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Biomedical subjects

J Wilkinson

Publications and source records attributed to J Wilkinson.

At least 19 recordsLinked to original sources
PubMed2007

IGF1, growth pathway polymorphisms and schizophrenia: a pooling study.

It has been hypothesized that insulin-like growth factors (IGFs) and components of the growth-hormone (GH)-IGF axis may underlie reported associations of poor fetal and childhood growth with schizophrenia. We have investigated the association of schizophrenia with 16 SNPs spanning the IGF1 gene with an inter-marker distance of approximately 2-3 kb. We also examined associations with four common functional polymorphisms of genes involved in aspects of the GH-IGF system--the IGF1 receptor (IGF1R), insulin receptor substrate (IRS1), growth hormone (GH1), and IGF binding protein-3 (IGFBP3). The study was based on an analysis of pooled DNA samples from 648 UK and Irish cases of schizophrenia and 712 blood donor controls and of 297 Bulgarian parent offspring trios. In replicated pool analyses, none of the 16 SNPs in IGF1 nor the 4 key SNPs in the other growth pathway genes were associated with schizophrenia. SNP coverage of IGF1 was extensive, so our findings do not support a major role for IGF-I in the aetiology of schizophrenia.

Bulgaria↗
PubMed2006

Reducing fluxes of faecal indicator compliance parameters to bathing waters from diffuse agricultural sources: the Brighouse Bay study, Scotland.

The European Water Framework Directive requires the integrated management of point and diffuse pollution to achieve 'good' water quality in 'protected areas'. These include bathing waters, which are regulated using faecal indicator organisms as compliance parameters. Thus, for the first time, European regulators are faced with the control of faecal indicator fluxes from agricultural sources where these impact on bathing water compliance locations. Concurrently, reforms to the European Union (EU) Common Agricultural Policy offer scope for supporting on-farm measures producing environmental benefits through the new 'single farm payments' and the concept of 'cross-compliance'. This paper reports the first UK study involving remedial measures, principally stream bank fencing, designed to reduce faecal indicator fluxes at the catchment scale. Considerable reduction in faecal indicator flux was observed, but this was insufficient to ensure bathing water compliance with either Directive 76/160/EEC standards or new health-evidence-based criteria proposed by WHO and the European Commission.

Agriculture↗
PubMed2006

A web-based study concept designed to progress clinical research for 'orphan' disease areas in haematological oncology in the elderly: the SHIELD programme.

Clinical randomised trials (RCT) in elderly populations with haematological malignant disease are rare and difficult to perform. This paper describes the methodology and process of organising an internet-based international programme for Hodgkin's lymphoma in the >60 years age group in a format which is compliant with the European Clinical Trials Directive (EUCTD). International agreement was obtained on the need for a web-based data collection system for basic registration and evaluation which incorporated an electronic case report system (eCRF) for a Phase II Study. Objective assessments of co-morbidity, activities of daily living (ADL) and instruments of daily living (IADL) were built-in to define objective frailty, linked to physician treatment choice or inclusion on the Study protocol. The programme is now operating effectively in the UK and Germany and provides an organisational model of how research in 'orphan' disease areas of haematological and solid tumour oncology, previously considered very difficult, might be overcome.

Activities of Daily Living↗
PubMed2006

Pharmacy diabetes care program: analysis of two screening methods for undiagnosed type 2 diabetes in Australian community pharmacy.

OBJECTIVE: To compare the efficacy and cost-effectiveness of two methods of screening for undiagnosed type 2 diabetes in Australian community pharmacy. METHODS: A random sample of 30 pharmacies were allocated into two groups: (i) tick test only (TTO); or (ii) sequential screening (SS) method. Both methods used the same initial risk assessment for type 2 diabetes. Subjects with one or more risk factors in the TTO group were offered a referral to their general practitioner (GP). Under the SS method, patients with risk factors were offered a capillary blood glucose test and those identified as being at risk referred to a GP. The effectiveness and cost-effectiveness of these approaches was assessed. RESULTS: A total of 1286 people were screened over a period of 3 months. The rate of diagnosis of diabetes was significantly higher for SS compared with the TTO method (1.7% versus 0.2%; p=0.008). The SS method resulted in fewer referrals to the GP and a higher uptake of referrals than the TTO method and so was the more cost-effective screening method. CONCLUSIONS: SS is the superior method from a cost and efficacy perspective. It should be considered as the preferred option for screening by community based pharmacists in Australia.

Australia↗
PubMed2006

Extreme Hodgkin's lymphoma: current problem areas.

In Hodgkin's lymphoma therapy, there remain areas of extreme difficulty. This article briefly explores these areas and provides evidence that risk-related therapy and web-based data collection programmes can facilitate progress. Unpublished data from the northern region of the UK suggest that risk-based therapy among poor-prognosis Hodgkin's lymphoma patients aged 15-19 years is improving outcome. An index developed at the Memorial Sloan-Kettering Cancer Centre (MSKCC) for patients undergoing salvage therapy shows that new second-line regimens are urgently needed for those with poor prognosis. In primary therapy and relapse, both adolescent and adult patients with Hodgkin's lymphoma should receive treatment tailored to their degree of risk. Elderly patients with Hodgkin's lymphoma are also difficult to treat and fewer than 2% enter randomised clinical trials. We require new means of encouraging international pooling of data and treatment evaluation in such patients. The SHIELD project (Study of Hodgkin's lymphoma in the Elderly Lymphoma Database; www.shieldstudy.co.uk) is now successfully providing on-line registration in the ongoing phase II study of VEPEMB (vinblastine, cyclophosphamide, procarbazine, prednisolone, mitoxantrone and bleomycin) in the elderly and guidance on obtaining ethical approval for participation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Applying to the European Research Area Network Scheme (ERA-NET): collaborative working for nursing and midwifery research.

AIM: This paper reports on work undertaken to achieve an application for monies from the European Commission's 6th Framework Programme by some key stakeholders, working with a nursing and midwifery research agenda at national policy levels. BACKGROUND: A short outline of the European Commission's European Research Area Network scheme is given in order to set the paper in context, and the vision underpinning the application is discussed. CONCLUSION: The paper describes the processes that were undertaken to bring to fruition such collaborative work, and some key lessons are outlined. Seeking opportunities to enhance nursing and midwifery research within a European context gives value to the application, which was ultimately successful.

Europe↗
PubMed2004

Decay of intestinal enterococci concentrations in high-energy estuarine and coastal waters: towards real-time T90 values for modelling faecal indicators in recreational waters.

Intestinal enterococci are the principal 'health-evidence-based' parameter recommended by WHO for the assessment of marine recreational water compliance. Understanding the survival characteristics of these organisms in nearshore waters is central to public health protection using robust modelling to effect real-time prediction of water quality at recreation sites as recently suggested by WHO and the Commission of the European Communities Previous models have more often focused on the coliform parameters and assumed two static day-time and night-time T90 values to characterise the decay process. The principal driver for enterococci survival is the received dose of irradiance from sunlight. In the water column, transmission of irradiance is determined by turbidity produced by suspended material. This paper reports the results of irradiated microcosm experiments using simulated sunlight to investigate the decay of intestinal enterococci in relatively turbid estuarine and coastal waters collected from the Severn Estuary and Bristol Channel, UK. High-turbidity estuarine waters produced a T90 value of 39.5 h. Low-turbidity coastal waters produced a much shorter T90 value of 6.6 h. In experiments receiving no irradiation, high-turbidity estuarine waters also produced a longer T90 of 65.1 h compared with corresponding low-turbidity coastal waters, T90 24.8 h. Irradiated T90 values were correlated with salinity, turbidity and suspended solids (r>0.8, p<0.001). The results suggest that enterococci decay in irradiated experiments with turbidity >200 NTU is similar to decay observed under dark conditions. Most significantly, these results suggest that modelling turbidity and or suspended solids offers a potential means of predicting T90 values in 'real-time' for discrete cells of a hydrodynamic model.

Dose-Response Relationship, Radiation↗
PubMed2004

Identification in 2 independent samples of a novel schizophrenia risk haplotype of the dystrobrevin binding protein gene (DTNBP1).

CONTEXT: Recent research suggests that variation in the gene encoding dystrobrevin binding protein (DTNBP1) confers susceptibility to schizophrenia. Thus far, no specific risk haplotype has been identified in more than 1 study. OBJECTIVES: To confirm DTNBP1 as a schizophrenia susceptibility gene, to identify and replicate specific risk and protective haplotypes, and to explore relationships between DTNBP1 and the phenotype. DESIGN: Genetic association study based on mutation detection and case-control analysis. SETTING: All subjects were unrelated and ascertained from general (secondary care) psychiatric inpatient and outpatient services. PARTICIPANTS: The Cardiff, Wales, sample included 708 white subjects from the United Kingdom and Ireland (221 females) who met DSM-IV criteria for schizophrenia and were individually matched for age, sex, and ethnicity to 711 blood donor controls (233 females). Mean +/- SD age at first psychiatric contact for cases was 23.6 +/- 7.7 years; mean age at ascertainment was 41.8 +/- 13.5 years. The Dublin, Ireland, sample included 219 white subjects from the Republic of Ireland who met DSM-III-R criteria for schizophrenia or schizoaffective disorder and 231 controls. The mean age of the Irish cases was 46.0 +/- 8.5 years; mean age at first psychiatric contact was 25.2 +/- 12.4 years. MAIN OUTCOME MEASURE: Evidence for association between the DTNBP1 locus and schizophrenia. RESULTS: In the Cardiff sample, there was no evidence for association with previously implicated haplotypes but strong evidence for association with multiple novel haplotypes. Maximum evidence was found for a novel 3-marker haplotype (global P<.001), composed of 1 risk haplotype (P =.01) and 2 protective haplotypes, 1 common (P =.006) and 1 rare (P<.001). Specific risk and protective haplotypes were replicated in the Dublin sample (P =.02,.047, and.006, respectively). The only phenotypic variable associated with any haplotype was between the common protective haplotype and higher educational achievement (P =.02, corrected for multiple tests). CONCLUSIONS: DTNBP1 is a susceptibility gene for schizophrenia. Specific risk and protective haplotypes were identified and replicated. Association with educational achievement may suggest protection mediated by IQ, although this needs to be confirmed in an independent data set.

Adult↗
PubMed2004

A rapid screening technique for feline odontoclastic resorptive lesions.

The feline odontoclastic resorptive lesion (FORL) status (presence or absence of odontoclastic resorptive lesions) of 423 clinically healthy cats was determined based on radiographic findings in a series of full mouth radiographs (eight views). This status was compared with the FORL status based on evaluation of only two views, namely the right and left mandibular premolar and molar views. Using the FORL status of the right and left third mandibular premolars (307 and 407) alone correctly predicted overall FORL status in 93.4 per cent of cats. The sensitivity of the new technique (FORL cases correctly diagnosed as positive by the test) was 78.5 per cent, while the negative predictive value (negative FORL cases correctly diagnosed by the test) was 91.3 per cent. Overall FORL status can therefore be confidently diagnosed in nine out of 10 cats by assessing FORL status in just two teeth (307 and 407) using two films, which has benefits for the cat (less anaesthetic time and reduced exposure to radiation) and the owner (reduced cost of screening).

Animals↗
PubMed2003

The genetic epidemiology of body attitudes, the attitudinal component of body image in women.

BACKGROUND: There were four purposes of the current study, including the investigation of the: (i) adequacy of a multidimensional measure of body image; (ii) genetic and environmental epidemiology of this measure; (iii) shared variance between genetic and environmental risk factors for body mass index (BMI) and body image; and (iv) Equal Environment Assumption (EEA) as it related to body attitudes. METHOD: Six types of body attitudes, as measured by the Body Attitudes Questionnaire (BAQ) and reported by 894 complete female-female twin pairs (mean age 32.35 years, S.D. = 41.8) from the Australian Twin Registry, were analysed. RESULTS: Confirmatory factor analysis of the BAQ supported the adequacy of the measure. Additive genetic and unique environmental influences best accounted for the variance of all six of the BAQ subscales. The relationship between BMI and body attitudes was primarily due to shared genes rather than environment but the majority of genetic and environmental effects on body attitudes were independent of BMI, with the exception of the Feeling Fat subscale, which shared 53% of its genetic risk factors with BMI. One violation of the EEA was suggested, namely similarity of childhood treatment influenced similarity on Lower Body Fatness subscale. CONCLUSIONS: Findings support the notion that: (i) body image is a multidimensional concept; (ii) it is relatively independent of BMI; and (iii) both genetic and non-shared environment are influential determinants of body attitudes.

Adult↗
PubMed2003

Young people with cancer--how should their care be organized?

The objective of this study was to assess the attitudes and views of young people receiving treatment for cancer, along with the views of their parents, their healthy peers and those involved in treating them without a cancer centre. The study analysed qualitative data collected using focus groups and patient interviews. Fourteen patients aged between 15 and 20 years were interviewed at a major cancer centre in Yorkshire. A focus group of healthy adolescents was held at a location away from the hospital to gain the perspectives of healthy adolescents. No disadvantages of a more centralized model of care for adolescents were discovered. The particular feature felt to be important was the expertise of the staff rather than the physical environment. Some suboptimal care was identified in referring units, though this appeared to apply to that associated with the treatment of solid tumours rather than leukaemias. The case for a more centralized approach to the management of young people with cancer is confirmed, and supports the model already implemented in the care of children with cancer.

Adolescent↗
PubMed2003

Immune response to a mucosally administered aflatoxin B1 vaccine.

In the present study, a mucosal vaccine was used in an effort to elicit serum IgG and intestinal secretory IgA against the mycotoxin aflatoxin B1 (AFB) in chickens. AFB was coupled to carrier proteins (BSA and porcine thyroglobulin) for use as a vaccine and ELISA coating antigen, respectively. Seven-day-old broiler chicks were divided into groups of 10 and immunized with one of four vaccine preparations: 1) AFB-BSA conjugate alone, 2) AFB-BSA linked to the B subunit of the recombinant heat-labile enterotoxin of Escherichia coli (rLT-B), 3) AFB-BSA admixed with rLT-B, or 4) AFB-BSA mixed with cholera toxin (CT). Each vaccine preparation was administered perorally, intrarectally, or intraperitoneally, with a booster immunization given 2 wk later. Sera and feces were collected weekly and assayed using isotype specific ELISA. All three routes of immunization elicited significant serum IgG responses; however, the intraperitoneal route was strongest for all vaccine preparations tested. The serum IgG immune response to the AFB-BSA conjugate was enhanced by co-administration of rLT-B but not by covalent coupling to rLT-B or coadministration with CT. Secretory IgA anti-CT and anti-rLT-B antibodies were detected in fecal supernatants, but no anti-AFB responses could be detected. As all 12 treatment groups produced significant levels of serum IgG anti-AFB, any of these approaches, including oral administration without adjuvant, may afford the chicken some level of protection through simple immuno-interception of free AFB.

Adjuvants, Immunologic↗
PubMed2002

Characterization of the phenotypic and lymphokine profile associated with strong CD8+ anti-HIV-1 suppressor activity (CASA).

A panel of 22 CD8+ T cell lines, with a broad range of CD8+ anti-HIV-1 suppressor activity (CASA) were generated from a single patient with HIV-1 infection. CD8+ T cell lines with either strong or weak CASA were examined and compared for cell surface and intracellular markers, constitutive chemokine and lymphokine mRNA levels and inducible lymphokine expression. Strong CASA significantly correlated with CD8+ T cell lines that highly coexpressed the molecule CD28+ (r=0.52, P=0.01) and Ki67+ (r=0.88, P=0.02), with strong CASA CD8+ T cell lines demonstrating significantly higher (P < 0.05) expression of CD8+CD28+ and CD8+Ki67+ compared to those with weak activity. No such correlations or findings were observed for the markers CD38, HLA-DR, CD57 or perforin. The Th1 cytokines were expressed at greater levels than the Th2 cytokines, with strong CASA significantly associated with an increased inducible level of IL-2 production (P=0.05). Constitutive RANTES, IP-10 and I-309 mRNA expression were significantly (P < 0.05) elevated in CD8+ T cell lines exhibiting strong CASA compared to those with weak CASA. There was no significant difference in the mRNA expression of the lymphokines IL-2, 4, 5, 8, 9, 10, 14, 15, or chemokines MIP-1alpha, MIP-1beta, MCP-1, and Ltn. Strong CASA was therefore associated with rapidly replicating CD8+ T cells of the phenotype CD8+CD28+Ki67+ that expressed greater levels of IL-2 and the ligands RANTES and I-309.

CD8-Positive T-Lymphocytes↗
PubMed2002

Diffuse esophageal leiomyomatosis with localized dense eosinophilic infiltration.

Diffuse esophageal leiomyomatosis is a rare cause of dysphagia. There is frequently a chronic inflammatory infiltrate, but here we present the first reported case in association with a dense infiltration of eosinophils and mast cells confined to the affected muscularis propria. This was successfully managed by long esophageal myotomy, with resolution of dysphagia and no symptomatic recurrence after 3 years.

Biopsy, Needle↗
PubMed2002

Interaction between arrival time and thrombolytic treatment in determining early outcome of acute myocardial infarction.

BACKGROUND: Shortening prehospital delay has been identified as an important means of improving responses to reperfusion treatment. If this increases the risk profile of the population delivered to hospital, it may paradoxically cause a deterioration in hospital mortality. OBJECTIVE: To examine the interaction between arrival time (time from onset of chest pain to arrival at hospital) and thrombolytic treatment in determining the early outcome of acute myocardial infarction. METHODS: Prospective cohort study of 1723 patients with acute myocardial infarction who were potentially eligible for thrombolytic treatment (ST elevation on ECG; arrival time < or = 12 hours). RESULTS: All patients were eligible for thrombolysis but only 1098 (80%) received it. Patients who did not receive thrombolytic treatment were older (66 (58-73) v 61 (53-70) years, p < 0.001), more commonly female (32.1% v 24.8%, p < 0.01), and had higher frequencies of previous infarction (28.6% v 15.6%, p < 0.001) and left ventricular failure (37.5% v 26.9%, p < 0.01) than patients who received thrombolytic treatment. For the group as a whole, 30 day mortality was 11.7% and was unaffected by arrival time, but in patients who did not receive thrombolysis an arrival time of < or = 6 hours was associated with significantly higher 30 day mortality than an arrival time of 6-12 hours (24.3% v 2.6%, p = 0.002). Conversely, in patients who did receive thrombolysis an arrival time of < or = 6 hours was associated with a lower 30 day mortality than an arrival time of 6-12 hours (8.5% v 14.5%, p < 0.02). CONCLUSIONS: Shortening prehospital delay in acute myocardial infarction will tend to increase the risk profile of patients presenting to emergency departments. The data presented here indicate that this may increase hospital mortality if underutilisation of thrombolytic treatment among high risk groups is not diminished.

Aged↗