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Biomedical subjects

A J Sinclair

Publications and source records attributed to A J Sinclair.

At least 73 records · Page 4Linked to original sources
PubMed1998

Electroretinograms of albino and pigmented guinea-pigs (Cavia porcellus).

PURPOSE/METHODS: The present study compares the electroretinogram responses of albino and pigmented guinea-pigs (Cavia porcellus) with data published for the rat and mouse. RESULTS: We found that albino guinea-pigs gave significantly larger amplitudes and faster implicit times for a-wave and peak-to-peak responses than did pigmented animals. In contrast, pigmented and albino rats and mice do not show such differences between strains. CONCLUSION: We suggest that the guinea-pig may be a better model of the retinal response in human albinism as their response characteristics are consistent with those published for humans.

Albinism↗
PubMed1998

Assessment and treatment of nutritional status in stroke patients.

Stroke illness imposes a heavy and costly work load on hospital and community care services, and life after stroke can be a miserable affair for stroke patients and their carers. Nutritional factors may have an important role in acute stroke and its outcome. From the limited amount of research undertaken it has been shown that a significant number of patients with stroke are undernourished on admission and their nutritional status deteriorates further as an in-patient. This is especially so for those who are most dependent, in whom undernutrition is also associated with increasing morbidity and mortality. There is some evidence that nutritional supplementation may improve nutritional status and reduce morbidity and mortality. However most clinically available nutrition screening instruments lack sensitivity and specificity, and abnormal nutritional indicators may simply reflect effects of age, functional disability, or severe underlying disease. Therefore, causal relationship cannot be assumed without a sufficiently powerful intervention study which adequately adjusts for the effects of non-nutritional factors, such as the number and severity of comorbid conditions on clinical outcome. Meanwhile, doctors, nurses and members of the multidisciplinary team looking after stroke patients should be made aware of the likely impact of poor nutritional status on clinical outcome.

Aged↗
PubMed1998

Interactions between Epstein-Barr virus and the cell cycle control machinery.

Epstein-Barr virus (EBV) persists in the majority of the world's human population. In the majority of cases the infection is asymptomatic, but EBV is associated with a number of human diseases, such as infectious mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, gastric carcinomas and other lymphomas and lymphoproliferative diseases. In this review the evidence linking EBV with these diseases is reviewed together with recent advances in understanding the interactions between EBV and the cell cycle control machinery.

Cell Cycle↗
PubMed1998

Effect of diet on the rate of depletion of n-3 fatty acids in the retina of the guinea pig.

This study has assessed the influence of maternal n-3 long chain polyunsaturated fatty acid supply and dietary manipulation after weaning on the retinal polyunsaturated fatty acid profile. Infant guinea pigs born of dams fed one of two commercial chow diets (differing in the amount of eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids) were raised in two separate experiments, and subsequently partitioned into two diet groups, one supplied with a high level of alpha-linolenic acid (canola oil supplemented), the other with a very low level of alpha-linolenic acid (safflower oil supplemented). Guinea pigs born of dams supplied with the longer chain n-3 fatty acids in the commercial pellets (experiment 2) showed higher levels of retinal docosahexaenoic acid at weaning compared with those born to dams fed chow containing only alpha-linolenic acid (experiment 1). The rate of depletion of retinal docosahexaenoic acid after weaning onto the safflower oil diet was described by a two-stage exponential decay, possibly reflecting systemic and local conservation mechanisms, in conditions of dietary n-3 fatty acid deprivation. The rate of docosahexaenoic acid depletion in the group with the lower retinal docosahexaenoic acid at weaning was more than double the rate of depletion in the group with the higher weaning docosahexaenoic acid value. The endpoint retinal docosahexaenoic acid level at 16 weeks post-weaning after dietary n-3 fatty acid depletion on the safflower oil diet in the group, which started with the lower retinal docosahexaenoic acid level, was approximately half that compared with the group from the dams fed long chain n-3 fatty acids (experiment 1, 5% (interpolated), experiment 2, 9%). These results suggest that an adequately supplied mother is capable of providing an infant with enough n-3 fatty acids to withstand a longer period of dietary deprivation imposed after weaning.

Animals↗
PubMed1997

Mitochondrial DNA mutations in Alzheimer's disease.

Several reports have indicated that point mutations of the mitochondrial DNA (mtDNA) contribute to the pathogenesis of Alzheimer's disease (AD). However, other groups have failed to find similar associations between these mutations and AD. A recent report described a set of mutations in the mtDNA encoded cytochrome oxidase genes which may account for 20% of all AD cases. We screened brain tissue from 65 AD patients for each of these previously reported mtDNA mutations but were unable to find an increased incidence of any of them in our AD sample. However, one patient with a mutation in the APP gene did harbour a novel mtDNA mutation (G to C at position 5705 in the tRNAAsn gene) that might have contributed to the very early onset of dementia in this individual. The role of mtDNA mutations in the pathogenesis of AD remains unclear, but they do not appear to be primary causes but may contribute to the onset of the disease.

Aged↗
PubMed1997

Mortality in older people with diabetes mellitus.

It is universally acknowledged that diabetes mellitus is a common cause of morbidity in the elderly population but it is less well established that the mortality of people with diabetes is greater at any given age. This comprehensive literature review aims to examine the evidence in order to clarify the relationship between diabetes and mortality risk in elderly diabetic patients. Information was obtained by carrying out a MEDLINE search for relevant papers published in 1980 and onwards; a key paper on mortality in non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) was used as an index paper; Diabetes, Diabetologia, Diabetic Medicine, Diabete et Metabolisme, and Diabetes Care were hand searched; and, finally, other experts in the field were contacted. Two reviewers independently extracted the data from each of the studies and disagreements were discussed and resolved. The studies in elderly study populations comprised mainly NIDDM. The review demonstrated that diabetes is a significant contributor to mortality and reduced life expectancy in elderly subjects. Demographic trends in our population indicate that diabetes will continue to be a challenging health problem.

Adult↗
PubMed1997

Non-insulin dependent diabetes mellitus in Psammomys obesus is independent of changes in tissue fatty acid composition.

Recently it has been postulated that membrane fatty acid composition may be involved in the pathogenesis of insulin resistance and non-insulin dependent diabetes mellitus (NIDDM). The aim of this study was to determine whether alterations in tissue phospholipid (PL) fatty acids are present in hyperglycemic and hyperinsulinemic Psammomys obesus. On a native diet of salt bush, P. obesus (Israeli sand rat) remains lean and free of diabetes; however, when placed on a normal laboratory chow, a significant proportion of these animals develops a number of metabolic disorders associated with NIDDM, providing an ideal animal model of obesity and NIDDM. Four groups of mature P. obesus were studied: group A: normoglycemic and normoinsulinemic; group B: normoglycemic and hyperinsulinemic; group C: hyperglycemic and hyperinsulinemic; and group D: hyperglycemic and hypoinsulinemic. In liver and red gastrocnemius muscle, there were no significant differences between groups A, B, and C in fatty acid composition of PL. Minor differences in individual fatty acids were demonstrated in group D animals (increased liver 20:4n-6 and increased muscle 22:5n-3); however, the unsaturation indices in liver and muscle were not significantly different between any of the groups. In considering that the minor changes in group D animals were not demonstrated in hyperinsulinemic group B animals or hyperglycemic, hyperinsulinemic group C animals, it is likely that the differences in group D animals were secondary to the more severe disturbances in glucose homeostasis and hypoinsulinemia present in these animals. The results of this study suggest that in this rodent diabetic model significant disturbances in glucose homeostasis and hyperinsulinemia may develop independently of changes in tissue fatty acid composition.

Animals↗
PubMed1997

A low-fat diet supplemented with monounsaturated fat results in less HDL-C lowering than a very-low-fat diet.

OBJECTIVE: The purpose of this study was to compare the effects of a very-low-fat diet with a low-fat diet supplemented with monounsaturated oil on plasma lipid levels in subjects with hypercholesterolemia. DESIGN: The 8-week study was divided into one 2-week baseline diet and two 3-week intervention periods in a randomized crossover design. SETTING: The study was conducted in an outpatient setting at the Deakin Institute of Human Nutrition, Deakin University, Geelong, Australia. SUBJECTS: Twenty-four free-living subjects with hypercholesterolemia participated in and completed the study. INTERVENTION: After a 2-week baseline period of a self-selected diet, subjects were assigned to one of two dietary interventions: a very-low-fat (10% of energy from fat), high-carbohydrate diet or a low-fat (26% of energy from fat) diet supplemented with olive oil and an olive oil-based margarine. MAIN OUTCOME MEASURES: Lipid measurements included total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride concentrations. Plasma cholesteryl esters were measured to monitor compliance. STATISTICAL ANALYSES: A paired t test was used to assess differences between treatment periods for each subject. The dependence of the difference between treatment periods on the covariates of age, sex, initial cholesterol concentration, and energy intake was analyzed using repeated measures and analysis of covariance. RESULTS: The low-fat diet supplemented with monounsaturated fat resulted in significantly less high-density lipoprotein cholesterol lowering than the very-low-fat diet (P=.005). Both interventions resulted in significant reductions in both low-density lipoprotein cholesterol and total cholesterol compared with the baseline diet. APPLICATIONS: This study suggests that a low-fat diet enriched with olive oil provides advantages over a very-low-fat diet in the control of serum lipoproteins among persons with hypercholesterolemia.

Adult↗
PubMed1997

A hospital-based case-control study of quality of life in older asthmatics.

Asthma is a common but neglected problem in older people, the impact of which is relatively unstudied. The aim of this study was to objectively assess quality of life and depression in older asthmatics. The subjects studied were 50 hospitalized known asthmatics, over 55 yrs of age (mean age 72 yrs). Of these, 40 had objective evidence of asthma, and were compared to 40 age- and sex-matched controls. Using a structured questionnaire, the Geriatric Depression Score, subjective health status (short form (SF)-36), and other comparative disability data were recorded. Spirometric results were also recorded. Depressive symptoms were common in both groups but were not significantly different. Mean SF-36 scores were significantly worse in the asthmatics, especially for components of physical function (p = 0.04), physical role limitation (p = 0.01), energy (p = 0.01), health change (p = 0.01), and general health perception (p = 0.01). However mental, mental role and social scores were similar in both groups. We conclude that quality of life is impaired in hospitalized asthmatics compared to controls. Physical components appear to be most adversely affected. Depressive symptoms are common but no overall difference was found for psychological disability. Older asthmatics appear to adapt well to adverse situations.

Activities of Daily Living↗
PubMed1997

Observations of diabetes care in long-term institutional settings with measures of cognitive function and dependency.

OBJECTIVE: To document the prevalence of known diabetes and quantity of diabetes care delivered in long-term institutional settings in South Glamorgan, Wales; to measure physical and mental performance of diabetic residents; and to ascertain the level of basic diabetes knowledge of both staff and diabetic residents. RESEARCH DESIGN AND METHODS: A postal questionnaire survey was sent to 31 nursing or dual registered homes and 88 residential homes in South Wales to determine the prevalence of known diabetes. Medical examination and a semistructured interview of 109 diabetic and 106 age- and sex-matched nondiabetic residents was followed by assessment of dependency (Barthel Activities of Daily Living Scale [15]; Behavioral Rating Scale [16]) and cognitive performance (Mini-Mental State Exam [12]). RESULTS: The prevalence of known diabetes was 7.2%. Forty percent of diabetic residents were taking long-acting sulfonylureas. Only half of the residents in both homes had regular blood glucose monitoring. Less than 1 in 10 diabetic residents were being followed in a hospital-based diabetic clinic. Diabetic residents had had more hospital admissions in the preceding year than nondiabetic control subjects, and their length of stay was double that of nondiabetic control subjects (P < 0.05). Health professional input was fragmented, with involvement of community nurses and dietitians being rare. Diabetic residents had significantly higher levels of arterial disease (P < 0.05), foot ulceration (P < 0.01), and dementia (P < 0.01), and more severe cognitive impairment and higher levels of dependency (P < 0.01). Knowledge of diabetes was poor among both diabetic and nondiabetic residents and care staff. CONCLUSIONS: There is an important need for a reappraisal of diabetes care in institutional settings.

Activities of Daily Living↗
PubMed1996

Epstein-Barr virus exploits the normal cell pathway to regulate Rb activity during the immortalisation of primary B-cells.

Infection of human primary B-lymphocytes with Epstein-Barr virus (EBV) drives quiescent cells into continual proliferation and results in the outgrowth of immortal cell lines. This requires re-programming of the mechanisms that, in the absence of appropriate antigenic stimulation, normally prevent the proliferation of B-lymphocytes. Since the Retinoblastoma protein (pRb) and its relatives, p107 and p130, play critical roles in controlling the mammalian cell division cycle, we have investigated the expression and phosphorylation status of these proteins following EBV immortalisation of primary B-lymphocytes. In this report, we show that EBV drives the hyperphosphorylation of pRb. This is achieved by a strategy involving the altered expression of several components of the signal transduction pathway that normally regulates the phosphorylation status of pRb, including the up regulation of a number of cyclins and cyclin-dependent kinases and the down regulation of a subset of cyclin-dependent kinase inhibitors. The net result is the formation of active cyclin-dependent kinase complexes that are capable of phosphorylating and inactivating pRb. The results presented here identify the activation of a normal signal transduction pathway as an important component of the strategy used by EBV to drive cell proliferation.

B-Lymphocytes↗
PubMed1996

The effect of docosahexaenoic acid on the electroretinogram of the guinea pig.

Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, is found in consistently high concentrations in the retinae of mammals, yet its role in vision remains unclear. In this study, a mammalian model of variable retinal DHA concentration has been developed, such that the retinal phospholipids of guinea pigs contained between 2.5 and 30.8% DHA. Visual function was assessed using full-field flash electroretinography, over a range of exposure levels spanning six log units. Trend analysis indicated that retinal function was altered by the tissue DHA level, and was described by a second-order polynomial "inverted U-shaped" function. The results suggested that although some amount of DHA is essential for normal retinal function, increases in the DHA level past an optimal amount, found to be 19%, provided diminishing returns. In this study, manipulation of the retinal DHA level accounted for 21-35% of the electroretinographic variability.

Animals↗