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Biomedical subjects

P Reid

Publications and source records attributed to P Reid.

At least 37 records · Page 2Linked to original sources
PubMed1999

Identification of residues in dendrotoxin K responsible for its discrimination between neuronal K+ channels containing Kv1.1 and 1.2 alpha subunits.

Dendrotoxin (DTX) homologues are powerful blockers of K+ channels that contain certain subfamily Kv1 (1.1-1.6) alpha- and beta-subunits, in (alpha)4(beta)4 stoichiometry. DTXk inhibits potently Kv1.1-containing channels only, whereas alphaDTX is less discriminating, but exhibits highest affinity for Kv1.2. Herein, the nature of interactions of DTXk with native K+ channels composed of Kv1.1 and 1.2 (plus other) subunits were examined, using 15 site-directed mutants in which amino acids were altered in the 310-helix, beta-turn, alpha-helix and random-coil regions. The mutants' antagonism of high-affinity [125I]DTXk binding to Kv1. 1-possessing channels in rat brain membranes and blockade of the Kv1. 1 current expressed in oocytes were quantified. Also, the levels of inhibition of [125I]alphaDTX binding to brain membranes by the DTXk mutants were used to measure their high- and low-affinity interactions, respectively, with neuronal Kv1.2-containing channels that possess Kv1.1 as a major or minor constituent. Displacement of toxin binding to either of these subtypes was not altered by single substitution with alanine of three basic residues in the random-coil region, or R52 or R53 in the alpha-helix; accordingly, representative mutants (K17A, R53A) blocked the Kv1.1 current with the same potency as the natural toxin. In contrast, competition of the binding of the radiolabelled alphaDTX or DTXk was dramatically reduced by alanine substitution of K26 or W25 in the beta-turn whereas changing nearby residues caused negligible alterations. Consistently, W25A and K26A exhibited diminished functional blockade of the Kv1.1 homo-oligomer. The 310-helical N-terminal region of DTXk was found to be responsible for recognition of Kv1.1 channels because mutation of K3A led to approximately 1246-fold reduction in the inhibitory potency for [125I]DTXk binding and a large decrease in its ability to block the Kv1.1 current; the effect of this substitution on the affinity of DTXk for Kv1.2-possessing oligomers was much less dramatic (approximately 16-fold).

Amino Acid Sequence↗
PubMed1998

The family impact of childhood atopic dermatitis: the Dermatitis Family Impact Questionnaire.

Little information is available about the effect of childhood atopic dermatitis (AD) on family function. The aim of this study was to identify the areas of family life most affected and their perceived importance. Intensive qualitative interviews with 34 families were conducted and 11 basic problem areas were identified. A detailed questionnaire was prepared, part of which addressed the perceived importance of particular issues using the framework of multi-attribute utility theory. The results from using this questionnaire in 41 families were analysed and a shorter 10-question one-page Dermatitis Family Impact (DFI) questionnaire designed (maximum score = 30). In affected families the mean DFI score was 9.6 +/- 7.0 (range 0-27, n = 56) and in unaffected families the mean score was 0.4 +/- 0.9 (range 0-3, n = 26, P < 0.0001). The DFI could potentially be used as an extra measure in clinical studies, or to help guide appropriate management of AD.

Adolescent↗
PubMed1997

Clwydian Community Care Trust: district nursing patients' questionnaire.

The aim of this project was to develop a reliable and valid consumer satisfaction questionnaire for users of the District Nursing Service in Clywd. During the qualitative phase 18 quality themes were identified. These were used to construct a draft questionnaire. Respondents were to rate their experience of the service (experience scale) as well as the importance to them of each service feature listed (importance scale). Following pilot testing and item analysis the importance scale was dropped. Factor analysis of the resulting 11-item questionnaire yielded four factors, similar to those identified in other studies. Makes some suggestions to improve the reliability and practical utility of the questionnaire, and describes its use in Clwyd.

Aged↗
PubMed1997

Subordinate appraisal of managers: "testing the theory".

Identifies the qualities of "ideal" line manager as perceived by three groups of professionals allied to medicine. Makes explicit the research methodology used to gather data, and reports the findings. Surveys three groups of professionals allied to medicine (PAM), namely, speech therapists, social workers (child health and adult physical health) and clinical psychologists. Offers an analysis of the data and draws some conclusions. Concludes with a reflection on the significance of the findings.

Allied Health Personnel↗
PubMed1997

Subordinate appraisal of managers: a useful tool for the NHS.

Problems in recruiting and retaining professional staff are an ongoing concern to many NHS Trusts and professional heads of service. There is evidence from a wide variety of sources that direct line managers are frequently cited as a source of worker's stress and a cause of staff turnover. Reviews these issues and suggests subordinate appraisal of managers as one possible response.

Employee Performance Appraisal↗
PubMed1997

Bridging the skull: electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) in psychiatry.

A brief account of repetitive transcranial magnetic stimulation (rTMS) with reference to electroconvulsive therapy (ECT) is given, identifying similarities and dissimilarities, and discussing their potential therapeutic roles. The insulating properties of the skull prevent specific, noninvasive stimulation of particular brain regions by direct electrical means. ECT allows electrical stimulation of the cortex, but its concomitant seizures and distributed electrical currents can have adverse effects on patients. By contrast, magnetic fields pass almost without attenuation through the skull, and can induce secondary electrical currents in localized areas of the brain. Subconvulsive rTMS does not require seizure or general anesthetic, and does not affect memory. Recent studies suggest that rTMS has therapeutic potential for mood disorders, for which ECT is well established. rTMS is a new technology with the potential to treat some mental disorders currently treated with ECT, with fewer side effects. ECT will almost certainly remain the treatment of choice in some situations, but ECT and rTMS may be alternatives for other patients. It is possible that rTMS will become established in some areas where ECT is not used. Further research will define these roles and evaluate the utility of rTMS.

Brain↗
PubMed1996

Antigen receptors on immature, but not mature, B and T cells are coupled to cytosolic phospholipase A2 activation: expression and activation of cytosolic phospholipase A2 correlate with lymphocyte maturation.

The Ag receptors on mature B and T cells are not coupled to the activation of cytosolic phospholipase A2 (cPLA2) and arachidonic acid release. Moreover, phorbol esters such as PMA, which can activate cPLA2 via mitogen-activated protein (MAP) kinase in most cell types, also failed to induce the release of arachidonate from mature cells, suggesting that the cPLA2 pathway may not be functional in mature lymphocytes. Interestingly, Western blot analysis revealed that cPLA2, which had previously been thought to be expressed ubiquitously, is not expressed in mature B or T cells and that cytosolic phospholipase A2 expression could not be up-regulated in lymphocytes following culture with a range of cytokines most likely to be involved in an immune response such as IL-1 alpha, IL-3, or TNF-alpha. In contrast, cPLA2 was shown to be expressed and activated in thymocytes and immature B cells under conditions in which ligation of the Ag receptors led to growth arrest and/or apoptosis. Taken together, these data suggest that cPLA2 does not play a role in Ag receptor-mediated lymphocyte activation, but may be involved in the molecular mechanisms underlying lymphocyte maturation and/or self tolerance by clonal deletion.

Animals↗
PubMed1996

Effects of regular salmeterol on lung function and exercise capacity in patients with chronic obstructive airways disease.

BACKGROUND: The aim of this study was to evaluate the effects of single and chronic dosing with salmeterol on exercise capacity and lung function in patients with chronic obstructive pulmonary disease. METHODS: Twenty nine patients of mean (SE) age 64 (1.5) years, forced expiratory volume in one second (FEV1) 42(3)% of predicted, and 5-15% reversibility to salbutamol 200 micrograms were randomised to receive four weeks treatment with salmeterol 50 micrograms twice daily or placebo in a double blind crossover fashion with a one week washout period in between. Measurements of spirometric parameters, static lung volumes, and exercise capacity were made one and six hours after a single dose, and six hours after the final dose of salmeterol or placebo. RESULTS: Salmeterol produced a small increase in FEV1 at one and six hours after a single dose, and this was maintained after chronic dosing (mean difference and 95% CI versus placebo): single dosing at one hour 0.07 (95% CI 0.02 to 0.11) 1, single dosing at six hours 0.16 (95% CI 0.09 to 0.22) 1, chronic dosing at six hours 0.11 (95% CI 0.03 to 0.19) 1. The increase in forced vital capacity (FVC) was greater with salmeterol than with placebo six hours after single but not chronic dosing: single dosing at six hours 0.17 (95% CI 0.04 to 0.29) 1, chronic dosing at six hours 0.02 (95% CI -0.18 to 0.22) 1. Slow vital capacity was increased after treatment with salmeterol compared with placebo one and six hours after single but not after chronic dosing. There were no significant differences in static lung volumes or exercise capacity after single or chronic dosing with salmeterol compared with placebo. Patients reported a significantly lower Borg score for perceived exertion following the six minute walk after chronic treatment with salmeterol compared with placebo. CONCLUSIONS: Salmeterol produced a small improvement in spirometric values compared with placebo consistent with the degree of reversibility originally shown by the subjects to salbutamol 200 micrograms. This was not associated with improvements in static lung volumes or exercise capacity, but there was some symptomatic benefit in that patients were able to walk the same distance in six minutes with less perceived exertion.

Albuterol↗
PubMed1996

Occupational disease trends in black South African gold miners. An autopsy-based study.

The change in prevalence in silicosis and pulmonary tuberculosis in black South African gold miners dying from unnatural causes from 1975 to 1991 was studied. Data were analyzed for 16,454 black gold miners. Information on age at death, duration of service, year of autopsy examination, and the prevalence of silicosis and tuberculosis was collected. Analyses were done to assess secular trends in the prevalence of tuberculosis and silicosis, and to determine predictors of the diseases at death. The prevalence of tuberculosis increased from 0.9% in 1975 to 3.9% in 1991. The prevalence of silicosis increased from 9.3% to 12.8%. The prevalence of both diseases increased with age and duration of service. Silicosis was the most significant predictor of tuberculosis (odds ratio [OR] = 1.78, confidence limits [CL] = 1.27 to 2.30). A significant trend for tuberculosis, for year of autopsy, remained after adjustment for the other variables in the model, such as age and duration of service (p = 0.0046). In view of current labor stabilization in the South African mines, one can expect further increases in the prevalence of tuberculosis and silicosis. Lowering of dust levels in the mines is urgently required to prevent the increase of disease burden.

Adolescent↗
PubMed1995

Sleep difficulties and their management in preschoolers with atopic eczema.

Sleep disruption is known to be common in preschool children. Those with atopic eczema (AE) would seem to be at particular risk because of itching. In this preliminary survey parents confirmed clinical impressions that sleep loss is a common feature when a child's atopic eczema is flaring. Sleep disturbance was reported by parents for 86% of the relevant nights with an average of 2.7 wakings per night and an average parental sleep loss of 2.6 h per night. Parents used a common core of strategies to help their children sleep at these times. Some of the strategies employed are likely to perpetuate sleep disturbance beyond the time of the flare. Parents gained most benefit from their own idiosyncratic approaches. For the majority of children (59%) sleep disruption is limited to times when their AE is flaring.

Acute Disease↗
PubMed1995

Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds.

Some human chronic dermal wounds treated with recombinant platelet-derived growth factor-BB (rPDGF-BB) show increased healing coupled with fibroblast activation and granulation tissue formation. To determine whether endogenous PDGF is associated with healing and nonhealing dermal ulcer phenotypes, we developed monoclonal antibodies capable of recognizing the three isoforms of PDGF, AA, AB, and BB dimers, and capable of discriminating between two alternatively spliced A chain transcripts. We detected little PDGF isoform expression in normal skin and in nonhealing dermal ulcers. In contrast, in surgically created acute wounds and chronic ulcers treated with rPDGF-BB, markedly upregulated levels of PDGF-AA (long form) were found. In both types of wounds, increased PDGF-AA was detected primarily in capillaries and fibroblasts, although in rPDGF-BB-treated chronic wounds, widespread expression of PDGF-AA was somewhat delayed. With continued treatment, the long form of PDGF-AA, which can preferentially bind extracellular matrix, was expressed only in capillaries, while fibroblasts began synthesizing the short form of PDGF-AA. Within capillaries, all endothelial cells and varying numbers of pericytes and smooth muscle cells contained PDGF-AA. In all wounds, macrophages and keratinocytes were not a major contributor. While PDGF-BB and PDGF-AB were present in a minority of healing wounds, they were usually present at lower levels than PDGF-AA. PDGF-beta receptors, which bind only PDGF-BB and not other isoforms, were found in normal skin and granulation tissue, providing a molecular basis for treating human chronic wounds with exogenous rPDGF-BB.

Adult↗
PubMed1995

A preliminary investigation of what happens to women complaining of menorrhagia but whose complaint is not substantiated.

This observational follow-up study determined the outcome, after a minimum of 3 years' follow up, in women complaining of excessively heavy menses, whose measured blood loss was within the normal range. Of the 81.7% of women followed up, 26% were happy with their periods, 19% were menopausal or taking hormone replacement therapy, 18% were taking a variety of other medical therapies and 28% had undergone surgery. The remainder were pregnant, lactating, or attempting conception. The decision to treat is not solely based on measured blood volume. Some women are intent upon an end to menstruation or have additional indications for surgical intervention. Others are happy with the reassuring knowledge that their menstrual blood loss is normal.

Adaptation, Psychological↗