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Biomedical subjects

K Wilson

Publications and source records attributed to K Wilson.

At least 55 records · Page 3Linked to original sources

Influence of atrial fibrillation on outcome following mitral valve repair.

BACKGROUND: To investigate the outcome of patients in atrial fibrillation (AF) following mitral valve repair, clinical and echocardiographic follow-up was undertaken in 400 consecutive patients who underwent mitral valvuloplasty from 1987 to 1999. METHODS AND RESULTS: The main indications for surgery were degenerative (81.4%), endocarditis (7.1%), rheumatic (6.6%), ischemic (4.6%), and traumatic (0.3%) mitral valve disease. After excluding 6 paced patients and 1 patient in nodal rhythm, we compared the outcomes of 152 patients in AF against 241 patients in sinus rhythm. For patients in AF versus those in sinus rhythm, more AF patients were older (mean age 67.2+/-8.8 versus 61.9+/-11.8 years, respectively; P<0.001), more were assigned to a poorer New York Heart Association (NYHA) class (77.6% versus 66.0% in NYHA III/IV, respectively; P=0.01), and more demonstrated impaired ventricular function (78.9% versus 46.2% with moderate or severe impairment, respectively; P<0.001). For patients in AF versus those in sinus rhythm, there was no difference in 30-day mortality (2.0% versus 2.1%, respectively; P=0.95), repair failure (5.4% versus 3.6%, respectively; P=0.41), stroke (5.4% versus 2.2%, respectively; P=0.11), or endocarditis (2.3% versus 0.9%, respectively; P=0.27) on follow-up at a median of 2.8 years (interquartile range 1.1 to 6.0). On echocardiography, the proportion of patients with mild regurgitation or worse was 13.3% (AF patients) versus 10.8% (patients in sinus rhythm) (P=0.70). Patients in AF versus those in sinus rhythm had lower survival at 3 years (83% versus 93%, respectively) and 5 years (73% versus 88%, respectively). Univariate analysis identified factors affecting survival as AF (P=0.002), age >70 years (P=0.041), and poor ventricular function (P<0.001). However, by use of a multivariate model, only poor ventricular function remained significant (P=0.01). CONCLUSIONS: AF does not affect early outcome or durability of mitral repair. The onset of AF may be indicative of disease progression because of its association with poor left ventricular function.

Aged↗

A policy analysis of major decisions relating to Creutzfeldt-Jakob disease and the blood supply.

Creutzfeldt-Jakob disease (CJD) is the first major challenge that the blood system has faced since the completion of the Krever inquiry in 1997. We report the results of a detailed policy analysis comparing 2 CJD-related decisions: a 1995 recall of blood from a donor with classic CJD and the 1999 decision to defer donations from individuals with a 6-month travel history to the UK between 1980 and 1996 due to concerns related to variant CJD. Overall, we observed that decision-making improved significantly from 1995 to 1999. In 1998/99 the potential threat of variant CJD was identified at an early stage, and a systematic risk assessment process was initiated. Decision-making was consultative and involved consumers. However, the perception existed that further improvement could take place in the areas of transparency of process and interaction of organizations. We observed that the presence of a second operator had an important impact on decision-making in 1998/99.

Blood Donors↗

[Meningitis].

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Child↗

Corrigendum.

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Journal Article↗

In vivo ventricular gene delivery of a beta-adrenergic receptor kinase inhibitor to the failing heart reverses cardiac dysfunction.

BACKGROUND: Genetic manipulation to reverse molecular abnormalities associated with dysfunctional myocardium may provide novel treatment. This study aimed to determine the feasibility and functional consequences of in vivo beta-adrenergic receptor kinase (betaARK1) inhibition in a model of chronic left ventricular (LV) dysfunction after myocardial infarction (MI). METHODS AND RESULTS: Rabbits underwent ligation of the left circumflex (LCx) marginal artery and implantation of sonomicrometric crystals. Baseline cardiac physiology was studied 3 weeks after MI; 5x10(11) viral particles of adenovirus was percutaneously delivered through the LCx. Animals received transgenes encoding a peptide inhibitor of betaARK1 (Adeno-betaARKct) or an empty virus (EV) as control. One week after gene delivery, global LV and regional systolic function were measured again to assess gene treatment. Adeno-betaARKct delivery to the failing heart through the LCx resulted in chamber-specific expression of the betaARKct. Baseline in vivo LV systolic performance was improved in Adeno-betaARKct-treated animals compared with their individual pre-gene delivery values and compared with EV-treated rabbits. Total beta-AR density and betaARK1 levels were unchanged between treatment groups; however, beta-AR-stimulated adenylyl cyclase activity in the LV was significantly higher in Adeno-betaARKct-treated rabbits compared with EV-treated animals. CONCLUSIONS: In vivo delivery of Adeno-betaARKct is feasible in the infarcted/failing heart by coronary catheterization; expression of betaARKct results in marked reversal of ventricular dysfunction. Thus, inhibition of betaARK1 provides a novel treatment strategy for improving the cardiac performance of the post-MI heart.

Adenoviridae↗

Thrombospondin-1 inhibits TCR-mediated T lymphocyte early activation.

Biological activities of the matrix glycoprotein thrombospondin-1 (TSP1) are cell type specific and depend on the relative expression or activation of several TSP1 receptors. Although engaging individual TSP1 receptors in T lymphocytes can elicit costimulating signals, in this study we show that intact TSP1 inhibits TCR-mediated T cell activation, assessed globally using cDNA microarrays. TSP1 signaling suppressed expression of several genes induced in Jurkat T cells, including the T cell activation markers CD69, early growth response gene-1 (Egr-1), and phosphatase of activated cells (PAC-1). TCR-stimulated and CD47-costimulated IL-2 secretion and cell surface CD69 expression were also inhibited by TSP1. The specific inhibitory effect of TSP1 was verified in freshly isolated human PBMCs. TSP1 inhibited TCR-mediated but not protein kinase C-mediated T cell activation. Using CD69 expression as a marker, we demonstrated that the inhibitory activity of TSP1 depended on two TSP1 receptors, CD47 and integrin-associated protein heparan sulfate proteoglycans. Signals from these receptors inhibited TCR signaling downstream of ZAP70, but upstream of NF-AT. Therefore, the expression of TSP1 induced during wound repair and in tumor stroma may limit T cell activation at these sites.

5' Untranslated Regions↗

Presynaptic neuronal antigens expressed by a small cell lung carcinoma cell line.

Small cell lung carcinoma (SCLC) is a tumour of neuroendocrine origin often found in association with autoimmune paraneoplastic neurological disorders. We established a SCLC cell line from a woman with Lambert-Eaton myasthenic syndrome (LEMS) who developed antibodies to both the P/Q-type voltage-gated calcium channels (VGCC) and the muscle acetycholine receptor (AChR). We used a range of techniques to establish which neuronal antigens were expressed in her tumour cell line. The results show that many proteins involved in exocytosis are present in the SCLC cells, and that depolarisation-dependent release of [(3)H]-serotonin is linked to calcium influx through P/Q-type VGCCs. In addition, some of the subunits encoding the AChR and both agrin and ARIA, molecules released from the motor nerve during development, were expressed. These results suggest that many potential antigenic targets are present in SCLC, and indicate a surprising 'motor nerve terminal'-like characteristic of this line.

Autoantibodies↗

Antidepressant versus placebo for depressed elderly.

BACKGROUND: Depression warranting intervention is found in ten percent of people over the age of 60. Older depressed people are more likely to die than non-depressed. Relatively few receive therapeutic interventions, and those that do, tend to receive low dose antidepressant therapy. Depression in older people is thought to differ in terms of aetiology, presentation, treatment and outcome than in younger people. Concomitant physical illness and increasing social, physical and neurophysiological diversity are associated with the ageing process. Consequently drug treatment of older patients is often carried out in institutions and on patients suffering from multiple physical problems. OBJECTIVES: To determine the efficacy of antidepressant medication compared with placebo in the treatment of depression in older patients. SEARCH STRATEGY: The search strategy incorporated: electronic literature searches of databases held by the Cochrane Collaboration Depression, Anxiety and Neurosis Review Group (CCDAN) (see Collaborative Review Group Search Strategy). Reference lists of related reviews and references of located studies. Contact was made with authors working in the field. SELECTION CRITERIA: All randomised, placebo controlled trials using antidepressants in the treatment of the presenting episode of depression in patients described as elderly, geriatric senile or older adult. DATA COLLECTION AND ANALYSIS: Two types of data were extracted (if available) from each study. The first type of data was dichotomous data, this consisted of recovered/not recovered. The second, continuous data,included: Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Rating Scale (MADRS) and other depression rating scale scores. An analysis using Peto Odds ratios for the dichotomous data and weighted mean difference for continuous data was performed using RevMan 3.1. The presence of heterogeneity of treatment effect was assessed. MAIN RESULTS: Seventeen trials contributed data to the analyses comparing the efficacy of antidepressant treatment and placebo. Analyses of efficacy was based on 245 patients treated with TCAs (223 with placebo), 365 patients treated with SSRIs (372 with placebo) and 58 patients treated with MAOIs (63 with placebo). The standardised effect size for the three groups respectively were: TCAs; OR: 0.32 (0.21,0.47), SSRIs; OR; 0.51 (0.36,0.72), MAOIs: 0.17 (0.07,0.39). REVIEWER'S CONCLUSIONS: TCAs, SSRIs and MAOIs are effective in the treatment of older community patients and inpatients likely to have severe physical illness. At least six weeks of antidepressant treatment is recommended to achieve optimal therapeutic effect. There is little evidence concerning the efficacy of low dose TCA treatment. Further trials are required before low dose TCA treatment is routinely recommended.

Aged↗

Public awareness and health education: findings from an evaluation of health services for incontinence in England.

Improving the health and well being of local populations is a feature of international and national health policy and initiatives. Promotion of health has been attempted traditionally via health education and public awareness campaigns. More recently, attention has been drawn to inter-agency collaboration and alliances in formalised health improvement programmes. This study has evaluated health services for incontinence in two health authorities in England in relation to health education and public awareness. One health authority had an established continence service and the other did not. A convenience sample of self selecting respondents from an earlier postal survey were interviewed via the telephone (n=376). Significantly, more people in the health authority with a continence service than the one without received information on incontinence from within formal health services (p<0.001) and read about services in health centres and clinics (p<0.001), whereas people in the health authority without a continence service were more likely to obtain information on incontinence from local newspapers (p<0.01) and local chemist shops (p<0.01). People in the health authority without a continence service were significantly more likely to feel that services could be improved than those where there was a service (p<0.0001). Only a minority of people with incontinence had received information about their condition or related health care and services. The availability of a continence service significantly influenced the information received. More information on incontinence had been obtained from informal sources than formal health sources. Local initiatives on the availability of services and how to access them, as well as health education information on incontinence may be more effective in raising public awareness and should supplement national campaigns.

Adult↗

Where do adolescents get their condoms?

PURPOSE: To determine where adolescents obtain their condoms; the availability and accessibility of condoms; condom availability in relationship to different sexually transmitted disease (STD) rates; and the availability of safer sex information in places where condoms are sold. METHODS: We conducted a random digit-dialed telephone survey of 259 14-19-year-old adolescents in Monroe County, New York. Self-reported health services use, knowledge and use of confidential services, and where adolescents obtained or intended to obtain condoms were assessed. Research assistants visited all retail establishments in five areas of similar population size with gonorrhea rates from 887 to 12,427 per 100,000 adolescents to assess how available and accessible condoms were in each store. Perceived access and actual condom availability and accessibility were compared using Chi-square and Student's t-tests. RESULTS: Trained interviewers dialed 11,800 numbers in 1993, identifying 4449 (40%) households among 11,065 numbers reached successfully. Of these, 393 (8.8%) had eligible adolescents and 259 (66%) completed interviews. Most adolescents reported obtaining, or planning to obtain, condoms in stores rather than from free health care settings. Adolescents who have used condoms more often reported having obtained them without cost than having purchased them. Condoms were available at 101 (83%) of 122 stores identified. All drug stores and 75% of supermarkets sold condoms and displayed them openly. Most small grocery stores also sold condoms (92%), but were less likely to openly display them. No stores displayed or provided safer sex information. Areas with higher STD rates had more stores (p <.01), and more stores that sold condoms (p <.01). There was no difference in condom cost by area. CONCLUSIONS: Many adolescents obtain their condoms in retail stores. Condom accessibility varied by store type and area STD rate. Increasing condom visibility in private grocery stores may increase the accessibility of condoms to adolescents in areas with highest STD rates.

Adolescent↗

Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands.

Skeletal mass is maintained by a balance between cells which resorb bone (osteoclasts) and cells which form bone (osteoblasts). Bone development and growth is an on-going, life-long process. Bone is formed during embryonic life, grows rapidly through childhood, and peaks around 20 years of age (formation exceeds resorption). For humans the skeleton then enters a long period, approximately 40 years, when bone mass remains relatively stable. Skeletal turnover continues but the net effect of resorption and formation on bone mass is zero. For women this ends when they enter menopause and similar bone loss occurs for men, but later in life. These opposite functions are coupled, resorption precedes formation, and osteoblasts, or their precursors, stromal cells, regulate osteoclast formation and activity. Until recently, the molecular nature of this regulation, was poorly understood. However, recent observations have identified members of the TNF family of ligands and receptors as critical regulators of osteoclastogenesis. Osteoprotegerin (OPG) a decoy receptor was first identified. Its ligand, receptor activator of nuclear factor-kappaB ligand (RANKL), was quickly found, and shown to be expressed on stromal cells and osteoblasts. Its cognate receptor, RANK, was found to be expressed in high levels on osteoclast precursors. The interaction between RANKL and RANK was shown to be required for osteoclast formation. These observations have provided a molecular understanding of the coupling between osteoclastic bone resorption and osteoblastic bone formation. Moreover, they provide a framework on which to base a clear understanding of normal (e.g. postmenopausal osteoporosis and age associated bone loss) and pathologic skeletal changes (e.g. osteopetrosis, glucocorticoid-induced osteoporosis, periodontal disease, bone metastases, Paget's disease, hyperparathyroidism, and rheumatoid arthritis).

Animals↗

A microsatellite polymorphism in the gamma interferon gene is associated with resistance to gastrointestinal nematodes in a naturally-parasitized population of Soay sheep.

Free-living Soay sheep (Ovis aries) on the island of Hirta, St Kilda, Scotland, are naturally parasitized by gastrointestinal nematodes, predominantly Teladorsagia circumcincta. In this paper we show that reduced faecal egg counts (FEC) are associated with an allele at a microsatellite locus located in the first intron of the interferon gamma gene (o(IFN)-gamma) in Soay sheep lambs and yearlings, measured at approximately 4 and 16 months of age, respectively. The same allele was also associated with increased T. circumcincta-specific antibody (IgA) in lambs, but not associated significantly in yearlings. Flanking control markers failed to show a significant association with either FEC or IgA. These results suggest that a polymorphic gene conferring increased resistance to gastrointestinal nematode parasites is located at or near the interferon gamma gene, and support previous reports which have mapped a quantitative trait locus (QTL) for resistance to this region in domestic sheep. Our data are consistent with the idea that a functional polymorphism leading to reduced expression or efficacy of (IFN)-gamma could enhance the immune response to gastrointestinal nematodes by favouring the activity of the Th2 cell subset and antibody associated immune mechanisms.

Animals↗

Degradation of mannan I and II crystals by fungal endo-beta-1,4-mannanases and a beta-1,4-mannosidase studied with transmission electron microscopy.

We have used the endo-beta-1,4-mannanase from Trichoderma reesei (Tr Man5A), the endo-beta-1,4-mannanase from Aspergillus niger (An Man5A) and the exo-beta-1,4-mannosidase from A. niger (An Mnd2A) to follow the enzymatic degradation of mannan I and II crystals. The degradation process was studied by transmission electron microscopy and also followed by analysis of the released soluble reducing sugars. The mannan crystals were degraded by the endo-beta-1,4-mannanases and to a lesser extent by the exo-beta-1,4-mannosidase. The observed hydrolysis pattern on mannan I crystals is fully consistent with the current view of the molecular structure of these crystals. The molecular organization of the mannan chains in mannan II crystals is less clear and the digestion results give some further information about the ultrastructure of mannan II. In addition, insight is provided into the mode of the enzymatic attack on the crystals of mannan I and mannan II.

Aspergillus niger↗

Comparison of brachial artery pressure and derived central pressure in the measurement of abdominal aortic aneurysm distensibility.

OBJECTIVE: AAA distensibility (Ep, beta) may predict growth and risk of rupture. However, distensibility measurements based on brachial rather than central pressure may be inaccurate. Our aim was to compare AAA distensibility using non-invasive brachial and derived central aortic pressure. DESIGN: brachial and central pressures were measured prospectively by automated sphygmomanometry (Omron) and pulse wave analysis (SphygmoCor) respectively. AAA distensibility was calculated using brachial (Ep(b), beta(b)) and central (Ep(c), beta(c)) pressures by ultrasonic echo-tracking (Diamove). Twenty-eight patients (18 males) were selected on a first come basis from a larger study of AAA patients. There were no exclusion criteria, so 54% had cardiac dysfunction (MI, angina) and 14% were hypertensive (BP >140/90 mmHg). RESULTS: median (IQR) age was 74 (70-77) years, median AAA (IQR) diameter was 44 (40-51) mm. Central and brachial systolic pressures were significantly different, [140 (121-153) vs 144 (130-164) mmHg respectively, p < or =0.01]. Central and brachial diastolic pressures were not significantly different [76 (72-86) vs 76 (71-86) mmHg respectively, p=0.5]. Ep(c)(3.0, [2.2-4.9]) and beta(c)(22.2 [15.5-33.2]) were significantly lower than Ep(b)(3.6, [2.4-5.1] 10(5)Nm(-2)) and beta(b)(24.7 [17.1-33.0] a.u., all p < 0.001. Brachial and central derived distensibility remained significantly different after adjusting for age and diameter (p<0.001). CONCLUSION: the use of brachial pressure leads to a small, systematic overestimate of Ep (18%) and beta (11%) independent of age and AAA diameter. This systematic error will not bias follow-up of changes in distensibility.

Aged↗

Racial and ethnic disparities in infant mortality: risk in social context.

This article presents the multifaceted efforts of Syracuse Healthy Start, a federally funded initiative of the Onondaga County Health Department and over 20 partnering agencies to reduce racial and ethnic disparities in infant mortality. The analyses presented in this article demonstrate that many women--Caucasian, African American, and Hispanic--have serious risks for low birth weight and infant death. In many cases, multiple, simultaneous risks complicate a pregnant woman's situation and in other cases the longitudinal cumulative risks impact health across generations. Infant mortality decreased overall, and for both Caucasian and African American infants during the first 3 years of the project.

Black or African American↗