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Biomedical subjects

R Jones

Publications and source records attributed to R Jones.

At least 433 records · Page 24Linked to original sources
PubMed1995

Setting priorities for research and development in the NHS: a case study on the interface between primary and secondary care.

Since 1991 the NHS has attempted to identify and prioritise its needs for research and development in a systematic manner. This has not been done before and there is little evidence on which to draw. Multidisciplinary expert groups have identified priorities in different topics using explicit criteria and after widespread consultation within the NHS and research community to identify pressing problems and opportunities for research. This paper focuses on a review completed in 1993 to identify research and development priorities for the NHS in relation to the interface between primary and secondary care. The review covered several recent developments which require evaluation. The authors describe the process used to identify research and development priorities in this complex subject and examine the strengths and weaknesses of the approach. This case study should help to stimulate a wider debate on methods of identifying priorities, particularly those using participatory approaches, in research and non-research contexts.

Health Priorities↗
PubMed1995

Evidence for endothelin-1-mediated vasoconstriction in severe chronic heart failure.

Heart failure is commonly associated with high plasma concentrations of endothelin-1, a powerful vasoconstrictor produced by endothelium. The role of endogenously released endothelin-1 in the maintenance of vascular tone in chronic heart failure was assessed by acute administration of an endothelin receptor antagonist, bosentan. 24 patients with chronic heart failure received randomly and double blind two intravenous infusions of either placebo or bosentan (100 mg followed after 60 min by 200 mg). Systemic haemodynamics and plasma endothelin-1 and big-endothelin-1 concentrations were determined before and repeatedly during the 120 min observation period. Baseline endothelin-1 and big-endothelin-1 concentrations, which were above the normal range in all patients, correlated directly with the extent of pulmonary hypertension, with left and right heart filling pressures, and with pulmonary vascular resistance and inversely with cardiac index. Compared with placebo, bosentan reduced mean arterial pressure by 7.7% (95% CI 7.1-9.7), pulmonary artery pressure by 13.7% (10.5-16.9), right atrial pressure by 18.2% (12.0-24.4), and pulmonary artery wedged pressure by 8.6% (5.3-12.0); it increased cardiac index by 13.6% (9.1-18.2), decreased systemic vascular resistance by 16.5% (13.2-19.8), and decreased pulmonary vascular resistance by 33.2% (22.4-44.0). Heart rate did not change. Plasma endothelin-1 concentrations rose more than twofold from baseline in bosentan recipients while big-endothelin-1 concentrations were unchanged. These findings indicate that, in patients with chronic heart failure who have high circulatory endothelin-1 concentrations, this peptide contributes to maintenance of vascular tone. The acute haemodynamic effects of bosentan suggest that chronic endothelin antagonism could be beneficial in such patients.

Adult↗
PubMed1995

Rectal bleeding: prevalence and consultation behaviour.

OBJECTIVES: To determine prevalence of rectal bleeding in the community and to examine factors that lead some patients to consult their general practitioner about rectal bleeding while others do not. DESIGN: Questionnaire survey followed by semistructured interviews of sample of respondents with rectal bleeding. SETTING: Two general practices on Tyneside. SUBJECTS: 2000 adult patients registered with the general practices were sent a validated questionnaire. Respondents with rectal bleeding were divided into consulters and non-consulters, and 30 patients from each group (matched for age, sex, and characteristics of bleeding) were interviewed. MAIN OUTCOME MEASURES: Prevalence of rectal bleeding, proportion of subjects with rectal bleeding who sought medical advice, and reasons for consulting or not consulting a doctor about rectal bleeding. RESULTS: 287 of the 1200 respondents to the questionnaire had noticed rectal bleeding at some time in their lives, and 231 had noticed it within previous 12 months. Only 118 (41%) of all respondents with rectal bleeding had ever sought medical advice for the problem. Those aged over 60 were most likely to have consulted, as were those who reported blood mixed with their stools. Main difference between those who had sought medical advice and those who had not was that consulters were more likely than non-consulters to perceive their symptoms as serious. CONCLUSIONS: Although rectal bleeding is common, only minority of patients seek medical of symptoms seems to be most important factor in deciding whether to consult a doctor for rectal bleeding.

Adult↗
PubMed1995

Synthesis of a photoaffinity analog of 3'-azidothymidine, 5-azido-3'-azido-2',3'-dideoxyuridine. Interactions with herpesvirus thymidine kinase and cellular enzymes.

Long term administration of 3'-azidothymidine (AZT) for the treatment of AIDS has led to detrimental clinical side effects in some patients, the biochemical causes of which are still being delineated. Base-substituted, azido-nucleotide photoaffinity analogs have routinely proven to be effective tools for identifying and characterizing nucleotide-utilizing enzymes. Therefore, we have synthesized 5-azido-3'-azido-2',3'-dideoxyuridine, which is a potential photoaffinity analog of two human immunodeficiency virus drugs, AZT and 3'azido-2',3'-dideoxyuridine. A partially purified herpes simplex virus type 1 thymidine kinase and [gamma-32P]ATP were used to make an AZT monophosphate analog, [32P]5-azido-3'-azido-2',3'-dideoxyuridine monophosphate. The photoaffinity properties of this analog were initially tested with herpes simplex virus type 1 thymidine kinase. Photoaffinity labeling of this enzyme was saturable (half-maximal, 30 microM) and could be specifically inhibited by AZT, AZT monophosphate, thymidine, and thymidine monophosphate. Photolabeling of rat liver microsomal membranes was also done, and several membrane proteins that interact with AZT monophosphate were identified. The antiviral and cytotoxic activities of 5-azido-3'-azido-2',3'-dideoxyuridine were determined using human immunodeficiency virus, type 1 strain IIIB and an AZT drug-resistant strain in human T lymphocyte H9 cells.

Affinity Labels↗
PubMed1995

Cloning and analysis of monkey fertilin reveals novel alpha subunit isoforms.

The fertilin complex, a heterodimeric surface membrane glycoprotein found on the head region of mammalian spermatozoa, has been reported to mediate membrane fusion with the egg plasma membrane during fertilization. We have employed PCR to generate products corresponding to monkey (Macaca fascicularis) fertilins from testis cDNA. These PCR products have been used to isolate full-length fertilin cDNA clones corresponding to both alpha and beta subunits. Both monkey fertilin alpha and beta cDNAs encode proteins which belong to an expanding family of metalloproteinase-like, disintegrin-like, cysteine-rich, mammalian proteins. Surprisingly, cDNAs for two fertilin alpha isoforms, alpha I and alpha II, were isolated, encoding proteins of 905 and 825 residues respectively. The predicted fertilin alpha isoforms share extensive identity, but differ significantly towards their N- and C-termini, suggesting the possibility of more than one type of fertilin complex in primates. Alignment of monkey alpha and beta fertilins with their respective guinea-pig counterparts suggests a high level of overall structural conservation throughout, whilst providing new insights into the domain function of each.

ADAM Proteins↗
PubMed1995

Mapping the melatonin receptor. 3. Design and synthesis of melatonin agonists and antagonists derived from 2-phenyltryptamines.

Three series of 2-phenyltryptamides were prepared as melatonin analogues to investigate the nature of the binding site of the melatonin receptor in chicken brain and in Xenopus laevis melanophore cells. The 5-methoxy-2-phenyltryptamides (6a-j) have high binding affinities for the chicken brain receptor, in some cases (6a-d) greater than that for melatonin, confirming and extending the work of Spadoni et al., and act as agonists in the Xenopus melanophore assay. Analogues lacking the 5-methoxyl group (2a-n) had a considerably lower affinity for the chicken brain receptor. In the Xenopus melanophore assay the compounds acylated on nitrogen by an alkyl group (2a-d) were agonists whereas the compounds acylated on nitrogen by an alicyclic group (2f-i) were antagonists. Introducing a methyl group at N1 (7) led to an increase in binding affinity in the chicken brain assay, whereas introducing an ethyl group (13) led to a decrease in binding affinity. A methyl substituent at the beta-position of the 3-amidoethane side chain (8, 11) also led to an increase in the binding affinity. The only analogue acylated on nitrogen with an alkyl group (acetyl) which showed antagonist activity was 9, which has a beta-methoxymethyl side chain. In the absence of the 5-methoxyl group the methoxymethyl function may cause the molecule to bind in a different configuration so that it is no longer able to activate the receptor. All of these observations are in agreement with a model of melatonin at the receptor site in which the 3-amidoethane side chain is in a conformation close to the 5-methoxyl group.

Animals↗
PubMed1995

Coronary anatomic and procedural characteristics of patients randomized to coronary angioplasty in the Bypass Angioplasty Revascularization Investigation (BARI).

The Bypass Angioplasty Revascularization Investigation (BARI) is a randomized multicenter clinical trial that compares a strategy of initial coronary angioplasty to initial coronary bypass surgery for patients with multivessel coronary artery disease. The purpose of this report is to describe the coronary anatomic characteristics of the 915 patients assigned to the angioplasty arm of the trial and the manner in which angioplasty was performed. Patients were eligible for BARI if they demonstrated multivessel coronary artery disease, had a clinical indication for revascularization, and were suitable for both coronary angioplasty and bypass surgery. Clinical and technical features of angioplasty procedures were systemically recorded. Coronary cineangiograms obtained before and during the angioplasty were interpreted by a central radiographic laboratory. Angioplasty was performed in 904 (98.8%) of the 915 patients assigned to that initial strategy. Of 6,530 coronary arterial lesions identified, 3,427 (52.5%) were significant (> 50% diameter reduction). The majority of patients had 2-6 significant lesions, with 3 being most common. Angioplasty was attempted in 92.2% of the lesions for which it was intended. Lesions most frequently attempted ranged between 50% and 79% in severity. Multilesion angioplasty was performed in 77.5% of patients and 69.7% had multivessel angioplasty. Factors that influenced whether a lesion was attempted included lesion severity, clinical significance, and complexity. For lesions presenting as total occlusions, a history of recent infarction and postinfarction angina favored attempting angioplasty. Patients assigned to the angioplasty arm of BARI had evidence of extensive multilesion and multivessel coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗