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Biomedical subjects

W B Hunt

Publications and source records attributed to W B Hunt.

15 recordsLinked to original sources
PubMed1996

Time course of physical and psychological responses to selegiline monotherapy in newly diagnosed, idiopathic parkinsonism.

RATIONALE: Poor specificity of face-value endpoints and the poor sensitivity of gross clinical examination may have militated against demonstrating prophylaxis by selegiline. METHODS: Objective measures of the four cardinal signs were used as primary outcome criteria in a randomised, double-blind, placebo-controlled, parallel group study of selegiline monotherapy in 25 newly diagnosed elderly sufferers from idiopathic parkinsonism, stratified for sex and Hoehn and Yahr functional staging. RESULTS: There was a significant interaction between time and nature of treatment with respect to rigidity. The effect of time during active treatment was highly significant: rigidity decreased by 1.3% per week. The worsening of rigidity on placebo was not statistically significant. Neuronal rescue is a possible explanation for the long term, progressive improvement produced by selegiline. No significant treatment effect was seen on the other cardinal signs. However, there was a significant quadratic time trend for arousal on active treatment suggesting tolerance to this effect. CONCLUSION: The difference in time course between the psychostimulant and physical effects suggests more than one mode of action.

Aged↗
PubMed1996

Objective measurement of activation of rigidity: diagnostic, pathogenetic and therapeutic implications in parkinsonism.

1. Quantification of the effect on rigidity of its 'activation', by isometric grip, of standardized pressure, of the contralateral hand, was explored. Torque required to move the forearm through a fixed angle of 40 degrees, at a controlled rate of 0.5 Hz, in a horizontal plane about a pivotal axis aligned to the elbow joint, was recorded before (12 'baseline' recordings), during (10), and after (> or = 8) activation. Work required per unit displacement was calculated. 2. Specificity: Pilot serial daytime measurements gave an overall mean ratio, work required on activation over baseline, of 2.94 (95% CI 2.53, 3.42) in two elderly untreated parkinsonians, and 3.19 (2.75, 3.71) in two elderly subjects with isolated, clinically activation phenomenon, compared with 1.90 (1.64, 2.21) in two elderly without (P < 0.001), whilst two young adults did not activate, 0.98 (0.85, 1.14). In elderly subjects, work required under activation decreased during the day in health (-10 (-5, -14)% h-1, P = 0.0002), showed no significant change in those with clinical activation (4 (-1, 9)% h-1), and increased in parkinsonians (6 (0, 12)% h-1, P = 0.05): there appeared to be a transitionary state. 3. Validation of methodology: Quantifying the same work ratio on a single occasion in 20 aged parkinsonians (P), their spouses (Ps), 20 index controls (C) without parkinsonism, matched to (P), and their spouses (Cs) gave corroborative evidence of a pre-clinical state, defined by other measurements, in the spouses of sufferers. Values for C, Cs and Ps, 1.89 (1.42, 2.52), 2.38 (1.79, 3.17) and 2.93 (2.20, 3.90) respectively, were in consecutive positions, from health to (P, 2.96 (2.22, 3.95)) disease (P = 0.001 for Ps c.f. C; P = 0.1 for Ps c.f. Cs). Data on change over the day may enhance discrimination. 4. Sensitivity to medicines was illustrated, in two parkinsonians, by randomised, placebo balanced and controlled challenges: 1 and 2 tablets, Sinemet CR (Du Pont Pharmaceuticals, each levodopa 200 mg/carbidopa 50 mg) and 1 tablet, Sinemet-Plus (levodopa 100 mg/carbidopa 25 mg), then two 2 mg tablets, benzhexol. The dopaminergic effect (P < 0.001) was selective for activation (treatment.test-condition interaction, P = 0.004), and showed the expected time profiles. The effect of benzhexol (P = 0.008) lacked such selectivity. Its onset (> 4, < or = 6 h) was delayed, compatible with a gastrointestinal anti-muscarinic action and the subjects' ages. 5. Reliability (Fleiss's criterion) was shown to be good in 30 untreated parkinsonians.

Adult↗
PubMed1993

Quantification of the cardinal signs of parkinsonism and of associated disability in spouses of sufferers.

Work on the causation of idiopathic parkinsonism is limited by relying on gross clinical definition and lack of studies in the old. A prognostic index for parkinsonism, based on hypo/bradykinesia of gait, had considerably higher values in spouses of 20 aged suffers, who had been cohabiting for about half a century, than in 40 controls. Postural abnormality, measured by standing sway and foot separation during walking, was also greater in these spouses. Marked differences remained after correction for relevant covariates. A blinded rigidity rating was greater in the spouses of sufferers, tremor rating was not. The differences found are difficult to explain by selective mating, learned or reactive behaviour. This suggests that environmental causative influences operate in adult life.

Aged↗
PubMed1988

Evaluation of the safety of enalapril in the treatment of heart failure in the very old.

We have introduced enalapril, in doses equal to or less than the 2.5 mg currently recommended, as an adjuvant to digoxin and diuretics in 17 patients of mean (SD) age 83 (5) years with severe heart failure. Only eleven patients tolerated its introduction. Unlike those reported in younger patients, all but one of the adverse drug reactions occurred 8 h or more after the first dose. Aged patients started on ACE inhibitors should be observed in hospital until stabilized on a maintenance dose. Three patients had an adverse reaction which differed in nature from those previously reported: acute confusional state, ataxia and mesenteric ischaemia. Ten patients were discharged on 5 mg or 10 mg maintenance doses of enalapril. In nine of them improvement on triple therapy was sustained for a minimum of three months. ACE inhibition was lost in the other patient when her compliance with enalapril therapy fell to around 75%: monitoring compliance is essential when ACE inhibitors are used in low dosages. Enalapril was withdrawn during follow up in three patients because of symptoms of mesenteric ischaemia and in four because of dramatic deterioration of renal function. One of the latter was found subsequently to have severe bilateral atheromatous renal artery stenosis. When isosorbide dinitrate was substituted for enalapril, symptoms of mesenteric ischaemia resolved and renal function returned to baseline. Continuing surveillance for adverse effects is essential in patients of this age group with severe heart failure, and the risk of occult renal artery stenosis requires regular biochemical screening during follow up.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1978

The production of morphine tolerance and physical dependence by the oral route in the rat. A comparative study.

A method for the chronical administration of morphine by the oral route is discussed and compared with the production of physical dependence to morphine by injection. The method recommends the administration of Morphine HCl dissolved in a 45% sucrose syrup and given orally for 4 weeks. The initial concentration of morphine in the syrup was 1 mg/ml and was increased weekly up to 4 mg/ml at the end of the experiment. This procedure rendered the animals physically dependent on morphine as observed by drug withdrawal, when abstinence symptoms were easily identified.

Administration, Oral↗