The Maudsley lecture, 1987. Changing disciplines in psychiatry.
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Biomedical subjects
Publications and source records attributed to M Shepherd.
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The effect of energy deprivation and H2O2 on the contraction, shape, and intracellular free Ca2+ concentration of myocardial muscle cells was investigated using suspensions of freshly isolated, electrically stimulated rat ventricle heart cells. The mitochondrial uncoupling agent carbonyl cyanide m-chlorophenylhydrazone (CCCP) was used to decrease the rate of ATP synthesis. At 0.9 mM extracellular Ca2+, CCCP (0.25 microM) reduced the number of contracting cells by 50% after 5 min, and the number of rod-shaped cells by 40% after 10 min. The effects of CCCP were associated with a substantial decrease in measured cellular ATP concentrations. The deleterious effect of exposure of myocytes to CCCP for periods of up to 5 min was enhanced by an increase in the extracellular Ca2+ concentration, but markedly reduced in the absence of electrical stimulation. Verapamil protected myocytes from the deleterious effects of CCCP during the first 5 min but not at later times. In the presence of 46 mM extracellular K+, CCCP caused a marked increase in the myoplasmic free Ca2+ concentration (measured using quin2). This effect was inhibited by verapamil and was not observed in the absence of K+-induced depolarization. Exposure of myocytes to H2O2 (0.5 mM) caused a substantial decrease both in the number of cells which exhibited normal end-to-end synchronous contraction and in the total number of cells which contracted either partially or fully. The effects of H2O2 were more pronounced at higher concentrations of the peroxide, with longer times of exposure to the agent, and at higher concentrations of extracellular Ca2+, and were partially reversed by dimethyl sulfoxide. The results indicate that both ATP deprivation and H2O2, possibly through the generation of free radicals, cause substantial and rapid damage to cardiac myocytes and induce the movement of additional Ca2+ across the sarcolemma to the myoplasm. In the case of ATP deprivation, this initially occurs through voltage-operated channels.
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Data from a large-scale (N greater than 3000) community survey (the 'West London Survey') were used to examine the effect of minor psychiatric morbidity on the probability of contact with primary medical care, and factors which influenced this effect. The presence of such morbidity was found to double the probability of consulting, and about one-fifth of consultations could be attributed to it. Logistic analysis was used to investigate the joint effect on general practice consultation of minor psychiatric morbidity, three other health-related variables and five sociodemographic variables. It was found, as expected, that the health variables exerted much more influence on consulting than the sociodemographic variables, but that the relationship was characterized by complex interactions between health and sociodemographic variables. In particular, sex, socioeconomic status and minor psychiatric morbidity interacted in their effect on the probability of general practitioner consultation. The findings are interpreted in the context of previous theoretical and empirical work.
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1. A controlled clinical trial has shown oral pimozide to be clinically at least as effective as fluphenazine decanoate in the continuation treatment of schizophrenia. 2. Pimozide was also associated with more favourable measures of social outcome. 3. Some implications of these findings are discussed.
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Mediastinoscopy, in the skilled hands of a thoracic surgeon has proved to be a safe, cosmetically accepted procedure with negligible complications. It has yielded a high rate of diagnostic lymph node tissue; overall greater than 82% among patients with sarcoidosis, including patients presenting with pulmonary mottling only or with a normal chest radiograph. Among patients with lymphatic tuberculosis it enabled the isolation of human M. tuberculosis following culture of the lymph node removed on Löwenstein-Jensen medium in greater than 79% of cases. A precise histological diagnosis was obtained in all 14 patients presenting with hilar and/or paratracheal lymphadenopathy attributable to malignant disease.
The epidemiological method is indispensable to the clinical investigator, the practising clinician and the public health worker. In the field of mood disorders epidemiological inquiry has been hampered by the subjective nature of the phenomena under study, the problems of assessment and diagnosis, observer bias and the unrepresentative nature of small population samples. Nontheless, it is argued that the difficulties are similar to those encountered elsewhere in medicine and examples are given of epidemiological contributions to an understanding of depression.
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Evidence from a controlled, comparative trial indicates that oral pimozide is clinically at least as effective as depot injections of fluphenazine decanoate in the continuation therapy of a group of schizophrenic patients discharged from hospital. The administration of pimozide was associated with fewer unwanted effects. The implications of the findings are discussed.
A blind social assessment at home carried out twice during a year's follow-up of 41 patients on continuation therapy, 21 randomly allocated to pimozide tablets and 20 to fluphenazine decanoate injections. Patients on pimozide were significantly more favourably rated on aspects of sociability, use of leisure, warmth of personal relationships, household tasks and child-rearing. The mode of production of this result is discussed.
The hypothesis that schizophrenia is caused by the release of prostaglandin E into the hypothalamus and may sometimes be accompanied by an elevation of temperature was examined by a clinical trial of the prostaglandin E suppressant N-acetyl-p-amino-phenol (paracetamol, acetaminophen). Ten acute schizophrenic patients were included in a double-blind, crossover trial of paracetamol and a placebo, in which each treatment was given for a week. Regular 4-hourly temperatures were recorded in all these cases and in 5 non-schizophrenic patients for comparison. The findings provided no evidence that paracetamol mitigated the symptoms of schizophrenia. The temperatures of the schizophrenics were not elevated more than those of the controls, but the number of cases used was probably too small for this finding to be conclusive.