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Biomedical subjects

D M Shaw

Publications and source records attributed to D M Shaw.

15 recordsLinked to original sources

The management of patients with an intrinsic supratentorial brain tumour.

The management of patients presenting with supratentorial glioma between 1978 and 1986 is reviewed. Complete follow-up in 517 cases was obtained. One hundred and fifty eight patients were not submitted to any form of surgery, 299 patients were biopsied and 60 patients underwent craniotomy and internal decompression. The no surgery group contained a higher proportion of patients with poor prognostic indicators than either the biopsy or craniotomy groups. The craniotomy group consisted of patients with better prognostic indicators than the biopsy group, in particular, younger age and more favourable site, type and grade of tumour. This was reflected in the difference in outcome between the groups. Median survival was 14 months in the craniotomy group, four months in the biopsy group and 2.2 months in the no surgery group. The outcome in patients with histologically proven malignant gliomas was best in those patients who received radiotherapy. The craniotomy group had a median survival of 18.5 months, a two year survival of 48% and a five year survival of 9%. The median survival following radiotherapy of those patients with proven malignant gliomas who had a biopsy was 9.5 months with a two year survival of 16% and a five year survival of 2%. These results compare favourably with studies which have adopted a more aggressive approach, suggesting that outcome is determined as much by patient selection using favourable prognostic indicators as by the treatment itself. The need for prospective trials of the management of unselected consecutive glioma patients randomizing them to conservative and radical treatment groups in order to define the role of both conventional therapy and radical therapy is discussed.

Adolescent

Distribution of tryptophan and tyrosine in unipolar affective disorders as defined by multicompartmental analysis.

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.

Adult

Multicompartmental analysis of amino acids. III. Tyrosine in 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.

Adult

Multicompartmental analysis of amino acids: II. Tryptophan in affective disorder.

Two of the tryptophan pools in the body and their associated fluxes, as defined by multicompartmental analysis, were studied in patients with unipolar affective disorder, bipolar patients (manic) and control subjects. The 2 pools were tentatively associated with extra- and intra-cellular compartments. The investigations were performed fasting and may have been mildly stressful. Under these conditions the concentration of tryptophan in plasma and perhaps amounts in the extracellular space were reduced in unipolar depression, with intermediate values after recovery. Some model parameters were lower in females than in males. The results in unipolar affective disorder were interpreted in terms of a previously presented hypothesis that this illness may result in an idiosyncratic response to stress in which patients are unable to maintain normal amounts of tryptophan in the body. In manic patients extracellular levels of tryptophan were unchanged but intracellular and total quantities of 'freely available' tryptophan may have been reduced.

Adult

Multicompartmental analysis of amino acid. 1. Preliminary data on concentrations, fluxes, and flow constants of tryptophan in affective illness.

The study of tryptophan metabolism using compartmental analysis suggested differences between males and females, and between control subjects and patients with affective illness, patients treated with tricyclic drugs, and those established on lithium therapy. The total mass of tryptophan in the body may be reduced in people prone to affective disorder, and in depressed patients(ill and well)turnover of tryptophan seemed to be reduced. The reduction of concentration of tryptophan in compartment S2 in affective illness could affect protein synthesis.

Antidepressive Agents, Tricyclic

Tricyclic antidepressants and tryptophan in unipolar depression.

Depressed patients (unipolar) were given one of the following combinations in an attempt to test aspects of the 'amine hypothesis' and to find a preferential therapy: (1) clomipramine; (2) clomipramine and tryptophan; (3) desipramine and clomipramine, and (4) desipramine and tryptophan. Treatment (2) should have given optimal potentiation of 5-HT neurones and (3) and (4) should have acted similarly on both serotoninergic and adrenergic pathways. In no group was there any evidence of accelerated recovery, indicating that the process of conversion to normal mood may be more complex than suggested by most versions of the amine hypothesis.

Clomipramine