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Biomedical subjects

B Ferguson

Publications and source records attributed to B Ferguson.

At least 37 records · Page 2Linked to original sources

Nurses' and GPs' views of the nurse prescribers' formulary.

This article presents the findings from the evaluation of nurse prescribing, undertaken in eight demonstration sites since October 1994. The authors examine in particular the nurses' prescribing behaviour and the type of items nurses and GPs would like to see added to the formulary. The opportunities for prescribing and the limitations of the formulary for health visitors and practice nurses are highlighted.

Attitude of Health Personnel↗

Axonal damage in acute multiple sclerosis lesions.

One of the histological hallmarks of early multiple sclerosis lesions is primary demyelination, with myelin destruction and relative sparing of axons. On the other hand, it is widely accepted that axonal loss occurs in, and is responsible for, the permanent disability characterizing the later chronic progressive stage of the disease. In this study, we have used an antibody against amyloid precursor protein, known to be a sensitive marker of axonal damage in a number of other contexts, in immunocytochemical experiments on paraffin embedded multiple sclerosis lesions of varying ages in order to see at which stage of the disease axonal damage, in addition to demyelination, occurs and may thus contribute to the development of disability in patients. The results show the expression of amyloid precursor protein in damaged axons within acute multiple sclerosis lesions, and in the active borders of less acute lesions. This observation may have implications for the design and timing of therapeutic intervention, one of the most important aims of which must be the reduction of permanent disability.

Acute Disease↗

Analysis of hospitalization rates by electoral ward: relationship to accessibility and deprivation data.

The objective of this paper is to investigate the relevance of access to hospital services in explaining utilization rates at a District Health Authority level in the UK. In order to test the hypothesis that access is important, it is necessary to develop a means of scoring access factors and then combining these scores with other more recognized influences on hospitalization rates e.g. deprivation measures. Acknowledging that hospitalization rates are not merely products of a population's socio-economic characteristics, the effect of accessibility to hospital services for the resident population is investigated through the derivation of an access score using both private and public transport from electoral ward of residence. Deprivation and accessibility to services were both found to be significant factors in determining hospitalization rates at electoral ward level. The chosen supply variable--number of GPs--was not found to be significant in any of the models developed using linear regression techniques. To conclude, it appears that access plays an important role in determining hospitalization rates within a given population. If high hospitalization rates are accepted as an indicator of effectively met demand then policy makers may have to consider increasing the accessibility of hospital services.

Catchment Area, Health↗

Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke.

Multiple sclerosis (MS) and stroke pathology are characterized blood-brain barrier breakdown, leucocyte emigration, and tissue destruction. Each process is thought to involve the matrix metalloproteinases (MMP), but little is known of their expression. We undertook to investigate whether MMP expression is dependent on the nature of the CNS lesion and whether expression would coincide with the histopathology. MS or cerebral-infarct tissue was examined for the presence of gelatinase-A, gelatinase-B, matrilysin and stromelysin-1. Gelatinases A and B and matrilysin expression was found to be up-regulated in microglia/macrophages within acute MS lesions. In active-chronic MS lesions, matrilysin and gelatinase-A expression was pronounced in the active borders. In chronic MS lesions, the expression of matrilysin was confined to macrophages within perivascular cuffs. The pattern of MMP expression in infarct lesions differed considerably. Gelatinase-B was strongly expressed by neutrophils in tissue from patients up to 1 week after an infarct, whereas gelatinase-A and matrilysin staining was much less marked. From 1 week to 5 years, neutrophils were absent and the large number of macrophages present were expressing matrilysin and gelatinase A. Only a low level of gelatinase-A and matrilysin expression was observed in normal brain controls. Thus, MMPs are expressed in inflammatory lesions in the CNS, but their individual expression is dependent on the nature and chronicity of the lesion. However, the general pattern of expression, in perivascular cuffs and in active lesions, supports a role for these enzymes as mediators of blood-brain barrier breakdown and tissue destruction, both in MS and in cerebral ischaemia.

Acute Disease↗

A study of the quality of life and cost-utility of renal transplantation.

The objective of this study was to assess the cost-utility of renal transplantation compared with dialysis. To accomplish this, a prospective cohort of pre-transplant patients were followed for up to two years after renal transplantation at three University-based Canadian hospitals. A total of 168 patients were followed for an average of 19.5 months after transplantation. Health-related quality of life was assessed using a hemodialysis questionnaire, a transplant questionnaire, the Sickness Impact Profile, and the Time Trade-Off Technique. Fully allocated costs were determined by prospectively recording resource use in all patients. A societal perspective was taken. By six months after transplantation, the mean health-related quality of life scores of almost all measures had improved compared to pre-transplantation, and they stayed improved throughout the two years of follow up. The mean time trade-off score was 0.57 pre-transplant and 0.70 two years after transplantation. The proportion of individuals employed increased from 30% before transplantation to 45% two years after transplantation. Employment prior to transplantation [relative risk (RR) = 23], graft function (RR 10) and age (RR 1.6 for every decrease in age by one decade), independently predicted employment status after transplantation. The cost of pre-transplant care ($66,782 Can 1994) and the cost of the first year after transplantation ($66,290) were similar. Transplantation was considerably less expensive during the second year after transplantation ($27,875). Over the two years, transplantation was both more effective and less costly than dialysis. This was true for all subgroups of patients examined, including patients older than 60 and diabetics. We conclude that renal transplantation was more effective and less costly than dialysis in all subgroups of patients examined.

Adult↗

X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein.

Ectodermal dysplasias comprise over 150 syndromes of unknown pathogenesis. X-linked anhidrotic ectodermal dysplasia (EDA) is characterized by abnormal hair, teeth and sweat glands. We now describe the positional cloning of the gene mutated in EDA. Two exons, separated by a 200-kilobase intron, encode a predicted 135-residue transmembrane protein. The gene is disrupted in six patients with X;autosome translocations or submicroscopic deletions; nine patients had point mutations. The gene is expressed in keratinocytes, hair follicles, and sweat glands, and in other adult and fetal tissues. The predicted EDA protein may belong to a novel class with a role in epithelial-mesenchymal signalling.

Adult↗

Substance abuse.

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Adolescent↗

Seven-year follow-up of speech/language impaired and control children: psychiatric outcome.

This study examined the 7-year psychiatric outcome of 202 speech/language (S/L) impaired and control children selected from a community sample at age 5 years. Children with S/L at age 5 years were more likely to be psychiatric cases at age 12.5 years than were normal controls, even if their S/L improved. Controlling for concurrent psychiatric disorder, S/L impairment at age 5 years was still associated with an increased rate of psychiatric disorder at 12.5 years. Psychiatric disorder at age 12.5 years was more likely to co-occur with language disorder than with speech disorder.

Articulation Disorders↗

A controlled trial of dothiepin and placebo in treating benzodiazepine withdrawal symptoms.

BACKGROUND: The possibility that treatment with tricyclic antidepressants, in the form of dothiepin, might attenuate benzodiazepine withdrawal symptoms was investigated in a double-blind trial. METHOD: Eighty-seven non-depressed psychiatric out-patients with putative normal dose benzodiazepine dependence had their benzodiazepines reduced in stepwise amounts of 20% of the original dose for eight weeks. The patients were randomised to receive dothiepin (with dosage increasing to 150 mg/day) or placebo as an aid to withdrawal before benzodiazepine reduction and these drugs were taken for four further weeks before being stopped. RESULTS: Fewer patients entered and completed the study than expected and a Type II error was possible in the results. Although there was some evidence of withdrawal symptoms being less marked in those patients allocated to dothiepin this was independent of any antidepressant effect as depression scores were lower in the placebo group in the early phase of withdrawal (P < 0.01). Of those completing the study, greater satisfaction (P = 0.03) was recorded by those who had received dothiepin; no other differences reached statistical significance. CONCLUSIONS: Dothiepin (and by implication other tricyclic antidepressants) might have some value in reducing benzodiazepine withdrawal symptoms but does not aid drug withdrawal.

Ambulatory Care↗

The Nottingham Study of Neurotic Disorder: influence of cognitive therapists on outcome.

BACKGROUND: In previously published papers from the Nottingham Study of Neurotic Disorder a short treatment package of cognitive-behaviour therapy was no more effective than placebo drug treatment after 10 weeks' assessment in a cohort of 210 patients with neurotic disorders. This paper examines the outcome over two years of the patients treated by cognitive-behaviour therapy separated into two therapist groups, those who were competent in administering treatment and those of uncertain competence. METHOD: The therapists (mainly community psychiatric nurses) of 70 patients with an original DSM-III diagnosis of either dysthymic, panic or generalised anxiety disorder were separated into two groups on the basis of their perceived competence by their supervisor (DK). Ratings of psychopathology were made at regular intervals over two years by assessors blind to knowledge of treatment or therapist. RESULTS: The patients treated by competent therapists (n = 30) generally showed greater improvement than those allocated to therapists of uncertain competence (n = 40), mainly with respect to depressive symptoms, and the difference persisted over two years, long after the cognitive-behaviour therapy had been completed. CONCLUSIONS: Cognitive-behaviour therapy given by competent therapists over a 10 week period is of lasting benefit in neurotic disorder.

Adult↗

Mutation of RGA1, which encodes a putative GTPase-activating protein for the polarity-establishment protein Cdc42p, activates the pheromone-response pathway in the yeast Saccharomyces cerevisiae.

We have selected yeast mutants that exhibit a constitutively active pheromone-response pathway in the absence of the beta subunit of the trimeric G protein. Genetic analysis of one such mutant revealed that it contained recessive mutations in two distinct genes, both of which contributed to the constitutive phenotype. One mutation identifies the RGA1 locus (Rho GTPase activating protein), which encodes a protein with homology to GAP domains and to LIM domains. Deletion of RGA1 is sufficient to activate the pathway in strains lacking the G beta subunit. Moreover, in wild-type strains, deletion of RGA1 increases signaling in the pheromone pathway, whereas over-expression of RGA1 dampens signaling, demonstrating that Rga1p functions as a negative regulator of the pheromone response pathway. The second mutation present in the original mutant proved to be an allele of a known gene, PBS2, which encodes a putative protein kinase that functions in the high osmolarity stress pathway. The pbs2 mutation enhanced the rga1 mutant phenotype, but by itself did not activate the pheromone pathway. Genetic and two-hybrid analyses indicate that an important target of Rga1p is Cdc42p, a p21 GTPase required for polarity establishment and bud emergence. This finding coupled with recent experiments with mammalian and yeast cells indicating that Cdc42p can interact with and activate Ste20p, a protein kinase that operates in the pheromone pathway, leads us to suggest that Rga1p controls the activity of Cdc42p, which in turn controls the magnitude of signaling in the pheromone pathway via Ste20p.

Amino Acid Sequence↗

Signal transduction and growth control in yeast.

An understanding of how an extracellular stimulus causes changes in cell growth is emerging from the study of four signal transduction pathways in Saccharomyces cerevisiae: the pheromone-response, pseudohyphal differentiation, osmolarity-response, and protein kinase C activated pathways. Each of these pathways contains at its core a distinct mitogen-activated protein kinase cascade. Biochemical and molecular studies have determined the functional order of the kinases in the pheromone-response pathway and have suggested that they are organized into a complex by a protein scaffold. The cell surface sensor system for the osmolarity-response pathway has been identified. It shows striking similarity to bacterial two-component sensor-responder systems. Finally, components that integrate information from these pathways and communicate it to cell growth regulators have been revealed.

Glycerol↗