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Biomedical subjects

R Thomson

Publications and source records attributed to R Thomson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Localization of H(+)-ATPases in soybean root nodules.

The localization of H(+)-ATPases in soybean (Glycine max L. cv. Stevens) nodules was investigated using antibodies against both P-type and V-type enzymes. Immunoblots of peribacteroid membrane (PBM) proteins using antibodies against tobacco and Arabidopsis H(+)-ATPases detected a single immunoreactive band at approximately 100 kDa. These antibodies recognized a protein of similar relative molecular mass in the crude microsomal fraction from soybean nodules and uninoculated roots. The amount of this protein was greater in PBM from mature nodules than in younger nodules. Immunolocalization of P-type ATPases using silver enhancement of colloidal-gold labelling at the light-microscopy level showed signal distributed around the periphery of non-infected cells in both the nodule cortex and nodule parenchyma. In the central nitrogen-fixing zone of the nodule, staining was present in both the infected and uninfected cells. Examination of nodule sections using confocal microscopy and fluorescence staining showed an immunofluorescent signal clearly visible around the periphery of individual symbiosomes which appeared as vesicles distributed throughout the infected cells of the central zone. Electron-microscopic examination of immunogold-labelled sections shows that P-type ATPase antigens were present on the PBM of both newly formed, single-bacteroid symbiosomes just released from infection threads, and on the PBM of mature symbiosomes containing two to four bacteroids. Immunogold labelling using antibody against the B-subunit of V-type ATPase from oat failed to detect this protein on symbiosome membranes. Only a very faint signal with this antibody was detected on Western blots of purified PBM. During nodule development, fusion of small symbiosomes to form larger ones containing multiple bacteroids was observed. Fusion was preceded by the formation of cone-like extensions of the PBM, allowing the membrane to make contact with the adjoining membrane of another symbiosome. We conclude that the major H(+)-ATPase on the PBM of soybean is a P-type enzyme with homology to other such enzymes in plants. In vivo, this enzyme is likely to play a critical role in the regulation of nutrient exchange between legume and bacteroids.

Microscopy, Electron↗
PubMed1999

Bifidobacterial supplementation reduces the incidence of necrotizing enterocolitis in a neonatal rat model.

BACKGROUND & AIMS: Neonatal necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of premature infants partly caused by intestinal bacterial proliferation. Because bifidobacteria are thought to reduce the risk for intestinal disturbances associated with pathogenic bacterial colonization, we hypothesized that exogenous bifidobacterial supplementation to newborn rats would result in intestinal colonization and a reduction in the incidence of neonatal NEC. METHODS: Newborn rat pups were given Bifidobacterium infantis (10(9) organisms per animal daily), Escherichia coli, or saline control and exposed to the NEC protocol consisting of formula feeding (Esbilac; 200 cal. kg(-1). day(-1)) and asphyxia (100% N(2) for 50 seconds followed by cold exposure for 10 minutes). Outcome measures included stool and intestinal microbiological evaluation, gross and histological evidence of NEC, plasma endotoxin concentration, intestinal phospholipase A(2) expression, and estimation of intestinal mucosal permeability. RESULTS: Bifidobacterial supplementation resulted in intestinal colonization by 24 hours and appearance in stool samples by 48 hours. Bifidobacteria-supplemented animals had a significant reduction in the incidence of NEC compared with controls and E. coli-treated animals (NEC, 7/24 B. infantis vs. 19/27 control vs. 16/23 E. coli; P < 0.01). Plasma endotoxin and intestinal phospholipase A(2) expression were lower in bifidobacteria-treated pups than in controls, supporting the role of bacterial translocation and activation of the inflammatory cascade in the pathophysiology of NEC. CONCLUSIONS: Intestinal bifidobacterial colonization reduces the risk of NEC in newborn rats.

Animals↗
PubMed1999

The lack of integration of clinical audit and the maintenance of medical dominance within British hospital trusts.

Concerns have been expressed repeatedly about the effectiveness of clinical audit. Some have argued that this is limited by the lack of integration within day-to-day practice and with other NHS policy initiatives. We aimed to explore what mechanisms were being used to develop annual clinical audit programmes within NHS Trusts, and to describe the influence of other initiatives on this; to understand how such influences are exerted; and to understand the role of key players, in order to inform future programme development. Semi-structured face-to-face interviews were performed with Chairs of Clinical Audit Committees, Clinical Audit Managers and Co-ordinators (N = 15) in the former Yorkshire Region of the NHS in England. Concerns about the development, planning and integration of clinical audit focused upon an almost exclusive medical dominance and upon how audit leadership could be delivered within the context of hospital management structures. The lack of an overall plan for the development of clinical audit in most sites was seen as enabling the doctors' agenda to dominate. Purchasing authorities were recognized as being important, but often with limited influence. Other influences on the audit agenda, such as research and development (R&D) and clinical risk management, were rarely well co-ordinated. These findings concur with previous studies in identifying a wide range of constraints on the progress of audit. Several of these constraints operate within the internal environment, for example the doctors' agenda, and concerns about management involvement. Such constraints require resolution in order to facilitate the integration of audit with other initiatives and to achieve the goals of audit effectively. Clinical effectiveness and clinical governance may offer a means of facilitating this integration.

Health Policy↗
PubMed1999

Models of commissioning health services in the British National Health Service: a literature review.

The commissioning of health services is an under-researched area and yet it is critical to the way services meet health needs and to the quality of care. Recent emphasis in the United Kingdom and elsewhere has been on a 'primary care led National Health Service', particularly on locality commissioning through primary care groups. However, there are other models of commissioning using 'programmes of care' (focused on diseases or patient groups rather than geography) which may offer greater benefits. There is little research comparing the benefits and costs of these models, and most are not even clearly enough described to be replicated. There will always be a political dimension to models of commissioning, dependent, for example, on the balance of power in the decision-making process. None the less, a broader knowledge of possible models and a willingness to evaluate rigorously are needed if commissioning of health services is to result in better patient care.

Health Care Reform↗
PubMed1999

Aiding clinical decisions with decision analysis.

As clinical decision making gets ever more complex, new analytical approaches are being developed to help. Decision analysis is used to structure complex decision problems in an uncertain environment by systematically linking decision choices with expected outcomes. Such models can include the probabilities of outcomes, patient preferences and costs. These models can help to advise about therapeutic avenues. This paper examines the nature of decision analysis, and explores the pitfalls that arise in interpreting the findings from published studies.

Decision Making↗
PubMed1998

Implications of applying widely accepted cholesterol screening and management guidelines to a British adult population: cross sectional study of cardiovascular disease and risk factors.

OBJECTIVE: To compare the implications of four widely used cholesterol screening and treatment guidelines by applying them to a population in the United Kingdom. DESIGN: Guidelines were applied to population based data from a cross sectional study of cardiovascular disease and risk factors. SETTING: Newcastle upon Tyne, United Kingdom. SUBJECTS: General population sample (predominantly of European origin) of 322 men and 319 women aged 25-64 years. MAIN OUTCOME MEASURES: Proportions recommended for screening and treatment. METHODS: Criteria from the British Hyperlipidaemia Association, the British Drugs and Therapeutics Bulletin (which used the Sheffield table), the European Atherosclerosis Society, and the American national cholesterol education programme were applied to the population. RESULTS: Proportions recommended for treatment varied appreciably. Based on the British Drugs and Therapeutics Bulletin guidelines, treatment was recommended for 5.3% (95% confidence interval 2.9% to 7.7%) of men and 3.3% (1.5% to 5.3%) of women, while equivalent respective values were 4.6 (2.3 to 6.9) and 2.8 (1.0 to 4.6) for the British Hyperlipidaemia Association, 23% (18.4% to 27.6%) and 10.6% (7.3% to 14.0%) for the European Atherosclerosis Society, and 37.2% (31.9% to 42.5%) and 22.2% (17.6% to 26.8%) for the national cholesterol education programme. Only the British Hyperlipidaemia Association and Drugs and Therapeutics Bulletin guidelines recommend selective screening. Applying British Hyperlipidaemia Association guidelines, from 7.1% (4.3% to 9.9%) of men in level one to 56.7% (51.3% to 62.1%) of men in level three, and from 4.4% (2.1% to 6.7%) of women in level one to 54.4% (48.9% to 59.9%) of women in level three would have been recommended for cholesterol screening. Had the Drugs and Therapeutics Bulletin guidelines been applied, 22.2% (16.5% to 27.9%) of men and 12.2% (8. 6% to 15.8%) of women would have been screened. CONCLUSIONS: Without evidence based guidelines, there are problems of variation. A consistent approach needs to be developed and agreed across the United Kingdom.

Adult↗
PubMed1998

Prevalence of atrial fibrillation and eligibility for anticoagulants in the community.

BACKGROUND: Anticoagulants are effective in the prevention of stroke in atrial fibrillation and flutter (AF). We aimed to find out the prevalence of AF in the UK and to estimate the proportion of patients with AF who might benefit from anticoagulation. METHODS: We screened with electrocardiography a random sample of 4843 people from the community aged 65 years and older for AF. Participants with AF had further investigations to identify risk factors for stroke and contraindications to anticoagulants. We used three sets of criteria to assess risk and eligibility for anticoagulation. FINDINGS: 228 (4.7%) participants had AF. According to analyses derived from risk stratifications based on the Stroke Prevention in Atrial Fibrillation (SPAF) study 61% of these patients would have benefited from anticoagulation, 49% according to pooled analysis of trial results, and 41% according to the inclusion criteria for the SPAF 3 study. Anticoagulants were used by 1114 (23%) of all patients and were least used among elderly women, who may be the most likely to benefit. Echocardiography would be useful to assess the need for anticoagulation only in patients younger than 75 years with no contraindications to treatment and no clinical risk factors for stroke. INTERPRETATION: Anticoagulants seem to be underused and misdirected in treatment of AF, according to various criteria. Efforts to promote and support wider and more appropriate use of anticoagulants would seem to be justified, and should decrease the incidence of stroke amongst elderly patients.

Age Distribution↗
PubMed1998

Guidelines on anticoagulant treatment in atrial fibrillation in Great Britain: variation in content and implications for treatment.

OBJECTIVE: To describe the content of guidelines on the use of anticoagulant treatment in patients with atrial fibrillation and the impact of variations in guidelines on treatment. DESIGN: Postal survey of guidelines, semistructured interview with lead developers of guidelines, and application of guidelines to patient sample. SUBJECTS: 15 lead developers of the 20 guidelines identified in the postal survey were interviewed. 100 patients over 65 with atrial fibrillation to whom the guidelines were applied. MAIN OUTCOME MEASURES: Evaluation of guidelines and the methods of dissemination, implementation, review, and evaluation; proportion of patients recommended for anticoagulant treatment by each guideline; and level of agreement between guidelines. RESULTS: There was considerable variation in whether anticoagulant treatment was recommended for subjects (range 13% to 100%, kappa = 0.12). Guidelines varied greatly in advice on treatment by age, the use of echocardiography, and the target value or range of the international normalised ratio (8 of the 20 guidelines included values unlikely to be effective). Development was unsystematic; evidence based approaches were rarely used, 9 of the 15 lead developers had developed the guidelines themselves, and the 6 guidelines developed by groups relied on informal consensus. Methods to support effective dissemination, implementation, and evaluation were limited. CONCLUSION: The widespread non-systematic production of guidelines has led to considerable variation with implications for the quality of care and clinical decision making. There is a need for a central, well funded programme of guideline development to ensure that valid guidelines are produced and disseminated.

Aged↗
PubMed1998

Ages of mutations on a coalescent tree.

Using the coalescent process, DNA sequences of a sample of individuals can be used to study the phylogenetic history of the individuals. Under the infinitely-many-sites mutation model, the DNA sequence data can be summarized by the number of segregating sites (which is numerically equivalent to the number of mutations on the tree). A number of methods exist, including a recursive method presented in this paper, that obtain an estimate of the age of the most recent common ancestor (MRCA), given the number of mutations. This paper introduces a method for finding the ages of mutations, given the total number of mutations on the tree. While the result is not useful in estimating the age of a specific segregating site, it is useful in examining the underlying assumption of a relatively constant population over time. This utilization of the result is illustrated using DNA sequence data obtained from a sample of Amerindians of the Nuu-Chah-Nulth tribe.

Base Sequence↗
PubMed1998

Decision support and disease management: a logic engineering approach.

This paper describes the development and application of PROforma, a unified technology for clinical decision support and disease management. Work leading to the implementation of PROforma has been carried out in a series of projects funded by European agencies over the past 13 years. The work has been based on logic engineering, a distinct design and development methodology that combines concepts from knowledge engineering, logic programming, and software engineering. Several of the projects have used the approach to demonstrate a wide range of applications in primary and specialist care and clinical research. Concurrent academic research projects have provided a sound theoretical basis for the safety-critical elements of the methodology. The principal technical results of the work are the PROforma logic language for defining clinical processes and an associated suite of software tools for delivering applications, such as decision support and disease management procedures. The language supports four standard objects (decisions, plans, actions, and enquiries), each of which has an intuitive meaning with well-understood logical semantics. The development toolset includes a powerful visual programming environment for composing applications from these standard components, for verifying consistency and completeness of the resulting specification and for delivering stand-alone or embeddable applications. Tools and applications that have resulted from the work are described and illustrated, with examples from specialist cancer care and primary care. The results of a number of evaluation activities are included to illustrate the utility of the technology.

Decision Support Systems, Clinical↗
PubMed1998

A community survey of patients with atrial fibrillation: associated disabilities and treatment preferences.

BACKGROUND: Anticoagulants are effective in preventing stroke in those with atrial fibrillation, but most patients remain untreated. AIM: To investigate the prevalence of disability, cognitive impairment, and problems with compliance in a representative sample of the elderly with atrial fibrillation, and to determine whether they would want treatment and how they would like services to be arranged. METHOD: In a survey of a random sample of 4843 elderly subjects, those with atrial fibrillation were identified using electrocardiograms. Views on treatment were obtained using a structured interview. Disability was assessed using the Office of Population Censuses and Surveys Disability Scale and cognitive status using the Mini Mental State Examination. General practitioners were asked, via questionnaire, for their views on each subject's compliance. RESULTS: Two hundred and seven elderly people with atrial fibrillation were identified. Almost all subjects expressed a willingness to undertake treatment to prevent stroke and preferred blood testing performed outside of hospital. Disability (82.7%), cognitive impairment (25.7%), and problems with compliance (25.0%) were common, but the prevalence of these difficulties was not substantially different from the general elderly population, and in many cases they could be overcome (e.g. only 10% of subjects had problems with compliance and no-one who could help them to comply). CONCLUSIONS: Most elderly people with atrial fibrillation would accept treatment to prevent stroke. Disability, cognitive impairment, and problems with compliance may make it difficult to treat this patient group. An increase in the use of anticoagulants should be accompanied by the development of services appropriate to this frail population.

Aged↗
PubMed1997

Drug misuse services. No quick fixes.

The Department of Health's new funding formula for drug misuse services will reduce funding in districts with the highest demand for services. Some regions will receive up to four times more per reported episode of drug misuse than others. This is due, in part, to the inclusion of numbers in rented accommodation in the funding formula.

Financing, Government↗