive therapies.

Aged↗

PubMed2002

Effects of the thromboxane synthetase inhibitor and receptor antagonist terbogrel in patients with primary pulmonary hypertension.

BACKGROUND: Circulating mediators, including thromboxane A2, the vasoconstrictor, platelet aggregant, and smooth muscle mitogen, may contribute to the progression of vascular narrowing in primary pulmonary hypertension (PPH). METHODS: To further understand the contribution of thromboxane and to provide novel therapy for PPH, we administered the potent orally active thromboxane synthetase inhibitor and thromboxane receptor antagonist terbogrel for 12 weeks to patients with New York Heart Association functional classification II and III PPH. The study had a multicenter randomized placebo-controlled design. The primary endpoint was a change in the distance walked during 6 minutes. The pharmacologic effects of terbogrel on thromboxane and prostacyclin metabolism also were studied. RESULTS: Although the planned enrollment was 135 patients, the study was halted after only 71 patients had been randomized because of the unforeseen side effect of leg pain, which occurred almost exclusively in patients with terbogrel treatment. Only 52 patients completed the 12-week study, and only 22 patients (31%) were fully compliant with the study medication. The leg pain confounded the primary endpoint of walking distance. On an intention-to-treat analysis, no improvements in 6-minute walk distance or in hemodynamics in patients with terbogrel treatment were seen. However, terbogrel was effective from a pharmacologic standpoint, reducing thromboxane metabolites by as much as 98% (P <.0001), with a modest but statistically insignificant (39%) rise in prostacyclin metabolites. CONCLUSION: Inhibition of thromboxane with an orally active agent is feasible in PPH, but the incidence of severe leg pain with terbogrel precludes its use in this disorder. Similar therapeutic efforts, with other thromboxane inhibitors, should be considered.

Double-Blind Method↗

PubMed2002

Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study.

STUDY OBJECTIVES: To evaluate the safety and efficacy of sitaxsentan, an endothelin-A receptor antagonist, in a 12-week, open-label trial of patients with pulmonary arterial hypertension (PAH). PATIENTS: Six children and 14 adults with New York Heart Association (NYHA) functional class II, III, or IV primary pulmonary hypertension or PAH associated with either congenital systemic-to-pulmonary shunts or collagen vascular disease were enrolled. MEASUREMENTS: Sitaxsentan was administered orally at 100 to 500 mg bid for 12 weeks. Cardiopulmonary hemodynamics via cardiac catheterization were obtained at baseline and week 12. Six-minute walk test distance was measured at baseline, week 6, and week 12. RESULTS: Sitaxsentan treatment resulted in significant improvement in exercise capacity as assessed by the 6-min walk distance (baseline [mean +/- SD], 466 +/- 132 m; week 12, 515 +/- 141 m, n = 20, p = 0.006). Mean pulmonary artery pressure and pulmonary vascular resistance index also improved (63 +/- 20 to 52 +/- 22 mm Hg, n = 17, p = 0.0002; and 20 +/- 11 to 14 +/- 13 U x m(2), n = 17, p = 0.008, respectively). Serious adverse events included two cases of acute hepatitis (fatal in one patient). CONCLUSIONS: Patients with NYHA functional class II, III, or IV PAH showed a significant improvement in exercise capacity and cardiopulmonary hemodynamics over a 12-week period of treatment with sitaxsentan, an endothelin-A receptor antagonist. Further investigation is warranted to evaluate the safety and efficacy of sitaxsentan in patients with PAH.

Adolescent↗