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Biomedical subjects

R J Hayes

Publications and source records attributed to R J Hayes.

At least 55 records · Page 3Linked to original sources
PubMed1997

Proportion of HIV infections attributable to other sexually transmitted diseases in a rural Ugandan population: simulation model estimates.

BACKGROUND: Unprotected heterosexual contact in the presence of other sexually transmitted diseases (STD) enhances the probability of HIV transmission. The objective of this study was to estimate the proportion of HIV infections attributable to STD in rural Uganda. METHODS: Simulation modelling scenarios of the transmission dynamics of HIV infection and of ulcerative and non-ulcerative STD were employed to address this objective, drawing on data from a specific rural population cohort of 10,000 in south-west Uganda. RESULTS: In simulations of the initial 10-year period of the HIV epidemic (1980-1990), over 90% of HIV infections were attributed to STD. Even given conservative assumptions about the prevalence of STD and about their enhancing effects on HIV transmission, STD played a critical role in the rapid and extensive spread of HIV infection. The role of STD decreased with progression of the HIV epidemic. CONCLUSIONS: In developing countries, control of the spread of HIV infection may benefit substantially from successful STD intervention programmes, and particularly in areas where HIV infection is not already well established.

Adolescent↗
PubMed1997

Profound immunosuppression across the spectrum of opportunistic disease among hospitalized HIV-infected adults in Abidjan, Côte d'Ivoire.

OBJECTIVES: To describe the spectrum of opportunistic disease in HIV-infected patients admitted to hospital in Abidjan, Côte d'Ivoire, and to describe the level of immunosuppression at which these diseases occur. DESIGN: Cross-sectional study. SETTING: In-patient wards of the University Hospital Infectious Diseases Unit. PATIENTS: A total of 250 adult patients recruited by systematic sampling at the point of hospital admission. MAIN MEASURES: HIV status; CD4 count; diagnoses, confirmed by microbiological/radiological investigations whenever possible; and outcome of hospitalization (death or discharge). RESULTS: Overall, 79% patients were HIV-positive. The most frequent diagnoses in HIV-positive patients were septicaemia (20%, with non-typhoid salmonellae, Escherichia coli and Streptococcus pneumoniae the most common organisms), HIV wasting (16%), meningitis (14%), tuberculosis (TB; 13%), isosporiasis (10%), cerebral toxoplasmosis (7%) and bacterial enteritis (7%). Most HIV-positive patients had evidence of severe immunosuppression: 39% had CD4 counts < 50 x 10(6)/l, 17% had 50-99 x 10(6)/l, and 20% had 100-199 x 10(6)/l. In-hospital mortality among HIV-positive patients was 38% compared with 27% among HIV-negative patients [age-adjusted odds ratio (OR), 1.5; 95% confidence interval (CI), 0.7-2.9]. Among HIV-positive patients, the highest case-fatality rates were among patients with meningitis, toxoplasmosis and TB: in a multivariate analysis the strongest independent risk factors for death were an abnormal level of consciousness (OR, 9.3; 95% CI, 3.5-24.6), a haemoglobin concentration below 8 g/dl (OR, 4.2; 95% CI, 1.4-12.8) and age > 40 years (OR, 3.9; 95% CI, 1.5-10.2). CONCLUSIONS: Our data show that, as in industrialized countries, most HIV-infected individuals admitted to and dying in hospital in Abidjan are profoundly immunosuppressed. Potentially preventable infections are the main causes of in-hospital morbidity and mortality among HIV-infected persons in Abidjan, and the evaluation of appropriate primary prophylactic regimes is a priority.

AIDS-Related Opportunistic Infections↗
PubMed1996

Blinding and exclusions after allocation in randomised controlled trials: survey of published parallel group trials in obstetrics and gynaecology.

OBJECTIVE: To assess the methodological quality of approaches to blind ing and to handling of exclusions as reported in randomised trials from one medical specialty. DESIGN: Survey of published, parallel group randomised controlled trials. DATA SOURCES: A random sample of 110 reports in which allocation was described as randomised from 1990 and 1991 volumes of four journals of obstetrics and gynaecology. MAIN OUTCOME MEASURES: The adequacy of the descriptions of double blinding and exclusions after randomisation. RESULTS: Through 31 trials reported being double blind, about twice as many could have been. Of the 31 trials only eight (26%) provided information on the protection of the allocation schedule and only five (16%) provided some written assurance of successful implementation of double blinding. Of 38 trials in which the authors provided sufficient information for readers to infer that no exclusions after randomisation had occurred, six (16%) reported adequate allocation concealment and none stated that an intention to treat analysis had been performed. That compared with 14 (27%) and six (12%), respectively, for the 52 trials that reported exclusions. CONCLUSIONS: Investigators could have double blinded more often. When they did double blind, they reported poorly and rarely evaluated it. Paradoxically, trials that reported exclusions seemed generally of a higher methodological standard than those that had no apparent exclusions. Exclusions from analysis may have been made in some of the trials in which no exclusions were reported. Editors and readers of reports of randomised trials should understand that flawed reporting of exclusions may often provide a misleading impression of the quality of the trial.

Double-Blind Method↗
PubMed1996

A DNA-bending protein interacts with an essential upstream regulatory element of the human embryonic beta-like globin gene.

The mammalian beta-like globin gene family has served as an important model system for analysis of tissue- and developmental state-specific gene regulation. Although the activities of a number of regulatory proteins have been implicated in the erythroid cell-specific transcription of globin genes, the mechanisms that restrict their expression to discrete stages of development are less well understood. We have previously identified a novel regulatory element (PRE II) upstream from the human embryonic beta-like globin gene (epsilon) that synergizes with other sequences to confer tissue- and stage-specific expression on a minimal epsilon-globin gene promoter in cultured embryonic erythroid cells. Binding of an erythroid nuclear protein (PRE II-binding factor [PRE-IIBF]) to the PRE II control element is required for promoter activation. Here we report on some of the biochemical properties of PREIIBF, including the characterization of its specificity and affinity for DNA. The embryonic and adult forms of PREIIBF recognize their cognate sequences with identical specificities, supporting our earlier conclusion that they are very similar proteins. PREIIBF binds DNA as a single polypeptide with an Mr of approximately 80,000 to 85,000 and introduces a bend into the target DNA molecule. These results suggest a mechanism by which PREIIBF may contribute to the regulation of the embryonic beta-like globin gene within the context of a complex locus.

Base Sequence↗
PubMed1995

Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials.

OBJECTIVE: To determine if inadequate approaches to randomized controlled trial design and execution are associated with evidence of bias in estimating treatment effects. DESIGN: An observational study in which we assessed the methodological quality of 250 controlled trials from 33 meta-analyses and then analyzed, using multiple logistic regression models, the associations between those assessments and estimated treatment effects. DATA SOURCES: Meta-analyses from the Cochrane Pregnancy and Childbirth Database. MAIN OUTCOME MEASURES: The associations between estimates of treatment effects and inadequate allocation concealment, exclusions after randomization, and lack of double-blinding. RESULTS: Compared with trials in which authors reported adequately concealed treatment allocation, trials in which concealment was either inadequate or unclear (did not report or incompletely reported a concealment approach) yielded larger estimates of treatment effects (P < .001). Odds ratios were exaggerated by 41% for inadequately concealed trials and by 30% for unclearly concealed trials (adjusted for other aspects of quality). Trials in which participants had been excluded after randomization did not yield larger estimates of effects, but that lack of association may be due to incomplete reporting. Trials that were not double-blind also yielded larger estimates of effects (P = .01), with odds ratios being exaggerated by 17%. CONCLUSIONS: This study provides empirical evidence that inadequate methodological approaches in controlled trials, particularly those representing poor allocation concealment, are associated with bias. Readers of trial reports should be wary of these pitfalls, and investigators must improve their design, execution, and reporting of trials.

Bias↗
PubMed1995

Modelling the impact of alternative HIV intervention strategies in rural Uganda.

OBJECTIVE: To assess the likely impact on HIV incidence of increased condom use, a reduction in casual sexual partners, treatment programmes for other sexually transmitted diseases (STD) and combinations of these in rural Uganda. METHODS: A simulation model for the transmission dynamics of HIV infection and STD was employed, drawing on data from a rural population cohort in South-West Uganda with an HIV prevalence of 9% among adults in 1990. RESULTS: For the scenario most consistent with data from the study population, 39% of all adult HIV infections were averted, in the 10 years from 1990, when condoms were used consistently and effectively by 50% of men in their contacts with one-off sexual partners (such as bar girls and commercial sex workers). Reducing by 50% the frequency of men's sexual contacts with one-off partners averted 68% of infections. Reducing by 50% the duration of all STD episodes averted 43% of infections. Combining these three interventions averted 82% of all adult infections in the 10 years from 1990. CONCLUSION: A substantial proportion of HIV infections may be averted in general populations through interventions targeted only on less regular sexual partnerships.

Adult↗
PubMed1995

The cofactor effect of genital ulcers on the per-exposure risk of HIV transmission in sub-Saharan Africa.

The goal was to estimate the cofactor effect of genital ulcer disease (GUD) on the risk of HIV transmission during a single heterosexual exposure. The relation between the risk ratio observed in an epidemiological study and the per-exposure cofactor effect was investigated. Given simple assumptions, we show that observed risk ratios are expected to be very much smaller than per-exposure cofactor effects and to decrease as the observation period increases. Data from longitudinal studies of female commercial sex workers and men in Nairobi were reanalysed. The data are consistent with GUD cofactor effects per sexual exposure of 10-50 for male to female transmission, and of 50-300 for female to male transmission. Although subject to wide margins of error, these estimates indicate that GUD may be responsible for a high proportion of heterosexually acquired HIV infections in sub-Saharan Africa, supporting the potential role of STD control as an effective intervention strategy against HIV.

Africa South of the Sahara↗
PubMed1995

The impact of human immunodeficiency virus on response to treatment and recurrence rate in patients treated for tuberculosis: two-year follow-up of a cohort in Lusaka, Zambia.

To examine the effect of HIV on response to treatment and recurrence rate in patients with tuberculosis (TB), we have followed 239 previously untreated, adult, TB patients in a prospective cohort study in Lusaka, Zambia. One hundred and seventy-four (73%) were HIV-1 antibody positive. Patients with sputum smear positive, miliary, or meningeal TB were prescribed 2 months daily streptomycin, thiacetazone, isoniazid, rifampicin, pyrazinamide followed by 6 months thiacetazone and isoniazid; others, 2 months streptomycin, thiacetazone and isoniazid followed by 10 months thiacetazone and isoniazid. Thirty-five per cent of HIV-positive (HIV+ve) and 9% of HIV-negative (HIV-ve) patients were known to have died before the scheduled end of treatment. Surviving HIV+ve patients showed weight gain and improvement in symptoms and laboratory and radiological findings similar to HIV-ve patients. The risk of cutaneous drug reaction was 17% (95% CI: 12-25%) in HIV+ve, and 4% (1-13%) in HIV-ve patients. Severe rashes were attributed to thiacetazone. Recurrence of active TB was examined among 64 HIV+ve and 37 HIV-ve patients who successfully completed treatment, with mean follow-up after the end of treatment of 13.5 and 16.8 months, respectively. The rate of recurrence was 22/100 person years (pyr) for HIV+ve patients and 6/100 pyr for HIV-ve patients, giving a recurrence rate ratio of 4.0 (95% CI 1.2-13.8, P = 0.03).

AIDS-Related Opportunistic Infections↗
PubMed1994

Plant proteins that bind to the 3'-terminal sequences of the negative-strand RNA of three diverse positive-strand RNA plant viruses.

The replication of positive-strand RNA plant viruses, which involves both virus-encoded and plant-encoded proteins, takes place in two stages: synthesis of a negative-strand RNA using the genomic positive-strand RNA as a template and synthesis of progeny positive-strand RNA using the negative-strand RNA as a template. Using gel mobility shift and photochemical crosslinking assays, we have identified three proteins of M(r) 32K, 50K and 100K in extracts of tobacco and spinach leaves that bind to the 3'-terminal sequences of the negative-strand RNA of three diverse positive-strand RNA plant viruses. The 32K protein was purified to near homogeneity by chromatography on columns of Macro-prep high Q, heparin-sepharose, single-stranded DNA cellulose and poly(U)-sepharose. No binding of any of the three proteins to the 3'-termini of the positive-strand RNA or the 5'-termini of the positive-strand RNA or negative-strand RNA of any of the three viruses, or the 3'-termini of the mRNAs of two chloroplast genes, psbA or petD, could be detected. We propose that 3'-terminal negative-strand RNA binding proteins, which may be widespread in the plant kingdom, could be utilised by at least three different positive-strand RNA plant viruses for the initiation of positive-strand RNA synthesis.

Base Sequence↗
PubMed1994

What is clinical malaria? Finding case definitions for field research in highly endemic areas.

In non-endemic areas, the diagnosis of clinical malaria may be made on the basis of fever and a positive blood film. However, in areas of high endemicity, asymptomatic parasitaemia is very common: to assume that a child who presents with fever and parasitaemia is ill from malaria will result in overdiagnosis. In this article, Jo Schellenberg, Tom Smith, Pedro Alonso and Richard Hayes discuss the relationship between fever and parasite density in such areas, and show how the proportion of fevers due to malaria (the attributable fraction) can be estimated and used to evaluate case definitions for use in field trials.

Journal Article↗
PubMed1994

A trial of the synthetic malaria vaccine SPf66 in Tanzania: rationale and design.

The development of a safe, affordable and effective malaria vaccine to form part of control schemes in malaria endemic countries is a priority for researchers and public health officials. SPf66 is the first malaria vaccine to have shown partial protection against natural challenge in a phase III trial carried out in a hypoendemic area of Colombia. This paper describes the rationale and design of the first field trial of SPf66 outside South America, and the first to be conducted in an area of high perennial transmission.

Adult↗
PubMed1994

The quantification of soft tissue cervicomental changes after mandibular advancement surgery.

Surgical mandibular advancement results in many soft tissue changes. The purpose of this study was to quantify the changes seen in the cervicomental angle and the lip-chin-throat angles in response to mandibular advancement, as well as hyoid bone positional changes. As a result of statistical analysis of hyoid bone and soft tissue linear and angular changes, prediction models are presented as to the soft tissue response to mandibular advancement in the cervicomental region.

Adaptation, Physiological↗
PubMed1994

Verbal autopsies for adult deaths: issues in their development and validation.

BACKGROUND: The verbal autopsy appears to be an attractive technique for the assessment of causes of adult death in settings where the proportion of people who die while under medical care is low. Verbal autopsies have been used extensively to assess causes of childhood deaths. The existing experience in verbal autopsies for adult deaths is limited mainly to maternal deaths. This paper aims to highlight the critical issues in verbal autopsies to assess causes of adult death which need further research. METHODS: This paper reviews the methods of verbal autopsy used in 35 published studies and discusses issues in the development of verbal autopsies, including mortality classification, design of questionnaires, interviewers, respondents, recall periods, procedures for deriving a diagnosis and the recording of single versus multiple causes of death. It also discusses issues in the validation of verbal autopsies, including the choice of reference diagnosis and the required sample size. RESULTS: The methodological approaches used in verbal autopsy studies have varied widely. Very few studies of the validity of verbal autopsies have been conducted. In these studies, the reported sensitivity and specificity varied widely between different causes of death and between studies. CONCLUSIONS: The information available is inadequate to draw firm conclusions on preferred methodological approaches for verbal autopsies for adult deaths. Before these tools are used more widely for adult deaths, further research is required to compare alternative methods and to evaluate the validity of this tool in a range of settings.

Adolescent↗
PubMed1994

Localization of functional regions of the cucumber mosaic virus RNA replicase using monoclonal and polyclonal antibodies.

Monoclonal antibodies were produced using a purified cucumber mosaic virus (CMV) replicase complex, and Escherichia coli-expressed CMV 1a and 2a proteins, as immunogens. Five out of eight monoclonal antibodies, which bound to the 1a and 2a proteins in immunoblots, inhibited the RNA-dependent RNA polymerase (RdRp) activity of the purified replicase complex in vitro. Epitope mapping showed that two of the inhibitory antibodies interacted with regions of the 1a protein containing putative helicase and methyltransferase domains respectively. Two other inhibitory antibodies mapped to a region of the 2a protein containing the GDD motif which is highly conserved in RdRps. Prior interaction of the latter antibodies with a peptide containing the GDD motif prevented the antibody-mediated inhibition of the replicase. Polyclonal antibodies which inhibited the RdRp activity of the replicase complex were also produced using peptides corresponding to conserved helicase and polymerase motifs in the 1a and 2a proteins. The greatest inhibition was shown by antibodies to a peptide containing the GDD motif. These results demonstrate the functional importance of the identified sequence motifs in CMV RNA replication and indicate that the motifs are located in the replicase complex at positions accessible to antibodies, consistent with roles in interacting with the RNA template, RNA primer and enzyme substrates.

Amino Acid Sequence↗
PubMed1994

Simultaneous regulation of tomato golden mosaic virus coat protein and AL1 gene expression: expression of the AL4 gene may contribute to suppression of the AL1 gene.

The tomato golden mosaic virus (TGMV) coat protein and AL1 genes are located in opposite directions on either side of an intergenic region. To enable the effects of the AL1, AL2 and AL3 gene products on expression of the coat protein and AL1 genes to be studied simultaneously, a plasmid was constructed, containing the intergenic region linked on one side to a 5'-terminal portion of the AL1 gene fused to a beta-glucuronidase (GUS) reporter gene (to replace most of the AL1 gene) and on the other side to a neomycin phosphotransferase (NEO) reporter gene (to replace the coat protein gene). This GUS-NEO plasmid was mixed with plant expression plasmids containing the AL1, AL2 or AL3 coding regions, the DNA was transformed into Nicotiana benthamiana protoplasts and GUS activities and NEO protein levels were measured. Control transformations were carried out with the GUS-NEO plasmid mixed with the AL1, AL2 or AL3 plasmids in which mutations were introduced to prevent translation of the open reading frames (ORFs). The results showed that transactivation of the coat protein gene by the AL2 gene product and suppression of the AL1 gene by the expression of AL1 DNA (both reported previously) can occur simultaneously. It was also shown that expression of AL4, a small ORF contained within AL1 DNA but in a different reading frame, as well as expression of ORF AL1, can cause significant suppression of AL1 gene expression. Neither the AL1 nor the AL3 gene products affected the expression of the coat protein gene.

Base Sequence↗
PubMed1994

Fish oil improves arterial compliance in non-insulin-dependent diabetes mellitus.

In a double-blind, placebo-controlled study we investigated the effects of dietary fish oil supplementation on arterial wall characteristics in 20 patients with non-insulin-dependent diabetes mellitus. Estimates reflecting compliance values in the large arteries and more peripheral vasculature, as measured by pulse-contour analysis, improved significantly after 6 weeks of fish oil therapy compared with values recorded at baseline and after 6 weeks' administration of olive oil. The large-artery compliance estimate increased from 1.50 (confidence interval [CI], 1.31 to 1.69) mL/mm Hg at baseline to 1.68 (CI, 1.52 to 1.84) mL/mm Hg after fish oil administration (P < .01). The oscillatory compliance value increased from 0.015 (CI, 0.011 to 0.019) mL/mm Hg at baseline to 0.022 (CI, 0.016 to 0.028) mL/mm Hg after fish oil ingestion (P < .05). No changes occurred in arterial blood pressure, cardiac output, stroke volume, or systemic vascular resistance with either intervention. The improved compliance estimates with fish oil ingestion occurred without altering fasting blood glucose and cholesterol concentrations. These results support the hypothesis that fish oils alter vascular reactivity and favorably influence arterial wall characteristics in patients with non-insulin-dependent diabetes mellitus. These direct vascular effects, expressed at the level of the vessel wall, may contribute to the cardioprotective actions of fish oil in humans.

Arteries↗