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Biomedical subjects

L Bell

Publications and source records attributed to L Bell.

At least 37 records · Page 2Linked to original sources

The development and benefits of nursing protocols for fractured neck of femur patients.

In this article the authors discuss the development, use and auditing of nursing care protocols, which have been implemented and form a guide for nurses caring for patients with fractured neck of femur in Southend Health Care NHS Trust. The development of these protocols occurred after an initial medical audit, which was followed by a far larger multidisciplinary audit, and both of these revealed there was need for changes in the clinical management of such patients; subsequently a large multidisciplinary working group worked together to develop care protocols/pathways to enable closure of the audit loop. The reasons for focusing on fractured neck of femur as a high priority condition are also discussed. All professional groups caring for these patients were involved in the multidisciplinary working group, which was formed to close the audit loop and to improve clinical practices by increasing the systemization and coordination of care. The development of the nursing protocols represented an extremely important part of this process, and the care of about 700 patients was examined during this work. The audit and associated subsequent work have resulted in direct improvements to both patient care and health outcomes, and the authors conclude that there is great value in developing multidisciplinary protocols, particularly those involving nurses, because they spend more time with patients whilst they are in hospital than any other professional group. The benefits of these nursing protocols have been multifold, in particular they have facilitated a clearer flow of patients through the hospital, increased awareness of responsibilities and reduced duplication of effort, and ensured patients receive the best possible care over the 24-hour period.

Emergency Nursing↗

G-protein alpha subunit Gi(alpha)2 mediates erythropoietin signal transduction in human erythroid precursors.

Erythropoietin induces a dose-dependent increase in cytosolic calcium in human erythroblasts that is mediated by a voltage-independent Ca2+ channel. Inhibition of this response to erythropoietin by pertussis toxin suggests involvement of guanine nucleotide-binding regulatory proteins (G-proteins). The role of G-proteins in regulation of the erythropoietin-modulated Ca2+ channel was delineated here by microinjection of G-protein modulators or subunits into human erythroid precursors. This is the first report on the use of microinjection to study erythropoietin signal transduction in normal precursor cells. Fura-2 loaded day-10 burst-forming units-erythroid-derived erythroblasts were used for microinjection and free intracellular calcium concentration ([Ca(i)]) was measured with digital video imaging. BCECF (1,2',7'-bis(2-carboxyethyl)-5-(and -6-)-carboxyfluorescein) was included in microinjectate, and an increase in BCECF fluorescence was evidence of successful microinjection. Cells were microinjected with nonhydrolyzable analogues of GTP, GTPgammaS or GDPbetaS, which maintain the alpha subunit in an activated or inactivated state, respectively. [Ca(i)] increased significantly in a dose-dependent manner after microinjection of GTPgammaS. However, injection of GDPbetaS blocked the erythropoietin-induced calcium increase, providing direct evidence that activation of a G-protein is required. To delineate which G-protein subunits are involved, alpha or betagamma transducin subunits were purified and microinjected as a sink for betagamma or alpha subunits in the erythroblast, respectively. Transducin betagamma, but not alpha, subunits eliminated the calcium response to erythropoietin, demonstrating the primary role of the alpha subunit. Microinjected antibodies to Gi(alpha)2, but not Gi(alpha)1 or Gi(alpha)3, blocked the erythropoietin-stimulated [Ca(i)] rise, identifying Gi(alpha)2 as the subunit involved. This was confirmed by the ability of microinjected recombinant myristoylated Gi(alpha)2, but not Gi(alpha)1 or Gi(alpha)3 subunits, to reconstitute the response of pertussis toxin-treated erythroblasts to erythropoietin. These data directly demonstrate a physiologic function of G-proteins in hematopoietic cells and show that Gi(alpha)2 is required in erythropoietin modulation of [Ca(i)] via influx through calcium channels.

Calcium↗

The economic evaluation of the FIRST study: design of a prospective analysis alongside a multinational phase III clinical trial. Flolan International Randomized Survival Trial.

Prospective economic assessments of new pharmaceutical therapies are increasingly being incorporated into phase III clinical trials. We report on the design of an economic evaluation integrated into the Flolan International Randomized Survival Trial (FIRST). Economic evaluation was considered a critical component of the assessment of this therapy given the resources required to administer epoprostenol (Flolan), a therapy that would require lifelong continuous intravenous infusion. Economic secondary endpoints were incorporated in the clinical trial. The economic evaluation of the treatment was integrated into all aspects of study development, including study design, implementation, and monitoring. Since this was a multinational trial, special care was required to ensure that the protocol design was appropriate for all study countries. The economic assessment required the development of several methodologic components: a set of background economic concepts to guide protocol development, a set of resource items to be recorded when required for study participants; a set of data collection instruments for assessment of health-related quality of life for study patients; and a protocol for a resource costing exercise for the study. We report the data elements included in the study design, as well as a discussion of some of the issues faced in developing the economic evaluation for this trial.

Antihypertensive Agents↗

Glutathione deficiency as a complication of methylmalonic acidemia: response to high doses of ascorbate.

A 7-year-old boy with deficient activity of methylmalonyl coenzyme A mutase (mut-methylmalonic acidemia) was seen in severe metabolic crisis. After hemodialysis and clearance of toxic metabolites, severe lactic acidosis persisted with multiorgan failure. Glutathione deficiency was noted and high-dose ascorbate therapy (120 mg/kg) commenced. Glutathione deficiency may contribute to the lactic acidosis observed during decompensation in patients with methylmalonic acidemia.

Acidosis, Lactic↗

Results of the economic evaluation of the first study. A multinational prospective economic evaluation. FIRST Investigators. Flolan International Randomized Survival Trial.

We present the prospective economic evaluation that served as a secondary endpoint for the FIRST study, a randomized international multicenter trial of patients with severe congestive heart failure. Although the clinical results of this study were disappointing, we demonstrated the feasibility of incorporating prospective economic evaluation in phase III clinical trials.

Aged↗

A strategy for collecting pharmacoeconomic data during phase II/III clinical trials.

This article presents an overview of the process and organisational aspects required to support the collection of pharmacoeconomic (PE) data during phase II and phase III clinical trials of pharmaceutical products. The process described requires early involvement of the PE study team in clinical trials design and planning, as well as continuing close collaboration between the PE study team and the clinical study team as the data collection plans are implemented. Adequate resources must be made available for staffing and funding the PE component of data collection and analysis. If the suggested procedures are adequately resourced and implemented, the result should be a comprehensive, complete and accurate database that will allow the PE study team to characterise the economic value of the new drug at the same time as the clinical study team characterise its safety and efficacy. Integrated clinical and economic evaluations are essential for the appropriate use of pharmaceutical products in rapidly changing markets.

Clinical Trials, Phase II as Topic↗

Why the NHS should abandon the search for the universal outcome measure.

This paper considers the use of outcome measures in the British National Health Service (NHS). Measuring outcomes is a major conceptual and practical problem. Many different measures are currently available yet no consensus has been reached on which should be preferred over others, or about which should take priority when they conflict. Some currently used measures are described, the relationship between these measures and the measured activities are discussed, and fundamental problems with both the measures and their use are revealed. It is shown that however assiduous the search, the 'perfect' outcome measure will always remain elusive.

Commerce↗

Progress in a Moscow children's burn unit: a joint Russian-American collaboration.

A joint Russian-American paediatric burn programme involving Childrens Hospital No. 9 in Moscow and Project HOPE in Millwood, Virginia emerged from the efforts of burn professionals from both countries in caring for a group of children seriously burned as a result of the train-pipeline catastrophe that occurred in June 1989 in the Ural Mountains. This paper describes the burn unit and its activities during the years 1985-93 and includes: (1) a general description of the physical and administrative structure of the unit; (2) the demography of burn admissions; (3) clinical activities; (4) a comparison of the clinical results of the years before the institution of the combined programme (1985-89) with those achieved during the first 4 years of the combined collaboration (1990-93). Among the important changes that have occurred since the onset of the combined programme are: (1) overall reduction in the crude burn mortality rate; (2) decrease in burn deaths in all burn size groups; (3) dramatic reduction in the length of stay of children with the deepest burns; (4) marked improvement in the take of skin grafts applied to burn wounds and an almost total elimination of complete skin graft failures.

Adolescent↗

Anterior hippocampal volume reductions predict frontal lobe dysfunction in first episode schizophrenia.

This study examined relations of mesiotemporal lobe tissue volumes with neuropsychological (NP) functions in a sample of patients with first episode schizophrenia. Three contiguous compartments of the mesiotemporal lobe were measured on magnetic resonance images, comprising primarily amygdaloid, anterior hippocampal, and posterior hippocampal tissue volumes. NP measures were derived from a comprehensive battery. Decreased volume selectively in the anterior hippocampal formation was associated with lower scores on measures of executive and motor functions usually considered sensitive to the integrity of frontal lobe systems. Measures of other NP functions, and global intellectual ability, were not related to mesiotemporal volumes. The findings that morphologic abnormalities in the mesiotemporal lobe are associated with impairment of frontal lobe functions point to a defect in an integrated functional system that includes both frontal and mesiotemporal components. The findings are consistent with the hypothesis that neurodevelopmental defects affecting the morphology of the anterior hippocampal formation may be manifest later in life as impairments in fronto-limbic control. .

Acute Disease↗

A randomized, controlled trial of the efficacy of a heparin and vancomycin solution in preventing central venous catheter infections in children.

OBJECTIVE: To determine whether adding vancomycin to central venous catheter (CVC) flush solution would significantly reduce the incidence of bacteremia attributable to luminal colonization with vancomycin-susceptible organisms. STUDY DESIGN: Fifty-five children with cancer and eight children given total parenteral nutrition by the surgery or nutrition support services were randomly assigned to receive a heparin CVC flush solution (n = 31) or a heparin-vancomycin CVC flush solution (n = 32). RESULTS: During 9158 catheter days, 6.5% of the patients in the heparin group and 15.6% of the patients in the heparin-vancomycin group had bacteremia attributable to luminal colonization with vancomycin-susceptible organisms (p = 0.43). The mean rates of bacteremia attributable to luminal colonization with vancomycin-susceptible organisms were 0.6/1000 catheter days in the heparin group and 1.4/1000 catheter days in the heparin-vancomycin group (p = 0.25). There was no significant difference between the groups when the time to the first episode of bacteremia attributable to luminal colonization with a vancomycin-susceptible organism was compared by means of Kaplan-Meier survival estimates. Streptococcus viridans infection was not attributable to luminal colonization. CONCLUSION: The addition of vancomycin to heparin CVC flush solution did not reduce bacteremia with vancomycin-susceptible organisms. Bacteremia with Streptococcus viridans was not related to the use of a CVC.

Adolescent↗

Involving patients in the provision of community care: a change in philosophy.

The National Health Service (NHS) has many different kinds of professionals and managers working underneath its large umbrella: non-clinical managers administer the work of health-care professionals, who in turn are concerned with the management of patients' treatments. Delivery of health-care services involves the managers and professionals working together to achieve a service that is good for, and acceptable to, patients. A change in the philosophy of the NHS is indicated by the growing acceptance, by both managers and professionals, of the necessity to elicit the views of patients (i.e. the expectations and perceptions of service users) and to incorporate these views into the planning and implementation of services. Discusses one such attempt to elicit the perceptions of service users, and reports on the preliminary findings of a patient-centred audit which has been undertaken in Southend Community Care Services NHS Trust. Discusses the effects that the audit has had on the chiropody services in Southend, for both non-clinical managers and health-care professionals, in order to highlight the usefulness of the approach.

Community Health Services↗

Steel factor affects SCL expression during normal erythroid differentiation.

Steel factor is one of the growth factors that controls the proliferation and differentiation of hematopoietic cells and SCL, also known as Tcl-5 or Tal-1, is a transcription factor involved in erythropoiesis. In this report, we studied the role of SCL in the proliferation of human peripheral blood burst-forming unit-erythroid (BFU-E) and the effects of Steel factor on SCL expression in proliferating erythroid cells. BFU-E-derived colonies increase progressively in size, as determined by cell number, from day 7 to day 14 of culture, with the greatest increase in colony size (10-fold expansion) occurring between day 7 and day 10. SCL protein levels in BFU-E-derived cells were highest in day 7 cells and decreased progressively from day 7 to day 14 of culture, suggesting an association of SCL with erythroid proliferation. In contrast, SCL mRNA levels did not decrease significantly between day 7 and day 14 cells, suggesting that posttranscriptional mechanisms are largely responsible for the decrease in SCL protein observed. The role of SCL in Steel factor-induced erythroid proliferation was then examined. In BFU-E-derived colonies cultured with Steel factor, colony size was significantly increased compared to control. In day 7 and day 10 erythroid precursors cultured with Steel factor, SCL protein was increased significantly compared to control. The increase in SCL protein levels in early erythroid precursors stimulated with Steel factor suggests one mechanism through which Steel factor may enhance normal erythroid proliferation. SCL mRNA levels assessed by Northern blot in day 7 cells did not increase significantly in response to Steel factor stimulation, suggesting that posttranscriptional mechanisms may also be important in the increase in SCL protein observed in response to Steel.

Base Sequence↗

Who is the NHS for?

The immediate, common sense answer to the question, "Who is the NHS for?" would obviously be, "The patients who use it". This may well be the fundamental purpose of the NHS, yet it would appear that differing views of how this is to be achieved contribute to a misreading between stakeholders of each others' remit. The different positions taken by the two most important NHS stakeholders, the professional clinicians and the administrative managers, affect their definitions of, and therefore their attitudes to their own contribution to the purpose of the NHS. Suggests that before priorities in health care can be considered and discussed, let along be set, consensual agreement needs to be reached concerning the views of professional clinicians and managers of ways of achieving their vision of who the NHS is for.

Administrative Personnel↗

Photoinhibition of smooth muscle cell migration: potential therapy for restenosis.

Evidence from animal, autopsy, and atherectomy studies demonstrates that migration and proliferation of smooth muscle cells of medial origin result in neointima formation and decreased luminal cross-sectional area. The purpose of this study was to evaluate whether low energy light irradiation can inhibit smooth muscle cell migration and therefore potentially reduce the degree of neointima formation and the incidence of restenosis. The migration kinetics of bovine aortic smooth muscle cell monolayers were examined using a fence assay. The effect on smooth muscle cell migration of irradiation with monochromatic light at wave-lengths ranging from 400 to 700 nm was compared to the migration of cells irradiated with broadband white light or maintained in the dark. Wavelength specific photoinhibition of smooth muscle cell migration was observed; 594-600 nm light reproducibly inhibited migration by 12-29% (P < 0.05). Migration rate was significantly reduced following daily radiant exposures of 1.0 J/cm2 as well as following a single radiant exposure of 0.09 or 0.9 J/cm2. The decrease in migration was not associated with any change in cell proliferation or [3H] thymidine incorporation. We conclude that 594-600 nm light inhibits smooth muscle cell migration in vitro and may potentially be used in vivo to decrease fibrointimal thickening following arterial injury. This application of photoinhibition may be useful in retarding restenosis following angioplasty.

Animals↗

Devising a multidisciplinary audit tool.

Discusses the audit processes in health care from the existing perspectives and argues the need to extend the current unidimensional approaches which include medical, clinical and managerial quality. Argues that one way of expanding these approaches is to develop an audit instrument based on the views of service users. The implementation of audit has been a process with regional variations, which have created centres of excellence and centres where there is very little happening. Considers elements that are involved in devising an audit tool which is based on customers' perceptions of service quality, and reports on an empirical study which is still in progress and which aims to develop a tool which is effective, efficient and based on patients' views.

Aged↗

Fibronectin expression correlates with U937 cell adhesion to migrating bovine aortic endothelial cells in vitro.

A blood vessel's response to denudation injury will determine its final luminal diameter as well as its function. The synthesis, deposition, and remodeling of extracellular matrix components and migration by vascular endothelial cells are major factors in determining luminal diameter, cellular proliferative and migratory responses, and mononuclear cell adhesion at sites of injury. Previously, we have shown that after in vivo and in vitro denudation injury, endothelial cell migration is dramatically influenced by the amount of fibronectin synthesized and deposited by the responding endothelial cell population. The aim of this study was to elucidate the roles of fibronectin in modulating mononuclear cell adhesion to the endothelial cell population during in vitro migration. In this report we demonstrate that U937 cell binding to the migrating fronts of endothelial cell monolayers is modulated by the amount of fibronectin synthesized and deposited by the endothelial cells. Agents which increase fibronectin deposition, such as transforming growth factor-beta 1, elicit greater U937 cell adhesion. Manipulations that decrease fibronectin deposition, such as transfection and overexpression of pp60c-src proto-oncogene in endothelial cells, reduce U937 cell adhesion. These results suggest that changes in endothelial cell extracellular matrix synthesis and deposition modulate, in part, the adhesive properties of the vessel wall after injury. In turn, the intensity and duration of mononuclear cell adhesion at sites of vessel wall injury determines, in part, the vessel wall response.

Animals↗