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Biomedical subjects

L Wright

Publications and source records attributed to L Wright.

At least 55 records · Page 3Linked to original sources
PubMed1998

Evaluation of acute physiology and chronic health evaluation III predictions of hospital mortality in an independent database.

OBJECTIVE: To assess the accuracy and validity of Acute Physiology and Chronic Health Evaluation (APACHE) III hospital mortality predictions in an independent sample of U.S. intensive care unit (ICU) admissions. DESIGN: Nonrandomized, observational, cohort study. SETTING: Two hundred eighty-five ICUs in 161 U.S. hospitals, including 65 members of the Council of Teaching Hospitals and 64 nonteaching hospitals. PATIENTS: A consecutive sample of 37,668 ICU admissions during 1993 to 1996; including 25,448 admissions at hospitals with >400 beds and 1,074 admissions at hospitals with <200 beds. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used demographic, clinical, and physiologic information recorded during ICU day 1 and the APACHE III equation to predict the probability of hospital mortality for each patient. We compared observed and predicted mortality for all admissions and across patient subgroups and assessed predictive accuracy using tests of discrimination and calibration. Aggregate hospital death rate was 12.35% and predicted hospital death rate was 12.27% (p =.541). The model discriminated between survivors and nonsurvivors well (area under receiver operating curve = 0.89). A calibration curve showed that the observed number of hospital deaths was close to the number of deaths predicted by the model, but when tested across deciles of risk, goodness-of-fit (Hosmer-Lemeshow statistic, chi-square = 48.71, 8 degrees of freedom, p< .0001) was not perfect. Observed and predicted hospital mortality rates were not significantly (p < .01) different for 55 (84.6%) of APACHE III's 65 specific ICU admission diagnoses and for 11 (84.6%) of the 13 residual organ system-related categories. The most frequent diagnoses with significant (p < .01) differences between observed and predicted hospital mortality rates included acute myocardial infarction, drug overdose, nonoperative head trauma, and nonoperative multiple trauma. CONCLUSIONS: APACHE III accurately predicted aggregate hospital mortality in an independent sample of U.S. ICU admissions. Further improvements in calibration can be achieved by more precise disease labeling, improved acquisition and weighting of neurologic abnormalities, adjustments that reflect changes in treatment outcomes over time, and a larger national database.

APACHE↗
PubMed1998

5-Lipoxygenase and 5-lipoxygenase activating protein (FLAP) immunoreactivity in lungs from patients with primary pulmonary hypertension.

Inflammatory infiltrates and endothelial cell proliferation have been appreciated in plexiform and concentric lesions, which characterize the vascular remodeling in primary pulmonary hypertension (PPH). Leukotriene production by perivascular and alveolar macrophages relies on activation of 5-lipoxygenase (5-LO), with translocation of the enzyme to the nuclear membrane, and association with the 5-LO activating protein (FLAP). Using immunohistochemical staining, we localized and semi-quantitatively estimated the abundance of 5-LO and FLAP in lungs obtained from patients with PPH, patients with interstitial lung disease (ILD), and normal control subjects. Expression of 5-LO and FLAP was prominent in alveolar macrophages in both the normal and PPH lungs; however, alveolar macrophages were more frequently clustered in the vicinity of remodeled blood vessel in PPH. Medium- and small-size pulmonary arteries in PPH showed more abundant FLAP expression than in control and ILD lungs. 5-LO expression in small arteries in PPH was more intense than in control and ILD patients. Endothelial cells in plexiform and concentric lesions in PPH expressed both 5-LO and FLAP. In situ hybridization confirmed the presence of 5-LO transcripts in macrophages and endothelial cells of the remodeled vessels in PPH. We propose that the overexpression of 5-LO and FLAP represents evidence for the participation of inflammation in the process of PPH vasculopathy or, alternatively, that the overabundance of the enzymes involved in generation of inflammatory mediators may themselves be related to vascular cell proliferation and cell growth.

5-Lipoxygenase-Activating Proteins↗
PubMed1998

Primary pulmonary hypertension between inflammation and cancer.

We believe that the monoclonal cell expansion in primary pulmonary hypertension is the result of autonomous growth of stem cell-like endothelial cells, whereas the polyclonal proliferation in secondary pulmonary hypertension occurs as a response of endothelial cells to exogenous stimuli (like viral infection or high shear stress). In this context, we propose that different transcriptional and translational events govern the growth and expansion of monoclonal when compared with polyclonal pulmonary endothelial cells. The availability of antibodies directed against specific tyrosine kinase proteins involved in vasculogenesis/angiogenesis now permits the identification and localization of the components of such a misguided angiogenesis cell proliferation program in the pulmonary hypertensive vascular lesions.

Animals↗
PubMed1998

Outcome measurement in adult stuttering therapy: a self-rating profile.

The speech and language therapy profession is committed to the use of outcome measurement to maximise both efficiency and efficacy. However, measuring change in adult stuttering therapy is particularly problematic. It is proposed that outcomes of therapy should include stuttering behaviours, reactions to stuttering and handicap resulting from stuttering. Current methods of measuring change are reviewed. The Wright & Ayre Stuttering Self-Rating Profile (WASSP) is described which includes clients' perceptions of stuttering behaviours, avoidance, feelings and disadvantage. Issues of reliability and validity are considered.

Adult↗
PubMed1998

The role of the general practitioner in the community care of people with HIV infection and AIDS: a comparative study of high- and low-prevalence areas in England.

BACKGROUND: Policy for the care of people suffering from HIV and AIDS has changed over the past decade. Schemes for shared primary and secondary care have been met with varying success, and patients may be reluctant to become involved. No systematic evaluation comparing the views of primary care providers and users in areas of varying HIV prevalence has been published. AIM: To examine the role of general practice in areas of England with low and high human immunodeficiency virus (HIV) prevalence and to compare barriers to general practice care in each area. METHOD: We used focus groups, semistructured questionnaires and interviews in north London (high HIV prevalence) and Nottingham (low HIV prevalence). RESULTS: Four focus groups took place in London. A total of 411 general practitioners (GPs) in London and 405 in Nottingham replied to postal questionnaires. Overall, 121 primary care staff in 40 London practices and 26 staff in five Nottingham practices were interviewed. In all, 54 people infected with HIV were interviewed in London and 20 in Nottingham. Providers and users regarded the 24-hour availability and the familiar environment of general practice as its key assets. Lack of expertise and time were its disadvantages. Providers were concerned about inadequate communication with specialist services. Although providers were concerned about confidentiality, whether they had liberal and sympathetic attitudes was more important in deciding whether people with HIV used the service. In the low-prevalence area, general practice involvement was the result of individual initiatives, and practices were not integrated into specialist care. In the high-prevalence area, HIV care was more usual in general practice, but there was also little integration with HIV services. CONCLUSIONS: In high-prevalence districts, a strategy to make HIV care routine for all GPs may be appropriate. In low-prevalence areas, a network of selected, strategically located, relatively high-involvement practices may be more effective in meeting the primary care needs of people with HIV infection and acquired immunodeficiency syndrome (AIDS).

Community Health Services↗
PubMed1997

Characterization of pigs transgenic for human decay-accelerating factor.

BACKGROUND: To prevent the central role played by complement activation in the hyperacute rejection of pig organs transplanted into primates, pigs transgenic for human decay-accelerating factor (HDAF) have recently been produced. The data presented here extend previous immunohistochemical findings by documenting the immunological characterization and the levels of expression of HDAF in these transgenic pigs. METHODS: Animals from 30 independently derived lines were included in this study. HDAF expression was characterized by immunoprecipitation and epitope mapping. Quantitative analysis was performed by radiometric assays followed by Scatchard analysis and by double-determinant radioimmunoassay. Deposition of iC3b on porcine aortic endothelial cells was determined by radioimmunoassay. DNA slot-blot analysis and densitometric scanning were used to evaluate HDAF transgene copy number. RESULTS: The integrity of HDAF expressed by these transgenic pigs could be demonstrated. HDAF was present in 72% of the organs analyzed, although considerable variation in expression occurred, both between animals and within the same pig. High levels of HDAF on porcine aortic endothelial cells resulted in iC3b deposition at levels as low as that detected on human endothelial cells. Twenty-six organs expressed levels of HDAF greater than those observed in the equivalent human tissue. HDAF expression did not correlate with the number of copies of the transgene incorporated into the porcine genome. CONCLUSIONS: Transgenic pigs, which express levels of functional HDAF even greater than those observed in humans, have successfully been produced. Pigs transgenic for human complement inhibiting molecules could represent a source of organs for future clinical xenotransplantation.

Animals↗
PubMed1996

Expression of glutamyl-tRNA reductase in Escherichia coli.

The biosynthesis of the hemes, chlorophylls, corrins and other tetrapyrroles begins with the synthesis of 5-aminolevulinic acid (ALA). The pathway is highly conserved except for the synthesis of ALA which is derived from glycine and succinyl CoA (C4) in most eukaryotes and from glutamate (C5) in most bacteria and in green plants. In C5, glutamyl-tRNA synthetase (GTS) converts glutamate to glutamyl-tRNA (glu-tRNA), which is reduced by glutamyl-tRNA reductase (GTR) to glutamyl-1-semialdehyde (GSA), which is converted by aminotransferase (GSA-AT) to ALA. Since GTS is also involved in protein synthesis and GSA can be converted to ALA non-enzymatically, it is highly probable that control of ALA synthesis and thus of the whole pathway resides in the GTR step. In Escherichia coli, GTR is the gene product of hemA. BL21(DE3), a protease-deficient strain which contains the T7 RNA polymerase gene in front of a lac promoter, was transformed with a pET14b-based vector, pWC01, harboring hemA in front of a T7 promoter and ORF1 which is transcribed in the opposite direction. The transformed strain, WC1201, secreted ALA and porphyrins into the medium. Induction of expression of hemA by WC1201 was optimized for concentration of inducer (IPTG, 5 mM), temperature (37 degrees C), presence of betaine and sorbitol (no change) and time of induction (2h). GTR was observable as a 46 kDa band by Brilliant blue G staining of SDS-PAGE gels. Sonicates of the induction mixture exhibited strong ALA synthesis activity which was enhanced by tRNAglu. Most of the activity was in the supernatant of the sonicate indicating that GTR is a soluble enzyme. The induced strain had more GTS activity than the uninduced strain which had more GTS activity than its parent wild-type strain. Autoradiography on native gradient PAGE showed that GTR expressed in vivo by induction of WC1201 had a molecular weight of approx. 117 kDa. Gel filtration of the induced sonicate showed a peak of enzymatic activity at about 126 kDa. When pET14b- or pUC19-based plasmids harboring hemA and ORF1, or importantly, a pUC19-based plasmid harboring only hemA and not ORF1, were expressed in an in vitro transcription-translation system, native gradient PAGE showed a product with a molecular weight of approximately 175 kDA. This expression was higher in the presence of tRNAglu. When the 117 kDa and 175 kDa proteins were excised from their native gels respectively, and run on SDS PAGE, autoradiography showed bands at 46 kDa. We conclude that GTR is present in both high molecular weight species. Since overexpression of hemA from pET14b-based plasmids is associated with increased glutamyl-tRNA synthetase activity, the 175 kDa species may represent different complexes of GTR, GTS and glutamyl-tRNA as observed in Chlamydomonas and the 117-126 kDa species may be an dimer of GTR associated with glu-tRNA or a complex of GTR, GTS and glu-tRNA. These possibilities are being investigated.

Aldehyde Oxidoreductases↗
PubMed1996

Evidence for the sensitivity of the SF-36 health status measure to inequalities in health: results from the Oxford healthy lifestyles survey.

OBJECTIVES: The short form 36 (SF-36) health questionnaire may not be appropriate for population surveys assessing health gain because of the low responsiveness (sensitivity to change) of domains on the measure. An hypothesised health gain of respondents in social class V to that of those in social class I indicated only marginal improvement in self reported health. Subgroup analysis, however, showed that the SF-36 would indicate dramatic changes if the health of social class V could be improved to that of social class I. DESIGN: Postal survey using a questionnaire booklet containing the SF-36 and a number of other items concerned with lifestyles and illness. A letter outlining the purpose of the study was included. SETTING: The sample was drawn from family health services authority (FHSA) computerised registers for Berkshire, Buckinghamshire, Northamptonshire, and Oxfordshire. SAMPLE: The questionnaire was sent to 13,042 randomly selected subjects between the ages of 17-65. Altogether 9332 (72%) responded. OUTCOME MEASURES: Scores for the eight dimensions of the SF-36. STATISTICS: The sensitivity of the SF-36 was tested by hypothesising that the scores of those in the bottom quartile of the SF-36 scores in class V could be improved to the level of the scores from the bottom quartile of SF-36 scores in class I using the effect size statistic. RESULTS: SF-36 scores for the population at the 25th, 50th, and 75th centiles were provided. Those who reported worse health on each dimension of the SF-36 (ie in the lowest 25% of scores) differ dramatically between social class I and V. Large effect sizes were gained on all but one dimension of the SF-36 when the health of those in the bottom quartile of the SF-36 scores in class V were hypothesised to have improved to the level of the scores from the bottom quartile of SF-36 scores in class I. CONCLUSIONS: Analysis of SF-36 data at a population level is inappropriate; subgroup analysis is more appropriate. The data suggest that if it were possible to improve the functioning and wellbeing of those in worst health in class V to those reporting the worst health in class I the improvement would be dramatic. Furthermore, differences between the classes detected by the SF-36 are substantial and more dramatic than might previously have been imagined.

Adolescent↗
PubMed1995

Regulation of the complement cascade by soluble complement receptor type 1. Protective effect in experimental liver ischemia and reperfusion.

The complement cascade was inactivated in a model of rat liver ischemia with the purpose of studying the role of complement in tissue injury after ischemia and reperfusion. Soluble human complement receptor type 1 (sCR1) was administered either in a single dose of 25 mg/kg or in 2 doses of 50 mg/kg i.v. over 24 hr after vascular occlusion. Sham-operated rats, nontreated rats submitted to liver ischemia, and rats pretreated with cobra venom factor and submitted to liver ischemia were used as controls. This experiment consists of the temporary interruption of arterial and portal blood flow to the left lateral and medial lobes of the liver for 45 min, followed by a 24-hr period of follow-up after reperfusion. Liver blood flow and hemoglobin saturation were recorded for 1 hr after declamping, with statistically significant differences between the experimental groups and the untreated control group, which received liver ischemia (P < 0.001). At 24 hr, galactose elimination was assayed as a liver function test; it was significantly better in the sCR1-treated rats when compared with control rats submitted to ischemia (P < 0.01). Alanine aminotransferase levels were also significantly lower in the sCR1-treated rats at 6 and 24 hr (P < 0.05). Complement activity was reduced to 25% and 12.5% of normal rats with the respective doses of sCR1. Immunoperoxidase stainings for C3 and C9 were performed on liver sections; they showed endothelial deposits of C3 and C9 in the control group subjected to ischemia. Few C3 deposits were present in the sCR1 (25 mg/kg)-treated rats, but not in the cobra venom factor or sCR1 (50 mg/kg) groups. These results confirm that complement is inactivated by sCR1 with amelioration of reperfusion injury in the rat liver.

Animals↗
PubMed1995

The relationship of various measures of time urgency to indices of physical health.

The degree of association with two general health indices was assessed for three separate measures of time urgency. The Speed and Impatience subscale of the Jenkins Activity Survey was found to have no significant relationships with the health indices. The Time Urgency/Perpetual Activation (TUPA) scale, as well as the Irritability and Impatience scale, did correlate in comparable ways with a majority of the health indicators. A very brief, 2-item impatience subscale of the Irritability and Impatience Scale also correlated with health indices in essentially the same manner as the complete Irritability and Impatience Scale and the TUPA Scale. It was concluded that because of its convenience of administration, the very brief 2-item impatience subscale of the Irritability and Impatience Scale may constitute the instrument of choice for assessing time urgency as it relates to noncardiovascular health. A question is raised regarding whether anger and time urgency constitute separate factors or are aspects of a single behavioral trait.

Adolescent↗
PubMed1995

Evaluation of children's sexual behaviors and incorporation of base rates in judgments of sexual abuse.

One hundred sixty-one professionals and 97 undergraduates were asked to (a) prioritize 12 hypothetical CPS cases on the basis of sexual behaviors displayed by children, and (b) estimate the probability of abuse in a single case involving a child who had displayed sexual behavior and came from a population with a known base rate of abuse. When asked to prioritize the 12 cases as "high," "medium," or "low" on the basis of sexual behaviors, professionals were more accurate than students. However, when asked to estimate the probability of abuse in the single case, both professionals and students failed to incorporate base rate information into their decisions. As a result, both groups misestimated the probability of abuse under some circumstances. Professionals' performance on both judgment tasks was unrelated to level of experience with sexual abuse cases.

Adult↗
PubMed1995

The control of hyperacute rejection by genetic engineering of the donor species.

Activation of endogenous complement is inhibited both in the soluble phase and at the membrane surface by a group of structurally similar proteins. A possible solution to hyperacute rejection is to produce donor animals transgenic for human complement regulators. 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. Hyperacute rejection of discordant organ xenografts is mediated by human complement. A 6.5 kilobase minigene for DAF has been microinjected into porcine fertilised ova. Forty-five pigs transgenic for human DAF have been produced. Of these, 65% transcribe message. The amount of message produced varied substantially from animal to animal and was independent of copy number integrated. Expression of human DAF on the porcine lymphocyte surface could be detected and this was able to downregulate human complement activation. Amounts of protein expressed on different tissues varied both from pig to pig and within animals from tissue to tissue. The pigs grow and develop normally with no evidence of ill effects due to possession of the transgene.

Animals↗
PubMed1994

The factor analytic structure of seven physical CHD risk factors: a replication study.

An attempt was made to replicate the results of an earlier confirmatory factor analysis of the seven traditionally employed physical risk factors for CHD. As with the first investigation, a two-factor solution was confirmed; only family history loaded on factor 1; the remaining six risk variables (smoking, serum cholesterol, blood pressure, diet, exercise, and weight control) comprised factor 2. These findings may reflect a broad personality trait, i.e., generalized lack of self-control, which could underlie much CHD risk not associated with a family history of heart disease. Implications are drawn for research and practice in the areas of cardiac rehab and prevention.

Adult↗