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Biomedical subjects

M Wright

Publications and source records attributed to M Wright.

At least 37 records · Page 2Linked to original sources
PubMed2003

A consideration of the time taken to do dacryo-cystorhinostomy (DCR) surgery.

PURPOSE: Comparison of surgical times for dacryocystorhinostomy (DCR) by three different approaches: (1) external, (2) endoscopic endonasal surgical (EES), and (3) endoscopic endonasal laser (EEL) using the holmium:YAG laser. The merits and limitations of each approach are considered and surgical throughput predicted. METHODS: Prospective study of adult patients undergoing primary DCR surgery for nasolacrimal duct obstruction. Surgical times were recorded. Subjective and objective outcomes were assessed at a minimum of 6 months. RESULTS: A total of 48 patients undergoing 51 DCR procedures were studied. The mean surgical time for primary external (n=20), EES-DCR (n=16), and EEL-DCR (n=15) was 41.1+/-10.3, 39.6+/-13.8, and 20.9+/-7.8 min, with symptomatic success achieved in 95, 88, and 60%, respectively. Follow-up was 6-36 months, mean 8 months. It was calculated that if six EEL-DCR, four EES-DCR, or three external DCRs are performed per list for 45 lists per annum, this equals a total of 270 EEL-DCR, 180 EES-DCR, and 135 external DCRs. Of these, 108 EEL-DCR, 22 EES-DCR, and seven external DCRs will fail. If 75% of these have redo surgery using the same technique, an extra 13.5 (EEL-DCR), four (EES-DCR), and two (external DCR) lists are needed. CONCLUSIONS: There was no significant difference between the time taken to do EES-DCR compared to external DCR, and their clinical outcomes. Only EEL-DCR was significantly faster (P<0.001). However, its lower success rate negates the apparent benefit from the greater surgical throughput.

Adolescent↗
PubMed2003

Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection: roles of MxA, OAS-1 and PKR.

Interferon stimulates the expression of a number of genes encoding enzymes with antiviral activities, including myxovirus resistance-1 (MxA), 2-5-oligoadenylate synthetase 1 (OAS-1) and double-stranded RNA-dependent protein kinase (PKR). We examined whether polymorphisms in these genes influenced the outcome of hepatitis C virus (HCV) infection. We observed a lower frequency of the GG genotype at position -88 in the MxA gene promoter in self-limiting HCV infection (OR=0.56; 95% CI: 0.35-0.8; P=0.010) and in nonresponders to therapy (OR=0.49; 95% CI: 0.25-0.95; P=0.020). This genotype predominantly influenced the outcome of treatment in patients with viral genotype 1 (OR=0.22 95% CI: 0.07-0.67; P=0.002). A polymorphism in the 3'-untranslated region of the OAS-1 gene was associated with outcome of infection (GG genotype less frequent in self-limiting infection: OR=0.43; 95% CI: 0.21-0.86; P=0.010). A polymorphism at position -168 in the promoter region of the PKR gene was associated with self-limiting infection (CT genotype: OR=2.75; 95% CI: 1.45-5.24; P=0.002). Further associations were found with a CGG trinucleotide repeat in the 5'UTR region of the PKR gene. Polymorphisms in the interferon-induced genes, MxA, OAS-1 and PKR appear thus associated with HCV outcome.

2',5'-Oligoadenylate Synthetase↗
PubMed2003

What is the problem with breast-feeding? A qualitative analysis of infant feeding perceptions.

AIMS AND OBJECTIVES: Breast-feeding rates are low in Northern Ireland (NI) compared with other regions of Europe. The aim of this study has therefore been to define and explore factors determining infant feeding decisions with a view to the planning of future research and intervention needs. METHOD: Participants were approached at convenience from the throughput of women attending a large teaching hospital antenatal clinic to take part in focus group discussion. RESULTS: Dominant themes indicated that the main barriers to breast-feeding are restricted freedom and independence associated with family issues, return to work, societal embarrassment and perceived social isolation. The dialogue suggested that breast-feeding leads to inability to carry out everyday activities and social exclusion. CONCLUSIONS: Incompatible social norms make it difficult for mothers to breast-feed successfully. This implies that future promotional efforts should take a societal approach.

Adult↗
PubMed2003

Motion analysis of stereotyped hand movements in Rett syndrome.

BACKGROUND: Rett syndrome is a genetic developmental disorder, and stereotyped hand movements are a striking feature of this condition. The aim of the present study was to subject these movements to objective analysis and compare the results in one girl at different ages. METHOD: The hand movements of a 10-year-old girl with Rett syndrome were subjected to accurate, three-dimensional (3D) computerized motion analysis and compared to two-dimensional (2D) video analysis of the same girl at 3 years of age. RESULTS: Three-dimensional computerized analysis revealed regular patterns with strong coupling between the hands. Frequency analysis showed a dominant frequency at 1.2 Hz, with a higher component at 2.4 Hz that may relate to the activity of basic rhythm generators. The same coupling characteristics were extracted from standard, 2D video recordings made at the same time as the 3D capture. CONCLUSION: An informal video of the same girl taken when she was 3 years of age was analysed in the same way as the 2D video and showed the same characteristics, indicating the possible future use of automated video analysis for early screening and intervention evaluation.

Child↗
PubMed2003

Measurement and determinants of the natural history of liver fibrosis in hepatitis C virus infection: a cross sectional and longitudinal study.

INTRODUCTION: The rate of development of liver fibrosis in hepatitis C virus (HCV) infection varies between individuals. This accounts for the variation in duration of progression to cirrhosis. The aims of this study were: (1) to determine whether fibrosis progresses linearly through the grading scales and (2) to identify factors which influence the rate of fibrosis. METHODS: HCV infected patients who had undergone at least one liver biopsy were identified. Biopsies were scored using the modified HAI (Ishak) and METAVIR systems, which were compared. Patients were treatment naïve at first biopsy. Demographic features were examined for their relationship to fibrosis rate (defined as fibrosis stage/infection duration) using univariate and multivariate analysis. A subgroup of patients with two biopsies was examined to test the assumption that fibrosis progresses in a linear fashion. RESULTS: A total of 917 patients were included. Male sex (p<0.00001), older age at infection (p</=0.00001), and viral genotype non-1 (p=0.005) were all associated with a rapid rate of fibrosis. On multiple linear regression they accounted for 29.5% of the variability in fibrosis rate (r(2)=0.295). METAVIR and Ishak scores were highly correlated (r=0.935, p<0.0001). In 137 patients who had two biopsies, the predicted probability for an increase of 1 on the fibrosis score was too low to assess linearity. CONCLUSIONS: Demographic features account for a minority of fibrosis rate variability. The Ishak and METAVIR scoring systems are equivalent. Linearity of fibrosis progression cannot be assessed in biopsies only a few years apart.

Adult↗
PubMed2003

Factor V Leiden polymorphism and the rate of fibrosis development in chronic hepatitis C virus infection.

BACKGROUND: The rate of progression to cirrhosis varies among individuals chronically infected with the hepatitis C virus (HCV). Coagulation pathway activation in models of hepatic fibrosis suggests variation in coagulation pathway components may influence the rate of fibrosis. We hypothesised that polymorphisms of the coagulation factors II and V affect the rate of progression to cirrhosis in HCV infected subjects. METHODS: We studied the relationship between rate of fibrosis (calculated by dividing the fibrosis stage by duration of infection) and genotypes of specific coagulation pathway genes in 352 White European patients infected with HCV. Genotyping was performed using reverse line blot hybridisation. RESULTS: The rate of fibrosis was significantly higher in patients with the factor V Leiden genotype (Arg560Gln) (ANOVA, p=0.004). In disease association studies, a significant association was seen (Fisher's exact test, p=0.029; odds ratio 3.28 for fast progression to cirrhosis (expected to reach cirrhosis in less than 30 years) if heterozygous for factor V Leiden). No associations were seen between factor II genotype and fibrosis rate. CONCLUSIONS: Possession of the factor V Leiden polymorphism significantly increases the risk of rapid disease progression in HCV, suggesting a role for the coagulation system in the pathogenesis of fibrotic liver disease.

Adult↗
PubMed2003

Shall-issue policy and criminal activity among applicants for permits to carry concealed firearms.

Permits to carry concealed firearms in public (CCW permits) remain controversial. A small scale natural experiment with shall-issue CCW permit policy in California, a may-issue state, is reported. During the mid-1990s, the chief of police of the Sacramento County town of Isleton issued permits to all county residents who applied and passed a standard background check. This program received national publicity. The incidence of subsequent criminal activity among 691 persons applying for CCW permits through Isleton's program in 1995 and that in a statewide sample of 965 CCW applicants from 1993-94 were compared. Subjects were followed up for three years from their application dates. The arrest rates for violent crime among Isleton and statewide applicants were 291 and 104 per 100 000 person-years, respectively (relative risk 2.8, 95% confidence interval 0.7 to 11.2, p = 0.18). This suggests that a shall-issue policy for CCW permits may result in higher rates of violent crime among permit holders, but the results do not reach statistical significance; larger studies are needed.

Adult↗
PubMed2003

Borjeson-Forssman-Lehmann syndrome and multiple pituitary hormone deficiency.

We describe two brothers with Borjeson-Forssman-Lehmann syndrome and the 22A-->T (Lys8X) PHF6 mutation, who presented with the symptoms and signs of multiple pituitary hormone deficiency. Biochemical investigations and radiology confirmed growth hormone (GH), thyroid stimulating hormone (TSH) and adrenocorticotrophic hormone (ACTH) as well as gonadotrophin deficiency. They were also found to have optic nerve hypoplasia. This family suggests that the BFL gene product may play an important role in midline neuro-development including the hypothalamo-pituitary axis.

Abnormalities, Multiple↗
PubMed2002

Association of low-density lipoprotein receptor polymorphisms and outcome of hepatitis C infection.

The low-density lipoprotein receptor (LDLR) has been proposed to promote hepatitis C virus endocytosis and the cell membrane protein CD81 may also promote HCV host cell entry. The CD81 gene was sequenced to screen for novel polymorphisms, but no SNPs were identified. Polymorphisms within the LDLR gene are associated with the pathogenesis of familial hypercholesterolemia, atherosclerosis and obesity. We therefore studied genetic variation within the LDLR gene and clinical features of hepatitis C infection. An amino acid change in exon 8 was associated with severity of fibrosis; a SNP in exon 10 correlated with viral clearance and overall inflammation, and a SNP in the 3'UTR appeared to influence treatment response. There were no other significant associations between any of the SNPs studied and the clinical measures of hepatitis C infection. We furthermore report on linkage disequilibrium within the gene and haplotype frequencies in our population. Our findings support a possible role for the LDLR in the modulation of disease progression by affecting immune responses, rather than functioning as receptor for HCV.

Adolescent↗
PubMed2002

Parent-reported health status of overweight and obese Australian primary school children: a cross-sectional population survey.

INTRODUCTION: Childhood overweight/obesity is associated with poor physical and psychosocial health in clinical samples. However, there is little information on the health status of overweight and obese children in the community, who now represent a large proportion of the child population. We examined parent-reported child health and well-being and parent concern about child weight by body mass index (BMI) category in a population sample of primary school children. DESIGN: A stratified two-stage random cluster sample of 24 primary schools representative of the state of Victoria, Australia. MEASURES: BMI (weight/height(2)) transformed to normalised Z-scores using the 1990 UK Growth Reference; the Child Health Questionnaire (CHQ), a 13-scale 50-item parent-completed measure of health and well-being; parent self-reported height and weight; parent concern about child's weight. RESULTS: Data were available for 2863 children aged 5-13 y (50.5% male), of whom 17% were overweight and 5.7% obese. Using logistic regression analyses with 'normal weight' as the referent category, obese boys were at greater risk of poor health (ie <15th centile) on seven of the 12 CHQ scales: Physical Functioning (odds ratio (OR) 2.8), Bodily Pain (OR 1.8), General Health (OR 3.5), Mental Health (OR 2.8), Self Esteem (OR 1.8), Parent Impact-Emotional (OR 1.7) and Parent Impact-Time (OR 1.9). Obese girls were at greater risk of poor health on only two scales: General Health (OR 2.1) and Self Esteem (OR 1.8). Forty-two percent of parents with obese children and 81% with overweight children did not report concern about their child's weight. Parents were more likely to report concern if the child was obese (OR 21.3), overweight (OR 3.5) or underweight (OR 5.4) than normal weight (P<0.05). Concern was not related to child gender, parental BMI or parental education after controlling for child BMI. Perceived health and well-being of overweight/obese children varied little by weight category of the reporting parent (overweight vs non-overweight). CONCLUSIONS: Parents were more likely to report poorer health and well-being for overweight and obese children (particularly obese boys). Parental concern about their child's weight was strongly associated with their child's actual BMI. Despite this, most parents of overweight and obese children did not report poor health or well-being, and a high proportion did not report concern. This has implications for the early identification of such children and the success of prevention and intervention efforts. DOI:10.1038/sj/ijo/0801974

Adolescent↗
PubMed2002

Assessing critical care unit performance: a global measure using graphical analysis.

Outcome measurement in critical care is difficult because of the wide variety of patients treated and the diverse therapeutic options and pathways available. Individual outcome measures for critical care are available but are naturally limited to only a single aspect of performance. Most importantly, better performance in one aspect of care may compromise the standard of care in another. A global measure of performance would be helpful. For the year 1999-2000, the five hospitals in the East Anglian Critical Care Network provided data on capacity, workload and performance. The data was transformed and displayed graphically on a radar chart so that the area of the polygon within the radar chart was proportional to each unit's overall performance. The results from the five hospitals suggest that there is little overall difference in the units' global performance but the graphical representation highlighted some individual deficiencies. Graphical analysis of complex processes such as critical care delivery may facilitate performance assessment, providing that the measures chosen, weightings assigned and scales used are standardised with care.

Bed Occupancy↗
PubMed2002

Vaccination against hepatitis B infection in patients with end stage renal disease.

BACKGROUND: Experience of hepatitis B vaccination in a contemporary renal replacement programme is reported. METHODS: A total of 406 patients were involved: 214 on haemodialysis, 97 on continuous ambulatory peritoneal dialysis, 67 predialysis (serum creatinine >400 micromol/l), and 28 with a failing transplant. Primary vaccination comprised recombinant hepatitis B vaccine (Engerix B) 40 microg intramuscularly at 0, 1, 2, and 3 months. Booster doses were administered three monthly if anti-HBs titre was <100 IU/l. RESULTS: Uptake of vaccine was 61% (haemodialysis 70%, continuous ambulatory peritoneal dialysis 62%, predialysis 31%, transplant 61%, p<0.0001). Primary seroconversion occurred in 64% of vaccinated patients (anti-HBs; 10-100 U/l, 33%; >100 U/l, 31%). Booster doses led to further improvement in immunity in 66/115 (57%) patients after a first and 8/20 (40%) patients after a second booster dose, but uptake was again poor (first booster 74%, second 31%). Seroprotection declined unexpectedly rapidly; after a mean of 16 months 71/115 patients (62 %) had a significant fall in their anti-HBs titres; 30/115 (26%) lost detectable antibody. CONCLUSIONS: Routine hepatitis B vaccination of patients with end stage renal failure is logistically difficult to administer on a large scale; primary seroconversion is relatively poor, but improves after repeated booster doses; protective anti-HBs titres decline rapidly, and yearly antibody checks with selective booster doses will be required to maintain seroprotection. The cost effectiveness of a vaccination programme will vary greatly depending on the prevalence of hepatitis B in the population at risk.

Female↗
PubMed2001

Investigation of relationship between reduced, oxidized, and protein-bound homocysteine and vascular endothelial function in healthy human subjects.

Previous studies investigating homocysteine and vascular disease have relied on total plasma homocysteine as the sole index of homocysteine status. We examined the dynamic relationship between vascular endothelial function and concentrations of total, protein-bound oxidized, free oxidized, and reduced homocysteine to identify the homocysteine form associated with endothelial dysfunction in humans. We investigated 14 healthy volunteers (10 men, 4 women). Brachial artery flow-mediated dilatation was measured at baseline and at 30, 60, 120, 240, and 360 minutes after oral (1) L-methionine (50 mg/kg), (2) L-homocysteine (5 mg/kg), and (3) placebo. Plasma concentrations of total, protein-bound oxidized, free oxidized, and reduced homocysteine were measured at each time point, and nitroglycerin-induced dilatation at was assessed at 0, 120, and 360 minutes. Flow-mediated dilatation fell, and concentrations of total, protein-bound oxidized, free oxidized, and reduced homocysteine increased after oral homocysteine and oral methionine (all P<0.05 for difference in time course compared with placebo). Flow-mediated dilatation showed a reciprocal relationship with reduced homocysteine during both homocysteine and methionine loading. In both loading studies, peak reduction in flow-mediated dilatation coincided with maximal reduced homocysteine concentrations. In contrast, there was no consistent relationship between flow-mediated dilatation and free oxidized homocysteine, protein-bound oxidized homocysteine, or related species. Nitroglycerin-induced dilatation was unchanged by oral homocysteine and oral methionine (P>0.10 compared with placebo). Reduced homocysteine is closely associated with endothelial dysfunction during oral methionine and oral homocysteine loading. Our observations support the hypothesis that reduced homocysteine is the deleterious form of homocysteine for vascular function in vivo and suggest a less important role for other homocysteine species.

Administration, Oral↗
PubMed2001

Biomarkers for assessing occupational exposures to 1,3-butadiene.

The overall objective of this study was to evaluate a continuum of biomarkers in blood and urine for their sensitivities as indicators of low level occupational exposures to 1,3 butadiene (BD). The study design was largely cross-sectional, with biological samples collected within a short timeframe. Personal 8-h BD exposure measures were made on several occasions over a 60-day period for each potentially exposed worker in order provide maximum accuracy for this independent variable and to accommodate the different expression intervals of the several biomarkers. Co-exposures to styrene, toluene and benzene were also measured. The study included 24 BD monomer production workers (mean BD exposure=0.642 mg/m(3)), 34 polymerization workers (mean BD exposure=1.794 mg/m(3)) and 25 controls (mean BD exposure=0.023 mg/m(3)). The several biomarkers were measured by a consortium of investigators at different locations in the US and Europe. These biomarkers included: (1) metabolic genotypes (CYP2E1, EH, GST M1, GST T1, ADH2, ADH3), determined in Prague and Burlington, VT; (2) urinary M1 and M2 metabolites (1,2-dihydroxy-4-[N-acetylcysteinyl]-butane and 1-hydroxy-2-[N-acetylcysteinyl]-3-butene, respectively), determined in Albuquerque, NM and Leiden; (3) hemoglobin adducts (N-[2-dihydroxy-3-butenyl]valine=HBVal and N-[2,3,4-trihydroxybutyl]valine=THBVal), determined in Amsterdam and Chapel Hill, NC, respectively; (4) HPRT mutations determined by autoradiographic assay in Galveston, TX, with slides re-read in Burlington, VT; (6) hypoxanthine-guanine phosphoribosyltransferase (HPRT) mutations determined by cloning assay in Leiden with mutational spectra characterized in Burlington, VT; (7) sister chromatid exchanges and chromosome aberrations determined by standard methods and FISH analysis in Prague. Urinary M1 and M2 metabolites and HBVal and THBVal hemoglobin adducts were all significantly correlated with BD exposure levels, with adducts being the most highly associated. No significant relationships were observed between BD exposures and HPRT mutations or any of the cytogenetic endpoints, regardless of method of assay.

Adult↗
PubMed2001

In vitro selection and characterization of Bcl-X(L)-binding proteins from a mix of tissue-specific mRNA display libraries.

The covalent coupling of an mRNA to the protein that it encodes (mRNA display) provides a powerful tool for analysis of protein function in the post-genomic era. This coupling allows the selective enrichment of individual members from libraries of displayed proteins and the subsequent regeneration of an enriched library using the RNA moiety. Tissue-specific libraries from poly(A)(+) mRNA were prepared by priming first and second strand cDNA synthesis with oligonucleotides containing nine random 3' nucleotides, the fixed regions of which encoded the requisite sequences for formation of mRNA display constructs and a library-specific sequence tag. Starting with a pool of uniquely tagged libraries from different tissues, an iterative selection was performed for binding partners of the anti-apoptotic protein Bcl-X(L). After four rounds of selection, the pool was deconvoluted by polymerase chain reaction amplification with library-specific primers. Subsequent clonal sequence analysis revealed the selection of three members of the Bcl-2 family known to bind to Bcl-X(L). In addition, several proteins not previously demonstrated to interact with Bcl-X(L) were identified. The relative binding affinities of individual selected peptides were determined, as was their susceptibility to competition with a BH3 domain peptide. Based on these data, a putative BH3 domain was identified in most peptides.

Amino Acid Sequence↗