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Biomedical subjects

A Thomas

Publications and source records attributed to A Thomas.

At least 37 records · Page 2Linked to original sources
PubMed2006

HLA class I diversity among rural rainforest inhabitants in Cameroon: identification of A*2612-B*4407 haplotype.

The population distribution of alleles of the classical HLA class I loci in Cameroon has not been well studied but is of particular interest given the AIDS and malarial epidemics afflicting this population. We investigated the genetic diversity of HLA-A, HLA-B and HLA-C alleles in remote populations of Cameroon. Subjects from seven small, isolated, indigenous populations (N = 274) in the rainforest of southern Cameroon were typed for HLA-A, HLA-B and HLA-C alleles using a polymerase chain reaction/sequence-specific oligonucleotide probe assay and sequence analysis. Multiple alleles of the HLA-A (N = 28), HLA-B (N = 41) and HLA-C (N = 21) loci were identified, of which A*2301[allele frequency (AF) = 12.8%], B*5802 (AF = 10.9%) and Cw*0401 (AF = 16.6%) were the most frequent individual alleles and A*02 (AF = 19.0%), B*58 (AF = 15.9%) and Cw*07 (AF = 22.4%) the most common serologically defined groups of alleles. Twenty-six (28.9%) alleles with a frequency of less than 1% (AF < 1%), 39 (43%) with a frequency of 2.0-15.0% (AF = 2.0-15.0%), three globally uncommon alleles [A*2612 (AF = 2.0%), B*4016 (AF = 0.7%) and B*4407 (AF = 1.4%)], and the A*2612-Cw*0701/06/18-B*4407 haplotype (haplotype frequency = 1.3%) were also identified. Heterozygosity values of 0.89, 0.92 and 0.89 were determined for HLA-A, HLA-B and HLA-C, respectively. The extensive allelic and haplotypic diversity observed in this population may have resulted from varied natural selective pressures on the population, as well as intermingling of peoples from multiple origins. Thus, from an anthropologic perspective, these data highlight the challenges in T-cell-based vaccine development, the identification of allogeneic transplant donors and the understanding of infectious disease patterns in different populations.

Cameroon↗
PubMed2006

Initial drug susceptibility profile of M. tuberculosis among patients under TB programme in South India.

SETTING: Pulmonary tuberculosis (PTB) patients enrolled for treatment at government health facilities in a sub-district of Thiruvallur district, Tamil Nadu, India. OBJECTIVES: To determine the drug susceptibility profile among PTB patients admitted to treatment according to the Revised National Tuberculosis Control Programme (RNTCP). METHODOLOGY: From May 1999 to December 2003, two additional sputum samples were collected from all patients at the start of anti-tuberculosis treatment under DOTS and were transported to a central laboratory for Mycobacterium tuberculosis culture and drug susceptibility testing (DST). RESULTS: DST results were available for 1603 new sputum smear-positive patients; 85% of patients had organisms fully susceptible to streptomycin (S), isoniazid (H) and rifampicin (R), 10.4% any resistance to H and 1.7% to HR. Of 443 patients with history of previous anti-tuberculosis treatment, 59% had organisms susceptible to S, H and R, 37% had any resistance to H and 11.7% to HR. CONCLUSION: The DST profile showed that the vast majority of patients have drug-susceptible organisms, and that currently recommended regimens under the RNTCP would be effective in the treatment of TB.

Antitubercular Agents↗
PubMed2006

Association of conversion & cure with initial smear grading among new smear positive pulmonary tuberculosis patients treated with Category I regimen.

BACKGROUND & OBJECTIVES: Early diagnosis of tuberculosis (TB) is important for initiating treatment to gain cure. The present investigation was undertaken to study the association of conversion and cure with initial smear grading among pulmonary tuberculosis (TB) patients registered in a directly observed treatment - short course (DOTS) programme in Tiruvallur district, south India. METHODS: All new smear positive cases registered from May, 1999 to December, 2002 were analysed for conversion and cure related to initial smear grading. RESULTS: Of the 1463 patients, 1206(82.4%) were converted at the end of the intensive phase and 1109 (75.8%) were declared 'cured' after the completion of treatment. The cure rate decreased as the initial smear grading increased and the decrease in trend was statistically significant (P=0.01). Similarly, a significant decrease in conversion rate was also observed with increase in initial smear grading (P<0.001). In multivariate analysis, lower cure rate was significantly associated with patient's age (AOR=1.5, 95% CI=1.1-2.1), alcoholism (AOR=1.7, 95% CI 1.2- 2.4) and conversion at the end of intensive phase (AOR=3.5, 95% CI= 2.6-4.8). INTERPRETATION & CONCLUSION: Cure and conversion rates were linearly associated with initial smear grading. High default and death rates were responsible for low cure and conversion. The proportion of patients who required extension of treatment and those who had an unfavourable treatment outcome were significantly higher among patients with a 3+ initial smear grading. This reiterates the need to pay more attention in motivating these patients to return to regular treatment and sustained commitment in the control of tuberculosis. There is a need to extend the treatment for one more month in the intensive phase of treatment.

Adult↗
PubMed2006

The relationship of neonatal serum vitamin B12 status with birth weight.

Earlier studies have shown a relationship between maternal vitamin B12 status and birth weight. This study extends those findings directly in terms of neonatal vitamin B12 status and birth weight. One hundred and twelve women were followed from the first trimester of pregnancy and maternal blood was obtained in all three trimesters along with cord blood at birth of their neonates. The maternal and cord serum vitamin B12 concentrations were examined in relation to birth weight. There was a significant correlation between vitamin B12 concentration in maternal antenatal serum during each of the trimesters of pregnancy and cord serum (all P< 0.01). Neonates that were born with lower birth weights (categories of <2500 g and 2500-2999g) had significantly lower mean cord serum vitamin B12 concentrations when compared to those who were > or = 3000g (P = 0.02 and P = 0.05 respectively). A similar, however, non significant trend was observed for antenatal vitamin B12 concentrations at first and third trimesters. Cord serum vitamin B12 concentrations were significantly correlated with birth weight, up to 40 weeks of pregnancy (r=0.28, P=0.01) but not beyond that (> or =40 weeks gestation). Vitamin B12 status in the mother was related to neonatal vitamin B12 status as measured by cord serum vitamin B12 concentration. In addition, low neonatal vitamin B12 concentrations were adversely associated with low birth weights.

Adult↗
PubMed2005

"De novo" design of peptides with specific lipid-binding properties.

In this study, we describe an in silico method to design peptides that can be made of non-natural amino acids and elicit specific membrane-interacting properties. The originality of the method holds in the capacities developed to design peptides from any non-natural amino acids as easily as from natural ones, and to test the structure stability by an angular dynamics rather than the currently-used molecular dynamics. The goal of this study was to design a non-natural tilted peptide. Tilted peptides are short protein fragments able to destabilize lipid membranes and characterized by an asymmetric distribution of hydrophobic residues along their helix structure axis. The method is based on the random generation of peptides and their selection on three main criteria: mean hydrophobicity and the presence of at least one polar residue; tilted insertion at the level of the acyl chains of lipids of a membrane; and conformational stability in that hydrophobic phase. From 10,000,000 randomly-generated peptides, four met all the criteria. One was synthesized and tested for its lipid-destabilizing properties. Biophysical assays showed that the "de novo" peptide made of non-natural amino acids is helical either in solution or into lipids as tested by Fourier transform infrared spectroscopy and is able to induce liposome fusion. These results are in agreement with the calculations and validate the theoretical approach.

Animals↗
PubMed2005

Treatment of active Crohn's disease in children using partial enteral nutrition with liquid formula: a randomised controlled trial.

BACKGROUND AND AIMS: Total enteral nutrition (TEN) with a liquid formula can suppress gut inflammation and induce remission in active Crohn's disease. The mechanism is obscure. Studies have suggested that long term nutritional supplementation with a liquid formula (partial enteral nutrition (PEN)) may also suppress inflammation and prevent relapse. The aim of this study was to compare PEN with conventional TEN in active Crohn's disease. PATIENTS AND METHODS: Fifty children with a paediatric Crohn's disease activity index (PCDAI)>20 were randomly assigned to receive 50% (PEN) or 100% (TEN) of their energy requirement as elemental formula for six weeks. The PEN group was encouraged to eat an unrestricted diet while those receiving TEN were not allowed to eat. The primary outcome was achievement of remission (PCDAI<10). Secondary analyses of changes in erythrocyte sedimentation rate (ESR), C reactive protein, albumin, and platelets were performed to look for evidence of anti-inflammatory effects. RESULTS: Remission rate with PEN was lower than with TEN (15% v 42%; p=0.035). Although PCDAI fell in both groups (p=0.001 for both), the reduction was greater with TEN (p=0.005). Moreover, the fall in PCDAI with PEN was due to symptomatic and nutritional benefits. With both treatments there were significant improvements in relation to abdominal pain, "sense of wellbeing", and nutritional status. However, only TEN led to a reduction in diarrhoea (p=0.02), an increase in haemoglobin and albumin, and a fall in platelets and ESR. CONCLUSIONS: TEN suppresses inflammation in active Crohn's disease but PEN does not. This suggests that long term nutritional supplementation, although beneficial to some patients, is unlikely to suppress inflammation and so prevent disease relapse.

Adolescent↗
PubMed2005

Identification and study of Utah pseudo-isolate populations-prospects for gene identification.

Isolate populations of varied types have proven powerful for gene identification for rare Mendelian disorders, and continue to show such promise for more complex phenotypes. Existing isolate populations are limited in the phenotypes available for study, and new population isolates are unlikely to arise. We utilize genealogical data available for the state of Utah, dating back to its European founders, to retrospectively define and examine pseudo-isolate subpopulations. These pseudo-isolate populations are defined by selection of a set of "founders" from the genealogical data, and then limitation of "immigration" by censoring of matings and offspring that do not match the isolate population design. A wide variety of pseudo isolate and other study designs are possible by varying the number and type of founders and the extent of immigration allowed. We present several different example Birth-Country pseudo-isolate populations defined within the Utah Population Database (UPDB). We utilize linked cancer phenotype data available for the Utah population to show the utility of this pseudo-isolate approach for identification of more genetically homogeneous prostate cancer pedigrees for predisposition gene identification. In conclusion, we present a unique approach to retrospective "creation" of isolate populations using existing genealogical data. We use the UPDB to exhibit the utility of this approach for the highly heterogeneous Utah population, and suggest the approach is feasible for any population for which high quality genealogy and phenotype data are available.

Databases as Topic↗
PubMed2005

Comprehensive statistical study of 452 BRCA1 missense substitutions with classification of eight recurrent substitutions as neutral.

BACKGROUND: Genetic testing for hereditary cancer syndromes contributes to the medical management of patients who may be at increased risk of one or more cancers. BRCA1 and BRCA2 testing for hereditary breast and ovarian cancer is one such widely used test. However, clinical testing methods with high sensitivity for deleterious mutations in these genes also detect many unclassified variants, primarily missense substitutions. METHODS: We developed an extension of the Grantham difference, called A-GVGD, to score missense substitutions against the range of variation present at their position in a multiple sequence alignment. Combining two methods, co-occurrence of unclassified variants with clearly deleterious mutations and A-GVGD, we analysed most of the missense substitutions observed in BRCA1. RESULTS: A-GVGD was able to resolve known neutral and deleterious missense substitutions into distinct sets. Additionally, eight previously unclassified BRCA1 missense substitutions observed in trans with one or more deleterious mutations, and within the cross-species range of variation observed at their position in the protein, are now classified as neutral. DISCUSSION: The methods combined here can classify as neutral about 50% of missense substitutions that have been observed with two or more clearly deleterious mutations. Furthermore, odds ratios estimated for sets of substitutions grouped by A-GVGD scores are consistent with the hypothesis that most unclassified substitutions that are within the cross-species range of variation at their position in BRCA1 are also neutral. For most of these, clinical reclassification will require integrated application of other methods such as pooled family histories, segregation analysis, or validated functional assay.

Amino Acid Sequence↗
PubMed2005

Summarizing data through a piecewise linear growth curve model.

Most of the research in clinical trials is based on longitudinal designs, which involve repeated measurements of a variable of interest. Such designs are very powerful, both statistically and scientifically. Recent advances in statistical theory and software development incorporate the covariance structures such as unstructured, compound symmetry, auto-regressive and random effects, etc., for analysing longitudinal data. Hathaway et al. propose a technique for summarizing longitudinal data using linear growth curve model and establish that the number of summary statistics is fixed as four irrespective of the length of study. In this paper, we develop a procedure for analysing the longitudinal data through a piecewise linear growth curve model on the lines of Hathaway et al. Under different covariance structures, the linear model is fitted for Leprosy data and the residual sum of squares computed. Goodness of fit has also been considered for various models. In order to prove that the proposed method is robust and better than the others in terms of goodness of fit, simulation studies are carried out and the results presented.

Biometry↗
PubMed2005

Measurement of helicity-dependent photoabsorption cross sections on the neutron from 815 to 1825 MeV.

Helicity-dependent total photoabsorption cross sections on the deuteron have been measured for the first time at ELSA (Bonn) in the photon energy range from 815 to 1825 MeV. Circularly polarized tagged photons impinging on a longitudinally polarized LiD target have been used together with a highly efficient 4pi detector system. The data around 1 GeV are not compatible with predictions from existing multipole analyses. From the measured energy range an experimental contribution to the GDH integral on the neutron of [33.9 +/- 5.5(stat) +/- 4.5(syst)] microb is extracted.

Journal Article↗
PubMed2005

Molecular tagging of a senescence gene by introgression mapping of a stay-green mutation from Festuca pratensis.

* Intergeneric hybrids between Lolium multiflorum and Festuca pratensis (Lm/Fp) and their derivatives exhibit a unique combination of genetic and cytogenetic characteristics: chromosomes undergo a high frequency of homoeologous recombination at meiosis; the chromosomes of the two species can easily be discriminated by genomic in situ hybridization (GISH); recombination occurs along the entire length of homoeologous bivalents; a high frequency of marker polymorphism is observed between the two species. * This combination of characters has been used to transfer and isolate a F. pratensis chromosome segment carrying a mutant 'stay-green' gene conferring a disrupted leaf senescence phenotype into L. multiflorum. * The genetic location within the introgressed F. pratensis segment of the senescence gene has been mapped using amplified fragment length polymorphisms (AFLPs), and F. pratensis-specific AFLP markers closely flanking the green gene have been cloned. * The use of these cloned sequences as markers for the stay-green locus in marker-assisted selection programmes has been tested. The potential application of Lm/Fp introgressions as a tool for the map-based cloning of introgressed Fp genes is discussed.

Chromosome Mapping↗
PubMed2005

Predictors of relapse among pulmonary tuberculosis patients treated in a DOTS programme in South India.

OBJECTIVE: To identify risk factors associated with relapse among cured tuberculosis (TB) patients in a DOTS programme in South India. DESIGN: Sputum samples collected from a cohort of TB patients registered between April 2000 and December 2001 were examined by fluorescence microscopy for acid-fast bacilli and by culture for Mycobacterium tuberculosis at 6, 12 and 18 months after treatment completion. RESULTS: Of the 534 cured patients, 503 (94%) were followed up for 18 months after treatment completion. Of these, 62 (12%) relapsed during the 18-month period; 48 (77%) of the 62 relapses occurred during the first 6 months of follow-up. Patients who took treatment irregularly were twice more likely to have a relapse than adherent patients (20% vs. 9%; adjusted odds ratio [aOR] 2.5; 95% CI 1.4-4.6). Other independent predictors of relapse were initial drug resistance to isoniazid and/or rifampicin (aOR 4.8; 95% CI 2.0-11.6) and smoking (aOR 3.1; 95% CI 1.6-6.0). The relapse rate among non-smoking, treatment adherent patients with drug-sensitive organisms was 4.8%. CONCLUSIONS: The relapse rate under the DOTS programme may be reduced by ensuring that patients take their treatment regularly and are counselled effectively about quitting smoking.

Adult↗
PubMed2004

Inner calvarial erosion from traumatic subdural haematoma in infancy.

CASE REPORT: This is a report of a case of a subdural haematoma in infancy of possible non-accidental aetiology with raised pericerebral pressure, which we postulate has eroded the inner table of the cranial bones and resulted in leakage of marrow precursor cells into the extradural space. RESULT: Subdural tapping via the fontanelle has created a channel allowing subsequent ingress of nucleated red cell precursors into the subdural space. This addition to the subdural collection has prolonged its course necessitating subduro-peritoneal shunting.

Erythrocytes↗