Mutation in the SPINK1 trypsin inhibitor gene, alcohol use, and chronic pancreatitis.
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Biomedical subjects
Publications and source records attributed to D O'Reilly.
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Several groups of large DNA viruses successfully utilise the rich resource provided by insect hosts. Defining the mechanisms that enable these pathogens to optimise their relationships with their hosts is of considerable scientific and practical importance, but our understanding of the processes involved is, as yet, rudimentary. Here we describe an informatics-based approach that uses comparison of viral genomic sequences to identify candidate genes likely to be specifically involved in this process. We hypothesise that such genes should satisfy two essential criteria, namely, that they should be (i) present in those members of a virus family that infect insects, but absent from those that infect other hosts, and (ii) found in at least two unrelated taxa of insect viruses. These criteria currently identify six groups of viral genes, including one that encodes the fusolin/gp37 proteins. Demonstration that the fusolin/gp37 proteins can enhance oral infectivity of insect viruses provides a primary validation of this approach to the examination of insect-virus relationships.
The Anticarsia gemmatalis nucelopolyhedrovirus (AgMNPV) egt gene was cloned, sequenced and its expression characterized by RT-PCR and western blot analysis. Sequence analysis of the gene indicated the presence of an open reading frame (ORF) of 1482 nucleotides, which codes for a polypeptide of 494 amino acids. ATATA box and a conserved regulatory sequence (CATT) found in other baculovirus early genes were present in the promoter region of the egt gene. A poly-A consensus sequence was present in the 3' untranslated region (3'-UTR) of the gene. Homology comparisons showed that the EGT protein of AgMNPV is most closely related (95.9% amino acid sequence identity) to the EGT from the Choristoneura fumiferana DEF nucleopolyhedrovirus (CfDEF). Transcriptional analysis of the AgMNPV egt gene showed that egt-specific transcripts can be detected both early and late in infection. The EGT protein was detected, by western blot analysis, in the intra- (from 12 to 48 h post-infection) and extra-cellular (from 12 to 96 h post-infection) fractions of infected insect cells. The AgMNPV Bgl II-F fragment, which has homology to the AcMNPV ie-1 gene, was cloned and used to cotransfect SF21 cells with the cloned AgMNPV egt gene. EGT activity was observed, suggesting that AgMNPV ie-1 can transactivate egt expression.
A recombinant Anticarsia gemmatalis multicapsid nucleopolyhedrovirus (AgMNPV) expressing beta-galactosidase under the control of the polyhedrin promoter was generated in our laboratory. To this end, we cloned the AgMNPV-2D genomic DNA fragment containing the polh gene and subcloned and sequenced the polyhedrin gene and its flanking regions. Based on this sequence information, sets of primers were designed to amplify the flanking regions by PCR, including appropriate restriction sites. The transfer vector (pAgPHZ) was constructed by the consecutive cloning of these PCR fragments flanking the Escherichia coli LacZ gene, in place of the polh gene. pAgPHZ was used for cotransfection of UFL-AG-286 insect cells with AgMNPV-2D DNA and the required recombinant, generated by homologous recombination with the polh locus, was identified by its polh(-)/LacZ+ plaque phenotype. Its genome structure was confirmed by PCR, restriction digestion and Southern blot analyses. The kinetics and levels of expression of beta-galactosidase in UFL-AG-286 cells infected with the recombinant were tested by SDS-PAGE and enzymatic activity assays.
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OBJECTIVE: To describe health and neurodevelopmental outcomes and parental satisfaction with hospital care among surviving intervention and control enrollees in a randomized, controlled trial of nitric oxide for persistent pulmonary hypertension of the newborn (PPHN). METHODS: All surviving enrollees 1 to 4 years of age were eligible for follow-up. Outcomes were assessed by telephone using a trained interviewer and standardized instruments. Domains assessed included parental report of specific conditions and hospital use, rating of general health, cognitive and motor development, behavior problems, temperament, and satisfaction with the hospital stay. Fisher's exact test and the Wilcoxon rank sum test assessed differences between intervention and control infants. RESULTS: Interviews were completed on 60 of 83 survivors (72%). Eighteen families (22%) could not be located, 2 (2%) were non-English-speaking, and 3 (4%) declined participation. No postdischarge deaths were ascertained. Among those interviewed, race, income, and education of parents of intervention and controls were comparable, as were entry oxygenation index, extracorporeal oxygenation utilization, and days of hospitalization. No differences were found in pulmonary, neurologic, cognitive, behavioral, or neurosensory outcomes; hospital readmission rates; or parental ratings of child's health. The overall neurologic handicap rate was 15%. The rate of hearing deficit was 7%. The rate of significant behavioral problems was 26%. Levels of satisfaction expressed were high for each group. No differences in parental ratings were found between the 2 groups. CONCLUSIONS: No adverse health or neurodevelopmental outcomes have been observed among infants treated with nitric oxide for PPHN. The parents of the critically ill infants enrolled in our clinical trial welcomed their child's inclusion and all expressed satisfaction with the care that their child received while at a tertiary care hospital. Enrollment in either arm of this randomized, controlled trial did not seem to affect parental satisfaction with the hospital care that their child received.
BACKGROUND: Cancer registries provide a basis for many epidemiological studies in cancer. Electronic data provide for prompt, economical data capture for disease registries; doubts, however, exist about their data quality. MATERIALS AND METHODS: We examined the accuracy for cancer registration of a subset of 7043 electronically captured hospital discharge data. RESULTS: Note availability was 82%. Of the notes available for examination demographic data accuracy was high; however, 7.4% of cases coded on discharge as cancer had no malignancy recorded in case notes while 4. 1% had in-situ or benign tumors. Almost a third had some inaccuracy in coding tumor site. Prevalent cases accounted for 17.2% of cases examined reflecting a new registry. Electronic data capture reduces time spent examining notes; only 40% of cases notified from PAS required a quick validation check. It enhances data completeness; without electronic discharge data 11.5% of the final database would have been missed. The validation check prevented overinflation of the cancer registration database by 7.5%. Measures of accuracy in the final database were high. CONCLUSION: This study shows that discharge data are a valuable data source for cancer registries but require a targeted note review aimed at cases without corroborating data.
As a group of academic skills, learning to search for, obtain, read and critically review literature represents a considerable achievement. For the many perioperative nurses who may never be able to pursue their own research project, reading literature reviews is an excellent alternative which enables individuals to become better and more critically informed. A review of the available literature may provide answers to questions or indicate where a subject is in need of further research. In this article by Denise O'Reilly, perioperative hypoxaemia is defined and a range of literature about the subject is critically reviewed.
This ex-vivo study investigated the effect that repeated bracket displacement has on sliding friction and the magnitude of bracket displacement, and hence tooth movement, required to release bracket/archwire binding. The design consisted of an ex-vivo laboratory study. A jig was designed that allowed repeated displacement of a bracket to occur, while the resistance to sliding (friction) was measured using an Instron universal testing machine. One type of stainless steel bracket was used in conjunction with four archwire types (0.016-inch stainless steel, 0.019 x 0.025-inch stainless steel, 0.021 x 0.025-inch stainless steel, 0.019 x 0.025-inch beta-titanium) and four magnitudes of displacement. Repeated bracket displacement has a significant effect on the sliding resistance at the bracket/archwire interface (P < 0.001). The reduction in sliding resistance noted with displacement depended on the archwire. Over the range of displacements tested, there was an 85 and 80 per cent reduction associated with 0.021 x 0.025-inch and 0.019 x 0.025-inch stainless steel, respectively. For 0.019 x 0.025-inch beta-titanium and 0.016-inch stainless steel, these reductions were 27 and 19 per cent, respectively. The importance of true friction, given the likelihood of bracket and/or archwire displacements in vivo, may be lessened.
BACKGROUND: The association between Belfast and research into the hazardous effects of asbestos exposure goes back many years. This paper aims to update previous papers and review the burden of asbestos related disease in Northern Ireland today. METHODS: A study was carried out of all deaths in Northern Ireland between 1985 and 1994 inclusive, in which an asbestos related disease was mentioned anywhere on the death certificate. RESULTS: During this 10 year period, 527 asbestos related deaths were recorded; 88 per cent of these were in men. A total of 410 (77.8 per cent) were registered as the primary cause of death but only 405 (76.9 per cent) of cases were the subject of an autopsy. Standardized rates of pleural cancer in males have been increasing at 3.2 per cent per year though the trend was not significant. Lower rates in the last two years may herald the commencement of a decline. Deaths were clustered around the Belfast estuary, the site of Northern Ireland's shipbuilding industry. High proportional mortality ratios were demonstrated for occupations associated with the shipbuilding and construction industries. Evidence is presented that casts doubt on the attribution of peritoneal cancers in females to asbestos exposure. If lung cancers are included, there may be an average of 81 asbestos related deaths in Northern Ireland every year. CONCLUSION: Asbestos related diseases continue to extract a heavy burden of ill health in Northern Ireland today. There are some indications that the upward trend may be on the wane but confirmation of this will have to await further data. Measures to reduce exposure in the workplace to both asbestos and to tobacco smoke are the only means of reducing this burden.
The herpes simplex virus protein VP22 is a major phosphoprotein of infected cells. In this study, we identify two serine phosphorylation sites within VP22 and show that the N-terminal site is a substrate for casein kinase II, while the extreme C-terminal site is a substrate for another, as yet unidentified, cellular kinase. Furthermore, we show that a mutant of VP22 which has both sites altered is unable to incorporate phosphate in vivo, confirming that there are no other phosphorylation sites within VP22.
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The objective of this study was to determine the efficiency of and annual demands for institutional long-term care placement in the St. John's region. The study population comprised all applicants assessed for institutional long-term care through the Community Health St. John's Region Single Entry System in 1995-96. The outcome measures used for the study included estimates of client resource utilization employing the RUGs III and Alberta Resident Classification System; hospital beds occupied; time to placement; and annual demands on long-term care. The study concludes that objective criteria for admission to supervised care and nursing home care may help reduce the number of inappropriate placements (thus maximizing the use of existing nursing home beds) and decrease annual demands. Investment in alternatives to nursing home care for those with modest disability is suggested.
The aim of this study was to assess the feasibility of providing i.v. antibiotic therapy outside hospital. The main outcome measures were the direct costs of providing i.v. antibiotic therapy in the community compared with standard hospital treatment and the perceptions of patients and General Practitioners (GPs). A total of 29 patients entered the study, of whom 15 received teicoplanin and 14 ceftriaxone. The costs of drugs exceeded the cost of the estimated alternative treatments (median Pound Sterling 208 and Pound Sterling 126 respectively) and this was only partially compensated for by a small reduction in costs of consumables. The staff time required to train patients was compensated for by savings in drug preparation and administration. Sensitivity analysis showed that these conclusions were sensitive to drug and patient selection, and that treatment of skin and soft tissue infections outside hospital with ceftriaxone was likely to have similar variable costs to treatment in hospital with drugs such as flucloxacillin. Non-inpatient i.v. (NIPIV) therapy was estimated to save a total of 532 bed days in the year of the study. Patients strongly preferred non-inpatient treatment to hospital treatment. GPs identified a number of potential disadvantages, mainly concerning safety and lack of support for patients at home. Following the study a strategy for development of NIPIV services in Tayside has been developed with local GPs and a plan has been agreed for funding a community liaison nurse based on the impact of NIPIV therapy on future bed requirements in Dundee Teaching Hospitals Trust.
BACKGROUND: The aim of this study was to examine differences in socio-economic standing and ill health between the two communities in Northern Ireland. METHODS: This was a descriptive epidemiological study. Deaths from 1991 to 1995 inclusive were used to calculate standardized mortality rates (SMR, under 75 years) at small level using the 1991 Census population estimates. The standardized limiting long-term illness ratios (SIR) were based on the appropriate Census question. Regression models were tested with SMR and SIR as dependent variables and a wide range of socio-economic indicators, including income support and family credit uptake, as independent predictors. RESULTS: Northern Ireland is a very polarized society. More than 60 per cent of the population live in areas which have more than 80 per cent of one religion. Areas with a preponderance of Catholics tend to be more deprived. Unemployment rates, percentage renting, car availability, and education attainment are all worse in Catholic areas. However, there is considerable heterogeneity between areas with similar levels of religious affiliation and the overall pattern varies with the indicator chosen. SMRs rise stepwise with increasing percentage of Catholics. SIRs increase with increasing polarization of areas, but this is much more marked in those with a predominantly Catholic affiliation. Altogether 46.8 per cent of the variance in SMR and 77.9 per cent of that of SIRs could be explained by socio-economic variables alone. Denomination did not have any residual predictive value. CONCLUSIONS: Policy-makers should continue to periodically monitor for differences between the two communities including any differences in service accessibility and uptake. Efforts should be directed towards reducing the inequalities in health for all sections of the community.
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BACKGROUND: Being struck off a general practitioner's list is a major event for patients and a subject for much media attention. However, it has not hitherto received much research attention. AIMS: To quantify the numbers of patients removed at doctors' request in Northern Ireland between 1987 and 1996. To describe the characteristics of those removed and to determine if the rate of removal has increased. METHODS: This is a descriptive epidemiological study involving a secondary data analysis of records held by the Central Services Agency. RESULTS: Six thousand five hundred and seventy-eight new patients were removed at general practitioner (GP) request between 1987 and 1996. This equated to 3920 removal decisions, a rate of 2.43 per 10,000 person-years. The very young and young adults had the highest rates of removal; most of the young being removed as part of a family. Ten point six per cent of removed patients had a repeat removal, and 16.3% of first removal decisions required an assignment to another practice. Family removals have decreased and individual removals have increased over the 10 years. Disadvantaged and densely populated areas with high population turnover were associated with higher rates of removal, though heterogeneity is evident between general practitioners serving similar areas. Compared to the period 1987 to 1991, removal rates for the years 1992 to 1993 were reduced by 20.0% (95% confidence interval (CI) for rate ratio (RR) 0.73-0.87), and those for the years 1994 to 1996 increased by 8% (95% CI = 1.01-1.16). The greatest increase was in the over-75 years age group (standardized RR = 1.60; 95% CI = 1.57-1.62). CONCLUSIONS: Removals are relatively rare events for both patients and practices, though they have been increasing in recent years. Further research is needed to understand the processes that culminate in a removal.