Biomedical subjects
Publications and source records attributed to D M Shaw.
Times in remission from affective illness were prolonged during treatment with lithium carbonate and carbamazepine, but lithium was the more effective. Similar global scores for the two drugs suggested that other factors may determine their acceptability.
Nine patients have been treated by subcaudate stereotactic tractotomy for bipolar affective disorder resistant to drug treatments. In the majority, after the operation there was a reduction in frequency and severity of depressive and manic episodes. There was a trend for the operation to have more effect on the manic than on the depressive phases. Drugs which had been inert previously sometimes became therapeutically useful after surgery.
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The nutritional status of 23 severely demented patients was compared with that of 23 similarly aged controls in the community. A 3-day weighed intake on all subjects showed lower mean intakes of energy, protein, ascorbic acid and nicotinic acid in the mean intakes of energy, protein, ascorbic acid and nicotinic acid in the patient group. This group had lower levels of plasma ascorbic acid and red cell folate and of urinary N-methylnicotinamide excretion relative to creatinine. Over a third of both controls and patients had evidence of thiamin deficiency, as judged by a raised percentage erythrocyte transketolase activity. An earlier finding in patients with senile dementia of reduced fasting plasma concentrations of tryptophan was confirmed for total and protein bound fractions. With the possible exception of ascorbic acid, the data could not be explained satisfactorily in terms of intake. It is suggested that the association between the phenomena of aging, senile dementia and nutritional status merits further investigation.
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The response of patients with major depressive illness to citalopram of amitriptyline was compared in a double-blind multi-centre trial. No differences in efficacy were observed, but citalopram had less hypnotic effect, and a remarkably lower profile of side-effects.
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Explore the source record for details and available documents.
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Fourteen depressed in-patients were treated with 150 mg clomipramine (CLO) daily, given as one oral dose. Using a gas-chromatographic method, concentrations of CLO and desmethyl clomipramine (DMCLO) were determined in plasma samples taken at frequent intervals during 24 h. The plasma level of each compound 12 h after the dose correlated well with the average value in the same patient, calculated over the whole 24-h period. Levels at other times gave poorer correlations, and at 24 h it was particularly poor. Plasma DMCLO concentrations were usually maximum 4-6 h after the dose. The ratios of maximum to minimum levels averaged only 1.31 +/- 0.15 SD. Peak CLO levels occurred 3 or 4 h after the dose. Maximum; minimum ratios averaged 2.72 +/- 0.73 SD, contrasting with the much smaller fluctuations of plasma nortriptyline (NT) levels observed in patients given this drug once daily. The difference is not due to a shorter half-life of CLO, but to the absorption and/or distribution behaviour of the two drugs. Although not fully understood, this difference between tertiary and secondary amines appears to hold generally among the tricyclic antidepressants.
The equilibrium binding constants of the interaction of tryptophan with albumin have been determined in plasma samples from both controls and patients suffering from affective disorders. The data corresponded with literature values for both the albumin concentration in plasma and the equilibrium constant for tryptophan binding to albumin. No differences in the equilibrium constants were detected between patients and controls but a small increase in the albumin concentration was noted in the depressives. It was agreed that this rise would be inadequate to lead to a significant effect on free tryptophan levels. Non-esterified fatty acid analysis indicated no differences between patient groups.
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Patients suffering from unipolar illness and anticipating a complex investigation, or the first of a series of ECTs, had lower total tryptophan levels than control subjects under the former circumstances. This suggested a qualitative or quantitative difference in response to stress, associated with a fall in the amino acid level. It was hypothesized that this might selectively decrease synthesis of both protein and 5-HT in serotoninergic neurones.
As requirements for tryptophan for synthesis of protein and 5-hydroxytryptamine were comparable in rat brain, during depletion of tryptophan there could be competition between the two pathways for the amino acid. This implied that tryptophan should be rate-limiting for protein synthesis and this was found in the short term when concentrations of the amino acid were reduced in rats. Multicompartmental studies of tryptophan and tyrosine in controls and patients subject to unipolar depression defined two main pools of the amino acid provisionally assigned to extracellular and intracellular spaces. For tyrosine, mean values for the extracellular space were comparable to those of controls. The concentration of tyrosine was low in the intracellular space in both depressed and recovered patients, but the raised fractional clearance rates for this compartment during depression had returned to normal on remission. Plasma tryptophan concentrations were significantly reduced in depression with intermediate values after recovery. This suggested that the procedure used may have been mildly stressful and that this had evoked an idiosyncratic response to the stress in the depressed patients, which was characterized by inability to maintain concentrations of this amino acid in plasma. The findings for both amino acids may have a bearing on the aetiology of unipolar affective disorder.
Multicompartmental studies of tyrosine in patients suffering from affective disorders and controls gave estimates of 2 major pools of amino acid, together with the associated fractional clearance rates and fluxes. The 2 pools were considered provisionally to represent extracellular and intracellular tyrosine. The concentration of tyrosine in plasma (representing the extracellular pool) and fractional clearance rates from this compartment were normal in ill and recovered patients. The observed abnormalities were confined to the intracellular compartment and consisted of low concentrations of tyrosine in both depressed and recovered patients. In addition, fractional clearance rates from the intracellular compartment were raised in the depressed patients but had returned to normal after recovery. A comparison of these data with those of a similar study of tryptophan described previously suggested that alterations in compartmental volume or dietary differences could not explain the 2 sets of findings. The disturbances in tryptophan metabolism in unipolar affective disorder had led to reduced amounts of this amino acid in the extracellular space. In contrast, the concentration of tyrosine in this compartment was normal, presumably as a result of a metabolic adjustment to the lower amounts found in the intracellular pool. The presence of illness-dependent and illness-independent alterations in tyrosine metabolism in unipolar affective disorder, together with the earlier findings for tryptophan, may have a bearing on the aetiology of the illness.