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C Williamson

Publications and source records attributed to C Williamson.

At least 37 records · Page 2Linked to original sources
PubMed2002

Obstetric cholestasis, outcome with active management: a series of 70 cases.

OBJECTIVE: To determine the nature and outcome of obstetric cholestasis in a United Kingdom population. DESIGN: Prospective analysis of clinical outcome in women diagnosed with obstetric cholestasis that is actively managed. SETTING: Antenatal population of three London hospitals between August 1999 and April 2001. POPULATION: Seventy women with obstetric cholestasis defined as abnormal liver function (one or more abnormality in gamma-glutamyl transpeptidase, alanine amino-transferase, aspartate amino-transferase and total bile acids) in a pregnant woman with pruritus, in the absence of other pathology. METHODS: All women were interviewed weekly regarding their symptoms. All were actively managed according to a standardised protocol, which included early delivery before 38 weeks. Obstetric outcome was recorded. RESULTS: Seventy women of mean age 30 (6) years delivered 73 infants. The median gestation at onset of pruritus was 30 (range 4-39) weeks and at diagnosis of obstetric cholestasis was 33.7 (range 21-40.7) weeks. Asian women were more likely to be diagnosed with obstetric cholestasis. Pruritus was usually severe and generalised, and commonly worst on the palms and/or soles of the feet. There were no stillbirths or perinatal deaths. Twenty-five women required caesarean section (36%); only four (16%) were for fetal distress. Twelve women (17%) delivered before 37 weeks, of which eight (67%) were iatrogenic. Ten (14%) infants required admission to the special care baby unit of which four (40%) were ventilated. CONCLUSIONS: Policies of active management result in increased intervention and associated complications. This must be balanced against possible reductions in perinatal mortality.

Adolescent↗
PubMed2002

Human immunodeficiency virus type 1 subtype C molecular phylogeny: consensus sequence for an AIDS vaccine design?

An evolving dominance of human immunodeficiency virus type 1 subtype C (HIV-1C) in the AIDS epidemic has been associated with a high prevalence of HIV-1C infection in the southern African countries and with an expanding epidemic in India and China. Understanding the molecular phylogeny and genetic diversity of HIV-1C viruses may be important for the design and evaluation of an HIV vaccine for ultimate use in the developing world. In this study we analyzed the phylogenetic relationships (i) between 73 non-recombinant HIV-1C near-full-length genome sequences, including 51 isolates from Botswana; (ii) between HIV-1C consensus sequences that represent different geographic subsets; and (iii) between specific isolates and consensus sequences. Based on the phylogenetic analyses of 73 near-full-length genomes, 16 "lineages" (a term that is used hereafter for discussion purposes and does not imply taxonomic standing) were identified within HIV-1C. The lineages were supported by high bootstrap values in maximum-parsimony and neighbor-joining analyses and were confirmed by the maximum-likelihood method. The nucleotide diversity between the 73 HIV-1C isolates (mean value of 8.93%; range, 2.9 to 11.7%) was significantly higher than the diversity of the samples to the consensus sequence (mean value of 4.86%; range, 3.3 to 7.2%, P < 0.0001). The translated amino acid distances to the consensus sequence were significantly lower than distances between samples within all HIV-1C proteins. The consensus sequences of HIV-1C proteins accompanied by amino acid frequencies were presented (that of Gag is presented in this work; those of Pol, Vif, Vpr, Tat, Rev, Vpu, Env, and Nef are presented elsewhere [http://www.aids.harvard.edu/lab_research/concensus_sequence.htm]). Additionally, in the promoter region three NF-kappa B sites (GGGRNNYYCC) were identified within the consensus sequences of the entire set or any subset of HIV-1C isolates. This study suggests that the consensus sequence approach could overcome the high genetic diversity of HIV-1C and facilitate an AIDS vaccine design, particularly if the assumption that an HIV-1C antigen with a more extensive match to the circulating viruses is likely to be more efficacious is proven in efficacy trials.

AIDS Vaccines↗
PubMed2001

Conserved domains of subtype C nef from South African HIV type 1-infected individuals include cytotoxic T lymphocyte epitope-rich regions.

We have characterized 43 nef sequences from subtype C HIV-1-infected South Africans and compared deduced amino acid sequences with other subtypes to identify areas of conservation. Our Nef amino acid sequences were aligned with a consensus subtype B, HXB2 reference strain and a consensus subtype C sequence. All were found to be highly homologous to subtype B in the central region of Nef, but more variable at the N and C termini of the molecule. Alignment of a consensus amino acid sequence generated from South African subtype C Nef with subtypes A, B, and D underscores cross-clade conservation in the central domain of the molecule. This domain is also rich in previously described cytotoxic T lymphocyte (CTL) epitopes that are restricted by commonly found HLA molecules in the South African population.

Amino Acid Sequence↗
PubMed2001

Characterization of full-length HIV type 1 subtype C sequences from South Africa.

Four full-length genome subtype C sequences from South Africa, three of which are being used for vaccine development, were characterized. Three isolates were obtained from recently infected individuals in KwaZulu/Natal: Du151, Du422, and Du179. A fourth isolate, CTSc2, was obtained from an individual residing in Cape Town. All four strains used the CCR5 coreceptor, although Du179 also used CXCR4. The four isolates clustered within subtype C, but the three Du isolates formed a subcluster with a bootstrap value of 100%, with CTSc2 outside the subcluster. None of the strains showed evidence of intersubtype recombination, as expected from the predominance of subtype C in South Africa. All 4 isolates had a 16-amino acid truncation on the 3' end of the Rev protein, identified in other subtype C isolates. Like many other subtype C strains, Du151, Du422, and Du179 had three NF-kappa B-binding sites in the LTR; however, CTSc2 had only two.

Genome, Viral↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

Drugs in pregnancy. Gastrointestinal disease.

Gastrointestinal diseases in pregnancy can be divided into diseases specific to pregnancy, for example, hyperemesis gravidarum, obstetric cholestasis, HELLP syndrome and acute fatty liver of pregnancy, and diseases incidental to pregnancy, for example, inflammatory bowel disease, dyspepsia, peptic ulcer disease and viral hepatitis. Disorders in the second category may present for the first time in pregnancy. This chapter considers the drug management of each of these conditions, with the exception of HELLP syndrome and acute fatty liver. The preferred drug treatment and the known complications associated with their use in pregnancy are also described. Where possible, studies relating to the safety of different therapeutic options are discussed.

Antiemetics↗
PubMed2001

Pruritus may precede abnormal liver function tests in pregnant women with obstetric cholestasis: a longitudinal analysis.

Obstetric cholestasis is a liver disorder unique to pregnancy, which typically presents with pruritus. However, pruritus is common in pregnancy and the diagnosis of obstetric cholestasis is confirmed by finding abnormal liver function. We report 10 cases in which pruritus occurred before any abnormality in liver function tests (including total serum bile acids) and discuss the implications of this for clinical practice.

Adult↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

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↗
PubMed2000

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↗