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Biomedical subjects

E Ferguson

Publications and source records attributed to E Ferguson.

At least 37 records · Page 2Linked to original sources
PubMed2000

The surgical management of bacterial valvular endocarditis.

Bacterial endocarditis is an important cause of cardiac valvular problems. The diagnosis of bacterial endocarditis can be difficult, and, often, an aggressive clinical evaluation including serial blood cultures is necessary. The pathophysiology of endocarditis is changing with the rise of intravenous drug use; staphylococci are an increasingly common cause. Endocarditis often warrants surgical intervention. Operations for bacterial endocarditis range from valve repair to valve replacement to homograft replacement. The operations are technically challenging, but new methods of myocardial protection have markedly improved the surgical outcomes. Valve excision is an option for intravenous drug users with tricuspid valve endocarditis. Surgical management of endocarditis is a technically challenging but rewarding procedure that should be offered to appropriate patients.

Debridement↗
PubMed2000

Hypochondriacal concerns and the five factor model of personality.

Using data from two studies (Ns = 205 and 161), this article examines the associations between the domains of the five factor model of personality and hypochondriacal concerns (HCs). These associations are explored once covariation due to other related traits (somatosensory amplification) and comorbidity factors (anxiety, depression, and somatic symptom reporting) have been controlled. As predicted, emotional stability was associated with most criteria related to HCs and agreeableness was negatively associated with the perceived inadequacy of a physician's explanation. Conscientiousness was negatively associated with HCs. These associations remained after partialing the comorbidity factors and somatosensory amplification. The discussion focuses on the particular role of agreeableness and conscientiousness in relation to HCs.

Adolescent↗
PubMed2000

Pupils' causal attributions for difficult classroom behaviour.

BACKGROUND: Studies of causal attributions within educational contexts have tended to concentrate on academic performance. There have been a smaller number of investigations of teachers' attributions for pupils' behaviour in school. AIMS: The present study examines the causal attribution made by pupils for difficult behaviour in classrooms. It reveals the structure of these attributions and serves as a comparison with the teacher studies. SAMPLE: The participants were 105 pupils (52 males and 53 females) in the first year of secondary schooling, all drawn from the same inner city school. METHOD: Four initial small group interviews were used to identify a wide range of factors that pupils viewed as being causes of difficult classroom behaviour in the 18 primary schools they had previously attended. A questionnaire was then constructed incorporating items from these discussions and administered to the whole of the year group of pupils, but omitting the participants in the initial group discussions. RESULTS: The results of a factor analysis indicated that pupils' attributions for misbehaviour at school were best represented by four factors: (1) 'fairness of teacher's actions', (2) 'pupil vulnerability', (3) 'adverse family circumstances' and (4) 'strictness of classroom regime'. While there were no gender differences, pupils saw the 'fairness of teacher's actions' and 'pupil vulnerability' as more significant contributors to pupil misbehaviour than either 'adverse family circumstances' or 'strictness of classroom regime'. CONCLUSION: The attributions by pupils for difficult classroom behaviour differ markedly from those obtained in studies of teachers. Policy and practice initiatives which do not attend to conflicting attributional styles are unlikely to succeed in improving levels of pupil behaviour in schools.

Child↗
PubMed2000

Hypochondriacal concerns, somatosensory amplification, and primary and secondary cognitive appraisals.

This paper uses data from four studies (N = 150, 150, 154 and 79) to examine the associations between hypochondriacal concerns (HCs) and stress appraisals (primary and secondary). A search activity account of HCs suggests that increased levels of HCs should be associated with positive appraisals of a stressful situation (i.e., increased levels of perceived challenge and perceived control). However, the results indicated that in terms of primary appraisals, increased perceptions of threat and not challenge were consistently associated with increased levels of HCs. Further, the results indicated that the association between threat and HCs is mediated by somatosensory amplification. Consistent with the search activity account it is shown that increased levels of perceived control (secondary appraisals) are associated with increased levels of HCs. The association for perceived control remains once variance due to somatosensory amplification is partialled and generalizes to a sample of patients with a sexually transmitted infection. The results are interpreted in relation to the transactional model of the stress process.

Adult↗
PubMed2000

Associations between primary appraisals and life-events while controlling for depression.

OBJECTIVES: The main objective of this paper was to explore the associations between life-events and primary appraisals (threat, challenge and loss) controlling for depression. It was predicted that specific associations between life-events and primary appraisals would remain once depression had been partialled. A subgoal of this paper was to develop a content analytic coding frame for student life-events. DESIGN: This study was a retrospective survey in which participants provided accounts of recent stressful encounters, and completed indices of primary appraisals and depression. METHOD: The participants were 979 undergraduates who provided descriptions of life-events. A subsample of 391 provided additional information on primary appraisals and depression. The primary outcomes were the partial correlations between life-events and primary appraisals. RESULTS: There were significant associations between life-events and primary appraisals above and beyond variance explained by depression. Results also indicated that the definition of loss appraisals could be extended to include events that were related to anticipated future loss, especially if the event was also perceived as threatening. Also certain self-defined negative life-events were appraised as positive. Life-events were shown to vary systematically as a function of external constraints (e.g. stage of the academic year). CONCLUSIONS: A variety of events were associated with loss appraisals and this may have implications for risk factors in depression.

Adaptation, Psychological↗
PubMed2000

A competency model for general practice: implications for selection, training, and development.

BACKGROUND: The role of the general practitioner (GP) has changed significantly over the past decade. This problem is compounded by growing concern over postgraduate attrition rates from medicine, with current estimates as high as 19%. AIM: To define a comprehensive model of the competencies required for the job role of GP. METHOD: Three independent studies were conducted to define GP competencies including (1) critical incidents focus groups with GPs, (2) behavioural coding of GP-patient consultations, and (3) critical incidents interviews with patients. Study 1 was conducted with GPs (n = 35) from the Trent region. Study 2 involved observation of GP-patient consultations (n = 33 consultations), and Study 3 was conducted with patients (n = 21), all from a Midlands-based medical practice. RESULTS: The data collected from the three studies provided strong evidence for a competency model comprising 11 categories with a summary of the associated behavioural descriptions. Example competencies included empathy and sensitivity, communication skills, clinical knowledge and expertise, conceptual thinking, and coping with pressure. CONCLUSIONS: Triangulation of results was achieved from three independent studies. The competencies derived imply that a greater account of personal attributes needs to be considered in recruitment and training, rather than focusing on academic and clinical competency alone. The model could be employed for future research in design of selection techniques for the role of GP.

Clinical Competence↗
PubMed1999

Role of electrophilic and general base catalysis in the mechanism of Escherichia coli uracil DNA glycosylase.

Escherichia coli uracil DNA glycosylase (UDG) catalyzes the hydrolysis of premutagenic uracil bases in DNA by flipping the deoxyuridine from the DNA helix [Stivers, J. T., et al. (1999) Biochemistry 38, 952]. A general acid-base mechanism has been proposed whereby His187 facilitates leaving group departure by protonating the O2 of uracil and Asp64 activates a water molecule for nucleophilic attack at C1' of the deoxyribose. Detailed kinetic studies on the H187Q, H187A, and D64N mutant enzymes indicate that Asp64 and His187 stabilize the chemical transition state by 5.3 and 4.8 kcal/mol, respectively, with little effect on substrate or product binding. The pH dependence of k(cat) for wild-type and H187Q UDG indicates that an unprotonated group in the enzyme-substrate complex (pK(a) = 6.2 +/- 0.2) is required for catalysis. This unprotonated group has a small DeltaH of ionization (-0.4 +/- 1.7 kcal/mol) and is absent in the pH profile for D64N UDG, suggesting that it corresponds to the general base Asp64. The pH dependence of k(cat) for wild-type, H187Q, and D64N UDG shows no evidence for an essential protonated group over the pH range of 5.5-10. Hence, the pK(a) of His187 must be outside this pH range if it serves as an electrophilic catalyst. These results support a mechanism in which Asp64 serves as the general base and His187 acts as a neutral electrophile, stabilizing a developing negative charge on uracil O2 in the transition state. In the following paper of this issue we establish by crystallography and heteronuclear NMR spectroscopy that the imidazole of His187 is neutral during the catalytic cycle of UDG.

Asparagine↗
PubMed1999

Characterization of the adduct formed from the reaction between homocysteine thiolactone and low-density lipoprotein: antioxidant implications.

Homocysteine thiolactone is a cyclic thioester that is implicated in the development of atherosclerosis. This molecule will readily acylate primary amines, forming a homocystamide adduct, which contains a primary amine and a thiol. Here, we have characterized and evaluated the antioxidant potential of the homocystamide-low-density lipoprotein (LDL) adduct, a product of the reaction between homocysteine thiolactone and LDL. Treatment of LDL with homocysteine thiolactone resulted in a time-dependent increase in LDL-bound thiols that reached approximately 250 nmol thiol/mg LDL protein. The thiol groups of the homocystamide-LDL adduct were labeled with the thiol-reactive nitroxide, methanethiosulfonate spin label. Using paramagnetic relaxing agents and the electron spin resonance spin labeling technique, we determined that the homocystamide adducts were predominately exposed to the aqueous phase. The homocystamide-LDL adduct was resistant to myoglobin- and Cu2(+)-mediated oxidation (with respect to native LDL), as measured by the formation of conjugated dienes and thiobarbituric acid reactive substances, and the depletion of vitamin E. This antioxidant effect was due to increased thiol content, as the effect was abolished with N-ethylmaleamide pre-treatment. We conclude that the reaction between homocysteine thiolactone and LDL generates an LDL molecule that is more resistant to oxidative modification than native LDL. The potential relationship between the homocystamide-LDL adduct and the development of atherosclerosis is discussed.

Antioxidants↗
PubMed1999

The Gulf War and illness by association.

The symptoms of Gulf War Syndrome (GWS) closely correspond to the physiological and behavioural sequelae of an interleukin-1 (IL-1) mediated sickness response. We propose that this response can account for the variability in its symptomatology. Furthermore, the persistence of GWS can be accounted for by an associative process, whereby the smells/tastes of war become linked with the physiological reaction to environmental stressors encountered in the Gulf and/or the 'cocktail' of drugs given to the soldiers. As required, the IL-1 response is conditionable.

Adaptation, Physiological↗
PubMed1998

Hypochondriacal concerns, symptom reporting and secondary gain mechanisms.

Hypochondriacal concerns (HCs) and somatic symptom reporting (SSR) are associated. However, HCs are believed to be linked to the ego-defence coping strategy of avoiding help and SSR is believed to be linked to secondary gain. One hundred and twenty undergraduate students completed measures of HCs, SSR and the Desire for Control (DC) Scale. Subscales of the DC scale were used as indices of help avoidance and secondary gain. Both hierarchical multiple linear regression and LISREL structural modelling were used to control for the confound between HCs and SSR and explore the links with help avoidance and secondary gain. HCs were found to be primarily associated with an increased desire to strive for independence (avoid help) and levels of SSR were associated with the desire to have others make decisions (secondary gain).

Adaptation, Psychological↗
PubMed1998

Generation and initial characterization of a novel polyclonal antibody directed against homocysteine thiolactone-modified low density lipoprotein.

Elevated plasma homocysteine (homocysteinemia) are presumed to be responsible for the development of coronary artery disease, however, the precise etiology is unclear. We examined the possibility that the adduct formed from the reaction between homocysteine thiolactone, a metabolic product of homocysteine, and apolipoprotein B-100 lysyl residues of low density lipoprotein (LDL) was immunogenic. New Zealand White rabbits were immunized with this adduct at 6-week intervals. Antisera collected following the 3rd immunization was assayed for antibody titers using solid phase ELISA techniques. Titers (defined as the inverse of the greatest serum dilution in which there was a significant difference (P < 0.05) between the percentage antibody bound from the antiserum and the pre-immune serum) were approximately 10(5). In competition-based ELISAs, homocysteine thiolactone-treated LDL competed for binding with the antiserum, as the 50% inhibitory concentration was approximately 10 microg/ml. Neither homocysteine, homocystine (homocysteine disulfide), nor Cu2-oxidized LDL competed for binding. LDL in which lysyl residues were derivatized by acetylation or methylation were not recognized by the antiserum. Homocysteine thiolactone-treated plasma competed for binding to the antiserum, whereas native plasma did not. All lipoprotein fractions from the homocysteine thiolactone-treated plasma competed for binding to the antiserum. We conclude that homocysteine thiolactone-modified LDL is highly immunogenic and specific for homocysteine thiolactone-modified lysines. The potential for using this antibody as a diagnostic tool for measuring plasma homocysteine concentrations and the implications for understanding diseases induced by homocysteinemia are discussed.

Antibody Specificity↗
PubMed1997

The mechanism of apolipoprotein B-100 thiol depletion during oxidative modification of low-density lipoprotein.

Oxidation of low-density lipoprotein (LDL) is recognized to be a key step in atherogenesis. Previous studies show that LDL contains low-molecular-weight antioxidants such as vitamin E, beta-carotene, and ubiquinol, which can retard oxidative modification. In this report, we have evaluated the antioxidant potential of apolipoprotein B-100 (apo-B) thiols during LDL oxidation. Both apo-B thiols and vitamin E were depleted concomitantly during the lag phase of Cu(2+)-mediated LDL oxidation. The rate of thiol depletion was significantly inhibited by the lipophilic spin trap N-tert-butyl-alpha-phenylnitrone (PBN) but not by the water-soluble spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN). Blocking apo-B thiols with sulfhydryl modifying agents increased the oxidizability of LDL. As with Cu2+, peroxynitrite also caused depletion of apo-B thiols, and again thiol depletion was inhibited by PBN but not by POBN. A PBN/lipid-derived radical adduct was observed by the electron spin resonance technique during oxidation of LDL with peroxynitrite. We conclude that apo-B thiol depletion is mediated by lipid peroxidation, prior to the onset of the propagation phase of LDL oxidation. The implications of apo-B thiols an intrinsic antioxidants of LDL are discussed.

Antioxidants↗
PubMed1997

Stress and blood donation: effects of music and previous donation experience.

Making a blood donation, especially for first-time donors, can be a stressful experience. These feelings of stress may inhibit donors from returning. This paper applies stress theory to this particular problem. The effects of a stress management intervention (the provision of music) and previous donor experience were examined in relation to pre- and post-donation mood, environmental appraisals and coping behaviour. Results indicated that the provision of music had detrimental effects on environmental appraisals for those who have donated up to two times previously, but beneficial effects for those who had donated three times before. These effects were, to an extent, moderated by coping processes but not perceived control. It is recommended that the provision of music is not used as a stress management technique in the context of blood donation.

Adaptation, Psychological↗
PubMed1997

Nurses' evaluations of sources of information about HIV and AIDS.

Reviews of the literature indicate that nurses feel ill-informed about HIV/AIDS and that poor knowledge is associated with anxiety and negative attitudes towards infected patients and their care. Although some studies have sought to identify the sources of HIV/AIDS information available to nurses, few have attempted to understand how nurses evaluate such sources. In this study in 1992, 15 sources of HIV/AIDS information were identified during group discussions with nursing staff and nurse tutors. 277 nursing staff evaluated each of the sources in terms of perceived frequency (how often the source is used) and six items chosen to assess the usability and usefulness of each source (e.g. how informative the source is, how easy it is to understand). The results indicate that in-service training, basic training and professional colleagues are the sources evaluated most highly while posters and advertisements, television and radio and popular newspapers are the most frequently used sources of information. Trades unions' journals and pamphlets are the least frequently used sources of information and receive only modest evaluations. 20% of respondents report never having received any training regarding HIV and AIDS. Implications for the future provision of HIV/AIDS information and directions for further research are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Selective inhibition of tumor necrosis factor-induced vascular cell adhesion molecule-1 gene expression by a novel flavonoid. Lack of effect on transcription factor NF-kappa B.

In the present studies, we examined the effect of flavonoids on the endothelial cell expression of adhesion molecules, an early step in inflammation and atherogenesis. Addition of tumor necrosis factor-alpha (TNF) to human aortic endothelial cells (HAECs) led to the induction of vascular cell adhesion molecule-1 (VCAM-1) expression and enhancement in expression of intercellular adhesion molecule-1 (ICAM-1). A flavonoid, 2-(3-amino-phenyl)-8-methoxy-chromene-4-one (PD 098063), markedly inhibited TNF-induced VCAM-1 cell-surface expression in a concentration-dependent fashion with half-maximal inhibition at 19 mumol/L but had no effect on ICAM-1 expression. Another structurally distinct flavonoid, 2-phenyl-chromene-4-one, similarly selectively decreased VCAM-1 expression. The inhibition in cell-surface expression of VCAM-1 by PD 098063 correlated with decreases in steady-state mRNA levels, but there was no effect on ICAM-1 mRNA levels. The decrease in VCAM-1 mRNA levels was not due to changes in mRNA stability but rather resulted from a reduction in the rate of transcription of the gene. However, electrophoretic mobility shift assays using nuclear extracts from TNF-induced HAECs treated with PD 098063 failed to show a decrease in the activation of NF-kappa B, indicating that inhibition of activation of this transcription factor may not be its mode of action. Similarly, PD 098063 did not affect chloramphenicol acetyltransferase reporter gene activity in TNF-inducible minimal VCAM-1 promoter constructs containing two NF-kappa B sites, suggesting that the compound does not affect the transactivation driven by these sites. We conclude that this compound selectively blocks agonist-induced VCAM-1 protein and gene expression in HAECs by NF-kappa B-independent mechanism(s).

Cells, Cultured↗
PubMed1995

Identification of a novel 85-kDa lipoprotein lipase binding protein on human aortic endothelial cell surface.

Lipoprotein lipase (LPL), bound to the luminal surface of vascular endothelium catalyzes lipoprotein triglyceride hydrolysis. Studies were performed to identify human aortic endothelial (HAEC) cell-surface proteins having high affinity for LPL. LPL-sepharose affinity chromatography of [35S]O4 labeled HAEC proteins identified a 220-kDa proteoglycan. Ligand blotting of HAEC plasma membrane proteins with LPL revealed two specific binding proteins of MW 116 kDa and 85 kDa, respectively, which were not released from the cell-surface by heparin treatment. Since the 220-kDa and 116-kDa proteins have been reported previously in bovine endothelial cells, we focused on the 85-kDa protein. The 85-kDa protein was not labelled by incubation of the cells with [35S]O4, suggesting that it is not a sulfated proteoglycan. Treatment of HAEC with tunicamycin markedly decreased detection of the 85-kDa protein, suggesting that it is likely a glycoprotein synthesized by HAEC. We conclude that HAEC cell surface has three specific LPL binding proteins, a 220-kDa proteoglycan, a 116-kDa protein and a novel 85-kDa protein.

Aorta↗
PubMed1995

Inhibition of tumor necrosis factor induced human aortic endothelial cell adhesion molecule gene expression by an alkoxybenzo[b]thiophene-2-carboxamide.

The effects of a novel anti-inflammatory agent, 5-methoxy-3-(1-methyl-ethoxy)benzo[b]thiophene-2-carboxamide-1-oxide (PD 144795) on adhesion molecule expression in tumor necrosis factor (TNF) stimulated human aortic endothelial cells (HAEC) were examined. PD 144795 treatment markedly inhibited the TNF-induced cell expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) protein and mRNA. Gel shift assays using nuclear extracts from HAEC treated with PD 144795 failed to show a decrease in the activation of NFkB by this compound, whereas pyrrolidine dithiocarbamate (PDTC), an antioxidant, markedly inhibited the activation of this transcription factor. Thus, PD 144795 inhibits agonist-stimulated VCAM-1 and ICAM-1 expression likely via an NFkB independent mechanism, distinct from that of PDTC. Such agents may provide a novel approach for control of adhesion molecule gene expression in inflammation.

Anti-Inflammatory Agents, Non-Steroidal↗