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Biomedical subjects

Andrew Clark

Publications and source records attributed to Andrew Clark.

12 recordsLinked to original sources
PubMed2006

Consistent effects of genes involved in reverse cholesterol transport on plasma lipid and apolipoprotein levels in CARDIA participants.

OBJECTIVE: To identify common variations in genes in the reverse cholesterol transport pathway with nongender-specific influence on plasma lipid and apolipoprotein levels. METHODS AND RESULTS: An average of 5 single nucleotide polymorphisms (SNPs) were genotyped within each of 45 genomic regions (54 genes) in blacks (1131 females and 812 males) and whites (1102 females and 954 males) from the Coronary Artery Risk Development in Young Adults (CARDIA) study. SNPs and gene-based 3-SNP haplotypes were evaluated for their ability to predict variation in plasma apolipoproteins (apo) A-I and apoB, total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides (TG). We identified 14 SNPs in 6 candidate gene regions that explained statistically significant variation in the same trait in both genders of at least one race and with evidence of consistent genotype mean trend across gender within race. Haplotype analyses identified 9 candidate gene regions that explained statistically significant variation in one or both races. CONCLUSIONS: Four gene regions, ABCA1, APOA1/C3/A4/A5, APOE/C1/C4/C2, and CETP, explained plasma lipoprotein variation most consistently across strata. Other gene regions that influence plasma lipid and apolipoprotein levels within race include CYP7A1, LPL, PPARA, SOAT1, and SREBF2.

ATP Binding Cassette Transporter 1↗
PubMed2006

Health changes and smoking: an economic analysis.

This article considers dynamic models of smoking under uncertainty, wherein individuals learn about the associated risks both through experimentation and observation. We use smokers' changes in self-reported health in long-run household panel data as an individualized measure of information about how dangerous smoking is for them. We find that own past health changes while smoking are often positively correlated with current cigarette consumption, implying learning. However, other household members' health changes have only a weak effect. We emphasize individual heterogeneity, using both fixed effects in the analysis of cigarette consumption and age and sex differences in how individuals react to health changes. We conclude that smokers do indeed react to personalized health information (but not necessarily from generalized information) and modify their behavior accordingly. The way in which they react differs sharply by sex and by age, suggesting that aggregate correlations may be misleading.

Adult↗
PubMed2006

Extensive introgression of mitochondrial DNA relative to nuclear genes in the Drosophila yakuba species group.

Studies of gene flow between recently diverged species can illuminate the role of natural selection in the formation of new species. Drosophila santomea and D. yakuba are recently diverged, partially reproductively isolated species that continue to hybridize in the wild, and appear to be reproductively isolated from the more distantly related species D. teissieri. We examine patterns of nucleotide polymorphism and divergence in these three species at multiple X-linked, Y-linked, and mitochondrial markers. All three species harbor drastically reduced variability on the Y chromosome relative to the X, as expected for a nonrecombining chromosome subject to variation-reducing selection. The three species are generally well differentiated at the nuclear markers, with little evidence for recent introgression for either the X- or Y-linked genes. Based on the nuclear genes, we estimate that D. santomea and D. yakuba diverged about one-half million years ago and split from D. teissieri about one million years ago. In contrast to the pattern at nuclear loci, all three species share a very similar mtDNA haplotype. We show that the mtDNA must have recently introgressed across species boundaries in the D. yakuba subgroup and that its fixation was driven by either selection on the mitochondria itself or other cytoplasmic factors. These results demonstrate that different regions of the genome can have distinct evolutionary dynamics in the context of species formation. Although natural selection is usually thought of as accentuating divergence between species, our results imply that it can also act as a homogenizing force.

Animals↗
PubMed2005

Prolonged electrical muscle stimulation exercise improves strength and aerobic capacity in healthy sedentary adults.

This investigation evaluated training responses to prolonged electrical muscle stimulation (EMS) in sedentary adults. Fifteen healthy subjects (10 men, 5 women) with a sedentary lifestyle completed a 6-wk training program during which they completed an average of 29 1-h EMS sessions. The form of EMS used by the subjects was capable of eliciting a cardiovascular exercise response without loading the limbs or joints. It achieved this by means of inducing rapid, rhythmical contractions in the large leg muscles. A crossover study design was employed with subjects undergoing their habitual activity levels during the nontraining phase of the study. The training effect was evaluated by means of a treadmill test to determine peak aerobic capacity [peak oxygen consumption (Vo(2))], a 6-min walking distance test, and measurement of body mass index (BMI) and quadriceps muscle strength. At baseline, the mean values for peak Vo(2), 6-min walking distance, quadriceps strength, and BMI were 2.46 +/- 0.57 l/min, 493.3 +/- 36.8 m, 360.8 +/- 108.7 N, and 26.9 +/- 3.4 kg/m(2), respectively. After training, subjects demonstrated statistically significant improvements in all variables except BMI. Peak Vo(2) increased by an average of 0.24 +/- 0.16 l/min (P < 0.05), walking distance increased by 36.6 +/- 19.7 m (P < 0.005), and quadriceps strength increased by 87.5 +/- 55.9 N (P < 0.005); we did not observe a significant effect due to training on BMI (P > 0.05). These results suggest that EMS can be used in sedentary adults to improve physical fitness. It may provide a viable alternative to more conventional forms of exercise in this population.

Adaptation, Physiological↗
PubMed2005

Electrical stimulation of unloaded muscles causes cardiovascular exercise by increasing oxygen demand.

BACKGROUND: The development of new strategies to encourage increased levels of physical activity can help to reduce the incidence of cardiovascular disease. A new system of electrical muscle stimulation (EMS) has been developed that attempts to cause an increase in energy expenditure by mimicking the action of shivering in the body. The purpose of this study was to show that this form of EMS is capable of eliciting a cardiovascular exercise response in healthy adults. DESIGN: An observational study. METHODS: Ten healthy volunteers completed a maximal treadmill test and four EMS sessions using a hand-held EMS device that delivered current to the body via five silicone rubber electrodes on each leg. At each session subjects completed 3 min stimulation at each of four stimulation outputs (10, 20, 30 and 40% of maximum output) while cardiopulmonary gas exchange and heart rate (HR) were measured. Physiological responses at increasing levels of stimulation were evaluated. RESULTS: Average (+/-SD) HR and oxygen consumption (VO2) levels of 67+/-11 bpm and 4.7+/-1.2 ml/kg per min at rest, respectively, were increased to 186+/-10 bpm and 44.9+/-9.8 ml/kg per min at peak exercise intensity on treadmill testing. The electrical stimulation was generally well tolerated by the subjects. Subjects demonstrated statistically significant increases in all physiological variables measured with successive increases in stimulation intensity. Peak HR and VO2 at 40% stimulation intensity were 101+/-12 bpm and 14.9+/-4.3 ml/kg per min, respectively. CONCLUSIONS: These results demonstrate that this form of EMS is capable of producing a physiological response consistent with cardiovascular exercise at mild to moderate intensities. It achieves this without producing gross movement of the limbs or loading of the joints. This EMS-induced cardiovascular exercise response could be used to promote increased levels of physical activity in populations unable to participate in voluntary exercise.

Adaptation, Physiological↗
PubMed2003

Update of clinical trials from the American College of Cardiology 2003. EPHESUS, SPORTIF-III, ASCOT, COMPANION, UK-PACE and T-wave alternans.

The American College of Cardiology provided much useful new information to inform those who care for patients with heart failure about what they should and should not adopt into current clinical practice. The EPHESUS trial suggests a much wider role for aldosterone antagonists for the management of heart failure and left ventricular systolic dysfunction. SPORTIF-III indicates we may have a safer, simpler warfarin substitute soon. ASCOT reinforces the potential futility of statin therapy unless it is well targeted. The results of the COMPANION study investigating cardiac resynchronisation devices and implantable defibrillators were encouraging but inconclusive and/or hard to interpret. UK-PACE again questions the use of dual chamber pacing. T-wave alternans is an interesting experimental technique that may be useful in selecting which patients need an implantable defibrillator, although the technology needs testing in an appropriate patient population.

Anticoagulants↗
PubMed2003

Control of the expression of inflammatory response genes.

The expression of genes involved in the inflammatory response is controlled both transcriptionally and post-transcriptionally. Primary inflammatory stimuli, such as microbial products and the cytokines interleukin-1 (IL-1) and tumour necrosis factor alpha (TNF alpha), act through receptors of either the Toll and IL-1 receptor (TIR) family or the TNF receptor family. These cause changes in gene expression by activating four major intracellular signalling pathways that are cascades of protein kinases: namely the three mitogen-activated protein kinase (MAPK) pathways, and the pathway leading to activation of the transcription factor nuclear factor kappa B (NF kappa B). The pathways directly activate and induce the expression of a limited set of transcription factors which promote the transcription of inflammatory response genes. Many of the mRNAs are unstable, and are stabilized by the p38 MAPK pathway. Instability is mediated by clusters of the AUUUA motif in the 3' untranslated regions of the mRNAs. Control of mRNA stability provides a means of increasing the amplitude of a response and allows rapid adjustment of mRNA levels. Not all mRNAs stabilized by p38 contain AUUUA clusters; for example, matrix metalloproteinase-1 and -3 mRNAs lack these clusters, but are stabilized. Inflammatory gene expression is inhibited by glucocorticoids. These suppress MAPK signalling by inducing a MAPK phosphatase. This may be a significant mechanism additional to that by which the glucocorticoid receptor interferes with transcription factors.

Animals↗
PubMed2002

Do health changes affect smoking? Evidence from British panel data.

This paper uses seven waves of British Household Panel Survey (BHPS) data to examine the link between health developments while smoking (both one's own and those of other smokers in the same household) and future cigarette consumption. We find those whose health worsens when smoking smoke less in the future, and are more likely to quit. This correlation is consistent with both a Grossman model of health demand (where all parameters are known) and with learning about the health consequences of smoking (where there is uncertainty). There is little effect on smoking from health developments amongst other smokers in the same household. As such, impersonal information provision may have less of an effect on smoking than the delivery of personalised health information, for example through the medical profession.

Adult↗
PubMed2002

Vascular recruitment in skeletal muscle during exercise and hyperinsulinemia assessed by contrast ultrasound.

The purpose of this study was to noninvasively quantify the effects of insulin on capillary blood volume (capBV) and RBC velocity (V(RBC)) in skeletal muscle in vivo with the use of contrast-enhanced ultrasound. We performed contrast ultrasound of the rat hindlimb adductor muscles at baseline and after 2-h infusions of either insulin (3 or 40 mU x kg(-1) x min(-1)) or saline. Saline-treated animals were also studied during contractile exercise. V(RBC) and capBV were calculated from the relation between pulsing interval and video intensity. Femoral artery blood flow, measured by a flow probe, increased with both contractile exercise and insulin. Contractile exercise increased capBV more than twofold and V(RBC) fivefold. Insulin also increased capBV more than twofold in a dose-dependent fashion but did not significantly alter V(RBC). Saline infusion did not significantly alter capBV, V(RBC), or femoral artery blood flow. We conclude that physiological changes in skeletal muscle capillary perfusion can be assessed in vivo with the use of contrast-enhanced ultrasound. Exercise increases both V(RBC) and capBV, whereas hyperinsulinemia selectively increases only capBV, which may enhance skeletal muscle glucose uptake.

Animals↗
PubMedDate not supplied

Is sensible use being made of an inpatient Holter monitoring and transthoracic echocardiogram service within acute medicine?

Transthoracic echocardiograms (TTE) and 24-hour Holter recordings are commonly requested investigations for patients presenting with symptoms thought to be due to underlying cardiac pathology. The objective of this study was to audit the use of inpatient TTE and Holter monitors in acute medical patients under the care of physicians other than cardiologists within a tertiary cardiology referral centre. This was accomplished by a retrospective analysis of 4,623 TTE and 3,145 Holters reported by cardiologists between 8 October 1999 and 3 November 2005. The age range for Holter monitoring was 16-104 years, mean 70 (SD 18) years. The age range for TTE was 16-101 years, mean 68 (SD 17) years. Of the Holters performed, 69.1% were within normal limits. Atrial fibrillation/flutter was the commonest arrhythmia, found in 787 patients (25.0%). A total of 99 patients were referred to a cardiologist; 47 of these patients were permanently paced. Of the TTE requests to assess left ventricular function, 44.8% were normal. A cardiac source of embolism was found in 1.8% of requests to assess for this. TTE requests for infective endocarditis confirmed the diagnosis in 4.1% of patients. Holter investigation and TTE were commonly requested investigations; a large proportion of both, however, were within normal limits. This suggests that more consideration is required before making the request for Holter investigation and TTE, as more appropriate investigations may be available.

Adolescent↗