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Biomedical subjects

I Harvey

Publications and source records attributed to I Harvey.

At least 19 recordsLinked to original sources
PubMed1996

Crystal structure of a eukaryotic (pea seedling) copper-containing amine oxidase at 2.2 A resolution.

BACKGROUND: Copper-containing amine oxidases catalyze the oxidative deamination of primary amines to aldehydes, in a reaction that requires free radicals. These enzymes are important in many biological processes, including cell differentiation and growth, would healing, detoxification and signalling. The catalytic reaction requires a redox cofactor, topa quinone (TPQ), which is derived by post-translational modification of an invariant tyrosine residue. Both the biogenesis of the TPQ cofactor and the reaction catalyzed by the enzyme require the presence of a copper atom at the active site. The crystal structure of a prokaryotic copper amine oxidase from E. coli (ECAO) has recently been reported. RESULTS: The first structure of a eukaryotic (pea seedling) amine oxidase (PSAO) has been solved and refined at 2.2 A resolution. The crystallographic phases were derived from a single phosphotungstic acid derivative. The positions of the tungsten atoms in the W12 clusters were obtained by molecular replacement using E. coli amine oxidase as a search model. The methodology avoided bias from the search model, and provides an essentially independent view of a eukaryotic amine oxidase. The PSAO molecule is a homodimer; each subunit has three domains. The active site of each subunit lies near an edge of the beta-sandwich of the largest domain, but is not accessible from the solvent. The essential active-site copper atom is coordinated by three histidine side chains and two water molecules in an approximately square-pyramidal arrangement. All the atoms of the TPQ cofactor are unambiguously defined, the shortest distance to the copper atom being approximately 6 A. CONCLUSIONS: There is considerable structural homology between PSAO and ECAO. A combination of evidence from both structures indicates that the TPQ side chain is sufficiently flexible to permit the aromatic grouf to rotate about the Cbeta-Cgamma bond, and to move between bonding and non-bonding positions with respect to the Cu atom. Conformational flexibility is also required at the surface of the molecule to allow the substrates access to the active site, which is inaccessible to solvent, as expected for an enzyme that uses radical chemistry.

Amine Oxidase (Copper-Containing)↗
PubMed1996

1H,13C-NMR and X-ray absorption studies of copper(I) glutathione complexes.

The tripeptide glutathione (gamma-L-Glu-L-Cys-Gly, GSH) is an important intracellular reducing agent for Cu(II) and complexation agent for Cu(I). We have studied the complexation of Cu(I) to GSH in aqueous solution at a range of pH values and Cu(I):GSH molar ratios by 1H-NMR and 13C-NMR spectroscopy and X-ray absorption spectroscopy. The NMR data are consistent with formation of a complex with approximate 1:1 stoichiometry [Cu(SG)] as the major species with only thiolate sulfur of GSH binding to Cu(I). The rate of exchange of GSH with GS-Cu was determined to 13 s(-1) at 283 K, pH 6.8. X-ray absorption spectroscopic measurements showed that Cu(I) is coordinated to 3.1+/-0.3 sulfur atoms at approximately 0.222 nm in solutions (and solids) containing GSH:Cu in 1:1 and 2:1 mol ratios. The possible structures of polymeric Cu(I)-glutathione complexes are discussed. The high thermodynamic stability of Cu(I)-S bonds in Cu(I)-glutathione complexes coupled with their kinetic lability may provide efficient and specific pathways for the transport of copper in cells.

Copper↗
PubMed1996

Do obstetric complications cause the earlier age at onset in male than female schizophrenics?

We compared the age at onset of 184 patients with functional psychoses with and without a history of obstetric complications (OCs) as defined by the scale of Lewis et al. (1989). OCs had no significant influence on the age at onset in those patients who had affective psychoses or were non-white. There were 73 white patients with a DSM-III-R diagnosis of schizophrenia. The mean age at onset of those 25 who had a history of at least one definite OC was 2.6 years earlier than that of the 48 patients with no history of OCs. This effect was entirely due to the male patients with histories of OCs who had, on average, a 3.5 years earlier age at onset. There were no gender differences in age at onset among schizophrenics without a history of OCs. We suggest that a subgroup of male patients with a history of OCs is responsible for the earlier age at onset in male compared to female schizophrenics.

Black or African American↗
PubMed1996

Variation in purchasing for the invasive management of coronary heart disease.

This paper reports the results of a postal questionnaire survey of Directors of Public Health in all health authorities in the United Kingdom (as at March 1994). Our aim was to examine variations in the purchasing of coronary artery bypass grafting, percutaneous transluminal coronary angioplasty and coronary angiography. Information on planned service developments in cardiology was also sought. The response rate was 62%. The mean rate of CABG was 374 per million total population (range 162-710); PTCA 183 (range: 18-648); and coronary angiography 1,010 (range 581-2,334). The mean ratio of invasive treatment to angiography was 1:2 Variations in provision were not related to mortality from coronary heart disease or the availability of a local provider. Those districts purchasing higher levels of CABG tended to purchase higher levels of PTCA (Spearman's r = 0.52). Observed variations in purchasing of invasive treatments and investigation for coronary heart disease do not relate to population "need' as defined by mortality rates from CHD. The greatest variations are seen in the purchasing of PTCA, an intervention whose place in the management of CHD is as yet not fully defined. Consensus guidelines on the appropriate use of these interventions and on population needs are required.

Angioplasty, Balloon, Coronary↗
PubMed1996

Psychopathological syndromes in the functional psychoses: associations with course and outcome.

The aim of this study was to identify underlying dimensions of psychopathology in a cohort of patients with functional psychosis of recent onset, and to examine their prognostic value. Factor analysis of the psychopathological features of 166 consecutively admitted patients with functional psychosis of recent onset revealed seven psychopathological dimensions, which explained 63% of the variance. Five of these seven syndromes bore differential associations with subsequent treatment and illness course, independent of: (i) associations with DSM-III-R diagnosis; (ii) associations with other prognostic factors; and (iii) associations with the baseline values of outcome variables. The most striking associations were shown for an early and insidious onset syndrome with affective flattening, which predicted a more disabled course of illness on three of four outcome dimensions, and which was more common in males and unmarried individuals. A second syndrome, characterized by bizarre behaviour, inappropriate affect, catatonia, and poor rapport showed similar, slightly less striking, associations with illness course, as well as with poor pre-morbid social functioning. A third syndrome, characterized by positive psychotic symptoms was to a lesser degree associated with poorer outcome, whereas a fourth syndrome distinguished by manic symptomatology predicted a more benign illness course. A fifth syndrome identified by lack of insight predicted more time in hospital and admission under a section of the Mental Health Act during the follow-up period. A further finding was that dimensional representations of psychopathological features were considerably more useful than categorical representations (DSM-III-R and ICD-10) as predictors of illness course and treatment decisions.

Adolescent↗
PubMed1996

A comparison of methods for measuring patient satisfaction with consultations in primary care.

BACKGROUND: Attention needs to be paid to comparing and standardizing methods for measuring patient satisfaction with consultations in primary care. OBJECTIVES: To compare the Medical Interview Satisfaction Scale (MISS) and the Consultation Satisfaction Questionnaire (CSQ) in terms of acceptability, distribution of responses, reliability and gather evidence of validity. In addition, to compare the scores of patients completing the questionnaires immediately after the consultation in the general practitioners' surgeries with those completing the questionnaires later at home. METHODS: The two questionnaires were bound as a single instrument with order determined at random. This was given to patients immediately after their consultations in eight practices in South Glamorgan. RESULTS: One hundred and ninety-eight of 316 (63%) patients completed and returned questionnaires. The distributions of patient satisfaction scores for the two questionnaires were very similar. For the MISS: mean 76.6% (SD 11.4); for the CSQ mean 7.2% (SD 12.6). Correlations between sub-scales ranged from 0.58-0.84 for the MISS and from 0.40-0.79 for the CSQ. The correlation between the overall scales was 0.82. Levels of reliability for the scales and sub-scales were fair to good ranging from 0.78-0.96 for the MISS and from 0.73-0.94 for the CSQ. CONCLUSIONS: The study does not identify one scale as being superior in psychometric terms, however by demonstrating consistency of responses it provides support for the scales as measures of patient satisfaction for use in primary care. The level of inter-correlation suggests that the sub-scales may not be clearly independent of each other and suggests that total scores may be preferred. Lower levels of satisfaction are expressed if patients complete questionnaires at home rather than in general practitioners' surgeries.

Adolescent↗
PubMed1995

Psychosis with good prognosis in Afro-Caribbean people now living in the United Kingdom.

OBJECTIVES: To compare the course and outcome of psychotic illness in a group of Afro-Caribbean patients resident in the United Kingdom and a group of white British patients. DESIGN: Cohort study of consecutive admissions followed up for four years. SUBJECTS: 113 patients with psychotic illness of recent onset admitted to two south London hospitals. MAIN OUTCOME MEASURES: Course of illness, history of self harm, social disability, treatment received, and hospital use adjusted for socioeconomic origin. RESULTS: The Afro-Caribbean group spent more time in a recovered state during the follow up period (adjusted odds ratio 5.0; 95% confidence interval 1.7 to 14.5), were less likely to have had a continuous illness (0.3; 0.1 to 0.8), were less at risk of self harm (0.2; 0.1 to 0.8), and were less likely to have been prescribed antidepressant treatment (0.3; 0.1 to 0.9). There were no differences in hospital use, but the Afro-Caribbean group had more involuntary admissions (8.9; 2.1 to 35.6) and more imprisonments over the follow up period (9.2; 1.6 to 52.3). CONCLUSIONS: Afro-Caribbean patients in the United Kingdom have a better outcome after psychiatric illness than do white people. The combination of high incidence and more benign course of illness of psychotic illness in this group may be due, at least in part, to a greater exposure to precipitants in the social environment.

Adolescent↗
PubMed1995

Against the laterality index as a measure of cerebral asymmetry.

The laterality index (right - left)/(right + left) has been widely used to measure cerebral asymmetry. However, its validity rests on the assumption that confounding effects of overall head and body size are symmetrical on both sides of the brain. We have found that this assumption may not always be justified. In magnetic resonance imaging data from a group of 43 right-handed normal control and schizophrenic subjects, the laterality index controlled poorly for the asymmetrical confounding effect of height, leading to a spurious (although statistically significant) correlation between height and apparent cerebral asymmetry. Regression modeling is advocated as a more rational and effective way to explore and control size effects confounding cerebral lateralization.

Adult↗
PubMed1995

X-ray absorption studies and homology modeling define the structural features that specify the nature of the copper site in rusticyanin.

Rusticyanin, a blue copper protein, possessing the highest redox potential among this class of proteins and a high stability at acidic pH reveals homology with the C-terminal end of the other single copper containing blue proteins and an interesting homology to parts of the blue copper domain of the multi-copper proteins such as the nitrite reductases. Extended X-ray absorption fine structure (EXAFS) data at pH 2.0 reveal that Cu is ligated to two His and a Cys in the inner coordination sphere, similar to other blue copper centers. Modeling studies suggest that His85 is the ligating histidine from the N-terminal end. Its neighboring residue is a serine rather than the asparagine found in all known blue Cu proteins. The high stability of the copper site may arise in part due to this substitution. The Cu binding site is surrounded by aromatic residues which may provide further protection for the metal in an acidic environment. In addition, the high number of solvent-exposed uncompensated lysine residues is likely to be of functional relevance under low pH conditions. EXAFS data show a very small change (relative to azurin) in the copper site upon reduction, consistent with a more constrained copper center in rusticyanin compared to azurin and a higher redox potential.

Absorptiometry, Photon↗
PubMed1995

Behavioural effects of norpethidine, a metabolite of pethidine, in rats.

This study investigated behavioural effects of the toxic pethidine metabolite, norpethidine, in rats and its interactions with reserpine, apomorphine and physostigmine. Following intraperitoneal administration, brain concentrations of norpethidine reached a plateau after 20-40 min and remained elevated for 2 h. In the dose range 0.06-0.18 mmol/kg, norpethidine induced myoclonic jerks, a characteristic splayed posture, and episodes of exaggerated shivering. Forward locomotion, grooming, yawning and rearing were suppressed. Seizures and reverse locomotion occurred occasionally. Administration of reserpine 1 h prior to norpethidine, or of apomorphine or physostigmine 15 min after norpethidine, did not alter the norpethidine-induced behaviours; neither did norpethidine block the effects of apomorphine or physostigmine. The characteristic profile of behaviours induced by norpethidine make this toxicant readily amenable to animal studies. Our results indicate that its mechanism of action is unlikely to involve dopaminergic or cholinergic pathways.

Animals↗
PubMed1995

Morbid risk of schizophrenia for relatives of patients with cannabis-associated psychosis.

Twenty-three patients admitted with acute psychosis who were cannabis positive on urinary screening were each matched, with respect to sex, with two psychotic controls who screened negatively for all substances. The lifetime morbid risk of psychiatric disorder was estimated among the first degree relatives of cases and controls, using RDC-FH criteria to define diagnoses, and Weinberg's shorter method of age correction. The cases had a significantly greater familial morbid risk of schizophrenia (7.1%) than the controls (0.7%), while the risks of other psychoses, and of non-psychotic conditions were similar. The same pattern of familial risk was evident when the analysis was restricted to patients with DSM-III schizophrenia. The data suggest that the development or recurrence of acute psychosis in the context of cannabis use may be associated with a genetic predisposition to schizophrenia.

Adult↗
PubMed1995

Cerebral hemispheric asymmetry revisited: effects of handedness, gender and schizophrenia measured by radius of gyration in magnetic resonance images.

Abnormal patterns of cerebral hemispheric asymmetry have been inconsistently reported in association with schizophrenia. Radius of gyration (Rg) is a measure of the mean dispersion of points in a radially organized structure about that structure's centre of gravity. We developed computerized methods for estimating Rg of the magnetic resonance image (MRI) boundary between cortex and subcortex, and applied these methods to measurement of cerebral hemispheric asymmetry in 37 schizophrenics (SZs) and 30 controls (CONs). In right-handed CONs, Rg of right brain boundaries was significantly greater than Rg of left brain boundaries; in left-handed CONs, Rg of left brain boundaries was significantly greater than Rg of right brain boundaries. In right-handed males (both SZ and CON) there were significant differences in Rg between hemispheres; whereas in females (both SZ and CON), there were no such differences. Right-handed male SZs (N = 26) were distinguished by reversal of the right-handed male CON pattern of interhemispheric difference in Rg, and by global reduction in Rg of right brain boundaries. These was no evidence for significant abnormality of Rg in right-handed female SZs (N = 7). There findings suggest an important interactive effect of gender and schizophrenia on lateralized cerebral structure.

Adult↗
PubMed1995

The invasive management of angina: issues for consumers and commissioners.

OBJECTIVE: To review, from the purchaser's perspective, the current state of knowledge of techniques for investigation and treating coronary artery disease. The study was based on evidence from past and continuing randomised controlled trials (RCTs). CRITERIA FOR INCLUSION OF REPORTS: Articles listed on Medline (1990-3) with the keywords coronary disease, angina, and unstable angina (combined with surgery, economics, therapy, or drug therapy) and percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) were included. Articles published before 1990 were obtained from two comprehensive literature reviews published by the Rand organisation in 1991 and from the papers obtained using the Medline search. A hand search of relevant journals published between July 1993 and June 1994 was also undertaken. Results from more recently published RCTs are included. RESULTS: CABG provides improved angina relief compared with drug treatment and may prolong life in patients with more severe illness. PTCA is also better than drug treatment, but less so than CABG, and its cost advantages over CABG decrease with time. Repeat intervention for return of symptoms is more frequently required after PTCA, but increasing numbers of patients are also undergoing second and third repeat CABG for graft occlusion in the years after the original operation. Newer PTCA techniques are not, as yet, fully evaluated. One technique, atherectomy, has been shown to be no more effective, and more expensive, than conventional balloon angioplasty. In the short term intracoronary stents reduce the problems associated with vessel occlusion after PTCA and therefore reduce the need for further intervention. PTCA should not be performed without ready access to cardiothoracic support. There is an increasing trend towards the development of coronary catheterisation units at peripheral sites. This may lead to increasing, inappropriate use of this investigation in suboptimal circumstances. CONCLUSIONS: Ischaemic heart disease is an important cause of morbidity and mortality and invasive management techniques are developing rapidly; some service expansion is occurring without trial evidence. More research is required to determine the optimum balance of PTCA, CABG, and angiography and population requirements for these procedures. In the meantime, in the absence of firm long term evidence of the superior cost effectiveness of PTCA compared with CABG, the rapid expansion of this procedure should be limited. Patients should be fully informed of the benefits and disadvantages of CABG and PTCA, where either procedure is indicated, to enable them to make fully informed choices.

Angioplasty, Balloon, Coronary↗
PubMed1995

Increased intracerebral cerebrospinal fluid spaces predict unemployment and negative symptoms in psychotic illness. A prospective study.

BACKGROUND: It has been suggested that the dimensions of cerebral ventricles are a risk factor for poor outcome in psychotic illness. METHOD: A cohort of 140 patients with functional psychoses of recent onset who had undergone CT scanning, were followed up for an average of 46 months and assessed on six dimensions of course and outcome of illness. RESULTS: Left and right sylvian fissure volumes and, to a lesser extent, third ventricular volume predicted negative symptoms and unemployment over the course of follow-up, the latter association being mediated by poor cognitive functioning. There was significant linear trend in risk over the distribution of sylvian fissure volumes in the cohort, and associations were especially evident in schizophrenic patients. No associations were found with global severity of illness, duration of hospital stay, homelessness, or affective symptoms. CONCLUSIONS: These findings support the notion that dimensions of the cerebral ventricles are a continuous risk factor for some measures of outcome in the functional psychoses.

Arousal↗
PubMed1995

Insight and psychotic illness. Cross-sectional and longitudinal associations.

BACKGROUND: Insight has recently re-emerged as an important aspect of psychopathology amenable to empirical study. We sought to examine the relationship between various aspects of insight into illness and clinical, sociodemographic and neuropsychological variables. METHOD: From an inner-London catchment area population, 150 in-patients with recent onset of psychosis were assessed on a variety of measures, including the Present State Examination (PSE). Subjects were followed up for a mean of four years and reassessed. RESULTS: High IQ was associated with better insight as rated on the PSE, while gender, ethnicity and a diagnosis of schizophrenia appeared to be unrelated. At follow-up, similar associations were found, as well as correlations with attitudes to treatment and a more elaborate measure of insight. Cerebral ventricular enlargement and tests of frontal lobe function did not correlate with insight, but there was a curious, strong association with left-handedness at both assessment points. Initial insight correlated significantly but weakly with insight at follow-up. CONCLUSIONS: The assessment of insight in psychosis has concurrent validity and is a distinct aspect of psychotic phenomenology. It may, in part, have a neuropsychological basis.

Adolescent↗
PubMed1994

Cannabis and acute psychosis.

The Present State Examination was used to assess the psychopathology of 23 psychotic patients who were cannabis positive on urinary screening, and 46 matched drug-free controls. Cases and controls were indistinguishable in terms of psychopathology, DSMIII diagnoses, onset of recent illness, the proportion of first admissions, ethnicity, and socio-economic class, differing only in their histories of substance use. These data suggest that psychosis which develops or recurs in the context of cannabis use does not have a characteristic psychopathology or mode of onset, and is not restricted to a particular ethnic or socio-demographic group. There is thus little evidence to support the validity of 'cannabis psychosis' as a diagnostic entity.

Acute Disease↗