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Biomedical subjects

R Murray

Publications and source records attributed to R Murray.

At least 73 records · Page 4Linked to original sources
PubMed1999

To what extent does symptomatic improvement result in better outcome in psychotic illness? UK700 Group.

BACKGROUND: The effectiveness of therapeutic interventions in psychosis is increasingly reported in terms of reductions in different symptom dimensions. It remains unclear, however, to what degree such symptomatic changes are accompanied by improvement in other measures such as service use, quality of life, and needs for care. METHODS: A sample of 708 patients with chronic psychotic illness was assessed on three occasions over 2 years (baseline, year 1 and year 2). A multilevel analysis was conducted to examine to what degree reduction in psychopathological scores derived from factor analysis of the Comprehensive Psychopathological Rating Scale (CPRS), was associated with improvement in service use, disability, subjective outcomes and measures of self-harm. RESULTS: Reduction in positive, negative, depressive and manic symptoms over the study period were all independently associated with lessening of social disability. Reduction in negative symptoms, and to a lesser extent in positive and manic symptoms, was associated with less time in hospital and more time living independently, whereas changes in positive and manic symptoms resulted in fewer admissions. Subjective outcomes such as improvement in quality of life, perceived needs for care and dissatisfaction with services showed the strongest associations with reduction in depressive symptoms. Reduction in positive symptoms was associated with decreased likelihood of parasuicide. Results did not differ according to diagnostic category. CONCLUSION: The findings suggest that changes in distinct psychopathological dimensions independently and differentially influence outcome. Therapeutic interventions aimed at reducing symptoms of more than one dimension are likely to have more widespread effects.

Adolescent↗
PubMed1999

Association between variants at the GABAAbeta2, GABAAalpha6 and GABAAgamma2 gene cluster and alcohol dependence in a Scottish population.

A role for the GABA/benzodiazepine receptor complex in alcohol dependence syndrome has been suggested by several lines of evidence. To elucidate the role of GABAA subunits in human alcohol dependence syndrome, we identified polymorphisms in the GABAAbeta2 and GABAAalpha6 receptor subunit genes on 5q33 and assessed their potential contribution in an association study, together with a NciI RFLP at the GABAAgamma2 receptor subunit gene. One hundred and eight alcohol-dependent subjects and 54 unrelated controls were recruited from Scotland. Two novel genetic markers were identified at the GABAAbeta2 and GABAAalpha6 receptor subunit genes and examined for association with the alcohol dependence syndrome and subgroups of subjects with Korsakoff's psychosis and without Korsakoff's psychosis, together with a NciI RFLP at the GABAAgamma2 receptor subunit gene. The chi2 tests demonstrated associations between all alcohol-dependent subjects (not stratified) and the BanI RFLP at the GABAAbeta2 receptor subunit gene (P = 0.015), and the AlwNI RFLP at the GABAAalpha6 receptor gene (P = 0.013). Significant associations were also found between the alcohol-dependent subjects with Korsakoff's psychosis and the BanI RFLP (P = 0.039) and the AlwNI RFLP (P = 0.003). Haplotype analysis also provided evidence of association when all alcohol-dependent subjects (P = 0.013) and the subjects with Korsakoff's psychosis (P = 0.007) were compared with controls. Our findings provide evidence for a role for the GABAA receptor subunit cluster on chromosome 5q33 in susceptibility to the alcohol dependence syndrome and Korsakoff's psychosis.

Adult↗
PubMed1999

Wavelet transform-based QRS complex detector.

In this paper, we describe a QRS complex detector based on the dyadic wavelet transform (Dy WT) which is robust to time-varying QRS complex morphology and to noise. We design a spline wavelet that is suitable for QRS detection. The scales of this wavelet are chosen based on the spectral characteristics of the electrocardiogram (ECG) signal. We illustrate the performance of the Dy WT-based QRS detector by considering problematic ECG signals from the American Heart Association (AHA) data base. Seventy hours of data was considered. We also compare the performance of Dy WT-based QRS detector with detectors based on Okada, Hamilton-Tompkins, and multiplication of the backward difference algorithms. From the comparison, results we observed that although no one algorithm exhibited superior performance in all situations, the Dy WT-based detector compared well with the standard techniques. For multiform premature ventricular contractions, bigeminy, and couplets tapes, the Dy WT-based detector exhibited excellent performance.

Algorithms↗
PubMed1999

A comparison of the gastric emptying characteristics of selected sports drinks.

The purpose of this study was to determine the effects of repeated ingestion of drinks containing varying concentrations of carbohydrate on gastric emptying rate during steady-state exercise. On five separate occasions, 14 subjects cycled for 90 min at an average power output of 151 +/- 2 W. At 15-min intervals, subjects ingested 227 +/- 3 ml of either water, 4% carbohydrate (CHO), 6% CHO, or 8% CHO. Gastric volume was determined prior to each drink and at 90 min using the modified double-sampling technique. Gross gastric volumes were significantly greater and mean gastric emptying rates and the percentage of ingested beverage emptied from the stomach were significantly less for 8% CHO. These data indicate that repeated ingestion of an 8% CHO beverage during exercise significantly reduces gastric emptying rate, whereas lower concentrations of carbohydrate do not. In addition, beverage osmolality is not as important as beverage energy content in influencing gastric emptying rate at these carbohydrate concentrations.

Adult↗
PubMed1999

Intestinal permeability in runners in the 1996 Chicago marathon.

Abdominal cramping, nausea, diarrhea, and GI bleeding are often reported in long-distance runners. This study set out to determine the effects of prolonged (2-4 hrs) exercise and NSAID ingestion on gastric and intestinal permeability during the first 5 hrs following the 1996 Chicago Marathon. Thirty-four healthy volunteers (20 M, 14 F; ages 30-50) completed the race and ingested the test solution (5 g sucrose, 5 g lactulose, 2 g rhamnose, in 40 ml water) within 10-15 min. The urinary excretion ratio of lactulose/rhamnose was used to assess small intestine permeability; sucrose excretion was used to evaluate gastric impairment. There were no significant differences for mean training mileage, postrace rectal temperature, and percent dehydration between runners who ingested NSAIDs and those who did not. In all, 75% of subjects reported aspirin or ibuprofen ingestion before or during the race. Runners who ingested ibuprofen had significant elevations in urinary lactulose excretion and lactulose/rhamnose ratio, whereas those who ingested aspirin or who did not ingest either NSAID had no significant differences in urinary excretion of lactulose, rhamnose, sucrose, or lactulose/rhamnose ratio compared to resting controls. Thirteen of the 26 NSAID users and 4 of the 8 non-users reported GI symptoms. It is concluded that (a) ibuprofen but not aspirin ingestion during prolonged exercise may increase gastrointestinal permeability and lead to GI symptoms, and (b) prolonged exercise alone can produce GI symptoms.

Adult↗
PubMed1999

A Jamaican psychiatrist evaluates diagnoses at a London psychiatric hospital.

BACKGROUND: Authors have suggested that the high rate of schizophrenia reported for African-Caribbeans living in the UK is due to misdiagnosis by British psychiatrists. AIMS: To compare the diagnoses made by a Black Jamaican psychiatrist with those of White British psychiatrists. METHOD: All in-patients on four wards at the Maudsley hospital were approached for the study; 66 participated: 24 White, 29 Black African-Caribbeans and 13 Blacks from other countries of origin. F.W.H., a Black Jamaican psychiatrist, conducted his standard clinical assessment and performed the Present State Examination (PSE) on these patients. His diagnoses were compared with the case note diagnoses made by British psychiatrists, and with the PSE CATEGO diagnoses. RESULTS: Of 29 African and African-Caribbean patients diagnosed with schizophrenia, the diagnoses of the British and the Jamaican psychiatrists agreed in 16 instances (55%) and disagreed in 13 (45%). Hence, interrater reliability was poor (kappa = 0.45). PSE CATEGO diagnosed a higher proportion of subjects as having schizophrenia than the Jamaican psychiatrist did (chi 2 = 3.74, P = 0.052). CONCLUSIONS: Agreement between the Jamaican psychiatrist and his UK counterparts about which patients had schizophrenia was poor. PSE CATEGO may overestimate rates of schizophrenia.

Africa↗
PubMed1999

Association analysis of sequence variants of GABA(A) alpha6, beta2, and gamma2 gene cluster and alcohol dependence.

Quantitative trait analyses in mice suggest a vulnerability locus for physiological alcohol withdrawal severity on a chromosomal segment that harbors the genes encoding the alpha1, alpha6, beta2, and gamma2 subunits of the gamma-aminobutyric acid type-A receptor (GABR). We tested whether genetic variation at the human GABA(A) alpha6, beta2, and gamma2 gene cluster on chromosome 5q33 confers vulnerability to alcohol dependence. The genotypes of three nucleotide substitution polymorphisms of the GABRA6, GABRB2, and GABRG2 genes were assessed in 349 German alcohol-dependent subjects and in 182 ethnically matched controls. To eliminate some of the genetic variance, three more homogeneous subgroups of alcoholics were formed by: (1) a history of alcohol withdrawal seizure or delirium (n = 106); (2) a history of parental alcoholism (n = 120); and (3) a comorbidity of dissocial personality disorder (n = 57). We found no evidence that any of the investigated allelic variants confers vulnerability to either alcohol dependence or severe physiological alcohol withdrawal symptoms or familial alcoholism (p > 0.05). The frequency of the T allele of the GABRA6 polymorphism was significantly increased in dissocial alcoholics [f(T) = 0.799] compared with the controls [f(T) = 0.658; p = 0.002; OR(T+) = 7.26]. Taking into account the high a priori risk of false-positive association findings due to multiple testing, further replication studies are necessary to examine the tentative phenotype-genotype relationship of GABRA6 gene variants and dissocial alcoholism.

Adult↗
PubMed1999

The effect of nefazodone on clozapine plasma concentrations.

The cytochrome enzyme p4503A4 (CYP3A4) is thought to play a major part in the human metabolism of clozapine. Nefazodone is a potent and specific in-vivo inhibitor of CYP3A4. We co-administered nefazodone and clozapine in six patients and found that mean clozapine levels rose by 4% of baseline and norclozapine levels by 16%. Based on these observations, it is inferred that inhibition of CYP3A4 in vivo has minimal effects on clozapine metabolism. Nefazodone appears to be safe when co-administered with clozapine.

Adult↗
PubMed1999

Functional MR imaging of confounded hypofrontality.

Comparatively reduced blood flow to frontal brain regions in patients with schizophrenia (hypofrontality) has been frequently observed in the last 25 years. However, there is an inconstant quality to hypofrontality, suggesting either confounded observation of a static (trait-like) abnormality, or that it is a genuinely dynamic (state-like) phenomenon. Possible confounds in functional magnetic resonance imaging (fMRI) studies of hypofrontality are classified. Methods for assessment and correction of stimulus correlated motion (an extracerebral confound) are reviewed in the context of fMRI data acquired from five schizophrenic patients and five comparison subjects during performance of a verbal fluency task. Factorial analysis of these and other data, acquired from the same subjects during a semantic decision task, is used to exclude a number of possible intracerebral confounds. By analogy to the historical controversy concerning the appearance of the planet Saturn viewed through early telescopes, understanding the inconstancy of hypofrontality in schizophrenia is likely to progress more by theoretically driven experiments that exploit the repeatability of fMRI than by further technological development alone.

Analysis of Variance↗
PubMed1998

IL-7 deficiency prevents development of a non-T cell non-B cell-mediated colitis.

IL-7 is a stromal cell-derived cytokine with a well-established physiologic role in lymphocyte biology. This report describes an unexpected role for IL-7 in the development of colitis in a T and B cell-deficient environment. Recombination-activating gene-2 (RAG-2)-deficient mice (RAG-2(-/-)) were exposed to and subsequently maintained a horizontally transmitted microbial flora that included Helicobacter hepaticus. These animals mounted a strong myeloid cell response and developed both systemic and local signs of a severe colitis. A striking infiltration of F4/80 and MHC class II-positive cells was seen in the colon and cecum of animals undergoing the disease. Mice mutant for both IL-7 and RAG-2 (IL-7/RAG-2(-/-)) that were colonized by the same flora showed no signs of myeloid responses or colitis, indicating that IL-7 plays a critical role in exacerbating a non-T cell/non-B cell-mediated chronic inflammatory response. Recombinant IL-10 protein therapy was able to prevent the occurrence of colitis in susceptible mice, suggesting a pivotal role for macrophages. The implications of a role for IL-7 in this disease model with respect to human inflammatory bowel disease are discussed.

Animals↗
PubMed1998

Early and late weight gain following smoking cessation in the Lung Health Study.

The authors examine weight gains associated with smoking cessation in the Lung Health Study (1986-1994) over a 5-year follow-up period. A cohort of 5,887 male and female smokers in the United States and Canada, aged 35-60 years, were randomized to either smoking intervention or usual care. Among participants who achieved sustained quitting for 5 years, women gained a mean of 5.2 (standard error, 5.0) kg in year 1 and a mean of 3.4 (standard error, 5.5) kg in years 1-5. Men gained a mean of 4.9 (standard error, 4.9) kg in year 1 and a mean of 2.6 (standard error, 5.8) kg in years 1-5. In regression analyses, smoking-change variables were the most potent predictors of weight change. Participants going from smoking to quit-smoking in a given year had mean weight gains of 2.95 kg/year (3.61%) in men and 3.09 kg/year (4.69%) in women. Over 5 years, 33% of sustained quitters gained > or = 10 kg compared with 6% of continuing smokers. Also among sustained quitters, 7.6% of men and 19.1% of women gained > or = 20% of baseline weight; 60% of the gain occurred in year 1, although significant weight gains continued through year 5. The average gains and the high proportions of sustained and intermittent quitters who gained excessive weight suggest the need for more effective early interventions that address both smoking cessation and weight control.

Adult↗
PubMed1998

Differences in distribution of ages of onset in males and females with schizophrenia.

An earlier age at onset of schizophrenia in men as opposed to women, has been widely reported, but hitherto, insufficient account has been taken of parameters that might confound this finding. Furthermore, few explanatory models have accounted for the differences in shape of the age-at-onset distributions in males and females with schizophrenia. A catchment area sample of 477 first contact cases with schizophrenia or related disorders was ascertained through a case register. Differences in age at onset distributions between males and females were determined, and adjustment made for potential confounding factors. The most powerful predictors of early illness-onset were poor premorbid occupational functioning, single marital status, and male sex. The earlier onset in males was robust to controlling for other parameters. The shape of the onset distribution also differed between the sexes: SKUMIX analysis revealed a two-peak distribution for males, and a three-peak distribution for females. The mean age at onset for schizophrenia is earlier in males, and the onset distribution differs between the sexes. Psychosocial variables cannot explain these findings. Possible explanations for these gender differences include males and females being differentially susceptible to subtypes of illness with different mean ages at onset; precipitating and/or ameliorating factors operating at different stages of life in males and females; and/or an X-linked susceptibility locus that determines the age at onset.

Age Factors↗
PubMed1998

Defective expression of granulocyte-macrophage colony-stimulating factor/interleukin-3/interleukin-5 receptor common beta chain in children with acute myeloid leukemia associated with respiratory failure.

Deficiency of the granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin-3 (IL-3)/IL-5 receptors common beta chain (betac) is a cause of fatal respiratory failure. betac deficiency manifests as pulmonary alveolar proteinosis (PAP). PAP has heterogenous etiologies that may be genetic or aquired. Some cases of PAP have been reported to be associated with hematologic malignancies such as acute myeloid leukemia (AML). In mice, the PAP phenotype was generated by targeted deletion of the gene for betac and can be treated by transplantation of wild-type bone marrow into betac -/- mice. Thus, our findings in betac -/- mice provide evidence for a causal relationship between the lung disease and the hematopoietic system. We describe here expression defects of betac or betac plus GM-CSF receptor alpha chain (GM-CSFR alpha) in 3 pediatric patients with AML and PAP symptoms. All of the patients' leukemic cells failed to express normal levels of betac. The leukemic cells of patients no. 2 and 3 additionally lacked the expression of GM-CSFR alpha, as shown by flow cytometry. Strikingly reduced or absent function of betac was demonstrated in clonogenic progenitor assays with absent colony-forming unit (CFU) growth after GM-CSF or IL-3 stimulation. The response to growth factors acting via a growth factor receptor distinct from the GM-CSF/IL-3/IL-5 system (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) was normal. After antileukemic treatment, the pulmonary symptoms resolved and betac or betac plus GM-CSFR alpha expression was normal. Our findings provide evidence that a defect in the expression of betac or betac plus GM-CSFR alpha on AML blasts can be associated with respiratory failure in patients with AML.

Acute Disease↗
PubMed1998

Mice deficient for the ecto-nicotinamide adenine dinucleotide glycohydrolase CD38 exhibit altered humoral immune responses.

CD38 is a membrane-associated ecto-nicotinamide adenine dinucleotide (NAD+) glycohydrolase that is expressed on multiple hematopoietic cells. The extracellular domain of CD38 can mediate the catalysis of NAD+ to cyclic adenosine diphosphoribose (cADPR), a Ca2+-mobilizing second messenger, adenosine diphosphoribose (ADPR), and nicotinamide. In addition to its enzymatic properties, murine CD38 has been shown to act as a B-cell coreceptor capable of modulating signals through the B-cell antigen receptor. To investigate the in vivo physiological function(s) of this novel class of ectoenzyme we generated mice carrying a null mutation in the CD38 gene. CD38-/- mice showed a complete loss of tissue-associated NAD+ glycohydrolase activity, showing that the classical NAD+ glycohydrolases and CD38 are likely identical. Although murine CD38 is expressed on hematopoietic stem cells as well as on committed progenitors, we show that CD38 is not required for hematopoiesis or lymphopoiesis. However, CD38-/- mice did exhibit marked deficiencies in antibody responses to T-cell-dependent protein antigens and augmented antibody responses to at least one T-cell-independent type 2 polysaccharide antigen. These data suggest that CD38 may play an important role in vivo in regulating humoral immune responses.

ADP-ribosyl Cyclase↗