DMP-266 and adefovir dipivoxil: 2 new AIDS drugs available to patients without treatment options.
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Biomedical subjects
Publications and source records attributed to R Baker.
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During the past three decades, general practice has evolved into a form of primary health care that provides a wide range of reactive, anticipatory, and preventive services, and now also purchases secondary care. As a result, practices now have more staff and more complex patterns of organization. However, most patients prefer smaller practices and personal list systems. There is a danger that a core feature of general practice--personal care--is gradually being eroded. If this trend is to be halted, the organization of general practices and the support available to them must be revised so that they can continue to provide personal care, yet also offer a wide range of effective services in the community.
Though many general practitioners (GPs) now take part in audit, there is still concern about the extent to which participation in audit leads to improvements in practice. Improved methods are needed for the incorporation of research evidence into criteria for use in audit. In this paper, a six-stage systematic method is described for developing audit protocols containing prioritized evidence-based criteria. The stages are: selection of a topic, identification of key elements of care, focused literature reviews, prioritization of the criteria on the strength of the evidence and impact on outcome, preparation of full documentation, and peer review.
Rheumatoid arthritis is an autoimmune disease that causes inflammation mainly in synovial tissues. RA manifests as a chronic polyarthritis with intermittent acute inflammatory episodes. The inflammatory sites are characterized by infiltration of activated lymphocytes and macrophages into the synovial membrane, and the proliferation of synovial cells. The local production of a number of cytokines by proliferative synovial cells as well as by infiltrating cells appears to account for many of the pathological and clinical manifestations in rheumatoid arthritis. Tissues were collected from twelve RA patients undergoing joint replacement surgery. The synovium was collected and the cell types were identified, and markers for chronic and acute inflammatory mediators were measured. The cells types found in the synovium are capable of secreting cytokines which are capable of both acute inflammation (IL-1, IL-6, IL-8, MCP-1 and TNF), as well as chronic inflammation (IL-2, IL-10, and IL-4). The results obtained showed that the macrophages-derived acute inflammatory cytokines (IL-1, IL-6 and IL-8) were easily detected at levels of 22.6 +/- 12 pg/mg protein; 48.5 +/- 42 pg/mg protein, and 76 +/- 31 pg/mg protein; respectively. T-cell derived chronic inflammation cytokines (IL-2, IL-4 and IL-10) were rarely detected. Retrieved tissues that immunostained positive for IL-6, IL-1 and IL-8 also is suggestive of an acute inflammatory response. The results clearly demonstrate that the acute response may be responsible for the subsequent need for joint arthroplasties.
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The preparation of a series of N-heteroarylpiperidine ether-based human NK1 antagonists is described. Two of the compounds 3-[-(2S,3S)-3-(((3,5-bis(trifluoromethyl)phenyl)methyl)oxy)- 2-phenylpiperidino}methyl]-1,2,4-triazole (11) and 5-[¿(2S,3S)-3-(((3,5-bis(trifluoromethyl)-phenyl)methyl)oxy)-2- phenylpiperidino}methyl]-3-oxo-1,2,4-triazolone (12)), in particular, are orally bioavailable and exhibited significant improvements in potency, both in vitro and in vivo, over the lead (carboxamidomethyl)piperidine ether 1. Rat liver microsome studies on a selected number of compounds from this series show the triazolone heterocycle to be considerably more stable than the others. Furthermore, both 11 and 12 have been profiled in a number of assays that may be predictive of the clinical utility of substance P antagonists.
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The design, synthesis, and biological activity of a novel series of CCK-B receptor antagonists (1) which incorporate a tetrazol-5-ylamino functionality attached to the phenyl ring of the arylurea moiety of L-365,260 are described. In these compounds, the acidity of the tetrazole was gradually modified by utilization of simple conformational constraints, and X-ray crystallographic data were obtained to support the conformational depenence of the pK(a) of the aminotetrazoles. Compounds to emerge from the present work such as 1f and 2c,d are among the highest affinity and, in the case of 1f, most selective (CCK-A/CCK-B, 37 000) antagonists so far reported for this receptor. The C(5)-cyclohexyl compound 2c (L-736,380) dose-dependently inhibited gastric acid secretion in anesthetized rats (ID(50), 0.064 mg/kg) and ex vivo binding of [(125)I]CCK-8S in BKTO mice brain membranes (ED(50), 1.7 mg/kg) and is one of the most potent acidic CCK-B receptor antagonists yet described.
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The rapid increase in numbers of homeless children in cities of the developed and developing world is a matter of grave concern. A multi-disciplinary study was undertaken to examine the health and lifestyles of the homeless in Nepal in comparison to other local children. Few studies have quantified the health of street-children in the developing world using anthropometric indicators, and to our knowledge this is the first to systematically compare the homeless with appropriate controls from both rural and urban areas. Heights and weights were measured for 307 six to fourteen year-old boys (III homeless 62 squatter, 82 privileged school and 52 village boys). Height for age (HAz), weight for age (WAz) and weight for height (WHz) I-scores relative to reference data from the National Center for Health Statistics (NCHS) were used as indicators of growth status. Stunting characterized all but the school-boys, but wasting was not observed. the homeless were less stunted than either poor squatter or village boys. On arrival on the streets, they were taller than village boys, and duration of homelessness had no effect on their growth status. Thus in terms of physical growth, and despite frequent health complaints, homeless boys in Nepal fare relatively better than control groups of poor urban and rural boys. Comparative studies which reveal some successful aspects of street-life show that urban homelessness may represent an appropriate response to circumstances of poverty.
These studies have compared the pharmacological profile of two non-peptide human type neurokinin1 (hNK1) receptor selective antagonists, L-741,671 and a quaternised compound L-743,310. In radioligand binding studies L-741,671 and L-743,310 had high affinity for ferret and cloned hNK1 receptors [Ki (nM) ferret 0.7 and 0.1; human 0.03 and 0.06, respectively] but low affinity for rodent NK1 receptors [Ki (nM) 64 and 17, respectively] suggesting that ferret receptors have hNK1-like binding pharmacology. Studies in vivo showed that L-741,671 and L-743,310 had equivalent functional activity in the periphery (ID50s of 1.6 and 2 micrograms/kg i.v., respectively) as measured by inhibition of plasma protein extravasation evoked in the oesophagus of guinea pigs by resiniferatoxin (7 nmol/kg i.v.). Using an in situ brain perfusion technique in anaesthetised rats, L-741,671 was shown to be much more brain penetrant than the quaternary compound L-743,310 which had an entry rate similar to the poorly brain penetrant plasma marker inulin. These compounds thus provided an opportunity to compare the anti-emetic effects of equi-active hNK1 receptor antagonists with and without brain penetration to central NK1 receptor sites. When tested against cisplatin-induced emesis in ferrets, L-741,671 (0.3, 1 and 3 mg/kg i.v.) produced marked dose-dependent inhibition of retching and vomiting but L-743,310 was inactive at 3 and 10 micrograms/kg i.v. In contrast, direct central injection of L-741,671 and L-743,310 (30 micrograms) into the vicinity of the nucleus tractus solitarius or L-743,310 (200 micrograms) intracisternally was shown to inhibit retching and vomiting induced by i.v. cisplatin. L-741,671 and L-743,310 had equivalent functional activity, at the same dose, against cisplatin-induced emesis when injected centrally. These observations indicated that had L-743,310 penetrated into the brain after systemic administration it would have been active in the cisplatin-induced emesis assay and so show that brain penetration is essential for the anti-emetic action of systemically administered NK1 receptor antagonists.
BACKGROUND: Recognizing the need to find new models for educating health professionals, the Institute for Healthcare Improvement (IHI) initiated the Interdisciplinary Professional Education Collaborative in April 1994. The goal of the Collaborative is to improve health care by working from upstream, to address the health professions workforce changes demanded by the need to deliver better care at a lower cost. With support and advice from IHI and others, faculty leaders in health professions education from the disciplines of medicine, nursing, and health administration framed a vision of the future in which "health professions education has evolved into an integrated teaching/learning environment in which health professionals are working together across discipline boundaries, using the best knowledge for improvement to continuously improve health care". This article describes the first year of the three-year project. SUMMARY: The 1994-1995 pilot year of the Collaborative involved more than 60 learners and 50 faculty members, across multiple disciplines. At each of the four sites, education was integrated with efforts to improve health care delivery. Education-oriented outcomes include assessment of student learning (applied knowledge and skills) and program evaluation (student and faculty feedback on the effect of the project on community-based experiential learning sites). Even at this early stage, there is evidence of change in participating institutions. The Collaborative in now planning how to increase the number of students and faculty involved in such a way that a deeper understanding of how to prepare new health professionals to improve health care may be determined.
BACKGROUND: Patient views are important in the evaluation of the quality of health care. The use of surveys needs to be evaluated to determine their cost-effectiveness and benefits. OBJECTIVES: To determine the costs of conducting patient opinion surveys in general practice and to find out how effective patient surveys are in stimulating changes which are beneficial for patient care. METHOD: Postal questionnaire to all 102 medical audit advisory groups (MAAGs) and 98 family health services authorities (FHSAs) in England and Wales, followed by postal questionnaire to 302 general practices reported to have conducted surveys, sampled by the type or questionnaire used. Numbers of MAAGs and FHSAs reporting surveys in general practice; types of questionnaire used; estimated costs; changes made; and benefits identified were measured. RESULTS: Eighty-five (83%) MAAGs and 75 (77%) FHSAs responded. One hundred and fifty-four (96%) of MAAGs or FHSAs reported survey activity. Types of questionnaire used were 1) designed by the practice, 2) designed by the MAAG or FHSA, possibly in collaboration with a practice, or 3) standard 'off-the-shelf'. One hundred and thirty-three (44%) practices responded. Total costs to a practice of conducting a survey ranged from nothing to over 2200 Pounds. Questionnaires designed by the practice are likely to be more costly than other designs. Some practices had surveys provided free of charge by MAAG or FHSA. Sixty-one per cent of practices said changes had been implemented and a further 22% of practices said changes were planned. The most common change was to appointment systems. Benefits were identified for patients, staff, the practice, the MAAG or FHSA and the NHS. Surveys also brought benefits in relationships and understanding. Only 8.2% of practices felt the costs of surveys outweighed the benefits. CONCLUSIONS: Many practices are surveying patients' opinions. Surveys can be costly but MAAGs and FHSAs can provide expertise and resources. Surveys using any of the types of questionnaire are likely to lead to changes and identifiable benefits. Benefits of surveys are perceived by the majority of practices to outweigh the costs.