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Biomedical subjects

A Power

Publications and source records attributed to A Power.

At least 19 recordsLinked to original sources
PubMed2005

Changes in practice of breast cancer radiotherapy 1998-2002: an Australasian survey.

In order to assess the impact on radiation oncology practice of the publication of evidence-based guidelines for technical aspects of therapeutic radiation for breast cancer, the Radiation Oncology Expert Advisory Group of the National Breast Cancer Centre conducted two postal surveys of radiation oncologists practising in Australia and New Zealand. Results from a survey conducted in 1998, prior to distribution of the guidelines, have been published previously. This article reports on results from a survey undertaken in 2002 and contains data from 102 respondents who manage women with breast cancer. The results show several important changes in practice since 1998, including increased use of CT scanning in breast cancer treatment planning and increased use of immobilization devices for patient treatment. There is also evidence of increased attention to technical aspects of treatment planning that reduce the potential risk of treatment toxicity. The influence of the guidelines, the wider availability of modern equipment and results from landmark clinical trials on change in radiation therapy practice is discussed.

Australia↗
PubMed2005

Problem-based, peer-facilitated education about antibiotic prescribing.

AIMS: To assess the feasibility and acceptability of a problem-based, peer-facilitated educational workshop about antibiotic prescribingfor GPs. METHOD PARTICIPANTS: All 39 GPs working in an average sized Local Health Care Co-operative (LHCC) in Glasgow. INTERVENTION: Prospective collection of information about 10 prescriptions for antibiotics to assess learning needs in relation to antibiotic prescribing. Two and a half hour workshop involving problem-based group work based on the needs assessment and discussions with a consultant microbiologist, prescribing adviser and academic GP. EVALUATION: Written feedback about the process of the educational intervention immediately after the workshop and outcome feedback collected after four weeks. Telephone interviews with non-participants. RESULTS: Twenty-four GPs agreed to participate in the study. 19 of these completed the Needs Assessment and 14 of these completed the workshop. The method of learning needs assessment and the educational workshop were highly acceptable. "No time, too busy" was the main reason given for not taking part in the study. CONCLUSION: Some GPs are unable to participate as fully as they would like in continuing professional learning activities due to competing workload pressures. Further research is required to investigate the necessary type and balance of learning activities and the barriers to engagement to ensure the most effective use of clinician time available for continuing educational activities.

Adult↗
PubMed1999

Decreased morbidity and use of hospital services in English HIV-infected individuals with increased uptake of anti-retroviral therapy 1996-1997. National Prospective Monitoring System Steering Group.

OBJECTIVE: To investigate the relationship between changing morbidity patterns, the use of hospital services by HIV-infected patients and the uptake of antiretroviral therapy (ART) in England. DESIGN: Prospective serial cross-sectional analyses based on data collected through the National Prospective Monitoring System (NPMS), a multi-centre prospective monitoring system. SETTING: HIV-infected patients seen in 10 clinics, five London and five non-London, during the three semesters, 1 January 1996 to 30 June 1997. MAIN OUTCOME MEASURES: The mean use of hospital services per patient-year, mean new HIV-related opportunistic illnesses per 1000 patient-years and percentage uptake of ART. RESULTS: The use of inpatient services changed particularly among AIDS patients. The mean number of inpatient days for AIDS patients decreased from 19.7 [95% confidence interval (CI) 13.7-25.7] in 1996 to 11.2 (95% CI 6.1-15.6) per patient-year in 1997. Concurrently the number of new AIDS-defining events decreased significantly from 567 (95% CI 529-607) to 203 (95% CI 183-225) per 1000 patient-years. The overall uptake of ART increased significantly from 33% (95% CI 31-35%) to 50% (95% CI 48-52%), and a switch from mono or dual to triple therapy or quadruple or more therapy was observed. However, by mid-1997 only 29% (95% CI 26-32%) of asymptomatic patients and 51% (95% CI 49-54%) of patients with symptomatic non-AIDS were on ART, compared with 69% (95% CI 66-71%) of AIDS patients. CONCLUSION: The observed reduction in new AIDS-defining events has led to a reduction in the need for inpatient hospital care and has been associated with an increased uptake of ART, including a switch to triple therapy. All of these factors are likely to have contributed to the observed reduction in mortality among English AIDS patients. As the overall uptake of ART remained relatively low in English centres further improvements can be anticipated. However, the medium to long-term effects of these treatment regimens will need to be closely monitored.

Anti-HIV Agents↗
PubMed1999

Multiple folding pathways for heterologously expressed human prion protein.

Human PrP (residues 91-231) expressed in Escherichia coli can adopt several conformations in solution depending on pH, redox conditions and denaturant concentration. Oxidised PrP at neutral pH, with the disulphide bond intact, is a soluble monomer which contains 47% alpha-helix and corresponds to PrPC. Denaturation studies show that this structure has a relatively small, solvent-excluded core and unfolds to an unstructured state in a single, co-operative transition with a DeltaG for folding of -5.6 kcal mol-1. The unfolding behaviour is sensitive to pH and at 4.0 or below the molecule unfolds via a stable folding intermediate. This equilibrium intermediate has a reduced helical content and aggregates over several hours. When the disulphide bond is reduced the protein adopts different conformations depending upon pH. At neutral pH or above, the reduced protein has an alpha-helical fold, which is identical to that observed for the oxidised protein. At pH 4 or below, the conformation rearranges to a fold that contains a high proportion of beta-sheet structure. In the reduced state the alpha- and beta-forms are slowly inter-convertible whereas when oxidised the protein can only adopt an alpha-conformation in free solution. The data we present here shows that the human prion protein can exist in multiple conformations some of which are known to be capable of forming fibrils. The precise conformation that human PrP adopts and the pathways for unfolding are dependent upon solvent conditions. The conditions we examined are within the range that a protein may encounter in sub-cellular compartments and may have implications for the mechanism of conversion of PrPC to PrPSc in vivo. Since the conversion of PrPC to PrPSc is accompanied by a switch in secondary structure from alpha to beta, this system provides a useful model for studying major structural rearrangements in the prion protein.

Circular Dichroism↗
PubMed1999

Reversible conversion of monomeric human prion protein between native and fibrilogenic conformations.

Prion propagation involves the conversion of cellular prion protein (PrPC) into a disease-specific isomer, PrPSc, shifting from a predominantly alpha-helical to beta-sheet structure. Here, conditions were established in which recombinant human PrP could switch between the native alpha conformation, characteristic of PrPC, and a compact, highly soluble, monomeric form rich in beta structure. The soluble beta form (beta-PrP) exhibited partial resistance to proteinase K digestion, characteristic of PrPSc, and was a direct precursor of fibrillar structures closely similar to those isolated from diseased brains. The conversion of PrPC to beta-PrP in suitable cellular compartments, and its subsequent stabilization by intermolecular association, provide a molecular mechanism for prion propagation.

Circular Dichroism↗
PubMed1999

Effects of seasonality on xenobiotic and antioxidant defence mechanisms of bivalve molluscs.

Levels of chemical pollutants in the environment often display wide seasonal variation in response to climatic and other factors. Use of bioindicators such as enzyme activities in biomonitoring studies is complicated by this variation. Many such enzyme activities themselves show considerable seasonal fluctuation and there is known to be seasonality also in natural exposure to oxidative stress. This review attempts to explore some consequences of seasonal variation for biomonitoring studies with bivalve molluscs. It is suggested that independence of seasonal variation should be seen as a desirable feature of a bioindicator molecule. Where such molecules show seasonal variation, however, this should be incorporated into interpretation of biomonitoring studies by the use of appropriate controls.

Animals↗
PubMed1999

Structural mobility of the human prion protein probed by backbone hydrogen exchange.

Prions, the causative agents of Creutzfeldt-Jacob Disease (CJD) in humans and bovine spongiform encephalopathy (BSE) and scrapie in animals, are principally composed of PrPSc, a conformational isomer of cellular prion protein (PrPC). The propensity of PrPC to adopt alternative folds suggests that there may be an unusually high proportion of alternative conformations in dynamic equilibrium with the native state. However, the rates of hydrogen/deuterium exchange demonstrate that the conformation of human PrPC is not abnormally plastic. The stable core of PrPC has extensive contributions from all three alpha-helices and shows protection factors equal to the equilibrium constant for the major unfolding transition. A residual, hyper-stable region is retained upon unfolding, and exchange analysis identifies this as a small nucleus of approximately 10 residues around the disulfide bond. These results show that the most likely route for the conversion of PrPC to PrPSc is through a highly unfolded state that retains, at most, only this small nucleus of structure, rather than through a highly organized folding intermediate.

Circular Dichroism↗
PubMed1998

The use and cost of HIV service provision in England in 1996. National Prospective Monitoring System (NPMS) Steering Group and NPMS Working Party on Costs.

OBJECTIVE: The aim of the study was to measure the use and estimate the cost of HIV service provision in England. DESIGN AND SETTING: Standardised activity and case-severity data were collected prospectively in 10 English HIV clinics (5 London and 5 non-London sites) for the periods 1 January 1996 to 30 June 1996 and 1 July 1996 to 31 December 1996 and linked to unit cost data. In total, 5440 patients with HIV infection attended during the first 6 months and 5708 during the second 6 months in 1996. MAIN OUTCOME MEASURES AND RESULTS: The mean number of inpatient days per patient-year for patients with AIDS was 19.7 [95% confidence interval (CI): 13.7 to 25.7] for January to June and 20.8 (95% CI: 15.3 to 26.4) for July to December 1996. The mean number of outpatient visits for asymptomatic patients with HIV infection was 14.8 (95% CI: 11.9 to 17.6) and 13.3 (95% CI: 10.8 to 15.7) for the respective periods and 16.1 (95% CI: 13.21 to 18.97) and 15.7 (95% CI: 11.2 to 20.2), respectively, for patients with symptomatic non-AIDS (i.e. symptomatic patients with HIV infection but without AIDS-defining conditions). Substantial centre-to-centre variation was observed, suggesting that many clinics can continue the shift from an inpatient- to an outpatient-based service. Cost estimates per patient-year for HIV service provision for 1996 varied from 4695 Pounds (95% CI: 3769 Pounds to 5648 Pounds) for asymptomatic patients, to 7605 Pounds (95% CI: 6273 Pounds to 8909 Pounds) for symptomatic non-AIDS patients to 20,358 Pounds (95% CI: 17,681 Pounds to 23,206 Pounds) for patients with AIDS. CONCLUSIONS: Different combinations of antiretroviral therapy affect the cost estimates of HIV service provision differently. Anticipated reduction in inpatient-related activity through the increased use of combination antiretroviral therapy will further shift service provision from an inpatient- to outpatient-based service and reduce costs per patient-year. The extent and duration of such effects are currently unknown. The long term effects of combination treatment on the morbidity and mortality patterns of individuals infected with HIV are also currently unknown, as are their implications on the use and cost of HIV service provision. Multicentre databases like the National Prospective Monitoring System (NPMS) will provide healthcare professionals with information to improve existing services and anticipate the impact of new developments.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Incidence and detection of multi-drug-resistant enterococci in Dublin hospitals.

In February 1994, an outbreak of vancomycin-resistant Enterococcus faecium (VREM) occurred in the oncology unit of a Dublin hospital. Between February and July 1994, VREM was isolated from 18 patients, one staff member and 14 environmental sites within the unit. The isolates also had high-level aminoglycoside and penicillin resistance. Three pulsed-field gel electrophoresis (PFGE) types were identified, two of them from multiple patients and environmental sites. Plasmid typing allowed subdivision of PFGE types. A retrospective study of enterococci isolated from blood cultures between January 1991 and January 1994 showed that, before the outbreak, fewer than 2% of isolates were vancomycin-resistant but that the incidence of high-level gentamicin resistance had increased from 17% to 60% and ampicillin resistance from 22% to 51%. Among clinically significant non-blood-culture enterococci isolated between September and December 1993, fewer than 1% were vancomycin-resistant, 13% were ampicillin-resistant and 44% highly gentamicin-resistant. None produced beta-lactamase. High-content gentamicin disks (120 micrograms) and low-content vancomycin disks (5 micrograms) allowed simple, reliable detection of resistant enterococci. MICs of vancomycin and teicoplanin determined by agar dilution and E-test agreed well, but values tended to be slightly lower by E-test.

Ampicillin Resistance↗
PubMed1996

The Genome Sequence DataBase (GSDB): meeting the challenge of genomic sequencing.

The genome sequence database (GSDB) is a complete, publicly available relational database of DNA sequences and annotation maintained by the National Center for Genome Resources (NCGR) under a Cooperative Agreement with the US Department of Energy (DOE). GSDB provides direct, client- server access to the database for data contributions, community annotation and SQL queries. The GSDB Annotator, a multi-platform graphic user interface, is freely available. Automatically updated relational replicates of GSDB are also freely available.

Amino Acid Sequence↗
PubMed1995

Drug metabolizing enzymes of mussels as bioindicators of chemical pollution.

The GSTs of M. edulis provide an easily assayed activity which would be expected to respond to changes in pollution status. The main GST and a related GSH-binding protein have been purified and biochemically characterized. The former protein is most similar to the Pi class while the latter is a catalytically inactive monomer which appears to be related to the Mu class. This enzyme activity has been assessed as a potential indicator of exposure to chemical pollutants in both Cork Harbour and Venice Lagoon (using the closely related species, M. galloprovincialis). Controlled exposure studies with mussels in holding tanks have indicated that the herbicide aldicarb gives a slight but significant increase in GST activity consistent with the inducibility of these enzymes by xenobiotics in this bivalve. At present, we are studying samples which have been deliberately exposed to PAH and PCB compounds. Studies of this type are important in helping to understand the effects and fate of chemical pollutants released into estuarine environments.

Animals↗
PubMed1994

An investigation of the adequacy of MEDLINE searches for randomized controlled trials (RCTs) of the effects of mental health care.

Valid reviews of the effects of mental health care depend on identifying as high a proportion as possible of relevant randomized controlled trials (RCTs). To investigate the sensitivity and precision both of MEDLINE and of hand-searching for RCTs in mental health, 12 journals specializing in mental health and indexed by the National Library of Medicine (NLM) for MEDLINE were searched for the years 1971, 1976, 1981, 1986 and 1991. The sensitivity of the hand-search was 94% (95% Confidence Interval (CI) 93-95%), but it had a precision of only 7% (CI 6-8%). The optimal MEDLINE search had a sensitivity of only 52% (CI 48-56%) and a precision of 59% (CI 55-63%). Of the reports of RCTs identified by the hand-search, 9% (CI 7-11%) were not included in MEDLINE at all. Authors had included methodological descriptions in 84% (CI 80-88%) of RCTs found by the hand-search but missed by the MEDLINE search. Systematic reviews of mental health care which are based solely on MEDLINE searches of the literature will miss a large proportion of the relevant RCTs, and are thus liable to random error and bias. A register of mental health RCTs is urgently required.

Bias↗
PubMed1992

Identifying constraints on the higher-order structure of RNA: continued development and application of comparative sequence analysis methods.

Comparative sequence analysis addresses the problem of RNA folding and RNA structural diversity, and is responsible for determining the folding of many RNA molecules, including 5S, 16S, and 23S rRNAs, tRNA, RNAse P RNA, and Group I and II introns. Initially this method was utilized to fold these sequences into their secondary structures. More recently, this method has revealed numerous tertiary correlations, elucidating novel RNA structural motifs, several of which have been experimentally tested and verified, substantiating the general application of this approach. As successful as the comparative methods have been in elucidating higher-order structure, it is clear that additional structure constraints remain to be found. Deciphering such constraints requires more sensitive and rigorous protocols, in addition to RNA sequence datasets that contain additional phylogenetic diversity and an overall increase in the number of sequences. Various RNA databases, including the tRNA and rRNA sequence datasets, continue to grow in number as well as diversity. Described herein is the development of more rigorous comparative analysis protocols. Our initial development and applications on different RNA datasets have been very encouraging. Such analyses on tRNA, 16S and 23S rRNA are substantiating previously proposed associations and are now beginning to reveal additional constraints on these molecules. A subset of these involve several positions that correlate simultaneously with one another, implying units larger than a basepair can be under a phylogenetic constraint.

Base Sequence↗