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Biomedical subjects

C Williamson

Publications and source records attributed to C Williamson.

At least 19 recordsLinked to original sources

Whose interests do lay people represent? Towards an understanding of the role of lay people as members of committees.

Increasingly, lay people are appointed as members to health service committees. The term 'lay' is used loosely and the reasons for involving lay people are seldom clearly defined. This paper argues that the different roles that lay people play need to be explicitly defined in order for their contributions to be realized. Although lay members of health service committees are generally assumed to be working for patients' interests, our observations lead us to think that some lay people tend to support professionals' or managers' interests rather than patients' interests as patients would define them. We suggest that lay people fall into three broad categories: supporters of dominant (professional) interests, supporters of challenging (managerial) interests and supporters of repressed (patient) interests. These alignments should be taken into account in appointments to health service bodies. Further research is needed on the alignments and roles of lay members.

Allied Health Personnel↗

Isolated familial hypomagnesaemia with novel neurological features: causal link or chance concurrence?

We report a patient with isolated familial hypomagnesaemia with hypocalciuria, a rare congenital disorder of magnesium metabolism. During adolescence the patient developed neurological and ophthalmological features not hitherto reported in this condition, including seizures, myoclonus, and retinal pigmentary degeneration. These suggested the phenotype of mitochondrial disease, which has been occasionally reported in association with hypomagnesaemia, but subsequent investigations of mitochondrial function were normal. The pathogenesis of this unusual neurological and ophthalmological syndrome therefore remains uncertain.

Adult↗

Violence, risk, and survival strategies of street prostitution.

The purpose of this qualitative study is to explore the risks and responses of street prostitutes to customer-related violence. Thirteen female street prostitutes, aged 18 to 40, were recruited from a moderate-size, midwestern city in the United States. Eight were non-Hispanic White and five were African American. Respondents participated in individual interviews to identify perceptions of work-related violence, personal risk, and self-protective survival strategies. The constant comparative method was used to analyze data.

Adolescent↗

The bile acid taurocholate impairs rat cardiomyocyte function: a proposed mechanism for intra-uterine fetal death in obstetric cholestasis.

Obstetric cholestasis is a liver disease of pregnancy that can be complicated by sudden, hitherto unexplained, intra-uterine fetal death. Because intra-uterine death occurs suddenly, and because fetal heart rate abnormalities have been reported in obstetric cholestasis, we hypothesized that intra-uterine death is caused by impaired fetal cardiomyocyte function, resulting in fetal cardiac arrest. Obstetric cholestasis is associated with raised levels of maternal and fetal serum bile acids, and we propose that these may alter cardiomyocyte function. It was not possible to investigate the effects of bile acids on the intact human fetal heart at a cellular level. Therefore we used the closest available model of fetal myocardium at term: a primary culture of neonatal rat cardiomyocytes in which cells beat synchronously and develop pacemaker activity. The effect of the primary bile acid taurocholate (0.3 mM and 3 mM) on cultures of single cardiomyocytes, each with its own independent rate of contraction, was a reversible decrease in the rate of contraction and in the proportion of beating cells (P < 0.001). Addition of taurocholate to a network of synchronously beating cells caused a similar decrease in the rate of contraction. Furthermore, the integrity of the network was destroyed, and cells ceased to beat synchronously. Taurocholate also resulted in altered calcium dynamics and loss of synchronous beating. These data suggest that raised levels of the bile acid taurocholate in the fetal serum in obstetric cholestasis may result in the development of a fetal dysrhythmia and in sudden intra-uterine death.

Animals↗

HIV/AIDS-related knowledge, attitudes and practices among South African military recruits.

OBJECTIVES: To assess the level of HIV-related knowledge, as well as high-risk behaviour and attitudes towards HIV, in a group of South African National Defence Force (SANDF) recruits. DESIGN: Cross-sectional study. SETTING: Tempe military base in Bloemfontein. SUBJECTS: Three hundred and thirty-nine recruits from one company. OUTCOME MEASURES: HIV-related knowledge, attitudes and practices based on a self-administered questionnaire. RESULTS: All of the recruits were male, and most of them (81.4%) were black. The majority of recruits (98.5%) were between 18 and 24 years old. They had a good level of knowledge regarding HIV and AIDS, with more than 80% giving a correct response in most cases. However, several important misconceptions regarding HIV/AIDS and its transmission still exist. Furthermore, several recruits still practised high-risk behaviour, such as not using condoms with casual or new partners. Most obtained their knowledge regarding HIV/AIDS from schools (34.8%), health and social services (27.1%) and the printed media (17.7%), while only 5.2% stated that they learnt about HIV/AIDS from the SANDF education programmes. CONCLUSION: Efforts towards initiating behaviour changes in military recruits should be intensified, and if necessary education programmes should be adapted to facilitate achievement of this goal.

Adolescent↗

Influenza virus (A/HK/156/97) hemagglutinin expressed by an alphavirus replicon system protects chickens against lethal infection with Hong Kong-origin H5N1 viruses.

Venezuelan equine encephalitis virus replicon particles (VRP) containing the gene expressing hemagglutinin (HA) from the human Hong Kong Influenza A isolate (A/HK/156/97) were evaluated as vaccines in chicken embryos and young chicks. Expressed HA was readily detected in bird-tissue staining with anti-H5 HA antibody and in chicken cells infected with the replicon preparations following immunoprecipitation with monoclonal antibody. Birds challenged with a dose of the lethal parent virus were protected to different extents depending on the age of the bird. In ovo and 1-day-old inoculated animals that received no boost with the VRP were partially protected; birds 2 weeks of age were completely protected with a single dose of VRP.

Age Factors↗

Heterozygous MDR3 missense mutation associated with intrahepatic cholestasis of pregnancy: evidence for a defect in protein trafficking.

Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy with serious consequences for the mother and fetus. Two pedigrees have been reported with ICP in the mothers of children with a subtype of autosomal recessive progressive familial intrahepatic cholestasis (PFIC) with raised serum gamma-glutamyl transpeptidase (gamma-GT). Affected children have homozygous mutations in the MDR3 gene (also called ABCB4 ), and heterozygous mothers have ICP. More frequently, however, ICP occurs in women with no known family history of PFIC and the genetic basis of this disorder is unknown. We investigated eight women with ICP and raised serum gamma-GT, but with no known family history of PFIC. DNA sequence analysis revealed a C to A transversion in codon 546 in exon 14 of MDR3 in one patient, which results in the missense substitution of the wild-type alanine with an aspartic acid. We performed functional studies of this mutation introduced into MDR1, a closely related homologue of MDR3. Fluorescence activated cell sorting (FACS) and western analysis indicated that this missense mutation causes disruption of protein trafficking with a subsequent lack of functional protein at the cell surface. The demonstration of a heterozygous missense mutation in the MDR3 gene in a patient with ICP with no known family history of PFIC, analysed by functional studies, is a novel finding. This shows that MDR3 mutations are responsible for the additional phenotype of ICP in a subgroup of women with raised gamma-GT.

ATP Binding Cassette Transporter, Subfamily B↗

Allelic frequencies of host genetic variants influencing susceptibility to HIV-1 infection and disease in South African populations.

OBJECTIVES: Limited information is available on the prevalence in African populations of host genetic polymorphisms conferring resistance to HIV-1 infection and disease. The objective of this study was to determine the allelic frequencies in South African populations of the chemokine receptor gene variants CCR5delta32, CCR5m303 and CCR2b-641 and the CXCR4 ligand gene variant SDF1-3'A. METHOD: Cross-sectional study to determine the prevalence of these gene variants in South African subjects of African and European descent. RESULTS: The CCR5delta32 genetic variant is rare in individuals of African origin, having an allelic frequency of 0.1% (n = 1247) compared with 9.8% (n = 144) in Caucasians. The CCR5m303 mutation was not detected in Africans (n = 687), whereas an allelic frequency of 0.9% (n = 145) was identified in Caucasians. The frequency of CCR2b-641 allele was 13.1% (n = 180) in Africans, which was significantly higher that the 7.2% (n = 146) detected in Caucasians. Finally the allelic frequency of the SDF1-3'A gene variant was only 1.0% (n = 198) in Africans compared with 19.8% (n = 145) in Caucasians. CONCLUSIONS: These results indicate that genetic polymorphisms conferring resistance to HIV-1 infection are rare in the South African Black population. Except for the CCR2b-641 gene variant, individuals of African origin also had a much lower prevalence of genetic variants associated with prolonged disease progression.

Alleles↗

Consumer and professional standards: working towards consensus.

Standards of treatment and care should be acceptable to healthcare consumers as well as to healthcare professionals. A simple categorisation of standards according to their acceptability to consumers is outlined. Professional/consumer groups which review and set standards are discussed, with emphasis on the principles of partnership. Working together towards consensus can be difficult but is now an important way forward.

Community Participation↗

Evidence for the involvement of the glutathione pathway in drug resistance in AML.

We have studied altered drug detoxification through the glutathione pathway as a possible mechanism of resistance in 38 patients with AML. GST alpha, mu and pi expressions were determined using immunocytochemistry, the median percentages of positive cells being 73% (range 0-98), 55% (range 0-99) and 97% (range 80-100) respectively. MRP expression was measured using MRPm6 MoAb and flow cytometry. Results were expressed as the ratio of fluorescence associated with MRP over that of an isotype matched control (median, 1.32; range 0.95-2.15). Statistical analyses showed a significant increase in GST alpha expression in blast cells showing in vitro resistance to doxorubicin, with a median value of 78% positive cells compared to 41% in the sensitive group (p < 0.02). There was a significant reduction, however, in GST mu expression from a median value of 60% in newly presenting patients to 40% in a group of patients who had received previous cytotoxic therapy (p < 0.02). Interestingly, patients with high GST mu expression appeared to co-express MRP (p < 0.05). In vitro drug modulation studies, comparing the cytotoxic effect of doxorubicin +/- ethacrynic acid at 6.5 microM resulted in only one significant increase in sensitivity (2.6-fold), out of 22 comparisons. These results support the theory that altered detoxification through the glutathione pathway contributes towards drug resistance in AML. Further studies using fresh blast cells are required to elucidate the importance of this mechanism for individual patients.

ATP-Binding Cassette Transporters↗

Readmission after cardiac operations: prevalence, patterns, and predisposing factors.

OBJECTIVES: This study was undertaken (1) to determine the prevalence of hospital readmission within 1 month of discharge after cardiac operations, (2) to categorize diagnoses responsible for readmission, and (3) to examine predischarge patient factors that influenced readmission. METHODS: Data at 1 month after discharge were obtained for 1665 (98.4%) of 1692 patients who underwent cardiac operations between January 1996 and July 1998. RESULTS: Two hundred twenty-five patients (13.5%) were readmitted to a hospital within a 1-month period after discharge. Forty-eight percent of readmissions were to other hospitals. The most common readmission problems were congestive heart failure (15.6%), atrial fibrillation (12.9%), chest pain (12.0%), wound problems (10.2%), and gastrointestinal problems (8.0%). Hospital discharge on or before the fifth postoperative day was associated with a lower prevalence of subsequent readmission. The independent predictors of a readmission for congestive heart failure were postoperative stay longer than 5 days, diabetes, New York Heart Association functional class IV, preoperative congestive heart failure, total blood product use, the need for postoperative inotropes, body mass index greater than 28 kg/m(2), and reoperation for bleeding. CONCLUSIONS: The prevalence of rehospitalization during the first month after discharge is not trivial. Other than postoperative atrial fibrillation, readmission is probably the single most likely adverse event to befall a patient in the early postoperative period. Patients who are discharged early do not appear to be at increased risk. Patterns in readmission diagnoses suggest opportunities for preventive strategies.

Aged↗

Restriction fragment length polymorphism analysis for rapid gag subtype determination of human immunodeficiency virus type 1 in South Africa.

A rapid method for identification of human immunodeficiency virus Type 1 (HIV-1) gag subtypes was developed based on restriction fragment length polymorphism (RFLP) analysis of 400 or 650 bp long polymerase chain reaction (PCR) fragments encompassing the start of the p17 (400 bp) and part of the p24 (650bp) regions. The consensus sequences of subtypes A-D, the only subtypes identified in South Africa, were analyzed to detect restriction endonucleases which generate unique patterns for each subtype. Four restriction endonucleases were identified: AluI, AccI, SwaI and XmnI. Digestion of a 400 bp fragment with AluI allowed identification of subtype C. Samples not identified were then reamplified, and a 650 bp fragment digested with AccI to identify subtype B, followed by SwaI and XmnI to distinguish between subtypes A and D. This strategy was applied to 87 samples previously subtyped by either sequence analysis of the gag p17 region (n = 33); or heteroduplex mobility assay (HMA) based on the env gene (n = 75); or both (n = 21). Out of the 87 samples, RFLP identified two samples as subtype A, 28 as subtype B, 56 as subtype C and one as a subtype D virus. No discrepancies were found between RFLP gag subtypes and gag sequence subtypes demonstrating the reliability of this method. There was also no discordance between gag RFLP subtypes and env HMA subtypes, suggesting that there were no recombinant viruses detected relating to the genomic regions analyzed. RFLP is an effective technique for the rapid screening in an HIV epidemic of limited diversity, such as in South Africa.

DNA, Viral↗