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Biomedical subjects

Michael Gould

Publications and source records attributed to Michael Gould.

5 recordsLinked to original sources
PubMed2006

Practice Audit in Gastroenterology (PAGE) program: a novel approach to continuing professional development.

BACKGROUND: Practice audit is an important component of continuing professional development that may more readily be undertaken if it were less complex. This qualitative study assessed the use of personal digital assistants to facilitate data collection and review. METHODS: Personal digital assistants programmed with standard questionnaires related to upper gastrointestinal endoscopies (Practice Audit in Gastroenterology-Endoscopy ['PAGE-Endo']) and colonoscopies (PAGE-Colonoscopy ['PAGE-Colo']) were provided to Canadian gastroenterologists, surgeons and internists. Over a three-week audit period, participants recorded indications, and the expected (E) and reported (R) findings for each procedure. Thereafter, participants recorded compliance with reporting, the ease of use and value of the PAGE program, and their willingness to perform another audit. RESULTS: Over 15 to 18 months, 173 participants completed PAGE-Endo (6168 procedures) and 111 completed PAGE-Colo (4776 procedures). Most respondents noted that PAGE was easy to use (99%), beneficial (88% to 95%), and that they were willing undertake another audit (92% to 95%). In PAGE-Endo, alarm features were prevalent (55%), but major reported findings were less common than expected: esophagitis (E 29.9%, R 14.8%), esophageal stricture (E 8.3%, R 3.6%), gastric ulcer (E 17.0%, R 4.7%), gastric cancer (E 4.3%, R 1.0%) and duodenal ulcer (E 11.5%, R 5.7%). In PAGE-Colo, more colonoscopies were performed for symptom investigation (55%) than for screening (25%) or surveillance (20%). There were marked interprovincial variations with respect to sedation, biopsies and technical aspects of colonoscopy. CONCLUSION: Secure, real-time data entry with review of aggregate and individual data in the PAGE program provided an acceptable, straightforward methodology for accredited practice audit activities. PAGE has considerable potential for continuing professional development in gastroenterology and other specialties.

Canada↗
PubMed2003

Anti-leukemia effect of perillyl alcohol in Bcr/Abl-transformed cells indirectly inhibits signaling through Mek in a Ras- and Raf-independent fashion.

PURPOSE: Perillyl alcohol (POH) displays preventive and therapeutic activity against a wide variety of tumor models, and it has been suggested that this might be associated with the ability of POH to interfere with Ras prenylation. POH also selectively induces G(1) arrest and apoptosis in Bcr/Abl-transformed hematopoietic cells. Because signaling through Ras is necessary for Bcr/Abl transformation, we examined whether POH induces its anti-leukemia effect by inhibiting Ras signaling. EXPERIMENTAL DESIGN: The ability of POH to inhibit posttranslational farnesylation and signaling from Ras as well as signaling through the Raf-Mek-Erk cascade was examined in Bcr/Abl-transformed and mock-transformed cells and related to the anti-leukemia effect of POH. RESULTS: POH does not affect Ras prenylation or Ras activity, but it blocks signaling downstream of Ras by reversing the state of activation of the Erk kinase, Mek. POH affects Mek activity only when it is added to intact cells. Treatment of either cell lysates or of purified Mek with POH has no effect on Mek activity. Inhibition of the Mek-Erk pathway seems to be related to the POH anti-leukemia effect for the following reasons: (a) the concentration of POH needed to block the Erk pathway, as well the kinetics with which POH inhibits this signaling cascade, both correlate with the anti-leukemia effect of POH; (b) both U0126 (a specific Mek inhibitor) and POH induce similar anti-leukemia effects; and (c) mock-transformed hematopoietic cells are simultaneously resistant to POH anti-leukemia effects and inhibition of the Mek-Erk pathway. CONCLUSION: Blocking Mek is sufficient to induce growth arrest and apoptosis in Bcr/Abl-transformed cells; therefore, POH represents a novel small molecule inhibitor of Mek that might be effective for treating Bcr/Abl leukemias.

Antineoplastic Agents↗
PubMed2003

Phase I trial of perillyl alcohol administered four times daily continuously.

PURPOSE: Previous experience with perillyl alcohol (POH) was with a formulation of 500-mg capsules each containing 250 mg POH and soybean oil. This formulation resulted in the ingestion of large amounts of soybean oil (>10 g/day). Dose-limiting toxicities (DLT) were primarily gastrointestinal. Prior studies also showed no further increase in POH metabolite concentrations with doses of >1600 mg/m2. Therefore, a new formulation of POH was developed (700 mg containing 675 mg POH) in an effort to improve dose and metabolite concentrations delivered and toxicity encountered with chronic dosing. EXPERIMENTAL DESIGN: Eligible patients had refractory solid malignancies. Dose escalation occurred in cohorts of three at the dose levels/dose of 1350 mg, 2025 mg, 2700 mg, 3375 mg and 4050 mg, administered orally four times a day in a 28-day cycle. RESULTS: A group of 19 patients were enrolled. One DLT occurred at dose level 5. This cohort was expanded to six patients, and no further DLT occurred. The maximum tolerated dose was not reached. The predominant toxicity was gastrointestinal. Nausea and vomiting occurred in 63% of patients (12/19, grade 1 in 10). The same proportion of patients (12/19) experienced heartburn and indigestion, primarily grade 1. Although the side effects were mild in nature, three patients withdrew from treatment, citing intolerable gastrointestinal toxicity. The AUCs of POH metabolites did not appear to increase from level 1 to level 2 or change significantly from day 1 to day 29. Inter- and intrapatient variability in metabolite levels was observed. CONCLUSIONS: This reformulation of POH appears to be an improvement upon the prior formulation, by reducing the number of capsules ingested and the degree of gastrointestinal toxicity per dose. It does not appear to offer any metabolite pharmacokinetic advantage. A dose of 2050 mg administered four times daily was easily tolerated. Higher doses can be administered but with increasing gastrointestinal toxicity that limits compliance.

Adult↗