Biomedical subjects

P Bennett

Publications and source records attributed to P Bennett.

At least 19 recordsLinked to original sources

PubMed2006

Changing attitudes to the management of ischaemic stroke between 1997 and 2004: a survey of New Zealand physicians.

AIM: In 1997, a survey of New Zealand physicians' opinions on the management of stroke was carried out. Since then, there have been a number of advances in stroke therapy. We have repeated the 1997 survey to assess changes in physicians' opinions on stroke management. METHODS: A questionnaire was sent to 293 physicians responsible for patients admitted with acute stroke to hospitals throughout New Zealand. It included questions on the management of acute stroke and secondary prevention and was based on the 1997 questionnaire. RESULTS: Responses were received from 211 physicians of whom 174 (82%) managed patients with an acute stroke. The number of respondents who thought that stroke units were efficacious has increased (57% in 1997 to 89%, P < 0.001). The use of aspirin acutely (P < 0.001) and intravenous tissue plasminogen activator (P = 0.006) has also increased. In 2004, antihypertensive therapy for secondary stroke prevention would be commenced if the blood pressure was 150/90 by 98% of respondents and 140/90 by 70% of respondents. In 2004, a statin would be commenced if the total cholesterol level was 4.0 mmol/L by 56% of respondents and 5.0 mmol/L by 91% of respondents. CONCLUSIONS: This survey has shown important changes in the management of ischaemic stroke over the past 7 years.

Antihypertensive Agents↗

PubMed2005

Quantitative determination of endogenous sorbitol and fructose in human erythrocytes by atmospheric-pressure chemical ionization LC tandem mass spectrometry.

Evaluation of different extraction methods for quantification of endogenous sorbitol and fructose in human red blood cells (RBCs) and matrix effects in ESI and APCI showed that protein-precipitation followed by mixed-mode solid-phase extraction was more effective extraction method and APCI more effective ionization method. Then the LC/APCI-MS/MS method was fully validated and successfully applied to analysis of clinical RBC samples. The concentrations of endogenous sorbitol and fructose were determined using calibration curves employing sorbitiol-13C6 and fructose-13C6 as surrogate analytes. The method has provided excellent intra- and inter-assay precision and accuracy with a linear range of 50.0-10,000 ng/mL (correlation coefficient >0.999) for sorbitol-13C6 and 250-50000 ng/mL (correlation coefficient >0.999) for fructose-13C6 in human RBCs.

Atmospheric Pressure↗

PubMed2005

A micro costing of NHS cancer genetic services.

This paper presents the first full micro costing of a commonly used cancer genetic counselling and testing protocol used in the UK. Costs were estimated for the Cardiff clinic of the Cancer Genetics Service in Wales by issuing a questionnaire to all staff, conducting an audit of clinic rooms and equipment and obtaining gross unit costs from the finance department. A total of 22 distinct event pathways were identified for patients at risk of developing breast, ovarian, breast and ovarian or colorectal cancer. The mean cost per patient were pound sterling 97- pound sterling 151 for patients at moderate risk, pound sterling 975- pound sterling 3072 for patients at high risk of developing colorectal cancer and pound sterling 675- pound sterling 2909 for patients at high risk of developing breast or ovarian cancer. The most expensive element of cancer genetic services was labour. Labour costs were dependent upon the amount of labour, staff grade, number of counsellors used and the proportion of staff time devoted to indirect patient contact. With the growing demand for cancer genetic services and the growing number of national and regional cancer genetic centers, there is a need for the different protocols being used to be thoroughly evaluated in terms of costs and outcomes.

Costs and Cost Analysis↗

PubMed2005

Quantitative determination of endogenous sorbitol and fructose in human nerve tissues by atmospheric-pressure chemical ionization liquid chromatography/tandem mass spectrometry.

Attachment of anions to sorbitol and fructose has been shown to enhance sensitivity in both electrospray ionization (ESI) and atmospheric-pressure chemical ionization (APCI) mass spectrometry. The post-column addition of CHCl3 produced Cl-adducts of sorbitol and fructose but their signals were suppressed due to the elevated background. Different chlorinated compounds and different additive methods were systematically investigated to form more abundant Cl-adduct precursor ions and deprotonated product ions. The major causes of the high background were explored and effective methods were developed to improve the signal-to-noise ratios and reproducibility. The compositions of mobile phase, percentages of organic modifiers (MeCN, MeOH and water), columns, oven temperature, flow rates and different gradients were investigated to separate sorbitol from fructose along with their isomers including glucose, galactose, mannose, sorbose, mannitol, and dulcitol. The optimized separation was achieved on a Luna 5 mu NH2 100A column (150 x 4.6 mm) using a mobile phase containing MeCN with 0.1% of CH2Cl2 and 50% MeOH in water at a flow rate of 800 microL/min and an oven temperature of 40 degrees C using a gradient liquid chromatography (LC) system. Human nerve tissue samples were extracted by protein precipitation followed by mixed-mode solid-phase extraction. The LC/ESI-MS/MS method produced higher peak intensities than LC/APCI-MS/MS. However, there were matrix effects from extracted tissues in LC/ESI-MS/MS but not in LC/APCI-MS/MS. Consequently, APCI proved to be the more effective method of ionization. Then the LC/APCI-MS/MS method was fully validated and successfully applied to analysis of clinical samples. The concentrations of endogenous sorbitol and fructose were determined using calibration curves employing sorbitol-13C6 and fructose-13C6 as surrogate analytes. The method has provided excellent intra- and inter-assay precision and accuracy with linear ranges of 0.2-80 ng/mg for sorbitol and 1-400 ng/mg for fructose in human nerve tissues.

Atmospheric Pressure↗

PubMed2005

Stage 2 of the Wellcome Trust UK-Irish bipolar affective disorder sibling-pair genome screen: evidence for linkage on chromosomes 6q16-q21, 4q12-q21, 9p21, 10p14-p12 and 18q22.

Bipolar affective disorder (BPAD) is a common psychiatric disorder with complex genetic aetiology. We have undertaken a genome-wide scan in one of the largest samples of bipolar affected sibling pairs (ASPs) using a two-stage approach combining sample splitting and marker grid tightening. In this second stage analysis, we have examined 17 regions that achieved a nominally significant maximum likelihood LOD score (MLS) threshold of 0.74 (or 1.18 for the X-chromosome) in stage one. The second stage has added 135 ASP families to bring the total stage 2 sample to 395 ASPs. In total, 494 microsatellite markers have been used to screen the human genome at a density of 10 cM in the first stage sample (260 ASPs) and 5 cM in the second stage. Under the broad diagnostic model, two markers gave LOD scores exceeding 3 with two-point analysis: D4S392 (LOD=3.30) and D10S197 (LOD=3.18). Multipoint analysis demonstrated suggestive evidence of linkage between BPAD and chromosomal regions 6q16-q21 (MLS=2.61) and 4q12-q21 (MLS=2.38). 6q16-q21 is of particular interest because our data, together with those from two recent genome scans, make this the best supported linkage region in BPAD. Further, our data show evidence of a gender effect at this locus with increased sharing predominantly within the male-male pairs. Our scan also provides support for linkage (MLS> or =1.5) at several other regions that have been implicated in meta-analyses of bipolar disorder and/or schizophrenia including 9p21, 10p14-p12 and 18q22.

Bipolar Disorder↗

PubMed2004

Method development and validation for quantitative determination of methadone enantiomers in human plasma by liquid chromatography/tandem mass spectrometry.

A high-throughput method for quantitative determination of methadone enantiomers in human plasma was developed and validated by liquid chromatography/tandem mass spectrometry. The effects of pH and of types and concentrations of mobile-phase modifiers on the enantioselectivity of (R)- and (S)-methadone were investigated on a Chiral-AGP column. A baseline separation of the enantiomers was achieved with a retention time of less than 5 min. Ionization suppression and other matrix effects were evaluated. Morphine, cocaine, 6-monoacetylmorphine, benzoylecgonine and ecgonine methyl ester did not interfere with the performance of the assay. The specificity, linearity, intra- and inter-assay precision and accuracy, and extraction recovery were fully evaluated. The method showed excellent reproducibility (overall coefficient of variance < 8%) and accuracy (overall bias < 2.7%) with a broad linear range. The enantiomers were stable in human plasma after five freeze-thaw cycles, under bench-top storage at room temperature (RT) for 6h, in the extract reconstitution solution at RT for 17 h, and in processed-extracts stored at RT for 142 h. This validated LC/MS/MS assay offers high-throughput and improved specificity, sensitivity, linear range and ruggedness over previously published methods and has been successfully applied to the analysis of clinical samples.

Calibration↗

PubMed2004

Estimating the survival benefits gained from providing national cancer genetic services to women with a family history of breast cancer.

The aim of this paper is to compare a service offering genetic testing and presymptomatic surveillance to women at increased risk of developing breast cancer with its predecessor of no service at all in terms of survival and quality-adjusted survival (QALYs) by means of a Markov cohort chain simulation model. Genetic assessment and presymptomatic care provided between 0.07-1.61 mean additional life years and 0.05-1.67 mean QALYs over no services. Prophylactic surgery and surveillance extended mean life expectancy by 0.41-1.61 and 0.32-0.99 years, respectively over no services for high-risk women. Model outcomes were sensitive to all the parameters varied in the sensitivity analysis. Providing cancer genetic services increase survival and as long as services do not induce adverse psychological effects they also provide more QALYs. The greatest survival and QALY benefits were found for women with identified mutations. As more cancer genes are identified, the survival and cost-effectiveness of genetic services will improve. Although mastectomy provided most additional life years, when quality of life was accounted for oophorectomy was the optimal strategy. Delayed entry into coordinated genetic services was found to diminish the average survival and QALY gains for a woman utilising these services.

Adult↗

PubMed2004

Psychological interventions for coronary heart disease.

BACKGROUND: Psychological interventions can form part of comprehensive cardiac rehabilitation programmes (CCR). These interventions may include stress management interventions, which aim to reduce stress, either as an end in itself or to reduce risk for further cardiac events in patients with heart disease. OBJECTIVES: To determine the effectiveness of psychological interventions, in particular stress management interventions, on mortality and morbidity, psychological measures, quality of life, and modifiable cardiac risk factors, in patients with coronary heart disease (CHD). SEARCH STRATEGY: We searched CCTR to December 2001 (Issue 4, 2001), MEDLINE 1999 to December 2001 and EMBASE 1998 to the end of 2001, PsychINFO and CINAHL to December 2001. In addition, searches of reference lists of papers were made and expert advice was sought. SELECTION CRITERIA: RCTs of non-pharmacological psychological interventions, administered by trained staff, either single modality interventions or a part of CCR with minimum follow up of 6 months. Adults of all ages with CHD (prior myocardial infarction, coronary artery bypass graft or percutaneous transluminal coronary angioplasty, angina pectoris or coronary artery disease defined by angiography). Stress management (SM) trials were identified and reported in combination with other psychological interventions and separately. DATA COLLECTION AND ANALYSIS: Studies were selected, and data were abstracted, independently by two reviewers. Authors were contacted where possible to obtain missing information. MAIN RESULTS: Thirty six trials with 12,841 patients were included. Of these, 18 (5242 patients) were SM trials. Quality of many trials was poor with the majority not reporting adequate concealment of allocation, and only 6 blinded outcome assessors. Combining the results of all trials showed no strong evidence of effect on total or cardiac mortality, or revascularisation. There was a reduction in the number of non-fatal reinfarctions in the intervention group (OR 0.78 (0.67, 0.90), but the two largest trials (with 4809 patients randomized) were null for this outcome, and there was statistical evidence of publication bias. Similar results were seen for the SM subgroup of trials. Provision of any psychological intervention or SM intervention caused small reductions in anxiety and depression. Few trials reported modifiable cardiac risk factors or quality of life. REVIEWERS' CONCLUSIONS: Overall psychological interventions showed no evidence of effect on total or cardiac mortality, but did show small reductions in anxiety and depression in patients with CHD. Similar results were seen for SM interventions when considered separately. However, the poor quality of trials, considerable heterogeneity observed between trials and evidence of significant publication bias make the pooled finding of a reduction in non-fatal myocardial infarction insecure.

Coronary Disease↗

PubMed2004

Levels of mental health problems among UK emergency ambulance workers.

This study examined the prevalence of post-traumatic stress disorder (PTSD), depression, and anxiety in a sample of emergency ambulance personnel. Of 1029 personnel in one ambulance service mailed a questionnaire, 617 were returned. Among respondents, the overall rate of PTSD was 22%. Levels of PTSD did not differ according to grade, but men had a higher prevalence rate than women (23% compared with 15%). Nearly one in ten reported probable clinical levels of depression, 22% reported probable clinical levels of anxiety based on Hospital Anxiety and Depression Scale scores.

Adult↗

PubMed2004

Detection of tet(M) gene from raw milk by rapid DNA extraction followed by a two-step PCR with nested primers.

The likelihood that milk and milk products may act as a vehicle for antibiotic-resistant bacterial genes has become a concern to the food industry and a public health issue, and the demand for rapid tests has increased. The purity of DNA extracted from food samples is a key issue in the sensitivity and usefulness of biological analyses, such as PCR for pathogens and nonpathogens. A rapid, phenol-chloroform free method based on a modification of a sodium iodide DNA extraction, followed by a two-step PCR was developed for direct detection of the tet(M) gene in milk samples within a single working day. This study compares the proposed method with a traditional phenol solvent extraction method and with a commercial kit (QIAamp DNA blood mini kit, Qiagen). The three DNA extraction methods were used to ensure access to the tet(M) gene from 1 ml of raw milk, inoculated with a strain of Enterococcus faecalis, which carries the tet(M) gene. The proposed method, followed by a two-step PCR with nested primers specific for the tet(M) gene, was able to reach a detection limit below 10 CFU/ml in less than 4 h, including the two amplification cycles, thus outperforming in sensitivity and rapidity both the traditional and the commercial method.

Animals↗

PubMed2003

Ionization enhancement in atmospheric pressure chemical ionization and suppression in electrospray ionization between target drugs and stable-isotope-labeled internal standards in quantitative liquid chromatography/tandem mass spectrometry.

The phenomena of ionization suppression in electrospray ionization (ESI) and enhancement in atmospheric pressure chemical ionization (APCI) were investigated in selected-ion monitoring and selected-reaction monitoring modes for nine drugs and their corresponding stable-isotope-labeled internal standards (IS). The results showed that all investigated target drugs and their co-eluting isotope-labeled IS suppress each other's ionization responses in ESI. The factors affecting the extent of suppression in ESI were investigated, including structures and concentrations of drugs, matrix effects, and flow rate. In contrast to the ESI results, APCI caused seven of the nine investigated target drugs and their co-eluting isotope-labeled IS to enhance each other's ionization responses. The mutual ionization suppression or enhancement between drugs and their isotope-labeled IS could possibly influence assay sensitivity, reproducibility, accuracy and linearity in quantitative liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). However, calibration curves were linear if an appropriate IS concentration was selected for a desired calibration range to keep the response factors constant.

Artifacts↗

PubMed2003

Effect of selective vs. non-selective cyclo-oxygenase inhibitors on fetal membrane prostaglandin synthesis.

Increased expression of the inducible isoform of cyclo-oxygenase (COX-2) and prostaglandin output from fetal membranes is a key stage in human parturition. Prostaglandin production can be inhibited by non-steroidal anti-inflammatory drugs (NSAIDs), but these may also inhibit cyclo-oxygenase enzymes in fetal tissues, and hence cause potentially serious side effects. We have compared the concentrations of NSAIDs that inhibit maximal PGE2 synthesis from intact human fetal membrane explants in vitro with those found in human plasma after standard anti-inflammatory treatment. The concentrations of all six drugs that caused a 50% inhibition of fetal membrane prostaglandin output were lower than average plasma levels achieved during treatment. This effect was greatest for nimesulide and indomethacin, indicating that these drugs require further study at low doses in vivo, as this could achieve the same tocolytic effect with diminished adverse fetal effect. These drugs were also the most potent inhibitors of fetal membrane prostaglandin output, consistent with their effects on COX-2 activity.

Adult↗

PubMed2003

Tail docking in dogs: can attitude change be achieved?

The debate about tail docking in domestic dogs continues to rage in many developed countries and attitudes expressed by different community groups remain diametrically opposed. Veterinary associations and welfare organisations typically want the practice banned, while many breeders and pure-bred dog associations just as vigorously oppose the introduction of anti-docking legislation. In recent years, much data have been accumulated concerning the welfare implications of tail docking. A recent evaluation of this literature suggests that the practice has little to recommend it and that, in the absence of reasonable case-by-case justification, it may constitute an unacceptable abuse of a sentient species. Given this situation, it is difficult to understand why many canine interest groups, presumably representing those people who care most about the welfare of companion dogs, should continue to hold such strong attitudes in favour of tail docking. In this review we attempt to explain why different community groups might espouse strong but opposing attitudes, despite having access to the same information. We argue that the theory of cognitive dissonance, popular among social psychologists, may provide a useful framework within which to understand, and attempt to alter, attitudes that persist even though they appear contrary to available empirical evidence.

Animal Welfare↗

PubMed2002

The Wellcome trust UK-Irish bipolar affective disorder sibling-pair genome screen: first stage report.

We have completed the first stage of a two-stage genome wide screen designed to identify chromosomal regions that may harbour susceptibility genes for bipolar affective disorder. The first stage screening sample included 509 subjects from 151 nuclear families recruited within the United Kingdom and Republic of Ireland. This sample contained 154 narrowly defined affected sibling pairs (DSM-IV BPI) and 258 broadly defined affected sibling pairs (DSM-IV BPI, SABP, BPII, BPNOS or MDD(R)), approximately two thirds of all families contained at least one other additional typed individual. All individuals were genotyped using 398 highly polymorphic microsatellite markers from Applied Biosystems's Linkage Mapping Set Version 2. The average inter-marker distance was 9.6 cM and the mean heterozygosity was 0.78. Analysis of these data using non-parametric linkage methods (MAPMAKER/SIBS) found no evidence for loci of major effect and no regions reached genome-wide significance for either suggestive or significant linkage. We identified 19 points across the genome where the MLS exceeded a value set for follow up in our second stage screen (MLS > or = 0.74 (equivalent to a nominal pointwise significance of 5%) under the narrowest diagnostic model). These points were on chromosomes 2, 3, 4, 6, 7, 9, 10, 12, 17, 18 & X. Some of these points overlapped with previous linkage reports both within bipolar affective disorder and other psychiatric illnesses. Under the narrowest diagnostic model, the single most significant multipoint linkage was on chromosome 18 at marker D18S452 (MLS=1.54). Overall the highest MLS was 1.70 on chromosome 2 at marker D2S125, under the broadest diagnostic model.

Adult↗

PubMed2002

Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor.

Identification of the genetic bases for bipolar disorder remains a challenge for the understanding of this disease. Association between 76 candidate genes and bipolar disorder was tested by genotyping 90 single-nucleotide polymorphisms (SNPs) in these genes in 136 parent-proband trios. In this preliminary analysis, SNPs in two genes, brain-derived neurotrophic factor (BDNF) and the alpha subunit of the voltage-dependent calcium channel were associated with bipolar disorder at the P<0.05 level. In view of the large number of hypotheses tested, the two nominally positive associations were then tested in independent populations of bipolar patients and only BDNF remains a potential risk gene. In the replication samples, excess transmission of the valine allele of amino acid 66 of BDNF was observed in the direction of the original result in an additional sample of 334 parent-proband trios (T/U=108/87, P=0.066). Resequencing of 29 kb surrounding the BDNF gene identified 44 additional SNPs. Genotyping eight common SNPs identified three additional markers transmitted to bipolar probands at the P < 0.05 level. Strong LD was observed across this region and all adjacent pairwise haplotypes showed excess transmission to the bipolar proband. Analysis of these haplotypes using TRANSMIT revealed a global P value of 0.03. A single haplotype was identified that is shared by both the original dataset and the replication sample that is uniquely marked by both the rare A allele of the original SNP and a novel allele 11.5 kb 3'. Therefore, this study of 76 candidate genes has identified BDNF as a potential risk allele that will require additional study to confirm.

Bipolar Disorder↗

PubMed2002

Are surgeons effective counsellors for women with a family history of breast cancer?

AIM: In the TRACE (Trial of Genetic Assessment in Breast Cancer) study, the data on the time spent by the surgeon with the women with a family history of breast cancer was analysed with respect to the changes in the anxiety scores and breast cancer worry scores. We wanted to see whether longer consultation times with surgeons improved these scores. METHODS: In the TRACE study, women with a family history of breast cancer attended a standard breast clinic to be seen by a surgeon and nurse specialist. Anxiety scores and breast cancer worry scores of these women were recorded prior to attending the clinic and immediately after their appointment. RESULTS: In the 274 evaluable women, there was a significant improvement in the anxiety and breast cancer worries after surgical consultation but it did not correlate with the length of surgical consultation. However, women in the high-risk group showed a significant reduction of breast cancer worry score with longer consultation (P=0.032). CONCLUSIONS: Spending more time with the women with a family history of breast cancer does not help to reduce anxiety scores and breast cancer worry scores except in the subset of women who were told that their risk of breast cancer was high.

Adult↗

PubMed2002

The proseal laryngeal mask: results of a descriptive trial with experience of 300 cases.

BACKGROUND: The ProSeal laryngeal mask airway (PLMA) is a new laryngeal mask device with a modified cuff and a drainage tube. METHODS: We assessed the PLMA in 300 anaesthetized adults either paralysed or breathing spontaneously. We assessed insertion characteristics, airway seal pressures, haemodynamic response to insertion, ease of gastric tube placement, gastric insufflation, and postoperative sore throat. RESULTS: Insertion was successful in 294 patients (98%) and graded as easy in 274 patients (91%). We found no difference in ease of insertion or success rate with either the introducer or the finger insertion method, or in paralysed or non-paralysed patients. Mean airway seal pressure was 29 cm H2O, and 59 patients (20%) had seal pressures greater than 40 cm H2O. No gastric insufflation was detected. Gastric tube placement was successful in 290 of 294 patients (98.6%). There was no cardiovascular response to insertion, with a small reduction in heart rate 5 min after insertion and significant decreases in mean arterial pressure at 1 and 5 min after insertion. Sore throat was noted in 23% patients after operation and in 16% of patients after 24 h, with 90% of the sore throats described as mild. CONCLUSIONS: The PLMA is a reliable airway management device that can give an effective glottic seal in paralysed and non-paralysed patients. The device allows the easy passage of a gastric tube, causes a minimal haemodynamic response to insertion, and an acceptable incidence of sore throat.

Adolescent↗

PubMed2001

Screening for diabetes in general practice: cross sectional population study.

OBJECTIVE: To assess the policy proposed by the American Diabetes Association of universal screening in general practice of all patients aged over 45 years for diabetes. DESIGN: Cross sectional population study. SETTING: Local general practice in the United Kingdom. PARTICIPANTS: All patients aged over 45 not known to have diabetes. MAIN OUTCOME MEASURES: Prevalence of diabetes in the screened population, cardiovascular risk profile of patients diagnosed as having diabetes after screening. RESULTS: Of 2481 patients aged over 45 and not known to have diabetes, 876 attended for screening. There were no significant demographic differences between the screened and unscreened patients. Prevalence of diabetes in patients with age as a sole risk factor was 0.2% (95% confidence interval 0% to 1.4%). Prevalence of diabetes in patients with age and one or more other risk factors (hypertension, obesity, or a family history of diabetes) was 2.8% (1.6% to 4.7%). Four hours a week for a year would be needed to screen all people over 45 in the practice's population; about half this time would be needed to screen patients with risk factors other than age. More than 80% of patients newly diagnosed as having diabetes had a 10 year risk of coronary heart disease >15%, 73% (45% to 92%) were hypertensive, and 73% (45% to 92%) had a cholesterol concentration >5 mmol/l. CONCLUSIONS: Screening for diabetes in general practice by measuring fasting blood glucose is feasible but has a very low yield in patients whose sole risk factor for diabetes is age over 45. Screening in a low risk population would best be targeted at patients with multiple risk factors.

Aged↗