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Biomedical subjects

R Walker

Publications and source records attributed to R Walker.

At least 55 records · Page 3Linked to original sources
PubMed2000

Angiotensin converting enzyme (ACE) inhibitors in the treatment of heart failure in general practice in north Cumbria.

BACKGROUND: A great deal of research has demonstrated the benefits of treating patients with chronic heart failure with Angiotensin Converting Enzyme (ACE) inhibitors. There is rather less research on the actual uptake of treatment in general practice, and in particular methods that might improve that uptake. AIM: To study the attitudes and practice of medical practitioners in North Cumbria in the treatment of heart failure. METHOD: Semi-structured interviews with 16 general practitioners and nine hospital physicians in the Carlisle area and an audit of general practice case notes. RESULTS: Two hundred and fifty-eight patients were identified with heart failure. Prevalence was 1.1%. Fifty percent were on an ACE inhibitor, the mean dose of which was less than half the typical research dose. Patients who had an echocardiogram were much more likely to be on an ACE inhibitor. General practitioners were enthusiastic to use ACE inhibitors, but felt that greater access to echocardiography was required. Hospital physicians were happy to improve access within an agreed protocol. CONCLUSION: Improved uptake of ACE inhibitors could be assisted by the development of a protocol for investigation and treatment. This protocol should be evidence-based and agreed between local GPs, hospital physicians and the Health Authority.

Adult↗
PubMed2000

Influencing NSAID prescribing in primary care using different feedback strategies.

The Audit Commission endorsed the role of the prescribing adviser in promoting safe, rational and cost-effective prescribing by general medical practitioners (GPs). However, whether such roles should involve practice visits, facilitation of educational meetings, production of local bulletins, or a combination of these and other approaches is unclear. Few UK studies have investigated the best methods to influence prescribing on a large scale in primary care. The present study was designed to determine the effectiveness of active compared to passive practice specific prescribing feedback. The programme focused on non-steroidal anti-inflammatory drugs (NSAIDs) since concern has been expressed about their use, which accounts for 4% of volume and 5% of the cost of UK National Health Service drugs prescribed in primary care, Sixty-six of the 91 general medical practices contracted to Gwent Health Authority agreed to participate in the study and were randomly stratified by practice size, locality, fund-holding and dispensing status into 2 groups. Group 1 received active feedback via practice visits from the pharmaceutical prescribing adviser to present prescribing analysis and cost data (PACT) concerning NSAID use. Group 2 received passive feedback, a practice specific prescribing analysis workbook that contained similar information to that given to Group 1 practices. Practices not wishing to enter the study were used as a self selected reference group (Group 3) which received no information on NSAIDs from the prescribing adviser. Practice visits and the distribution and completion of workbooks occurred between September 1993 and March 1994, PACT data for all NSAIDs was used to identify changes in prescribing before and after the programme. A combination of 27 indicators, in terms of items and cost per 1000 patients, were chosen to identify overall changes and potential switches between individual drugs, or to generic alternatives. Comparison of the practices in each of the three groups at analysis revealed similar distribution in terms of stratification criteria. Eleven (38%) Group 2 practices returned completed workbooks. Overview indicators (those not targeted) showed similar trends of either increase or decrease, in cost and volume, across all three groups, whereas targeted indicators demonstrated a more mixed picture between groups. In summary the total number of statistically significant changes for targeted indicators in Groups 1, 2, and 3 were 10, 8 and 1 (changes in items per 1000 patients), and 12, 10 and 3 (changes in cost per 1000 patients) respectively. Targeted indicators revealed more statistically significant changes in Group 1 (active feedback) than Group 2 passive feedback) which showed more changes than Group 3 (reference group). Active feedback was more effective at bringing about a required change than the use of passive feedback; both approaches had more impact than that registered by the reference group. The Group 2 analysis presented included both responders and non-responders, thus a more marked benefit of the workbook was perhaps masked. These results have implications for the future provision of prescribing advice to practices. Advisers currently use both active and passive methods to provide prescribing feedback to practices. The high resource intensiveness of practice visits leads many authorities to rely increasingly on less effective methods such as bulletins. Evaluation of the cost effectiveness of methods used to influence prescribing are required.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Is oestrogen therapy justified in the treatment of hereditary haemorrhagic telangiectasia: a biochemical evaluation.

Systemic and topical oestrogen can provoke squamous metaplasia of epithelium. In Hereditary Haemorrhagic Telangiectasia (HHT) the underlying telangiectasia may be protected from trauma and epistaxis reduced. Oestrogens have been advocated but their efficacy is unclear. Recent advances have now identified two oestrogen and one progesterone receptors. The aim of this study is to analyse the sex receptor status of HHT nasal mucosa to determine if oestrogen therapy is biochemically justified. Five HHT patients (three men, two women) and eight controls (four men, four women) underwent nasal mucosa biopsy. Samples were fixed in formalin and paraffin embedded. Alpha oestrogen (ERalpha) and beta oestrogen (ERss) and progesterone (PgR) receptors were identified using mouse monoclonal antibodies by the Streptavidin-biotin peroxidase method. ERss was detected in two HHT subjects (1 M: 1F) and two control subjects. ERalpha and PgR was absent in HHT subjects. This pilot study demonstrated that a subgroup of HHT patients were ERss positive. Oestrogen therapy therefore has a potential therapeutic role on a biochemical basis in these patients. ERss status should be determined before considering oestrogen therapy.

Administration, Intranasal↗
PubMed2000

Is oestrogen therapy justified in the treatment of hereditary haemorrhagic telangiectasia: a biochemical evaluation

INTRODUCTION: Systemic and topical oestrogen can provoke squamous metaplasia of epithelium. In Hereditary Haemorrhagic Telangiectasia (HTT) the underlying telangiectasia may be protected from trauma and epistaxis reduced. Oestrogens have been advocated but their efficacy is unclear.1 Recent advances have now identified two oestrogen and one progesterone receptors. The aim of this study is to analyse the sex receptor status of HHT nasal mucosa to determine if oestrogen therapy is biochemically justified. METHOD: Five HHT patients (three men, two women) and eight controls (four men, four women) underwent nasal mucosa biopsy. Samples were fixed in formalin and paraffin embedded. Alpha oestrogen (ERalpha ), beta oestrogen (Erbeta) and progesterone receptors (PgR) receptors wre identified using mouse monoclonal antibodies by the Streptavidin-biotin peroxidase method. RESULTS: Erbeta was detected in two HHT patients (one man, one woman) and two control patients. ERalpha and PgR was absent in HHT patients. CONCLUSION: This pilot study demonstrated that a subgroup of HHT patients is Erbeta positive. Oestrogen theraphy therefore has a potential therapeutic role on a biochemical basis in these patients. Erbeta status should be determined before considering oestrogen therapy.

Journal Article↗
PubMed2000

Melanin-concentrating hormone, melanocortin receptors and regulation of luteinizing hormone release.

Melanin-concentrating hormone (MCH) is a neuropeptide, identified by its ability to either mimic or antagonize the melanin-dispersing action of alpha-melanocyte stimulating hormone (alphaMSH) on skin melanophores. MCH and alphaMSH also have antagonistic actions in the brain affecting feeding behaviour, aggression, anxiety, arousal and reproductive function through the release of luteinizing hormone (LH). It is not clear, however, how they exert their opposite effects in the central nervous system (CNS). One possibility is that they act via a common receptor. In this study we have examined the effect of a number of MC receptor antagonists, with relative selectivity for the MC3, 4 and 5 subtypes, on the actions of MCH on LH release. We confirmed that bilateral administration of MCH (100 and 200 ng/side) into the medial preoptic area of oestrogen-primed (oestradiol benzoate 5 microgram) ovariectomized anaesthetized rats, stimulated the release of LH. This effect was blocked by the concomitant administration into the medial preoptic area of the MC4/5 antagonist ([D-Arg8]ACTH(4-10) and the MC3/5 antagonist ([Ala6]ACTH(4-10)-both at 500 ng/side-but not by the MC3/4 antagonist, SHU9119 (200 ng/side). Furthermore, the MC3 agonist [Nle3]-gamma2 MSH failed to affect LH release. These results indicate that the MC3 and MC4 receptors are not involved in mediating the action of MCH but are consistent with an action via the MC5 subtype. Preputial glands, which express MC5 receptors, were also stimulated by MCH which is in keeping with this idea. In HEK293 cells transfected with the MC5 receptor MCH increased the production of IP3. However, it was much less potent than alphaMSH and unlike alphaMSH, had no effect on the production of cAMP. MCH (10-10 to 10-5 M) also failed to displace I125NDP-MSH from cells transfected with MC5 receptors indicating that it was not acting as a competitive antagonist and its binding site was distinct from that of alphaMSH. Thus while MCH may function as an agonist at the MC5 receptor, its stimulation of LH release is more likely to be mediated via a specific MCH receptor that has common properties with the MC5 receptor.

Adrenocorticotropic Hormone↗
PubMed2000

Postgraduate courses in quality improvement: achievements and future directions.

Since 1996, the Centre for Clinical Epidemiology and Biostatistics at the University of Newcastle has offered courses in Quality Improvement in Health Care. The courses are offered at Graduate Certificate, Graduate Diploma and Masters levels, principally by distance learning. They offer training in research methods as well as the concepts and application of quality improvement. Feedback from students, many of whom are quality coordinators in Australian health care facilities, has been positive. Enrolments are taken mid-year as well as at the beginning of the academic year.

Australia↗
PubMed2000

Approaches to changing the use of time in a public hospital.

This article describes a qualitative study that used documentary sources and interviews with a cross-section of clinical managers and staff to identify the ways in which use of time changed in two clinical units following the introduction of casemix-based funding in Victoria. For staff at all levels within the hospital system, changes in the use of time were experienced that affected both the organisation of work and the care provided. The two units approached the management of time in different ways. From the introduction of casemix-based funding to the conclusion of this study there were improvements in efficiency in both clinical units. The case studies are compared and the consequences of different approaches to managing time in clinical units are described.

Diagnosis-Related Groups↗
PubMed2000

The safety evaluation of monosodium glutamate.

L-Glutamic acid and its ammonium, calcium, monosodium and potassium salts were evaluated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 1988. The Committee noted that intestinal and hepatic metabolism results in elevation of levels in systemic circulation only after extremely high doses given by gavage (>30mg/kg body weight). Ingestion of monosodium glutamate (MSG) was not associated with elevated levels in maternal milk, and glutamate did not readily pass the placental barrier. Human infants metabolized glutamate similarly to adults. Conventional toxicity studies using dietary administration of MSG in several species did not reveal any specific toxic or carcinogenic effects nor were there any adverse outcomes in reproduction and teratology studies. Attention was paid to central nervous system lesions produced in several species after parenteral administration of MSG or as a consequence of very high doses by gavage. Comparative studies indicated that the neonatal mouse was most sensitive to neuronal injury; older animals and other species (including primates) were less so. Blood levels of glutamate associated with lesions of the hypothalamus in the neonatal mouse were not approached in humans even after bolus doses of 10 g MSG in drinking water. Because human studies failed to confirm an involvement of MSG in "Chinese Restaurant Syndrome" or other idiosyncratic intolerance, the JECFA allocated an "acceptable daily intake (ADI) not specified" to glutamic acid and its salts. No additional risk to infants was indicated. The Scientific Committee for Food (SCF) of the European Commission reached a similar evaluation in 1991. The conclusions of a subsequent review by the Federation of American Societies for Experimental Biology (FASEB) and the Federal Drug Administration (FDA) did not discount the existence of a sensitive subpopulation but otherwise concurred with the safety evaluation of JECFA and the SCF.

Animals↗
PubMed2000

The establishment of an industry-based education program in public health.

Commonwealth reforms have led to staff of the Department of Health and Aged Care needing a greater knowledge of public health, to more effectively evaluate evidence and to quickly acquire competence in new emerging areas. The department's requirements of a training program could not be met by existing university-based public health courses. A consortium of five universities and the department worked together to develop an industry-based course that would meet the Commonwealth's needs. The course was constituted within university regulations; had an incremental and articulated structure with exit points at certificate, diploma and Masters levels; was relevant to the work of staff; offered subjects which complemented the staff's existing skills, training and career aspirations; drew upon expertise across the universities; and was flexible in its delivery. The Commonwealth's and universities' experience has been sufficiently positive to conclude that a corporate public health postgraduate program has a place alongside university-based programs.

Australia↗
PubMed2000

Recommendations for HER2 testing in the UK.

Determining the HER2 status of breast carcinomas is a prerequisite for the use of the monoclonal antibody trastuzumab (Herceptin), which has recently been licensed for the treatment of metastatic disease. This necessitates a test based on archival material. The preferred analyses are immunohistochemistry with fluorescent in situ hybridisation (FISH) as a follow up test for ambiguous results. Guidelines have been developed for standardised, well controlled procedures for the provision of reliable results. A group of three reference laboratories has been established to provide advice, quality assurance, and materials, where needed.

Biomarkers, Tumor↗
PubMed2000

Immunohistochemical detection of steroid receptors in breast cancer: a working protocol. UK Receptor Group, UK NEQAS, The Scottish Breast Cancer Pathology Group, and The Receptor and Biomarker Study Group of the EORTC.

The biochemical assay for the oestrogen receptor has shown the clinical value of knowing the concentration of the receptor within tissue. The immunohistochemical assay is rapidly taking over from the biochemical assay. Therefore, it is vital to have an equivalent scoring system that will have the same predictive value. This paper reports both a practical protocol and a scoring system that should achieve this aim. This approach should be applicable to many more biomarkers detected by immunohistochemistry.

Biomarkers, Tumor↗
PubMed2000

Type C botulism in dairy cattle from feed contaminated with a dead cat.

Four hundred twenty-seven of 441 adult Holstein dairy cattle from a 1,200-cow dairy died over a 1-week period during early spring 1998. Affected animals were from 4 late lactation pens, one of which included the bull string. Signs included weakness, recumbency, watery diarrhea, and death. Eighty animals from the 4 pens were dead approximately 8 hours after the first ill cows were noted. Affected cows would collapse on stimulation and extend all 4 limbs with moderate rigidity. Several lacked lingual tonus and had abdominal breathing patterns. The animals had been fed a load of total mixed ration that included a rotten bale of oat hay containing a dead cat. No common toxicants were identified, and pathologic examination revealed no consistent lesions. Testing of tissue from the cat carcass found in the feed sample using mouse protection bioassay identified the presence of type C botulinum toxin. Samples of feed, tissue from affected animals, cat tissue from feed, milk, and serum were also tested using an enzyme-linked immunosorbent assay (ELISA) specific for type C botulinum. Two samples of rumen contents were tested and found to be positive for botulism by ELISA, and 1 of 3 liver samples had a weak positive finding. No botulinum toxin was found in milk or sera using the ELISA.

Animal Feed↗
PubMed2000

Serotyping of Mannheimia (Pasteurella) haemolytica isolates from the upper Midwest United States.

Mannheimia (Pasteurella) haemolytica biotype A serotype1 (A1) is the primary bacterial agent responsible for the clinical signs and pathophysiologic events in bovine pneumonic pasteurellosis. The goal of this study was to determine the prevalence of other serotypes of M. haemolytica biotype A organisms obtained from the upper Midwest diagnostic laboratories. A total of 147 M. haemolytica isolates were collected from Minnesota, South Dakota, and Michigan. Isolates were tested against M. haemolytica antisera obtained from the National Animal Disease Center, Ames, Iowa. Results indicated that M. haemolytica serotype 1 represented approximately 60%, serotype 6 represented 26%, and serotype 2 represented 7% of the total examined isolates. In addition, 7% of the isolates were serotype 9, 11, or untypable. This finding suggests that M. haemolytica serotypes other than serotype 1 can be isolated from the lung lesions of diseased cattle and seem to be capable of causing the pathologic changes observed in the lung with pneumonic pasteurellosis.

Animals↗
PubMed2000

Fate of the mushroom hydrazine agaritine in the rat and mouse.

The fate of the mushroom hydrazine [14C]agaritine was investigated in the mouse and rat strains previously employed in carcinogenicity studies with the edible mushroom Agaricus bisporus. Agaritine was rapidly absorbed in both species, achieving higher blood levels in the mouse, but with similar area under the curve. Covalent binding of agaritine material to proteins was detected only in the liver and kidney, but the extent of binding was the same in the rat and mouse. Most of the radioactivity was excreted during the first 24 hours in both animal species: in the rat it was distributed equally between urine and feces, whereas in the mouse more of the radioactivity was excreted in the urine. No qualitative differences in the metabolic profile were evident, but quantitative differences were observed. Treatment of the urine with deconjugating enzymes did not reveal the presence of any conjugates. Agaritine, N'-acetyl-4-(hydroxymethyl)phenylhydrazine, and 4-(hydroxymethyl)benzene diazonium ion were not detected in the urine or in the plasma of either species. No mutagens or promutagens were detected by the Ames mutagenicity assay in the urine of either species after exposure to agaritine. Repeated administration of agaritine to rats and mice did not alter the urinary metabolic profile and excretion of radioactivity. Similarly, feeding mice a raw mushroom diet, according to the protocol employed in the carcinogenicity studies, did not modulate the excretion of radioactivity or the urinary metabolic pattern. No major species differences in the fate of agaritine in rat and mouse were noted that could provide a rationale for the carcinogenicity of A. bisporus in the mouse, but not in the rat.

Agaricus↗
PubMed2000

Wegener's granulomatosis: an unusual cause of upper airway obstruction.

A 10-year-old child with a 2-month history of tracheitis presented with acute stridor, for which he required tracheostomy. Granulation tissue was found in the subglottic region and he was treated with antibiotics and corticosteroids. A week after successful decannulation of his tracheostomy, his stridor recurred and, on endoscopy under general anaesthesia, circumferential granulomas extending into both main bronchi were found. A diagnosis of Wegener's granulomatosis was made and confirmed on histology.

Airway Obstruction↗
PubMed1999

Proliferation of hepatic peroxisomes in rats following the intake of green or black tea.

Rats maintained on green, black or decaffeinated black tea (2.5%, w/v) as their sole drinking fluid displayed higher hepatic CN- insensitive palmitoyl CoA oxidase activity than controls; the extent of increase was similar with the three types of tea. Morphological examination of the liver using electron microscopy revealed an increase in the number of peroxisomes in the tea-treated animals. The same treatment of the animals with green and black tea resulted in a similar rise in hepatic microsomal lauric acid hydroxylation. Analysis by HPLC of the aqueous tea extracts employed in the current study showed that the total flavanol content of the green variety was much higher than the black varieties, and confirmed the absence of caffeine in the decaffeinated black tea. It may be concluded from the present studies that neither caffeine nor flavanoids are likely to be responsible for the proliferation of peroxisomes observed in rats treated with tea.

Animals↗