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Biomedical subjects

S Brandon

Publications and source records attributed to S Brandon.

At least 37 records · Page 2Linked to original sources

Interactions of vitamin E and penicillamine in the treatment of hereditary avian muscular dystrophy.

Our prior work demonstrated that penicillamine treatment of dystrophic chickens delayed the onset of symptoms, partially alleviated contractures, improved muscle function, and lowered serum creatine kinase. Penicillamine, a sulfhydryl compound with reducing properties, also prevented inactivation of glycolytic enzymes by protecting thiol groups. The present study shows that vitamin E enhances the therapeutic effects of penicillamine. Interaction of these two reductants is dose related. With vitamin E as adjunct therapy, the dosage level of penicillamine could be lowered by 50%, thereby minimizing side effects. The therapeutic rationale for two antioxidants is that penicillamine may act primarily in the cytoplasm to prevent oxidative damage, whereas the more hydrophobic vitamin E may protect membrane bilayers. Additionally, penicillamine may prevent collagen cross-linking and, deposition of insoluble collagen in muscle and thus decrease contracture formation. General applications of combined penicillamine and vitamin E therapy are discussed regarding prevention of free radical and oxidative damage in Duchenne dystrophy and a wide range of human diseases.

Animals

Mechanism of attenuated hydrochlorothiazide response during indomethacin administration.

Indomethacin antagonizes the natriuretic and chloruretic response to hydrochlorothiazide in most studies. Neither the mechanism nor nephron site of this antagonism has been determined. To identify sites and potential mechanisms, cortical micropuncture was performed during hydrochlorothiazide treatment in control and indomethacin rats. Indomethacin reduced (P less than 0.005) FeCl from 5.20 +/- 0.49% to 2.26 +/- 0.49% (mean +/- SE). MAP, CIn, and plasma volume were not different between groups. SNGFR and fractional proximal fluid and chloride delivery were not different between groups. Fractional chloride delivery to early distal tubules was 10.8 +/- 0.4% in control but 6.2 +/- 0.3% in indomethacin rats (P less than 0.001). Calculated loop chloride reabsorption was greater in indomethacin than control rats during hydrochlorothiazide administration (41.0 +/- 1.6% vs. 34.3 +/- 2.3%; P less than 0.05). Fractional chloride delivery to late distal tubules was 7.8 +/- 0.7% in control and 4.6 +/- 0.3% in indomethacin rats (P less than 0.005), but distal tubule chloride reabsorption was not different between groups. Papillary tissue chloride was less in control than indomethacin rats during hydrochlorothiazide (P less than 0.05). Urinary PGE2 excretion was reduced (P less than 0.001) by indomethacin during hydrochlorothiazide. Thus indomethacin induced reductions in hydrochlorothiazide response result in part from increased chloride reabsorption in the loop segment. This suggests indomethacin antagonizes hydrochlorothiazide by reducing chloride delivery to hydrochlorothiazide's site of action in the distal tubule rather than by effects of indomethacin on hydrochlorothiazide pharmacokinetics.

Animals

Leicester ECT trial: results in schizophrenia.

As part of the Leicester electroconvulsive therapy (ECT) study, the role of ECT in schizophrenia was investigated in a double-blind trial. The Present State Examination criteria for schizophrenia were fulfilled by 22 patients, of whom 19 gave consent and entered the trial. Neuroleptic medication was restricted during the trial period. Patients were randomly allocated to eight real ECT or eight simulated ECT. At the end of the four-week trial period, patients receiving real ECT showed a significantly greater improvement when measured on the Montgomery-Asberg Schizophrenia Scale (MASS), the visual analogue global psychopathology scale, and the depression scale. The differences on the MASS and visual analogue global psychopathology scale were not due to improvement in depressive symptoms. The superiority of real ECT was not demonstrated at the 12- and 28-week follow-up, when treatment was not controlled.

Adult

How likely is it that a district health authority can close its large mental hospitals?

A cross-sectional survey assessed all 1,087 patients who were in psychiatric beds provided by a large district health authority. The elderly predominated in all length of stay categories, and a high proportion of them had levels of social and physical incapacity which made it unlikely that they could be cared for other than in residential care. A substantial minority of younger patients with a length of stay between one and two years had levels of incapacity which suggested the need for major treatment, rehabilitation, or training efforts. The findings have major implications for Government policy to replace large mental hospitals.

Activities of Daily Living

Electroconvulsive therapy: results in depressive illness from the Leicestershire trial.

Electroconvulsive therapy was investigated in a double blind trial. Altogether 186 clinically selected patients were referred to the trial, but 48 of these did not participate. According to the present state examination, 95 of the remaining 138 patients fell into one of the classes of major depression. Patients were randomly allocated to a course of real or simulated electroconvulsive therapy. Treatment was given twice a week with a maximum of eight treatments. On the Hamilton depressive rating scale the improvement in the group given real treatment was significantly greater than that in the group given simulated treatment both at two weeks (p = 0.014) and at four weeks (p = 0.0001). At follow up at 12 and 28 weeks there was no difference between the treatment groups. At the end of the four week trial consultants, who were blind to the allocation of treatment, rated the patients who had received real treatment as having made a significantly greater improvement than the patients who had received simulated treatment (p less than 0.00005). Further analysis showed that electroconvulsive therapy was effective in depression associated with delusions and in depression associated with retardation.

Clinical Trials as Topic