Educational objectives and requirements of an undergraduate clerkship in general practice. The outcome of a consensus procedure

OBJECTIVES: The main aim of this study was to reach consensus between students, faculty and general practice teachers on the educational objectives and requirements of the clerkship in general practice. METHOD: The consensus procedure consisted of four steps and all active general practice teachers (n = 116) were asked to participate in the study. RESULTS: We identified 189 educational objectives: 127 complaints (problems, symptoms, syndromes), 29 clinical skills and 37 objectives concerning the theoretical dimensions of general practice. Educational requirements crystallized to 16 essential preconditions of a teaching practice and 35 didactic activities to be performed by the general practice teachers. CONCLUSIONS: These consensus results will be used to structure the medical curriculum and as guidelines for the educational process during the clerkship.      

Chemopreventive effects of 2-(allylthio)pyrazine on hepatic lesion, mutagenesis and tumorigenesis induced by vinyl carbamate or vinyl carbamate epoxide

2-(Allylthio)pyrazine (2-AP), synthesized for its possible use as a hepatoprotective agent, has been found to selectively inhibit rat hepatic cytochrome P450 2E1 (Kim et al., Biochem. Pharmacol., 53, 261- 269, 1997), while it enhances the activities of phase II detoxification enzymes such as glutathione S-transferase and epoxide hydrolase. As part of a program in evaluating the chemopreventive potential of 2-AP, we have determined its effects on hepatotoxicity, mutagenicity and tumorigenicity of vinyl carbamate (VC), a prototypic hepatocarcinogen preferentially activated by P450 2E1 to the ultimate carcinogenic metabolite vinyl carbamate epoxide (VCO), which undergoes detoxification by glutathione conjugation and oxirane hydrolysis. Administration of 2-AP (100 mg/kg body wt) to male Sprague-Dawley rats by gavage, 2 days, 1 day and 4 h prior to VC or VCO, markedly ameliorated the hepatotoxicity of these compounds as determined by decreased serum aspartate aminotransferase and alanine aminotransferase activities. Furthermore, 2-AP pre-treatment significantly suppressed the VC-induced hepatocarcinogenesis in infant male B6C3F1 mice. In a separate experiment, the multiplicities of skin tumors formed in female ICR mice treated with 5.8 micromol of VC or VCO were inhibited 58 and 70%, respectively, by pre-treatment with 2-AP by oral administration. The mutational spectrum of ras-oncogene in papillomas was not altered by 2-AP pre-treatment. 2-AP also inhibited the mutagenicity of VC in the Salmonella-microsome assay. Taken together, these findings suggest that 2-AP is a potential chemopreventive agent.      

Glomus jugulare tumors. Long-term control by radiation therapy.

The records of 49 patients with glomus jugulare tumor seen at the University of Virginia from 1932 to 1985 were retrospectively reviewed with the objective of assessing long-term results of treatment. Follow-up ranged from 5 to 31 years, with a minimum of 10 years in 36 patients (73%). According to McCabe's classification, 17 patients (35%) were Group I, 11 patients (22%) were Group II, and 21 patients (43%) were Group III. Analysis by therapeutic technique revealed that 20 patients received surgery alone (41%), 15 patients received radiation therapy alone (31%), and 14 patients received combined therapy (28%). Only 7 patients (14%) have had clinical or radiologic evidence of disease progression. Three of these patients were treated by surgery alone and three by a combination of surgery and radiation, but the dose was less than 4000 cGy. Only one patient treated by radiation therapy alone or with surgery and radiation to a dose in excess of 4000 cGy demonstrated disease progression. Salvage radiation therapy was given to three of the seven patients when progressive disease was detected. Radiation therapy is an effective treatment for glomus jugulare tumor with minimal late progression of disease in adequately treated patients and no significant long-term complications.     

Effects of the tumor inhibitor, vernolepin, and of its thioether adduct, on the activity of catechol O-methyltransferase in vitro.

The activity of cat erythrocyte lysate catechol O-methyltransferase (COMT) in vitro is shown to be amenable to control by a variety of reagents including an SH reactive tumor inhibitor (vernolepin), its non-SH reactive derivative (the bis-n-propanethiol adduct of vernolepin), n-propanethiol itself, and the organic solvent, methanol. The ability of the adduct to modify COMT activity extends to all other sources examined (partially purified rat liver COMT and 78,000 g supernatant from rat liver, kidney, spleen and brain). Alterations in kinetic parameters (apparent K_m and Vmax) were observed when the adduct of vernolepin enhanced cat erythrocyte COMT activity.