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Biomedical subjects

M J Prince

Publications and source records attributed to M J Prince.

At least 37 records · Page 2Linked to original sources

The treatment of hypertension in older people and its effect on cognitive function.

The benefits of antihypertensive drug therapy for older people have been clearly established. Meta-analysis suggests a 12% reduction in all-cause mortality, a 20% reduction in coronary heart disease and a 36% reduction in stroke. The absolute benefits of treatment are great due to the high incidence of vascular disease among older people. Clinicians may nevertheless have been deterred from initiating treatment because of concerns regarding adverse effects on cognition, mood, functional ability and quality of life. Recent evidence from randomised controlled trials suggests that these concerns are groundless. In the light of this evidence it is therefore disturbing that up to 50% of all older people with hypertension may remain untreated; and in over 50% of those who are treated, blood pressure may be inadequately controlled.

Activities of Daily Living↗

Impairment, disability and handicap as risk factors for depression in old age. The Gospel Oak Project V.

BACKGROUND: An association between disablement and late-life depression is often reported in cross-sectional studies. However, many lack effect sizes, and do not control for confounding. Therefore, it is difficult both to quantify the overall impact of poor health on depression and to understand which aspects are most salient. METHODS: A catchment area survey of all over 65-year-old residents of an electoral district in London, UK, using a population register derived from a door-to-door census was undertaken. Depression was measured using SHORT-CARE, and the consequences of disease classified according to the WHO International Classification of Impairments, Disabilities and Handicaps. RESULTS: Six hundred and fifty-four subjects were interviewed out of an older population of 889. The prevalence of SHORT-CARE pervasive depression was 17%. Impairment, disability and, particularly, handicap were strongly associated with depression. The adjusted odds ratio for depression in the most handicapped quartile compared with the least was 24.2 (8.8-66.6). The population attributable fraction (PAF) for depression attributable to handicap was 0.78. The PAFs for recent life events and female gender were much lower. Handicap explained most of the depression associated with individual impairments and disabilities. Adjusting for handicap abolished or weakened the associations between depression and social support, income, older age, female gender and living alone. CONCLUSIONS: Even given some uncertainty in distinguishing handicap and depression as constructs, and the impossibility of deciding direction of causality, it seems likely that handicap is of central significance to late-life depression. Handicap may be more amenable to intervention than either impairment or disability.

Activities of Daily Living↗

Social support deficits, loneliness and life events as risk factors for depression in old age. The Gospel Oak Project VI.

BACKGROUND: A companion paper reported a very strong cross-sectional association between handicap and late-life depression. Adjusting for handicap weakened associations between sociodemographic variables and depression. It was unclear whether handicap was a confounder, or a useful summary variable, mediating the effect of a range of sociodemographic disadvantages. This paper focuses on the cross-sectional relationship between depression and demographic variables, social support, and life events. METHOD: A community survey of all residents over the age of 65 years of an electoral district in London, UK. RESULTS: There was a moderate association between SHORT-CARE pervasive depression and the number of life events experienced over the previous year. Personal illness, bereavement and theft were the most salient events. There was a stronger, graded, relationship between the number of social support deficits (SSDs) and depression. Number of SSDs also related to age, handicap, loneliness and use of homecare services. Loneliness was itself strongly associated with depression; odds ratio 12.4 (7.6-20.0). CONCLUSIONS: Problems of collinearity, and the cross-sectional design of the study limited interpretation of the exact nature of the relationship between social support, loneliness, handicap and depression. However, the clustering of these four factors can be used to define a large part of the elderly population with a poor quality of life. An important avenue for future research will be the development and implementation of population intervention strategies designed to address some or all of these problems among older people in general.

Aged↗

Do n-3 fatty acids improve glucose tolerance and lipemia in diabetics?

A protective effect of habitual fish consumption on the development of impaired glucose tolerance and diabetes is once again suggested in a recent trial. In nondiabetic individuals with essential hypertension, a group known to be insulin resistant, fish oil was not associated with a negative impact on glycemic control, insulin secretion or peripheral insulin sensitivity, even in a subgroup who had impaired glucose tolerance. Furthermore, more recent, long term, placebo-controlled trials in type II patients have failed to demonstrate a significant impact of fish oil supplementation on glycemic control. Additional information is available regarding qualitative changes in VLDL- and LDL-lipoproteins in type II diabetes patients in response to dietary fish oil supplementation. The impact of fish oil on LDL oxidation is the focus of two recent trials. Vitamin E supplementation may mitigate much of the enhanced oxidation of LDL that is potentially seen with dietary fish oil supplementation.

Animals↗

The SOCRATES curriculum: an innovative integration of technology and theory in medical education.

This article describes the pilot study of an innovative medical school curriculum module that utilizes a modified problem-based learning (PBL) approach to teach medical students about management of diabetes mellitus. The PBL-based curriculum incorporated computer simulations and analysis of videotaped patient encounters in addition to independent study and group discussion. At the conclusion of the study, student knowledge and clinical decision-making skills were evaluated via questionnaires and examinations. Twenty-three students completed the workshop and all evaluation assessments. Students performed well on the case-study examinations (mean score of 3.39 out of 4) but not on the short answer essay examination, which assessed basic knowledge. Students rated the quality and appeal of the activities using Likert-type scales. In general, students perceived the activities as very worthwhile, with reasonable complexity and adequate time devoted to each activity. Students were very positive about the workshop and preceptor; 15 of the 16 items used to rate workshop appeal yielded mean scores greater than 4 (on a scale of 1 to 5, with 5 being the highest). The results of the pilot study suggest future enhancements that would further improve the outcomes of the training.

Adult↗

Is the cognitive function of older patients affected by antihypertensive treatment? Results from 54 months of the Medical Research Council's trial of hypertension in older adults.

OBJECTIVE: To establish whether initiation of treatment with diuretic or beta blocker is associated over 54 months with change in cognitive function. DESIGN: A cognitive substudy, nested within a randomised, placebo controlled, single blind trial. SETTING: 226 general practices from the Medical Research Council's general practice research framework. SUBJECTS: A subset of 2584 subjects sequentially recruited from among the 4396 participants aged 65-74 in the trial of treatment of hypertension in older adults. The 4396 subjects were randomised to receive diuretic, beta blocker, or placebo. Subjects had mean systolic pressures of 160-209 mm Hg and mean diastolic pressures <115 mm Hg during an eight week run in. OUTCOME MEASURES: The rate of change in paired associate learning test (PALT) and trail making test part A (TMT) scores (administered at entry and at 1, 9, 21, and 54 months) over time. RESULTS: There was no difference in the mean learning test coefficients (rate of change of score over time) between the three treatments: diuretic -0.31 (95% confidence interval -0.23 to -0.39), beta blocker -0.33 (-0.25 to -0.41), placebo -0.30, (-0.24 to -0.36). There was also no difference in the mean trail making coefficients (rate of change in time taken to complete over time) between the three groups: diuretic -2.73 (95% confidence interval -3.57 to -1.88), beta blocker -2.08 (-3.29 to -0.87), placebo -3.01, (-3.69 to -2.32). A less conservative protocol analysis confirmed this negative finding. CONCLUSION: Treating moderate hypertension in older people is unlikely to influence, for better or for worse, subsequent cognitive function.

Adrenergic beta-Antagonists↗

Predicting the onset of Alzheimer's disease using Bayes' theorem.

Bayes' theorem describes the effect of new information (e.g., a test result) on the probability of an outcome (e.g., a disease). Likelihood ratios for separate tests can be combined to assess the joint effect of their results on disease probability. This approach has been used to develop a test package for Alzheimer's disease that consists of some simple cognitive tests (Paired Associate Learning Test, Trailmaking Test, and Raven's Progressive Matrices) combined with age and family history of dementia. A total of 1,454 subjects who had been recruited into the Medical Research Council Elderly Hypertension Trial between 1983 and 1985 completed cognitive tests at entry to the trial (when they were without signs of dementia) and 1 month later. Their dementia status was ascertained in 1990-1991. The test package identified 52% of Alzheimer's disease cases with a 9% false-positive rate or 90% of Alzheimer's disease cases with a 29% false-positive rate. The author proposes the use of a similar test package in conjunction with a test for apolipoprotein E e4 status, which is a powerful risk factor for late-onset Alzheimer's disease, as a likelihood ratio approach to the prospective identification of Alzheimer's disease cases. This approach could be followed by ethically sound trials of new therapeutic agents for subjects who have a high probability of developing Alzheimer's disease.

Aged↗

The hypotriglyceridemic effect of fish oil in adult-onset diabetes without adverse glucose control.

Diabetic control as judged by five criteria did not deteriorate after 6 months of fish oil compared to 6 months of olive oil supplementation in 16 patients with NIDDM who were eating a low fat, high complex carbohydrate diet. Plasma total and VLDL triglyceride and cholesterol decreased significantly after fish oil supplementation; plasma total and HDL cholesterol concentrations did not change. The LDL cholesterol level was significantly increased with fish oil supplementation, suggesting that patients with NIDDM who are given a fish oil supplement to decrease the plasma total and VLDL triglyceride levels may also need further dietary and/or pharmaceutical therapy to maintain an LDL cholesterol level compatible with a low risk of coronary disease. The study emphasizes the safe use of fish oil over a 6-month period in diabetic patients.

Aged↗

Environmental scanning for Social Services.

This article describes the development of a process of systematic regional environmental scanning as part of strategic planning in the Ministry of Social Services (MSS) in British Columbia, over the 1987-1990 period. Social Services, a large regionalized social service organization, adopted a formal strategic planning process in early 1988. Ministry services are delivered in ten regions with widely varying characteristics. To ensure that this diversity is reflected in the planning process, it is essential that regional environmental information receive consideration. A simple format was developed and regional directors asked to consult with their staff and to scan their regions for issues that may impact the ministry over the medium term. The information obtained was presented by regional directors at a Senior Management Committee meeting and included in the ministry's annual Business Plan, a document which informs staff, contractors, stakeholders, and the community at large of the ministry's values, objectives, and operational goals. The inclusion of regional analyses adds useful information to the Plan. A second output of the planning process is the ministry budget. The systematic regional scans were found to be extremely useful to regional staff, other directors, and to the ministry executives while setting priorities.

British Columbia↗

Autophosphorylation of cultured skin fibroblast insulin receptors from patients with severe insulin resistance and acanthosis nigricans.

The severe insulin resistance with acanthosis nigricans seen in young women without insulin-receptor autoantibodies is characterized by hyperinsulinemia and decreased in vivo responsiveness to insulin. We evaluated the potential cellular defects in insulin-receptor binding and autophosphorylation in 12 subjects with this syndrome. When evaluated as a group, insulin binding to freshly isolated monocytes was 55% that of controls. Specific binding of insulin to skin fibroblasts in monolayer culture was 49% that of controls. Maximal insulin-stimulated receptor autophosphorylation was only 27% that of controls. Individual data demonstrated that the diminished autophosphorylation activity was out of proportion to the diminished fibroblast insulin binding in cell lines from most subjects and was less than 50% of the predicted activity in 6 of the 12 studied cell lines. These data are consistent with genetically determined defects leading to diminished numbers of cell surface insulin receptors with intact tyrosine kinase autophosphorylation in many of our cell lines. However, in at least half, there appeared to be an additional defect beyond insulin binding, resulting in a disproportionate decrease in insulin-sensitive phosphorylation of the insulin-receptor beta-subunit.

Acanthosis Nigricans↗

Bed-rest-induced insulin resistance occurs primarily in muscle.

Treatment of trauma victims and patients with severe illness may contribute to their metabolic derangements by severely restricting physical activity. We sought to quantitate the impact of absolute bed rest alone on insulin regulation of glucose metabolism in six healthy subjects. Six to seven days of strict bed rest resulted in moderate deterioration in oral glucose tolerance and increased both fasting plasma insulin concentration and the insulin response to an oral glucose challenge by more than 40%. Euglycemic insulin clamp studies demonstrated the development of resistance to insulin's stimulation of whole-body glucose utilization. This change was characterized by a rightward shift of the insulin dose-response curve (insulin concentration at which 50% of maximal stimulation occurred was 45 +/- 3 (SE) microU/mL in the base line period and 78 +/- 8 microU/mL after seven days of bed rest, P less than .01) with little alteration in the maximal response in the rate of glucose uptake (baseline 15.4 +/- 1.4 mg/kg.min and bed rest 14.0 +/- 1.3 mg/kg.min). In contrast to the shift of sensitivity of whole-body glucose utilization to insulin, suppression of hepatic glucose output by insulin was unchanged by seven days of bed rest. Insulin binding to circulating mononuclear cells was not changed by bed rest. These studies demonstrate that the limited physical activity dictated by bed rest for as little as seven days is associated with substantial resistance to insulin's effects on glucose metabolism. Further, the data suggest that these effects occur primarily in skeletal muscle with little change in insulin action on the liver.

Adult↗

Insulin responsiveness of protein metabolism in vivo following bedrest in humans.

To test the influence of bedrest on insulin regulation of leucine metabolism, six normal young men were subjected to a five-step hyperinsulinemic euglycemic clamp before and after 7 days of strict bedrest. A primed-constant infusion of [1-13C]leucine at 0.12 +/- 0.02 mumol.kg-1.min-1 was used. Before bedrest, the basal rate of appearance (Ra) of intracellular leucine and leucine oxidation were 2.79 +/- 0.17 and 0.613 +/- 0.070 mumol.kg-1.min-1, respectively. Insulin caused a dose-dependent reduction of the intracellular leucine Ra and leucine oxidation to a minimum of 1.64 +/- 0.08 and 0.322 +/- 0.039 mumol.kg-1.min-1, respectively, in nonbedrested subjects (P less than 0.001). Insulin also caused a dose-dependent reduction of plasma leucine concentration from 95 +/- 4 to 38 +/- 2 mumol/l (P less than 0.001). After bedrest, subjects exhibited decreased glucose tolerance and increased endogenous insulin secretion, but basal and insulin-suppressed intracellular leucine Ra and leucine oxidation rates were not different from control. Magnetic resonance imaging of the back and lower extremities revealed a 1-4% decrease in muscle volume and a 2-5% increase in fat volume secondary to bedrest. Bedrest also resulted in a negative nitrogen balance as compared with the control period, with an average cumulative loss of 6.3 g of nitrogen after 6 days. Urinary 3-methyl-L-histidine excretion was unchanged by bed rest. Thus because negative nitrogen balance and skeletal muscle atrophy occurred in six rested subjects in the absence of changes in the two indices of protein breakdown used in this study (3-methyl-L-histidine release and leucine release), it seems likely that muscle protein synthesis was inhibited.

Adipose Tissue↗