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Biomedical subjects

M Sharpe

Publications and source records attributed to M Sharpe.

At least 91 records · Page 5Linked to original sources
PubMed1997

Chronic fatigue syndrome: a qualitative investigation of patients' beliefs about the illness.

The chronic fatigue syndrome is a disabling chronic condition of uncertain cause. Previous studies have found that patients seen in hospital clinics with the syndrome often strongly believe that their illness is physical in nature and minimize the role of psychological and social factors. There is also evidence that patients cope by avoiding activity. However, almost all of these studies have assessed illness beliefs only by questionnaire. The aim of this study was to explore the nature and origin of illness beliefs in more detail using in-depth interviews and a qualitative analysis of patient responses. Sixty-six consecutive referrals meeting Oxford criteria for chronic fatigue syndrome were recruited. Analysis of responses indicated that, whereas the most commonly described explanation for the illness was a physical one, more than half the patients also believed "stress" had played a role. Patients believed that they could partially control the symptoms by reducing activity but felt helpless to influence the physical disease process and hence the course of the illness. Patients reported that they had arrived at these beliefs about the illness after prolonged reflection on their own experience combined with the reading of media reports, self help books, and patient group literature. The views of health professionals played a relatively small role. There is potentially a considerable opportunity to help patients arrive at a wider and more enabling explanation of their illness when they first present to primary care.

Adaptation, Psychological↗
PubMed1997

Chronic fatigue syndrome. A practical guide to assessment and management.

Chronic fatigue and chronic fatigue syndrome (CFS) have become increasingly recognized as a common clinical problem, yet one that physicians often find difficult to manage. In this review we suggest a practical, pragmatic, evidence-based approach to the assessment and initial management of the patient whose presentation suggests this diagnosis. The basic principles are simple and for each aspect of management we point out both potential pitfalls and strategies to overcome them. The first, and most important task is to develop mutual trust and collaboration. The second is to complete an adequate assessment, the aim of which is either to make a diagnosis of CFS or to identify an alternative cause for the patient's symptoms. The history is most important and should include a detailed account of the symptoms, the associated disability, the choice of coping strategies, and importantly, the patient's own understanding of his/her illness. The assessment of possible comorbid psychiatric disorders such as depression or anxiety is mandatory. When the physician is satisfied that no alternative physical or psychiatric disorder can be found to explain symptoms, we suggest that a firm and positive diagnosis of CFS be made. The treatment of CFS requires that the patient is given a positive explanation of the cause of his symptoms, emphasizing the distinction among factors that may have predisposed them to develop the illness (lifestyle, work stress, personality), triggered the illness (viral infection, life events) and perpetuated the illness (cerebral dysfunction, sleep disorder, depression, inconsistent activity, and misunderstanding of the illness and fear of making it worse). Interventions are then aimed to overcoming these illness-perpetuating factors. The role of antidepressants remains uncertain but may be tried on a pragmatic basis. Other medications should be avoided. The only treatment strategies of proven efficacy are cognitive behavioral ones. The most important starting point is to promote a consistent pattern of activity, rest, and sleep, followed by a gradual return to normal activity; ongoing review of any 'catastrophic' misinterpretation of symptoms and the problem solving of current life difficulties. We regard chronic fatigue syndrome as important not only because it represents potentially treatable disability and suffering but also because it provides an example for the positive management of medically unexplained illness in general.

Adaptation, Psychological↗
PubMed1997

Chronic fatigue syndrome and occupational health.

Chronic fatigue syndrome (CFS) is a controversial condition that many occupational physicians find difficult to advise on. In this article we review the nature and definition of CFS, the principal aetiologic hypotheses and the evidence concerning prognosis. We also outline a practical approach to patient assessment, diagnosis and management. The conclusions of this review are then applied to the disability discrimination field. The implications of the new UK occupational health legislation are also examined. Despite continuing controversy about the status, aetiology and optimum management of CFS, we argue that much can be done to improve the outcome for patients with this condition. The most urgent needs are for improved education and rehabilitation, especially in regard to employment. Occupational physicians are well placed to play an important and unique role in meeting these needs.

Employment↗
PubMed1997

Ligation, inhibition, and activation of cytochrome c oxidase by fatty acids.

Free fatty acids bind to beef heart cytochrome c oxidase and induce spectral shifts similar to those obtained with high spin ligands. Oleic (18:1(n-9)) and linoleic (18:2(n-6)) acids induce substantial blue shifts of the Soret peak of oxidized enzyme. Small saturated fatty acids (< 15 carbon atoms) shift the Soret peak to the red, and longer chain acids induce smaller blue shifts. Formate-induced spectral shifts are modified by short chain fatty acids but are unaffected by longer chain fatty acids for which effects are additive with those of formate. Inhibition by formate is partially relieved by all fatty acids tested. Palmitic and linoleic acids increase turnover at low cytochrome c levels and decrease the K(m) for cytochrome c at high cytochrome c levels. Oleic acid protects the enzyme against acid denaturation during turnover. Bovine serum albumin produces a red shift in the oxidase Soret peak and inhibits turnover of the isolated enzyme. Oleic acid and serum albumin modify the electron paramagnetic resonance spectrum of oxidized oxidase, oleic acid shifting the g = 3 (cytochrome a) peak towards low field and albumin towards higher field strengths. The oxidase may possess at least two fatty acid binding sites at one of which cytochrome c binding is modulated and at another spectral changes may be induced. One site is close enough to the binuclear centre to interact allosterically with ligand binding at that centre.

Animals↗
PubMed1996

Fatty acids as modulators of cytochrome c oxidase in proteoliposomes.

The control of cytochrome c oxidase turnover in proteoliposomes by membrane potential (delta psi) and by pH gradient (delta pH) is probably kinetic in nature, and inhibition by valinomycin and stimulation by nigericin indicate that delta pH exerts a greater influence than does an equivalent delta psi. Oleic acid at 100 microM removes all delta psi and delta pH control, whereas a similar concentration of palmitic acid increases turnover but does not completely abolish control. Valinomycin acts synergistically with both fatty acids, indicating that the latter can act as H+/K+ exchangers, but neither fatty acid alone markedly affects delta pH, showing that they cannot fully mimic nigericin. Oleate, but not palmitate, diminishes delta psi, and can move electrophoretically as oleate anion. Submicromolar palmitic acid concentrations partly stimulate turnover in delta psi- and delta pH-controlled proteoliposomes, as reported by Labonia, Muller and Azzi [(1988) Biochem. J. 254, 130-145], which might represent a direct effect on cytochrome c oxidase. The ubiquity of fatty acids in biological membranes suggests that these substances might be responsible for limiting respiratory control and enzyme activity in vivo.

Animals↗
PubMed1996

Increased prolactin response to buspirone in chronic fatigue syndrome.

We studied the endocrine and subjective responses that followed acute administration of the 5-HT1A receptor agonist buspirone (0.5 mg/kg orally) in 11 male patients with chronic fatigue syndrome (CFS) and a group of matched healthy controls. Patients with CFS had significantly higher plasma prolactin concentrations and experienced more nausea in response to buspirone than did controls. However, the growth hormone response to buspirone did not distinguish CFS patients from controls. Our data question whether the enhancement of buspirone-induced prolactin release in CFS is a consequence of increased sensitivity of post-synaptic 5-HT1A receptors. It is possible that the increased prolactin response to buspirone in CFS could reflect changes in dopamine function.

Adolescent↗
PubMed1996

Fatty acids stimulate activity and restore respiratory control in a proton channel mutant of cytochrome c oxidase.

(1) Removal of a carboxyl at residue 132 of subunit I of Rhodobacter sphaeroides cytochrome c oxidase significantly inhibits electron transfer and makes proton pumping undetectable [Fetter et al. (1995) Proc. Natl. Acad. Sci. USA 92, 1604-1608]. When reconstituted into phospholipid vesicles (COV), wild-type oxidase shows respiratory control that is partially released by either valimomycin or nigericin and fully released by the two ionophores combined. Under the same conditions, the D132A mutant COV show anomalous ionophore responses, including inhibition by valinomycin or by CCCP. Nevertheless, oxidase activity results in development of a similar membrane potential in COV containing either wild-type or D132A oxidase, and the ionophore responses of the membrane potential are similar for both enzymes. (2) Long chain fatty acids such as arachidonic acid, but not fatty alcohols, stimulate steady-state electron transfer activity 3-7-fold, with either detergent-solubilized (purified) D132A oxidase or the reconstituted form. The effect is specific for this mutant and is not seen with wild-type or other mutants of similar overall activity. Arachidonate-treated D132A COV show normal ionophore responses to valinomycin and nigericin and full release of respiration in presence of both ionophores or of CCCP. Thus, arachidonate and some other fatty acids abolish the ionophore anomalies seen when the D132A enzyme is reconstituted in their absence. (3) Fatty acid addition does not restore proton pumping, likely because fatty acids also induce proton permeability and some degree of uncoupling. A model of D132A function is presented and possible roles for the fatty acids in 'chemical rescue' of the mutant are discussed.

Alcohols↗
PubMed1996

Action of bovine serum albumin on cytochrome c oxidase activity and proton pumping: a role for fatty acids in enzyme function?

Bovine serum albumin (BSA) at micromolar concentrations causes a red shift of the Soret band of bovine cytochrome c oxidase with a slow biphasic time course. It also inhibits the turnover of detergent-isolated enzyme in a similarly slow manner; the progress of this inhibition is halted by palmitate and other fatty acids. The inhibitory bovine serum albumin effect may involve fatty acid depletion from the enzyme. Respiration by cytochrome c oxidase vesicles (proteoliposomes) in the presence of ionophores (uncontrolled) shows only a small inhibition by BSA but preincubation of such vesicles with BSA induces a loss of proton pumping activity. After incubation of BSA-depleted proteoliposomes in the presence of reductant with combinations of fatty acids, pumping activity can be fully restored, suggesting a supportive or even essential role of endogenous fatty acids in H+ translocation by this membranous enzyme.

Animals↗
PubMed1996

Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial.

OBJECTIVE: To evaluate the acceptability and efficacy of adding cognitive behaviour therapy to the medical care of patients presenting with the chronic fatigue syndrome. DESIGN: Randomised controlled trial with final assessment at 12 months. SETTING: An infectious diseases outpatient clinic. SUBJECTS: 60 consecutively referred patients meeting consensus criteria for the chronic fatigue syndrome. INTERVENTIONS: Medical care comprised assessment, advice, and follow up in general practice. Patients who received cognitive behaviour therapy were offered 16 individual weekly sessions in addition to their medical care. MAIN OUTCOME MEASURES: The proportions of patients (a) who achieved normal daily functioning (Karnofsky score 80 or more) and (b) who achieved a clinically significant improvement in functioning (change in Karnofsky score 10 points or more) by 12 months after randomisation. RESULTS: Only two eligible patients refused to participate. All randomised patients completed treatment. An intention to treat analysis showed that 73% (22/30) of recipients of cognitive behaviour therapy achieved a satisfactory outcome as compared with 27% (8/30) of patients who were given only medical care (difference 47 percentage points; 95% confidence interval 24 to 69). Similar differences were observed in subsidiary outcome measures. The improvement in disability among patients given cognitive behaviour therapy continued after completion of therapy. Illness beliefs and coping behaviour previously associated with a poor outcome changed more with cognitive behaviour therapy than with medical care alone. CONCLUSION: Adding cognitive behaviour therapy to the medical care of patients with the chronic fatigue syndrome is acceptable to patients and leads to a sustained reduction in functional impairment.

Adaptation, Psychological↗
PubMed1996

Chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a medically unexplained illness characterized by chronic, disabling fatigue, impaired concentration, muscle pain, and other somatic symptoms. The conceptual difficulties associated with all medically unexplained illnesses contribute to the controversy surrounding CFS, which has centered around whether it is best regarded as a medical or as a psychiatric condition. Clinically, such an approach is not helpful, and current research suggests that both pathophysiologic changes and psychosocial factors are important. Pragmatic management based on a detailed assessment of the individual is outlined.

Fatigue Syndrome, Chronic↗
PubMed1995

Scatter factor/hepatocyte growth factor is essential for liver development.

Polypeptide growth factors are important effectors of cell growth and differentiation in vitro and are thought to be critical for processes such as specification of cell fate, tissue growth and organogenesis in vivo. Scatter factor/hepatocyte growth factor (SF/HGF) is the prototype of an emerging family of growth factors that resemble in their domain structure and mechanism of activation the blood proteinase plasminogen. The cellular responses of SF/HGF are mediated by the c-Met tyrosine kinase receptor. Here we report that mice lacking SF/HGF fail to complete development and die in utero. The mutation affects the embryonic liver, which is reduced in size and shows extensive loss of parenchymal cells. In addition, development of the placenta, particularly of trophoblast cells, is impaired. Thus, SF/HGF is essential for the development of several epithelial organs.

Animals↗
PubMed1995

Chronic fatigue syndrome: a cognitive approach.

Observations concerning the characteristics of patients who presented to a medical clinic with a principal complaint of chronic medically unexplained fatigue (Chronic Fatigue Syndrome or CFS) are described, including the cognitions (thoughts and assumptions) elicited from a sample of these patients who were treated using cognitive behavioural therapy. On the basis of these observations a cognitive theory of the aetiology of CFS is proposed. These observations have implications for the treatment of patients with CFS.

Adaptation, Psychological↗