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Biomedical subjects

A Hall

Publications and source records attributed to A Hall.

At least 19 recordsLinked to original sources
PubMed2006

Association of HLA-DRB1*13 with susceptibility to uveitis in juvenile idiopathic arthritis in two independent data sets.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is the commonest rheumatic disease of childhood. Uveitis is the commonest eye complication of JIA, potentially leading to eye surgery and/or visual loss. JIA is a complex genetic trait with well-established HLA-DRB1 associations. The aim of this study was to investigate the involvement of HLA-DRB1 in JIA-associated uveitis. METHODS: A set of 130 UK Caucasian simplex families consisting of healthy parent(s) and a child affected with juvenile oligoarticular idiopathic arthritis (of which 31 had developed uveitis) had previously been screened for multiple markers in the major histocompatibility complex region. Associations with uveitis were investigated through haplotype pattern mining (HPM) and the extended transmission disequilibrium test (ETDT). A further set of 228 UK Caucasian patients with long-standing JIA were fully genotyped for HLA-DRB1 using PCR with sequence-specific primers. Associations of HLA-DRB1 alleles in patients with uveitis (n = 50) were examined individually using the chi 2 test. RESULTS: In the first cohort, HPM identified significant associations of HLA-DRB1*13 with uveitis in juvenile oligoarthritis (P = 0.002). The ETDT confirmed overtransmission of this allele in the families (empirical global P = 0.018). In the second cohort, the significant association of uveitis with HLA-DRB1*13 was replicated (P = 0.0002, odds ratio 3.4, 95% confidence interval 1.7-6.5). CONCLUSIONS: This study has established the HLA-DRB1*13 association with uveitis in JIA. Further work is necessary in order to explore the prognostic potential of this marker.

Alleles↗
PubMed2005

Rho GTPases and the control of cell behaviour.

Rho, Rac and Cdc42, three members of the Rho family of small GTPases, each control a signal transduction pathway linking membrane receptors to the assembly and disassembly of the actin cytoskeleton and of associated integrin adhesion complexes. Rho regulates stress fibre and focal adhesion assembly, Rac regulates the formation of lamellipodia protrusions and membrane ruffles, and Cdc42 triggers filopodial extensions at the cell periphery. These observations have led to the suggestion that wherever filamentous actin is used to drive a cellular process, Rho GTPases are likely to play an important regulatory role. Rho GTPases have also been reported to control other cellular activities, such as the JNK (c-Jun N-terminal kinase) and p38 MAPK (mitogen-activated protein kinase) cascades, an NADPH oxidase enzyme complex, the transcription factors NF-kappaB (nuclear factor kappaB) and SRF (serum-response factor), and progression through G1 of the cell cycle. Thus Rho, Rac and Cdc42 can regulate the actin cytoskeleton and gene transcription to promote co-ordinated changes in cell behaviour. We have been analysing the biochemical contributions of Rho GTPases in cell movement and have found that Rac controls cell protrusion, while Cdc42 controls cell polarity.

Actins↗
PubMed2005

Increasing cataract surgery to meet Vision 2020 targets; experience from two rural programmes in east Africa.

BACKGROUND: The numbers of cataract surgeries done in sub-Saharan Africa fall short of Vision 2020 targets. Over a few years, two programmes in rural east Africa both achieved significant increases in the number of cataract surgeries they provide, resulting in cataract surgical rates of 1583 for Kwale District in Kenya and 1165 for Kilimanjaro Region in Tanzania. Key components of success in these two programmes are described. METHODS: Data were collected on standard indicators and key personnel interviewed to describe the results and compare the methods employed to increase cataract surgical rates by the Kwale District Eye Centre programme and the Kilimanjaro regional Vision 2020 programme. RESULTS: Key components of success shared by the programmes included: (1) programmes in the community and at the hospital are closely linked so that they increase capacity together; (2) community programmes are "patient friendly," providing service in one stop; (3) the examination team includes eye workers with enough skill to provide treatment and decide who is operable so that patients are not transported needlessly or sent through a lengthy referral chain; (4) sites for visits in the community are selected according to population distribution and they are visited according to a regular schedule. CONCLUSION: The development of "bridging strategies" that create a strong link between hospitals providing clinical service and communities needing these services is a key component to realising Vision 2020 goals in sub-Saharan Africa.

Cataract Extraction↗
PubMed2005

Cost-effectiveness of alternative strategies for the initial medical management of non-ST elevation acute coronary syndrome: systematic review and decision-analytical modelling.

OBJECTIVES: To identify and prioritise key areas of clinical uncertainty regarding the medical management of non-ST elevation acute coronary syndrome (ACS) in current UK practice. DATA SOURCES: Electronic databases. Consultations with clinical advisors. Postal survey of cardiologists. REVIEW METHODS: Potential areas of important uncertainty were identified and 'decision problems' prioritised. A systematic literature review was carried out using standard methods. The constructed decision model consisted of a short-term phase that applied the results of the systematic review and a long-term phase that included relevant information from a UK observational study to extrapolate estimated costs and effects. Sensitivity analyses were undertaken to examine the dependence of the results on baseline parameters, using alternative data sources. Expected value of information analysis was undertaken to estimate the expected value of perfect information associated with the decision problem. This provided an upper bound on the monetary value associated with additional research in the area. RESULTS: Seven current areas of clinical uncertainty (decision problems) in the drug treatment of unstable angina patients were identified. The agents concerned were clopidogrel, low molecular weight heparin, hirudin and intravenous glycoprotein antagonists (GPAs). Twelve published clinical guidelines for unstable angina or non-ST elevation ACS were identified, but few contained recommendations about the specified decision problems. The postal survey of clinicians showed that the greatest disagreement existed for the use of small molecule GPAs, and the greatest uncertainty existed for decisions relating to the use of abciximab (a large molecule GPA). Overall, decision problems concerning the GPA class of drugs were considered to be the highest priority for further study. Selected papers describing the clinical efficacy of treatment were divided into three groups, each representing an alternative strategy. The strategy involving the use of GPAs as part of the initial medical management of all non-ST elevation ACS was the optimal choice, with an incremental cost-effectiveness ratio (ICER) of 5738 pounds per quality-adjusted life-year (QALY) compared with no use of GPAs. Stochastic analysis showed that if the health service is willing to pay 10,000 pounds per additional QALY, the probability of this strategy being cost-effective was around 82%, increasing to 95% at a threshold of 50,000 pounds per QALY. A sensitivity analysis including an additional strategy of using GPAs as part of initial medical management only in patients at particular high risk (as defined by age, ST depression or diabetes) showed that this additional strategy was yet more cost-effective, with an ICER of 3996 pounds per QALY compared with no treatment with GPA. Value of information analysis suggested that there was considerable merit in additional research to reduce the level of uncertainty in the optimal decision. At a threshold of 10,000 pounds per QALY, the maximum potential value of such research in the base case was calculated as 12.7 million pounds per annum for the UK as a whole. Taking account of the greater uncertainty in the sensitivity analyses including clopidogrel, this figure was increased to approximately 50 million pounds. CONCLUSIONS: This study suggests the use of GPAs in all non-ST elevation ACS patients as part of their initial medical management. Sensitivity analysis showed that virtually all of the benefit could be realised by treating only high-risk patients. Further clarification of the optimum role of GPAs in the UK NHS depends on the availability of further high-quality observational and trial data. Value of information analysis derived from the model suggests that a relatively large investment in such research may be worthwhile. Further research should focus on the identification of the characteristics of patients who benefit most from GPAs as part of medical management, the comparison of GPAs with clopidogrel as an adjunct to standard care, follow-up cohort studies of the costs and outcomes of high-risk non-ST elevation ACS over several years, and exploring how clinicians' decisions combine a normative evidence-based decision model with their own personal behavioural perspective.

Acute Disease↗
PubMed2004

Inheritance of the Md-ACS1 gene and its relationship to fruit softening in apple ( Malus x domestica Borkh.).

The 1-aminocyclopropane-1-carboxylic acid synthase (ACS) gene is a member of the ACS gene family that is involved in apple ( Malus x domestica Borkh.) fruit ripening. Presence of an allele ( Md-ACS1-2) of this gene is associated with low internal ethylene concentration in some apple cultivars. In this study, inheritance of Md-ACS1 was determined for 50 apple cultivars/advanced selections and 101 F(1) seedlings from five populations. Following this, the softening pattern of apples stored at 20 degrees C for up to 40 days was examined using 35 fruiting cultivars/selections of defined Md-ACS1 status. Md-ACS1 is inherited in a Mendelian fashion and was found to be linked to fruit softening. Maturity season of genotypes also significantly affected fruit softening. Late-season genotypes in the Md- ACS1-2/2 class had the slowest rate of softening, while early-season Md- ACS1-1/1 genotypes had the most rapid softening rate. The implications of these results are discussed in relation to parental selection and breeding for storage ability in apple.

Alleles↗
PubMed2004

Conclusions about differences in linear growth between Bangladeshi boys and girls depend on the growth reference used.

OBJECTIVE: To examine sex differences in height-for-age z-scores and the percentage stunting among Bangladeshi children estimated using three growth references. DESIGN, SETTING AND SUBJECTS: Data collected between 1990 and 1999 by Helen Keller International's nutritional surveillance system in rural Bangladesh were analyzed for 504 358 children aged 6-59 months. Height-for-age z-scores were estimated using the 1977 NCHS, 2000 CDC and 1990 British growth references. RESULTS: The shape of the growth curves for Bangladeshi boys and girls, and their positions relative to one another, depend on which of the three growth references is used. At 6 months of age the British reference showed no sex difference whereas the NCHS and CDC showed girls to have higher average z-scores than boys by 0.14 and 0.28 s.d., respectively. While all references showed a faster deterioration of girls' z-scores from 6 to 24 months, the magnitude and direction of the sex differences, and how they changed with age, were different. There was greater disagreement about girls' z-scores than boys. Discontinuities at 24 months in the NCHS and CDC produced jagged curves whereas the British curves were smooth. CONCLUSIONS: The assessment of sex differences in linear growth depends on the growth reference used. Reasons for the different results need to be determined and may aid the final development of the new WHO international growth reference and the guidelines for its use. The findings suggest that anthropometry as a tool to explore the effects of societal gender inequality must be used with caution.

Anthropometry↗
PubMed2004

Domestic risk factors for wheeze in urban and rural Ethiopian children.

BACKGROUND: To identify which environmental exposures underpin the emergence of asthma epidemics, we need to study epidemics as they appear, as is now happening in the Jimma region of Ethiopia. We have previously studied risk factors for asthma in adults in Jimma and have now completed a survey of young children. AIM: To establish the prevalence of asthma in urban and rural children in Jimma, and to identify locally important risk factors. DESIGN: Cross-sectional survey. METHODS: All children aged 1-5 years living in Jimma town and three surrounding rural regions were identified. Data were collected using an interviewer-led questionnaire, and consenting children had skin prick tests to house dust mite and cockroach. RESULTS: We surveyed 7155 children, of whom 3623 (51%) were female and 4285 (60%) lived in the urban area. The prevalence of wheeze in the last year was 3.4%, and was lower in the rural area (OR 0.47; 95%CI 0.34-0.66). In the urban area, the main risk factors for wheeze were a longer duration of breastfeeding, use of kerosene, and environmental tobacco smoke, while living with animals was protective. In rural children, the main risk factors were a positive skin prick test and living with animals. DISCUSSION: The prevalence of wheeze in children in the Jimma region is low, particularly in rural children. In addition to having an impact on disease prevalence, place of residence also appears to modify the impact of environmental risk factors for wheeze.

Animals↗
PubMed2004

Anxiety in medical students: is preparation for full-time clinical attachments more dependent upon differences in maturity or on educational programmes for undergraduate and graduate entry students?

INTRODUCTION: The transition to full-time clinical studies holds anxieties for most medical students. While graduate entry medical education has only recently begun in the UK, the parallel undergraduate and graduate entry MBBS courses taught at our school allowed us to study how 2 differently prepared groups perceived this vital time at a comparable stage in their training. METHOD: An anonymous questionnaire collected demographic data and graded anxiety in 13 statements relating to starting full-time clinical attachments. Two open questions allowed free text comment on the most positive and negative influences perceived during this time. Both a statistical analysis and a qualitative assessment were performed to compare the 2 groups of students. RESULTS: The 2 groups were similar with respect to gender but the graduate entry students were significantly older. The graduate entry students were significantly less anxious about most aspects of the transition period compared to the undergraduates. These course differences remained after adjusting for age and sex. When adjusted for course and age, male students expressed less anxiety. The main positive qualitative statements related to continual clinical and communication skills training in the graduate entry group. The main qualitative concerns in both groups related to 'fitting in' and perceived lack of factual knowledge. DISCUSSION: These data support the early introduction of clinical skills teaching, backed up by a fully integrated clinically relevant curriculum with continued assessment, in preparing students and reducing levels of anxiety before they start full-time clinical attachments. These course design differences appear to be more important than any differences in maturity between the 2 groups.

Adaptation, Psychological↗
PubMed2004

IgA antibodies of coeliac disease patients recognise a dominant T cell epitope of A-gliadin.

BACKGROUND: In coeliac disease (CD) patients, the dominant DQ2-Alpha-I-gliadin peptide recognised by CD4 T cells is contained within peptide sequence 57-73 (p57-73) of Alpha-gliadin. This peptide sequence is also located within a 33-mer protease resistant gliadin fragment and therefore is likely to play an important role in the pathogenesis of CD. AIMS: Our aim was to determine whether a B cell epitope was present within the immunodominant T cell epitope of Alpha-gliadin and, if so, to elucidate its sequence and determine the importance of deamidation and/or modification of the amino acid at position 65 for IgA binding. PATIENTS AND METHODS: A cohort of CD patients, disease controls, and healthy individuals were examined. Serum IgA antibodies to the native and modified p57-73 fragment of Alpha-gliadin were analysed using enzyme linked immunosorbent assays. Peptide scanning experiments were further used to elucidate the B cell epitope. RESULTS AND CONCLUSION: IgA antibodies to p57-73 were found in 29/72 (40.2%) endomysial antibody positive patients, all of whom had CD. The peptide antibody appeared to be present when patients were on a diet containing gluten and declined on a gluten free diet. The p57-73 antibody was very specific for CD (98%) and had a sensitivity of 56%. The amino acid at position 65 was not important for IgA binding but was crucial for T cell recognition of p57-73. Pentapeptide PXPQP emerges as a potentially strong candidate for the IgA binding motif in this region of Alpha-gliadin. This study shows that a significant proportion of newly diagnosed CD patients have an antibody response to the immunodominant T cell epitope.

Amino Acid Sequence↗
PubMed2004

A review of potential new diagnostic modalities for caries lesions.

This paper aims to present a simple overview of potential new diagnostic methods for dental caries. There are several novel methods of caries detection (with potential application to diagnosis) which have been proposed in the last few years, in addition to those that are gaining some commercial exposure and clinical acceptance. For the most part, these methods have been demonstrated in laboratories and are generally many years away from routine clinical application. They include multi-photon imaging, infrared thermography and infrared fluorescence, optical coherence tomography, ultrasound, and terahertz imaging.

Dental Caries↗
PubMed2003

Prevalence of multiple endocrine neoplasia type 1 in young patients with apparently sporadic primary hyperparathyroidism or pancreaticoduodenal endocrine tumours.

BACKGROUND: The appropriate treatment for a sporadic endocrine tumour may be different from those that present as part of the multiple endocrine neoplasia type 1 (MEN1) syndrome. As primary hyperparathyroidism (pHPT) and pancreaticoduodenal endocrine tumours (PETs) are the most common organ manifestations of MEN1, the prevalence of germline mutations in the MEN1 gene was determined in young patients with apparently sporadic pHPT or PETs. METHODS: Eighteen of 705 patients with pHPT and 11 of 93 patients with PETs operated on between 1987 and 2001 had no family history of MEN1, only one organ manifestation and were aged 40 years or less at the time of diagnosis. Fifteen patients with pHPT and eight with PETs agreed to MEN1 gene mutation analysis, which was performed by single-strand conformational variant analysis and direct DNA sequencing. RESULTS: Two of 15 patients (13.3 (95 per cent confidence interval (c.i.) 1.6 to 40.4) per cent) with apparently sporadic pHPT had a MEN1 germline mutation. Both mutations were found in patients with pHPT due to multiglandular disease, whereas the remaining 13 patients had a solitary adenoma. None of the eight patients with PETs carried a MEN1 germline mutation. CONCLUSION: Sporadic pHPT due to multiglandular disease in patients younger than 40 years may represent the first organ manifestation of MEN1 despite a negative family history.

Adolescent↗
PubMed2003

Psychiatric adjustment in chronic fatigue syndrome of childhood and in juvenile idiopathic arthritis.

BACKGROUND: High rates of psychopathology and of personality problems have been reported in children and adolescents with chronic fatigue syndrome (CFS). It is not clear whether this is consequent on the experience of chronic physical ill health. We compare psychiatric adjustment in children with CFS and in children suffering from another chronic physical disorder (juvenile idiopathic arthritis or JIA). METHOD: Our sample consisted of 28 children with CFS and 30 with JIA attending tertiary paediatric centres (age range, 11 to 18 years, mean 15, S.D. 2.3). In order to assess psychiatric status and functioning, we used the K-SADS psychiatric interviews, CGAS and Harter Self-Esteem Questionnaire with child subjects; behavioural questionnaires (CBCL) and child personality assessment interviews (PAS) with parent informants. RESULTS: Psychiatric disorders in the year prior to interview had been present significantly more commonly in the CFS group (72% v. 34% in JIA) and were more impairing to them (CGAS scores of 45 v. 77). Most common diagnoses in both groups were depressive and anxiety disorders. Personality problems were also significantly more frequent in CFS subjects (48% disorder and 26% difficulty v. 11% and 11% in JIA). There were few differences between the two groups in self-esteem. CONCLUSIONS: Psychopathology and personality problems are common in children and adolescents with severe forms of CFS and cannot be explained strictly through the experience of chronic physical illness.

Adaptation, Psychological↗
PubMed2003

Uranium(VL) interactions with OPC/PFA grout.

The sorption of uranium on to Ordinary Portland Cement (OPC)/Pulverized Fuel Ash (PFA, fly ash) grout material has been investigated with respect to time, pH, grout:uranium ratio and the chemical composition of the supporting solution. The information obtained is of relevance to the disposal of low-level nuclear waste. The grout material has been chemically characterised and is negatively charged above pH 2.3. At the uranium concentrations studied (2 microM) all uranyl hydroxide aqueous species are expected to be monomeric, rather than polymeric. Uranium(VI) sorption on to the grout material has been explained in terms of inner sphere complexation binding by means of hydroxide bridge formation between the uranium and grout surface. It is also proposed that oligomeric uranyl species are formed across the grout surface, perhaps stabilising the repulsive effects of the negatively charged grout surface and anionic uranyl hydroxide species. Thermodynamic modelling has been used to explain the sorption variation versus solution pH and identifies potential binding mechanisms.

Adsorption↗
PubMed2002

Global distribution of halogenated dimethyl bipyrroles in marine mammal blubber.

Four halogenated dimethyl bipyrroles (HDBPs), hypothesized to be naturally produced, were quantitated in marine mammal blubber from a number of species obtained from various locations worldwide. HDBPs were found in samples from all locations studied. Concentrations of total HDBPs (SigmaHDBPs) ranged from 0.4 ng/g lipid weight in ringed seals (Phoca hispida) from the White Sea to 2,540 ng/g lipid weight in Dall's porpoise (Phocoenoides dalli) from the northwestern North Pacific Ocean. At their highest levels, SigmaHDBPs made up 11% of the total quantitated organohalogen body burden of adult male Dall's porpoises. In two beluga (Delphinapterus leucas) data subsets, it was found that males contained significantly higher concentrations of SigmaHDBPs than females. No significant effects of age or sex on SigmaHDBPs were observed in harbor seal (Phoca vitulina) and bowhead whale (Balaena mysticetus) data subsets. The geographical distribution of concentrations did not resemble that of the ubiquitous anthropogenic organohalogen, polychlorinated biphenyl congener CB-153. Higher concentrations of HDBPs and different patterns of congeners were observed in samples from Pacific as opposed to non-Pacific Ocean influenced environments. Concentrations of HDBPs in beluga from the Arctic and St. Lawrence River were similar. Their high abundance in north Pacific Ocean biota and widespread occurrence suggest that HDBPs undergo extensive transport from a source located primarily in the Pacific Ocean. Evidence from HDBP congener patterns indicates that both ocean currents and atmospheric transport likely play a role in the movement of HDBPs. These results imply that HDBPs and anthropogenic organohalogens have different sources and support the natural production hypothesis.

Adipose Tissue↗