BACKGROUND: We have investigated the association between serum copper, zinc and selenium concentrations, dietary intake, and demographic characteristics, including individual coronary risk factors, in healthy subjects. METHODS: Serum copper, zinc and selenium were measured by atomic absorption spectrometry in 189 healthy subjects. Serum glutathione peroxidase and caeruloplasmin were also determined for each subject. A previously validated food frequency questionnaire was used to estimate the dietary trace element intake. RESULTS: Male subjects had significantly lower serum copper (P<0.001) and caeruloplasmin (P<0.001), and higher serum zinc (P<0.05) and zinc:copper ratio (P<0.001) than female subjects. Significant differences were observed in serum copper and caeruloplasmin concentrations (P<0.01) with age. Weak but significant associations between dietary trace elements and their serum concentrations were observed for zinc (r=0.18, P=0.02), copper (r=0.17, P=0.03) and selenium (r=0.19, P=0.02). Obese subjects had significantly lower serum concentrations of zinc (P<0.05). In multifactorial analysis, dietary zinc (P<0.05), serum high-density lipoprotein-cholesterol (HDL-C) (P<0.05), diastolic blood pressure (P<0.05) and age (P=0.05) emerged as major predictors of serum zinc concentrations. The corresponding predictors for serum copper were C-reactive protein (CRP) (P<0.001), serum HDL-C (P<0.001), gender (P=0.01), physical activity levels (P<0.05) and dietary copper (P<0.05). Serum selenium concentrations were predicted by serum total cholesterol (P<0.01), serum CRP concentrations (P<0.05) and dietary selenium (P<0.03). CONCLUSION: Serum copper, zinc and selenium concentrations are influenced by physiological conditions such as age, diet and gender. Their serum concentrations are also associated with coronary risk factors, including body mass index, levels of physical activity, serum HDL-C and CRP.

Adult↗

PubMed2004

Mannheim intima-media thickness consensus.

Intima-media thickness (IMT) is increasingly used in clinical trials as a surrogate end point for determining the success of interventions that lower risk factors for atherosclerosis. The necessity for unified criteria to distinguish early atherosclerotic plaque formation from thickening of IMT and to standardize IMT measurements is addressed in this consensus statement. Plaque is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness of > or =1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. Standard use of IMT measurements is recommended in all epidemiological and interventional trials dealing with vascular diseases to improve characterization of the population investigated. The consensus concludes that there is no need to 'treat IMT values' nor to monitor IMT values in individual patients apart from few exceptions. Although IMT has been suggested to represent an important risk marker, it does not fulfill the characteristics of an accepted risk factor. Standardized methods recommended in this consensus statement will foster homogenous data collection and analysis. This will help to improve the power of studies incorporating IMT measurements and to facilitate the merging of large databases for meta-analyses.

Arteriosclerosis↗

PubMed2004

The DNA sequence and comparative analysis of human chromosome 10.

The finished sequence of human chromosome 10 comprises a total of 131,666,441 base pairs. It represents 99.4% of the euchromatic DNA and includes one megabase of heterochromatic sequence within the pericentromeric region of the short and long arm of the chromosome. Sequence annotation revealed 1,357 genes, of which 816 are protein coding, and 430 are pseudogenes. We observed widespread occurrence of overlapping coding genes (either strand) and identified 67 antisense transcripts. Our analysis suggests that both inter- and intrachromosomal segmental duplications have impacted on the gene count on chromosome 10. Multispecies comparative analysis indicated that we can readily annotate the protein-coding genes with current resources. We estimate that over 95% of all coding exons were identified in this study. Assessment of single base changes between the human chromosome 10 and chimpanzee sequence revealed nonsense mutations in only 21 coding genes with respect to the human sequence.

Animals↗

PubMed2004

Pituitary suppression in ultrasound-monitored frozen embryo replacement cycles. A randomised study.

BACKGROUND: This study was designed to assess the value of using a gonadotrophin-releasing hormone (GnRH) agonist prior to exogenous steroid supplementation for endometrial preparation in frozen-thawed embryo replacement (FER) cycles. METHODS: A prospective randomized trial of 234 patients undergoing FER cycles was conducted. The study population was randomly divided into two groups according to a computer-generated list. In group A (n = 117), a daily dose of 6 mg of oral estradiol valerate was initiated on menstrual day 1 following pituitary suppression using 400 mcg buserelin acetate daily. In group B (n = 117), the same dose of estradiol valerate was initiated on day 1 of bleeding without prior GnRH agonist therapy. In both groups, ovulation monitoring was not undertaken and progesterone pessaries (800 mg daily) were administrated when the endometrial thickness had reached 8 mm or more with embryo transfer taking place 2 days later. RESULTS: The two groups were comparable with respect to cause of infertility, age at stimulation (32.8 +/- 4 vs 33.2 +/- 3.9 years, P = 0.4), basal FSH level (6.3 +/- 1.7 vs 6.4 +/- 2 IU/l, P = 0.5), number of oocytes collected (16.9 +/- 7.3 vs 16.5 +/- 7.4, P = 0.7) and fertilized normally in the retrieval cycle (11.5 +/- 4.9 vs 11 +/- 4.9, P = 0.4) and number of embryos cryopreserved (6.6 +/- 3.6 vs 6.2 +/- 3.6, P = 0.3). There was no significant difference between the two groups in age at frozen replacement (33.6 +/- 4.2 vs 34 +/- 3.9 years, P = 0.4), duration of the proliferative phase (20.7 +/- 8.6 vs 21 +/- 9.2 days, P = 0.7) and number of thawed embryos replaced (2.3 +/- 0.6 vs 2.2 +/- 0.6, P = 0.2). However, compared with group B, group A achieved significantly higher pregnancy (37.6% vs 24%, OR 1.8, 95%CI 1.1-3.4), clinical pregnancy (24% vs 11.3%, OR 2.5, 95%CI 1.2-5.5) and live birth rates (20% vs 8.5%, OR 2.9, 95%CI 1.2-8). CONCLUSION: Medicated frozen embryo replacement cycles timed by endometrial thickness measurement alone without monitoring or suppression of ovarian activity are associated with reduced outcome.

Adult↗

PubMed2004

Incidence of hepatitis C virus infection and associated risk factors among Scottish prison inmates: a cohort study.

To gauge the incidence of hepatitis C virus (HCV) infection and associated risk factors among inmates during their imprisonment, the authors recruited adult males in a long-stay Scottish prison into a cohort study between April 1999 and October 2000. On two occasions (at 0 and 6 months), saliva was collected for anonymous HCV antibody testing and risk behavior data were obtained through a self-administered questionnaire. The participation rate was 85% at both initial recruitment (612/719) and follow-up (375/441; 171 men were ineligible for follow-up). For inmates who reported never having injected drugs, ever having injected drugs, having injected drugs during follow-up, and having shared needles/syringes during follow-up, HCV incidences per 100 person-years of incarceration risk were 1, 12, 19, and 27, respectively. Ever having injected drugs (relative risk = 13.0, 95% confidence interval: 1.5, 114.3) and having shared needles/syringes during follow-up (relative risk = 9.0, 95% confidence interval: 1.1, 71.7) were significantly associated with HCV seroconversion. The effectiveness of existing interventions, including the provision of bleach tablets for sterilizing injection equipment, was suboptimal. The development of methadone maintenance programs in prisons and the creation of drug courts to keep offending drug injectors out of prison might help to reduce transmission in this setting.

Adult↗

PubMed2004

Co-occurrence of ADHD and low IQ has genetic origins.

Previous studies show that the symptoms of attention deficit hyperactivity disorder (ADHD) and lower intelligence quotient (IQ) covary in children. We investigated the aetiology of this association in a large population-based sample of 5-year-old twins. The twins were individually assessed on an IQ test, and data on ADHD symptoms were obtained from mother interviews and teacher ratings. Confirming previous studies, the phenotypic correlation between ADHD symptom scores and IQ was -0.3 and, in a categorical analysis, children with a Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) ADHD research diagnosis obtained IQ scores nine points lower, on average, than comparison children. We show here that the co-occurrence of ADHD and lower IQ has genetic origins: 86% of the association between ADHD symptom scores and IQ, and 100% of the association between ADHD diagnosis and IQ, was accounted for by genetic influences that are shared by ADHD and IQ. Some candidate genes for ADHD could also contribute to variation in IQ or vice versa.

Analysis of Variance↗

PubMed2004

Diet but not aerobic exercise training reduces skeletal muscle TNF-alpha in overweight humans.

AIMS/HYPOTHESIS: Our aim was to test the hypothesis that TNF-alpha protein levels in skeletal muscle are important in mediating the improvements in glucose homeostasis that are associated with diet and exercise regimens intended to reduce cardiovascular risk. METHODS: We recruited 20 people with a body mass index of 32.1 +/- 1.2 kg/m2 (mean +/- SEM) and one other component of the metabolic syndrome. The average age was 51.2 +/- 8.1 years (mean +/- SD). Of the 20 subjects, 6 were men and 14 were women. All subjects completed an 8-week control period, followed by randomisation to 8 weeks of moderate cycling exercise (30 min, three times per week) or to a diet with the following characteristics: low in saturated fat, high in fibre, low glycaemic index, rich in complex carbohydrates. RESULTS: Diet induced a small reduction in body mass index (3.0 +/- 0.7%, p<0.05), although weight loss was not intended. Exercise training increased maximum oxygen consumption by 12 +/- 6% (p<0.05). Both interventions reduced fasting plasma insulin levels by about 20%. Diet reduced skeletal muscle TNF-alpha protein by 54 +/- 10% (p<0.05), an effect that was independent (p=0.94 in covariate analysis) of the small concurrent weight loss (-2.8 +/- 0.7 kg). Levels of GLUT4 protein were unchanged in the diet group. In contrast, exercise training did not significantly change TNF-alpha protein expression, but GLUT4 protein expression increased by 105 +/- 37% (p<0.05). CONCLUSIONS/INTERPRETATION: These data indicate that the metabolic benefits of a diet aimed at cardiovascular risk reduction are associated with a decrease in skeletal muscle TNF-alpha protein.

Adult↗

PubMed2004

Quantitative measurement of the stresses induced during polymerisation of bone cement.

When bone cement cures, residual stresses due to bulk and thermal shrinkage will result. Present finite element (FE) simulations of implanted constructs often do not account for these stresses as an initial condition; this may lead to overestimations of the fatigue life of the cement. In the present study, an instrumented stem equipped with strain gauges and a thermocouple was employed to experimentally quantify the residual stresses induced as a result of bone cement curing within a simulated bone/cement/stem construct. Residual stresses as high as 10 MPa were observed in the cement mantle. Residual stresses of this magnitude are potentially high enough to initiate damage within the cement mantle or at the stem/cement interface immediately post-implantation. The acoustic emission technique has demonstrated that cracking and sliding mechanisms are occurring during curing, resulting in partial relaxation of these stresses. The implications for FE simulations of the implanted construct are discussed.

Bone Cements↗

PubMed2004

Role of Gas6/Axl signaling in lens epithelial cell proliferation and survival.

Axl is a receptor tyrosine kinase that is activated by Gas6, a growth factor that belongs to the vitamin K-dependent protein family. Although Gas6 binding to Axl has been shown to transmit mitogenic and/or antiapoptotic signals to a variety of cell types, the role of the Axl-Gas6 system in normal and pathological lens biology is not known. We demonstrate for the first time that Axl protein is expressed in normal rat and bovine lens and that its ligand, Gas6, is present in bovine aqueous humor. In addition, we have detected tyrosine-phosphorylated Axl in normal rat and bovine lens epithelial tissues. We further show that human recombinant Gas6 is able to act as a growth factor in cultured human lens epithelial cells by activating Axl and then the AKT signaling pathway. Gas6 mediates a survival and anti-apoptotic response in cultured human lens epithelial cells subjected to serum-starvation (48-72hr), or treated with transforming growth factor beta1 (5 ng ml(-1), 48hr) or tumor necrosis alpha (100 ng ml(-1), 48hr), as demonstrated by increased number of viable cells, and decreased DNA condensation or caspase-3 activity. In contrast, Gas6 is not able to block apoptosis induced by staurosporin (1microM, 5-24hr) in human lens epithelial cells. Taken together, these data suggest that the Gas6/Axl signaling plays an important role in the control of lens epithelial cell growth and survival and hence in the maintenance of lens homeostasis.

Animals↗