Search PubMed⌕ Search

Biomedical subjects

M Turner

Publications and source records attributed to M Turner.

At least 19 recordsLinked to original sources
PubMed2006

Transfusion safety with regards to prions: ethical, legal and societal considerations.

The purpose of these vignettes is to illustrate that although the dominant ethical, legal and societal position is based on the precautionary principle of deontological non-maleficence, in reality a degree of utilitarian proportionality arises because there is little choice but to balance proposed variant CJD risk management strategies against other ethical imperatives including failure of beneficence, non-maleficence with regard to others, autonomy and justice. There are no easy answers in balancing these issues, but it is important that it is more widely recognised that such moral judgements have to be made and that a wider debate in society occurs over where the balance should lie.

Blood Transfusion↗
PubMed2006

Paternal insulin resistance and its association with umbilical cord insulin concentrations.

AIMS/HYPOTHESIS: Fetal growth is influenced by genetic factors as well as the intra-uterine environment. We hypothesised that some genetic factors may alter fetal insulin secretion and insulin action. SUBJECTS, MATERIALS AND METHODS: To assess this, we analysed plasma insulin concentration in umbilical cord blood from 644 normal, term, UK Caucasian deliveries from the Exeter Family Study of Childhood Health. We tested for associations between cord insulin and each of parental anthropometry, fasting glucose, insulin and lipids. RESULTS: As expected, cord insulin concentrations correlated with all measures of birth size (weight, length, head and arm circumferences, sum of skinfold thicknesses, ponderal index: r=0.16-0.4, p<0.01 for all) and maternal BMI (r=0.11, p=0.005), maternal glucose (r=0.25, p<0.001) and maternal insulin resistance (r=0.23, p<0.001). Paternal fasting insulin and insulin resistance were correlated with cord insulin (r=0.15, p=0.006; r=0.13, p=0.001, respectively), and this was independent of paternal BMI. Multiple linear regression analysis revealed paternal insulin resistance to be a predictor of cord insulin concentrations, independently of maternal factors. CONCLUSION: Our results show an independent relationship between paternal insulin resistance and cord insulin concentrations. This is consistent with heritability of insulin resistance from father to offspring and a compensatory increase in fetal insulin secretion, the latter occurring pre-natally before the homeostatic feedback loop between glucose and insulin is established.

Adult↗
PubMed2006

An analysis of injuries resulting from professional horse racing in France during 1991-2001: a comparison with injuries resulting from professional horse racing in Great Britain during 1992-2001.

BACKGROUND: It has been previously shown that professional jockeys suffer high rates of fatal and non-fatal injuries in the pursuit of their occupation. Little is known, however, about differences in injury rates between countries. AIM: To determine the rate of fatal and non-fatal injuries in flat and jump jockeys in France and to compare the injury rates with those in Great Britain and Ireland Method: Prospectively collected injury data on professional jockeys were used as the basis of the analysis. RESULTS: Limb fractures occur four times more often in both flat and jump racing in France than in Great Britain. Similarly dislocations are diagnosed 20 times more often in flat and three times more often in jump racing. This difference is surprising given that French jockeys have fewer falls per ride than their British counterparts in flat racing, although they do have more falls than the British in jump racing. Similarly concussion rates seem to be higher in French jockeys, although there may be a difference in the diagnostic methods used in the different countries. By contrast, soft tissue injuries account for a far smaller percentage of injuries than in Great Britain. CONCLUSION: There are striking differences in injury rates between countries which may be explained in part by a difference in track conditions-for example, harder tracks in France-or different styles of racing--for example, larger fields of horses per race in France.

Accidental Falls↗
PubMed2006

A genome-scale assessment of peripheral blood B-cell molecular homeostasis in patients with rheumatoid arthritis.

OBJECTIVE: While rheumatoid arthritis (RA) is considered a prototypical autoimmune disease, the specific roles of B-cells in RA pathogenesis is not fully delineated. METHODS: We performed microarray expression profiling of peripheral blood B-cells from RA patients and controls. Data were analysed using differential gene expression analysis and 'gene networking' analysis (characterizing clusters of functionally inter-relelated genes) to identify both regulatory genes and the pathways in which they participate. Results were confirmed by quantitative real-time polymerase chain reaction and by measuring the levels of 10 serum cytokines involved in the pathways identified. RESULTS: Genes regulating and effecting the cell-cycle, proliferation, apoptosis, autoimmunity, cytokine networks, angiogenesis and neuro-immune regulation were differentially expressed in RA B-cells. Moreover, the serum levels of several soluble factors that modulate these pathways, including IL-1beta, IL-5, IL-6, IL-10, IL-12p40, IL-17 and VEGF were significantly increased in this cohort of RA patients. CONCLUSIONS: These results outline aspects of the multifaceted role B-cells play in RA pathogenesis in which immune dysregulation in RA modulates B-cell biology and thereby contributes to the induction and perpetuation of a pathogenic humoral immune response.

Adult↗
PubMed2006

Simulated clinical evaluation of four fluid warming devices*.

The fluid warming capabilities of the Bair Hugger, Hotline, Standard Ranger and Fluido devices were evaluated in the laboratory with gravity flow via a 14G cannula (1 m head of fluid) and with the fluid bag pressurised to 300 mmHg. The resulting flows (70-450 ml.min(-1)) were recorded. At a room temperature of 22 degrees C, no device warmed the fluid to 37 degrees C. However, the Standard Ranger with gravity flow and the Fluido with both gravity and pressurised flow achieved 35 degrees C, whereas the Bair Hugger and Hotline with both gravity and pressurised flow, and the Standard Ranger with pressurised flow, achieved only 24-31 degrees C. However, from the way delivered temperatures changed with flow, we calculated that all four devices would achieve close to 37 degrees C at the flows specified by the manufacturers: 17, 83, 150 and 800 ml.min(-1) for the Bair Hugger, Hotline, Standard Ranger and Fluido, respectively.

Equipment Design↗
PubMed2006

Phase I/II study of vaccination with dendritic-like leukaemia cells for the immunotherapy of acute myeloid leukaemia.

Twenty-two patients with acute myeloid leukaemia were recruited into a phase I/II clinical trial investigating the vaccination of patients in complete remission (CR) with autologous dendritic-like leukaemia cells (DLLC). At trial entry, leukaemia cells were harvested and tested for their ability to undergo cytokine-induced dendritic cell differentiation. Patients were then treated with intensive chemotherapy. Five patients achieved both CR and had leukaemia cells that successfully underwent differentiation and therefore proceeded to vaccination. Four escalating doses of DLLC were administered weekly by subcutaneous injection. Vaccination was generally well tolerated although one patient developed extensive eczema and an increased antinuclear factor titre possibly indicating induction of autoimmunity. Development of anti-leukaemic T-cell responses was assessed by enzyme-linked immunospot analysis of gamma-interferon secreting T lymphocytes and by human leucocyte antigen tetramer analysis for WT1-specific T cells. Increases in anti-leukaemic T-cell responses were demonstrated in four patients, but only two of the five remained in remission more than 12 months postvaccination. The study has demonstrated that generation of DLLC is feasible in only a subgroup of patients and is currently neither broadly applicable or clinically effective.

Acute Disease↗
PubMed2006

Fuzzy balls.

Explore the source record for details and available documents.

Humans↗
PubMed2006

Neuropsychological dysfunction following repeat concussions in jockeys.

BACKGROUND: Single and repeat concussions have a high prevalence in sport. However, there is limited research into longterm risks associated with single and repeat concussions. OBJECTIVES: To determine the effects of single and repeat historical concussions on the neuropsychological functioning and neurological reports of licensed jockeys. METHODS: Six hundred and ninety eight licensed jockeys in the UK were assessed for neurological and neuropsychological symptoms of concussion at least three months after potential episodes. RESULTS: Jockeys reporting multiple historical injuries versus a single injury showed reliable decrements on a measure of response inhibition and, to a less robust degree, on divided attention. Younger adults showed greater vulnerability. CONCLUSIONS: Repeated concussion is associated with reliable decrements in cognitive performance--even after a three month window for recent recovery.

Adolescent↗
PubMed2005

Cross-sectional imaging in non-melanoma skin cancer of the head and neck.

AIM: To investigate in head and neck non-melanoma skin cancers (NMSCs) the accuracy of cross-sectional imaging for detection of local tumour extent, recurrent tumour and prediction of patient outcome. METHODS: This retrospective study included 33 NMSC patients (22 men, 11 women, median age 69 years) with 8 primary and 25 suspected recurrent tumours. The findings of magnetic resonance imaging (MRI) and computed tomography (CT) were compared with histopathology, and accuracy of MRI or CT in detecting local recurrence was determined. Extent of disease on imaging was compared with patient outcome assessed by clinical follow-up to a mean of 26.4 months. RESULTS: Lesions were identified in 29 patients, whose mean disease-free survival (DFS) was 25.5 months. In 4 of these cases, where imaging showed no invasion of deep structures, DFS was 56 months. In the other 25 cases DFS was 20.6 months, irrespective of treatment but varying with site of involvement. Of 19 patients treated with surgery, imaging of 16 showed deep invasion, which was confirmed at histology in 15 (93.7% accuracy), and 3 had superficial tumours on imaging all confirmed by histology (100% accuracy). Imaging accuracy for identifying recurrent tumour was 96% (24 of 25 patients). CONCLUSION: In NMSC, cross-sectional imaging accurately identifies tumour extent and local recurrence. The extent of disease and invasion of deeper structures predicts patient outcome.

Adult↗
PubMed2005

Proving the concept of a data broker as an emergent alternative to supra-enterprise EPR systems.

Electronic Patient Records systems configured into large enterprise models have become the assumed best route forward. In England, as in several other countries, this has expanded to a major meta-enterprise procurement programme. However, concerns are raised that such systems lack user ownership, and experience from other sectors shows difficulties with large enterprise systems. At a time of great change and once again shifting organizations, is this move simply building large and ponderous edifices with unstable materials? Latest software engineering research is now demonstrating the potential of an alternative model, enabling trusted information brokers to search out in real time at point of use data held in registered local and departmental systems. If successful, this could enable a new and less cumbersome paradigm. The data could move where needed whatever the service configuration. A concept demonstrator has been built set in the context of health and social care in England. It is important for all technological support to the health sector to be reviewed as new technologies emerge so as to identify and exploit new opportunities, and the results of this 3 year project show that the health record information broker route merits further investigative research.

Efficiency, Organizational↗
PubMed2005

Time for tea, anyone?

There have been suggestions that urine samples positive for benzoylecognine, the diagnostic metabolite of cocaine, may be the result of consumption Mate de Coca, a commercially available tea made from coca (Erythroxylon coca) leaves. The Jockey Club in Great Britain commissioned research into this subject as several jockeys have tested positive for benzoylecognine over the past few years. Urine samples collected at various time points within 24 h after ingestion of a 250 ml infusion of Mate de Coca tea were analysed using three different methods. All samples tested positive for benzoylecognine.

Coca↗
PubMed2005

Atypical anti-psychotics in the real world--a naturalistic comparative outcome study.

BACKGROUND: There are few real life independent comparative studies of atypical antipsychotics. We prospectively examined five commonly used atypical antipychotics in the UK, without support from the pharmaceutical industry. METHOD: Prospective naturalistic systematic clinical evaluation. Patients being newly prescribed atypical anti-psychotics over a one year period were assessed by psychiatrists at initiation and after six months treatment using five outcome measures: clinical global impression; positive and negative psychotic symptoms; drug related side effects; and quality of life. RESULTS: 373 patients participated in total. Olanzapine and risperidone produced statistically significant reductions in all ratings at six months. Amisulpride, clozapine, and quetiapine were also studied. There was limited variance between the different drugs, although some sample sizes were small. CONCLUSION: Atypical anti-psychotics were found to be clinically effective, and produced similar outcomes. Routine monitoring of outcomes in psychiatry is feasible.

Adolescent↗
PubMed2005

Peripheral genotype-phenotype correlations in Asian Indians with type 2 diabetes mellitus.

OBJECTIVE: A genome-wide scan of gene expression in leucocytes in Asian Indians with type 2 diabetes was performed and correlated with their known phenotype. METHODS: Microarray gene profiling of 13,474 sequence-verified, non-redundant human cDNAs was done to study leukocyte gene expression in Asian Indians with type 2 diabetes (DM: n=3) and matched controls (n=3). RESULTS: Significant differential expression (fold change <0.3 or >3) was noted for 897 genes in DM vs. controls. The 147 known genes in this category belonged to following broad functional groups (%): enzyme (32), nucleic acid binding (22), ligand binding or carrier (10), signal transducer (9), transporter (7), structural protein (6), cell adhesion (3), tumor suppressor (3), transcription factor binding (2), enzyme inhibitor (2), chaperone (2), cell cycle regulator (1), and defense/immunity protein (1). The 20 genes with at least a 3-fold change, annotated with known phenotypic associations in the current gene databank (phenotype association, fold change) were aspartoacylase (Canavan disease, 9.96), growth hormone receptor (Laron dwarfism, idiopathic short stature, 8.25), lipoprotein lipase (familial chylomicronemia syndrome, lipoprotein lipase deficiency, 8.00), vitamin D (1,25- dihydroxyvitamin D3) receptor (involutional osteoporosis, vitamin D resistant rickets, 7.94), intercellular adhesion molecule 1 human rhinovirus receptor (cerebral malaria susceptibility, 7.16), peroxisomal membrane protein 3 35-kDa (Refsum disease, infantile form, Zellweger syndrome-3, 6.00), Bardet-Biedl syndrome 2 (Bardet-Biedl syndrome, 5.87), ribosomal protein S19 (Diamond Blackfan anemia, 5.85), apolipoprotein C-III (hypertriglyceridemia, 5.44), argininosuccinate lyase (argininosuccinicaciduria, 5.22), myosin VA (Griscelli syndrome-type pigmentary dilution with mental retardation, 4.92), lysozyme (renal amyloidosis, 4.17), SAM domain, SH3 domain and nuclear localisation signals 1 (Cherubism, 4.12 ), von Hippel-Lindau syndrome (hemangioblastoma, cerebellar, somatic, von Hippel-Lindau syndrome, 3.94), early-onset breast cancer 1 (BRCA1, papillary serous carcinoma of the peritoneum, 3.73), UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (inclusion body myopathy, autosomal recessive, sialuria, 3.53), apolipoprotein A-I (amyloidosis, 3 or more types, hypoalphalipoproteinemia, 3.29), midline 1 Opitz/BBB syndrome (Opitz G syndrome, type I, 3.28), ATPase, Na+/K+ transporting, alpha 2 (+) polypeptide (familial hemiplegic migraine, 3.05). Canavan disease, Zellweger syndrome, infantile Refsum disease, Griscelli syndrome, cherubism, breast cancer, peritoneal papillary serous carcinoma, Opitz G/BBB syndrome, and familial hemiplegic migraine (FHM) are phenotypes not previously reported in association with type 2 DM, but whose underlying genes were up-regulated in this peripheral genome scan of Asian Indians. CONCLUSION: Rare and/or previously unknown phenotypes linked to known genes with significant differential expression in type 2 DM are reported. Further testing of heterogeneity in diabetes phenotype syndromes may reveal common pathogenic mechanisms and potential candidate genes responsible for type 2 DM.

Asian People↗
PubMed2005

Is there a relationship between anti-HPA-1a concentration and severity of neonatal alloimmune thrombocytopenia?

There is uncertainty about the relationship between anti-HPA-1a levels and severity of neonatal alloimmune thrombocytopenia (NAIT). To investigate this relationship further,the concentration of anti-HPA-1a in HPA-1b homozygous women was determined, using a newly developed quantitative ELISA that uses purified anti-HPA-1a to obtain a standard curve. Seventy-eight samples collected from 22 HPA-1b homozygous pregnant women at various stages of pregnancy were tested. These included five women who had delivered babies with severe NAIT. A national HPA-1a antibody standard (NIBSC 93/710), designated as 1 arbitrary unit/mL (AU/mL),was used in each ELISA to calibrate the purified anti-HPA- 1a, enabling the presentation of results as AU/mL. Moreover, selected samples were also assayed by PAK 12 and their reactivity compared with quantity of antibody. The use of the purified HPA- 1a antibody yielded consistent sigmoid curves, enabling the measurement of HPA-1a antibody concentration in the test samples. The antibody concentration was significantly correlated with the antibody titer in the 78 samples studied (R = 0.54, p < 0.001). Furthermore, there was a significant correlation between PAK 12 and the quantitative ELISA in a selected number of cases, with or without NAIT (R = 0.71, n = 10; p < 0.02). On the other hand, there was no correlation of antibody concentration with NAIT incidence (R = -0.046). This study indicates that there is no relationship between anti-HPA-1a concentration and severity of NAIT when ELISA is used, although the correlation between ELISA and other methods, such as monoclonal antibody immobilization of platelet antigens (MAIPA) assay, remains to be determined.

Antigens, Human Platelet↗
PubMed2004

BCR activation of PI3K is Vav-independent in murine B cells.

BCR (B-cell antigen receptor)-induced Ca(2+) signalling is initiated by activation of tyrosine kinases, which in concert with adaptor proteins and lipid kinases regulate PLC (phospholipase C) gamma2 activation. Vav and PI3K (phosphoinositide 3-kinase) are required for optimal Ca(2+) responses, although it has not been established, in primary B-cells, if both proteins are components of the same pathway. In vitro evidence suggests that binding of the PI3K lipid product PIP3 to Vav pleckstrin homology domain contributes to Vav activation. However, pharmacological inhibition of PI3K by wortmannin or deletion of the p110delta catalytic subunit has no effect on Vav activation in response to BCR engagement, suggesting that this mechanism does not operate in vivo. We also show that PI3K recruitment to phosphorylated-tyrosine-containing complexes is Vav-independent. Taken together with our previous observation that protein kinase B phosphorylation is normal in Vav-deficient B-cells, we suggest that PI3K activation is Vav-independent in response to strong signals delivered by multivalent cross-linking.

Androstadienes↗
PubMed2004

The p110delta subunit of phosphoinositide 3-kinase is required for the lipopolysaccharide response of mouse B cells.

PI3K (phosphoinositide 3-kinase) I(A) family members contain a regulatory subunit and a catalytic subunit. The p110delta catalytic subunit is expressed predominantly in haematopoietic cells. There, among other functions, it regulates antigen receptor-mediated responses. Using mice deficient in the p110delta subunit of PI3K, we investigated the role of this subunit in LPS (lipopolysaccharide)-induced B cell responses, which are mediated by Toll-like receptor 4 and RP105. After injection of DNP-LPS (where DNP stands for 2,4-dinitrophenol), p110delta(-/-) mice produced reduced levels of DNP-specific IgM and IgG when compared with wild-type mice. In vitro, the proliferation and up-regulation of surface activation markers such as CD86 and CD25 induced by LPS and an antibody against RP105 were decreased. We analysed the activation state of key components of the LPS pathway in B cells to determine whether there was a defect in signalling in p110delta(-/-) B cells. They showed normal extracellular-signal-regulated kinase phosphorylation, but anti-RP105-induced protein kinase B, IkappaB (inhibitor of nuclear factor kappaB) and c-Jun N-terminal kinase activation was severely reduced. This demonstrates that the p110delta subunit of PI3K is involved in the LPS response in B cells and may represent a link between the innate and the adaptive immune system.

Animals↗
PubMed2004

The usual medical care for irritable bowel syndrome.

AIMS: To determine what constitutes usual medical care for irritable bowel syndrome, which patient characteristics influence choice of treatment and how satisfied patients are with care. METHODS: Patient encounters in a health maintenance organization were prospectively monitored to identify visits coded irritable bowel syndrome, abdominal pain, constipation or diarrhoea. Within 2 weeks these patients were sent postal questionnaires (n = 1770, 59% participation) to assess patient characteristics and treatment recommendations. Responders were sent follow-up questionnaires 6 months later (77% participation) to assess adherence and satisfaction with treatment. RESULTS: Treatments employed most frequently were dietary advice, explanation, exercise advice, reassurance, advice to reduce stress and antispasmodic medications. Primary care physicians and gastroenterologists provided similar treatments. Patient confidence was higher for lifestyle advice (63-67, 100-point scale) than for medications (46-59). However, adherence was greater for medications (62-79 vs. 59-69, 100-point scale). Satisfactory relief was reported by 57%, but only 22% reported that symptom severity was reduced by half. Usual medical treatment was less effective for irritable bowel syndrome than for constipation, diarrhoea, or abdominal pain. CONCLUSIONS: Usual medical care for irritable bowel syndrome emphasizes education and lifestyle modification more than drugs; patients have a greater expectation of benefit from lifestyle modification than drugs. Overall 57% of irritable bowel syndrome patients report satisfactory relief.

Adolescent↗