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Biomedical subjects

R Viner

Publications and source records attributed to R Viner.

At least 19 recordsLinked to original sources
PubMed2002

Splitting hairs.

Explore the source record for details and available documents.

Age Factors↗
PubMed2001

A structure-based design approach to the development of novel, reversible AChE inhibitors.

Chimeras of tacrine and m-(N,N,N-Trimethylammonio)trifluoroacetophenone (1) were designed as novel, reversible inhibitors of acetylcholinesterase. On the basis of the X-ray structure of the apoenzyme, a molecular modeling study determined the favored attachment positions on the 4-aminoquinoline ring (position 3 and the 4-amino nitrogen) and the favored lengths of a polymethylene link between the two moieties (respectively 5-6 and 4-5 sp(3) atoms). Seven compounds matching these criteria were synthesized, and their inhibitory potencies were determined to be in the low nanomolar range. Activity data for close analogues lacking some of the postulated key features showed that our predictions were correct. In addition, a subsequent crystal structure of acetylcholinesterase complexed with the most active compound 27 was in good agreement with our model. The design strategy is therefore validated and can now be developed further.

Acetophenones↗
PubMed2000

The new system of review by multicentre research ethics committees: prospective study.

OBJECTIVE: To assess the function of the new system of review by multicentre research ethics committees and to highlight areas where improvement is still needed. DESIGN: Prospectively collected data from a multicentre study was examined with respect to the ethics review process. Administrative, financial, and time elements of the review process were audited. SETTING: A single multicentre research ethics committee and 125 local ethics committees from six regions of England. MAIN OUTCOME MEASURES: Time to reply, time to approval, and number of non-local changes to the application requested. RESULTS: Only 40% of local ethics committees considered our study in the manner specified in the 1998 directive. Less than a third of committees replied within the 21 day period stipulated, although committees acting by executive subcommittee replied more quickly than those not acting by executive subcommittee. There was a tendency for executive subcommittees to approve studies in a shorter time. Local ethics committees asked for a large number of non-local changes to the application. The financial cost of applying to multiple ethics committees remains high, mainly because multiple copies of research applications are being requested. CONCLUSIONS: The new system of approval by multicentre research ethics committee for multicentre studies was introduced to reduce administrative costs, speed up the process of reviews by multiple research ethics committees, and standardise the conclusions of the local research ethics committees. Since its introduction an improvement has been seen, but the system is not yet universally functioning as intended. Ethics review still remains a hindrance to the financial resources and commencement of national studies. We strongly support the structure of review by multicentre research ethics committees but suggest that the system has yet to achieve its aims.

Costs and Cost Analysis↗
PubMed1999

Crystallographic analysis of triclosan bound to enoyl reductase.

Molecular genetic studies with strains of Escherichia coli resistant to triclosan, an ingredient of many anti-bacterial household goods, have suggested that this compound works by acting as an inhibitor of enoyl reductase (ENR) and thereby blocking lipid biosynthesis. We present structural analyses correlated with inhibition data, on the complexes of E. coli and Brassica napus ENR with triclosan and NAD(+) which reveal how triclosan acts as a site-directed, picomolar inhibitor of the enzyme by mimicking its natural substrate. Elements of both the protein and the nucleotide cofactor play important roles in triclosan recognition, providing an explanation for the factors controlling its tight binding to the enzyme and for the emergence of triclosan resistance.

Anti-Infective Agents, Local↗
PubMed1996

Melanie Klein and Anna Freud: the discourse of the early dispute.

Divisions in the field of the psychoanalysis of children can be traced to a dispute over the infantile super-ego between the theorists Melanie Klein and Anna Freud beginning in 1927. These divisions are understood within the analytic world as the result of scientific disputation between alternative valid theories. An examination of the language, claims, and epistemology of Klein's and Freud's publications in 1927 that marked the public commencement of the conflict, reveals a personalized discourse in which authority was derived from the allegiance, experience, and personal analytic standing of the contestants as much as from theoretical insight. The structure and rhetoric of the debate suggest that, rather than terminating the dispute, the publications of 1927 served to encourage professionalization in child analysis and establish Anna Freud and Melanie Klein as authoritative alternative theorists.

Adolescent↗
PubMed1996

Family stress and metabolic control in diabetes.

The common clinical assumption that stress has a deleterious effect on metabolic control in insulin dependent diabetes mellitus (IDDM) has not been confirmed in children and adolescents. This cross sectional study of 43 children and adolescents with IDDM and their families examined the relations between family life stress, family social support, and metabolic control. High family life stress was found to be strongly correlated with HbA1c in the whole group (n = 43) and in children under 12 years (n = 27) when considered separately. Family social support was not found to be directly related to HbA1c, but was found to buffer the effects of family life stress. These findings support the hypotheses that family stress affects metabolic control in IDDM and that good social support buffers these deleterious effects.

Adolescent↗