Peer-assisted learning in clinical examination.
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Biomedical subjects
Publications and source records attributed to David McAllister.
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Infection with the protozoan parasite Neospora caninum is emerging as a major cause of reproductive loss in cattle worldwide. Recent advances in research with the ultimate goal of devising effective and sustainable control measures were discussed at Neospora 2001. Neospora 2001 was held, 13-15 September 2001, at the Moredun Research Institute, Edinburgh, UK. The international meeting covered many aspects of bovine neosporosis including diagnosis, epidemiology and immunology.
2-Methoxyestradiol (2-MEO), a metabolite of estrogen, is an attractive lead compound for the development of novel antitumor and anti-inflammatory agents, because it embodies antiproliferative and antiangiogenic activities in one molecule. However, the affinity of 2-MEO for the estrogen receptor would lead to undesirable side effects. As a prelude to the design of 2-MEO-like compounds with an optimal activity profile, we assayed 2-MEO and a series of analogs for their ability to cause G(1) cell-cycle arrest (by measuring inhibition of DNA synthesis in human cultured airway smooth muscle) and to inhibit binding of [(3)H]estradiol at the estrogen receptor (ER; from rat uterine smooth muscle). One compound, a diacetoxy enediol derivative, was identified with reasonable potency for DNA synthesis (pIC(50) = 5.97) but showed negligible affinity for the ER (pIC(50) < 5). Three-dimensional quantitative structure-activity relationships were developed for these activities using comparative molecular field analysis (CoMFA) techniques. Comparison of optimized CoMFA models revealed distinct structural requirements for DNA synthesis inhibition and ER binding. For example, DNA synthesis inhibition is enhanced by electropositive substitutions in the 2-position below the plane of the steroid A-ring, whereas ER binding is favored by electronegative substitution in this position. Similarly, DNA synthesis inhibition correlates negatively with increased steric bulk in regions clustered around the A and B rings; changes in steric bulk in these regions has little correlation with ER binding. These observations will guide the design of new analogs with improved potency for desired characteristics (e.g., DNA synthesis inhibition) with minimal unwanted activities (e.g., ER binding).
BACKGROUND: Posterior laxity occurring after posterior cruciate ligament reconstruction with a tibial tunnel could be related to thinning and permanent elongation of the graft as it is cyclically loaded in vivo. HYPOTHESIS: The orientation and position of the bone block within the tibial tunnel will have a significant effect on thinning and elongation of the graft after cyclic loading. STUDY DESIGN: Controlled laboratory study. METHODS: In test series 1 (27 fresh-frozen graft pairs), all bone blocks were positioned flush with the posterior opening of the tibial tunnel; 1 graft was oriented with the bone block facing posteriorly, whereas its pair was tested with the bone block facing anteriorly. In test series 2 (20 graft pairs), all grafts were oriented with the bone block facing posteriorly; 1 graft had the bone block positioned flush with the posterior tunnel opening, whereas its pair was tested with the bone block recessed 1 cm from the posterior opening. RESULTS: In series 1, 3 of 27 grafts with posterior bone block orientations failed at the tunnel edge before 2000 cycles of testing could be completed; all specimens with anterior bone block placements survived the testing intact. In series 2, 3 of 20 grafts with recessed bone blocks failed at the tunnel edge, whereas all those with flush bone blocks survived. CONCLUSIONS: The best position for the bone block of a bone-patellar tendon-bone graft was flush with the posterior tunnel opening with the bone block facing anteriorly in the tibial tunnel.