Biomedical subjects

Michael Kane

Publications and source records attributed to Michael Kane.

3 recordsLinked to original sources

PubMed2002

A phase I trial of a potent P-glycoprotein inhibitor, Zosuquidar.3HCl trihydrochloride (LY335979), administered orally in combination with doxorubicin in patients with advanced malignancies.

PURPOSE: The purpose of this study was to investigate the safety and tolerability of Zosuquidar.3HCl, a potent inhibitor of P-glycoprotein (Pgp), when administered p.o. alone and in combination with doxorubicin and to determine whether Zosuquidar.3HCl affects doxorubicin pharmacokinetics and inhibits Pgp function in peripheral blood natural killer lymphocytes. EXPERIMENTAL DESIGN: Patients with advanced nonhematological malignancies were eligible for this Phase I trial. Zosuquidar.3HCl and doxorubicin were administered separately during the first cycle of therapy and then administered concurrently. Zosuquidar.3HCl was administered over 4 days, with doses escalated until the occurrence of dose-limiting toxicity. Subsequently, doxorubicin doses were increased from 45 to 75 mg/m(2). Zosuquidar.3HCl, doxorubicin, and doxorubicinol pharmacokinetics were analyzed, and dual fluorescence cytometry was used to determine the effects of Zosuquidar.3HCl on Pgp function in natural killer cells. RESULTS: A total of 38 patients were treated at nine dose levels. Neurotoxicity was dose-limiting for oral Zosuquidar.3HCl, characterized by cerebellar dysfunction, hallucinations, and palinopsia. The maximum-tolerated dose for oral Zosuquidar.3HCl administered every 12 h for 4 days is 300 mg/m(2). Zosuquidar.3HCl did not affect doxorubicin myelosuppression or pharmacokinetics, and Zosuquidar.3HCl pharmacokinetics were similar in the absence and presence of doxorubicin. Higher plasma concentrations of Zosuquidar.3HCl were associated with greater Pgp inhibition in natural killer cells. CONCLUSION: Zosuquidar.3HCl can be coadministered with doxorubicin using a 4-day oral dosing schedule, with little effect on doxorubicin toxicity or pharmacokinetics. Further refinement in Zosuquidar.3HCl dosing and scheduling should be explored to optimize Pgp inhibition while minimizing cerebellar toxicity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Using Error/Tolerance Analysis to Design an Empirical Practice Analysis.

Practice analyses, in which professional practitioners describe their work, provide essential content-related validity evidence for licensure and certification tests by providing an empirical base for the test plan. This paper examines the precision of the category weights generated by practice analyses employing activity inventories. The standard errors in estimates of category weights are compared to the tolerance for error in these weights. The tolerance for error specifies how large errors can be before they interfere with the intended use of the measurement procedure. As an example, data from a practice-analysis study is used to assign weights to nine categories in a test plan. Estimates of standard errors are derived from G studies with activity statements nested within categories and crossed with respondents and occasions. The tolerance for error is specified in terms of the level of precision typically found in test plans. The results are used to determine the minimum number of activities needed for each category to satisfy the tolerance requirement.

Journal Article↗

PubMedDate not supplied

Comparison of the moisturization efficacy of two vaginal moisturizers: Pectin versus polycarbophil technologies.

This study was designed to compare the vaginal deposition and moisturization of two vaginal moisturizers, Summer's Eve (SE), based on pectin, and Replens (Rp), based on polycarbophil, in a double-blind crossover study design. Fifty-one female patients were each randomly assigned to one of two treatment groups. After a one-week washout period, the products were used for two weeks. After another one-week washout period, product assignments were switched. Colposcopy examinations were performed at the beginning and at the end of each product use. Of the forty-seven patients completing the study, 41 (87%) were found to have no vaginal residue after SE vaginal moisturizer, while only 25 (53%) were found to have no vaginal residue after using Rp vaginal moisturizer. No difference in relief of vaginal dryness or in product acceptance was found between the two products. This study shows that the use of SE vaginal moisturizer, based on pectin, resulted in significantly less vaginal residue compared to Rp vaginal moisturizer, based on polycarbophil, and in comparable relief of vaginal dryness. These results strongly suggest that bioadhesion is not important in vaginal moisturizers.

Acrylic Resins↗