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R Murray

Publications and source records attributed to R Murray.

At least 55 records · Page 3Linked to original sources

Activity of exemestane in metastatic breast cancer after failure of nonsteroidal aromatase inhibitors: a phase II trial.

PURPOSE: To evaluate the antitumor activity and toxicity of a new steroidal aromatase inactivator, exemestane, in postmenopausal women with metastatic breast cancer who had progressive disease (PD) after treatment with a nonsteroidal aromatase inhibitor. PATIENTS AND METHODS: In this phase II trial, eligible patients were treated with exemestane 25 mg daily (n = 241) followed, at the time PD was determined, by exemestane 100 mg daily (n = 58). RESULTS: On the basis of the intent-to-treat analysis by independent review, exemestane 25 mg produced objective responses in 6.6% of patients (95% confidence interval [CI], 3.8% to 10.6%) and overall success (complete response + partial response + no change for 24 weeks or longer) in 24.3% (95% CI, 19.0% to 30.2%). The median durations of objective response and overall success were 58.4 weeks (95% CI, 49.7 to 71.1 weeks) and 37.0 weeks (95% CI, 35.0 to 39.4 weeks), respectively. Increasing the dose of exemestane to 100 mg upon the development of PD produced one partial response (1.7%; 95% CI, 0.0% to 9.2%). Both dosages were well tolerated and were discontinued because of adverse events in only 1.7% of patients. CONCLUSION: Exemestane 25 mg once daily seems to be an attractive alternative to chemotherapy for the treatment of patients with metastatic breast cancer after multiple hormonal therapies have failed.

Administration, Oral↗

[Lack of gender effect on familial schizophrenia. A Brazilian study].

Epidemiological studies on schizophrenia have showed different age at onset between gender, in which male schizophrenics present symptoms earlier than females. However this gender effect is not observed within familial schizophrenia. The present study investigates the age at onset in 31 RDC-schizophrenics from 13 Brazilian families. No differences in age at onset were found between gender, confirming previous studies in other populations. This result may indicate genetic influences on age at onset in a subgroup of patients affected by schizophrenia and can be explored by molecular genetic studies.

Adolescent↗

The doctor and the rebels--the diary of Charles Molteno Murray, recorded during the 1914 Boer rebellion.

Just 12 years after the conclusion of the Anglo-Boer war, South Africa was led by ex-Boer Generals Botha and Smuts into what was to become the Great War, on the side of the British. This was utterly unacceptable to thousands of Boers who had engaged in a bitter struggle, against overwhelming odds, to prevent their country from becoming part of the mighty British Empire. Led by Generals de Wet, Beyers, and de la Rey, Lieutenant-Colonel Maritz and Major Kemp, they took up arms in a doomed rebellion, without proper weapons, equipment or organisation--by the time they were defeated the casualty figures for both sides exceeded those that would later result from the German South West campaign. Charles Molteno Murray, 37 years old, was a GP in Kenilworth, Cape Town, at the time. His father was an Irish immigrant doctor, his mother the daughter of the first Prime Minister of the Cape, Sir John Charles Molteno. In spite of having a busy and successful practice, with a surgical appointment at Victoria Hospital, Charles Murray volunteered for duty and soon found himself in the Orange Free State and northern Cape, caring for the wounded and dying of both sides in the rebellion. He kept a meticulous record of his experiences, written on loose-leaf pages sent as letters to his wife, which were later bound into leather-backed diaries. These diaries were passed on to his grandson, Dr Robert Murray, who had them transcribed into modern format. They contain details of daily life in the midst of military action, and also insights into important and little-publicised events of the Boer Rebellion of 1914.

History, 20th Century↗

Lack of normal pattern of cerebral asymmetry in familial schizophrenic patients and their relatives--The Maudsley Family Study.

Lack of the normal cerebral asymmetry has been reported in schizophrenia. We wished to test the hypothesis that this lack of the normal pattern of asymmetry is familial and that it can be found in both schizophrenic and non-schizophrenic family members. In particular, we wanted to know whether those relatives who appear to be transmitting liability to the illness also demonstrate the loss of normal asymmetry. We studied families with several members affected with schizophrenia. We carried out volumetric measurements of prefrontal, premotor, sensorimotor and occipitoparietal regions in each hemisphere using 3D reconstructed MRI images in 29 schizophrenic patients, 55 of their first degree relatives, and 39 unrelated control subjects on contiguous thin slices of the brain. Nine of the unaffected relatives appeared to be transmitting the liability for schizophrenia (e.g. the mother of a schizophrenic patient who, although not psychotic herself, had a schizophrenic parent or sibling). We termed them presumed obligate carriers and the remaining 46 relatives presumed non-obligate carriers. The healthy control subjects showed larger right than left prefrontal regions and larger left than right sensorimotor and occipitoparietal regions. The schizophrenic patients showed lack of this normal brain asymmetry in the prefrontal, sensorimotor and occipitoparietal cortical regions. The presumed obligate carriers were similar to the schizophrenic patients in exhibiting lack of asymmetries in these cortical regions, while the presumed non-obligate relatives showed lack of asymmetry only in the occipitoparietal region. There was no overall reduction in total or regional brain volumes among the groups. Our findings indicate that lack of the normal pattern of frontal and occipital asymmetry is a marker for genetic liability to schizophrenia in families multiply affected with schizophrenia.

Adult↗

Hippocampal volume reduction in schizophrenia: effects of genetic risk and pregnancy and birth complications.

BACKGROUND: Hippocampal volume reduction has been repeatedly demonstrated in schizophrenia. The relative contribution of genetic and environmental factors to this is unclear. METHODS: To address this question, we compared volumetric measurements of the left and right hippocampus, obtained using stereological methods from brain MRI scans, from two groups of patients with schizophrenia as well as healthy controls (n = 26). Patients (n = 27) in the first group, had no family history of schizophrenia and had experienced severe pregnancy and birth complications (PBCs). The second group comprised of patients (n = 21) without a history of severe PBCs from families multiply affected with schizophrenia. RESULTS: Reduction of the left hippocampal volume was associated with the diagnosis of schizophrenia but was present only in patients with a history of severe PBCs; in this group the smaller hippocampal volume, the earlier the onset of psychosis. CONCLUSIONS: Our findings suggest that environmental factors, in this case severe PBCs, make a significant contribution to hippocampal abnormalities in schizophrenia.

Adult↗

A comparison of the utility of dimensional and categorical representations of psychosis. UK700 Group.

BACKGROUND: The usefulness of any diagnostic scheme is directly related to its ability to provide clinically useful information on need for care. In this study, the clinical usefulness of dimensional and categorical representations of psychotic psychopathology were compared. METHOD: A total of 706 patients aged 16-65 years with chronic psychosis were recruited. Psychopathology was measured with the Comprehensive Psychopathological Rating Scale (CPRS). Lifetime RDC, DSM-III-R, and ICD-10 diagnoses and ratings of lifetime psychopathology were made using OPCRIT. Other clinical measures included: (i) need for care; (ii) quality of life; (iii) social disability; (iv) satisfaction with services; (v) abnormal movements; (vi) brief neuropsychological screen; and (vii) over the last 2 years--illness course, symptom severity, employment, medication use, self-harm, time in hospital and living independently. RESULTS: Principal component factor analysis of the 65 CPRS items on cross-sectional psychopathology yielded four dimensions of positive, negative, depressive and manic symptoms. Regression models comparing the relative contributions of dimensional and categorical representations of psychopathology with clinical measures consistently indicated strong and significant effects of psychopathological dimensions over and above any effect of their categorical counterparts, whereas the reverse did not hold. The effect of psychopathological dimensions was mostly cumulative: high ratings on more than one dimension increased the contribution to the clinical measures in a dose-response fashion. Similar results were obtained with psychopathological dimensions derived from lifetime psychopathology ratings using the OCCPI. CONCLUSIONS: A dimensional approach towards classification of psychotic illness offers important clinical advantages.

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗