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Biomedical subjects

T Meade

Publications and source records attributed to T Meade.

18 recordsLinked to original sources
PubMed2002

WISDOM: history and early demise - was it inevitable?

In 1989, the UK Medical Research Council (MRC) agreed that, if feasible, a randomized controlled trial to assess the long-term risks and benefits of hormone replacement therapy (HRT) was a priority. Feasibility work began in 1990 and demonstrated that a large-scale multicenter trial was possible. An application for funding for a main trial was submitted to MRC in 1993 and, after extensive review, funding was released in late 1996. Set-up work for the trial - the Women's International Study of long Duration Oestrogen after Menopause (WISDOM) - began in 1997 with recruitment in 1999. In October 2002, following the early discontinuation of one arm of the US Women's Health Initiative HRT trial, the MRC decided to stop the WISDOM trial. This article, by the principal UK investigators of WISDOM, sets out the background and history of the trial.

Clinical Trials Data Monitoring Committees↗
PubMed1994

Use of personal medical records for research purposes.

The established practice of doctors using medical records for research purposes is threatened by the recent proposed guidelines from the Department of Health, the BMA, and the European Commission. The European Commission has proposed that explicit consent should be obtained from each patient before his or her medical records can be used; the proposals from the Department of Health and the BMA would require all research that needs access to personal medical records to be submitted to an ethics committee. We believe that these proposals would seriously impair an entire category of research and suggest therefore that another set of guidelines, proposed by a Royal College of Physicians' working group, should be used to modify the proposals. The guidelines of the working group encourage the use of medical records for research and ensure that such use can be made in a confidential manner without causing harm.

Biomedical Research↗
PubMed1993

Knee joint contact pressure decreases after chronic meniscectomy relative to the acutely meniscectomized joint: a mechanical study in the goat.

Several studies have shown that meniscectomy causes an immediate, acute increase in knee joint contact pressure and that changes in pressure distribution cause remodeling of bone and soft tissue. Presumably, this remodeling in turn affects contact pressures. This study tested the hypothesis that medial compartment contact pressure increases immediately after medial meniscectomy and then decreases with time. Supporting hypotheses regarding medial compartment contact area and lateral compartment pressures also were tested. Unilateral medial meniscectomy was performed on seven adult goats. Four or 8 months later, contact pressure and area were measured in vitro in the involved joints, as well as in the contralateral joints, before and after removal of the meniscus. The medial compartment pressures of the chronically meniscectomized joints were significantly less than those of the acutely meniscectomized paired joints but remained significantly greater than those of the intact joints. For the 4 and 8 month groups combined, the mean pressures of the acutely and chronically meniscectomized joints were greater than the pressures of the paired intact joints by 70 and 42%, respectively. The mean medial compartment contact areas of the acute and chronic joints were lower than those of the intact joints by 60 and 50%, respectively; mean lateral compartment pressures remained the same. This study indicates that joint remodeling reduces joint contact pressures. It also suggests that the effectiveness of a treatment to reduce pressure concentrations may be determined only by comparison, at the same postoperative time, of the pressure with that of the chronically meniscectomized joint, since pressures decreased with time without treatment.

Animals↗
PubMed1992

Emergency hospital admissions and readmissions of patients aged over 75 years and the effects of a community-based discharge scheme.

This paper reports the results of a retrospective review which analysed emergency admissions and readmissions of elderly patients to a district general hospital. All patients received standard after-care allocated by the community health and social services departments following referral by hospital staff. In addition, half of the cohort was randomly allocated to receive care attendant support for a maximum of 12 hours a week for two weeks following the first and any subsequent discharge from hospital. The effect of this additional community support on emergency readmissions was also reviewed. The findings show that the patients randomly allocated to receive the modest domiciliary after-care service were less likely to have another emergency readmission or multiple readmissions. The results suggest that patients over 75 years-of-age, living alone, or having two or more emergency admissions within six months, should have a domiciliary assessment and follow-up after hospital discharge.

Aftercare↗
PubMed1991

Restriction fragment length polymorphisms of the apolipoprotein A-I, C-III, A-IV gene locus. Relationships with lipids, apolipoproteins, and premature coronary artery disease.

Data from various laboratories have indicated associations of various alleles determined by RFLPs within or adjacent to several apolipoprotein genes with abnormalities in plasma lipids and/or premature coronary artery disease (CAD). In order to assess such relationships we have examined allele frequencies of 8 different RFLPs within or adjacent to the apo A-I, C-III and A-IV gene complex on the long arm of chromosome 11 (MspI, 5' to the apo A-I gene; MspI, within the apo A-I gene; PstI, 3' to the apo A-I gene; SstI, 3' to the apo C-III gene; PvuII, within the apo C-III gene; PvuII, 5' to the apo C-III gene; XbaI, within the apo A-IV gene; and XbaI, 3' to the apo A-IV gene) in 202 patients with CAD (50% narrowing of one or more coronary arteries) prior to age 60 and 145 normal controls. None of the allele frequencies of these RFLPs were significantly different in cases as compared to controls. With regard to associations with plasma lipids and apolipoprotein levels, the rare allele determined by the absence of the PstI site was associated with elevated triglyceride levels (P less than 0.05) in cases, but not in controls. In contrast, the rate MspI allele 5' to the apo A-I gene was associated with elevated triglyceride levels (P less than 0.05) in controls but not in cases. In both cases and controls, subjects with the uncommon SstI allele had triglyceride levels that were 9 and 38% higher than in those without this allele. These differences were significant (P less than 0.05) only in controls. Our data indicate that the rare allele determined by the SstI site within this gene complex deserves further study in order to understand its association with elevated triglycerides in Caucasian populations. However, at the present time all these DNA markers lack sufficient specificity to be clinically useful for CAD risk assessment.

Age Factors↗
PubMed1990

DNA polymorphisms of the apolipoprotein B gene in patients with premature coronary artery disease.

Elevated plasma levels of low density cholesterol and their major apolipoprotein (apo B) are associated with an increased risk of coronary artery disease (CAD). We have examined allele frequencies of restriction fragment length polymorphisms (RFLP) of the apo B gene in 111 male Caucasians with premature CAD (mean age 49 +/- 7 years) and in 122 elderly Caucasian males (mean age, 73 +/- 5 years), free of clinical cardiovascular disease. The rare allele (R1) of the EcoR1 RFLP in exon 29, resulting in an amino acid change (Glu----Lys4154) was seen more frequently in CAD than in controls (0.270 vs 0.207, P less than 0.05). The R1 RFLP and the MspI insertion polymorphisms (MI) within the 3' hypervariable region (HVR) were observed together in 87% and are likely in linkage disequilibrium. The MI RFLP were slightly more frequent in CAD than control (0.239 vs. 0.211, P = 0.08). A second MspI RFLP in exon 26 results in an amino acid change (Arg----Glu3611); the rare allele M2 was seen more frequently in patients than in controls (0.150 vs. 0.057, P less than 0.005). No significant differences in allele frequencies were observed for the Xba1 RFLP in exon 26 (0.500 vs. 0.529, P = ns) or for the PvuII RFLP near the 5' end (P2) (0.105 vs. 0.088, P = ns). No statistically significant differences in lipid, lipoprotein cholesterol or apolipoproteins A-I and B were observed in patients or in controls. Two of the RFLPs examined (R1 and M2) result in changes in amino acid sequence and their allele frequencies are increased in CAD cases when compared with controls. Genetic variability within the apo B gene may thus contribute to cardiovascular risk. The physiological effects of individual mutations within apo B remain to be determined. It is unlikely, however that the single site polymorphisms examined in this study, will impart further information about CAD risk than conventional lipid parameters.

Adult↗
PubMed1980

Design problems in research on rehabilitation after brain damage.

This paper is based on a report to the Committee on Coordination of Research into Rehabilitation after Closed Head Injury and Stroke, sponsored by the Medical Research Council (MRC). A review is presented of some of the most important factors to be considered in rehabilitation studies, drawing attention to some of the more common pitfalls.

Brain Injuries↗
PubMed1980

Effect of dietary ascorbic acid on the susceptibility of steelhead trout (Salmo gairdneri) to nitrite toxicity.

Four diets, each containing different levels of ascorbic acid were fed to duplicate groups of steelhead trout (Salmo gairdneri) in two four-week periods. Tolerance to nitrites increased when the concentration of ascorbic acid was high. Flow-through bioassays in fingerlings showed that when the temperature increased the percent of methemoglobin in their blood also increased. The tolerance to nitrite toxicity was less in large fish than in those smaller fed the same concentration of ascorbic acid. Possibly ascorbic acid acts in the reduction of methemoglobin to hemoglobin, and also it has a protective effect against stress in the fish. A "safe" level of 200 mg/kg of ascorbic acid in practical diets was reached.

Animal Feed↗
PubMedDate not supplied

A common genetic polymorphism associated with lower coagulation factor VII levels in healthy individuals.

We have identified a genetic polymorphism of factor VII that is strongly associated with plasma factor VII coagulant activity (factor VIIc) in healthy individuals from the United Kingdom. This polymorphism was detected after Msp I digestion of polymerase chain reaction-amplified genomic DNA. In a sample of 284 men, the frequency of the M2 allele (loss of cutting site) is 0.1, and individuals with the M1M2 genotype have factor VIIc levels 22% below the sample mean (p less than 0.0001). Msp I genotype was found to be the strongest predictor of factor VIIc, accounting for 20.2% of the variance, with cholesterol accounting for an additional 3.5%. The base change that gives rise to the Msp I polymorphism is a G-to-A substitution in the codon for amino acid 353, leading to replacement of arginine (Arg) with glutamine (Gln) in the protein product of the M2 allele (designated Gln 353). Three individuals homozygous for the M2 allele have both low factor VIIc and low factor VII protein concentrations. The conformation of the Gln 353 molecule may be different from that of the Arg 353 protein, affecting its intracellular processing, secretion, turnover in plasma, or activity. In view of its association with lower factor VIIc levels, possession of the M2 allele may confer protection against thrombosis and myocardial infarction.

Aged↗