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Biomedical subjects

M White

Publications and source records attributed to M White.

At least 19 recordsLinked to original sources
PubMed2006

A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii.

Toxoplasma gondii strains differ dramatically in virulence despite being genetically very similar. Genetic mapping revealed two closely adjacent quantitative trait loci on parasite chromosome VIIa that control the extreme virulence of the type I lineage. Positional cloning identified the candidate virulence gene ROP18, a highly polymorphic serine-threonine kinase that was secreted into the host cell during parasite invasion. Transfection of the virulent ROP18 allele into a nonpathogenic type III strain increased growth and enhanced mortality by 4 to 5 logs. These attributes of ROP18 required kinase activity, which revealed that secretion of effectors is a major component of parasite virulence.

Alleles↗
PubMed2006

Removing the health domain from the Index of Multiple Deprivation 2004-effect on measured inequalities in census measure of health.

The Index of Multiple Deprivation (IMD) 2004 is a summary measure of area-level deprivation in England that combines weighted scores in seven deprivation domains. IMD 2004 is used extensively by local public health departments and researchers to describe and monitor socioeconomic inequalities in health. However, the inclusion of a health domain in IMD 2004 leads to the possibility of 'mathematical coupling' where a relationship between IMD 2004 and markers of health is predicated by the inclusion of health in IMD 2004-effectively placing measures of health on both sides of the correlation equation. We explored the effect of removing the health domain from IMD 2004 on assignment of small areas to deprivation groups and measured inequalities in health. There was excellent agreement between the deprivation quintiles that small areas were assigned to by IMD 2004 and IMD 2004-minus-health (kappa = 0.895). Removing the health domain had little, practical, effect on measured socioeconomic inequalities in census measures of health. These findings may not hold for other measures of health, and in the context of socioeconomic inequalities in health, removing the health domain from IMD 2004 probably represents best practice.

Censuses↗
PubMed2006

Factors associated with non-participation in a physical activity promotion trial.

BACKGROUND: Non-participation can bias outcome in intervention studies of physical activity. OBJECTIVES: To compare characteristics, knowledge and attitudes to physical activity in participants and non-participants of a physical activity intervention trial in primary care. STUDY DESIGN: Cross-sectional survey. METHODS: Patients aged 40-64 years were recruited opportunistically during surgery visits in an inner city general practice in Newcastle upon Tyne, UK. Attitudes to physical activity, views of its health benefits, and barriers to participation were elicited in interviews with participants, and by postal questionnaire from non-participants. Data held by general practitioners were used to compare anthropometry and lifestyle between groups. RESULTS: Of 842 eligible patients, 276 (33%) refused outright (non-volunteers) and 566 volunteered for the intervention study, of which 353 (42%) attended a baseline assessment and 213 (25%) subsequently defaulted. The initial refusal rate was higher amongst men, smokers and those with addresses in more deprived areas. The response rate to the postal survey of non-volunteers was 45%. Compared with participants, the non-volunteers were more likely to be an adult carer and to report poorer health, and were less likely to have had higher education or to have children living at home. Far more non-volunteers considered that they already did enough exercise to maintain health. Non-volunteers had slightly less knowledge of the benefits of physical activity; attached far less importance to it in maintaining health; were more likely to cite 'fear of leaving their home unattended', 'do not enjoy exercise' and 'poor health' as barriers to exercise; and were less likely to cite 'no one to exercise with' as a barrier to exercise. CONCLUSION: Recruitment of 'hard to engage' individuals requires careful phrasing of the message to focus on their personal goals and to address gaps in their knowledge about physical activity and the principal barriers they perceive. Differential uptake across population subgroups could lead to a widening of health inequalities.

Adult↗
PubMed2006

Pharmacokinetics of S(+) ketamine derived from target controlled infusion.

BACKGROUND: A computer controlled infusion device for S(+) ketamine was used in combination with a Diprifusor device to provide anaesthesia for 20 ASA I or II patients undergoing elective colonoscopy. The aim of the study was to assess the performance of the pharmacokinetic model for S(+) ketamine used in the delivery algorithm of the device. RESULTS: It was observed that during the first 30 min of infusion there was systematic underprediction by the delivery system of the measured levels of S(+) ketamine. New pharmacokinetic constants were derived from the observed data which provided, on pharmacokinetic simulation, improved prediction of the measured values of S(+) ketamine. Prospective application of this modified model for S(+) ketamine in a further nine study patients was performed and the pharmacokinetic performance of the model was reassessed. The data from all 29 patients was subsequently used to calculate the population distribution of S(+) ketamine clearance. The distribution was found to be normal only in the logarithmic domain. In the normal domain the mode of S(+) ketamine clearance was found to be 35.8 ml kg(-1) min(-1) with 5 and 95% confidence limits of, respectively, 11.5 and 111.1 ml kg(-1) min(-1). CONCLUSION: It was necessary to modify the original published pharmacokinetic parameters incorporated into the S(+) ketamine delivery system in order to simulate improved PK performance during short procedures (<1 h duration) where propofol was concurrently administered. This improved performance was confirmed in a further prospective study.

Adolescent↗
PubMed2005

Is the disease risk associated with good self-reported health constant across the socio-economic spectrum?

BACKGROUND: Self-reported health is likely to be dependent on two key assessments: that of one's own health and that of the best health that could be expected. As many health outcomes are known to vary according to socio-economic position (SEP), it is possible that assessments of the best health that could be expected will vary with SEP. It is, therefore, possible that the disease risk associated with different levels of self-reported health varies according to SEP. We investigated this using data from the 1998 Health Survey for England. METHODS: Disease risk was measured as systolic blood pressure and body mass index (BMI), and SEP was measured as occupational social class. Associations between social class and the markers of disease risk were investigated in those reporting different levels of self-reported health using linear regression in order to control for age. RESULTS: There were statistically significant socio-economic variations in systolic blood pressure and BMI (in women only) in those who reported their health as good or very good. No such socio-economic variations in disease risk were seen amongst those reporting their health as less than good. CONCLUSIONS: The meaning of self-reported health, in terms of disease risk, may not be comparable across the socio-economic spectrum.

Adult↗
PubMed2005

The Biomolecular Interaction Network Database and related tools 2005 update.

The Biomolecular Interaction Network Database (BIND) (http://bind.ca) archives biomolecular interaction, reaction, complex and pathway information. Our aim is to curate the details about molecular interactions that arise from published experimental research and to provide this information, as well as tools to enable data analysis, freely to researchers worldwide. BIND data are curated into a comprehensive machine-readable archive of computable information and provides users with methods to discover interactions and molecular mechanisms. BIND has worked to develop new methods for visualization that amplify the underlying annotation of genes and proteins to facilitate the study of molecular interaction networks. BIND has maintained an open database policy since its inception in 1999. Data growth has proceeded at a tremendous rate, approaching over 100 000 records. New services provided include a new BIND Query and Submission interface, a Standard Object Access Protocol service and the Small Molecule Interaction Database (http://smid.blueprint.org) that allows users to determine probable small molecule binding sites of new sequences and examine conserved binding residues.

Animals↗
PubMed2005

Modification of the Bu/Cy myeloablative regimen using daily parenteral busulfan: reduced toxicity without the need for pharmacokinetic monitoring.

Pharmacokinetic and clinical outcome measures among three groups of patients undergoing hematopoietic transplant were assessed: group A: Parenteral busulfan (Bu) 3.2 mg/kg i.v. given qd, n=20; group B: parenteral Bu 0.8 mg/kg i.v. given every 6 h, n=11; group C: Bu 1 mg/kg p.o. given every 6 h, n=25. All groups received Bu over 4 days followed by Cy 60 mg/kg i.v. qd over 2 days; followed by an infusion of allogeneic stem cells. Median Bu clearance was 3.21 ml/min/kg and median daily AUC was 4071 micromol/min for the group A patients. The dosing formula for Bu i.v. qd was highly predictive of the AUC for patients whose mass < or =IBW+20%. For patients of greater mass, the dosing formula uniformly resulted in lower-than-predicted AUC. Neurologic toxicity, hepatic toxicity, hematologic engraftment, and relapse at 100 days were comparable across all three groups. Severe AGVHD was least among group A, followed by group B when compared with group C. Bu i.v. qd is a safe and effective regimen for allogeneic transplantation and is at least clinically equivalent to every 6 h dosing schemes using either oral or parenteral Bu.

Administration, Oral↗
PubMed2005

Nutritional status and energy expenditure in children pre-bone-marrow-transplant.

The aims of this study were to establish the nutritional status of children pre-BMT and to determine whether predictive methods of assessing nutritional status and resting energy expenditure (REE) are accurate in this population. We analysed the body cell mass (BCM) (n=26) and REE (n=24) in children undergoing BMT. BCM was adjusted for height (BCM/HT(p)) and expressed as a Z score to represent nutritional status. To determine whether body mass index (BMI) was indicative of nutritional status in children undergoing BMT, BMI Z scores were compared to the reference method of BCM/HT(p) Z scores. Schofield predictive equations of basal metabolic rate (BMR) were compared to measured REE to evaluate the accuracy of the predictive equations. The mean BCM/HT(p) Z score for the subject population was -1.09+/-1.28. There was no significant relationship between BCM/HT(p) Z score and BMI Z score (r=0.34; P>0.05); however there was minimal difference between measured REE and predicted BMR (bias=-11+/-149 kcal/day). The results of this study demonstrate that children undergoing BMT may have suboptimal nutritional status and that BMI is not an accurate indication of nutritional status in this population. However, Schofield equations were found to be suitable for representing REE in children pre-BMT.

Adolescent↗
PubMed2005

No consistent association between birthweight and parental risk of diabetes and cardiovascular disease.

INTRODUCTION: The fetal insulin hypothesis proposes that the inverse relationship between birthweight and risk of diabetes and cardiovascular disease is partly as a result of inherited factors which influence the effect of insulin and insulin-like growth factors. It has been proposed that an inverse relationship between birthweight and parental risk of diabetes and cardiovascular disease is evidence in support of this hypothesis. PATIENTS AND METHODS: Data from a prospective birth cohort study, followed up to age 50, was used to assess the relationship between birthweight and reported parental diabetes, hypertension, angina and stroke using logistic regression. RESULTS: Of the 832 cohort members traced at age 50, 574 (69%) returned questionnaires that included questions on parental illness. Complete data was available for 541 (94%) of these on maternal illness and for 531 (92%) on paternal illness. Birthweight, standardized for sex and gestational age and adjusted for social class at birth, was inversely associated with maternal stroke (odds ratio = 0.75, 95% confidence intervals 0.60-0.95). There were no other statistically significant associations between birthweight and risk of parental illness. DISCUSSION: We found little evidence of a consistent inverse relationship between birthweight and parental risk of diabetes or cardiovascular disease. This may be because of the quality of our data--which is limited by the problems of collecting robust data over two generations.

Angina Pectoris↗
PubMed2005

Treatment options for paraphimosis.

Paraphimosis is a frequently presented complaint in the emergency department. This review outlines the treatment options available for resolving this condition: manual reduction methods, osmotic methods, puncture and aspiration methods and treatments using sharp incision. The technique of penile block local anaesthesia is described. A technique sequence for treatment is suggested.

Ambulatory Surgical Procedures↗
PubMed2004

How accurate are Townsend Deprivation Scores as predictors of self-reported health? A comparison with individual level data.

OBJECTIVES: To determine the accuracy of area based Townsend Deprivation Scores (TDSs) as proxies for individual level deprivation and to compare the ability of TDSs and individual level measures of deprivation to predict selfreported health. METHODS: Using data from a self completed health and behaviour survey sent to a random sample of households in Newcastle upon Tyne, UK, the ability of TDSs, calculated at the enumeration district and ward level, to predict selfreported health was compared to that of an individual level measure of deprivation similar to TDSs. The correlation between each of these measures of deprivation was also investigated. RESULTS: Enumeration district TDSs were similarly predictive of self-reported health as the individual level measure of deprivation. Ward-level TDSs showed a much weaker association with self-reported health. Although statistically significant, no deprivation measure accounted for more than 3 per cent of the variation in self-reported health. There was a strong correlation between the individual level measure of deprivation and enumeration district, but not ward-level TDSs. CONCLUSIONS: TDSs calculated at the enumeration district level are strongly correlated with a similar measure of deprivation calculated at the individual level and are similarly predictive of health. This is not the case for TDSs calculated at the ward level. Enumeration district TDSs are good proxies for individual level deprivation in Newcastle upon Tyne. This may not be the case in more mobile populations.

Adolescent↗
PubMed2004

Why don't stage-based activity promotion interventions work?

Despite the well-described benefits of regular physical activity, around 70% of adults in the UK fail to meet current activity recommendations. Interventions based on the Transtheoretical, or Stages of Change, Model of behaviour change have been proposed as one potentially effective method of promoting physical activity levels. However, two recent reviews have found little evidence that individualized stage-based activity promotion interventions are any more effective than control conditions in promoting long-term adherence to increased levels of physical activity. Possible reasons for this are: that exercise behaviour is a more complex group of behaviours than currently recognized; that many algorithms for determining current stage of activity change have not been validated; that exercise behaviour is determined by a number of factors not addressed by stage-based interventions; that the stages of change model encourages focus on stage progression which is not always associated with behaviour change; and that truly stage-based interventions are highly complex requiring more than one level of development and evaluation--a challenge that has not yet been met. Thus, stage-based activity promotion interventions may simplify exercise behaviour beyond what is useful for practitioners and health promoters. Paradoxically, stage-based activity promotion interventions that have been developed to date may have failed to appreciate the true complexity of the task.

Attitude to Health↗
PubMed2004

Serological evidence of Helicobacter pylori infection in UK South Asian and European populations: implications for gastric cancer and coronary heart disease.

OBJECTIVES: To describe the prevalence of serological evidence of infection with Helicobacter pylori among people of South Asian and European ethnic origins and to assess its association with prevalent coronary heart disease (CHD). METHODS: We used a quantitative method to compare IgG antibodies to H. pylori in a population sample of 300 South Asians and 302 Europeans in Newcastle upon Tyne, UK. RESULTS: For men and women, respectively, H. pylori IgG (95% confidence interval) was 16.7 microg/ml (13.9, 20.2) and 11.3 (9.4, 13.5) among Europeans and 11.6 (9.8, 13.7) and 14.3 (12.1, 16.9) among South Asians. Levels were higher in older participants and in those of lower socioeconomic status. The ratio of geometric mean IgG, (95% confidence interval) adjusted for age, sex and socioeconomic status, in those with and without CHD was 1.02 (0.49, 2.11) among Europeans and 1.79 (1.01, 3.17) among South Asians. Antibodies against staphylococcal enterotoxins A and B were higher among South Asians than Europeans. CONCLUSIONS: The prevalence of H. pylori infection among UK South Asians does not reflect that of their countries of origin, nor their lower prevalence of gastric cancer. The association with CHD in South Asians requires corroboration in other studies.

Adult↗
PubMed2003

No barrier to diffusion between cell soma and neurite membranes in sympathetic neurons for a GPI-anchored glycoprotein.

As neurons extend their axons, it is thought that newly synthesised membrane components travel in vesicles along the axon, fuse with the growth cone membrane, and diffuse back along the axonal membrane. However, it is difficult to explain how axons continue to be populated with membrane proteins as they extend in length. To investigate this problem, we have used a CEPU-green fluorescent protein (GFP) chimeric protein to study the site of insertion of new glycosyl phosphatidyl inositol (GPI)-anchored glycoproteins and their subsequent behaviour in chick dorsal root ganglia (DRG) neurons. Infection of cultures grown for 24 h revealed rapid expression of CEPU-GFP over the whole surface of the neuron, more rapidly than could be accounted for by diffusion from the growth cone, and fluorescence intensity was uniform along the length of the neurite. Photobleaching experiments of neurite membrane revealed that recovery of fluorescence was due to diffusion from adjacent membranes and there was no evidence for membrane flow in either direction. Photobleaching of membrane adjacent to the cell body also showed rapid recovery, with chimera diffusing both from cell body membrane and the distal neurite membrane into the bleached area. These results suggest there is no barrier to diffusion between the cell body and neurite membrane in DRG and sympathetic neurons cultured for 1 or 2 days in vitro. We propose that the neurite is populated by newly synthesised chimera by diffusion from both regions. This situation may also occur in neurons in the early stages of extending axons in vivo prior to polarisation and the development of the dendritic field.

Adrenergic Fibers↗