PubMed Health⌕ Search

Biomedical subjects

I S Young

Publications and source records attributed to I S Young.

At least 19 recordsLinked to original sources
PubMed2006

Homocysteine and coronary heart disease risk in the PRIME study.

INTRODUCTION: Despite recent meta-analyses suggesting that homocysteine is an independent predictor of coronary heart disease (CHD), there is debate regarding whether elevated homocysteine may be deleterious only in the presence of other risk factors, with which it acts synergistically to exert a multiplicative effect on CHD risk, emerging only as a CHD predictor in patients with pre-existing risk factors. The Prospective Epidemiological Study of Myocardial Infarction (PRIME) Study is a multicentre prospective study of 10593 men from France and Northern Ireland, investigating cardiovascular risk factors. We investigated: (1) whether higher homocysteine is associated with increased CHD risk in the PRIME case-control cohort; (2) whether homocysteine interacts synergistically with pre-existing CHD risk factors. METHODS: Homocysteine was measured in 323 participants who had developed CHD at 5-year follow-up and in 638 matched controls. RESULTS: There was no significant difference in homocysteine between cases and controls (p=0.18). Homocysteine was significantly higher in current smokers (geometric mean mumol/l (interquartile range mumol/l) 9.45 (7.43, 11.75)) compared with non-smokers (8.90 (7.32, 10.70); p=0.007). There was a significant interaction between homocysteine, smoking and CHD risk (chi2=10.29, d.f.=2, p=0.006). CONCLUSIONS: These findings suggest that elevated homocysteine is significantly associated with CHD risk in current smokers.

Biomarkers↗
PubMed2005

The effect of pravastatin on intima media thickness of the carotid artery in patients with normal cholesterol.

OBJECTIVE: Carotid intima media thickness (IMT) is a good indicator of the severity of atherosclerotic disease. Statins have been found to reduce carotid IMT in patients with hypercholesterolaemia. The aim of this study was to investigate if pravastatin is effective in reducing IMT in normocholesterolaemic patients with carotid artery disease. METHODS: Patients with carotid artery stenosis and normal cholesterol levels who were not on a statin, were recruited. Patients were randomised to receive pravastatin or placebo daily. Serum concentration of cholesterol and IMT of common carotid arteries were measured before randomisation and at 3 monthly intervals thereafter, for 9 months. IMT was analysed to give the mean of a standardised 2 cm of the common carotid artery (CCA). Results are expressed as median (IQR) and comparison made using the Wilcoxon signed ranks test. RESULTS: Fifty-four patients were examined. Twenty-eight patients were randomised to active treatment. There was no difference in demographic details and co-morbid states between the two groups. A significant reduction in cholesterol concentration was observed from 3 months in patients randomised to the pravastatin group [5.14(4.72-5.88) vs. 4.11(3.44-5.33), p < 0.05], while there was also a significant decrease in combined IMT form 6 months [1.53(1.36-1.87) vs. 1.41 (1.33-1.78), p < 0.05]. CONCLUSIONS: The results demonstrate that pravastatin reduces intima media thickness of the common carotid artery in normocholesterolaemic patients with moderate carotid stenosis.

Aged↗
PubMed2005

Brisk walking, fitness, and cardiovascular risk: a randomized controlled trial in primary care.

STUDY OBJECTIVE: To examine the effects of 30 min of self-paced, non-supervised, brisk walking, 5 days per week on the health and fitness of people aged 50-65 years. DESIGN: Randomized controlled trial. Members of the intervention group (n = 21) were directed to walk briskly for 30 min, 5 days per week, for 12 weeks. Individuals were given the choice to complete the 30 min of walking in one session or in shorter bouts of no less than 10 min. They were asked to record in a diary the time spent walking and the number of steps taken during a single walk using a pedometer. Participants in the control group (n = 10) were asked to maintain their habitual lifestyle and not change their activity or dietary habits. Measurements of body mass index (BMI), waist/hip ratio (WHR), blood pressure, functional capacity, total cholesterol, triglyceride, and lipoprotein subfractions were taken before and after the program. Changes in 10-year risk estimate for coronary heart disease and stroke were calculated using Framingham risk equations. SETTING: Three urban general practices patients: 31 healthy, sedentary 50- to 65-year-old participants recruited following contact by their general practitioner. MAIN RESULTS: The mean time spent walking by the intervention group was 27.72 (+/-9.79) min/day: their adherence to the protocol was 90.3%. Significant decreases in systolic and diastolic blood pressure, reduction in stroke risk, and increased functional capacity were found within the walking group between baseline and 12-week measurements. No changes were found in these parameters within the control group. Significant reductions in 10-year risk of CHD were observed in both groups. No significant changes were found in lipid levels or anthropometric measurements in either group. CONCLUSIONS: The study provides evidence for the benefit to fitness and cardiovascular risk of the "30-min brisk walking, 5 days a week" message to people aged 50-65 years who participated in an unsupervised home-based walking program. Further study to overcome the problem of poor recruitment and determine the minimum effective dose of exercise to improve cardiovascular risk prediction scores is required.

Aged↗
PubMed2005

Ten-year trends for fatness in Northern Irish adolescents: the Young Hearts Projects--repeat cross-sectional study.

OBJECTIVE: To examine secular trends in measures of fatness over a 10-y period (the 1990s) in Northern Irish schoolchildren. DESIGN: Repeat cross-sectional surveys. SUBJECTS: In total, 12- and 15-y-old children randomly selected from post-primary schools. A total of 1015 children studied between 1989 and 1990, and 2017 studied between 1999 and 2001. MEASUREMENTS: The same study methods were applied in both surveys. Body mass index (BMI) was calculated from height and weight, and percentage body fat (%BF) was derived from skinfold measurements at four sites. Dietary intake was assessed using a diet history method and habitual physical activity (PA) was estimated from a self-report questionnaire. RESULTS: Increases were seen in both height and weight in all age-sex groups. The overall prevalence of overweight/obesity increased from 15.0 to 19.6%, but 12-y-old girls contributed most to this increase (15.9-26.3%), with a modest increase observed also in 15-y-old boys. Increases in mean BMI (19.2-20.3 kg/m2) and mean %BF (25.8-27.1%) were seen in 12-y-old girls, with no significant changes in any of the other subgroups. Mean energy intake increased in girls but not in boys, while mean PA score decreased in 12-y-old girls, but was unchanged in the other three groups. All age-sex groups showed substantial increases in the sugar intake while fat intake increased in girls and decreased in boys. CONCLUSION: Increases in indices of fatness were seen among school-age children in Northern Ireland during the 1990s. Trends differed between age-sex groups with the largest changes seen in 12-y-old girls. It remains to be seen whether the large increase in overweight/obesity in this group tracks into adulthood, with consequences for chronic disease incidence in women.

Adolescent↗
PubMed2005

Endothelial function, insulin action and cardiovascular risk factors in young healthy adult offspring of parents with Type 2 diabetes: effect of vitamin E in a randomized double-blind, controlled clinical trial.

BACKGROUND AND AIMS: Endothelial dysfunction, insulin resistance and oxidative stress are believed to be central and associated mechanisms in atherogenesis. We aimed to determine the effect of the antioxidant vitamin E on endothelial function, insulin action and cardiovascular risk markers in young healthy adult offspring of parents with Type 2 diabetes. METHODS: Healthy, glucose-tolerant adults (18-38 years), 14 (12 male/2 female) with at least one parent with Type 2 diabetes, and 14 (12 male/2 female) subjects with no family history of diabetes (controls) were studied. Insulin action was assessed by euglycaemic hyperinsulinaemic clamp (1 mU/kg/min). Endothelial function was assessed by forearm blood flow (FBF) responses to intra-brachial artery infusions of acetylcholine (ACh) (endothelium-dependent vasodilation), sodium nitroprusside (SNP) (endothelium-independent vasodilation) and N(G)-monomethyl L-arginine (LNMMA) (nitric oxide synthase inhibition). Thirteen offspring (18-38 years, 11 male/2 female, BMI < 30 kg/m2) completed a randomized, double-blind, crossover trial (12 weeks vitamin E 800 IU/day or placebo, 6-week washout). RESULTS: Exogenous glucose infusion rates to maintain euglycaemia were positively associated with response to acetylcholine in offspring (r = 0.61, P < 0.05), and were linked with triglycerides. Vitamin E had no effect on endothelial function, insulin action or cardiovascular risk markers in healthy adult offspring of parents with Type 2 diabetes. CONCLUSIONS: Our results support a positive association between insulin action and endothelial-dependent vasodilation in young healthy adult offspring of parents with Type 2 diabetes, but indicate no effect of vitamin E on these parameters.

Adolescent↗
PubMed2005

Screening for microalbuminuria by use of microproteinuria.

We aimed to develop a reliable, low cost method to assess the early stages of renal impairment in diabetes, for use in high-risk populations in countries with limited resources. We evaluated a trichloroacetic acid (TCA) turbidimetric method for microproteinuria screening in patients with diabetes. The method was compared with an immunoturbidimetric procedure for the detection of microalbumuniuria. Both methods performed within limits of allowable uncertainty based on inter- and intra-individual variation. A urinary albumin/creatinine ratio of 3.0 g/mol, assumed as diagnostic of microalbuminuria, was found to correlate with a cut-off value of 24 mg/L for microproteinuria. The clinical sensitivity and specificity of the TCA method determined against this ratio were 86% and 90% respectively. The reliability and practicability of the TCA method renders it suitable for the detection of early stage renal damage, with emphasis on screening high-risk populations in countries with limited resources.

Albuminuria↗
PubMed2004

Total homocysteine is not a determinant of arterial pulse wave velocity in young healthy adults.

AIMS: Hyperhomocysteinaemia has been associated with reduced pulse wave velocity (PWV) in patients with end-stage renal disease and in those with hypertension. The aim of this study was to examine the association between total homocysteine (tHcy) concentrations, the biochemical and genetic determinants of tHcy and PWV in healthy young adults. METHODS AND RESULTS: A total of 489 subjects aged 20-25 years participated. A fasting blood sample was taken and PWV measured using a non-invasive optical method. tHcy did not correlate with PWV, whether assessed at the aorto-iliac segment (P = 0.18), the aorto-radial segment (P = 0.39) or the aorto-dorsalis-pedis segment (P = 0.22). When tHcy was classified into normal (<15) and high (> or =15micromol/l), PWV did not differ between the two groups at any segment. PWV did not differ by MTHFR C677T or NOS3 G894T genotype, even when smoking and folate sub-groups were considered. Considering aortic PWV as a dependent variable, stepwise regression analysis showed that the only parameter entering the model for all segments was systolic blood pressure (aorto-iliac, P < 0.001; aorto-radial, P = 0.01; aorto-dorsalis-pedis, P = 0.001). Age, sex, COL1A1 genotype and triglycerides entered the model significantly for two of three segments. CONCLUSION: This study shows that arterial PWV is not associated with tHcy in a healthy young population.

Adult↗
PubMed2004

The Diabetes and Pre-eclampsia Intervention Trial.

OBJECTIVE: Rates of pre-eclampsia in women with type 1 diabetes are two to four times higher than in normal pregnancies. Diabetes is associated with antioxidant depletion and increased free radical production, and an increasing body of evidence suggests that oxidative stress and endothelial cell activation may be relevant to disease pathogenesis in pre-eclampsia. The Diabetes and Pre-eclampsia Intervention Trial (DAPIT) aims to establish if pregnant women with type 1 diabetes supplemented with vitamins C and E have lower rates of pre-eclampsia and endothelial activation compared with placebo treatment. METHODS: DAPIT is a randomised multicentre double-blind placebo-controlled trial that will recruit 756 pregnant women with type 1 diabetes from 20 metabolic-antenatal clinics in the UK over 4 years. Women are randomised to daily vitamin C (1000 mg) and vitamin E (400 IU) or placebo at 8-22 weeks of gestation until delivery. Maternal venous blood is obtained at randomisation, 26 and 34 weeks, for markers of endothelial activation and oxidative stress and to assess glycaemic control. The primary outcome of DAPIT is pre-eclampsia. Secondary outcomes include endothelial activation (PAI-1/PAI-2) and birthweight centile.

Ascorbic Acid↗
PubMed2004

Oxygen consumption is increased relative to work rate in patients with McArdle's disease.

BACKGROUND: Patients with McArdle's disease suffer exercise incapacity as a result of myophosphorylase deficiency, and for a given work rate have excessive circulatory and ventilatory responses. We hypothesized that the rate of increase of oxygen consumption with work rate (DeltaVO2-DeltaWR slope) would also be elevated in such patients as a result of these excessive responses. PATIENTS AND METHODS: Five patients with McArdle's disease and five matched controls carried out a maximal incremental cardiopulmonary exercise test. Controls then carried out a second test matched to the maximal test of a paired patient. Venous blood was sampled at rest, peak exercise and recovery. RESULTS: During the matched test, the DeltaVO2-DeltaWR slope was higher in the patients than in the controls [19.9 (15.0-24.6) vs. 11.7 (9.2-13.5) mL min(-1) W(-1); mean (range); P = 0.022], and the peak-achieved VO2 was also greater in the patient group [1201 (890-1575) vs. 918 (599-1248) mL min(-1); P = 0.003]. A similar pattern was observed for heart rate [173 (165-182) vs. 108 (105-134) b.p.m.; P = 0.001] and plasma norepinephrine levels [12.6 (9.2-19.9) vs. 2.9 (2.2-4.9) nmol l(-1); P = 0.003]. CONCLUSION: There is an increased rate of rise in VO2 relative to work rate during exercise in patients with McArdle's disease. There is also a greater rise in catecholamines, which may be the result of a physiological response to substrate starvation, and is likely to contribute to the increase in VO2.

Adult↗
PubMed2004

Malondialdehyde and measures of antioxidant activity in subjects from the Belfast Elderly Longitudinal Free-living Aging Study.

Glutathione and glutathione peroxidase activity are important components in the complex body defense against oxidative damage. In this study, we have measured malondialdehyde (MDA) as a marker of oxidative stress, the antioxidant glutathione (GSH), and activity of the antioxidant enzyme (GSHPx), in a cohort of free-living elderly subjects from the Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST), hypothesizing that free-living Senieur-approximated nonagenarians might demonstrate enhanced antioxidant defense mechanisms. The main finding in the BELFAST octo/nonagenarians was that plasma antioxidant glutathione increased in nonagenarian compared with septo/octogenarian subjects (P =.015), whereas conversely antioxidant glutathione peroxidase activity fell in the nonagenarian group (P <.0001). In the same subject group, malondialdehyde, a measure of lipid peroxidation, showed no change across the age groups (P =.73). These results might overall represent a situation in which elderly survivors in the BELFAST study have evolved a sort of free radical/antioxidant equilibrium as a mechanism of successful aging.

Aged↗
PubMed2003

Oxidative modification of triacylglycerol-rich lipoproteins.

Lipoprotein oxidation is thought to play a pivotal role in the evolution of atherosclerosis. Low-density lipoprotein (LDL) is the main source of oxidized lipid in the arterial wall. Oxidation of LDL alters its properties in a number of ways, making it more atherogenic, but oxidation of other lipoprotein classes may also be important. Common mechanisms are likely to contribute to the oxidation of all lipoprotein classes, with enzyme-mediated oxidation likely to be most important. Antioxidant content, fatty acid composition, particle size and the presence of seeding hydroperoxides also influence oxidative reactions. Larger triglyceride-rich lipoproteins are less likely to enter the arterial wall than LDL, but when oxidized will deliver a greater oxidant load to the arterial wall.

Animals↗
PubMed2003

The effect of lower limb ischaemia-reperfusion on intestinal permeability and the systemic inflammatory response.

OBJECTIVES: a relationship has been demonstrated between increased intestinal permeability, endotoxaemia and the development of the systemic inflammatory response syndrome (SIRS) after aortic surgery. The aim of this study was to evaluate whether isolated lower limb ischaemia-reperfusion (I/R) injury affects intestinal mucosal barrier function and cytokine release. PATIENTS AND METHODS: four groups of patients were investigated, group I, patients with critical limb ischaemia (CLI) undergoing infra-inguinal bypass surgery (n=18); group II, patients with intermittent claudication (IC) undergoing infra-inguinal bypass surgery (n=14); group III, patients with CLI unsuitable for arterial reconstruction, undergoing major amputation (n=12); and group IV, patients undergoing carotid endarterectomy for symptomatic carotid stenosis (n=13). Intestinal permeability, endotoxaemia and urinary soluble tumour necrosis factor receptors were assessed (p55TNF-R). RESULTS: an increase in intestinal permeability was observed on the 3rd postoperative day only in CLI group. This was found to correlate with arterial clamp time. Patients who had a femoro-distal bypass had significantly higher intestinal permeability compared to those who had femoro-popliteal bypass. Endotoxaemia was not detected in any of the groups. Postoperative urinary p55TNF-R concentrations were significantly higher in CLI group compared to the other groups. These did not correlate with the increased intestinal permeability. CONCLUSIONS: our results support the hypothesis that revascularisation of critically ischaemia limbs leads to intestinal mucosal barrier dysfunction and cytokine release. They also suggest that the magnitude of the inflammatory response following I/R injury is related to the degree of initial ischaemia.

Aged↗
PubMed2003

Genetics of the lipoprotein lipase gene and hypertriglyceridaemia.

The aim of this study is to assess whether genetic variation at the lipoprotein lipase (LPL) gene is related to fasting triglyceride levels or to the presence of vascular disease. Hypertriglyceridaemic patients are genotyped for the N291S, G188E, and P207L variants and the HindIII and PvuII restriction fragment length polymorphisms of the LPL gene. Sequence analysis is carried out on exons 1-9 of the LPL gene for patients with severe hypertriglyceridaemia, to search for new gene variants. No differences were found between the patient and control group for the N291S, G188E and P207L variants. The HindIII and PvuII allelic frequencies were found to be similar for patients and controls; however, the frequency of the PvuII P2 allele was higher in patients with vascular disease (allele frequency: 0.56) than patients with no vascular disease (allele frequency, 0.42) (P=0.03). Sequence analysis revealed no exon sequence variants in the LPL gene but two intron sequence variants were found in intron 5 in two patients.

Adult↗
PubMed2003

Vitamin C improves endothelial function in healthy estrogen-deficient postmenopausal women.

OBJECTIVE: Estrogen deficiency is associated with increased cardiovascular risk and endothelial dysfunction. Improvements in endothelial function with antioxidants, including vitamin C, have been reported. We aimed to determine the acute effect of vitamin C on endothelial function in healthy women with established menopause. SUBJECTS: Subjects (aged 47-59 years) were at least 1 year postmenopause. Ten (serum estradiol < 50 pmol/l) were not receiving hormone replacement therapy, while eight hysterectomized subjects received subcutaneous estradiol. DESIGN: Forearm blood flow (FBF; strain-gauge plethysmography) responses to intrabrachial artery infusions of incremental doses of acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation) were determined at baseline, and following 1.5 g vitamin C given intravenously. RESULTS: At baseline, estrogen-treated subjects had a lower index of insulin resistance (homeostasis model assessment, HOMA) and lower fibrinogen than those of estrogen deficient subjects. There was a trend towards higher baseline FBF and larger baseline FBF response to acetylcholine in estrogen-treated subjects. FBF responses to acetylcholine were significantly enhanced after vitamin C in estrogen-deficient subjects (area under the dose-response curve (AUC): estrogen-deficient 9.9 +/- 2.6 vs. 15.1 +/- 3.2 (mean +/- SEM), p = 0.02; estrogen-treated 17.0 +/- 2.9 vs. 21.0 +/- 3.2, p = 0.07). Resting FBF and response to sodium nitroprusside were unchanged in either group by vitamin C. Plasminogen activator inhibitor-1 levels fell after vitamin C in the estrogen-deficient group (17.0 +/- 1.6 vs. 14.7 +/- 0.9 IU/ml, p = 0.03). CONCLUSIONS: These results indicate that endothelial function may be improved acutely by antioxidant treatment in postmenopausal women with established estrogen deficiency.

Acetylcholine↗
PubMed2002

A longitudinal study through adolescence to adulthood: the Young Hearts Project, Northern Ireland.

The Young Hearts (YH) Project is an ongoing study of biological and behavioural risk factors for cardiovascular disease in a representative sample of young people from Northern Ireland, a region of high coronary mortality. This article describes the cross-sectional clinical, dietary and lifestyle data obtained from individuals (aged 20-25 y) who participated in phase 3 of the project (YH3). A total of 489 individuals (251 males, 238 females) participated in YH3 (48.2% response rate). Some 31.1% of participants at YH3 were overweight (BMI >25 kg/m(2)) with 4.4% of males and 8.0% of females were obese (BMI >30 kg/m(2)). More females than males had a very poor fitness (55.0 vs 22.1%, chi-squared 51.70, d.f. 1, P<0.001) and did not participate in any sporting or exercise activity (38.4 vs 24.9%, chi-squared 10.26, d.f. 1, P=0.001). Over 20% of participants had a raised total serum cholesterol (>5.2 mmol/l). More females had a raised serum LDL-cholesterol (>3.0 mmol/l) than males (44.6 vs 34.6%, chi-squared 4.39, d.f. 1, P<0.05). Over 46% of participants reported energy intakes from fat above recommended levels, and 68.5% of participants had saturated fat intakes above those recommended (Dietary reference values for food energy and nutrients for the United Kingdom. HMSO: London, 1991). Just over half of the study population reported alcohol intakes in excess of recommended sensible limits set by the Royal College of Physicians (A great and growing evil: the medical consequences of alcohol abuse. Tavistock: London, 1987), with 36.7% of males and 13.4% of females reporting intakes over twice these recommended limits. A total of 37% of the study population smoked. During young adulthood, individuals may be less amenable to attend a health-related study and recruitment of participants to the current phase of the study proved a major problem. However, these data constitute a unique developmental record from adolescence to young adulthood in a cohort from Northern Ireland and provide additional information on the impact of early life, childhood and young adulthood on the development of risk for chronic disease.

Adolescent↗