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Biomedical subjects

G M Stern

Publications and source records attributed to G M Stern.

At least 109 records · Page 6Linked to original sources

Electroconvulsive therapy in Parkinsonian patients with the "on-off" syndrome.

Marked, abrupt and disabling oscillations in motor performance--the "on-off" phenomenon--frequently occur in the course of long-term levodopa therapy for Parkinson's disease. Although these fluctuations are usually refractory to available medications it has recently been suggested that electroconvulsive therapy (ECT) may be beneficial Five Parkinsonian patients with incapacitating and unpredictable "on-off" changes who were free of significant depression were given conventional bilateral ECT while usual drug regimens were maintained. While ECT was well tolerated, after a total of six treatments no significant improvement in Parkinsonian disabilities or "on-off" changes were seen.

Depression↗

The impact of treatment with levodopa on Parkinson's disease.

The progress of 178 patients with Parkinson's disease who began treatment with levodopa between November 1969 and December 1972 is reviewed after six years. One hundred and twenty-five patients showed an initial improvement of their individual total disability scores exceeding 25 per cent, but after six years of sustained treatment only 37 patients still obtained similar benefit. By 1978 only five patients had maintained their initial improvement compared to 69 patients after two years therapy; however, 47 patients were still better than before treatment. The overall mortality ratio--the ratio of observed to expected death rate--for all the patients was 1.45:1. In those patients who unable to tolerate levodopa for longer than two years the ratio was 2.38:1; in those who were able to tolerate sustained medication, life expectancy was normal (ratio of 0.91:1 for males and 1.14:1 for females). Involuntary movements were the commonest complication of treatment. Three main types were distinguished. Peak dose dyskinesias, beginning 20 to 90 minutes after an oral dose and most severe midway through the inter-dose period, affected 80 per cent of patients. Early morning and end-of-dose dystonia occurred in 20 per cent of patients and biphasic dyskinesia--two distinct episodes of involuntary movements within each inter-dose period--was the least common pattern affecting 3 per cent of patients. Involuntary movements increased in frequency and severity as treatment continued. End-of-dose deterioration ('wearing-off' effect of individual doses) occurred in 65 per cent of patients: unpredictable oscillations in motor performance (the 'on-off' phenomenon) unrelated to the time and dosage of levodopa, occurred in 10 per cent. Psychiatric side effects included toxic confusional states, visual pseudohallucinations and paranoid psychoses and constituted the most frequent reason for stopping medication. Forty (22 per cent) of the patients had suffered severe depression before the onset of disease and levodopa had no sustained antidepressant effect in this group. After six years of treatment with levodopa, 32 per cent of the patients had unequivocal dementia.

Dyskinesia, Drug-Induced↗

Tiapride in levodopa-induced involuntary movements.

Tiapride, a substituted benzamide derivative closely related to metoclopramide, reduced levodopa-induced peak dose involuntary movements in 16 patients with idiopathic Parkinson's disease. However, an unacceptable increase in disability from Parkinsonism with aggravation of end-of-dose akinesia led to its cessation in 14 patients. Tiapride had no effect on levodopa-induced early morning of "off-period" segmental dystonia. These results fail to support the notion that levodopa-induced dyskinesias are caused by overstimulation of a separate group of dopamine receptors.

Aged↗

Chip fractures of the os triquetrum: the mechanism of injury.

Studies derived from analyses of radiographs and dissections of cadaveric wrists have been directed at testing and disproving the commonly held theories that link chip fractures of the os triquetrum with avulsion. The authors found that the mechanism of such injuries involved a chisel action of the ulnar styloid upon the dorsum of the os triquetrum; furthermore, the impact of a fall on the outstretched arm with the hand rigidly held in strong dorsiflexion and ulnar deviation could be forceful enough to fracture the body of the os triquetrum as well. In all cases a striking prolongation of the ulnar styloid, beyond the surface of the ulnar head, was consistently noted.

Carpal Bones↗

Deprenyl administration in man: a selective monoamine oxidase B inhibitor without the 'cheese effect'.

After pretreatment with the selective monoamine oxidase B inhibitor, (-)-deprenyl, in doses sufficient for complete inhibition of the platelet enzyme, 4 normal and 6 parkinsoniam volunteers (2 receiving levodopa and 2 levodopa plus carbidopa) suffered no adverse pressor reaction ('cheese effect') after challenge with oral tyramine in amounts considerably greater than those likely to be encountered in a normal diet. Nor did the levodopa-deprenyl combination itself result in a pressor response. Normal human intestinal mucosa was shown predominantly to contain the deprenyl-insensitive A form of the enzyme, which presumably degraded administered tyramine in the deprenyl-treated volunteers; even those receiving the drug for prolonged periods manifested no 'cheese effect', suggesting that the A form remained uninhibited. Intestinal monoamine oxidase A was able to oxidise dopamine, whereas in human platelet or striatum the amine is a monoamine oxidase B substrate. Like tyramine, oral phenylethylamine challenge with amounts greater than those known to be present in a normal diet similarly gave rise to no adverse reaction in (-)-deprenyl-treated subjects; the reasons for this remain to be determined.

Adult↗

Bromocriptine in parkinsonism. A long-term study.

Bromocriptine was given in a controlled trial to 86 parkinsonian patients. Eight of 30 previously untreated patients with early and mild disease showed sustained benefit for two years and did not develop "on-off" effects or dyskinesias. Only two of 23 patients unable to tolerate or failing to respond to levodopa benefited from bromocriptine. Thirty-three patients with residual disabilities despite maximum tolerated doses of levodopa were also given bromocriptine: although benefit accrued, treatment was abandoned because of unacceptable side effects, and there was no improvement in the 11 with severe "on-off" disabilities. Although it was found that benefit from 70 mg daily of bromocriptine was comparable to that from 750 mg of levodopa with carbidopa, bromocriptine seems to offer no advantage to the majority of patients who have received or are receiving levodopa and/or carbidopa.

Anorexia↗

Absence of "cheese effect" during deprenyl therapy: some recent studies.

Although the selective monoamine oxidase (MAO) B inhibitor, (-)deprenyl, has been shown to be free from the "cheese effect" in man after tyramine challenge, the reason for this is far from clear: it may well be independent of the selective inhibitory action of the drug, for during chronic administration there is some evidence to suggest that both A and B forms of the enzyme are equally inhibited. By-passing the putative MAO A gut barrier in the pig (chosen because it possesses MAO B alone in all other tissues) by intravenous tyramine administration into the deprenyl-pretreated animal failed to provoke a pressor response, despite substantial MAO inhibition. Conversely, clorgyline (MAO A inhibitor) pretreatment, which resulted in minimal MAO inhibition, produced a profound hypertensive response, resembling that observed with the non-MAO-inhibiting drug, isoniazid. The most parsimonious explanation for these findings may be that two separate but closely associated pharmacological effects are normally found with "orthodox" MAO inhibitors, enzyme inhibition proper and facilitation of noradrenaline release from its binding sites during tyramine challenge.

Amphetamines↗

Endocrine aspects of bromocriptine therapy in Parkinsonism.

Plasma growth hormone (GH) concentrations in Parkinsonian patients following 3 months optimum therapy with bromocriptine showed no significant change from pretreatment values, whilst plasma prolactin concentrations were uniformly suppressed. Pretreatment GH and prolactin levels were unrelated to clinical disability, and no correlation between hormonal changes and therapeutic response was found. These results suggest the presence of different dopaminergic receptor mechanisms for GH and prolactin release as well as between the extrapyramidal and neuroendocrine systems.

Bromocriptine↗

Triceps tendon avulsion with or without fracture of the radial head--a rare injury?

The rarity of triceps tendon avulsion is called into question by our series of 6 cases collected over a 5-year period in a small, isolated Israeli community. The even rarer occurrence of triceps avulsion accompanying fractures of the radial head is more obviously contradicted by the 3 or 4 instances of such combined injuries in our series. Awareness that a fall on the outstretched arm, with or without fracture of the radial head, is sufficient cause of the triceps avulsion or tear ought to increase the frequency of the diagnosis. Just as fractures of the proximal ulna oblige the clinician to look for dislocations of the radial head (Monteggia or Hume fractures) (6), so must falls on the outstretched arm bring to mind the possibility of triceps tendon tears. Seemingly trivial findings then become significant, and the clinical entity thus crystallizes into the diagnostic syndrome.

Adult↗

Baclofen in Parkinson's disease.

In a controlled trial, baclofen (mean dose 45 mg daily) signficantly increased disability from Parkinsonism in 12 patients with the long-term levodopa syndrome. Peak dose choreoathetosis was not improved but benefit was observed in all four patients with "off period dystonia." Adverse side effects were common and severe, and included visual hallucinations, vomiting, and dizziness.

Aged↗