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Biomedical subjects

A Hay

Publications and source records attributed to A Hay.

At least 19 recordsLinked to original sources
PubMed2006

The use of telomere biology to identify and develop superior nitrone based anti-oxidants.

We have employed a biological chemistry approach to dissect the mechanisms underpinning cellular responses to oxidant stress and to develop biologically relevant anti-oxidants. We have used telomere biology to define cellular stress responses and have observed telomere independent, p21- and p16-dependent stasis following oxidative insult in human fibroblasts. This was accompanied by a [corrected] reduction in XRCC5 expression and a reduction in [corrected] SIRT 1 expression. Using these markers in conjunction with senescence-associated beta-galactosidase expression, we have developed and screened novel nitrone based anti-oxidant compounds. We have identified functional compounds that are unsuitable for use in primary human cells. This has allowed subsequent identification of suitably structured compounds that act as superior biological anti-oxidants, which have potential for use in clinical interventions.

Antioxidants↗
PubMed2006

Suicide in farmers in Scotland.

INTRODUCTION: Farmers and farm workers have higher than expected rates of suicide and undetermined deaths in UK studies, and some rural areas of Scotland have higher than average male suicide rates. Firearm access seems to be an influencing factor in England and Wales. Type of farming, and farming social networks may also be important. This article describes suicide and undetermined deaths in male farmers and farm workers in Scotland from 1981-1999 using anonymised, routine data. METHOD: Deaths of men aged 15-74 years from suicide or undetermined cause were identified from anonymised Scottish death records. Farmers and farm workers were identified using occupation codes. Methods of suicide used by farmers were compared with those of the general male population of the same age. A multiple linear regression was used to examine the influence of farm type, and the proportion of farmers in the working population of an area. RESULTS: 307 male farmers or farm workers died by suicide or undetermined cause in the time period. The overall rate was 31.4/100,000 per year (95% CI 28.1-35.1). Deaths using firearms were over-represented (29% of farming deaths compared with 3.6% in the general male population). There was no significant association between the male suicide rate in an area, and the farming suicide rate. Areas with lower proportions of farmers tended to have higher rates of farming suicide and undetermined deaths. This one factor described 85% of the variance among areas. CONCLUSION: Deaths were substantially more likely to involve firearms than suicide and undetermined deaths in the general male population. Less use of other methods did not completely compensate for this, indicating that method availability is likely to contribute to farming suicide rates. Farmers in areas where farming is less common were more likely to die by suicide, and this described most of the differences among areas. Networks and social supports may be important protective factors for farmers.

Accidental Falls↗
PubMed2006

Postoperative serum urea is associated with 30-day mortality in patients undergoing emergency abdominal surgery.

BACKGROUND: Emergency abdominal surgery carries considerable postoperative morbidity and mortality. Hypovolaemia is considered to be a cause of renal hypoperfusion, which is associated with a decreased clearance of serum urea and creatinine. This study examines whether the perioperative serum urea and creatinine concentrations are predictors of mortality in patients undergoing emergency abdominal surgery. METHODS: Consecutive patients (n=300) who underwent emergency abdominal surgery were studied. Age- and sex-specific reference intervals were used for the data analysis. Patients with incomplete biochemical (n=51) or mortality data (n=31) or with pre-existing renal failure (n=9) were excluded from the analysis. RESULTS: 209 patients were analysed, of whom 162 (78%) remained alive and 47 (22%) died following surgery. The non-survivors were older (P<0.05), had undergone more extensive surgery (P<0.001) and were more likely to have been admitted to the intensive care unit (P<0.001). The serum urea concentration was higher preoperatively (P<0.05) and on day one postoperatively (P<0.001) in the non-survivors. On multivariate logistic regression analysis, age (odds ratio [OR] 3.27, 95% confidence interval [CI] 1.43-7.47, P<0.005), severity of surgery (OR 2.21, 95% CI 1.14-4.29, P<0.019), admission to intensive care (OR 0.54, 95% CI 0.11-0.54, P<0.001), seniority of anaesthetist (OR 0.50, 95% CI 0.27-0.90, P<0.022) and day one urea (OR 3.33, 95% CI 1.39-7.99, P<0.007) were independently associated with 30-day mortality. CONCLUSIONS: These results indicate that an increased serum urea concentration, but not serum creatinine concentration, in the postoperative period is associated with an increase in 30-day mortality in patients undergoing emergency abdominal surgery.

Abdomen↗
PubMed2006

Two clusters of human infection with influenza A/H5N1 virus in the Republic of Azerbaijan, February-March 2006.

Following the appearance of influenza A/H5 virus infection in several wild and domestic bird species in the Republic of Azerbaijan in February 2006, two clusters of potential human avian influenza due to A/H5N1 (HAI) cases were detected and reported by the Ministry of Health (MoH) to the World Health Organization (WHO) Regional Office for Europe during the first two weeks of March 2006. On 15 March 2006, WHO led an international team, including infection control, clinical management, epidemiology, laboratory, and communications experts, to support the MoH in investigation and response activities. As a result of active surveillance, 22 individuals, including six deaths, were evaluated for HAI and associated risk infections in six districts. The investigations revealed eight cases with influenza A/H5N1 virus infection confirmed by a WHO Collaborating Centre for Influenza and one probable case for which samples were not available. The cases were in two unrelated clusters in Salyan (seven laboratory confirmed cases, including four deaths) and Tarter districts (one confirmed case and one probable case, both fatal). Close contact with and de-feathering of infected wild swans was considered to be the most plausible source of exposure to influenza A/H5N1 virus in the Salyan cluster, although difficulties in eliciting information were encountered during the investigation, because of the illegality of some of the activities that might have led to the exposures (hunting and trading in wild birds and their products). These cases constitute the first outbreak worldwide where wild birds were the most likely source of influenza A/H5N1 virus infection in humans. The rapid mobilisation of resources to contain the spread of influenza A/H5 in the two districts was achieved through collaboration between the MoH, WHO and its international partners. Control activities were supported by the establishment of a field laboratory with real-time polymerase chain reaction (RT-PCR) capacity to detect influenza A/H5 virus. Daily door-to-door surveillance undertaken in the two affected districts made it unlikely that human cases of influenza A/H5N1 virus infection remained undetected.

Azerbaijan↗
PubMed2005

A randomised comparison of treosulfan and carboplatin in patients with ovarian cancer: a study by the Scottish Gynaecological Cancer Trials Group (SGCTG).

The management of older and unfit women with advanced ovarian cancer requires post-operative chemotherapy but many of these patients are not suitable for high-dose cisplatin-based regimes. Carboplatin has been an easier alternative and can be given in the ambulatory setting. Historical data suggests that oral alkylating agents to be just effective with similar efficacy. In this study we have compared platinum-based carboplatin to the alkylating agent treosulfan in a population unfit to receive high-dose cisplatin. The trial randomised patients to either intravenous carboplatin or treosulfan as single agent. The trial was stopped prematurely after the interim analysis showed improved survival and response rates in the carboplatin arm. We conclude that carboplatin is a safe and effective drug in a population that is unfit for high-dose cisplatin. Treosulfan showed limited activity but may be considered along with other oral drugs in limited circumstances. With the exception of myelosuppression, toxicity was mild in both arms. Carboplatin remains the gold standard in this older and less fit group of patients.

Aged↗
PubMed2005

Audit in infection control.

Audit is a key function of infection control teams. Infection control audit programmes should include audits of infection control policies in wards and departments, and microbiological safety audits of the healthcare environment. This paper reviews the literature on healthcare audit with particular emphasis on published audits in infection control. Evidence of the efficacy of audit and feedback in improving infection control outcomes is presented, together with the nature of interventions necessary to bring about change.

Humans↗
PubMed2005

Detailed analysis of the genetic evolution of influenza virus during the course of an epidemic.

The genetic variability of influenza virus is usually studied with sequences selected over numerous years and countries, and rarely within a single season. Here we examined the viral evolution and the correlation between genetic and clinical features during an epidemic. From a French prospective household-based study in 1999-2000, 99 infected patients were randomly selected. The HA1 genomic domain was sequenced. Phylogenetic analysis showed the existence of two groups of A/H3N2 viruses. We found no distinct pattern of genomic evolution within either group according to time. A spatial correlation with the nucleotide distances was shown. The average nucleotide diversity was 3.4x10-3 nucleotides per site, and did not differ between the groups. A lower number of segregating sites was observed in patients who experienced influenza-like symptoms during the previous epidemic. These results suggest that the influenza virus undergoes regular HA1 nucleotide changes, but without clonal expansion of mutant strains within a single epidemic.

Adult↗
PubMed2004

Recent changes among human influenza viruses.

Recurrent epidemics of influenza are due to the frequent emergence of antigenic variants. With co-circulation of two influenza A subtypes and two antigenically distinct lineages of B viruses, genetic reassortment also has an important role in antigenic drift, as illustrated by recent changes in both A and B viruses. The H1N2 subtype viruses, which emerged during 2001, possessed a H1 HA similar to those of contemporary A/New Caledonia/20/99 (H1N1)-like viruses and seven genes closely related to those of recent H3N2 viruses, and did not represent a significant increase in the antigenic diversity of circulating viruses. The re-emergence of B/Victoria/2/87-lineage viruses, previously prevalent during the 1980s, in 2000 has been followed by the predominant circulation of reassortant B viruses possessing a B/Victoria-lineage HA and a B/Yamagata-lineage NA similar in sequence to those of recent B/Sichuan/379/99-like viruses. These events emphasize not only the lack of divergence in the complementary functional characteristics of the HA and NA of divergent influenza B lineages, but also the apparent convergence in compatibility between the H1 and N2 components of the two influenza A subtypes.

Antigenic Variation↗
PubMed2004

Detecting human CD34+ and CD34- hematopoietic stem and progenitor cells using a Sysmex automated hematology analyzer.

In clinical medicine, particularly in the newly developing stem cell therapies required to support the practice of regenerative medicine, the measurement of both CD34+ and CD34- hematopoietic stem cells (HSC)/hematopoietic progenitor cells (HPC) is important in obtaining more accurate information about the total HSC/HPC content in various stem/progenitor cell sources. We report the results of an investigation into methods of detecting CD34+ and CD34- HSC/HPC using the immature information (IMI) channel incorporated into the Sysmex XE-2100 and SE-9000 automated hematology analyzers. In this study, CD34+ and CD34- HSC/HPC were separated by immunologic methods and quantified by flow cytometry (FACScan) and IMI channel analysis. In addition, CD34-/CD133+ HSC were prepared by a sequential antibody-based positive selection strategy. These cells appeared in the same area as CD34+ cells in the IMI channel of the automated hematology analyzer. These findings confirmed that an automated hematology analyzer can be used to measure both CD34+ and CD34- HSC. These results may explain the difference in HSC/HPC counts sometimes observed between the automated hematology analyzer and flow cytometric methods for CD34+ measurement. The results of this study demonstrated the potential of automated cell counting methods for measuring HSC content in cellular products for both research and clinical applications.

AC133 Antigen↗
PubMed2003

Human infection by a swine influenza A (H1N1) virus in Switzerland.

The isolation of A/Switzerland/8808/2002 provides further evidence of sporadic human infection by contemporary swine influenza A H1N1 viruses, antigenically and genetically distinct from H1N1 viruses circulating in the human population. Together with the recent emergence of human-swine-avian reassortant viruses in pig populations in Europe and North America, frequent transmission between swine and human populations emphasises the potential for the emergence in pigs of novel subtypes with the capacity to cause major human epidemics.

Agricultural Workers' Diseases↗
PubMed2003

Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir.

The influenza virus neuraminidase (NA) inhibitors zanamivir and oseltamivir were introduced into clinical practice in various parts of the world between 1999 and 2002. In order to monitor the potential development of resistance, the Neuraminidase Inhibitor Susceptibility Network was established to coordinate testing of clinical isolates collected through the World Health Organization influenza surveillance network from different regions of the world (M. Zambon and F. G. Hayden, Antivir. Res. 49:147-156, 2001). The present study establishes the baseline susceptibilities prior to and shortly after the introduction of the NA inhibitors. Over 1000 clinical influenza isolates recovered from 1996 to 1999 were tested. Susceptibilities were determined by enzyme inhibition assays with chemiluminescent or fluorescent substrates with known NA inhibitor-resistant viruses as controls. The 50% inhibitory concentrations (IC(50)s) depended upon the assay method, the drug tested, and the influenza virus subtype. By both assays, the mean zanamivir IC(50)s were 0.76, 1.82, and 2.28 nM for the subtype H1N1 (N1), H3N2 (N2), and B NAs, respectively, and the oseltamivir IC(50)s were 1.2, 0.5, and 8.8 nM for the N1, N2, and B NAs, respectively. The drug susceptibilities of known zanamivir- and oseltamivir-resistant viruses with the NA mutations E119V, R292K, H274Y, and R152K fell well outside the 95% confidence limits of the IC(50)s for all natural isolates. Sequence analysis of the NAs of viruses for which the IC(50)s were above the 95% confidence limits and several control isolates for which the IC(50)s were in the normal range revealed variations in some previously conserved residues, including D151, A203, T225, and E375 (N2 numbering). Known resistance mutations are both influenza virus subtype and drug specific, but there was no evidence of naturally occurring resistance to either drug in any of the isolates.

Acetamides↗
PubMed2003

Influenza AH1N2 viruses, United Kingdom, 2001-02 influenza season.

During the winter of 2001-02, influenza AH1N2 viruses were detected for the first time in humans in the U.K. The H1N2 viruses co-circulated with H3N2 viruses and a very small number of H1N1 viruses and were isolated in the community and hospitalized patients, predominantly from children <15 years of age. Characterization of H1N2 viruses indicated that they were antigenically and genetically homogeneous, deriving the hemagglutinin (HA) gene from recently circulating A/New Caledonia/20/99-like H1N1 viruses, whereas the other seven genes originated from recently circulating H3N2 viruses. Retrospective reverse transcription-polymerase chain reaction analysis of influenza A H1 viruses isolated in the U.K. during the previous winter identified a single H1N2 virus, isolated in March 2001, indicating that H1N2 viruses did not widely circulate in the U.K. before September 2001. The reassortment event is estimated to have occurred between 1999 and early 2001, and the emergence of H1N2 viruses in humans reinforces the need for frequent surveillance of circulating viruses.

Genetic Variation↗
PubMed2002

Emergence of influenza A H1N2 reassortant viruses in the human population during 2001.

Influenza A H1N2 viruses, which emerged during 2001, are genetic reassortants between H1N1 and H3N2 subtype viruses which have cocirculated in the human population since 1977. They possess a H1 hemagglutinin antigenically and genetically similar to contemporary A/New Caledonia/20/99 (H1N1)-like viruses and seven genes closely related to those of recent A/Moscow/10/99 (H3N2)-like viruses. The viruses have spread to many regions of the world and have predominated over H1N1 viruses in several countries. Since half of the amino acid changes which accumulated in the HAs of H1N1 viruses since 1995 are in residues implicated in receptor binding, functional changes in the H1 HA may have facilitated its replacement of the H3 HA and may contribute to the future epidemiologic significance of these H1N2 viruses.

Geography↗
PubMed2002

Antigenic and genetic diversity among swine influenza A H1N1 and H1N2 viruses in Europe.

Three subtypes of influenza A viruses, H1N1, H1N2 and H3N2, co-evolve in pigs in Europe. H1N2 viruses isolated from pigs in France and Italy since 1997 were closely related to the H1N2 viruses which emerged in the UK in 1994. In particular, the close relationship of the neuraminidases (NAs) of these viruses to the NA of a previous UK H3N2 swine virus indicated that they had not acquired the NA from H3N2 swine viruses circulating in continental Europe. Moreover, antigenic and genetic heterogeneity among the H1N2 viruses appeared to be due in part to multiple introductions of viruses from the UK. On the other hand, comparisons of internal gene sequences indicated genetic exchange between the H1N2 viruses and co-circulating H1N1 and/or H3N2 subtypes. Most genes of the earlier (1997-1998) H1N2 isolates were more closely related to those of a contemporary French H1N1 isolate, whereas the genes of later (1999-2000) isolates, including the HAs of some H1N2 viruses, were closely related to those of a distinct H1N1 antigenic variant which emerged in France in 1999. In contrast, an H3N2 virus isolated in France in 1999 was closely related antigenically and genetically to contemporary human A/Sydney/5/97-like viruses. These studies reveal interesting parallels between genetic and antigenic drift of H1N1 viruses in pig and human populations, and provide further examples of the contribution of genetic reassortment to the antigenic and genetic diversity of swine influenza viruses and the importance of the complement of internal genes in the evolution of epizootic strains.

Animals↗
PubMed2002

Suicide in the Highlands of Scotland.

OBJECTIVE: The Highlands have one of the highest suicide rates in Scotland. This paper describes suicide and deliberate self-harm in the Highlands in the last 20 years and explores possible reasons for the differences from the Scottish average. DESIGN: Retrospective analysis of routine data from the SMRI/SMR01 scheme and information on deaths from the Registrar General. Suicide and undetermined deaths were combined in the analysis. SETTING: Highland and Scotland 1978-98. RESULTS: The high rates in Highland are caused by an excess of male deaths. Highland has had consistently high male suicide rates over the 20 year period compared to Scotland. These differences do not disappear when deaths of non-Highland residents are excluded. By comparison, deliberate self-harm admissions follow a similar pattern to Scotland as a whole. Causes of death differed from Scotland as a whole, with an over-representation of drowning, gases and firearm deaths. CONCLUSION: Highland suicide rates are elevated compared to Scotland. This is mainly due to an excess of deaths in men up to the age of 74 years, and is not accounted for by deaths of non-residents. Female deaths are not elevated in comparison to the rest of Scotland. Male attempted suicide rates do not differ from Scotland. Lethality of method--drowning, car exhausts and firearms--may contribute to the elevated male death rates.

Female↗
PubMed2001

Rapid molecular analysis of the haemagglutinin gene of human influenza A H3N2 viruses isolated in spain from 1996 to 2000.

A simple molecular technique was used for the rapid preliminary genetic characterization of human influenza A H3N2 viruses isolated in Spain from 1996 to 2000. Subtyping, based on RT-PCR, was followed by subtype-specific restriction enzyme fragment length polymorphism (RFLP) analyses of an amplified region of the HA1 domain of the H3 haemagglutinin (HA) gene to distinguish variants differentiated by common amino acid substitutions in HA1. The approach was tested using 135 Spanish H3N2 isolates and included nucleotide sequencing and phylogenetic analyses of a region of the HA1 domain of 41 representative isolates. The viruses were distinguished by haemagglutination inhibition (HI) assays into two antigenically discernible groups, the A/Wuhan/359/95-like and A/Sydney/5/97-like viruses. The results of PCR-RFLP analysis allowed a finer classification into five genetic variant subgroups, corresponding to those distinguished by phylogenetic analyses. This rapid, simple and variant-specific procedure could, therefore, be used to rapidly screen clinical specimens prior to more detailed antigenic and genetic analyses.

Hemagglutinin Glycoproteins, Influenza Virus↗