Georgetown University

About: Georgetown University is a education organization based out in Washington D.C., District of Columbia, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 23377 authors who have published 43718 publications receiving 1748598 citations. The organization is also known as: GU & Georgetown.

Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6.

Abstract: We performed comprehensive kinetic, inhibition, and correlation analyses in human liver microsomes and experiments in expressed human cytochromes P450 (P450s) to identify primary and secondary metabolic routes of tamoxifen (TAM) and the P450s catalyzing these reactions at therapeutically relevant concentrations. N-Desmethyl-TAM formation catalyzed by CYP3A4/5 was quantitatively the major primary metabolite of TAM; 4-hydroxy-TAM formation catalyzed by CYP2D6 (and other P450s) represents a minor route. Other minor primary metabolites include alpha -, 3-, and 4'-hydroxyTAM and one unidentified metabolite (M-I) and were primarily catalyzed by CYP3A4, CYP3A5, CYP2B6/2C19, and CYP3A4, respectively. TAM secondary metabolism was examined using N-desmethyl- and 4-hydroxy-TAM as intermediate substrates. N-Desmethyl-TAM was predominantly biotransformed to alpha-hydroxy N-desmethyl-, N-didesmethyl-, and 4-hydroxy N-desmethyl-TAM (endoxifen), whereas 4-hydroxy-TAM was converted to 3,4-dihydroxyTAM and endoxifen. Except for the biotransformation of N-desmethyl-TAM to endoxifen, which was exclusively catalyzed by CYP2D6, all other routes of N-desmethyl- and 4-hydroxy-TAM biotransformation were catalyzed predominantly by the CYP3A subfamily. TAM and its primary metabolites undergo extensive oxidation, principally by CYP3A and CYP2D6 to metabolites that exhibit a range of pharmacological effects. Variable activity of these P450s, brought about by genetic polymorphisms and drug interactions, may alter the balance of TAM effects in vivo.

Accounting Quality and Firm-Level Capital Investment

Abstract: This study examines how accounting quality relates to firm-level capital investment efficiency. Our first hypothesis is that higher quality accounting enhances investment efficiency by reducing information asymmetry between managers and outside suppliers of capital. Our second hypothesis is that this effect should be stronger in economies where financing is largely provided through arm's-length transactions compared with countries where creditors supply more capital. Our results are consistent with these hypotheses both across and within countries. They are robust to alternative econometric specifications, different measures of accounting quality and investment-cash flow sensitivity, and numerous control variables.

Reexamining the empirical evidence for an environmental kuznets curve

Abstract: This paper uses an updated and revised panel data set on ambient air pollution in cities worldwide to examine the robustness of the evidence for the existence of an inverted U-shaped relationship between national income and pollution. We test the sensitivity of the pollution-income relationship to functional forms, to additional covariates, and to changes in the nations, cities, and years sampled. We find that the results are highly sensitive to these changes, and conclude that there is little empirical support for an inverted U-shaped relationship between several important air pollutants and national income in these data.

Clinical Significance of Mitral Regurgitation After Acute Myocardial Infarction

Abstract: Background Mitral regurgitation (MR) may complicate acute myocardial infarction (MI). However, it is not known whether mild MR is an independent predictor of post-MI outcome. Methods and Results The study cohort consisted of 727 Survival and Ventricular Enlargement Study patients who underwent cardiac catheterization, including left ventriculography, up to 16 days after MI. Left ventriculograms were analyzed for diastolic and systolic volumes, global left ventricular sphericity, extent of wall motion abnormality, and endocardial curvature. The presence of MR was related to the risk of developing a cardiovascular event during 3.5 years of follow-up. MR was present in 141 patients (19.4%). Severe (3+) MR was present in only 2 patients. Patients with MR were more likely to have a persistently occluded infarct artery (MR versus no MR, 27.3% versus 15.2%; P=.001). Although the ejection fractions were similar, MR patients had larger end-systolic and end-diastolic volumes and more spherical ventricles than patie...