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Biomedical subjects

A Wales

Publications and source records attributed to A Wales.

11 recordsLinked to original sources

Integrating electronic information resources for NHS Glasgow staff at the point of need: a model of interlibrary collaboration and resource sharing.

The Glasgow NHS Libraries Consortium has harnessed the political imperative of collaboration and the capability of electronic information resources to address inequalities in access to the knowledge base across NHS Glasgow. They have negotiated consortium arrangements to an extensive range of electronic databases and journals which no single Glasgow NHS library could afford independently. A Project Officer was appointed to undertake the administration, technical work and promotion required to build a Web-based electronic library to deliver resources to all NHS Glasgow staff on an equitable basis. Close partnership with online content providers enabled the Project Officer to find solutions to problems caused by authentication systems and license restrictions. These efforts have culminated in the production of a fully integrated virtual library--the NHS Glasgow e-Library--delivering 11 major electronic databases, 440 full-text electronic journals, 48 electronic textbooks and over 5000 journal contents pages. The NHS Glasgow e-Library is without precedent within the NHS in terms of its wealth of resources, and it provides a model for Scotland-wide access to the knowledge base. The sustainability and transferability of the resource is dependent on a number of key areas-maintenance, user training, evaluation, IT infrastructure and ongoing collaboration and unification. Ongoing research will monitor how far the NHS Glasgow e-Library has strengthened the connection between research evidence and clinical practice.

Communication↗

Electrophysiologic effects of the new class III antiarrhythmic drug dofetilide compared to the class IA antiarrhythmic drug quinidine in experimental canine atrial flutter: role of dispersion of refractoriness in antiarrhythmic efficacy.

INTRODUCTION: Previous studies suggest that class III antiarrhythmic drugs are more effective in reentrant arrhythmias because they prolong refractoriness (ERP) and wavelength and reduce dispersion of refractoriness compared to Class IA antiarrhythmic drugs, which slow conduction velocity (CV) in addition to their effects on refractoriness. METHODS AND RESULTS: To test this hypothesis, the Class III drug dofetilide and the Class IA drug quinidine were studied in the experimental canine crush-injury model of atrial flutter, utilizing right atrial multipoint programmed stimulation and activation mapping. In seven dogs dofetilide prolonged ERP by 23%, slowed CV by 9% at 200-msec cycle length (P < 0.001) and by 39% at 150-msec cycle length (P < 0.001), and increased wavelength by 11% (P < 0.02). Dofetilide reduced dispersion of ERP by 20% (P = 0.003) and adjacent electrodes with ERP difference > or = 20 msec by 76% (P < 0.001). Dofetilide slowed atrial flutter by 37% (P = 0.003) prior to terminating and suppressing it in all dogs. In eight dogs quinidine prolonged ERP by 14% (P < 0.001), slowed CV by 14% at 200-msec length cycle (P < 0.001) and by 19% at 150-msec cycle length (P < 0.001), and reduced wavelength by 2% (P = NS). Quinidine did not reduce dispersion of refractoriness. Quinidine slowed atrial flutter by 57% (P < 0.001), terminating and suppressing it in only three dogs. Efficacy of dofetilide was greater than quinidine (P = 0.026) and correlated with reduced dispersion of ERP (r = -0.653, P = 0.01), reduced adjacent electrodes with ERP difference > or = 20 msec (r = -0.637, P = 0.012), and prolonged wavelength (r = 0.61, P = 0.018). Dofetilide and quinidine terminated atrial flutter by similar mechanisms. Myocardial fiber orientation was nonuniform around the crush injury. CONCLUSIONS: Antiarrhythmic efficacy of dofetilide was greater than that of quinidine and correlated with drug-induced prolongation of wavelength and reduction in dispersion of refractoriness, effects produced only by dofetilide.

Action Potentials↗

Effects of irradiation on surface carbohydrates of larvae of Schistosoma mansoni.

Ultra-violet irradiated larvae of Schistosoma mansoni stimulate high levels of resistance to challenge infection in experimental animals. In the experiments presented here, the binding patterns of antisera specific for the cercarial glycocalyx, and of various lectins, demonstrate that u.v. irradiation causes a pronounced modification of the carbohydrate antigens expressed at the surface of cercariae and newly transformed schistosomula. These alterations were dependent on the irradiation dose, and on the batch of cercariae used in each experiment. Our results strongly suggest that the changes in carbohydrate antigens consequent upon u.v. irradiation may be important in generating the enhanced immunogenicity of irradiated cercariae.

Animals↗

Inhibition of protein synthesis in irradiated larvae of Schistosoma mansoni.

UV-irradiated and gamma-irradiated schistosomula of Schistosoma mansoni induce high levels of resistance to challenge infection in experimental hosts. It was observed that both types of irradiation severely inhibited protein synthesis by the parasite larvae. Schistosomula were treated with the metabolic inhibitor actinomycin D to simulate this effect of irradiation. The ability of these drug-treated larvae to induce immunity was tested in animal protection experiments. Our results suggest that inhibition of protein synthesis may help to generate the enhanced immunogenicity of irradiated schistosomula. In explanation, we propose that irradiated schistosomula may be such potent immunogens because they express antigens in disrupted, abnormal conformations. Inhibition of protein synthesis may both directly create such modified antigens, and also ensure that they persist and accumulate for presentation to the host immune system.

Animals↗

Effects of irradiation and tunicamycin on the surface glycoproteins of Schistosoma mansoni.

The cercarial glycocalyx and schistosomulum surface contains a number of glycoproteins which are expressed in very variable amounts within a parasite population. Tunicamycin inhibits glycoprotein synthesis of schistosomula if the parasites are incubated for 24 hr with the drug (10 micrograms ml-1). An unexpected increase in lectin binding to the parasite surface was observed but no other changes were detected. Schistosomula treated in this way did not develop in the host past the lung stage. Ultraviolet irradiation (400 microW min cm-2) also inhibited glycoprotein synthesis. Synthesis of other proteins, and in particular heat shock proteins, were also inhibited. Sera from mice (NIH strain) infected with irradiated cercariae contained antibodies which bound to normal schistosomula with lower affinity than to irradiated parasites. This is evidence that irradiation modifies the surface and secreted glycoproteins of schistosomula, so they are processed in a different way to normal glycoproteins by the host's immune system. The effects of irradiation on heat shock protein synthesis may allow the parasite to release a variety of proteins and glycoproteins in abnormal conformations. This may explain the enhanced immunogenicity of irradiated cercariae.

Animals↗