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Biomedical subjects

E C Johnstone

Publications and source records attributed to E C Johnstone.

At least 19 recordsLinked to original sources

3-Methoxy-4-hydroxyphenylglycol excretion in acutely schizophrenic patients during a controlled clinical trial of the isomers of flupenthixol.

Urinary MHPG excretion in patients with acute schizophrenia was studied before and during a trial of the isomers of flupenthixol and placebo. Pretrial MHPG excretion was not related to severity of illness before the trial or to other pretrial clinical variables. In male subjects higher pretrial MHPG excretion was associated with a better outcome 1 year post-trial. However in females no relationship between MHPG excretion and outcome was established. During the trial there was a reduction in MHPG excretion in patients treated with beta-flupenthixol but no decrease in the group treated with alpha-flupenthixol or chlorpromazine. In patients on placebo there was a reduction in MHPG excretion in those who did well clinically, but not in those who did poorly. Thus low MHPG excretion may be a predictor of poor outcome in schizophrenia, but MHPG excretion also changes both as a function of clinical state and of neuroleptic drug administration.

Adult

Characteristics of patients with schizophrenia or neurological disorder and virus-like agent in cerebrospinal fluid.

A virus-like agent (V.L.A.) with a cytopathic effect on cultured cells was found in the cerebrospinal fluid of 18 of 47 patients with schizophrenia, of whom 10 had nuclear schizophrenic symptoms. In most patients with V.L.A., blood and C.S.F. protein concentrations were normal. Patients with and without V.L.A. had similar clinical characteristics but serum IgA levels were higher in those with V.L.A. V.L.A. was also detected in the C.S.F. of 8 of 11 patients with serious or chronic neurological disease (Huntington's chorea, multiple sclerosis, and unexplained alterations of consciousness).

Acute Disease

Acetylation of phenelzine.

Microsome-free preparations of rodent and human liver were shown to contain N-acetyl transferase from experiments using procainamide as substrate. These preparations then acetylated phenelzine from the quantitative transfer of radiolabeled acetate. This in vitro demonstration of phenelzine acetylation in rodent and human liver was corroborated by the finding of a negative correlation between excretion of phenelzine in urine and sulphadimidine acetylation in 27 patients.

Acetyl Coenzyme A

Blood levels of flupenthixol in patients with acute and chronic schizophrenia.

Plasma levels of flupenthixol were estimated by three methods in 30 patients with acute schizophrenia and 29 patients with chronic schizophrenia. These levels were related to clinical response, anterior pituitary hormone secretion, platelet monoamine oxidase activity, the effects of the concurrent administration of anticholinergic drugs, and body weight. No clearcut relationships between plasma flupenthixol levels and any of these variables were demonstrated. The practical clinical value of the estimation of plasma flupenthixol is limited at the present time.

Acute Disease

Skin conductance responsivity during acute episodes of schizophrenia as a predictor of symptomatic improvement.

Skin conductance responses to a series of tones were measured in 41 patients during an acute episode of schizophrenia before they received treatment and after 4 weeks of treatment with either alpha-flupenthixol, beta-flupenthixol or placebo. Patients who did not habituate to the tones prior to treatment tended to show no symptomatic improvement during the course of treatment. Patients who habituated and also showed an acute onset of their current symptoms ('Feighner negative' patients) showed a marked improvement even without active medication. Skin conductance responsivity did not change with improvement in symptoms alone, but decreased in patients on active medication (alpha-flupenthixol). Non-habituation of skin conductance and insidious onset (i.e. fulfilment of the Feighner criteria) were found to be independent predictors of poor outcome. Taken together, these criteria may define a group of patients with particularly poor prognosis.

Acute Disease

The outcome of severe acute schizophrenic illnesses after one year.

Forty-five patients with acute schizophrenic illnesses (defined by PSE criteria) were assessed in clinical, cognitive and social terms before being entered in a four week study of the isomers of flupenthixol and placebo. At the end of one year they were re-assessed in the same terms. The clinical and psychological features of the acute illness and the drug treatment given did not predict outcome. Poor outcome in social terms was significantly related to severe social isolation in the initial assessment and to the presence of nuclear symptoms and negative schizophrenic features at follow-up.

Acute Disease

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Clinical Trials as Topic

Mechanism of the antipsychotic effect in the treatment of acute schizophrenia.

In a double-blind trial in which 45 patients with acute schizophrenia took part the alpha-isomer of flupenthixol (which blocks the dopamine receptor) was found to be significantly more effective than both beta-flupenthixol (which does not) and placebo. The drug effect was confined to the "positive" symptoms--delusions, hallucinations, and though disorder--and appeared only in the 3rd and 4th weeks of the trial. It was as great in patients with evidence of deterioration (Feighner-positive patients) as in patients without deterioration and was less in patients who had affective disturbance in addition to schizophrenia symptoms. The findings are consistent with the hypothesis that dopamine-receptor blockade is the only requirement for antipsychotic activity and suggest that the antipsychotic effect occurs in patients with typically schizophrenic illnesses but may be limited to positive symptoms.

Acute Disease

Neuroendocrine changes in acute schizophrenia as a function of clinical state and neuroleptic medication.

Changes in levels of prolactin, growth hormone, luteinizing hormone, and follicle stimulating hormone in serum, and testosterone in plasma, have been studied in 38 patients with acute schizophrenic illnesses in a 4-week double-blind comparison of the 2 isomers of flupenthixol and placebo. Only prolactin showed changes which could be related either to changes in clinical state or to the effects of medication. Prolactin levels increased during treatment with the therapeutically active alpha-isomer of flupenthixol but were unchanged with the inactive beta-isomer and placebo. Although there was a significant relationship between prolactin level and antipsychotic effect in patients on alpha-flupenthixol, in the individual case prolactin level was not a strong predictor of therapeutic response; and in patients on inactive medication changes in prolactin level could not be related to sympton change. There was a time lag of at least 2 weeks between the increase in prolactin secretion in patients on alpha-flupenthixol and the therapeutic effect attributable to medication. This delay suggests that if the antipsychotic effect is dependent upon dopamine receptor blockade it is not a direct consequence of this action. Perhaps dopamine receptor blockade permits other, and slower, changes to take place and it is these changes, rather than dopamine receptor blockade itself, which are reflected in clinical improvement.

Acute Disease