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Biomedical subjects

D Collins

Publications and source records attributed to D Collins.

At least 91 records · Page 5Linked to original sources
PubMed1994

A Canadian survey of current methotrexate prescribing practices in rheumatoid arthritis.

OBJECTIVE: To conduct a cross sectional survey of methotrexate (MTX) prescribing practices of Canadian rheumatologists in their treatment of rheumatoid arthritis (RA). METHODS: A 15-item questionnaire was mailed to 197 rheumatologists with a 79% response rate after 3 mailings. RESULTS: The usual starting dose was 7.5 mg/week (range = 2.5-15.0) and the usual maximum dose prescribed was 15 mg/week (range = 10-50); 81% routinely coadministered MTX and non-steroidal antiinflammatory drugs; 28% routinely used folic acid prophylaxis; 97% of respondents performed regular assessments of liver function. Only 17% requested a liver biopsy after a certain time and 23% after a certain cumulative dose. Sixty-two percent performed pre-MTX liver biopsy on patients with liver function abnormalities. Only 14% of respondents routinely performed pulmonary function tests. Ninety-one percent of respondents noted that 1-50% (mode = 10%) of patients refused to accept MTX therapy after it had been recommended, usually because of fear of side effects. CONCLUSION: Despite potential toxicity, the majority of respondents used MTX in the treatment of adult RA.

Arthritis, Rheumatoid↗
PubMed1994

Germ-line mutations in the von Hippel-Lindau tumor-suppressor gene are similar to somatic von Hippel-Lindau aberrations in sporadic renal cell carcinoma.

von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome predisposing to multifocal bilateral renal cell carcinomas (RCCs), pheochromocytomas, and pancreatic tumors, as well as angiomas and hemangioblastomas of the CNS. A candidate gene for VHL was recently identified, which led to the isolation of a partial cDNA clone with extended open reading frame, without significant homology to known genes or obvious functional motifs, except for an acidic pentamer repeat domain. To further characterize the functional domains of the VHL gene and assess its involvement in hereditary and nonhereditary tumors, we performed mutation analyses and studied its expression in normal and tumor tissue. We identified germline mutations in 39% of VHL disease families. Moreover, 33% of sporadic RCCs and all (6/6) sporadic RCC cell lines analyzed showed mutations within the VHL gene. Both germ-line and somatic mutations included deletions, insertions, splice-site mutations, and missense and nonsense mutations, all of which clustered at the 3' end of the corresponding partial VHL cDNA open reading frame, including an alternatively spliced exon 123 nt in length, suggesting functionally important domains encoded by the VHL gene in this region. Over 180 sporadic tumors of other types have shown no detectable base changes within the presumed coding sequence of the VHL gene to date. We conclude that the gene causing VHL has an important and specific role in the etiology of sporadic RCCs, acts as a recessive tumor-suppressor gene, and appears to encode important functional domains within the 3' end of the known open reading frame.

Adult↗
PubMed1993

Selectivity information on desogestrel.

Improvement in oral contraceptive formulations was originally achieved through dose reduction of the estrogen and progestogen components. Recently, further improvement was achieved by increasing the selectivity of contraceptive progestins. The ratio between the affinity for the progesterone receptor and the affinity for the androgen receptor is an indicator of progesterone (or androgen) selectivity of a progestin. This ratio (selectivity index) reflects the relative amount of androgenic or progestational effect at a given dose. Relative selectivity can be characterized with in vitro receptor-binding studies and animal pharmacologic experiments. In comparison with levonorgestrel, desogestrel displays markedly lower androgenicity and slightly increased relative progestational activity. In receptor-binding experiments and animal pharmacologic studies, 3-keto-desogestrel, the active metabolite of desogestrel, shows the highest selectivity index. The favorable effect of desogestrel-containing oral contraceptives on lipoprotein metabolism and preexisting androgen-dependent skin disorders and the absence of adverse effects on blood pressure and body weight are attributed to the increased progestin selectivity of desogestrel.

Animals↗
PubMed1993

Regional binding of 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) to muscarinic receptors in rat brain and comparative analysis of minimum energy conformations.

The binding of the muscarinic antagonist 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP), which has been suggested as an M3-selective antagonist in peripheral tissues, was examined through quantitative autoradiographic techniques in brain. The ability of 4-DAMP to displace [3H](R)-quinuclindinyl benzilate (QNB) binding to rat brain sections was compared with the known distribution of M1 and M2 muscarinic receptor subtypes as measured previously with pirenzepine and AF-DX 116 (Messer et al., 1989a). 4-DAMP displayed a high affinity for [3H](R)-QNB binding sites in rat brain sections. Analysis of 4-DAMP binding to various brain regions revealed heterogeneous binding profiles, suggesting an interaction with multiple receptor sites. Quantification of the autoradiograms indicated that 4-DAMP bound with the highest affinity to muscarinic receptors in the midline thalamus (IC50 values < 30 nM), and had a slightly lower affinity for hippocampal receptors (IC50 values between 30 and 46 nM). 4-DAMP also displayed a lower affinity for cortical receptors with IC50 values between 30 and 50 nM. The binding profile of the putative M3 muscarinic antagonist did not exhibit a marked selectivity for any single region of brain. The data suggest that whereas 4-DAMP may be selective for M3 receptors in peripheral tissues, it has limited selectivity in the CNS. Minimum energy conformations for 4-DAMP were calculated using molecular mechanics calculations. 4-DAMP displayed two global minimum energy conformations, differing in the relative position of the piperidine ring with respect to the aromatic rings. The minimum energy conformations of 4-DAMP were compared with conformations generated for pirenzepine (Messer et al., 1989a). The lowest energy conformation of 4-DAMP was superimposable on the lowest energy conformation of pirenzepine (RMS = 0.297 A). It is suggested that the conformations available to 4-DAMP permit binding to several muscarinic receptors in the CNS.

Animals↗
PubMed1993

Ethical dilemmas in continuing a zidovudine trial after early termination of similar trials.

Ethical dilemmas caused by external events and an interim subset analysis raised concerns about continuing a long-term VA clinical trial comparing early with later zidovudine therapy for symptomatic human immunodeficiency virus (HIV) infection. The first external event was the early termination of other, apparently similar, trials conducted by the AIDS Clinical Trials Group (ACTG) and the announced clear benefits for the zidovudine-treated patients. Interim analysis of the VA trial at this time did not show similar benefits. Subset analyses were performed to explore factors that might explain the different results. These suggested a difference in response to zidovudine in white and minority groups. The Data Monitoring Board and a special advisory panel reviewed these data and concluded that, since the VA results were neutral overall and the subset analyses based on small numbers, the trial should continue. By conference call, the study cochairmen and biostatistician discussed this decision with study personnel without revealing interim results, and study personnel passed the information on to patients at the participating centers. The second event was in March 1990, when the Food and Drug Administration (FDA) approved earlier use of zidovudine, which applied to patients still in the VA trial. Patients were asked to reaffirm their participation by signing a new informed consent that explained the findings reported by the ACTG, the FDA-approved revised recommendations, and the rationale for continuation of the VA trial. The consent form emphasized that continued masked therapy was optional and that unmasked treatment and follow-up would be provided to patients requesting it. Seventy-four percent of the participants chose to continue masked therapy. We conclude that when new external data are announced, informed participation in a long-term clinical trial may require a revised consent form and that it is ethical and practical to present this without disclosure of interim study results.

Acquired Immunodeficiency Syndrome↗
PubMed1993

The self-efficacy-performance link in maximum strength performance.

To examine whether manipulating self-efficacy affects strength performance on a bench press, and to see if these situation-specific changes would affect levels of physical self-efficacy, 24 undergraduates untrained in weightlifting were randomly assigned to three groups: 'light', who lifted less weight than they believed; 'heavy', who lifted more weight than they believed; and control, for whom there was no manipulation. Self-efficacy measures were taken before and after the manipulation. Physical self-efficacy was measured using the Physical Self-Efficacy Scale (PSE). 'Light' subjects lifted significantly greater increases in weight than the other subjects. 'Heavy' subjects significantly decreased self-efficacy following the manipulation. Initial self-efficacy was found to be a significant predictor of baseline maximum, while manipulated self-efficacy was significant for performance change. The PSE scores did not change pre- to post-study. The results suggest that self-efficacy is a situation-specific construct which can be manipulated, and which relates to both past performance experience and future performance.

Adult↗
PubMed1993

Systemic versus nonsystemic reperfusion of the transplanted liver.

Reperfusion of the orthotopically transplanted liver can result in severe hemodynamic instability. This instability can result in the postreperfusion syndrome (PRS), which includes decreases in mean arterial pressure (MAP), systemic vascular resistance (SVR), and heart rate, and increases in central venous pressure and pulmonary capillary wedge pressure. This syndrome appears to be mediated by the left ventricular mechanoreceptor reflex (LVMRR), which can be activated by changes in preload, afterload, or left ventricular contractility, and by the infusion of alkaloids or potassium into the right atrium. In an attempt to prevent activation of the LVMRR and PRS, we have inserted a cannula into the retrohepatic vena cava and have allowed the initial 500-600 cc of portal blood reperfusing hepatic allografts to be discarded. We compared this nonsystemic reperfusion (NSRP) of livers with systemic reperfusion (SRP), in which the initial portal blood reperfusing livers is allowed to enter the systemic circulation. In the NSRP group (n = 14) there was no decrease in MAP, heart rate, or SVR, and the serum potassium did not increase after reperfusion. In the SRP group (n = 14), six patients (42%) developed PRS and there were statistically significant decreases in MAP and SVR, and increases in pulmonary capillary wedge pressure and serum potassium, as compared with the NSRP group. In conclusion, NSRP results in less hemodynamic instability during reperfusion, and should be considered the preferred method for reperfusion of the transplanted liver.

Adult↗
PubMed1992

The effect of in vitro aging on human lung fibroblast beta-adrenergic receptor density, coupling and response.

Age-related changes in regulation of receptor response have been observed in several tissues and include regulation of beta-adrenergic receptor (beta-receptor) responses. The role of cellular aging in age-related changes in receptor response is not clear. We have examined the effect of aging in vitro on human fibroblast beta-receptor function. MRC-5 (embryonic lung) fibroblasts were aged by replication to produce cells of early, middle and late stages corresponding to the following cumulative population doublings: 15-20, 35-45 and greater than 50, respectively. Fibroblast membrane beta-receptor responses to isoproterenol (ISO, 0.1 mM) did not differ between the three stages. Adenylate cyclase responses to prostaglandin E1 (PGE1, 1 microM), guanosine triphosphate (GTP, 0.1 mM) and 5'-guanylimidodiphosphate (Gpp(NH)p, 0.1 mM) were also similar between the stages. Beta-receptor density (Bmax) was unaffected by in vitro aging. Beta-receptor agonist affinity, an indication of the capacity for beta-receptor coupling to the nucleotide binding protein (NS), was also unaffected by cell aging. These findings suggest that cellular aging in fibroblasts alone is not accompanied by changes in beta-receptor function.

Adenylyl Cyclases↗
PubMed1992

Edge displacement and deformation of glenoid components in response to eccentric loading. The effect of preparation of the glenoid bone.

The effect of different methods of preparation of glenoid bone on displacement and deformation of a glenoid component under eccentric loading was investigated in a series of scapulae of cadavera. Handburring of the osseous surface was associated with less displacement and deformation than simple removal of cartilage with a curet. Reaming resulted in the least displacement and deformation. Substantial posterior deficiency of the bone of the reamed glenoid was not associated with significant increases of displacement and deformation.

Biomechanical Phenomena↗
PubMed1991

An autopsy study of the peritoneal cavity from patients on continuous ambulatory peritoneal dialysis.

Sixteen autopsies were performed on patients aged 56 +/- 15 (SD) years who were on continuous ambulatory peritoneal dialysis (CAPD) for 834 +/- 766 (SD) days. Lactate-buffered dialysate and povidone-iodine antiseptic were used in all cases. Multiple peritoneal sections were taken to evaluate peritoneal membrane thickening, inflammation, neovascularization, fibrosis, and adhesions. Peritoneal thickening, inflammation, or adhesions were not related to sex, race, or etiology of renal failure. Time on dialysis was also not a direct determinant of peritoneal adhesions or neovascularization. Peritonitis episodes correlated with chronic peritoneal serosal changes. This study supports the hypothesis that peritoneal alterations in patients on CAPD are related to episodes of peritonitis.

Adult↗
PubMed1991

Cerebral activity prior to motion task performance: an electroencephalographic study.

Cerebral activity, as reflected by power in the alpha waveband (8-13 Hz), was examined prior to the performance of three tasks with different effort and accuracy requirements. The study aimed to further investigate changes in activity observed in an earlier study in which expert karate performers exhibited significant increases in alpha band power during preparation for a training task. In contrast to the earlier research, the high effort task produced a significant decrease in 'alpha' power prior to performance. 'Alpha' power prior to the high accuracy task showed significant differences mediated by the outcome. Successful performance was preceded by higher levels of 'alpha' power than unsuccessful attempts. The reported use of a cognitive strategy on the first task produced a significant difference in activity, lower alpha power being associated with the use of such a technique.

Attention↗
PubMed1991

Effects of a school-based alcohol education program with a media prevention component.

The effects of an alcohol education presentation with a media component of public service announcements were evaluated. The presentation was conducted over three (consecutive) days with 10th and 11th grade students in a rural area of South Carolina. The professionally produced announcements focused on drinking and driving. 52 subjects were assigned by classroom to either of two treatment groups or a control condition. Both treatment groups received the educational presentation but differed in that Group 2 was also exposed to the videotaped announcements. Effects of exposure were evaluated in separate measures of knowledge, attitudes, and alcohol involvement, using a pre-posttest design, with a 1-mo. follow-up. Analysis showed an effect of over-all program on knowledge at follow-up, but none on attitudes or alcohol involvement. These findings and their implications are discussed in the context of previous evaluations of alcohol education programs and media efforts.

Accidents, Traffic↗