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Biomedical subjects

M Renshaw

Publications and source records attributed to M Renshaw.

At least 19 recordsLinked to original sources

Specialty audit leads--has this concept been effective in implementing clinical audit in an acute hospital?

Clinical audit has a pivotal role to play in improving the quality of patient care. As part of the programme for co-ordinating clinical audit across the trust each clinical area has a nominated doctor to lead and co-ordinate the audit programme in their specialty. This qualitative survey reviews the effectiveness of having specialty audit leads and reviews the progress that specialties have made in developing their audit programme. The semi-structured interviews with 30 clinical audit leads identified an uneven level of development of clinical audit across the trust, and demonstrated that dedicated time would be needed to make these posts more universally successful. Although one size will not fit all, the interviews highlighted some recurring themes--seeds of success--in functioning audit programmes.

Attitude of Health Personnel↗

Heterosubtypic immunity against human influenza A viruses, including recently emerged avian H5 and H9 viruses, induced by FLU-ISCOM vaccine in mice requires both cytotoxic T-lymphocyte and macrophage function.

Induction of heterosubtypic immunity to influenza viral antigens is of paramount importance to the prevention of epidemics and potential pandemics. The 1997 incidence of avian influenza infections in humans in Hong Kong heightened the need for pandemic preparedness and a search for vaccines and vaccine delivery systems that can confer broad protection. In this report, we demonstrate that the delivery of H1N1 subtype influenza viral antigens as immunostimulating complexes (ISCOM) induces broad cross-protection in mice against challenge with various influenza virus subtypes, including the avian H9 and the H5 strains that were recently responsible for deaths in humans. The ISCOM delivery system induced high and long-lived serum antiviral antibodies and class I-restricted cytotoxic T-lymphocytes (CTL). Studies with perforin, IFN-gamma, and mu-chain gene knock-out mice demonstrated that the heterosubtypic protection required cross-reactive, functional cytotoxic T cells and nonhemagglutination inhibiting serum antibodies. Interferon-gamma, a major player in viral clearance by nonlytic mechanisms, did not appear to play a role in heterosubtypic immunity. Nonformulated H1N1 influenza antigens failed to induce significant CTL or long-lasting antibody responses or to protect mice against challenge with heterosubtypic viruses. Furthermore, while influenza virus infection induced a dominant nucleoprotein (NP)-specific CTL response in H2 mice, the ISCOM delivery system induced a dominant hemagglutinin-specific CTL response. Moreover, non-neutralizing but cross-reactive antibodies played a role in reducing viral titers by macrophages. These results suggest that exogenous delivery of influenza antigens as ISCOM can influence their antigen processing and presentation, their ability to induce/recall CTL specificities, and their capacity to mediate broad cross-protection against influenza virus variants.

Animals↗

Mutations in the genes regulating methylene tetrahydrofolate reductase (MTHFR C-->T677) and cystathione beta-synthase (CBS G-->A919, CBS T-->c833) are not associated with myocardial infarction in African Americans.

Moderate hyperhomocysteinemia is a putative risk factor for cardiovascular disease. Molecular studies have demonstrated increased plasma homocysteine levels in the presence of DNA mutations in either the methylenetetrahydrofolate reductase (MTHFR) enzyme found in the remethylation pathway or the enzyme cystathione beta-synthase (CBS) of the transsulfuration pathway. To determine whether the mutation C-->T677 in the MTHFR gene or the T-->C833/844ins68 and G-->A919 mutations in the CBS gene are associated with myocardial infarction (MI) in African Americans, DNA was analyzed from samples obtained from a case-control study conducted at a large, inner-city hospital. One-hundred ten African American subjects with a diagnosis of MI and 185 race- and age-matched controls were recruited. Our results demonstrated that 15% of the MI cases were heterozygous for the C-->T677 (MTHFR) mutation, while 1.8% were homozygous. When compared to the controls in which 15% were heterozygous and 2.1% were homozygous, no significant association with MI was observed. In addition, 34% of the cases were heterozygous for the T-->C833 (CBS) mutation while 6% were homozygous. This is compared to 32% and 5% of the controls having the heterozygous and homozygous genotype, respectively. No significant association was observed for the T-->C833 (CBS) mutation among the cases and controls. Although this mutation has no significant association with MI, the prevalence of the heterozygous state was higher than what has been reported for whites (12%). No mutations for G-->A919 (CBS) were detected in the cases or controls. The racial differences of the CBS T-->C833 polymorphism suggest that further investigation into the other areas of the CBS gene is needed.

Adult↗

Immunity to influenza A H9N2 viruses induced by infection and vaccination.

Avian influenza A H9N2 viruses are widespread among domestic poultry and were recently isolated from humans with respiratory illness in China. Two antigenically and genetically distinct groups of H9N2 viruses (G1 and G9) are prevalent in China. To evaluate a strategy for vaccination, we compared G1 and G9 viruses for their relative immunogenicity and cross-protective efficacy. Infection of BALB/c mice with representative viruses of either group protected against subsequent challenge with the homologous or heterologous H9N2 virus in the absence of detectable cross-reactive serum hemagglutination inhibition antibody. Mice injected intramuscularly with inactivated G1 whole virus vaccine were completely protected from challenge with either H9N2 virus. In contrast, mice administered inactivated G9 vaccine were only partially protected against heterologous challenge with the G1 virus. These results have implications for the development of human vaccines against H9N2 viruses, a priority for pandemic preparedness.

Animals↗

Mucosal delivery of inactivated influenza vaccine induces B-cell-dependent heterosubtypic cross-protection against lethal influenza A H5N1 virus infection.

Influenza vaccines that induce greater cross-reactive or heterosubtypic immunity (Het-I) may overcome limitations in vaccine efficacy imposed by the antigenic variability of influenza A viruses. We have compared mucosal versus traditional parenteral administration of inactivated influenza vaccine for the ability to induce Het-I in BALB/c mice and evaluated a modified Escherichia coli heat-labile enterotoxin adjuvant, LT(R192G), for augmentation of Het-I. Mice that received three intranasal (i.n.) immunizations of H3N2 vaccine in the presence of LT(R192G) were completely protected against lethal challenge with a highly pathogenic human H5N1 virus and had nasal and lung viral titers that were at least 2,500-fold lower than those of control mice receiving LT(R192G) alone. In contrast, mice that received three vaccinations of H3N2 vaccine subcutaneously in the presence or absence of LT(R192G) or incomplete Freund's adjuvant were not protected against lethal challenge and had no significant reductions in tissue virus titers observed on day 5 post-H5N1 virus challenge. Mice that were i.n. administered H3N2 vaccine alone, without LT(R192G), displayed partial protection against heterosubtypic challenge. The immune mediators of Het-I were investigated. The functional role of B and CD8+ T cells in Het-I were evaluated by using gene-targeted B-cell (IgH-6(-/-))- or beta2-microglobulin (beta2m(-/-))-deficient mice, respectively. beta2m(-/-) but not IgH-6(-/-) vaccinated mice were protected by Het-I and survived a lethal infection with H5N1, suggesting that B cells, but not CD8+ T cells, were vital for protection of mice against heterosubtypic challenge. Nevertheless, CD8+ T cells contributed to viral clearance in the lungs and brain tissues of heterotypically immune mice. Mucosal but not parenteral vaccination induced subtype cross-reactive lung immunoglobulin G (IgG), IgA, and serum IgG anti-hemagglutinin antibodies, suggesting the presence of a common cross-reactive epitope in the hemagglutinins of H3 and H5. These results suggest a strategy of mucosal vaccination that stimulates cross-protection against multiple influenza virus subtypes, including viruses with pandemic potential.

Adjuvants, Immunologic↗

The role of the t-PA I/D and PAI-1 4G/5G polymorphisms in African-American adults with a diagnosis of myocardial infarction or venous thromboembolism.

To determine whether or not the PAI-1 4G/5G and t-PA I/D polymorphisms in African-Americans were linked to cardiovascular disease, the association of these polymorphisms to disease expression was analyzed in a recently completed case-control study of myocardial infarction or venous thromboembolism among African-Americans. All African-Americans patients with a history of venous thromboembolism attending an anticoagulant clinic, and patients with a history of a MI attending a cardiology clinic at a large local urban public hospital were eligible for inclusion as cases in the study. In this study it was observed that there was a statistically significant association between the D allele of the t-PA I/D polymorphism and venous thromboembolism and a nonsignificant association between the D allele and myocardial infarction among African-Americans. t-PA antigen levels were statistically significantly higher among both myocardial infarction and venous thromboembolism cases compared with control subjects. The genotypes were unrelated to t-PA plasma levels. There was no association between either myocardial infarction or venous thromboembolism and the 4G/5G PAI-1 genotype. It was also found that genotype frequencies for both PAI-1 4G/5G and t-PA I/D polymorphisms in African-American adults were different from those reported for both U.S. Causcians and Europeans.

Adult↗

Clinical audit. Count the cost.

A system for calculating the cost of clinical audits in terms of money and staff time has been in operation at Brighton Health Care trust since 1995. The information has proved useful in cost-benefit analysis. At th e end of each audit an action plan is agreed with the lead clinician over required changes. Making the cost of audits explicit increases the likelihood of recommendations being implemented.

Cost-Benefit Analysis↗

Will reduced sulphur emissions under the Second Sulphur Protocol lead to recovery of acid sensitive sites in UK?

A conceptual model of the combined effects of acid deposition and land-use, Model of Acidification of Groundwater In Catchments (MAGIC), was applied to 21 upland sites in the UK Acid Waters Monitoring Network (AWMN) to assess the likely future recovery in response to the latest international agreements controlling anthropogenic sulphur emissions throughout Europe. Future estimates of sulphur deposition were generated by the Hull Acid Rain Model (HARM), based on the agreed reductions outlined in the Second Sulphur Protocol. The results indicate only a limited degree of recovery in surface-water chemistry at all sites over the next 50 years; moreover, a continuing decline in soil base status is predicted to occur at 70% of sites, resulting in longer term reacidification of surface-water at 38% of sites. However, compared with a 'business as usual' scenario the recovery is pronounced, although acidified sites will require further reductions in acidic deposition if recovery to pre-industrial chemical conditions are to be achieved. Furthermore, land-use scenarios at afforested sites suggest that replanting of felled forest will lead to a further increase in acidification. This strengthens the argument that plantation forestry should be avoided in areas considered geologically sensitive to acidic deposition.

Journal Article↗

Predicting the effect of atmospheric pollution on soil and surface water acidification in the Middle Hills of Nepal.

Rapid population growth and the expansion of South East Asian economies have lead to recent concerns regarding the effects of anthropogenic pollution on the environment. The RAINS-ASIA source-receptor, atmospheric transport model, is used to produce scenarios of future anthropogenic sulphur deposition. This is used as an input to the MAGIC model for prediction of future changes in the hydrochemistry of two catchments of the Likhu Khola watershed in the Middle Hills region of Nepal. Since much of this region is under intense cultivation and the application of mineral fertilisers may be contributing to soil and surface water acidification and loss of soil fertility, a best- and worse-case scenario for fertiliser application are incorporated to assess the overall anthropogenic influence upon soil and surface water acidification. The results indicate a decrease of soil base saturation and streamwater ANC, especially under the worst-case scenario of increased acidic deposition and increased fertiliser use. However, the pH status of soils and surface water are predicted to decrease only marginally as a result of the abundant supply of base cations from the highly weathered bedrock and deep soil. The problem of increased acidification of soils and water at a regional scale, however, should be addressed.

Acid Rain↗

Managing death. Room to mourn.

More than a quarter of deaths occurred on wards which offered relatives and staff no privacy. In a fifth of cases no information was available on how to register a death. Almost half of the staff had received no training in bereavement. More than half of the staff wanted training or further training.

Attitude of Health Personnel↗

A survey of larval and adult mosquitoes on the flood plains of Bangladesh, in relation to flood-control activities.

A mosquito survey was carried out between October 1991 and November 1992 on the flood plains of Bangladesh, as part of a baseline study designed to help predict the effects on vector-borne diseases of embanking rivers under the Bangladesh Government's Flood Action Plan. Overall, 15 species of larval and 15 species of adult anophelines were collected, along with 13 larval and 21 adult culicines. Anophelines made up only 6% of the mosquitoes caught at human bait. The most abundant anopheline biting man was Anopheles vagus, the dominant species in all nine sampling villages. The other recognized malaria vectors in the flood plains of Bangladesh, namely An. philippinensis, An. aconitus and An. annularis, were collected but in relatively low numbers. Culex vishnui was the most abundant biting culicine in all villages. Biting mosquitoes showed a bimodal seasonality of biting, with peaks between February and April and September and October. All biting mosquitoes showed a significant preference for outdoor biting. The densities of the mosquito populations are more likely to be affected by the large-scale environmental changes which have occurred in Bangladesh, as well as the dramatic increase in the density of the human population, than by the river embankments per se.

Animals↗

Differential lipid reserves influence host-seeking behaviour in the mosquitoes Aedes cantans and Aedes punctor.

Lipid reserves of bait-caught female Ae.cantans and Ae.punctor mosquitoes (Diptera: Culicidae) were significantly higher than in teneral females. Female Ae.cantans given access to 10% w/v sucrose solution post-emergence showed an ability to synthesize lipid and, after 192 h, they were willing to take a bloodmeal from a human volunteer. At this point, mean lipid reserves were not significantly different from mean lipid reserves of bait-caught females. Prior to 192h, females would not take a bloodmeal and lipid reserves were significantly lower than in bait-caught females. Female Ae.punctor given access to 10% w/v sucrose solution post-emergence also showed an ability to synthesize lipid. Females of this species were willing to feed from a human host after only 48 h, at which point lipid content was not significantly different from that in bait-caught females. The level of lipid reserves in females coming to bait differs significantly between species: Ae.cantans has lipid reserves approximately double those of Ae.punctor. In addition, Ae.punctor is able to synthesize lipid to a level comparable with that found in bait-caught females after only 24 h, whilst it takes 192 h for Ae.cantans females to synthesize the amount of lipid found in host-seeking females, when allowed free access to sugar. Physiological differences in lipid synthesis and the level of lipid reserves required may therefore explain the differences observed between the species in the time taken to initiate host seeking.

Aedes↗

The effects of Onchocerca lienalis infection on vitellogenesis in the British blackfly, Simulium ornatum.

We have previously described the major yolk protein, vitellin, in the British blackfly Simulium ornatum Meigen. Here we demonstrate that vitellogenin, synthesized in the fat body and secreted into the haemolymph, is composed of subunits with the same approximate molecular weight as vitellin, namely 200 and 68 kDa. Simulium ornatum is the natural vector for the cattle filarial nematode Onchocerca lienalis Stiles, which induces host fecundity depletion. A significant reduction in ovarian vitellin content was associated with infection by intrathoracic injection of 20 O. lienalis microfilariae immediately after blood-feeding. Fat body synthesis of vitellogenin was significantly reduced as early as 8 h post-infection in comparison with sham-injected flies. When total haemolymph protein from infected and sham injected flies was compared, titres were significantly depressed 6 h post-infection. However, later in the infection, titres were elevated by 30%, the major component being vitellogenin. The injection of dead microfilariae had no effect. An infection burden of a single parasite caused a significant reduction in ovarian protein content in comparison with shams, but no further significant decrease was observed as the parasite burden was increased from 5 to 20. Possible mechanisms underlying the disturbance of Simulium reproductive physiology are proposed.

Animals↗

Size variation and reproductive success in the mosquito Aedes cantans.

A link between density-dependent larval competition and adult size of the mosquito Aedes cantans was demonstrated in northern England. Ponds containing high larval densities produced smaller larvae which, in turn, resulted in smaller adults at emergence. In both 1989 and 1990, parous mosquitoes caught at human bait were larger than nulliparous ones, suggesting that larger mosquitoes are more successful at host location and egg-laying and also that they may be longer lived. Larger mosquitoes produced larger egg clutches than smaller females: however, there was no difference in the size of eggs laid by large and small females.

Aedes↗

Host finding, feeding patterns and evidence for a memorized home range of the mosquito Aedes cantans.

ELISA tests of Aedes cantans bloodmeals in woodland near Liverpool during 1989 and 1990, revealed preferences for sheep and cows, these hosts representing more than 60% of the total. Dispersal studies carried out on newly-emerged adults and those caught at human bait, indicated that individuals move freely between the two woods studied, mixing as a single population. Mean recapture rates for mosquitoes marked with paint were 2.28% in 1989 and 6.3% in 1990. Recapture rates for mosquitoes marked with powder were 3.66% in 1989 and 6.25% in 1990. The patterns of dispersal of adult females suggest that Aedes cantans has a learned and memorized familiar area map and possesses a sense of location.

Aedes↗