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David A Davis

Publications and source records attributed to David A Davis.

22 records · Page 2Linked to original sources
PubMed2002

Randomized controlled trials of continuing medical education: what makes them most effective?

INTRODUCTION: It is essential that professional standards of excellence are demonstrated in the continuing medical education (CME) curriculum and research. METHODS: This review examines 20 randomized controlled trial (RCT) studies in CME and their effect on physician performance and/or patient health care outcomes. A systematic evaluation of the 20 RCT articles was performed. The investigators of the trials were interviewed using a standardized interview schedule. Citations from science and social science publications were compiled to obtain an unobtrusive measure of the influence of the trials. RESULTS: Investigators were most often motivated to build on earlier research of others, their own earlier research, or a combination of others' earlier research and their own. The most effective educational strategies used multiple interventions, two-way communications, printed and graphic materials in person, and locally respected health personnel as educators. Statistically significant findings more often related to physician performance than to patient health care outcomes. The most effective studies were the ones in which the educational methods were cost effective, findings could be generalized to other physician groups, the studies were implemented elsewhere in multisite health care and health-related programs and had the most citations. Investigators interviewed about their RCTs provided advice for future directions of CME curriculum development and research. DISCUSSION: CME program directors should determine what physicians need to learn, should reach out to nonparticipating physicians, and should focus on relevant problem areas. These problem areas should be ones in which it is possible to make changes, particularly in patient health care outcomes.

Curriculum↗
PubMed2002

Minimal reactivation of Kaposi's sarcoma-associated herpesvirus by corticosteroids in latently infected B cell lines.

Corticosteroid use in transplant recipients increases the incidence and severity of Kaposi's sarcoma (KS), a disease associated with KS-associated herpesvirus (KSHV) infection. Recently, the prototypic corticosteroid, hydrocortisone, was shown to directly induce lytic cycle reactivation of KSHV in latently-infected BCBL-1 cells. The purpose of this study was to examine this phenomenon in further detail. After incubation with dexamethasone (<or= 30 microM) or hydrocortisone (<or= 30 microM) for 1-4 days, we evaluated KSHV reactivation in latently infected B cell lines (BC-1, BC-3, and BCBL-1) by assessing early-lytic PF-8 and late-lytic gpK8.1 protein expression using flow cytometry. Viral particle production was monitored by quantifying KSHV minor capsid protein levels in cell culture supernatants. A small increase in the percentage of cells expressing viral lytic proteins was observed in BCBL-1, but not in the other cell lines. In combination with 3 nM 12-O-tetradecanoyl-phorbol-13-acetate, a known chemical inducer of KSHV replication, corticosteroids (0.3 microM) enhanced KSHV reactivation twofold in some cell lines, but not in others. In all experiments, lytic viral protein expression by flow cytometry correlated with production of viral particles in culture supernatants. In summary, we found that corticosteroids were limited inducers of KSHV reactivation in latently infected cells. Thus, our findings suggest that corticosteroids do not enhance the incidence and severity of KS in transplant recipients by direct cellular effects on KSHV reactivation.

Adrenal Cortex Hormones↗
PubMed2002

Oxidative modifications of kynostatin-272, a potent human immunodeficiency virus type 1 protease inhibitor: potential mechanism for altered activity in monocytes/macrophages.

Previous studies have indicated that human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) are less active at blocking viral replication in HIV-1 infected peripheral blood monocytes/macrophages (M/M) than in HIV-1-infected T cells. We explored the hypothesis that oxidative modification and/or metabolism of the PIs in M/M might account for this reduced potency. We first tested the susceptibility of several PIs (kynostatin-272 [KNI-272], saquinavir, indinavir, ritonavir, or JE-2147) to oxidation after exposure to hydrogen peroxide (H(2)O(2)): only KNI-272 was highly susceptible to oxidation. Treatment of KNI-272 with low millimolar concentrations of H(2)O(2) resulted in mono-oxidation of the sulfur in the S-methyl cysteine (methioalanine) moiety, as determined by reversed-phase high-performance liquid chromatography and mass spectrometry (RP-HPLC/MS). Higher concentrations of H(2)O(2) led to an additional oxidation of the sulfur in the thioproline moiety of KNI-272. None of the PIs were metabolized or oxidized when added to T cells and cultured for up to 12 days. However, when KNI-272 was added to M/M, the concentration of the original KNI-272 steadily decreased with a corresponding increase in the production of three KNI-272 metabolites as identified by RP-HPLC/MS. The structures of these metabolites were different from those produced by H(2)O(2) treatment. The two major products of M/M metabolism of KNI-272 were identified as isomeric forms of KNI-272 oxidized solely on the thioproline ring. Both metabolites had reduced capacities to inhibit HIV-1 protease activity when tested in a standard HIV-1 protease assay. These studies demonstrate that antiviral compounds can be susceptible to oxidative modification in M/M and that this can affect their antiviral potency.

Dose-Response Relationship, Drug↗