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Biomedical subjects

R W Stout

Publications and source records attributed to R W Stout.

At least 19 recordsLinked to original sources

Insulin and atherogenesis.

A number of processes are involved in the pathogenesis of atherosclerosis. These include an "injury" to the endothelial cell barrier of the inner lining of the artery, infiltration of the artery by lipid filled monocyte-macrophages, proliferation of smooth muscle cells, synthesis of connective tissue and thrombus formation. Insulin may be involved in several of these processes. Over 40 years ago it was shown that insulin is necessary for the production of experimental atherosclerosis in cholesterol fed, alloxan diabetic rabbits. Insulin inhibits regression and stimulates formation of lipid containing lesions in a number of species, and can promote lesions in animals fed normal diets. Insulin is also related to lipid metabolism in the artery wall and interacts with blood pressure to stimulate lipid synthesis in arteries. Arterial smooth muscle cells cultured from a number of species including humans proliferate in response to levels of insulin similar to those found in normal human physiology. The proliferative effects of insulin are mediated by the insulin-like growth factor receptor and hence may not be impaired in states of insulin resistance. Insulin also stimulates arterial smooth muscle cell migration. Insulin stimulates cholesterol synthesis in cultured smooth muscle cells and enhances LDL receptor activity in a number of cell types. Insulin stimulates connective tissue synthesis, and promotes clotting.

Arteries

Readmissions to a geriatric medical unit: is prevention possible?

Of the 622 patients admitted to a geriatric medical unit during the period November 1985 to October 1986, 211 (33.9%) had been discharged from hospital within the previous year. Of these, 117 (55.5%) had previously been admitted to the geriatric medical unit (18.8% of all admissions). The reasons for readmission were deterioration of existing disease (47.4%), new medical events (33.2%), poor management of previous discharge (9.5%), and social problems (5.7%). Age was not a significant factor influencing readmission. Readmission was judged preventable by better management of the previous admission and discharge in only 33 cases (15.6% of readmissions). A prospective study of the patients discharged in the same year revealed that 19.3% were readmitted in the following year, and of these readmissions 2.3% were considered to be preventable. There was no difference in medical causes for readmission in the two years. A significant number of the patients readmitted in both years studied was categorized as "high dependency". The figures suggest that although unplanned readmission is common, it is generally not preventable by better management of the previous admission, and often reflects a highly dependent and medically frail group of patients, in whom early intervention with readmission is appropriate.

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A comparison of community care of elderly people in Wales and Northern Ireland.

This study compares the provision of community services for elderly people in Wales and Northern Ireland using data from two independent surveys. Despite sampling and definitional problems, certain interesting comparisons can be obtained. In general, elderly people in the Northern Ireland sample seem more likely to be dependent and more disabled than those in Wales. Northern Ireland people receive less help, but the help given is more likely to be from statutory services than in Wales; in many cases statutory help is the sole source of support. Further, in Wales there is more specialized care for very disabled elderly people living in the community, and the work is more likely to be shared by carers and the statutory services. There is however still considerable unmet need in both countries. A comparative study using common definitions and methods would be of considerable interest in relation to the debate concerning the relative shares of health care resources in the United Kingdom.

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Seasonal variations in fibrinogen concentrations among elderly people.

Mortality and morbidity in elderly people are higher in winter than in summer months, with seasonal variations in rates of both fatal and non-fatal myocardial infarction and stroke. To identify factors that might contribute to the excess winter frequency of cardiovascular disease in the elderly, we studied 100 subjects aged 75 and over who lived in either their own homes or in sheltered or residential accommodation. Each person was visited each month for one year, body and environmental temperatures were noted, and cardiovascular risk factors were measured. 32 subjects withdrew from the study. Significant seasonal effects were found for fibrinogen, plasma viscosity, and HDL cholesterol (p less than 0.003, Bonferroni adjustment). Plasma fibrinogen concentrations showed the greatest seasonal change and were 23% higher in the coldest six months compared with summer months. Fibrinogen was significantly (p less than 0.05) and negatively related to core body temperature and all measures of environmental temperature. Those living in institutions had greater changes in plasma fibrinogen than those living in the community. The seasonal variation in plasma fibrinogen concentration is large enough to increase the risk of both myocardial infarction and stroke in winter.

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Separation and purification of oligonucleotides using a new bonded-phase packing material.

We describe a new bonded-phase packing material, based upon surface-stabilised microparticulate silica, suitable for the rapid separation and purification of oligonucleotides. Columns packed with this material were demonstrated to give rapid separations of individual oligonucleotide species of up to 44 base units with high purity; agarose gel electrophoresis showed that the products were essentially single bands, with only trace quantities of the (n-1)-mer present. Baseline resolution of the desired oligomer from (n +/- 1)-mer was achieved under preparative loading conditions, where up to 200-300 micrograms of oligonucleotide could be separated. The separation was essentially independent of structure or sequence of the oligonucleotides. The retention mechanism of the oligonucleotides was investigated, and the results used to determine the optimum column configuration and separation conditions.

Base Sequence

Insulin as a mitogenic factor: role in the pathogenesis of cardiovascular disease.

Evidence has been accumulating that insulin has actions that may promote the development of atherosclerosis. Research has involved three broad areas: actions of insulin on cultured arterial cells, the effect of insulin on isolated artery preparations, and the development of lipid-containing lesions in the arteries of experimental animals. Insulin, in concentrations similar to those found in physiologic conditions, stimulates proliferation of cultured arterial smooth muscle cells from a number of species, including humans. Insulin also stimulates migration of smooth muscle cells. Cholesterol synthesis and low-density lipoprotein interaction with its receptor in smooth muscle cells are stimulated by insulin. Insulin's mitogenic action appears to be mediated by the insulin-like growth factor receptor. Endothelial cells cultured from large vessels are resistant to the actions of insulin, but hyperglycemia inhibits their proliferation. Insulin deficiency protects animals from experimental atherosclerosis; this protection is lost with insulin treatment. Insulin administration results in lipid-containing lesions in chickens and rats fed a normal diet, and in increased lipid synthesis in the arteries of pigs and dogs. Isolated artery preparations from insulin-deficient or insulin-treated animals undergo lipid metabolism at a rate that correlates with the insulin concentrations in the donor animals. The biological actions of insulin (and glucose) on arterial tissue suggest that hyperglycemia and hyperinsulinemia may promote the development of atherosclerosis.

Animals

The development of a programme of care for elderly people in Northern Ireland.

This paper describes the development of a Programme of Care for elderly people in Northern Ireland. The problems of the elderly were previously identified, and a classification system was designed in key areas which allocated groups of individuals with similar needs to particular services. It was thus possible to quantify the resources required to meet the future needs of elderly people in Northern Ireland. The major implications for the Health and Social Services were then stressed on the basis of certain assumptions. Generally, resources are currently being channelled in the right direction but considerable expansion of resources is necessary in the future especially in community care. In showing one method of planning services for the elderly people and the possible results, this study also offers a methodology to assist the planning process in general.

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A comparison of single-dose versus conventional-dose antibiotic treatment of bacteriuria in elderly women.

The efficacy of single-dose antibiotic therapy for the treatment of bacteriuria in a group of non-catheterized elderly women was compared with that of conventional 7-10 day courses of antibiotic therapy. Thirty-one women received single-dose treatment and 22 conventional-dose treatment. The cure rates at 1 and 6 weeks for the single-dose treatments were 52% and 38%, respectively, and the cure rates for the conventional-dose treatments at 1 and 6 weeks were 59% and 52%, respectively. It is concluded that there may be a place for the use of single-dose antibiotic therapy for the treatment of selected elderly women with bacteriuria, but larger studies are needed.

Age Factors

Sensitive, colorimetric enzyme amplification cascade for determination of alkaline phosphatase and application of the method to an immunoassay of thyrotropin.

A highly sensitive flavin adenine dinucleotide-3'-phosphate (FADP)-based enzyme amplification cascade has been developed for determining alkaline phosphatase (ALP; EC 3.1.3.1). The cascade detects ALP via the dephosphorylation of the novel substrate FADP to produce the cofactor FAD, which binds stoichiometrically to inactive apo D-amino acid oxidase (D-AAO). The resulting active holo D-AAO oxidizes D-proline to produce hydrogen peroxide, which is quantified by the horseradish peroxidase-mediated conversion of 3,5-dichloro-2-hydroxybenzenesulfonic acid and 4-aminoantipyrine to a colored product. The FADP-based enzyme amplification cascade has been used in a novel releasable linker immunoassay (RELIA) to quantify thyrotropin (TSH). In the assay, TSH is first captured onto antibody-coated chromium dioxide particles. After formation of an antibody-TSH sandwich with a dethiobiotinylated second antibody, the complex is reacted with a streptavidin-ALP conjugate. Biotin is then used to release the conjugate into solution, and ALP is quantified in an automated version of the FADP-based amplification cascade on the aca discrete clinical analyzer (Du Pont). The sensitivity of the colorimetric RELIA assay for TSH (less than 0.1 milli-int. unit/L) is comparable with that of fluorometric assays. This technology provides a way to adapt to the aca high-sensitivity immunoassays for a wide range of analytes via colorimetric detection.

Clinical Enzyme Tests

Tuberculosis.

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BCG Vaccine

The effects of acute moderate exercise on leukocyte and lymphocyte subpopulations.

The extent and duration of changes in circulating leukocyte and lymphocyte subpopulations, cortisol, and catecholamines were examined in 12 women who walked 45 min at 60% VO2max in a laboratory setting. A two-factor, 2 x 6 design with repeated measures on both factors was utilized. The first factor was condition (exercise and rest), and the second factor was time (six points of measurement over a 24-h period), with treatment order counterbalanced. The 45-min walk, in comparison with rest in a seated position, was associated with a significant but moderate leukocytosis and lymphocytosis immediately following the walk. The leukocytosis was still evident after 3 h of recovery and was primarily due to a neutrophilia. The change in lymphocyte count, relative to baseline levels and the control condition, lasted less than 1.5 h, with an increase in the natural killer (CD16 and/or CD56) and cytotoxic T cell component (CD3 and CD16 and/or CD56) (NKCT) representing approximately two-thirds of the lymphocytosis and T cells (CD5) the other third. A significant decrease in the CD4:CD8 ratio was seen, with cytotoxic/suppressor (CD8) cells increasing and helper/inducer (CD4) cells demonstrating little change in comparison with baseline. This seems to have been due to a subpopulation of CD8 (low density antigen) cells, probably natural killer cells. The 45-min walk had no effect on plasma cortisol and epinephrine levels relative to the rest condition but was associated with a moderate increase in norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Identification of the needs of elderly people in Northern Ireland.

This paper presents the results of a survey on persons over the age of 65 in Northern Ireland. One of the aims of this research was to identify and measure the needs of the elderly population in order to develop a Programme of Care. It would seem logical that the problems of the elderly tend to increase with age. Since the population is becoming older and given the commitment to community care, this will have serious implications for the National Health and Social Services. The present survey was carried out using a questionnaire to extract details concerning the individuals' mental state, ability for self-care and household duties, mobility, accommodation, social activities, general health, strain imposed on others and current support from the statutory services. The results for each category were then presented for 5 age-groups: 65-69, 70-74, 75-79, 80-84 and 85+. Specific problems in relation to home help provision and social facilities such as day care are also discussed.

Activities of Daily Living

The impact of private residential and nursing care on statutory residential and hospital care of elderly people in south Belfast.

Dependency levels were compared in residents of private, voluntary and statutory residential homes, private nursing homes and patients in geriatric continuing-care wards in South Belfast. Dependency levels were least in private and voluntary residential homes, were similar in residential and private nursing homes, but were very much greater in the geriatric wards. Evidence of dementia was found in 23% of residents of voluntary homes, 35% of residents of private residential homes, 61% of residents of statutory residential homes, 54% of those in private nursing homes and 80% of patients in geriatric wards. Severe degrees of immobility and incontinence were commoner in nursing than in residential homes, but much commoner in geriatric wards. The number of private residential and nursing home places in the area studied has increased three- to five-fold since a previous survey in 1985. In this time, dependency levels, and frequencies of dementia, immobility and incontinence have increased in both statutory residential homes and geriatric continuing-care wards. It appears, therefore, that private residential and nursing homes take rather less dependent old people and that highly dependent old people are being concentrated in hospital.

Activities of Daily Living

Insulin and atheroma. 20-yr perspective.

Many clinical studies have shown an increased insulin response to oral glucose in patients with ischemia of the heart, lower limbs, or brain. Hyperinsulinemia also occurs in patients with angiographically proved atherosclerosis without ischemia and thus appears to be related to arterial disease and not to be a nonspecific response to tissue injury. Fasting insulin levels and insulin responses to intravenous stimuli, including glucose, tolbutamide, and arginine, are normal, suggesting a gastrointestinal factor may be involved in the increased insulin response to oral glucose. In patients with atherosclerosis, insulin sensitivity appears to be normal or enhanced with respect to both glucose and lipid metabolism. Five population studies have shown that insulin responses to glucose are higher in populations at greater risk of cardiovascular disease. Many of the hyperinsulinemic populations also had upper-body obesity, hypertriglyceridemia, lower high-density lipoprotein (HDL) levels, and hypertension. These prospective studies support an independent association between hyperinsulinemia and ischemic heart disease, although their results differ in detail. Hyperinsulinemia is associated with raised triglyceride and decreased HDL cholesterol levels. Total and low-density lipoprotein (LDL) cholesterol is less closely related to hyperinsulinemia. Upper-body adiposity is associated (in separate studies) with coronary heart disease, diabetes, hyperinsulinemia, and hypertriglyceridemia. Insulin and blood pressure are closely related in both normotensive and hypertensive people. Although obesity and diabetes are often found in hypertensive people, hyperinsulinemia also occurs in nonobese nondiabetic hypertensive people. Thus, hyperinsulinemia is closely associated with a cluster of cardiovascular risk factors, i.e., hypertriglyceridemia, low HDL levels, hypertension, hyperglycemia, and upper-body obesity. There is a possibility that insulin has a role in the sex differences in ischemic heart disease incidence and their absence in diabetes, but additional work is required for its clarification. Long-term treatment with insulin results in lipid-containing lesions and thickening of the arterial wall in experimental animals. Insulin also inhibits regression of diet-induced experimental atherosclerosis, and insulin deficiency inhibits the development of arterial lesions. Insulin stimulates lipid synthesis in arterial tissue; the effect of insulin is influenced by hemodynamic factors and may be localized to certain parts of the artery. In physiological concentrations, insulin stimulates proliferation and migration of cultured arterial smooth muscle cells but has no effort on endothelial cells cultured from large vessels. Insulin also stimulates cholesterol synthesis and LDL binding in both arterial smooth muscle cells and monocyte macrophages.(ABSTRACT TRUNCATED AT 400 WORDS)

Arteriosclerosis

Functional decline and survival in dependent elderly people.

A survey of dependency levels was carried out in 1985 and 1989 in 41 residents of old peoples homes and 25 patients in geriatric continuing care wards. There was an increase in all levels of dependency for those in both types of care. In the hospital patients surveyed in 1985, mortality was greatest in the most dependent, particularly those with impaired mental function. There was a positive correlation between length of survival and mental function. The results of this study emphasise the important role of dementia in the health and survival of old people.

Activities of Daily Living

New porous organic microspheres for high-performance liquid chromatography.

A process for producing spherical porous organic microspheres, based on urea-formaldehyde (UF) polymer, has been developed. These microspheres exhibit exceptional mechanical strength and resiliency and have minimal tendency toward shrinking or swelling in aqueous, organic, or hydroorganic media. The geometric parameters of the microspheres are conveniently adjusted by process variables, which allow precise control of pore and particle dimensions. The surface of the UF microsphere contains organic functional groups suitable for chemical modification so that ligands of choice may be covalently attached for operation in the anion-exchange or hydrophobic interaction modes.

Chromatography, High Pressure Liquid

Evaluation of four screening tests for bacteriuria in elderly people.

Four screening tests for bacteriuria were assessed at ward level in 418 elderly subjects and were compared with standard methods of bacterial culture. The tests were visual appearance; microscopy; dipstick for nitrite, leucocyte esterase, protein, and blood; and dipstick for nitrite and organisms. The sensitivity of the tests varied from 85.6% to 98.3%, and the specificity from 18.4% to 82.9%. A combination of visual appearance and dipstick testing for nitrite and leucocyte esterase gave a sensitivity of 96.1% with a specificity of 50.6%, and could have reduced by almost one-third the number of urine samples submitted to the laboratory for processing.

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