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Biomedical subjects

L Bell

Publications and source records attributed to L Bell.

At least 19 recordsLinked to original sources
PubMed2000

Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates.

OBJECTIVE: Neuropsychological impairments are well documented in schizophrenia and are important targets of treatment. Information about the severity and pattern of deficits after treatment for the first psychotic episode and about relationships between these deficits and syndromal characteristics remains limited. METHOD: Comprehensive neuropsychological assessments including 41 individual tests were given to 94 patients with first-episode schizophrenia after initial stabilization of psychosis and to a comparison group of 36 healthy volunteers. Profiles of neuropsychological deficits and the relationship of deficits to sex and handedness were examined. Correlations of neuropsychological deficit with a broad range of historical and clinical characteristics, including outcome, were explored. RESULTS: Patients had a large generalized neuropsychological deficit (1.5 standard deviations compared to healthy volunteers). Patients also had, superimposed on the generalized deficit, subtle relative deficits (less than 0.5 standard deviation compared to their own average profile) in memory and executive functions. Learning/memory dysfunction best distinguished patients from healthy individuals; after accounting for this difference, only motor deficits further distinguished the groups. Patients with higher neuropsychological ability had only memory deficits, and patients with lower ability had both memory and executive deficits. No sex differences were observed beyond the normal advantage for men in motor speed. Dextral patients had less severe generalized deficit. Severity of residual symptoms was associated with greater generalized deficit. Executive and attentional deficits were most linked to global functional impairment and poor outcome. CONCLUSIONS: The results document a large generalized deficit, and more subtle differential deficits, in clinically stabilized first-episode patients. Learning/memory deficits were observed even in patients with less severe generalized deficit, but the pattern was unlike the amnestic syndrome and probably reflects different mechanisms. Executive and attentional deficits marked the more severely disabled patients, and may portend relatively poor outcome. Failure to develop typical patterns of cerebral dominance may increase the risk for greater generalized deficit.

Adult↗
PubMed1999

Growth during maintenance hemodialysis: impact of enhanced nutrition and clearance.

Growth of children during maintenance hemodialysis has been reported to be uniformly poor, with a mean annual loss of 0.4 to 0.8 SD in height. We adopted an intensive program of closely monitored energy and protein intake with dialysis urea clearances exceeding conventional recommendations. Twelve prepubertal or early pubertal children (aged 7 months to 14 years) were monitored for an average of 2.2 years (range 4 to 81 months) while receiving maintenance hemodialysis. These children received an average of 90.6% and 155.9% of their recommended energy and protein nutritional intake, respectively. With a prescribed urea clearance of 5 mL/kg/min, we achieved a mean single treatment urea clearance normalized for total body water of 2.00, a urea reduction ratio of 84.7%, and an average time of hemodialysis of 14.8 h/wk, all well beyond current guidelines. Over the course of dialysis treatment, the improvement in height SD score was+0.31 SD/y (+0.32 excluding the 2 children treated with recombinant human growth hormone). Normal growth was achieved without overt obesity and was associated with normal pubertal growth spurt. These findings suggest that the combination of increased dialysis and adequate nutrition can promote normal growth in children treated with long-term hemodialysis.

Adolescent↗
PubMed1999

A homolog of the fungal nuclear migration gene nudC is involved in normal and malignant human hematopoiesis.

The filamentous fungus Aspergillus nidulans nudC gene has an essential function in movement of nuclei following mitosis and is required for normal colony growth. Here, the molecular cloning and role in hematopoiesis of a human gene (designated HnudC) homologous to A. nidulans nudC is reported. The amino terminus of the larger human protein (HNUDC = 45 kDa) does not overlap with A. nidulans NUDC (22 kDa). However, NUDC and the C-terminal 94 amino acids of HNUDC are 67% identical. The C-terminal region of the HnudC gene fully complements the A. nidulans temperature-sensitive nudC3 mutation, suggesting that nudC has an essential function in cell growth that is conserved from filamentous fungi to humans. In initial studies, HNUDC levels were much higher in erythroid precursors compared to most other human tissues. Therefore, the potential role of HnudC in hematopoiesis was explored. In normal human bone marrow, HNUDC protein and mRNA are highly expressed in early myeloid and erythroid precursors and decline as these cells terminally differentiate. To determine whether hematopoietic growth factors induce HnudC expression, TF-1 cells were stimulated by granulocyte-macrophage colony-stimulating factor. This induced a significant increase in HNUDC protein and HnudC mRNA, suggesting that enhancement of HnudC expression in response to growth factor stimulation may be mediated at the transcription level. Furthermore, HNUDC was significantly enhanced in lysates of bone marrow aspirates from patients with acute myelogenous and acute lymphoblastic leukemia compared to aspirates from normal controls, suggesting that HnudC is involved in malignant hematopoietic cell growth as well. These data demonstrate that HNUDC is highly expressed in normal and malignant human hematopoietic precursors and suggest it is of functional importance in the proliferation of these cells.

Antibody Specificity↗
PubMed1999

Recovery of human skeletal elements from a recent UK murder inquiry: preservational signatures.

Factors that control bone preservation are not fully understood but generally include those that reflect "natural" taphonomic or diagenetic processes and also those reflecting anthropogenic activity. The aim of this paper is to examine whether the survival of skeletal elements from a recent UK serial murder investigation (n = 12) and three archaeological cemetery sites from England (n = 112, 95, 182; Roman to early-medieval), share a similar recovery signature. Examination of this data demonstrates that even when clear evidence of traumatic and perimortem dismemberment exists within an assemblage, the distribution of missing elements can be almost identical to archaeological material buried in normal attrition cemeteries. Given that these preservational signatures are so similar, it is concluded that careful observation of bone surfaces is necessary to confidently interpret bone loss, particularly where dismemberment and/or element excision is suggested by the non-anatomical position of the skeleton within the grave. Where postmortem excision of bone is suspected, careful examination of contiguous bone surfaces, both macroscopic and microscopic, is suggested to detect fine cutmark lesions indicative of anthropogenic excision. Without this evidence other preservational factors must be considered both taphonomic and diagenetic.

Adolescent↗
PubMed1998

Bcl-3 expression and nuclear translocation are induced by granulocyte-macrophage colony-stimulating factor and erythropoietin in proliferating human erythroid precursors.

Bcl-3 is a proto-oncogene involved in the chromosomal translocation t(14;19) found in some patients with chronic lymphocytic leukemia. It shares structural similarities with and is a member of the IkappaB family of proteins. In this report, involvement of Bcl-3 in hematopoietic growth factor-stimulated erythroid proliferation and differentiation was examined. In TF-1 cells, an erythroleukemia cell line, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo) greatly enhanced Bcl-3 expression at both the protein and mRNA levels in association with stimulation of proliferation. Bcl-3 protein was also highly expressed in early burst-forming unit-erythroid (BFU-E)-derived erythroid precursors (day 7) and decreased during maturation (days 10 and 14), suggesting that Bcl-3 is involved in normal erythroid proliferation. In these hematopoietic cells, Bcl-3 was hyperphosphorylated. GM-CSF and Epo modulated the subcellular localization of Bcl-3. Upon stimulation of TF-1 cells with GM-CSF or Epo, the nuclear translocation of Bcl-3 was dramatically enhanced. Overexpression of Bcl-3 in TF-1 cells by transient transfection along with the NF-kappaB factors p50 or p52 resulted in significant induction of an human immunodeficiency virus-type 1 (HIV-1) kappaB-TATA-luceriferase reporter plasmid, demonstrating that Bcl-3 has a positive role in transactivation of kappaB-containing genes in erythroid cells. Stimulation with GM-CSF enhanced c-myb mRNA expression in these cells. Bcl-3 in nuclear extracts of TF-1 cells bound to a kappaB enhancer in the c-myb promoter together with NF-kappaB2/p52 and this binding activity was enhanced by GM-CSF stimulation. Furthermore, cotransfection of Bcl-3 with p52 or p50 in TF-1 cells resulted in significant activation of a c-myb kappaB-TATA-luceriferase reporter plasmid. These findings suggest that Bcl-3 may participate in the transcriptional regulation of certain kappaB-containing genes involved in hematopoiesis, including c-myb.

B-Cell Lymphoma 3 Protein↗
PubMed1998

NF-kappaB transcription factors are involved in normal erythropoiesis.

NF-kappaB/Rel designates a widely distributed family of transcription factors involved in immune and acute phase responses. Here, the expression and function of NF-kappaB factors in erythroid proliferation and differentiation were explored. In an erythroleukemia cell line, TF-1, high levels of p105/p50, p100/p52, p65, and IkappaBalpha were detected 24 hours after growth factor deprivation. In response to granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation, significant induction of p52 expression was observed. GM-CSF also induced nuclear translocation of both p52 and p65. No induction of NF-kappaB factors was observed with erythropoietin stimulation of TF-1 cells. Overexpression of p52 and p65 in TF-1 cells by transient transfection resulted in significant induction of a kappaB-TATA-luciferase reporter plasmid, showing that these factors are functional in vivo in erythroid cells. To determine whether NF-kappaB factors may play a role in normal erythropoiesis, levels of these factors were determined in burst-forming unit-erythroid (BFU-E)-derived cells at different stages of differentiation. The NF-kappaB factors p105/p50, p100/p52, and p65 were highly expressed in early BFU-E-derived precursors, which are rapidly proliferating, and declined during maturation. Furthermore, nuclear levels of NF-kappaB factors p50, p52, and p65 were higher in less mature precursors (day 10 BFU-E-derived cells) compared with more differentiated (day 14) erythroblasts. In nuclear extracts from day 10 BFU-E-derived cells, p50, p52, and p65 were able to form complexes, which bound to kappaB sites in the promoters of both the c-myb and c-myc genes, suggesting that c-myb and c-myc may be among the kappaB-containing genes regulated by NF-kappaB factors in normal erythroid cells. Taken together, these data show that NF-kappaB factors are modulated by GM-CSF and suggest they function to regulate specific kappaB containing genes involved in erythropoiesis.

Cell Division↗
PubMed1998

A concept analysis of parent-infant attachment.

A concept analysis, the clarification of a concept, is the first step towards building the foundations of nursing theory, research and practice. As a relevant concept for nurses working with childbearing families, parent-infant attachment is an important part of the body of nursing knowledge. Wilson's method of concept analysis was used to generate antecedents, critical attributes and consequences of parent-infant attachment, highlighting the need to refine measurements of this concept.

Canada↗
PubMed1998

Communicate: organisational issues and their relevance for clinical evaluation.

This paper reports the first findings of a two year project funded by the NHS Executive North Thames to provide an independent evaluation of Communicate, Action for Dysphasic Adults' training programme for carers of older people with communication impairments. The project comprises an organisational evaluation (January-July 1998) to review the use of Communicate by purchasers nationally and in the North Thames health region, and (from September 1998) a clinical evaluation in North Thames region, to investigate outcomes for communicatively impaired people themselves and for training participants. The paper outlines the research design and progress so far before presenting initial findings. It concludes by discussing the relevance of organisational issues and social science research insights to the forthcoming clinical evaluation.

Aphasia↗
PubMed1997

Sex lethal controls dosage compensation in Drosophila by a non-splicing mechanism.

Dosage compensation in Drosophila requires the male-specific lethal (msl) proteins (MSL) to make gene expression from the single male X chromosome equivalent to that from both female X chromosomes. Expression of ms12 is repressed post-transcriptionally by Sex lethal (SXL), a female-specific RNA-binding protein that regulates alternative splicing in the sex-determination hierarchy. Although msl2 RNA is alternatively spliced in males and females, this does not alter its coding potential and splicing is not required for male-specific expression of MSL2 protein. Instead, our results suggest that the association of SXL protein with multiple sites in the 5' and 3' untranslated regions of the mx12 transcript represses its translation in females. Thus, this well characterized alternative splicing factor regulates at least one target transcript by a distinct mechanism.

Alternative Splicing↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗