Expression of thiopurine methyltransferase in South Asians.
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Asia, Southeastern↗
Biomedical subjects
M Browne
Publications and source records attributed to M Browne.
Low-probability event-detection and separation via statistical wavelet thresholding: an application to psychophysiological denoising.
OBJECTIVES: The aim of this paper is to introduce and test a general, wavelet-based method for the automatic removal of noise and artefact from psychophysiological data. METHODS: Statistical wavelet thresholding (SWT) performs blind source separation by transforming data to the wavelet domain, and subsequent filtering of wavelet coefficients based on a statistical framework. The observed wavelet coefficients are modelled using a Gaussian distribution, from which low-probability outliers are attenuated based on their z-scores. RESULTS: The technique was applied to both simulated and real event-related potentials (ERP) data. SWT applied to artificial data displayed increased signal-to-noise ratio (SNR) improvements as noise amplitude increased. ERP averages of filtered experimental data displayed a correlation of 0.93 with operator-filtered data, compared with a correlation of 0.56 for unfiltered data. The energy of operator-designated contaminated trials was attenuated by a factor of 7.46 relative to uncontaminated trials. SNR improvement was observed in simulated tests. CONCLUSIONS: Variations of SWT may be useful in situations where one wishes to separate uncommon/uncharacteristic structures from time series data sets. For artefact removal applications, SWT appears to be a valid alternative to expert operator screening.
Artifacts↗
Ischaemic optic neuropathy following bilateral neck dissection.
Two cases of ischaemic optic neuropathy, which occurred as a complication of oncological neck surgery, are reported. These cases are submitted because of the apparent scarcity in the literature of this complication after head and neck surgery. They are also unusual because they presented with different clinical manifestations of ischaemic optic neuropathy after separate forms of bilateral neck dissection. A literature review identifies a small number of similar cases and risk factors and preventative measures are discussed.
Carcinoma, Squamous Cell↗
Expandable metal stents in the palliation of malignant dysphagia and oesophageal-respiratory fistulae.
The use of self expandable metal stents in the palliation of malignant dysphagia and oesophago-respiratory fistulae has increased in recent years. The aim of this study was to report a comprehensive 4 year audit of a Specialist Unit's experience with the expandable stent. 200 expandable metal stents were deployed for palliation of non operable malignant dysphagia or fistulae. Per-operative, early (<30 days) and late (>30 days) complications specific to the stent were documented. Stents were successfully positioned in all patients. There was no mortality associated with the insertion and no perforation. Dysphagia was palliated initially in 93 per cent of cases. The mean dysphagia score improved significantly from 3.2 to 1.5 (p<0.01). This significant benefit persisted at 3 months and 6 months of follow-up. The commonest complication was stent migration (5.5%) and 23 patients (11%) required a second stent insertion. Oesophago-respiratory fistulae were successfully palliated in all cases. This study demonstrates the effectiveness of self expandable metallic stents in the palliation of non operable malignant dysphagia and oesophago-respiratory fistulae. The minimal risk of significant complications and low incidence of reintervention should establish this approach as first line palliation in these patients.
Aged↗
Adaptive wavelet filtering for analysis of event-related potentials from the electro-encephalogram.
A challenging task in psychophysiology is the extraction of event-related potentials (ERPs) from the background electro-encephalogram. The task is made more difficult by the properties of ERPs, which typically consist of multiple features of variable latency, localised in time and frequency. A novel technique is described for analysis of ERPs, adaptive wavelet filtering (AWF), which is proposed as an alternative to trial averaging. Band-limited detail representations of each trial are obtained using wavelet analysis. The Woody adaptive filter is then used to align trials with respect to the evoked response. In a simulation study, the AWF extracts 39% of higher-frequency signal variance from background noise, compared with less than 1% for standard averaging and the Woody filter. The AWF is applied to a data-set of 448 ERPs, comprising right-finger button presses from eight subjects. Average split-half reliability of the AWF on scales up to 12 Hz was 0.51.
Electroencephalography↗
Implementation of a large-scale ENU mutagenesis program: towards increasing the mouse mutant resource.
Systematic approaches to mouse mutagenesis will be vital for future studies of gene function. We have begun a major ENU mutagenesis program incorporating a large genome-wide screen for dominant mutations. Progeny of ENU-mutagenized mice are screened for visible defects at birth and weaning, and at 5 weeks of age by using a systematic and semi-quantitative screening protocol-SHIRPA. Following this, mice are screened for abnormal locomotor activity and for deficits in prepulse inhibition of the acoustic startle response. Moreover, in the primary screen, blood is collected from mice and subjected to a comprehensive clinical biochemical analysis. Subsequently, secondary and tertiary screens of increasing complexity can be used on animals demonstrating deficits in the primary screen. Frozen sperm is archived from all the male mice passing through the screen. In addition, tail tips are stored for DNA. Overall, the program will provide an extensive new resource of mutant and phenotype data to the mouse and human genetics communities at large. The challenge now is to employ the expanding mouse mutant resource to improve the mutant map of the mouse. An improved mutant map of the mouse will be an important asset in exploiting the growing gene map of the mouse and assisting with the identification of genes underlying novel mutations-with consequent benefits for the analysis of gene function and the identification of novel pathways.
Animals↗
Effect of mechanical surface pretreatment on metal ion release.
The degree of metal ion dissolution from Ti-6Al-4V alloy hip replacement stems subjected to various mechanical and chemical surface pretreatments was analysed in vitro. High-dissolution rates were observed for nitric acid passivated samples that had been mechanically surface treated to increase the implant surface area. Significantly lower ion release levels were observed for mechanically treated samples which had been aged in de-ionised water. The application of an hydroxyapatite coating decreased the metal ion release from the nitric acid passivated samples (compared to the uncoated sample) and increased the metal ion dissolution from the aged samples. The dissolution behaviour of the samples is explained in terms of the diffusion processes occurring at the stem/solution interface and the morphological and chemical characteristics of the surface treated stems.
Alloys↗
A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse.
As the human genome project approaches completion, the challenge for mammalian geneticists is to develop approaches for the systematic determination of mammalian gene function. Mouse mutagenesis will be a key element of studies of gene function. Phenotype-driven approaches using the chemical mutagen ethylnitrosourea (ENU) represent a potentially efficient route for the generation of large numbers of mutant mice that can be screened for novel phenotypes. The advantage of this approach is that, in assessing gene function, no a priori assumptions are made about the genes involved in any pathway. Phenotype-driven mutagenesis is thus an effective method for the identification of novel genes and pathways. We have undertaken a genome-wide, phenotype-driven screen for dominant mutations in the mouse. We generated and screened over 26,000 mice, and recovered some 500 new mouse mutants. Our work, along with the programme reported in the accompanying paper, has led to a substantial increase in the mouse mutant resource and represents a first step towards systematic studies of gene function in mammalian genetics.
Animals↗
Optimization of routine plasma homocysteine monitoring.
An elevated plasma homocysteine (Hcy) level is now considered to be an important risk factor in arterial and venous thromboembolic events. As a result of this relatively recent finding, there has been a dramatic increase in the number of requests for Hcy measurement. In our laboratory, this demand has been met by employing an automated immunoassay and improving the pre-analytical handling of blood samples. An automated fluorescent polarization immunoassay (FPIA) gave similar results to a reference high-pressure chromatographic (HPLC) method (r2 = 0.98, enzyme immunoassay = 0.998 HPLC - 0.3) and excellent between-run reproducibility (coefficient of variation <3%). The new assay also required less specialized technical input, and improved the sample throughput two-fold. Pre-analytical stability of plasma Hcy concentrations in blood samples is crucial to the accuracy of Hcy monitoring. This stability was improved 10-fold by adopting the anticoagulant acidic citrate instead of ethylenediamine tetraacetic acid for Hcy screening by FPIA. Acidic citrate dramatically inhibits time-related plasma contamination by red-cell Hcy, resulting in improved accuracy and a reduced number of 'spoiled' specimen discards.
Drug Monitoring↗
Professional roller hockey injuries.
OBJECTIVE: To study the incidence and types of injuries sustained by professional roller hockey players in practices and games, and to compare these statistics with those from ice hockey. DESIGN: This injury survey used a strict definition of injury, standardized reporting strategies, and diagnosis by a team physician as standards by which to analyze the characteristics of roller hockey injuries. SETTING: The injuries were recorded after the players had been examined by a team physician at the game or practice site or in the physician's office. PARTICIPANTS: During three seasons for one roller hockey team and one season for another team, an average of 22 players per team participated in the study. Due to personnel changes, the team rosters were modified between seasons. Each player injury was included in the study. An injury was defined as any physical impairment caused during a practice or game that eliminated the player from that practice or game or the next day's practice session or contest, or any physical ailment that necessitated a physical examination by the team physicians. MAIN OUTCOME MEASURE: Injury data were categorized and injury rates were calculated. RESULTS: 122 injuries were recorded during four professional roller hockey seasons, resulting in an overall participation injury rate of 14.4 per 1,000 player hours. The game injury rate was 304.9 per 1,000 player hours. The players were 105.1 times more likely to be injured during a game than during practice. Preseason practices produced 4.5 times more injuries than regular season practices. In comparison, sample data from the only other published study of roller hockey injuries and from several studies of ice hockey have indicated game injury rates of 139.0 (roller hockey), 119.0, 96.1, 78.4, 78.8, and 66.0 per 1,000 player hours, respectively. CONCLUSION: Results of this study demonstrate that roller hockey produces a higher rate of both contact and noncontact injuries than ice hockey; this contradicts the findings of the only other published research study on injuries in roller versus ice hockey. This increased incidence of injury may be due in part to the differences in surfaces, and can prove hazardous to even the recreational roller hockey player or in-line skater.
Adolescent↗
Community hospitals. Cornish hops.
A joint health and social services trial initiative to facilitate transfers from acute hospitals to four community hospitals in east Cornwall has increased placements. Discharge planning from the community hospitals has also been improved with the appointment of a specialist social worker. Staff involved believe the project has improved communication between agencies.
Adult↗
Effect of residency program merger on undergraduate medical student education in obstetrics and gynecology.
OBJECTIVE: To evaluate the effect of residency program merger on third-year medical student clerkships using student evaluations of their experiences and standardized subject examination scores. METHODS: End-of-clerkship ratings from student evaluations and National Board of Medical Examiners standardized subject examination scores in obstetrics and gynecology were used from clerkship sites where three separate military residency programs in obstetrics and gynecology recently merged into two new programs. Mean student evaluation scores and subject examination scores for the year preceding and the year following the merger were compared. RESULTS: The mean differences in medical student evaluation scores before and after merger of the residency programs were 0.1 (Mann-Whitney rank sum, P = .1), -0.1 (Mann-Whitney rank sum, P = .8), and 0.2 (Mann-Whitney rank sum, P = .3). The mean differences for subject examination scores before and after merger of the residency programs were -3.5 (95% confidence interval [CI] -33.2, 26.2; paired t test), -30.1 (95% CI -58.9, -1.4; paired t test), and -35.3 (95% CI -74.8, 4.3; paired t test). CONCLUSION: Merger of residency programs in obstetrics and gynecology does not appear to have a deleterious effect on medical students' satisfaction with the clerkship or their performance on standardized subject examinations at our institution.
Clinical Clerkship↗
Reliability theory for load bearing biomedical implants.
At present, load-bearing implants are designed on a deterministic basis in which the structural strength and applied loading are given fixed values, and global safety factors are applied to (i) cover any uncertainties in these quantities, and (ii) to design against failure of the component. This approach will become increasingly inappropriate as younger and more active patient demands become more exacting and as devices become more complex. The present work describes a preliminary investigation in which a scientific and probabilistic technique is applied to assess the structural integrity of the knee tibial tray. It is envisaged that by applying such a technique to other load bearing biomedical devices, reliability theory may aid in future lifing procedures and materials/design optimisation.
Models, Theoretical↗
Vascular actions of 17beta-oestradiol in rat aorta and mesenteric artery.
1. It has been proposed that the cardiovascular protective actions of 17beta-oestradiol may involve calcium antagonistic actions. We have examined the effects of 17beta-oestradiol on contractions to noradrenaline and KCl in male rat small mesenteric artery and aorta. 2. In rat mesenteric artery, 17beta-oestradiol (10 microM) significantly reduced the maximum contraction to noradrenaline (67.7 +/- 5.8% of control) and KCl (38.8 +/- 3.1% of control) without affecting potency. 3. In rat aorta, 17beta-oestradiol (10 microM) also significantly reduced contractions to noradrenaline (77.5 +/- 4.8% of control), and the effects were mimicked by droloxifene (10 microM). The effect of oestrogen was not prevented by the protein synthesis inhibitor cycloheximide (10 microM). In experiments carried out in calcium-free solution in which calcium stores were depleted, 17beta-oestradiol (10 microM) significantly reduced the contraction to calcium restoration in rat aorta. 4. In aorta from female rats, 17beta-oestradiol (10 microM) significantly reduced contractions to noradrenaline (73.6 +/- 10.8% of control), but this effect of oestrogen was not prevented by cycloheximide (10 microM). 5. In summary, 17beta-oestradiol diminishes the maximum contractile response to noradrenaline in both rat small mesenteric artery and aorta, an effect which at least in the aorta is mimicked by the oestrogen receptor antagonist/partial agonist droloxifene, and may be due to restriction of calcium entry by a nongenomic action.
Animals↗
Bone marrow and recombinant human bone morphogenetic protein-2 in osseous repair.
Bone marrow stem cells and recombinant human bone morphogenetic protein-2 each has the capacity to repair osseous defects. Recombinant human bone morphogenetic proteins require the presence of progenitor cells to function. It is hypothesized that a composite graft of recombinant human bone morphogenetic protein-2 and marrow would be synergistic and could result in superior grafting to autogenous bone graft. Syngeneic Lewis rats with a 5-mm critical sized femoral defect were grafted with recombinant human bone morphogenetic protein-2 and marrow, recombinant human bone morphogenetic protein-2, marrow, syngeneic cancellous bone graft, or carrier alone (control). Serial radiographs (3, 6, 9, 12 weeks) and torque testing (12 weeks) were performed. Bone formation and union were determined. The recombinant human bone morphogenetic protein-2 and marrow composite grafts achieved 100% union at 6 weeks. Recombinant human bone morphogenetic protein alone achieved 80% union by week 12. Both groups yielded a higher union rate and superior mechanical properties than did either syngeneic bone graft (38%) or marrow (47%) alone. The superior performance of recombinant human bone morphogenetic protein-2 combined with bone marrow in comparison with each component alone strongly supports a biologic synergism. This experimentation shows the clinical importance of establishing operative site proximity for the osteoinductive factors and responding progenitor cells.
Animals↗
Alkaline phosphatase activity measurement in the UK by AMP-buffered methods: an appraisal of current practice.
Most UK clinical laboratories use alkaline phosphatase (ALP) methods similar to that proposed by the International Federation of Clinical Chemistry (IFCC), based on the use of 2-amino-2-methyl-1-propanol (AMP) buffer. We present evidence of significant differences in results produced by apparently similar commercial ALP methods using an AMP buffer. We compared Bayer DAX, Dade Dimension and Boehringer Mannheim Hitachi 717 methods. Boehringer and Dade results were higher than Bayer results (Bland and Altman analysis, log transformed data): Boehringer (+23.0%, limits of agreement 1.16-1.31 times Bayer); Dade (+21.9%, limits of agreement 1.13-1.32 times Bayer). Biases were predominantly due to differences in reagents rather than analyser characteristics. Compared to a reagent system prepared exactly as described by the IFCC, Bayer was sub-optimal and Dade and Boehringer methods produced results higher than the IFCC method. Reference ranges and results on patients' samples by the various methods showed large differences but no clinically significant difference was observed in external quality assessment schemes either between Bayer and Boehringer or against method means. Apparently similar methods produce different results in patients' sera: external quality assessment schemes are not useful in highlighting these differences.
Alkaline Phosphatase↗
Porphyria cutanea tarda and hematologic malignancy--a report of 4 cases.
Porphyria cutanea tarda has been reported in association with a variety of myeloproliferative and lymphoproliferative disorders, suggesting a possible association between these conditions. We describe four patients presenting within a 12 month period with sporadic porphyria cutanea tarda shortly following the diagnosis of hematologic malignancy. A review of the literature and evidence supportive of a causal association are presented.
Aged↗
Quantitative EEG in the prediction of antidepressant response to imipramine.
The purpose of this study was to examine the utility of quantitative electroencephalography (QEEG) in the prediction of response to imipramine in depressed patients. Forty patients with a diagnosis of unipolar depression were subjected to a placebo washout and were assessed at pre-drug, 3 h after their first dose of imipramine, and again 2 weeks into treatment. Following 4 weeks of open imipramine treatment, patients were separated into responder (R) and non-responder (NR) groups. Statistical analysis of the 29 patients who completed the study focused on group comparisons of power spectral estimates in four frequency bands from multi-channel recordings. Results showed that theta power differentiated R and NR groups prior to treatment, in response to an acute test dose, as well as after 2 weeks of active drug treatment. Results based on this exploratory study suggest that QEEG may be a useful early predictor of response to imipramine.
Adult↗