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Biomedical subjects

A Donald

Publications and source records attributed to A Donald.

At least 19 recordsLinked to original sources

Genetic consequences of human management in an introduced island population of red deer (Cervus elaphus).

We investigated phylogeography and spatial genetic structure in an introduced island population of red deer (Cervus elaphus) on the Isle of Rum, Scotland, experiencing spatial variation in management regime. Five different mitochondrial DNA (mtDNA) haplotypes were present among female red deer on Rum. These comprised two phylogenetically divergent groups, one of which clustered with red deer from Sardinia and North Africa, while the other four grouped with other Western European red deer. Recent and historical red deer management practices explain this result. The Rum population is descended from recent introductions from at least four different UK mainland populations, and translocation of red deer within the UK and across Europe is well documented. We found significant spatial genetic structure across Rum in both mtDNA haplotypes and microsatellite markers. Mitochondrial spatial structure was over an order of magnitude greater than structure in nuclear markers. This extreme difference is explained by the fact that the Rum population was introduced from different source populations, the highly male-biased dispersal patterns of red deer and the much smaller effective population size of mitochondrial compared to nuclear markers. Spatial structure in mtDNA conformed to a pattern of isolation by distance, while nuclear DNA did not. Apparent structure in the nuclear markers was driven by differences between the North Block and the rest of the island. We suggest that recent differences in the management regimes in different parts of the island have led to differences in effective male migration that would account for this observation.

Animal Migration↗

Superficial wrinkles in stretched, drying gelatin films.

When a thin film of initially hydrated gelatin is allowed to dry from the surface, superficial changes in the structure of the material affect the local mechanical properties of the drying region. If the film is simultaneously subjected to large strain deformation (above 20%), a periodic pattern of wrinkles appears on the surface of the gelatin along the length of the sample in the direction of the applied force. These wrinkles are uniformly distributed on the surface of the gelatin with a wavelength that is much smaller than the sample thickness, which changes with sample composition, aging time, and deformation rate. We investigate these patterns via in situ environmental scanning electron microscopy (ESEM) and provide a theory for their origin.

Chemistry, Physical↗

Rapidly declining fine-scale spatial genetic structure in female red deer.

A growing literature now documents the presence of fine-scale genetic structure in wild vertebrate populations. Breeding population size, levels of dispersal and polygyny--all hypothesized to affect population genetic structure--are known to be influenced by ecological conditions experienced by populations. However the possibility of temporal or spatial variation in fine-scale genetic structure as a result of ecological change is rarely considered or explored. Here we investigate temporal variation in fine-scale genetic structure in a red deer population on the Isle or Rum, Scotland. We document extremely fine-scale spatial genetic structure (< 100 m) amongst females but not males across a 24-year study period during which resource competition has intensified and the population has reached habitat carrying capacity. Based on census data, adult deer were allocated to one of three subpopulations in each year of the study. Global F(ST) estimates for females generated using these subpopulations decreased over the study period, indicating a rapid decline in fine-scale genetic structure of the population. Global F(ST) estimates for males were not different from zero across the study period. Using census and genetic data, we illustrate that, as a consequence of a release from culling early in the study period, the number of breeding females has increased while levels of polygyny have decreased in this population. We found little evidence for increasing dispersal between subpopulations over time in either sex. We argue that both increasing female population size and decreasing polygyny could explain the decline in female population genetic structure.

Animals↗

Does oral folic acid lower total homocysteine levels and improve endothelial function in children with chronic renal failure?

BACKGROUND: Accelerated vascular disease is common in chronic renal failure (CRF) and accounts for significant mortality and morbidity. Elevated homocysteine levels may contribute by an effect on endothelial function. METHODS AND RESULTS: We performed a double-blind placebo-controlled randomized crossover trial of folic acid at 5 mg/m2 in 25 normotensive children 12+/-3 (7 to 17) years of age with CRF (glomerular filtration rate 26.8+/-13.2 mL/min per 1.73 m2) of noninflammatory etiology. Each subject underwent two 8-week periods of folic acid and placebo separated by an 8-week washout period. The effect of folic acid on homocysteine levels, LDL oxidation, and both endothelial-dependent and -independent vascular function were measured. After oral folic acid, serum folate levels rose from 11.7+/-4.25 to 635+/-519 microg/L (P=0.001), red cell folate levels rose from 364+/-195 to 2891+/-2623 microg/L (P<0.001), and total homocysteine levels fell from 10.28+/-4.16 to 8.62+/-2.32 micromol/L (P=0.03). In addition, there was a significant improvement in flow-mediated dilatation (FMD) (endothelial-dependent dilatation) from 7.21+/-2.8% to 8.47+/-3.01% (P=0.036) with no change in response to glyceryl trinitrate (endothelial-independent dilatation). There was no significant change in FMD or glyceryl trinitrate during the placebo phase. There was, however, no significant difference in final FMD after placebo or folic acid. Lag times for LDL oxidation were prolonged during the treatment phase (58.4+/-18.7 to 68.1+/-25.9 minutes, P=0.01). CONCLUSION: Folic acid supplementation in children with CRF may improve endothelial function with an increased resistance of LDL to oxidation.

Administration, Oral↗

Vascular dysfunction after repair of coarctation of the aorta: impact of early surgery.

BACKGROUND: Patients with repaired coarctation are at increased risk of hypertension and cardiovascular disease despite successful repair. We studied the function of conduit arteries in upper and lower limbs of patients late after successful coarctation repair and its relation to age at surgery. METHODS AND RESULTS: Flow-mediated dilatation (FMD) and the dilatation after sublingual nitroglycerin (NTG, 25 microgram) were measured by using high-resolution ultrasound in the brachial artery in 64 coarctation patients (44 males and 20 females, aged 19+/-10 years; median age at operation 4 months) and 45 control subjects (28 males and 17 females, aged 19+/-10 years) and in the posterior tibial artery in 37 patients and 22 control subjects. Arterial stiffness was determined by pulse-wave velocity (PWV) of the brachioradial and femoral-dorsalis pedis tracts. Patients, compared with control subjects, had lower brachial FMD (7.16+/-3.4% versus 8.62+/-2.3%, respectively; P=0.02) and NTG (11.46+/-4.3% versus 13.21+/-4.6%, respectively; P=0.046) and higher brachioradial PWV (9.17+/-3.1 versus 8.06+/-1.9 m/s, respectively; P=0.05). In contrast, posterior tibial FMD, NTG, and lower limb PWV were comparable. Age (months) at the time of repair was related to brachioradial PWV (r=0.42, P=0.002) but not to brachial FMD or NTG. CONCLUSIONS: Patients with repaired aortic coarctation have impaired conduit artery function, with abnormal responses to flow and NTG, and increased vascular stiffness confined to the upper part of the body. Early repair is associated with preserved elastic properties of conduit arteries, but reduced reactivity remains.

Adult↗

Contribution of self-reported health ratings to predicting frailty, institutionalization, and death over a 5-year period.

Cross-sectional data from Phase 1 of the Canadian Study of Health and Aging was used to examine the relationship between two self-report health measures: "How would you say your health is these days?"(HEALTH) and "How much do your health troubles stand in the way of your doing the things you want to do?"(TROUBLE). The contribution of these measures to predictive models for institutionalization and mortality is examined, using linked data from Phases 1 and 2. Their relationship to a proposed frailty measure is also examined. At CSHA-1, a majority of respondents perceived that they were in good health and did not feel that their health problems interfered with their preferred activities. At all frailty levels, a majority of both males and females rated their health as "very good" or "pretty good." As frailty increased, health problems increasingly interfered with normal activities. Logistic regression of the longitudinal data indicated that, despite their correlation, HEALTH and TROUBLE cannot act as proxies for each other. They appear to predict independently; adding one to the other significantly improved prediction of institutionalization and mortality.

Activities of Daily Living↗

The Wal-Marting of American psychiatry: an ethnography of psychiatric practice in the late 20th century.

OBJECT: U.S. psychiatry has been radically reorganized by changes in the way the psychiatric hospital, the asylum, is funded. The imposition and internalization of cost control measures are major elements of this reorganization. This paper traces the ways in which cost control methods associated with managed care have produced new ways of organizing and patterning clinical work and clinical knowledge. METHODS: Participant observation, used in qualitative sociological research, was undertaken in three settings: a public hospital, a private hospital with roots in the history of the asylum, and a for-profit hospital chain. The research consisted of observation of usual clinic practices and interviews with clinicians and ancillary staff, such as utilization reviewers, concerning their construction of and understandings about their work experience. In addition, interviews with personnel at a number of managed care companies was arranged although actual ethnographic experience was not performed in these companies due to declined permission. Interviews included clinicians whose experiences bridged the pre- and post-managed care eras. RESULT: This paper argues that the widespread adoption of Quality Assurance and Utilization Management procedures has created new standards of evaluation and treatment. These standards grow out of a transition from a person-centered to a population-based data base. They are justified by a conviction on the part of managed care proponents that good clinical treatment is equivalent to efficient cost control. This epistemological change results in the development of a clinical knowledge patterned along algorithmic pathways rather than subjective understanding. An increased and more rapid rationalization of psychiatry is the result. This rationalization process has produced moral dilemmas for practicing clinicians as they struggle to redefine their professional purposes and identities within a new order. CONCLUSION: The rise of the 'Quality Movement' has led to the reconstruction of clinical knowledge as a result of the imposition of social practices influenced by the cultural consequences of capitalism. A peculiarly American psychiatry is the result.

Algorithms↗

Dialysis improves endothelial function in humans.

BACKGROUND: Circulating inhibitors of endothelial function have been implicated in the pathogenesis of vascular disease in chronic renal failure. The aim of this study was to determine if lowering the plasma concentration of these and other dialysable toxins improves endothelial function. To do this we compared the acute effects on endothelial function of single episodes of haemodialysis with automated peritoneal dialysis. We hypothesized that endothelial function would improve after dialysis, with a greater effect seen after haemodialysis due to more substantial clearance of endothelial toxins per-treatment. METHODS: Subjects with end-stage renal failure undergoing haemodialysis (n=16) or automated peritoneal dialysis (n=14) were investigated. Endothelial function was determined using vascular ultrasound to measure flow-mediated dilatation of the brachial artery and was compared with the dilatation caused by sublingual glyceryl trinitrate. Endothelial function was assessed before and after a single dialysis treatment. Plasma concentrations of the inhibitors of endothelial function, asymmetric dimethyl-l-arginine and homocysteine were measured. Flow-mediated dilatation was expressed as percentage change from basal diameter and analysed using Student's t test. RESULTS: The plasma concentration of circulating inhibitors of endothelial function was reduced after haemodialysis but not peritoneal dialysis. Haemodialysis increased flow-mediated dilatation from 4.0+/-1.0% to 5.8+/-1.2% (P<0.002). These changes persisted for 5 h but returned to baseline by 24 h. Automated peritoneal dialysis had no acute effect on flow-mediated dilatation (5.9+/-1.1% vs 5.4+/-0.8% after, P>0.5). There were no effects of either dialysis modality on dilatation to glyceryl trinitrate. CONCLUSIONS: Short-term reduction of circulating inhibitors of endothelial function by haemodialysis is associated with increased flow-mediated dilatation. These data suggest that dialysable endothelial toxins have deleterious effects on endothelial function that are rapidly reversible.

Adult↗

Underestimation of the importance of homocysteine as a risk factor for cardiovascular disease in epidemiological studies.

BACKGROUND: In epidemiological studies, within-person variability in plasma total homocysteine (tHcy) measurements may dilute the association of 'usual' levels of tHcy with risk of cardiovascular disease, referred to as 'regression dilution'. The aim of this report was to estimate the magnitude of regression dilution after varying intervals of follow-up. METHODS: Regression dilution ratios (RDR) for tHcy were calculated using replicate tHcy measurements obtained after 3, 6 and 8 years from the Rotterdam, Hordaland and Framingham studies, respectively, and after 3, 6, 9 and 12 years from the United Kingdom Prospective Study of type 2 Diabetes Mellitus (UKPDS). RESULTS: The RDR for tHcy decreased with increasing interval in the three population-based studies and in the UKPDS. Moreover, the rate of decline of the RDR in the population-based studies was similar to that obtained in the UKPDS. Using linear regression analysis for the population-based studies, these results suggest an RDR of 0.83 at 2 years, 0.71 at 6 years and 0.53 at 12 years. CONCLUSIONS: These results have important implications for the interpretation of prospective studies of tHcy and cardiovascular disease. Failure to correct for increasing regression dilution using lower RDRs for longer follow-up may underestimate the relative risks of cardiovascular disease associated with tHcy by about one-fifth after 2 years and one-half after 10 years.

Aged↗

Evaluating screening tests for dementia and cognitive impairment in a heterogeneous population in the presence of verification bias.

This article reviews two potentially serious sources of error in the evaluation of screening tests, namely, verification bias and the influence of demographic covariates. It demonstrates how to deal with these problems statistically. Verification bias arises when not all subjects receive a definitive diagnosis following a screening test. If only a small proportion of those who screen negative are sent for diagnosis, the calculated test sensitivity is an overestimate and the calculated specificity an underestimate. The methodology outlined in this article may be extended to psychological and medical screening tests in general.

Aged↗

Effects of streptozotocin-induced diabetes on neuronal sigma receptors in the rat brain.

To study the effect of diabetes mellitus on the density of sigma receptors, in vitro binding experiments were conducted in whole brain homogenate membranes of 5-week and 10-week control rats and streptozotocin (STZ)-induced diabetic rats. sigma-1 Receptors were labelled with [3H](+)-pentazocine while sigma-2 receptors were labelled with [3H] 1,3-di-o-tolylguanidine (DTG) in the presence of 0.5 microM (+)-pentazocine to mask sigma-1 sites. Non-specific binding was determined in the presence of 20 microM haloperidol. Scatchard analysis revealed a 27% (p<0.01) decreased in sigma-1 receptor density and a 33% (p<0.01) decreased in sigma-2 receptor density in whole brain of 10-week STZ-diabetic rats. No statistically significant difference was found in the sigma receptor content of 5-week STZ-diabetic rats. These results provide evidence that neuronal sigma receptors are reduced in 10-week STZ-diabetic rats and suggest that changes in sigma receptors may play a role in diabetes related abnormalities. Further evaluation is required to determine whether changes observed in the brain are homogeneous for either or both sigma receptor subtypes as well as potential links between other CNS receptor changes previously observed in STZ-induced diabetic rats.

Analgesics, Opioid↗

Evidence-based practice. Data day.

A project assessing the feasibility of using research data in routine clinical practice showed that most clinicians found it too time-consuming. Obtaining relevant research articles took an average of three days with an on-site library, and a week without one. The most serious barrier was the poor state of the information itself. Investment should focus on developing the information, followed by effective and easy-to-use search methods.

Attitude of Health Personnel↗

Blood lipids and endothelial function in glycogen storage disease type III.

We have assessed early indicators of arterial disease in patients with glycogen storage disease type III (GSD III; McKusick 232400), investigating the plasma lipid and lipoprotein profile and endothelial function. Eleven patients, aged 10-39 years, were recruited together with age-, sex- and smoking status-matched controls. Brachial artery responses were assessed by high-resolution ultrasonographic measurement of the diameter of the brachial artery at baseline, after reactive hyperaemia and in response to sublingual glyceryl trinitrate (GTN). The means of plasma cholesterol (total and HDL and LDL subfractions), triglycerides, apo-A1, apo-B, Lp(a) and the atherogenic index were similar in both groups. Cardiac troponin I was below the lower limits of detection (< 0.03 g/L) in all subjects. The GSD III patients had similar body mass index (BMI) and brachial artery diameter to the control group (BMI 22.6 +/- 5.6 vs 22.3 +/- 5 kg/m2; brachial artery diameter 3.4 +/- 0.5 vs 3 +/- 0.7 mm). When compared to the baseline diameter, the maximal flow-mediated dilatation of the brachial artery after reactive hyperaemia was 9.3% +/- 2.1% (mean +/- SD) in the GSD III patients and 6.5% +/- 3.5% in the control group, a difference of 1.8% (95% CI 0.07% to 5.5%). The maximal dilatation of the brachial artery after GTN administration was 18.3% +/- 6.4% in the GSD III patients and 17.9% +/- 6.5% in the control group, a difference of 0.4% (95% CI-6.9% to 7.7%). In conclusion, we found no evidence of abnormal plasma lipid and lipoprotein profile or endothelial dysfunction in patients with GSD III. They are unlikely to be at increased risk of premature atherosclerosis.

Adolescent↗

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↗

Determinants of the response of human blood vessels to nitric oxide donors in vivo.

The potency of the nitric oxide (NO) donors glyceryltrinitrate (GTN) and 3-morpholinosydnonimine was compared in human dorsal hand veins, the radial artery, and the forearm resistance vessels. NO donors were more potent in veins and the radial artery (vessels with minimal basal NO-mediated dilatation) than in the resistance vascular bed (where basal NO is a major determinant of vascular tone). In contrast, 8-bromoguanosine 3',5'-cyclic monophosphate (a cGMP mimetic) was approximately equipotent in resistance arteries and veins and was less potent in the radial artery. Inhibition of phosphodiesterase V with dipyridamole did not alter the arteriovenous profile of GTN. Increasing the local concentration of NO in veins (by infusing sodium nitroprusside) reduced their sensitivity to GTN but not to 8-bromoguanosine 3',5'-cyclic monophosphate. Conversely, reducing endogenous NO production in the resistance vasculature led to time-dependent increases in the response to GTN. These data suggest that soluble guanylate cyclase rather than cGMP-dependent protein kinase or phosphodiesterase V is the site in the second messenger pathway that determines the arteriovenous profile of NO donors. Moreover, the sensitivity of soluble guanylate cyclase to NO donors might be regulated by the ambient concentration of NO, with increased local NO down-regulating the dilator response to NO donors.

Adult↗