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Biomedical subjects

A J Hall

Publications and source records attributed to A J Hall.

At least 19 recordsLinked to original sources
PubMed2006

Similar long-term vaccine efficacy of two versus three doses of HBV vaccine in early life.

WHO currently recommends three vaccinations against hepatitis B to provide optimal protection against infection and carriage. However, immunological theory and mathematical modelling suggest that similar protection could be induced with two doses, and trials among adolescents and adults have shown comparable rates for both primary seroprotection and geometric mean titres following vaccination. We determined vaccine efficacy among 60 children who only received two doses of hepatitis B vaccine as infants and among 463 children who had received three doses after 4-7 years of follow-up. Vaccine efficacy among the two-dose group was 86.3% against anti-HBc positivity (infection) and 92.3% against HBsAg positivity (carriage), which was similar to the vaccine efficacy found among the participants who had received three doses. To confirm this comparable vaccine efficacy a randomised controlled non-inferiority trial with long-term follow-up is needed.

Child, Preschool↗
PubMed2006

Gastric mucosal cell model for estimating relative gastrointestinal toxicity of non-steroidal anti-inflammatory drugs.

The study objective was to characterize the AGS human gastric mucosal cell line as a model for estimating gastrointestinal toxicity of COX-inhibiting compounds. Rofecoxib, celecoxib, nimesulide, ibuprofen, indomethacin, aspirin, salicylic acid, naproxen and acetaminophen were tested for inhibition of COX-2-mediated prostaglandin E2 synthesis in A549 and AGS cells. The IC50 ratio AGS/A549 was calculated as an estimate of the therapeutic index (TI) for gastrointestinal toxicity. Calculated IC50 values of non-steroidal anti-inflammatory drugs (NSAIDs) in A549 cells were in excellent agreement with published values (r = 0.996; P < 0.005). Calcium ionophore induction of arachidonic acid release in AGS cells provided TI similar to those using platelets and A549 cells (r = 0.918; P < 0.01). The AGS/A549 model exhibited lower TI than the platelet/A549 model. Spearman ranking correlated clinical NSAID gastropathy with lower AGS TI values. The AGS cell line has excellent potential to serve as a model for assessing the gastrointestinal effects of COX-inhibiting compounds.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Long-term protection against carriage of hepatitis B virus after infant vaccination.

BACKGROUND: Carriage of hepatitis B virus (HBV) is a major risk factor for liver cirrhosis and hepatocellular carcinoma. Infant vaccination has been effective in preventing horizontal transmission during early childhood. It is unknown whether protection is maintained into early adulthood. METHODS: In 1984, early childhood vaccination was introduced in 2 rural Gambian villages. In 2003, serological assessment of 81.5% of 1,350 eligible participants 1-24 years old was done, to determine vaccine efficacy against infection and carriage. RESULTS: Overall vaccine efficacy against infection and carriage was 83.4% (95% confidence interval [CI], 79.8%-86.6%) and 96.5% (85% CI, 93.9%-98.9%), respectively. Vaccine efficacy against infection was similar when restricted to primary responders (85.3%), but a significant effect of peak antibody concentration was found. Both vaccine efficacy and levels of hepatitis B surface antibody (anti-HBs) decreased with age, resulting in a vaccine efficacy against infection and carriage among 20-24-year-old participants of 70.9% (95% CI, 60.4%-80.5%) and 91.1% (95% CI, 75.8%-100%), respectively. Fifteen years after vaccination, fewer than half of the vaccinees had detectable anti-HBs. The prevalence of carriage in the unvaccinated population was similar to the prevalence 20 years earlier. CONCLUSIONS: HBV vaccination early during life can provide long-lasting protection against carriage, despite decreasing antibody levels. The role played by subclinical boosting and the necessity of a booster need to be evaluated.

Adolescent↗
PubMed2006

Incidence of diagnosed polymyalgia rheumatica and temporal arteritis in the United Kingdom, 1990-2001.

OBJECTIVE: To investigate time trends, geographical variation, and seasonality in the incidence of diagnosis of polymyalgia rheumatica (PMR) and temporal arteritis (TA) in the United Kingdom. METHODS: Analysis of computerised medical records from UK general practices. Participants were registered with a practice contributing to the General Practice Research Database during the period 1990-2001. The main outcome measures were rates of diagnosis by year, age, sex, geographical region, and calendar month. RESULTS: 15 013 people had a first diagnosis of PMR and 3928 a first diagnosis of TA during 17 830 028 person-years of observation. The age adjusted incidence rate of PMR was 8.4/10 000 person-years (95% CI 8.3 to 8.6), rising from 6.9/10 000 person-years in 1990 to 9.3/10 000 in 2001. The age adjusted incidence rate of TA was 2.2/10 000 person-years (95% CI 2.1 to 2.3) with no increase observed. Both PMR and TA were more common in the south than in the north of the UK, and both were more commonly diagnosed in the summer months. CONCLUSIONS: The explanation for the findings is unclear. Variations in diagnostic practice and accuracy are likely to have contributed in part to the patterns seen. However, the findings are also likely to reflect, at least in part, variations in the incidence of disease. The striking geographical pattern may be partly attributable to a risk factor which is more prevalent in the south and east of the United Kingdom.

Adult↗
PubMed2005

Risk factors for multidrug resistant tuberculosis in Europe: a systematic review.

BACKGROUND: The resurgence of tuberculosis (TB) in western countries has been attributed to the HIV epidemic, immigration, and drug resistance. Multidrug resistant tuberculosis (MDR-TB) is caused by the transmission of multidrug resistant Mycobacterium tuberculosis strains in new cases, or by the selection of single drug resistant strains induced by previous treatment. The aim of this report is to determine risk factors for MDR-TB in Europe. METHODS: A systematic review was conducted of published reports of risk factors associated with MDR-TB in Europe. Meta-analysis, meta-regression, and sub-grouping were used to pool risk estimates of MDR-TB and to analyse associations with age, sex, immigrant status, HIV status, occurrence year, study design, and area of Europe. RESULTS: Twenty nine papers were eligible for the review from 123 identified in the search. The pooled risk of MDR-TB was 10.23 times higher in previously treated than in never treated cases, with wide heterogeneity between studies. Study design and geographical area were associated with MDR-TB risk estimates in previously treated patients; the risk estimates were higher in cohort studies carried out in western Europe (RR 12.63; 95% CI 8.20 to 19.45) than in eastern Europe (RR 8.53; 95% CI 6.57 to 11.06). National estimates were possible for six countries. MDR-TB cases were more likely to be foreign born (odds ratio (OR) 2.46; 95% CI 1.86 to 3.24), younger than 65 years (OR 2.53; 95% CI 1.74 to 4.83), male (OR 1.38; 95% CI 1.16 to 1.65), and HIV positive (OR 3.52; 95% CI 2.48 to 5.01). CONCLUSIONS: Previous treatment was the strongest determinant of MDR-TB in Europe. Detailed study of the reasons for inadequate treatment could improve control strategies. The risk of MDR-TB in foreign born people needs to be re-evaluated, taking into account any previous treatment.

Adult↗
PubMed2005

Dietary exposure to aflatoxin from maize and groundnut in young children from Benin and Togo, West Africa.

Aflatoxins are a family of fungal toxins that are carcinogenic to man and cause immunosuppression, cancer and growth reduction in animals. We conducted a cross-sectional study among 480 children (age 9 months to 5 years) across 4 agro-ecological zones (SS, NGS, SGS and CS) in Benin and Togo to identify the effect of aflatoxin exposure on child growth and assess the pattern of exposure. Prior reports on this study [Gong, Y.Y.,Cardwell, K., Hounsa, A., Egal, S., Turner, Hall, A.J., Wild, C.P., 2002. Dietary aflatoxin exposure and impaired growth in young children from Benin and Togo: cross sectional study. British Medical Journal 325, 20-21, Gong, Y.Y., Egal, S., Hounsa, A., Turner, P.C., Hall, A.J., Cardwell, K., Wild, C.P., 2003. Determinants of aflatoxin exposure in young children from Benin and Togo, West Africa: the critical role of weaning and weaning foods. International Journal of Epidemiology, 32, 556-562] showed that aflatoxin exposure among these children is widespread (99%) and that growth faltering is associated with high blood aflatoxin-albumin adducts (AF-alb adducts), a measure of recent past exposure. The present report demonstrates that consumption of maize is an important source of aflatoxin exposure for the survey population. Higher AF-alb adducts were correlated with higher A. flavus (CFU) infestation of maize (p=0.006), higher aflatoxin contamination (ppb) of maize (p<0.0001) and higher consumption frequencies of maize (p=0.053). The likelihood of aflatoxin exposure from maize was particularly high in agro-ecological zones where the frequency of maize consumption (SGS and CS), the presence of aflatoxin in maize (SGS) or the presence of A. flavus on maize (NGS and SGS) was relatively high. Socio-economic background did not affect the presence of A. flavus and aflatoxin in maize, but better maternal education was associated with lower frequencies of maize consumption among children from the northernmost agro-ecological zone (SS) (p=0.001). The impact of groundnut consumption on aflatoxin exposure was limited in this population. High AF-alb adduct levels were correlated with high prevalence of A. flavus and aflatoxin in groundnut, but significance was weak after adjustment for weaning status, agro-ecological zone and maternal socio-economic status (resp. p=0.091 and p=0.083). Ingestion of A. flavus and aflatoxin was high in certain agro-ecological zones (SS and SGS) and among the higher socio-economic strata due to higher frequencies of groundnut consumption. Contamination of groundnuts was similar across socio-economic and agro-ecological boundaries. In conclusion, dietary exposure to aflatoxin from groundnut was less than from maize in young children from Benin and Togo. Intervention strategies that aim to reduce dietary exposure in this population need to focus on maize consumption in particular, but they should not ignore consumption of groundnuts.

Aflatoxins↗
PubMed2005

Polybrominated diphenyl ethers and selected organochlorine chemicals in grey seals (Halichoerus grypus) in the North Sea.

Blubber samples from grey seal (Halichoerus grypus) pups were collected in 1998 through to 2000. Twenty four newly weaned pups were sampled in November 1998, 13 of which were re-sampled during their first year of life, between March and December 1999, and an additional 48 and 25 samples (new cohorts) were obtained in 1999 (November-December) and 2000 (May-September) respectively. SimgaPBDE concentrations (sum of Di-HxBDEs) ranged from 45 to 1500 ng/g lipid, with a geometric mean of 290 ng/g lipid. BDE 47 dominated the congener profile, followed by BDEs 100, 99, 153 and 154. SimgaPCB concentrations (sum of 41 congeners) ranged from 100 to 93000 ng/g lipid, with a geometric mean of 4600 ng/g lipid, with CB congeners 153, 138 and 180 making up 84% of the total PCB concentrations. The predominant OC pesticides were p,p'-DDE (geometric mean=860 ng/g lipid, range=160-3800 ng/g lipid) and p,p'-DDT (geometric mean=120 ng/g lipid, range=30-670 ng/g lipid). No significant differences were found between males and females, probably due to the young age of the animals. Significant decreases (P<0.01 for PBDEs and P<0.05 for PCBs/OCs) were observed between newly weaned seals in 1998 and 1999, but not for the majority of juveniles in 1999 and 2000. Significant differences (P<0.01) were also found between the different seasons in 1999 newly weaned and juvenile seals, reflecting changes in blubber mass.

Adipose Tissue↗
PubMed2005

Effect of aspirin on phase gradient of 2F1-F2 distortion product otoacoustic emissions.

It is well known that aspirin consumption temporarily reduces overall otoacoustic emission (OAE) amplitude in humans. However, little is known about changes in the separate components of distortion product otoacoustic emissions (DPOAE), which may be distinguished by examining phase gradients. The effects of aspirin on the phase gradient of the DPOAE 2F1-F2 obtained with fixed frequency ratio sweeps were studied longitudinally in a group of twelve subjects in whom a temporary hearing loss was induced by aspirin consumption. DPOAE were recorded daily for two days pre-aspirin consumption, during the three days of aspirin consumption and two days afterwards. DP-grams were recorded over a restricted frequency range centered on 2,3,4 and 6 kHz with the following stimulus levels: L1/L2 of 60/50-80/70 in 10-dB steps. The effects of aspirin on the phase gradients varied between the subjects and across frequency: the general trend was that the phase gradient became steeper across successive sessions for the higher frequencies, while no significant effect was found at the lower frequencies. These results suggest that aspirin may have more persistent effects on cochlear function than are disclosed by measurements of hearing threshold level or DPOAE amplitude. Particularly, DPOAE phase gradient appears to be increased by aspirin consumption and has not recovered two days after cessation of aspirin intake, despite almost complete recovery of DPOAE amplitude and hearing threshold levels. These findings may suggest differential effects on the distortion and reflection mechanisms considered to underlie DPOAE generation.

Acoustic Stimulation↗
PubMed2005

Estimation of allele frequencies in polyploids under certain patterns of inheritance.

Allele frequencies have long been studied by biologists interested in evolution and speciation. More recently, with the application of molecular markers in human DNA profiling we have also seen the need for reliable population allele frequency estimates for making probabilistic inferences. There is now interest in applying the same DNA profiling technology to identification of plant varieties. HortResearch maintains a large germplasm of horticultural plant species. It is becoming evident that accurate identification of these accessions through DNA fingerprinting is essential for effective utilisation and maintenance of this germplasm. Microsatellites are the markers of choice for this fingerprinting. However, such markers do not reveal the dosage of alleles in a polyploid. Polyploidy is common amongst horticultural plants. Estimating allele frequencies in a polyploid population is, therefore, complicated because of some marker genotypes being phenotypically indistinguishable. For example, in a tetraploid, with four alleles at a locus showing polysomic inheritance, although 35 genotypes are possible, these will fall into only 15 marker phenotypic classes. Furthermore 'null' individuals are rarely detected in polyploids. Furthermore, some polyploids can be cryptic exhibiting disomy, instead of the polysomic inheritance. We will discuss the implications of these factors and present an EM-type algorithm for estimating allele frequencies of a polyploid population under certain patterns of inheritance. The method will be demonstrated on simulated data. We also discuss the nature of some of the additional problems that may be encountered with estimating allele frequencies in polyploids for which other solutions still need to be developed.

Algorithms↗
PubMed2005

Tuberculosis treatment outcomes in Europe: a systematic review.

In order to facilitate the control of tuberculosis (TB), the World Health Organization (WHO) has defined a standardised short-course chemotherapy and a strategy, directly observed therapy. In 2000, WHO surveillance of TB treatments in Europe recorded a successful outcome rate of 77%. The aim of this report is to estimate treatment outcomes in European countries based on published studies and to identify their determinants. A systematic review was conducted of published reports of TB treatment outcomes in Europe. Meta-analysis, meta-regression and subgrouping were used to pool treatment outcomes and analyse associations with mean age, sex, immigration status and multidrug resistance. Of the 197 articles identified in the search, 26 were eligible for the review; 74.4% of outcomes were successful, 12.3% were unsuccessful and 6.8% of patients died. Heterogeneity was high for all outcomes. National estimates were possible for six countries. Multidrug resistance was inversely associated with successful outcome, which were fewer in populations with >9% multidrug-resistant TB, and in patients aged <44 yrs. Successful tuberculosis treatment outcomes were below the 85% threshold suggested by the World Health Organization. There was an inverse association with levels of multidrug-resistant tuberculosis. The unexplained heterogeneity between the studies for unsuccessful outcomes seems to be due to differing interpretations given to World Health Organization definitions.

Adult↗
PubMed2004

Antinuclear antibodies (ANA) in chronic hepatitis C virus infection: correlates of positivity and clinical relevance.

We examined correlates of antinuclear antibody (ANA) positivity (ANA+) in individuals with chronic hepatitis C virus (HCV) infection and the effect of positivity on clinical outcome of HCV. Pretreatment sera from 645 patients from three centres in Sweden (n = 225), the UK (n = 207) and Italy (n = 213) were evaluated by indirect immunofluorescence on Hep-2 cells for ANA pattern and titre by a single laboratory. Liver biopsies were all scored by one pathologist. A total of 258 patients were subsequently treated with interferon monotherapy. There was a significant difference in the prevalence of ANA (1:40) by geographic location: Lund 4.4%, London 8.7%, Padova 10.3% [odds ratio (OR) = 0.66; 95% CI: 0.46-0.94; P = 0.023]. Duration of HCV infection, age at infection, current age, route of infection, viral genotype, alcohol consumption, fibrosis stage and inflammatory score were not correlated with ANA+ or ANA pattern. Female gender was correlated with ANA+ and this association persisted in multivariable analyses (OR = 3.0; P = 0.002). Increased plasma cells were observed in the liver biopsies of ANA-positive individuals compared with ANA-negative individuals, while a trend towards decreased lymphoid aggregates was observed [hazard ratio (HR) = 9.0, P = 0.037; HR = 0.291, P = 0.118, respectively]. No correlations were observed between ANA positivity and nonresponse to therapy (OR = 1.4; P = 0.513), although ANA+ was correlated with faster rates of liver fibrosis, this was not statistically significant (OR = 1.8; P = 0.1452). Low titre ANA+ should not be a contraindication for interferon treatment. Our observation of increased plasma cells in ANA+ biopsies might suggest B-cell polyclonal activity with a secondary clinical manifestation of increased serum immunoglobulins.

Adult↗
PubMed2003

Intraocular lymphoma: a series of 14 patients with clinicopathological features and treatment outcomes.

AIMS: To assess the clinical features, pathology, mortality (systemic outcome) and ocular complications (visual outcome) of a cohort of patients treated for intraocular lymphoma. METHODS: Retrospective case analysis of medical records and review of pathology of a consecutive series of patients presenting with intraocular lymphoma in Melbourne over 11 years between 1990 and 2000. Categorical factors influencing survival were examined by the Kaplan-Meier estimator and groups compared with the log rank test. RESULTS: A total of 14 patients were included. The median age of onset of symptoms was 62.5 years. Most were male (64%) and had bilateral eye involvement (64%). The commonest presentation was vitritis in 12 patients, with a median delay of 4 months before diagnosis. In all, 10 patients had B-cell lymphoma, three patients T-cell lymphoma and one null-cell. Four patients had prior systemic lymphoma. Eight patients had primary central nervous system non-Hodgkin's lymphoma (PCNSL). Treatment included combined radiation to the eye and chemotherapy in 10 patients. Complications of radiotherapy included cataract in five (50%), dry eyes in four (40%), punctate keratopathy in two (20%), radiation retinopathy in two (20%), and optic atrophy in one (10%). A total of 11 patients died of lymphoma (79%). One has residual ocular disease, while two have survived for more than 5 years from initial presentation. Although currently disease free, one of these has a poor visual outcome with acuity less than 6/60 secondary to ocular complications of treatment. CONCLUSIONS: Our study had 29% with prior systemic lymphoma, 57% associated with PCNSL and 14% with intraocular disease only. Overall survival is low (21%) and relapses common in those surviving beyond 12 months. Visual outcome in survivors is very poor due, in large part, to significant complications from radiotherapy.

Adult↗
PubMed2003

Estimation of the risk of hepatitis B virus, hepatitis C virus and human immunodeficiency virus infectious donations entering the blood supply in England, 1993-2001.

BACKGROUND AND OBJECTIVES: The frequency of hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infectious donations entering the blood supply in England is too low to monitor using observational studies. The expected frequency of infectious donations can be estimated and these estimates may be used to contribute to monitoring of blood safety and used in the design of strategies to decrease the risk of transfusion-transmitted infections. MATERIALS AND METHODS: The prevalence and incidence of hepatitis B surface antigen (HBsAg), and antibodies to HCV and HIV (anti-HCV and anti-HIV, respectively) in donors in England, between 1993 and 2001, were used together with data about the length of negative 'window-periods' of current assays for each of these markers and data about test performance, to estimate the number of infectious donations that enter the blood supply. The risks were calculated separately for donations from new donors and from repeat donors, and for the three time periods 1993-95, 1996-98 and 1999-01. RESULTS: The estimated frequency of infectious donations entering the blood supply in England, between 1993 and 2001 was 1 in 260,000 for HBV and 1 in 8 million for HIV. For HCV, the frequency of infectious donations was 1 in 520,000 during 1993-98 and fell to 1 in 30 million during 1999-2001 when all donations were tested for HCV RNA. The frequency of HBV- and HCV-infectious donations entering the blood supply fell over these 9 years: the frequency of HIV-infectious donations remained essentially unchanged. The risk from donations from new donors was found to be approximately sevenfold higher than the risk from donations from repeat donors. CONCLUSIONS: The risks of HBV-, HCV- or HIV-infectious donations entering the blood supply in England are very low, and have decreased since 1993. Although the accuracy of these estimates is imperfect, mainly owing to uncertainty in some assumptions and to small numbers of infections, they provide some quantification of the risk of HBV, HCV or HIV transmission by transfusion, and allow comparison of the magnitude of these risks for each infection and over time. The methods we have used have been developed and improved from previously published methods.

Blood Donors↗
PubMed2003

Determinants of aflatoxin exposure in young children from Benin and Togo, West Africa: the critical role of weaning.

BACKGROUND: Dietary exposure to high levels of the fungal toxin, aflatoxin, occurs in West Africa, where long-term crop storage facilitates fungal growth. METHODS: We conducted a cross-sectional study in Benin and Togo to investigate aflatoxin exposure in children around the time of weaning and correlated these data with food consumption, socioeconomic status, agro-ecological zone of residence, and anthropometric measures. Blood samples from 479 children (age 9 months to 5 years) from 16 villages in four agro-ecological zones were assayed for aflatoxin-albumin adducts (AF-alb) as a measure of recent past (2-3 months) exposure. RESULTS: Aflatoxin-albumin adducts were detected in 475/479 (99%) children (geometric mean 32.8 pg/mg, 95% CI: 25.3-42.5). Adduct levels varied markedly across agro-ecological zones with mean levels being approximately four times higher in the central than in the northern region. The AF-alb level increased with age up to 3 years, and within the 1-3 year age group was significantly (P = 0.0001) related to weaning status; weaned children had approximately twofold higher mean AF-alb adduct levels (38 pg AF-lysine equivalents per mg of albumin [pg/mg]) than those receiving a mixture of breast milk and solid foods after adjustment for age, sex, agro-ecological zone, and socioeconomic status. A higher frequency of maize consumption, but not groundnut consumption, by the child in the preceding week was correlated with higher AF-alb adduct level. We previously reported that the prevalence of stunted growth (height for age Z-score HAZ) and being underweight (weight for age Z-score WAZ) were 33% and 29% respectively by World Health Organziation criteria. Children in these two categories had 30-40% higher mean AF-alb levels than the remainder of the children and strong dose- response relationships were observed between AF-alb levels and the extent of stunting and being underweight. CONCLUSIONS: Exposure to this common toxic contaminant of West African food increases markedly following weaning and exposure early in life is associated with reduced growth. These observations reinforce the need for aflatoxin exposure intervention strategies within high-risk countries, possibly targeted specifically at foods used in the post-weaning period.

Aflatoxins↗