Biomedical subjects
Publications and source records attributed to D J Evans.
It remains unclear whether "sucrose analgesia" is related to a pre- or postabsorptive mechanism. In a double blind cross over study sucrose reduced the pain response of preterm infants exposed to heel prick blood samples only when it was administered into the mouth. It was ineffective when administered intragastrically.
Extramammary Paget disease of the vulva was found in association with vulval adenocarcinoma in an elderly woman who also had a uterine prolapse. The characteristic histological appearances of extramammary Paget disease were masked by striking reactive changes in the squamous epithelium. Primary excision of both the intraepithelial and invasive disease appeared complete. However, a subsequent hysterectomy with repair of the prolapse revealed extramammary Paget disease in the upper vaginal mucosa and cervix, a finding which is very rarely described. Pathogenesis and diagnosis of extramammary Paget disease is discussed, with differential diagnosis and reference to immunohistochemical methods.
Protein kinase (PK) C is an increasingly diverse family of enzymes that has been implicated in a range of cellular functions within the eosinophil. Using isoform-specific polyclonal antibodies, we have explored the expression of PKC isoforms in circulating eosinophils. Initial studies demonstrated the presence of the alpha, betaI, betaII, and zeta and the low-level expression of the delta, epsilon, iota, and micro isoforms but no detectable expression of the gamma, eta, and theta isoforms in both normal and asthmatic subjects. There was no difference in the total protein expression between these two groups. Subsequent studies examined the expression and activation of PKC isoforms in circulating eosinophils from asthmatic patients before and 24 h after a late asthmatic response to an inhaled allergen. Cellular fractionation showed PKC-alpha and PKC-betaII to be mainly located in the cytosol, whereas PKC-betaI was constitutively more expressed in the membrane. No changes in expression or subcellular localization of these isoforms were seen after allergen challenge. In contrast, PKC-zeta expression was increased after allergen challenge, and we demonstrated a significant PKC-zeta translocation to the membrane, in keeping with activation of the enzyme. Our results suggest that 24 h after allergen exposure of asthmatic patients, there is increased expression and activation of eosinophil PKC-zeta that correlates with late asthmatic responses recorded between 4 and 10 h postallergen challenge.
PROBLEM BEING ADDRESSED: The Geriatric Day Program (GDP) of the Capital Health Region in Victoria, BC, is concerned with effective team processes, accountability for health service outcomes, and improving the quality of programs. The GDP identified a need to improve its interdisciplinary processes and generate useful patient outcome data. OBJECTIVE OF PROGRAM: To determine whether Goal Attainment Scaling (GAS) could be introduced to facilitate interdisciplinary processes and to generate useful health outcome data. MAIN COMPONENTS OF PROGRAM: The GAS procedures were incorporated into clinical routines based on published guidelines. The authors determined GAS outcome scores for patients who completed the program and developed outcome scores for specific geriatric problem areas requiring intervention. Outcome scores were made available to the clinical care team and to program managers for continuous quality improvement purposes. CONCLUSIONS: The GAS process was successfully implemented and was acceptable to clinicians and managers at the GDP. Team processes were thought to be improved by focusing on patient goals in a structured way. The GAS provided data on both patient outcomes and outcomes of interventions in specific problem areas. Accountability for patient care increased. Goal Attainment Scaling provided indicators of care for which clinicians could develop program quality improvements.
OBJECTIVE: To develop a strategy for a campaign aimed at general medical practitioners (GPs) and pharmacists and to evaluate the effectiveness of the campaign on (a) awareness of the role of liquid oral medicines containing sugar in dental disease and (b) changing prescribing and dispensing of sugar-containing medicines. DESIGN: Pre- and post-campaign questionnaires were sent to community pharmacists and GPs and following a series of qualitative interviews with them, a campaign was developed. Following post campaign questionnaires, changes due to the effects of the campaign were evaluated. SETTING: The test area was Newcastle and North Tyneside Health Authority area with Sunderland and South Tyneside Health Authority areas as control. INTERVENTIONS: An information pack followed up by a personal contact was the main form of intervention. The pack comprised a Smile for Sugar-Free Medicines leaflet used in the north west campaign, abstracts from professional journals illustrating the benefits of sugar-free medicines, local dental health information and computing information which could be used to adapt computer terminals in surgeries to display sugar-free options more prominently. MAIN OUTCOME MEASURES: Changes in the knowledge and awareness of both pharmacists and GPs to liquid oral medicines containing sugar as assessed by questionnaires. RESULTS: Increased knowledge and awareness of both pharmacists and GPs to the role of liquid oral medicines containing sugar and the use of sugar-free medicines had taken place but these were not statistically significant. CONCLUSION: The campaign created awareness amongst GPs and pharmacists about dental issues and it is hoped that this awareness can be built upon in future oral health promotion campaigns. However, it is likely that facilitation of sugar-free medicines use will occur only if sustained and constant reinforcement is available. The methodology used presented several difficulties in evaluating change.
OBJECTIVE: The aim of the study was to evaluate the effectiveness of a sugar-free medicines campaign using suitable prescribing and purchasing indicators. BASIC RESEARCH DESIGN: Quantitative analysis of sugar-free medicine use, before (1995) and after (1996) the campaign. CLINICAL SETTING: Two test and two control districts in north east England. PARTICIPANTS: General medical practitioners (GPs) and community pharmacists. INTERVENTION: A 12-month campaign involving development and distribution of information packs designed to increase the proportion of prescriptions dispensed sugar-free for paediatric use. MAIN OUTCOME MEASURES: Changes in the proportion of the following which were sugar-free: (a) for target prescribed medicines (i) number of prescriptions dispensed. (ii) number of prescribed daily amounts (PDA); (b) for target over the counter (OTC) medicines, (i) number of bottles sold, (ii) number of standard daily amounts (SDA) sold. RESULTS: Quantitative analysis of prescriptions and OTC sales showed statistically highly significant changes towards sugar-free prescribing and dispensing of prescribed medicines but only small increases in the proportion of some sugar-free OTC sales. CONCLUSIONS: The impact of the campaign was shown to be greatest in changing prescribing habits of GPs with less effect on OTC medicine use. The outcome measures used were suitable for quantitative evaluation of the campaign. POST-CAMPAIGN DEVELOPMENT: Sustainable changes in GPs' prescribing behaviour can be facilitated by software suppliers' modifications to computing software used for prescription writing.
OBJECTIVE: The study was designed to explore parents' and head teachers' understanding of and attitudes to the process, objectives and perceived outcomes of a school dental screening. BASIC RESEARCH DESIGN: Qualitative methods were used as a source for questionnaire development and questionnaires were subsequently used to test the strength of agreement with the qualitative findings. PARTICIPANTS: Head teachers and parents of a sample of 5- and 10-year-old children attending primary schools in Sunderland. RESULTS: Questionnaire responses from 83 (79%) of the head teachers and 934 (82%) parents of 5- and 10-year-old children showed that the exercise was well accepted by the majority. Gaps were identified in many aspects of communication between the Community Dental Service, schools and parents. CONCLUSIONS: It is recommended that, taking into account the views of all involved, the objectives of the exercise should be clearly defined and then clearly communicated. Evaluation should follow, measuring the extent to which the defined objectives are met. In this way the process will make a more positive and relevant contribution to oral health and the provision of primary dental care.
OBJECTIVE: This paper reports the results of standardised clinical caries examinations of 176,781 5-year-old children from across the United Kingdom. These 1997/98 co-ordinated surveys are the latest in a series which seek to monitor the dental health of children and to assess the delivery of dental services. METHOD: The criteria and conventions of the British Association for the Study of Community Dentistry were used. Representative samples were drawn from participating health authorities and boards and caries was diagnosed at the caries into dentine threshold using a visual method without radiography or fibre-optic transillumination. RESULTS: The results again demonstrated a wide variation in prevalence across the UK, with mean values for d3mft for the current English regions (of the National Health Service) and the other UK 'territories' ranging from 1.02 in the West Midlands to 2.92 in Northern Ireland. Mean d3mft across the UK was 1.68 (d3t = 1.18, mt = 0.26, ft = 0.23). Overall, 43% of children had evidence of caries experience (d3mft > 0), although the means ranged between 33% (West Midlands) and 63% (Northern Ireland). The distribution of caries was highly skewed. Thus the UK mean caries experience for those with disease was 3.94, as opposed to the overall mean of 1.68. Trends over time demonstrate a modest improvement of 8.7% in overall d3mft for Great Britain since 1995/96, compared to the small improvement seen two years ago and the deterioration seen four years previously. Both dt and mt have fallen while ft remained unchanged. The care index has increased in all but one region/territory (14% in 1997/8, compared to 12% in 1995/6). Regional/country means for 1997/8 ranged from 9-23%. This indicator has not, however, regained the levels seen in the past. CONCLUSION: There has been some improvement in the dental health of 5-year-old children. Overall, the provision of operative care for those with dentinal decay has also improved; however, significant groups remain within the population of 5-year-old children who have dental disease and who are in need of dental care.
The biochemical properties of the molecular interactions mediating viral-cell recognition are poorly characterized. In this study, we use surface plasmon resonance to study the affinity and kinetics of the interaction of echovirus 11 with its cellular receptor decay-accelerating factor (CD55). As reported for interactions between cell-cell recognition molecules, the interaction has a low affinity (KD approximately 3.0 microM) as a result of a very fast dissociation rate constant (kon approximately 10(5) M-1.s-1, koff approximately 0.3 s-1). This contrasts with the interaction of soluble ICAM-1 (sICAM-1, CD54) with human rhinovirus 3 which has been reported to have a similar affinity but 10(2)-10(3)-fold slower kinetics (Casasnovas, J. M., and Springer, T. A. (1995) J. Biol. Chem. 270, 13216-13224). The extracellular portion of decay-accelerating factor comprises four short consensus repeat domains (domains 1-4) and a mucin-like stalk. By comparison of the binding affinity for echovirus 11 of various fragments of decay-accelerating factor, we are able to conclude that short consensus repeat domain 3 contributes approximately 80% of the binding energy.
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CagA, a product of cytotoxin-associated gene A cagA, is an important virulence-related antigen of Helicobacter pylori (HP). CagA varies in size from 128 kDa to about 140 kDa and this variation is believed to be generated by a 102-nucleotide (NT) repeat sequence in the so-called variable region of cagA. However, this explanation has not previously been tested by comparing the NT sequences of cagA derived from a number of different isolates of HP. In this study we first compared the size of PCR products obtained from 54 different isolates of HP with oligonucleotide primers designed to amplify a cagA fragment predicted to be at least 1059 NT, including the variable region of the gene. As expected, the size of the PCR products varied considerable, from 1110 to 1822 NT, but the majority (50 of 54) measured 1335 NT or less. The deduced amino acid (AA) sequences of 9 representative amplicons and 4 other known sequences were compared with the following result: Within the variable region of cagA there are actually two adjacent variable regions, which we label as proximal and distal. The proximal-variable region of CagA extends from a motif of 4 to 6 asparagine residues to a 7-AA repeat sequence (KIDQLNQ); the distal-variable region is confined between KIDQLNQ and a well-conserved duplicate, KIDNLNQ. Despite these shared features CagA of every HP strain examined to date has a variable region with a unique AA sequence.
Recent studies have identified at least nine distinct receptors used by the piconaviruses for cell entry. Does the evolution of receptor usage correlate with the different tropisms observed in this group of viruses, and does this influence pathogenesis, or is it the consequence of another selection mechanism that favours virus survival?
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BACKGROUND: Goodpasture's, or antiglomerular basement membrane (GBM), disease presents with rapidly progressive glomerulonephritis, and is caused by auto-immunity to the NC1 domain of the alpha 3 chain of type IV collagen. In order to investigate mechanisms involved in the induction and regulation of glomerulonephritis, experimental models of Goodpasture's disease have been developed in the rat which share many characteristics with the human disease. Induction of experimental autoimmune glomerulonephritis (EAG) involves immunization of susceptible strains with either heterologous or homologous GBM in FCA. However, pathological changes have tended to be mild and/or variable, except in certain protocols using Wistar-Kyoto (WKY) rats. METHODS: We studied the susceptibility of inbred WKY rats from two different suppliers to the development of EAG. These substrains of rat had different MHC haplotypes (WKY/CR, RT1-1; WKY/Olac, RT1-k), so we proposed that they might show differences in their immune response to GBM antigens. Both substrains were immunized with sheep GBM, pH 7, or rat GBM buffered to pH 3, pH 5 or pH 7. RESULTS: All immunized rats developed circulating anti-GBM antibodies detectable at 14 days and rising until 28 days, at which time there was linear deposition of IgG on the GBM. WKY/CR rats developed severe focal segmental proliferative and necrotizing glomerulonephritis, with heavy albuminuria, following immunization with rat GBM, pH 7, but only moderate disease following sheep GBM. WKY/Olac rats showed a more variable response, with moderate disease following both rat and sheep GBM. Immunization of either substrain with rat GBM, pH 5, produced a response similar to that with rat GBM, pH 7, but disease was mild following rat GBM, pH 3. CONCLUSION: EAG in the WKY rat varies in severity according to the substrain of animal and preparation of GBM used for immunization. The model with the most severe and consistent changes was that induced in the WKY/CR rat by rat GBM at pH 7. This model of EAG will be of value for investigating mechanisms of autoimmunity and inflammation in glomerulonephritis, and for attempting novel forms of immunotherapy prior to trials in man.
Several echoviruses (EVs) have previously been shown to use decay accelerating factor (DAF) as a cellular receptor. Since DAF is expressed on erythrocytes, EVs that use this receptor cause haemagglutination. Here we show that all EVs that haemagglutinate do so via attachment to DAF and that this interaction can be inhibited by a monoclonal antibody (MAb) specific for DAF domain SCR3. Although the viruses haemagglutinate via DAF some can bind to rhabdomyosarcoma cells from which DAF has been removed and infect in the presence of a MAb against DAF. This suggests that some EVs have the capacity to interact with more than one cellular receptor.
The presence of cellular factors that bind to the 3' untranslated region (UTR) of picornaviruses was investigated by electrophoretic mobility shift assays (EMSAs). A cellular factor(s) that binds specifically the 3' UTR of polio-, coxsackie- and rhinoviruses was detected. Furthermore, this factor(s) is distinct from those which bind to the 5' terminal 88 nt (the 'cloverleaf') of poliovirus. Mutations within the 3' UTR which decrease the affinity of the RNA for the cellular factor in EMSAs decrease RNA replication and virus viability. Revertants of these mutants display changes which are predicted to stabilize the RNA secondary structure of the 3' UTR. These results indicate that binding of a cellular factor to the UTR plays a role in virus replication and that RNA secondary structure is important for this function.
The inclusion of a foreign marker gene, chloramphenicol acetyltransferase (CAT) gene, into the poliovirus genome allows its replication and encapsidation to be easily monitored using a simple enzyme assay. Such poliovirus replicons require the presence of helper virus for their successful propagation and thus are similar to defective interfering (DI) viruses. In genomes containing the CAT gene, the majority of the P1 virus capsid region of the poliovirus genome could be removed without destroying viability. The smallest replicon was significantly smaller than any naturally occurring DI particle so far reported, yet it retained the ability to replicate and be encapsidated by structural proteins provided by helper virus in trans. The efficiency with which the replicons were encapsidated was investigated using a direct immunostaining technique that allows individual cells infected with either a replicon or helper virus to be quantified. These results were compared to the frequencies of trans-encapsidation of polioviruses and coxsackievirus B4 using a two-stage neutralization assay. Poliovirus types 1, 2 and 3 but not coxsackievirus B4, coxsackievirus A21 or rhinovirus 14 provided efficient trans-encapsidation of poliovirus type 3 or type 3-derived replicons. These results suggest that a specific encapsidation process operates and that it does not involve RNA sequences within the region of the genome encoding the capsid proteins.