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Biomedical subjects

K Wilson

Publications and source records attributed to K Wilson.

At least 37 records · Page 2Linked to original sources

Hepatitis C virus among self declared non-injecting sexual partners of injecting drug users.

While much is known about hepatitis C virus (HCV) among injecting drug users (IDUs), there is scant information about the risk of HCV infection to non-injecting sexual partners of injecting drug users; it is possible that such individuals may have a greater risk of acquiring HCV than any other group barring injecting drug users. This study examines the prevalence of HCV among a population of non-injecting sexual partners of injecting drug users. Unlinked anonymous testing for anti-HCV of residual sera stored following the named HIV testing of specimens originally from persons who had indicated to their attending clinicians that they were non-injecting sexual partners of injecting drug users. The prevalence of anti-HCV among the sexual partners was 4.1% (25/611) overall, 6.4% (13/202) among heterosexual male and 3.0% (12/397) among the heterosexual female partners. None of the homosexual/bisexual partners were HCV antibody positive (0/12). Although we cannot be sure how non-injecting partners of injecting drug users acquire their HCV infection, having a relationship with someone who injects drugs may place an individual at appreciable risk of being infected; such individuals should consider being tested for HCV.

Adult↗

Costs of resistance: genetic correlations and potential trade-offs in an insect immune system.

Theory predicts that natural selection will erode additive genetic variation in fitness-related traits. However, numerous studies have found considerable heritable variation in traits related to immune function, which should be closely linked to fitness. This could be due to trade-offs maintaining variation in these traits. We used the Egyptian cotton leafworm, Spodoptera littoralis, as a model system to examine the quantitative genetics of insect immune function. We estimated the heritabilities of several different measures of innate immunity and the genetic correlations between these immune traits and a number of life history traits. Our results provide the first evidence for a potential genetic trade-off within the insect immune system, with antibacterial activity (lysozyme-like) exhibiting a significant negative genetic correlation with haemocyte density, which itself is positively genetically correlated with both haemolymph phenoloxidase activity and cuticular melanization. We speculate on a potential trade-off between defence against parasites and predators, mediated by larval colour, and its role in maintaining genetic variation in traits under natural selection.

Analysis of Variance↗

Hepatitis C virus among childbearing women in Scotland: prevalence, deprivation, and diagnosis.

OBJECTIVES: (A) To examine the prevalence and demographic characteristics of hepatitis C virus (HCV) infection among childbearing women in Scotland; and (B) to determine the extent of maternal HCV infection diagnosed prior to birth. METHODS: (A) Residual dried blood spot samples from routine neonatal screening, collected throughout Scotland during March-October 2000, were unlinked from identifiers and tested anonymously for HCV antibodies; and (B) electronic record linkage of Scotland's databases of births and diagnosed HCV infections was performed. RESULTS: (A) Of 30,259 samples, 121 were enzyme linked immunosorbent assay repeat reactive and 88 of these were confirmed as anti-HCV positive in the recombinant immunoblot assay, representing a seroprevalence of 0.29-0.40%. HCV seroprevalence was high among 25-29 year olds (0.4-0.57%), in high deprivation areas (0.92-1.07%), and in Greater Glasgow (0.83-0.96%) and Grampian (0.38-0.62%). Adjusted relative risk for HCV infection was highest among residents in high deprivation areas of Glasgow (7.2 (95% confidence interval 2.0-25.5)). (B) Of 121 HCV infections found among women at delivery, 24% and 46% were estimated to have been diagnosed prior to pregnancy and birth, respectively. CONCLUSIONS: HCV prevalence among Scottish childbearing women is consistent with that expected from injecting drug use. Based on reported rates of mother to child transmission, 8-11 paediatric infections are expected per annum. Diagnosis in only 24% of infected women prior to pregnancy indicates the extent to which HCV goes unrecognised in the injecting community. The current HCV screening approach-to test only those with a history of injecting drug use (or other risk factors for infection)-identifies approximately a quarter of previously undetected infections among pregnant women.

Adult↗

Linking perceptions of neighbourhood to health in Hamilton, Canada.

STUDY OBJECTIVE: To investigate the association between perceptions of neighbourhood physical and social characteristics and three health outcomes (self assessed health status, chronic conditions, and emotional distress). DESIGN: Cross sectional survey data analysed in small neighbourhoods. SETTING: Hamilton, Ontario, Canada, a medium sized industrial city, located at the western end of Lake Ontario (population at the time of the study about 380 000). PARTICIPANTS: Random sample of 1504 adults aged 18 years and older residing in four contrasting neighbourhoods. MAIN RESULTS: Significant differences across the four neighbourhoods are apparent in self assessed health status and emotional distress, but not in chronic conditions. Neighbourhoods with lower SES reported poorer health and more emotional distress. Perceptions of the physical environment dominated social concerns in all neighbourhoods. For all three health outcomes, individual risk factors followed expectations, with measures of poverty, age, and lifestyle all significantly associated with poor health outcomes. Physical environmental problems were positively and significantly associated with poor physical and emotional health. Specifically, people reporting they dislike aspects of their neighbourhood's physical environment are 1.5 times more likely to report chronic health conditions (OR 1.56, 95% CI 1.19 to 2.05), while those reporting physical likes with their neighbourhood are less likely to report fair/poor health (OR 0.50, 95% CI 0.28 to 0.90) or emotional distress (OR 0.45, 95% CI 0.26 to 0.80). CONCLUSIONS: These results demonstrate the importance of neighbourhood perceptions as a determinant of health, as well as conventional factors such as low income, lifestyle, and age. The dominance of physical environmental concerns may have arisen from the industrial nature of Hamilton, but this result merits further investigation.

Adolescent↗

Soay rams target reproductive activity towards promiscuous females' optimal insemination period.

Female promiscuity is thought to have resulted in the evolution of male behaviours that confer advantages in the sperm competition that ensues. In mammalian species, males can gain a post-copulatory advantage in this sperm 'raffle' by inseminating females at the optimal time relative to ovulation, leading to the prediction that males should preferentially associate and copulate with females at these times. To the best of our knowledge, we provide the first high-resolution test of this prediction using feral Soay sheep, which have a mating system characterized by male competition for access to highly promiscuous females. We find that competitive males time their mate guarding (and hence copulations) to occur close to the optimal insemination period (OIP), when females are also increasingly likely to 'cooperate' with copulation attempts. Subordinate males practice an alternative mating tactic, where they break the integrity of the consort pair and force copulations on females. The timing of these forced copulations is also targeted towards the OIP. We thus provide quantitative evidence that female promiscuity has resulted in the evolution of reproductive strategies in which males 'load' the sperm raffle by targeting their mating activity towards female OIPs, when the probability of sperm-competition success is at its greatest.

Animals↗

Cyclo-oxygenase-2 over-expression in sporadic colorectal carcinoma without lymph node involvement.

BACKGROUND: Cyclo-oxygenase-2 over-expression has been reported in most advanced human colorectal cancers. AIMS: To assess the prevalence of cyclo-oxygenase-2 over-expression in non-advanced colorectal cancers, to investigate the correlation between cyclo-oxygenase-2 status and tumour clinicopathological features and molecular phenotype, and to determine the impact of cyclo-oxygenase-2 status on long-term clinical outcome. METHODS: Sixty-one patients who had undergone surgery for colorectal cancer without lymph node involvement were evaluated retrospectively. Cyclo-oxygenase-2 expression was determined by immunohistochemistry. The tumour replication error phenotype was assessed by amplification of the two microsatellites, BAT-25 and BAT-26. RESULTS: Thirty-six tumours were classified as cyclo-oxygenase-2 positive and 25 as cyclo-oxygenase-2 negative. No correlation was found between cyclo-oxygenase-2 over-expression and clinicopathological features or molecular phenotype. Cyclo-oxygenase-2 over-expression was an independent predictor of a poor prognosis. Indeed, the relative risk of tumour recurrence or death for patients with cyclo-oxygenase-2-positive tumours was 2.13 times that of patients with cyclo-oxygenase-2-negative tumours (P=0.008; 95% confidence interval, 1.22-3.73). This difference remained significant when post-operative deaths were censored in the multivariate analysis (P=0.014). CONCLUSION: Cyclo-oxygenase-2 over-expression is not associated with tumour phenotype, but is indicative of a poorer clinical outcome in patients with non-advanced colorectal carcinoma.

Aged↗

Hemodynamic and ventilatory effects of manual respiratory physiotherapy techniques of chest clapping, vibration, and shaking in an animal model.

Chest clapping, vibration, and shaking were studied in 10 physiotherapists who applied these techniques on an anesthetized animal model. Hemodynamic variables (such as heart rate, blood pressure, pulmonary artery pressure, and right atrial pressure) were measured during the application of these techniques to verify claims of adverse events. In addition, expired tidal volume and peak expiratory flow rate were measured to ascertain effects of these techniques. Physiotherapists in this study applied chest clapping at a rate of 6.2 +/- 0.9 Hz, vibration at 10.5 +/- 2.3 Hz, and shaking at 6.2 +/- 2.3 Hz. With the use of these rates, esophageal pressure swings of 8.8 +/- 5.0, 0.7 +/- 0.3, and 1.4 +/- 0.7 mmHg resulted from clapping, vibration, and shaking respectively. Variability in rates and "forces" generated by these techniques was <20% in average coefficients of variation. In addition, clinical experience accounted for 76% of the variance in vibration rate (P = 0.001). Cardiopulmonary physiotherapy experience and layers of towel used explained approximately 79% of the variance in clapping force (P = 0.004), whereas age and clinical experience explained >80% of variance in shaking force (P = 0.003). Application of these techniques by physiotherapists was found to have no significant effects on hemodynamic and most ventilatory variables in this study. From this study, we conclude that chest clapping, vibration, and shaking 1). can be consistently performed by physiotherapists; 2). are significantly related to physiotherapists' characteristics, particularly clinical experience; and 3). caused no significant hemodynamic effects.

Adult↗

Overt and covert competition in a promiscuous mammal: the importance of weaponry and testes size to male reproductive success.

Male contests for access to receptive females are thought to have selected for the larger male body size and conspicuous weaponry frequently observed in mammalian species. However, when females copulate with multiple males within an oestrus, male reproductive success is a function of both pre- and postcopulatory strategies. The relative importance of these overt and covert forms of sexual competition has rarely been assessed in wild populations. The Soay sheep mating system is characterized by male contests for mating opportunities and high female promiscuity. We find that greater horn length, body size and good condition each independently influence a male's ability to monopolize receptive females. For males with large horns at least, this behavioural success translates into greater siring success. Consistent with sperm-competition theory, we also find that larger testes are independently associated with both higher copulation rates and increased siring success. This advantage of larger testes emerges, and strengthens, as the number of oestrous females increases, as dominant males can no longer control access to them all. Our results thus provide direct quantitative evidence that male reproductive success in wild populations of mammals is dependent upon the relative magnitude of both overt contest competition and covert sperm competition.

Animals↗

The role of district nursing: perspectives of cancer patients and their carers before and after hospital discharge.

The role of the district nurse (DN) is difficult to define. Knowledge about the perspectives of patients with cancer, and their informal carers, on the roles of DNs and community services is lacking. The aim of this study is to identify the roles of DNs and community services as perceived by patients with cancer and their carers before and after hospital discharge. Seventy-one pre- and post-discharge conversational interviews were conducted with cancer patients and carers, and analysed thematically. Some interviewees lacked knowledge about services, were confused about differential roles and/or held stereotypical views. Some failed to disclose needs to services, received insufficient support or experienced unnecessary and inconvenient visits. Patients with few or no physical care needs were surprised to receive DN visits. Those receiving personal care from agency carers expressed dissatisfaction. Cancer patients and carers may benefit from post-discharge/ongoing assessment by DNs. However, effectiveness could be inhibited by limited disclosure caused by confusion, stereotyping, negative experiences and ideas that other patients have greater needs. Information might diminish these factors but, first, services need to clarify their roles. Organization and delivery of personal care services varies locally and DNs provide personal care during terminal illness. Community services should perform intra- and interservice clarification before publicizing differential roles to cancer patients and carers. This might facilitate disclosure of need to DNs. Patient and carer needs for information on service roles, and patients' preferred roles in self-care are under-researched.

Attitude to Health↗

The cost of allogeneic red blood cells--a systematic review.

Several reports suggest that the cost of RBCs may have risen over time, but there exists very little published evidence of that. The objective was to determine whether published studies documenting cost data on RBCs suggest an increase over time and to assess the quality of cost studies. We used the terms 'cost', 'allogeneic/allogenic' and 'blood' to identify cost studies between 1966 and 2002 from Medline, ISIesource and Ingenta electronic databases. Furthermore, we manually searched a number of transfusion and health economics journals for completeness. We included studies that used an established methodology and conducted an economic evaluation using primary/secondary cost data to calculate the cost of RBCs and RBC transfusion. Studies without allogeneic RBCs as comparator were excluded. Two individuals independently reviewed the studies and included studies upon reaching a consensus. Fourteen studies qualified the selection criteria and were included in the review. Ten studies were identified from Medline, two from Ingenta, one from ISIesource and one was a conference paper. Of the 14 studies reviewed, 10 had focused on RBC transfusion and four had focused on both RBCs and RBC transfusion. Ten studies were from the US, and two each from Canada and the UK, respectively. Two studies had explicit objective of cost calculation, and others had calculated costs towards fulfilling other objectives. Most of the reviewed studies were dated and of poor quality. Despite these limitations, it appears that the cost of RBCs has increased over time in the UK, Canada and the US. More studies are needed to fully assess the trend of costs over time. Future cost studies should try to follow the economic evaluation guidelines for greater research implications.

Canada↗

Cost-effectiveness of salmeterol in patients with chronic obstructive pulmonary disease: an economic evaluation.

Chronic obstructive pulmonary disease (COPD) is associated with a large economic and social burden. Few economic studies have examined the benefits of inhaled therapy for patients with COPD. This 16-week study examined the cost-effectiveness of salmeterol in this patient group. Patients with a history of COPD were randomised to treatment with salmetrol 50 mcg (229 patients) or placebo (227 patients) twice daily administered by metered-dose inhaler in addition to normal therapy. Forced expiratory volume (FEV1) was measured and patients recorded the impact of their symptoms in a daily diary. Health status was assessed using the St Georges Respiratory Questionnaire. A significantly higher proportion of salmeterol-treated patients had an increase of >15% in FEV1. Salmeterol patients had a higher mean proportion of symptom-free days and nights than those in the placebo group. More salmeterol patients had a clinically significant improvement in health status. Total healthcare costs were increased in the salmeterol group, but hospital and GP visit costs and concurrent COPD medication costs were lower. The reduction in hospital costs was sufficient to offset a substantial portion of the acquisition cost of salmeterol. Addition of salmeterol to COPD patients' current therapy improved lung function, health status at the expense of a modest increase in costs compared with usual therapy.

Administration, Inhalation↗

Lambda spectra in 11.6A GeV/c Au-Au collisions.

E896 has measured Lambda production in 11.6A GeV/c Au-Au collisions over virtually the whole rapidity phase space. The midrapidity p(t) distributions have been measured for the first time at this energy and appear to indicate that the Lambda hyperons have different freeze-out conditions than protons. A comparison with the relativistic quantum molecular dynamics model shows that while there is good shape agreement at high rapidity the model predicts significantly different slopes of the m(t) spectra at midrapidity. The data, where overlap occurs, are consistent with previously reported measurements.

Journal Article↗

Heritability of immune function in the caterpillar Spodoptera littoralis.

Phenoloxidase (PO) is believed to be a key mediator of immune function in insects and has been implicated both in non-self recognition and in resistance to a variety of parasites and pathogens, including baculoviruses and parasitoids. Using larvae of the Egyptian cotton leafworm, Spodoptera littoralis, we found that despite its apparent importance, haemolymph PO activity varied markedly between individuals, even amongst insects reared under apparently identical conditions. Sib-analysis methods were used to determine whether individuals varied genetically in their PO activity, and hence in one aspect of immune function. The heritability estimate of haemolymph PO activity was high (h(2) = 0.690 +/- 0.069), and PO activity in the haemolymph was strongly correlated with PO activity in both the cuticle and midgut; the sites of entry for most parasites and pathogens. Haemolymph PO activity was also strongly correlated with the degree to which a synthetic parasite (a small piece of nylon monofilament) was encapsulated and melanized (r = 0.622 +/- 0.142), suggesting that the encapsulation response is also heritable. The mechanism maintaining this genetic variation has yet to be elucidated.

Animals↗

(E)-2(R)-[1(S)-(Hydroxycarbamoyl)-4-phenyl-3-butenyl]-2'-isobutyl-2'-(methanesulfonyl)-4-methylvalerohydrazide (Ro 32-7315), a selective and orally active inhibitor of tumor necrosis factor-alpha convertase.

Tumor necrosis factor-alpha (TNF-alpha), a cytokine secreted by inflammatory cells, has been implicated in several inflammatory disease states. (E)-2(R)-[1(S)-(Hydroxycarbamoyl)-4-phenyl-3-butenyl]-2'-isobutyl-2'-(methanesulfonyl)-4-methylvalerohydrazide (Ro 32-7315), is a potent, orally active inhibitor of the TNF-alpha convertase (TACE), an enzyme responsible for proteolytic cleavage of the membrane bound precursor, pro-TNF-alpha. Ro 32-7315 inhibited a recombinant form of TACE (IC(50) = 5.2 nM) with selectivity over related matrix metalloproteinases. In a cellular assay system, THP-1 cell line, and in human and rat whole blood, Ro 32-7315 significantly reduced lipopolysaccharide (LPS)-induced TNF-alpha release with IC(50) values of 350 +/- 14 nM (n = 5), 2.4 +/- 0.5 microM (n = 5), and 110 +/- 18 nM (n = 5), respectively. Oral administration of Ro 32-7315 to Wistar rats caused a dose-dependent inhibition of LPS-induced release of systemic TNF-alpha with an ED(50) of 25 mg/kg. Treatment (days 0-14) of Allen and Hamburys hooded rats with Ro 32-7315 (2.5, 5, 10, and 20 mg/kg, i.p., twice daily) significantly reduced adjuvant-induced secondary paw swelling (42, 71, 83, and 93%, respectively) as compared with the vehicle group. In the Ro 32-7315-treated group, the reduced paw swelling was associated with improved lesion score and joint mobility. Furthermore, in a placebo-controlled, single-dose study, Ro 32-7315 given orally (450 mg) significantly suppressed ex vivo, LPS-induced TNF-alpha release in the whole-blood samples taken from healthy male and female volunteers (mean inhibition of 42% over a 4-h duration, n = 6). These data collectively support the potential use of such a compound for the oral treatment of inflammatory disorders.

ADAM Proteins↗

Ventricular dysfunction after cardioplegic arrest is improved after myocardial gene transfer of a beta-adrenergic receptor kinase inhibitor.

BACKGROUND: Acute cardiac contractile dysfunction is common after cardiopulmonary bypass (CPB). A potential molecular mechanism is enhanced beta-adrenergic receptor kinase (betaARK1) activity, because beta-adrenergic receptor (betaAR) signaling is altered in cardiomyocytes after cardioplegia. Therefore, we examined whether adenovirus-mediated intracoronary delivery of a betaARK1 inhibitor (Adv-betaARKct) could prevent post-CPB dysfunction. METHODS AND RESULTS: Rabbits were randomized to receive 5x10(11) total viral particles of Adv-betaARKct or PBS. After 5 days, hearts were arrested with University of Wisconsin solution, excised, and stored at 4 degrees C for 15 minutes or 4 hours before reperfusion on a Langendorff apparatus. Left ventricular (LV) function measured by end-diastolic pressure response to preload augmentation, contractility (LV dP/dt(max)), and relaxation (LV dP/dt(min)) was assessed by use of increasing doses of isoproterenol and compared with a control group of nonarrested hearts acutely perfused on the Langendorff apparatus. In the PBS-treated hearts, LV function decreased in a temporal manner and was significantly impaired compared with control hearts after 4 hours of cardioplegic arrest. LV function in Adv-betaARKct-treated hearts, however, was significantly enhanced compared with PBS treatment and was similar to control nonarrested hearts even after 4 hours of cardioplegia. Biochemically, several aspects of betaAR signaling were dysfunctional in PBS-treated hearts, whereas they were normalized in betaARKct-overexpressing hearts. CONCLUSIONS: Myocardial gene transfer of Adv-betaARKct stabilizes betaAR signaling and prevents LV dysfunction induced by prolonged cardioplegic arrest. Thus, betaARK1 inhibition may represent a novel target in limiting depressed ventricular function after CPB.

Adenoviridae↗

Interaction of anandamide with the M(1) and M(4) muscarinic acetylcholine receptors.

The M(1) and M(4) muscarinic acetylcholine receptors are the most abundant muscarinic receptor subtypes in the brain, and are involved in learning and memory. Because cannabinoid receptors are also abundantly expressed in similar brain regions and mediate opposite effects to acetylcholine on cognition, the present study investigated whether the endocannabinoid agonist, anandamide, and its metabolically stable derivative, methanandamide, directly modified the binding properties of the human M(1) and M(4) receptors individually expressed in CHO cell membranes. Experiments utilized the antagonists, [(3)H]N-methylscopolamine and [(3)H]quinuclidinyl benzilate. When acetylcholine was used as the inhibiting ligand, shallow, biphasic isotherms were observed at both receptors, characterised by similar apparent dissociation constants for high and low affinity binding at each receptor but with a greater proportion of high affinity sites at the M(4) (40-45%) than at the M(1) receptor (17-20%). In contrast, anandamide and methanandamide inhibited the binding of both radioligands over a narrow (low micromolar) concentration range, with monophasic isotherms characterized by Hill coefficients significantly greater than 1 at both receptors. These effects were not due to the vehicle used. Further saturation binding analyses found anandamide able to significantly reduce the apparent affinity and maximal density of binding sites labeled by [(3)H]quinuclidinyl benzilate. Interestingly, no significant inhibition of radioligand binding was noted using the synthetic cannabinoid agonist, WIN55212-2, or the cannabinoid CB(1) receptor antagonist, SR141716A. These data thus provide evidence for a direct role of anandamides in modulating muscarinic receptor binding properties through a non-competitive mechanism that is unrelated to their actions on cannabinoid receptors.

Acetylcholine↗