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R Edwards

Publications and source records attributed to R Edwards.

At least 19 recordsLinked to original sources
PubMed2001

Noncommunicable diseases in sub-Saharan Africa: where do they feature in the health research agenda?

There is no doubt that communicable diseases will remain the predominant health problem for the populations in sub-Saharan Africa, including adults, for the next 10-20 years. Concern has been expressed that the available resources to deal with this problem would be reduced by increasing the emphasis on noncommunicable diseases. The latter, however, already present a substantial burden because their overall age-specific rates are currently higher in adults in sub-Saharan Africa than in populations in Established Market Economies. There is also evidence that the prevalence of certain noncommunicable diseases, such as diabetes and hypertension, is increasing rapidly, particularly in the urban areas, and that significant demands are being made on the health services by patients with these diseases. To ignore the noncommunicable diseases would inevitably lead to an increase in their burden; the provision of health services for them would be largely undirected by issues of clinical and cost effectiveness, and their treatment and prevention would be left to the mercy of local and global commercial interests. Improved surveillance of all diseases within sub-Saharan Africa is needed in order to place noncommunicable diseases properly within the context of the overall burden of disease. Research is needed to guide improvements in the clinical and cost effectiveness of resources currently committed to the care of patients with noncommunicable diseases, and to direct and evaluate preventive measures.

Adult↗
PubMed2001

The structure of a zeta class glutathione S-transferase from Arabidopsis thaliana: characterisation of a GST with novel active-site architecture and a putative role in tyrosine catabolism.

The cis-trans isomerisation of maleylacetoacetate to fumarylacetoacetate is the penultimate step in the tyrosine/phenylalanine catabolic pathway and has recently been shown to be catalysed by glutathione S-transferase enzymes belonging to the zeta class. Given this primary metabolic role it is unsurprising that zeta class glutathione S-transferases are well conserved over a considerable period of evolution, being found in vertebrates, plants, insects and fungi. The structure of this glutathione S-transferase, cloned from Arabidopsis thaliana, has been solved by single isomorphous replacement with anomalous scattering and refined to a final crystallographic R-factor of 19.6% using data from 25.0 A to 1.65 A. The zeta class enzyme adopts the canonical glutathione S-transferase fold and forms a homodimer with each subunit consisting of 221 residues. In agreement with structures of glutathione S-transferases from the theta and phi classes, a serine residue (Ser17) is present in the active site, at a position that would allow it to stabilise the thiolate anion of glutathione. Site-directed mutagenesis of this residue confirms its importance in catalysis. In addition, the role of a highly conserved cysteine residue (Cys19) present in the active site of the zeta class glutathione S-transferase enzymes is discussed.

Amino Acid Sequence↗
PubMed2001

Tamoxifen for the prevention of breast cancer: psychosocial impact on women participating in two randomized controlled trials.

PURPOSE: The purpose of this study was to evaluate the psychosocial implications of tamoxifen versus placebo in women who are at increased risk of breast cancer. PATIENTS AND METHODS: The 488 women in the psychosocial study were recruited from participants in two placebo-controlled, double-blind, randomized, controlled trials that investigated the efficacy of tamoxifen in the prevention of breast cancer in women who are at high familial risk. During a 5-year period, repeated assessments were made of anxiety, psychological distress, and sexual functioning using standardized questionnaires before treatment at baseline and at 6-month intervals during the trial. RESULTS: Questionnaire completion over 5 years was good, with 71.1% of women returning at least 8 of 10 follow-up assessments. Although scores from individuals showed considerable fluctuation and variation over time, changes in anxiety, mood, and sexual functioning were not associated with treatment group. The number of symptoms reported at 48 months via a self-report checklist were not associated with treatment group, but vasomotor symptoms were more frequent among tamoxifen-treated women. Symptoms of low energy, breast sensitivity, and visual blurring were reported most frequently in the placebo group. CONCLUSION: In general, these results are comparable to those from the National Surgical Adjuvant Breast and Bowel Project psychosocial study despite differences in study populations, methodology, and instruments. The long-term use of tamoxifen and other selective estrogen response modulators as preventive agents in high-risk groups has been questioned, but we found no evidence of treatment-related side effects that affect women's psychosocial and sexual functioning.

Adult↗
PubMed2001

Ocular side effects possibly associated with isotretinoin usage.

PURPOSE: To evaluate reported ocular side effects associated with isotretinoin usage. METHODS: One thousand seven hundred forty-one case reports received from spontaneous reporting systems, data from the Drug Safety Section of Roche Pharmaceuticals, and the world's literature were evaluated using the World Health Organization Causality Assessment Guide of Suspected Adverse Reactions. RESULTS: Thirty-eight different signs or symptoms of ocular abnormalities associated with isotretinoin usage have been classified as "certain," "probable/likely," "possible," "unlikely," or "conditional/unclassifiable." CONCLUSION: Adverse ocular side effects secondary to isotretinoin that are "certain" include abnormal meibomian gland secretion, blepharoconjunctivitis, corneal opacities, decreased dark adaptation, decreased tolerance to contact lens, decreased vision, increased tear osmolarity, keratitis, meibomian gland atrophy, myopia, ocular discomfort, ocular sicca, photophobia, and teratogenic ocular abnormalities. Those that are "probable/likely" are decreased color vision (reversible) and permanent loss of dark adaptation. Those that have a "possible" association include permanent keratoconjunctivitis sicca. Suggested guidelines for ocular examination for patients on isotretinoin are given.

Adolescent↗
PubMed2001

Illness perceptions and mood in chronic fatigue syndrome.

BACKGROUND: Individual beliefs and cognitions may affect adjustment to chronic fatigue syndrome (CFS) and illness perceptions, in particular, have been reported to correlate with both disability and psychological adjustment to CFS in self-diagnosed cases. OBJECTIVES: The aim of the present study was to examine these relationships in a clinic sample of CFS patients assessed by both a physician and psychiatrist. METHOD: A sample of 173 patients referred to a multidisciplinary CFS clinic and fulfilling current operational criteria for CFS [Ann Intern Med 121 (1994) 953; J R Soc Med 84 (1991) 118.] were randomly selected from the clinic database and surveyed with the Hospital Anxiety and Depression scale, Fatigue Questionnaire and Illness Perceptions Questionnaire [J Psychosom Res 37 (1993) 147; Psychol Health 11 (1996) 431; Acta Psychiatr Scand 67 (1983) 361.]. RESULTS: A total of 126 patients responded (73% response rate). The illness perception components studied were consequences (of illness), illness identity, causes (of illness), the ability to control/cure the illness and (expected) timeline of the illness. These components accounted for 15%, 28% and 30% of the variance in levels of fatigue, depression and anxiety, respectively. Two of the illness perception components (consequences and illness identity) were stronger predictors of fatigue score than mood scores. CONCLUSIONS: These findings confirmed in a clinical sample that illness perceptions are associated with variation in both disability and psychological adjustment in CFS. Illness perceptions may have an important and long-lasting effect on adaptation to CFS, and it is necessary to have a greater understanding of their role in order to tailor effective interventions for the condition.

Adult↗
PubMed2001

Evaluation of VOC measurments in the EXPOLIS study. Air Pollution Exposure Distributions within Adult Urban Urban Populations in Europe.

Personal exposures and microenvironment concentrations of 30 target VOCs were measured for 401 participants living in five European cities as a part of the EXPOLIS (Air Pollution Exposure Distributions within Adult Urban Populations in Europe) study. Measurements in Basel used an active charcoal (Carbotech) adsorbent as opposed to the Tenax TA used in the other study centres. In addition, within each centre, personal and microenvironment VOC sampling required different sampling pumps and, because of different sampling durations, different sampling flow rates. Thus, careful testing of the sampling and analysis procedures was required to ensure accuracy and comparability of collected data. Monitor comparison tests using Tenax TA showed a mean VOC concentration ratio of 0.95 between the personal and microenvironment monitors. The LODs for the target VOCs using Tenax TA ranged from 0.7 to 5.2 microg m(-3). The LODs for the 14 target compounds quantifiable using Carbotech ranged from 0.9 to 3.2 microg m(-3). Tenax TA field blanks showed no remarkable contamination with the target VOCs, except benzaldehyde, a known artefact with this adsorbent. Thus, the diffusion barrier system used prevented contamination of Tenax TA samples by passive diffusion during non-sampling periods. Duplicate and parallel evaluations of the Tenax TA and Carbotech showed an average difference of < 17% in VOC concentrations within the sampling methods, but a systematic difference between the methods (Tenax TA: Carbotech concentration ratio = 1.18-2.36). These field evaluations and quality assurance tests showed that interpretation and comparison of the results in any VOC monitoring exercise should be done on a compound by compound basis. It is also apparent that carefully planned and realised QA and QC (QA/QC) procedures are needed in multi-centre studies, where a common sampling method and laboratory analysis technique are not used, to strengthen and simplify the interpretation of observed VOC levels between participating centres.

Air Pollution↗
PubMed2001

Use of a journal club and letter-writing exercise to teach critical appraisal to medical undergraduates.

INTRODUCTION: There is growing interest in methods of teaching critical appraisal skills at undergraduate and postgraduate levels. We describe an approach using a journal club and subsequent letter writing to teach critical appraisal and writing skills to medical undergraduates. METHODS: The exercise occurs during a 3-week public health medicine attachment in the third year of the undergraduate curriculum. Students work in small groups to appraise a recently published research paper, present their findings to their peers in a journal club, and draft a letter to the journal editor. Evaluation took place through: informal and formal feedback from students; number of letters written, submitted and published, and a comparison of marks obtained by students submitting a literature review assignment with and without critical appraisal teaching during the public health attachment. RESULTS: Feedback from students was overwhelmingly positive. In the first 3(1/2) years, 26 letters have been published or accepted for publication, and 58 letters published on the Internet. There were no significant differences in overall marks or marks for the critical appraisal component of the literature review assignments between the two student groups. DISCUSSION: We believe our approach is an innovative and enjoyable method for teaching critical appraisal and writing skills to medical students. Lack of difference in marks in the literature review between the student groups may reflect its insensitivity as an outcome measure, contamination by other critical appraisal teaching, or true ineffectiveness.

Communication↗
PubMed2001

Neutrophil activation and hyperamylasaemia after endoscopic retrograde cholangiopancreatography: potential role for the leukocyte in the pathogenesis of acute pancreatitis.

BACKGROUND AND STUDY AIMS: Hyperamylasaemia occurs in up to 60% of patients following endoscopic retrograde cholangiopancreatography (ERCP), and in a small proportion of patients (1-5%) acute pancreatitis may develop. We evaluated the role of the neutrophil in post-ERCP hyperamylasaemia and acute pancreatitis by measuring circulating CD11b adhesion receptor expression--an indicator of leukocyte activation. PATIENTS AND METHODS: A total of 43 patients undergoing elective ERCP were studied. Peripheral blood measurements of amylase activity and neutrophil CD11b content (by flow cytometry) were made immediately before ERCP (baseline), and at 2 and 24 hours after the procedure. RESULTS: ERCP induced an increase in amylase level above baseline in 41 of 43 patients. The 2-hour and 24-hour post-ERCP amylase levels were directly related (R = 0.9, P < 0.01). Baseline CD11b receptor status was positively correlated with post-ERCP amylase activity (R = 0.4, P < 0.05), and this relationship was stronger when pancreatography had been performed (R = 0.67, P < 0.01). Three patients (7%) developed clinical acute pancreatitis, with post-ERCP amylase levels persistently elevated above 1000 IU/l. Multiple linear regression identified CD11b expression as the most significant explanatory variable for amylase level after ERCP (multiple R = 0.74, P < 0.01). CONCLUSIONS: The findings from this pilot study indicate an association between neutrophil activation and hyperamylasaemia following ERCP, and suggest a role for this leukocyte in the pathogenesis of pancreatitis. Further study of neutrophil characteristics may allow identification of individual susceptibility to ERCP-induced pancreatic injury.

Acute Disease↗
PubMed2001

Cross-resistance testing of antihepadnaviral compounds using novel recombinant baculoviruses which encode drug-resistant strains of hepatitis B virus.

Long-term nucleoside analog therapy for hepatitis B virus (HBV)-related disease frequently results in the selection of mutant HBV strains that are resistant to therapy. Molecular studies of such drug-resistant variants are clearly warranted but have been difficult to do because of the lack of convenient and reliable in vitro culture systems for HBV. We previously developed a novel in vitro system for studying HBV replication that relies on the use of recombinant baculoviruses to deliver greater than unit length copies of the HBV genome to HepG2 cells. High levels of HBV replication can be achieved in this system, which has recently been used to assess the effects of lamivudine on HBV replication and covalently closed circular DNA accumulation. The further development of this novel system and its application to determine the cross-resistance profiles of drug-resistant HBV strains are described here. For these studies, novel recombinant HBV baculoviruses which encoded the L526M, M550I, and L526M M550V drug resistance mutations were generated and used to examine the effects of these substitutions on viral sensitivity to lamivudine, penciclovir (the active form of famciclovir), and adefovir, three compounds of clinical importance. The following observations were made: (i) the L526M mutation confers resistance to penciclovir and partial resistance to lamivudine, (ii) the YMDD mutations M550I and L526M M550V confer high levels of resistance to lamivudine and penciclovir, and (iii) adefovir is active against each of these mutants. These findings are supported by the limited amount of clinical data currently available and confirm the utility of the HBV-baculovirus system as an in vitro tool for the molecular characterization of clinically significant HBV strains.

2-Aminopurine↗
PubMed2001

Salmonella enterica serovar Typhi possesses a unique repertoire of fimbrial gene sequences.

Salmonella enterica serotype Typhi differs from nontyphoidal Salmonella serotypes by its strict host adaptation to humans and higher primates. Since fimbriae have been implicated in host adaptation, we investigated whether the serotype Typhi genome contains fimbrial operons which are unique to this pathogen or restricted to typhoidal Salmonella serotypes. This study established for the first time the total number of fimbrial operons present in an individual Salmonella serotype. The serotype Typhi CT18 genome, which has been sequenced by the Typhi Sequencing Group at the Sanger Centre, contained a type IV fimbrial operon, an orthologue of the agf operon, and 12 putative fimbrial operons of the chaperone-usher assembly class. In addition to sef, fim, saf, and tcf, which had been described previously in serotype Typhi, we identified eight new putative chaperone-usher-dependent fimbrial operons, which were termed bcf, sta, stb, ste, std, stc, stg, and sth. Hybridization analysis performed with 16 strains of Salmonella reference collection C and 22 strains of Salmonella reference collection B showed that all eight putative fimbrial operons of serotype Typhi were also present in a number of nontyphoidal Salmonella serotypes. Thus, a simple correlation between host range and the presence of a single fimbrial operon seems at present unlikely. However, the serotype Typhi genome differed from that of all other Salmonella serotypes investigated in that it contained a unique combination of putative fimbrial operons.

Base Sequence↗
PubMed2001

Design of a multicentre randomised trial to evaluate flexible sigmoidoscopy in colorectal cancer screening.

A randomised, controlled trial in progress in 14 United Kingdom and six Italian centres is evaluating screening for colorectal cancer using a single flexible sigmoidoscopy (FS) at around the age of 60 with removal during FS of all small adenomas, and colonoscopy for "high risk" polyps. The regimen aims to ensure that 95% of people (with either no polyps or only low risk polyps) complete the entire screening process in a single visit. This paper describes the rationale and design of the trial. Participants were patients aged between 55 and 64 on the lists of designated general practitioners (GPs) who were not excluded by their GP. A two stage recruitment procedure was employed to raise compliance rates in the intervention group. Potentially eligible persons were sent an "interest in screening" questionnaire; those who responded positively were randomised to the intervention or control groups. The trial is sufficiently large to estimate within narrow confidence intervals the magnitude of benefit and the duration of effect and optimum age for a single screen. It also examines the feasibility and acceptability of the screening regimen, and will identify training and quality assurance issues. Recruitment and screening are now complete and all baseline data have been collected. The first analysis of the effect on colorectal cancer incidence and mortality rates and suitability for a national screening programme can be expected in 2004.

Age Factors↗
PubMed2001

Occurrence of metronidazole and imipenem resistance among Bacteroides fragilis group clinical isolates in Hungary.

During the period between 1987 and 1997, various surveillances of the antibiotic resistance of B. fragilis group isolates revealed that practically all the isolates tested were susceptible to imipenem, metronidazole and chloramphenicol; very few isolates (2.5%) exhibited resistance to amoxicillin/clavulanic acid. However, similarly as in some southern European countries, the percentages of the isolates that were resistant to ampicillin, tetracycline and clindamycin were high throughout this period, and the resistance to cefoxitin increased from 6% to 16%. In 2000, isolates with intermediate or high resistance to imipenem and isolates with increased MICs to metronidazole were emerging among the clinical isolates of B. fragilis. The presence of the cfiA gene was demonstrated by PCR in 7 of 242 isolates (2.9%); 2 of them with high MICs to carbapenems harboured the IS942 element immediately upstream of the resistance genes. In the 2 B. fragilis isolates with increased MICs to metronidazole, the nim gene could be detected by PCR. The IS1186 element was found in these isolates upregulating the metronidazole resistance gene.

Anti-Bacterial Agents↗
PubMed2001

Safety of the insect repellent N,N-diethyl-M-toluamide (DEET) in pregnancy.

The safety of daily application of N, N-diethyl-m-toluamide (DEET) (1.7 g of DEET/day) in the second and third trimesters of pregnancy was assessed as part of a double-blind, randomized, therapeutic trial of insect repellents for the prevention of malaria in pregnancy (n = 897). No adverse neurologic, gastrointestinal, or dermatologic effects were observed for women who applied a median total dose of 214.2 g of DEET per pregnancy (range = 0-345.1 g). DEET crossed the placenta and was detected in 8% (95% confidence interval = 2.6-18.2) of cord blood samples from a randomly selected subgroup of DEET users (n = 50). No adverse effects on survival, growth, or development at birth, or at one year, were found. This is the first study to document the safety of DEET applied regularly in the second and third trimesters of pregnancy. The results suggest that the risk of DEET accumulating in the fetus is low and that DEET is safe to use in later pregnancy.

Administration, Cutaneous↗
PubMed2001

In vitro model of infectious crystalline keratopathy: tissue architecture determines pattern of microbial spread.

PURPOSE: To develop an in vitro model of infectious crystalline keratopathy using human corneal buttons and to test the hypothesis that the compactness of the corneal stroma determines the pattern of microbial spread. METHODS: Twenty human corneal buttons obtained after penetrating keratoplasty for keratoconus (KC) and eight human corneal buttons obtained from eye bank (EB) donor eyes were maintained in organ culture. Fourteen buttons (10 KC and 4 EB donors) were maintained in a turgid state (swollen, edematous) and 14 in a nonturgid state (compact, normal state of deturgescence) by the omission or addition of 5% dextran to the culture medium. Eight KC and four EB nonturgid buttons and eight KC and four EB turgid buttons were inoculated with Streptococcus viridans (Lancefield group G, gram-positive) organisms. Two KC nonturgid and two KC turgid buttons were inoculated with Klebsiella oxytoca (gram-negative) organisms. Bacterial migration and spread in the tissue were observed by light and electron microscopy. RESULTS: Of the nonturgid buttons, six KC buttons and all four EB buttons inoculated with S. viridans and both KC buttons inoculated with K. oxytoca demonstrated an arborizing, crystallike pattern of bacterial spread. In the turgid buttons, five KC and all four EB buttons inoculated with S. viridans and both KC buttons inoculated with K. oxytoca demonstrated globular, amorphous colonies. This was in complete contrast to the needlelike branching appearance seen in nonturgid corneal buttons. Electron microscopy confirmed an interlamellar spread of the bacterial colonies. CONCLUSIONS: This is the first in vitro model of bacterial keratitis. It demonstrates that the pattern of spread of bacteria within corneal tissue is largely determined by the compactness of the corneal stroma. Altering tissue architecture changed the pattern of bacterial migration and spread. This model has considerable potential in further understanding host-microbe interactions and microbial spread that occurs during infection.

Adult↗