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Biomedical subjects

L Wright

Publications and source records attributed to L Wright.

At least 73 records · Page 4Linked to original sources

Criterion validity and reliability of the SF-36 in a population sample.

This study aimed to determine the criterion validity of the Short Form 36 health survey questionnaire (SF-36) in a large community sample, and to explore the instrument's internal consistency and validity in groups reporting different levels of ill-health. A postal survey was undertaken using a questionnaire booklet, containing the SF-36 and a number of other items concerned with lifestyles and illness. The questionnaire booklet was sent to 13,042 randomly selected subjects between the ages of 18-64 years, drawn from Family Health Services Authority (FHSA) computerized registers for Berkshire, Buckinghamshire, Northamptonshire and Oxfordshire. This paper is based upon the 9332 (72%) responses gained. Scores for the functional status and well-being scales of the SF-36 were used as outcome measures. The response rate for the questionnaire booklet was 72%. Internal consistency of domains was found to be high, both for the sample as a whole, and when broken down by specific subgroups. Criterion validity was assessed by comparing scores for the seven multi-item dimensions assessing functional status and well being with a single global health question. The global question was the first item of the SF-36 and asks respondents to evaluate their health 'overall'. Statistically significant trends were observed for decreasing SF-36 scores (i.e., those indicating greater health problems) with worsening self-rated general health. These results provide further psychometric evidence for the use of the SF-36 when used with groups reporting varying extents of ill-health.

Adolescent↗

Cytokine activity after allogeneic bone marrow transplantation. V. Analysis of IL-2 and IFN production by isolated CD4+ and CD8+ cells.

Previous studies from this laboratory have shown that PBMC from recipients of an HLA-identical sibling bone marrow transplant produce levels of IL-2 which are 10-100-fold lower than those produced by the same number of PBMC from healthy controls, whereas production of IFN-gamma is normal. The present study examined IL-2 and IFN production over a range of cell numbers for PBMC and for isolated CD4+ and CD8+ cells for controls and marrow transplant recipients. There was a 5-fold lower IL-2 production in marrow transplant recipient CD8+ cells compared with equivalent numbers of control cells, whereas no difference was found in IL-2 production by CD4+ cells. In contrast, IFN production by CD4+ cells from marrow transplant recipients was 4-fold higher than in controls, whereas CD8+ cells from both populations produced similar amounts of IFN. When the observed production of cytokine by PBMC was compared with the expected production based on the CD4+ and CD8+ content of the PBMC, control values were similar, but the expected values for both cytokines were approximately 2-fold higher than the observed values for marrow transplant recipients. The results suggest that the capacity of T cells from marrow transplant recipients to produce IL-2 and IFN is not impaired, but that the frequency of cytokine-producing cells may be reduced, and that a negative interaction present in recipient PBMC, eliminated by isolating T-cell subsets, is responsible for the observed low levels of cytokine production.

Adult↗

Validation of a single point flow cytometric assay for determining P-glycoprotein activity in multidrug resistant cell lines.

P-glycoprotein, a transmembrane protein which acts as an energy dependent efflux pump, has been implicated as one mechanism of multidrug resistance (MDR) in human tumours. Commonly employed assays measure P-glycoprotein immunohistochemically or mdr1 messenger RNA. In this study we compared a single point flow cytometric assay for determining activity of P-glycoprotein with cellular expression of P-glycoprotein determined by Western blot. Five cell lines, with varying levels of multiple drug resistance, were incubated with daunorubicin (DNR) in the presence (treated) and absence (control) of cyclosporine or verapamil, agents known to inhibit the activity of P-glycoprotein. The treated cell lines, along with non-treated controls were examined for intracellular concentrations of DNR measured by fluorescence intensity using a flow cytometer. The ratio of fluorescence intensity expressed in the treated/control was used as an index of functional activity of P-glycoprotein. Functional activity of the P-glycoprotein as determined by flow cytometry correlates highly with cellular content of P-glycoprotein measured by western blot (correlation coefficients of r = 0.90-0.98 for the various cell line combinations). This method represents a rapid single point flow cytometric assay which may be suitable for screening clinical samples for P-glycoprotein activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Stuttering therapy with British-Asian children. I: A survey of service delivery in the United Kingdom.

The results of a UK survey of speech and language therapy services offered to Asian children and adolescents who stutter are set in the context of current therapy approaches favoured in the UK. Eighty-seven speech and language therapists from the major centres of Asian population in the UK completed a postal questionnaire. This yielded data on: service delivery to stuttering children in general; the size and nature of the Asian populations served; therapists' own cultural backgrounds; steps taken by therapists to increase their skill in this area; interpreter services available; changes made to usual working practices aimed at accommodating the cultural needs of Asian clients. The results revealed a service mostly provided by non-specialist therapists, who treated small numbers of both stuttering and Asian clients. Therapists were serving clients from up to four different cultural and linguistic backgrounds, yet access to interpreter services was poor. Therapists were on the whole poorly trained and equipped to treat Asian clients. A range of changes to working practices are described, but no cohesive approach was apparent. The issues involved in appropriate and accessible service delivery are discussed.

Adolescent↗

Stuttering therapy with British-Asian children. II: Speech and language therapists' perceptions of their effectiveness.

This paper tested hypotheses arising from the literature on the treatment of stuttering in British-Asian children and adolescents, using data obtained from a postal questionnaire completed by 87 therapists. The results showed therapists treating lower numbers of Asian clients than expected, but perceiving their therapy to be less effective with their Asian clients than with their British ones. The variables affecting therapists' perceived success were not those expected. Greater experience with Asian clients did not increase perceived success, nor did Asian therapist and client sharing broadly the same cultural background guarantee success. A satisfactory interpreter service did not lead to a higher perceived success rate, nor did postgraduate training or making special changes to usual working practices. On the contrary, therapists in the last two categories were less likely to perceive success with their Asian clients. Therapists identified a very wide range of cultural factors needing special consideration in therapy, but consensus centred around parental attitudes to stuttering and to therapy.

Adolescent↗

Differences between American Indian and non-Indian children referred for psychological services.

The physical and social characteristics of 60 American Indian children referred for psychological services were compared to those of 60 matched, non-Indian controls. Data were obtained from detailed records available in a multidisciplinary, medical school-related child study clinic. Indian children exhibited more health and social risk factors, but were superior to non-Indians on a variety of motor variables. Interpretations are offered concerning better psychological services for American Indian children based on better understanding of their possible exposure to physical health and social risks which may be related to psychological development.

Adolescent↗

Detection and prevention of treatable visual failure in general practice: room for improvement?

An ageing population, the introduction of sight test charges and a problem that has never been adequately addressed since the inception of the National Health Service presents general practitioners with the increasing burden of detecting and preventing visual failure which they feel poorly equipped to deal with. Ophthalmology in general practice is a fundamental requirement for the reduction of avoidable visual failure and this is probably especially true for elderly patients and diabetic patients. A postal survey of general practitioners in Brent and Harrow suggests that there is potential for major improvements in the delivery of eye care by general practitioners, often without much additional expenditure (the equipment is there but it is not used) and with minimal training requirements. Simple changes in already existing screening programmes could potentially have an immediate effect on the visual well-being of the community.

Aged↗

Short form 36 (SF36) health survey questionnaire: normative data for adults of working age.

OBJECTIVES: To gain population norms for the short form 36 health survey questionnaire (SF36) in a large community sample and to explore the questionnaire's internal consistency and validity. DESIGN: Postal survey by using a booklet containing the SF36 and several other items concerned with lifestyles and illness. SETTING: The sample was drawn from computerised registers of the family health services authorities for Berkshire, Buckinghamshire, Northamptonshire, and Oxfordshire. SAMPLE: 13,042 randomly selected subjects aged 18-64 years. MAIN OUTCOME MEASURES: Scores for the eight health dimensions of the SF36. RESULTS: The survey achieved a response rate of 72% (n = 9332). Internal consistency of the different dimensions of the questionnaire was high. Normative data broken down by age, sex, and social class were consistent with those from previous studies. CONCLUSIONS: The SF36 is a potentially valuable tool in medical research. The normative data provided here may further facilitate its validation and use.

Adolescent↗

The VCOP Scale: a measure of overprotection in parents of physically vulnerable children.

A scale is developed for measuring the overprotecting vs. optimal developmental stimulation tendencies for parents of physically "vulnerable" children. A series of items were administered to parents whose parenting techniques had been rated as either highly overprotective or as optimal by a group of MDs and other professionals. Correlations were estimated between each of the items and parental tendencies as rated by professionals. Twenty-eight items were selected that provided maximum prediction of over-protection. The resulting R2 was extraordinarily high (.94). Coefficient alpha and test-retest coefficients were acceptable. It is hoped that release of the new instrument (VCOPS) at this time will allow others to join in determining the clinical and experimental validity of this scale.

Adolescent↗

Platelet activating factor (PAF) enhances mitosis in preimplantation mouse embryos.

Preimplantation mouse embryos were used to determine whether the reported significant increase in embryo metabolism and viability achieved through supplementation of the culture medium with the ether phospholipid 1-o-alkyl-2-acetyl-sn-glycero-3-phosphocoline (platelet activating factor, PAF) is attributable to an enhanced rate of mitosis. Blastocyst-stage embryos cultured in the presence of 0.186 to 18.6 microM exogenous PAF had a significantly (P < 0.01) higher mitotic index (the proportion of cells arrested in metaphase following incubation in colchicine) than those cultured without PAF. At the 8-cell stage, 29% more blastomeres were in metaphase in the PAF-treated group (P < 0.01) 8 h after the addition of colchicine, but by 16 h there was no difference between groups; thus, PAF increased the rate at which cells entered metaphase but did not increase the total number. The mitotic index showed a negative correlation with the number of cells within blastocysts. PAF had a significantly (P < 0.01) greater impact on the mitotic index of blastocysts with fewer cells. The action of PAF was specific, being completely blocked by the PAF-receptor antagonist WEB 2086 (33 microM). In the absence of exogenous PAF the mitotic index was lower with WEB 2086 than without, suggesting inhibition of the action of endogenous embryo-derived PAF. These results show that PAF stimulates the rates at which cells within the preimplantation mouse embryo enter metaphase in vitro and suggest that it would decrease their doubling time, perhaps accounting for the embryotrophic actions of PAF.

Animals↗

Prevalence of glaucoma in the west of Ireland.

County Roscommon in the west of Ireland is a relatively remote rural area whose population of 55,000 is served by two community medical ophthalmologists and three optometrists. Eye surgical services are not available within the county. In order to assess the needs of the community for prevention of blindness from glaucoma, a simple random sample of the population of County Roscommon was taken for a community based glaucoma survey. A total of 2186 people over the age of 50 were examined which represented a 99.5% response rate. The high response rate was achieved by the community basis of the study and vigorous follow up of non-attenders. Intraocular pressure was measured using applanation tonometry, disc evaluation by both direct ophthalmoscopy and stereoscopic biomicroscopy, and visual field analysis using the Henson CFS 2000 and experimental computer controlled video perimetry. Diagnostic criteria were consistent with the preferred practice pattern of the American Academy of Ophthalmology. A crude prevalence of approximately 2% for primary open angle and normal tension glaucoma was found. The population profile of intraocular pressure showed a pattern which decreased with increasing age unlike the Framingham and Ferndale studies but similar to Japanese data.

Age Factors↗

Ribozyme-mediated cleavage of the bcr/abl transcript expressed in chronic myeloid leukemia.

The bcr/abl transcript is specifically expressed in the hematopoietic cells of patients with chronic myeloid leukemia (CML). The Haseloff and Gerlach model was used to design a ribozyme targeted to this transcript. When tested against a synthetic substrate covering the translocation sequence, the ribozyme exhibited site specificity and an absolute requirement for divalent metal ions. Cleavage of the normal bcr was also noted but at a reduced efficiency compared to that exhibited for the bcr/abl substrate. Importantly, cleavage of the full-length bcr/abl mRNA was achieved at physiologic temperature, demonstrating effective ribozyme-mediated cleavage.

Base Sequence↗

Effect of serotonin and thromboxane A2 on blood flow through moderately well developed coronary collateral vessels.

This study was performed to determine whether thromboxane A2 (as the analogue U46619) and serotonin can cause vasoconstriction of moderately well developed coronary collateral vessels. Studies were carried out in seven adult mongrel dogs 2 to 4 months after embolic occlusion of the left anterior descending coronary artery had been performed to stimulate collateral vessel growth. At the time of study this artery was cannulated to determine interarterial collateral flow from measurements of retrograde blood flow. Radioactive microspheres were administered during retrograde flow collection to determine continuing tissue flow for evaluation of microvascular collateral communications. Serotonin (50 micrograms/min) resulted in a 48 +/- 11% decrease in retrograde flow (p less than 0.01), with a 36 +/- 10% decrease in total collateral blood flow (p less than 0.02). Infusion of U46619 (0.01 microgram/kg per min) caused a 38 +/- 13% decrease in retrograde blood flow (p less than 0.01), with a 34 +/- 13% decrease in total collateral flow (p less than 0.05). Serotonin caused a significant increase in tissue flow to the subepicardium of the collateral-dependent region, whereas U46619 caused no change in tissue blood flow. These data demonstrate that both serotonin and thromboxane A2 can cause vasoconstriction of interarterial coronary collateral vessels. The findings suggest that platelet activation in coronary arteries from which collateral vessels originate has potential for causing collateral vasoconstriction, thereby compromising blood flow to the dependent myocardium.

Animals↗

A factor analytic study of physical risk variables for CHD.

The scores of 40 hospitalized male coronary heart disease (CHD) patients, for seven traditionally employed physical CHD risk factors, were subjected to a confirmatory factor analysis that employed a LISREL program. An attempt was made to confirm a two-factor solution that involved family history as one factor, and smoking, serum cholesterol level, blood pressure, physical exercise, diet, and weight control as the second. The obtained goodness-of-fit index (.84) suggests that the two-factor solution is a moderately valid one. These findings raise the question whether many of the physical risk factors for CHD simply may be manifestations of a single behavioral characteristic, perhaps best described as "lack of self-control."

Adult↗

Are the physical and TABP risk factors for heart disease unique to CHD?

Scores of 40 hospitalized CHD patients on 11 Type A-related and 7 physical CHD risk factors were compared to those of 40 hospitalized non-CHD patients. Family history for CHD was the only physical risk factor for which a significant difference was found. CHD patients scored significantly higher on all seven interview-measured Type A and Type A subcomponent variables. Only two of the four Jenkins Activity Survey-measured Type A variables produced significant differences, with one higher for non-CHD subjects. It was concluded that some CHD risk scores also may be associated with other diseases, to the experience of being seriously ill, and/or to the experience of hospitalization.

Adult↗

Expression of human decay accelerating factor or membrane cofactor protein genes on mouse cells inhibits lysis by human complement.

Mouse cells expressing the human complement regulatory proteins decay accelerating factor (DAF) or membrane cofactor protein (MCP) were produced both by hybridoma technology and by transfection with the appropriate cDNAs. The expression of either or both of these products protected the mouse cell from lysis by human (though not rabbit) complement in the presence of naturally occurring human anti-mouse antibody. This effect could be abrogated by the addition of monoclonal antibody against DAF or MCP. These data suggested that the production of animals transgenic for human complement regulatory proteins should in principle be similarly protected from hyperacute xenograft rejection.

Animals↗

Inhibition of rejection of hamster-to-rat heart xenografts.

Prolonged survival of concordant organ xenografts as typified by hamster-to-rat heart transplants is difficult to produce. Studies have revealed that T cells are not primarily involved in rejecting such xenografts and that the rat recipients produce high titres of lytic anti-hamster antibodies. In this study, 200 hamster-to-rat cardiac xenografts performed in 30 different experiments revealed that cyclophosphamide (CyP) and cyclosporin A (CyA) could inhibit this antibody production. CyP alone was relatively ineffective in prolonging graft survival (the median survival time was 14 days versus 3 days in untreated controls). Combining CyP and CyA virtually abolished rejection in this model. Four critically timed doses of CyP combined with continuous CyA resulted in recipients not producing anti-hamster antibodies, despite cessation of CyP therapy, and prolonged graft survival time (median survival time was more than 100 days). Cessation of CyA at 60 and 100 days resulted in the rejection of the xenografts and the appearance of the rat anti-hamster antibodies. Xenografts in recipients given only one or two doses of CyP (and continuous CyA) had a median survival time of 7 and 12 days respectively. However xenograft rejection in rats given only 1 or 2 doses of CyP could be averted by complement depletion using a 3-week course of cobra venom factor (CoF) starting on day 4 or day 7 post-transplantation respectively. Discontinuation of CoF after 3 weeks did not result in graft rejection. These results showed that immunosuppressive therapies directed at inhibiting antibody production may be of value in preventing rejection of concordant xenografts. Short-term complement depletion could rescue xenografts from rejection such that rescued grafts appear to be accommodated.

Animals↗