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Biomedical subjects

P Clarkson

Publications and source records attributed to P Clarkson.

At least 19 recordsLinked to original sources
PubMed2000

Association between high-risk HPV types, HLA DRB1* and DQB1* alleles and cervical cancer in British women.

Cervical scrapes from 116 British women referred with cervical cancer were tested for the presence of high oncogenic risk human papillomavirus (HPV) genotypes (HPV(hr)). Ninety-four per cent of the scrapes had one or more of these virus types and 66% were HPV16-positive. HPV18 was more frequent in adenocarcinoma. No evidence was found for an increased cancer risk associated with the HPV16 E6 350G variant. The HLA DRB1* and DQB1* alleles in these women and in 155 women with normal cytology and negative for HPV(hr) DNA were compared. DQB1*0301 alone (2P = 0.02) and in combination with DRB1*0401 (2P = 0.02) was found to be associated with cervical cancer. This was more marked in cancers positive for HPV types other than HPV16. In contrast, DRB1*1501 alone and in combination with DQB1*0602 was not significantly elevated in cancers overall, but did show some excess in HPV16-positive cancers (2P = 0.05), associated with HPV16-positive cervical cancers. Taking all cancers together, a marginally significant protective effect was found for DQB1*0501 (2P = 0.03) but no protective effect could be seen for DRB1*1301.

Adenocarcinoma↗
PubMed2000

American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation.

Creatine (Cr) supplementation has become a common practice among professional, elite, collegiate, amateur, and recreational athletes with the expectation of enhancing exercise performance. Research indicates that Cr supplementation can increase muscle phosphocreatine (PCr) content, but not in all individuals. A high dose of 20 g x d(-1) that is common to many research studies is not necessary, as 3 g x d(-1) will achieve the same increase in PCr given time. Coincident ingestion of carbohydrate with Cr may increase muscle uptake; however, the procedure requires a large amount of carbohydrate. Exercise performance involving short periods of extremely powerful activity can be enhanced, especially during repeated bouts of activity. This is in keeping with the theoretical importance of an elevated PCr content in skeletal muscle. Cr supplementation does not increase maximal isometric strength, the rate of maximal force production, nor aerobic exercise performance. Most of the evidence has been obtained from healthy young adult male subjects with mixed athletic ability and training status. Less research information is available related to the alterations due to age and gender. Cr supplementation leads to weight gain within the first few days, likely due to water retention related to Cr uptake in the muscle. Cr supplementation is associated with an enhanced accrual of strength in strength-training programs, a response not independent from the initial weight gain, but may be related to a greater volume and intensity of training that can be achieved. There is no definitive evidence that Cr supplementation causes gastrointestinal, renal, and/or muscle cramping complications. The potential acute effects of high-dose Cr supplementation on body fluid balance has not been fully investigated, and ingestion of Cr before or during exercise is not recommended. There is evidence that medical use of Cr supplementation is warranted in certain patients (e.g.. neuromuscular disease); future research may establish its potential usefulness in other medical applications. Although Cr supplementation exhibits small but significant physiological and performance changes, the increases in performance are realized during very specific exercise conditions. This suggests that the apparent high expectations for performance enhancement, evident by the extensive use of Cr supplementation, are inordinate.

Adult↗
PubMed1999

Angiotensin-converting-enzyme gene insertion/deletion polymorphism and response to physical training.

BACKGROUND: The function of local renin-angiotensin systems in skeletal muscle and adipose tissue remains largely unknown. A polymorphism of the human angiotensin converting enzyme (ACE) gene has been identified in which the insertion (I) rather than deletion (D) allele is associated with lower ACE activity in body tissues and increased response to some aspects of physical training. We studied the association between the ACE gene insertion or deletion polymorphism and changes in body composition related to an intensive exercise programme, to investigate the metabolic effects of local human renin-angiotensin systems. METHODS: We used three independent methods (bioimpedance, multiple skinfold-thickness assessment of whole-body composition, magnetic resonance imaging of the mid-thigh) to study changes in body composition in young male army recruits over 10 weeks of intensive physical training. FINDINGS: Participants with the II genotype had a greater anabolic response than those with one or more D alleles for fat mass (0.55 vs -0.20 kg, p=0.04 by bioimpedance) and non-fat mass (1.31 vs -0.15 kg, p=0.01 by bioimpedance). Changes in body morphology with training measured by the other methods were also dependent on genotype. INTERPRETATION: II genotype, as a marker of low ACE activity in body tissues, may conserve a positive energy balance during rigorous training, which suggests enhanced metabolic efficiency. This finding may explain some of the survival and functional benefits of therapy with ACE inhibitors.

Adipose Tissue↗
PubMed1999

Exercise training enhances endothelial function in young men.

OBJECTIVES: The present study was designed to assess whether exercise training can enhance endothelium-dependent dilatation in healthy young men. BACKGROUND: Exercise has been shown to reduce cardiovascular morbidity and mortality, but the mechanisms for this benefit are unclear. Endothelial dysfunction is an early event in atherogenesis, and animal studies have shown that exercise training can enhance endothelial function. METHODS: We have examined the effect of a standardized, 10-week, aerobic and anaerobic exercise training program on arterial physiology in 25 healthy male military recruits, aged 17 to 24 (mean 20) years, of average fitness levels. Each subject was studied before starting, and after completing the exercise program. Baseline vascular reactivity was compared with that of 20 matched civilian controls. At each visit, the diameter of the right brachial artery was measured at rest, during reactive hyperemia (increased flow causing endothelium-dependent dilation) and after sublingual glyceryltrinitrate (GTN; an endothelium-independent dilator), using high-resolution external vascular ultrasound. RESULTS: At baseline, flow-mediated dilatation (FMD) and GTN-mediated dilatation were similar in the exercise and control groups (FMD 2.2+/-2.4% and 2.4+/-2.8%, respectively, p = 0.33; GTN 13.4+/-6.2 vs. 16.7+/-5.9, respectively, p = 0.53). In the military recruits, FMD improved from 2.2+/-2.4% to 3.9+/-2.5% (p = 0.01), with no change in the GTN-mediated dilation (13.4+/-6.2% vs. 13.9+/-5.8%, p = 0.31) following the exercise program. CONCLUSION: Exercise training enhances endothelium-dependent dilation in young men of average fitness. This may contribute to the benefit of regular exercise in preventing cardiovascular disease.

Administration, Sublingual↗
PubMed1999

The stability of free and bound prostate-specific antigen.

OBJECTIVE: To determine if the assay for free prostate specific antigen (fPSA) and the calculated ratio of fPSA to total PSA (f/tPSA) is stable in conditions likely to be met in routine clinical practice. MATERIALS AND METHODS: Two blood samples were obtained from 27 patients attending a routine urology clinic. Sample 1 was centrifuged immediately, assayed for fPSA and tPSA, and the f/tPSA calculated. This sample was then stored at 4 degrees C for 24 h, 48 h and 1 week, or at -20 degrees C for 24 h, 1 week and 1 month before the assays for fPSA and tPSA were repeated. The second sample was left at room temperature for 24 h before assay and processing, as for sample 1. RESULTS: tPSA is a highly stable analyte; if whole blood samples are processed immediately, fPSA is stable for 24 h at 4 degrees C and 1 month at -20 degrees C. There was a significant reduction in the calculated f/tPSA in samples stored for >/=24 h at 4 degrees C (P<0.01); if the sample was stored at -20 degrees C the calculated f/tPSA was stable. After 24 h storage at room temperature, fPSA decreased by 6.3% and f/tPSA by 6.4%. Subsequent storage of serum at 4 degrees C for 1 week resulted in a 25% decrease from the baseline value. After 1 month at -20 degrees C the fPSA value was 13% lower than the baseline value. CONCLUSION: These results indicate that if there is to be confidence in the accuracy of the f/tPSA value, then blood samples must be handled and processed correctly. Total PSA is sufficiently stable to permit whole blood samples to remain at room temperature for 24 h before serum is separated. If fPSA is to be determined accurately then the whole blood sample must be centrifuged promptly. As the fPSA values in blood samples left at room temperature for 24 h are up to 25% lower than those on immediate assay, and the subsequent f/tPSA 29% lower, then for the optimum use of this test, these samples should also be handled appropriately.

Humans↗
PubMed1999

Endothelial dysfunction in Type 2 diabetic subjects with and without microalbuminuria.

AIMS: The primary aim of this study was to determine whether microalbuminuria is associated with endothelial dysfunction in Type 1 diabetes mellitus. The secondary aim was to determine whether any reported biochemical markers of cardiovascular risk are associated with endothelial dysfunction in this group. METHODS: Measurements were made of the vasodilatory responses of the brachial artery to post-ischaemic hyperaemia and to sublingual glyceryl trinitrate (GTN) (causing endothelium-dependent and endothelium-independent dilation, respectively) using a high-resolution ultrasound technique in 18 Type 1 diabetic patients with microalbuminuria, 18 age and sex-matched normoalbuminuric Type 1 diabetic patients and 18 non-diabetic control subjects. RESULTS: There was a significant reduction in flow-mediated dilation (FMD) in microalbuminuric and normoalbuminuric diabetic patients compared with control subjects (2.4% (95% confidence interval (CI) 1.0-3.8%) and 2.3% (95% CI 0.7-3.9%) respectively vs. 6.3% (95% CI 5.1-7.5%), P<0.0001) but no difference in GTN-mediated dilation (14.7% (95% CI 10.7-18.7%) and 15.2% (95% CI 11.2-19.2%) vs. 18.7% (95% CI 16.1-21.3%), P = 0.09). There was no significant difference in FMD, however, between the microalbuminuric group and normoalbuminuric group (P=0.45). FMD was not significantly associated with urinary albumin-creatinine ratio, glycosylated haemoglobin, plasma glucose, lipid or lipoprotein concentrations in diabetic patients. There was a positive correlation between active transforming growth factor (TGF)-beta concentration, a novel biochemical marker of macrovascular disease, and FMD in diabetic patients (r=0.36, P<0.05). GTN-mediated dilation was positively associated with HDL-cholesterol concentration (r = 0.49, P = 0.002) but not with other biochemical variables (including active TGF-beta concentration). Active TGF-beta concentration was not associated with degree of microalbuminuria or other biochemical parameters. CONCLUSIONS: These data suggest that endothelial dysfunction occurs in Type 1 diabetic patients regardless of urine albumin status. Endothelial dysfunction appears therefore to predate the development of microalbuminuria as a marker for the development of coronary artery disease. It is also concluded that low plasma levels of active TGF-beta are associated with an impaired endothelial response and this may provide a useful tool for identifying Type 1 diabetic patients at a greater risk of coronary artery disease.

Adult↗
PubMed1999

Outcomes and costs of a community support worker service for the severely mentally ill.

There has recently been an expansion of paraprofessional staff involved in the provision of care for the severely mentally ill. In this paper we shall evaluate the effects of a community support worker (CSW) service in South London. A sample of patients with severe mental illness receiving the service was assessed over a 6-month period in order to examine the effects of continuing use of CSWs on outcomes, service use and costs. During the study period there were improvements in outcome reflecting service satisfaction, needs, quality of life and social behaviour. Whilst provision of the CSW service did not lead to extra total service costs, service use and cost data suggest that CSWs are associated with the substitution of in-patient use by community-based services.

Adult↗
PubMed1998

Links between social network and quality of life: an epidemiologically representative study of psychotic patients in south London.

Quality of life has been found to be associated with social networks in patients with psychiatric disorders. We aimed to determine whether quality of life was related to social network size in group of severely mentally ill subjects living in the community. In a population-based, prospective controlled study of two sector mental health teams in South London, a random sample of representative 1-year prevalent cases of non-organic psychosis was identified. Patients were interviewed at baseline, and associations between quality of life and social network size were analyzed cross-sectionally. For average quality of life there was increase up to a certain level of social network size (about 20 social contacts). For the quality of life subscore on social relations there appeared to be an optimal middle level of network size (10-12), with lower subscores for smaller and larger networks. Multivariate analysis confirmed the associations between quality of life and social network size. In analyses of network subgroups the importance of confiding contacts was underlined.

Adolescent↗
PubMed1998

Effect of enalapril on endothelial function in young insulin-dependent diabetic patients: a randomized, double-blind study.

OBJECTIVES: We sought to determine whether 6 months of treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril can improve conduit artery endothelial function in young subjects with insulin-dependent diabetes mellitus (IDDM). BACKGROUND: Endothelial dysfunction is an early event in atherogenesis and has been demonstrated in young subjects with IDDM. ACE inhibitors have been shown to enhance conduit artery endothelial function in animal experiments and in patients with established coronary atherosclerosis, although their effect in IDDM is not known. METHODS: Ninety-one subjects (mean age 30.9 years, range 18 to 44) with stable IDDM but no clinical evidence of vascular disease were randomized to receive enalapril (20 mg once daily) (46 subjects) or placebo (45 subjects) in a randomized, double-blind, parallel-group study. Brachial artery flow-mediated dilation (FMD), an endothelium-dependent stimulus, and response to glyceryl trinitrate (GTN), which acts directly on vascular smooth muscle, were assessed noninvasively by means of high resolution external vascular ultrasound at baseline and after 12 and 24 weeks of treatment. RESULTS: FMD was inversely correlated with total cholesterol (r=0.22, p=0.041) but not with any diabetic variables. Treatment with enalapril had no significant effect on FMD (p=0.67) or response to the endothelial-independent dilator GTN (p=0.45). CONCLUSIONS: These data suggest that impairment of endothelial-dependent dilation in young subjects with IDDM is not improved by treatment with the ACE inhibitor enalapril. This lack of improvement may reflect the complex nature of vascular disease in IDDM, which can affect both endothelial and smooth muscle function.

Adolescent↗
PubMed1998

Early endothelial dysfunction in adults at risk from atherosclerosis: different responses to L-arginine.

OBJECTIVES: We sought to examine endothelial responses to L-arginine in three groups with isolated risk factors: hypercholesterolemia, smoking and insulin-dependent diabetes mellitus (IDDM). BACKGROUND: Endothelial dysfunction occurs early in atherosclerosis, predating clinical disease. We hypothesized that the nature of endothelial injury associated with individual cardiovascular risk factors might be different and that this might affect the response to L-arginine, the substrate for endothelial nitric oxide synthase. METHODS: We studied the effects of intravenous L-arginine on brachial artery flow-mediated dilation (FMD) and glyceryl trinitrate (GTN)-mediated dilation in 36 young subjects (18 to 40 years old) without clinical atherosclerosis: 9 each of normal control subjects, hypercholesterolemic subjects, cigarette smokers and subjects with IDDM. RESULTS: Baseline FMD was significantly impaired in hypercholesterolemic subjects (mean +/- SD 1.7 +/- 2.3%), smokers (1.6 +/- 1.8%) and diabetic subjects (1.8 +/- 1.5%) compared with that in control subjects (6.9 +/- 3.3%, p = 0.001). The response to GTN was not significantly different between the subjects with risk factors and control subjects, apart from those with IDDM, in whom it was significantly impaired (p = 0.026). After infusion of L-arginine, there was no change in FMD in control or diabetic subjects. In hypercholesterolemic subjects and smokers, FMD improved from 1.9 +/- 1.9% to 4.1 +/- 2.1% (p = 0.01) and from 2.0 +/- 1.71% to 3.1 +/- 2.5% (p = 0.02), respectively. CONCLUSIONS: FMD was impaired in all three risk factor groups; however, they responded differently to L-arginine, FMD being improved in hypercholesterolemic subjects and smokers but unchanged in diabetic subjects. These results indicate differing underlying pathophysiologies that may facilitate the design of treatment strategies for subjects with different risk factors.

Adolescent↗
PubMed1998

Frequency and predictors of adverse events. PRiSM Psychosis Study. 3.

BACKGROUND: Community care has been criticised as a hazardous policy associated with high rates of adverse events. There is little research evidence as to the truth of this claim. METHOD: Best available evidence from public records, interviews, case notes, key workers and general practitioners was assembled to establish: (a) which of the 514 subjects initially identified as having psychotic illnesses had died during an average follow-up of 4.9 years; (b) care currently received by all 286 subjects originally selected for interview; and (c) rates of major adverse events and of admission for these 286 individuals. RESULTS: Twenty-eight natural and II unnatural deaths had occurred. Among subjects still living at the end of the follow-up, 84% were in contact with specialist mental health services and 11% only with primary care services. Rates of serious violence, imprisonment and homelessness were relatively low. Forty-one per cent had been admitted at least once during a mean follow-up of 3.2 years and 20% at least once under the Mental Health Act. After adjustment, there were no significant differences between standard and intensive care sectors. CONCLUSIONS: Rates of adverse events and 'slipping through the net' are relatively low among individuals receiving community-based services, whether intensive or standard care.

Cause of Death↗
PubMed1998

Impact of community mental health services on users' social networks. PRiSM Psychosis Study. 7.

BACKGROUND: Social networks are important for people with severe mental illness, and services need to assess whether they succeed in improving social contacts. METHODS: In a prospective controlled study, social network data were obtained in an epidemiologically representative sample of people with psychotic disorders both before (Time 1) and two years after (Time 2) the introduction of two sectorised community mental health services in south London (one intensive service with two specialist teams, one standard service with a generic team). RESULTS: There were significant baseline differences between sectors with social networks being smaller in the sector later served by the intensive service. Social network size increased within the intensive service sector, but not in the standard service sector. There was a significant sector effect for the network component of relatives (intensive > standard) and in the other ('non friends') component (standard > intensive) after adjusting for baseline differences. CONCLUSIONS: The findings suggest that the intensive sector community mental health service enhanced people's social networks with their relatives, relative to the standard service. The reverse is the case for other contacts.

Community Mental Health Services↗
PubMed1998

Quality of life outcomes for intensive versus standard community mental health services. PRiSM Psychosis Study. 9.

BACKGROUND: We report the impact on the quality of life (QOL) of people with psychosis of an intensive compared with a standard model of community care. METHOD: People with psychosis, in two sectors in south London, were interviewed with a variety of measures at baseline, and at two-year follow-up (n = 138). After baseline, services within one sector were reorganised, and a more intensive model of community care was introduced. QOL was measured using the Lancashire Quality of Life Profile. RESULTS: The two overall QOL measures, global QOL and the average of the domain-specific scores, were remarkably stable over time. There was weak evidence for an improvement in living situation domain in the intensive sector; this may be accounted for by a large drop in in-patient admissions. In both sectors objective QOL was poor, and there was little change in any of the objective indicators except in-patient admissions, and a suggestion of increased social activity in the intensive sector. CONCLUSIONS: We failed to find an effect of intensive community care on QOL in people with psychosis. This may indicate an insensitivity to change in QOL measures, or that the intervention failed to produce the kind of changes in mental health and functioning which would be reflected in improved QOL.

Adult↗
PubMed1997

Endothelium-dependent dilatation is impaired in young healthy subjects with a family history of premature coronary disease.

BACKGROUND: A family history of premature coronary artery disease (CAD) in a first-degree relative is an independent risk factor for coronary disease. Both genetic and environmental influences are likely to be responsible and may interact, but their relative importance is unclear. METHODS AND RESULTS: We studied endothelial function in 50 first-degree relatives (31 men, 19 women; mean age, 25+/-8 years) of patients (men < or = 45 years, women < or = 55 years) with proven CAD. All subjects were well, lifelong nonsmokers, not diabetic, and not hypertensive and took no medications. Using high-resolution external vascular ultrasound, we measured brachial artery diameter at rest and in response to reactive hyperemia (with increased flow causing an endothelium-dependent vasodilatation) and to sublingual glyceryltrinitrate (GTN, an endothelium-independent dilator). Vascular responses were compared with those of 50 healthy control subjects matched for age and sex. Flow-mediated dilatation (FMD) was impaired in the family history group (4.9+/-4.6% versus 8.3+/-3.5% in control subjects, P<.005). In contrast, GTN caused dilatation in all subjects (family history, 17.1+/-8.8%; control subjects, 19.0+/-6.3%; P=NS), suggesting that reduced FMD was due to endothelial dysfunction. When the family history subjects were subdivided, those found to have a serum cholesterol > 4.2 mmol/L (group A, n=10) had mildly impaired FMD compared with control subjects (5.5+/-5.1% versus 8.3+/-3.5%). In others whose affected relative had coronary risk factors (group B, n=24), FMD was also only slightly reduced (6.2+/-4.8% versus 8.3+/-3.5%). In contrast, subjects with no risk factors and whose affected relative had a normal cardiovascular risk factor profile (group C, n=16) had markedly impaired FMD (2.9+/-3.7% versus 8.3+/-3.5%). Although ANOVA of the three family history subgroups did not reach statistical significance (F=2.55, P=.09), pairwise analysis showed that FMD in group C was significantly impaired compared with group B (P=.026). CONCLUSIONS: Healthy young adults with a family history of premature coronary disease may have impaired endothelium-dependent dilatation, even in the absence of other cardiovascular risk factors. Those subjects, who were free of risk factors and whose affected first-degree relative was free of risk factors, had the most impaired endothelial function, suggesting a genetic influence on early arterial physiology that may be relevant to later clinical disease.

Adult↗
PubMed1997

Association of angiotensin-converting enzyme gene I/D polymorphism with change in left ventricular mass in response to physical training.

BACKGROUND: The absence (deletion allele [D]) of a 287-base pair marker in the ACE gene is associated with higher ACE levels than its presence (insertion allele [I]). If renin-angiotensin systems regulate left ventricular (LV) growth, then individuals of DD genotype might show a greater hypertrophic response than those of II genotype. We tested this hypothesis by studying exercise-induced LV hypertrophy. METHODS AND RESULTS: Echocardiographically determined LV dimensions and mass (n=140), electrocardiographically determined LV mass and frequency of LV hypertrophy (LVH) (n=121), and plasma brain natriuretic peptide (BNP) levels (n=49) were compared at the start and end of a 10-week physical training period in male Caucasian military recruits. Septal and posterior wall thicknesses increased with training, and LV mass increased by 18% (all P<.0001). Response magnitude was strongly associated with ACE genotype: mean LV mass altered by +2.0, +38.5, and +42.3 g in II, ID and DD, respectively (P<.0001). The prevalence of electrocardiographically defined LVH rose significantly only among those of DD genotype (from 6 of 24 before training to 11 of 24 after training, P<.01). Plasma brain natriuretic peptide levels rose by 56.0 and 11.5 pg/mL for DD and II, respectively (P<.001). CONCLUSIONS: Exercise-induced LV growth in young males is strongly associated with the ACE I/D polymorphism.

Adult↗