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Biomedical subjects

D B Calne

Publications and source records attributed to D B Calne.

At least 217 records · Page 12Linked to original sources

Atenolol vs. propranolol in essential tremor. A controlled, quantitative study.

The beta-1 selective, hydrophilic adrenoceptor blocking drug atenolol (100 mg daily) was compared to the non-selective, lipid-soluble beta-blocker propranolol (240 mg daily), and to placebo, in a double-blind cross-over study in 24 patients with essential tremor. Atenolol and propranolol caused a similar decrease in heart rate. Both beta-blockers also suppressed the tremor intensity; there was no significant difference between them, but both were significantly better than placebo. These drugs did not affect tremor frequency. Twelve of the patients preferred propranolol subjectively, one preferred atenolol and none preferred placebo. No marked side-effects were observed. It was concluded that atenolol and other cardio-selective blockers offer an alternative for patients unable to tolerate the non-selective drugs. The site of action and receptor sub-type involved have still to be determined.

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Lisuride versus bromocriptine treatment in Parkinson disease: a double-blind study.

Twenty-eight parkinsonian patients were studied in a double-blind, crossover comparison of lisuride and bromocriptine. All but two patients completed the study, with each drug adjusted to an optimal dose (mean daily intake of 4.5 mg for lisuride and 56.5 mg for bromocriptine). Treatment with each drug was given for 7 to 10 weeks; three assessments were made at biweekly intervals with optimal dose levels. Conventional antiparkinsonian medications, including levodopa, were not changed. Efficacy and adverse effects were assessed by objective and subjective techniques. The only significant difference was slightly better control of akinesia with bromocriptine. There was considerable variability in the optimal dose of each drug, though the clinical profile of lisuride was quite similar to that of bromocriptine.

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Metabolism of (-) deprenyl to amphetamine and methamphetamine may be responsible for deprenyl's therapeutic benefit: a biochemical assessment.

The urinary excretion of some important phenylethylamines, catecholamines, their metabolites, amphetamine, and methamphetamine were measured in parkinsonian patients on Sinemet (L-dopa plus carbidopa, a peripheral dopadecarboxylase inhibitor) and depressed patients after chronic (-) deprenyl treatment. Deprenyl was efficiently metabolized to amphetamine and methamphetamine. It increased the excretion of phenylethylamine and of m- and p-tyramine, and reduced the output of norepinephrine metabolites, but failed to alter the excretion of dopamine-deaminated metabolites. These changes were attributed more to amphetamine and methamphetamine than to inhibition of monoamine oxidase type B. Sinemet treatment alone increased the excretion of dopamine, 3-methoxytyramine, and their respective deaminated metabolites, 3, 4-dihydroxyphenylacetic acid and homovanillic acid. It is concluded that conversion of deprenyl to amphetamine and methamphetamine may contribute to some of the therapeutic benefits of deprenyl.

3,4-Dihydroxyphenylacetic Acid↗

Assessment of hypokinesia in Parkinsonism.

The measurement of movement time provides a satisfactory objective measure of hypokinesia in parkinsonism. It is relatively constant in normal subjects, and it is often greatly prolonged in parkinsonism and correlates with clinical disability. The reaction time is only of limited value, because of small difference from normal values and wide individual variations.

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Recent advances in the treatment of Parkinson's disease: the role of bromocriptine.

We have treated 102 Parkinson patients with bromocriptine for up to 6 years; most of these posed problems of management when referred to us. Forty-two continue to take bromocriptine, at a mean dose of 49 mg daily (range 10-160), in combination with some 50% of their previous optimal dose of levodopa (with or without a decarboxylase inhibitor). We consider the main indications for bromocriptine are severe dyskinesia, early morning dystonia, and "wearing off" reactions. Contraindications include hallucinations, delusions, substantial confusion, acute myocardial infarction, active peptic ulceration, and active pleuropulmonary disease.

Bromocriptine↗

Reaction time in Parkinson's disease.

Both reaction time and movement time tend to be prolonged in Parkinson's disease, but they are often impaired independently of each other. Prolongation of RT is relatively slight, while MT undergoes more substantial and consistent disturbance. Choice RT and kinaesthetic RT do not have any advantage over simple visual RT as measurements of neurological deficit in parkinsonism, since they are all impaired to the same extent. MT is more useful than RT as an objective indicator of therapeutic efficacy, but further studies of RT (with tests requiring programming of displacement, velocity, and accuracy) may provide insights into the nature of the central motor disorder in Parkinson's disease.

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Deprenyl in Parkinson disease.

(-)Deprenyl, a specific monoamine oxidase subtype B inhibitor (MAOI-B), has been reported to be a safe and valuable adjunct to conventional treatment of parkinsonism. A double-blind, clinical comparison of (-)deprenyl with placebo was undertaken in 11 parkinsonian patients; the efficacy of 10 mg daily was studied over 4 weeks. In four cases the clinical score for parkinsonian deficits improved during deprenyl therapy, and in five it deteriorated; there was no change in one patient. Two subjects failed to complete the study. (-)Deprenyl induced euphoria and insomnia. It was concluded that any advantages deriving from the use of (-)deprenyl in parkinsonism are limited, and probably dominated by its elevation of mood. Biochemical analysis failed to reveal any significant increase in platelet or plasma catecholamine concentrations during deprenyl therapy. There was, however, a significant decrease in plasma epinephrine (p < 0.05) and platelet MAO activity (p < 0.005).

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Prolactin secretion in Parkinson disease.

We studied the dopaminergic control of lactotroph cells in the anterior pituitary of parkinsonian patients and age-matched normal subjects. The resting levels of prolactin and the TRH-induced rise in prolactin were normal in Parkinson disease. Levodopa elicited a normal suppression of prolactin concentrations in parkinsonian subjects; the major abnormality to emerge was attenuation of the response to thyrotropin-releasing hormone (TRH) in the parkinsonian patients following administration of Sinemet (levodopa plus carbidopa) or bromocriptine. These findings imply pathology of extrastriatal dopamine systems in Parkinson disease. Since the addition of carbidopa enhanced the suppression of prolactin induced by levodopa, exogenous levodopa probably acts predominantly through the formation of dopamine in the hypothalamus, but inside the blood-brain barrier, rather than as a direct effect of circulating dopamine on the anterior pituitary or areas of the hypothalamus outside the blood-brain barrier.

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Erythromelalgia-like eruption in parkinsonian patients treated with bromocriptine.

In a previous report about the chronic use of bromocriptine in Parkinson disease, a distinctive cutaneous eruption was noted and termed "erythromelalgia." This eruption has occurred in 9 of 110 patients on chronic bromocriptine therapy; histopathologic examination in 3 patients showed a prominent perivascular lymphocytic infiltration and perivascular edema of the dermis, without frank vasculitis. This is a reversible unwanted effect of bromocriptine therapy.

Aged↗

Absorption of levodopa after rectal administration.

Absorption of levodopa was studied after administration by mouth and rectum. Given by mouth, levodopa benefited all 12 patients studied, and levodopa blood levels rose significantly (p less than 0.01). When it was given rectally, there was no rise in levodopa concentration in the blood and no clinical benefit. Rectally administered levodopa is therefore of no value in the management of postoperative parkinsonian patients who cannot take oral medication.

Absorption↗

Lisuride in parkinsonism.

We studied the actions of lisuride, a dopaminergic ergot derivative, in 20 parkinsonian patients. When the dose was increased gradually, most patients tolerated up to 5 mg daily. Clinical assessment and objective, computer-assisted evaluation revealed improvement in akinesia, rigidity and tremor. Adverse reactions were similar to those seen with levodopa and bromocriptine, but somnolence tended to occur more often with lisuride.

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Cross tolerance between two dopaminergic ergot derivatives--bromocriptine and lergotrile.

1. When initially given to patients with idiopathic parkinsonism, lergotrile induced marked supine arterial hypotension. Tolerance to this hypotensive effect developed and larger doses of lergotrile were administered without this adverse effect. 2. Cross tolerance occurred between lergotrile and a structurally related ergot derivative, bromocriptine. A high dose of lergotrile given to patients who had been on long term bromocriptine therapy did not induce any significant hypotension when compared to placebo whereas hypotension still occurred when lergotrile was given after previous treatment with levodopa.

Aged↗

Studies of parkinsonian movement: 1. Programming and execution of eye movements.

Rapid voluntary eye movements in bradykinetic parkinsonian patients and normal subjects were recorded when the movement was executed with visual feedback (closed-loop mode) and in darkness without visual feedback (open-loop mode). The patients had a tendency to generate abnormal saccades consisting of multiple small steps (multiple step saccade), both in the closed-loop and open-loop mode. They were, however, also capable of generating large amplitude saccades. The amplitude-velocity relation of both the small step saccades and the large saccades was normal. The presence of multiple step saccades in the open loop mode suggests that the patients used internal rather than external (visual) feedback to compare the actual eye position with the desired (programmed) eye position and the program for rapid movement is normal but its execution is defective. Horizontal eye movements were also recorded when the head was stationary with a target moving sinusoidally, and when the target was stationary with the head rotated sinusoidally. In both cases the amplitude of the eye movement relative to the head was about 50 degrees. The patients were observed to generate irregular, saccadic eye movements in pursuit of a slowly moving target when the head was stationary, but their eyes could follow a stationary target smoothly when their eyes could follow a stationary target smoothly when their head was moved sinusoidally. These findings suggest that the neuronal circuitry in the paramedian pontine reticular formation, responsible for the final integration of different types of eye movements, is physiologically normal in Parkinsonism.

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Studies of parkinsonian movement: 2. Initiation of fast voluntary eye movement during postural disturbance.

Delay in initiation of rapid voluntary eye movements (saccades) in bradykinetic parkinsonian patients and normal subjects was recorded with and without postural disturbances (rotation of the body and head). Parkinsonian patients as a group exhibited longer delays in the initiation of saccades. The delay increased during postural disturbance in both the patients and the normal subjects. The study failed to substantiate the hypothesis that postural reflexes interfere with the initiation of voluntary movement in Parkinsonism.

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Action tremor in Parkinson's disease.

Electromyographic activity of the biceps muscle was examined in 38 parkinsonian patients and 33 normal subjects during (i) rapidly alternating pronation-supination movements (RAM) of the forearm, and (ii) single pronation or supination movements in response to visual (light) or to kinesthetic signals (displacements of the hand). Biceps electromyography (EMG) displayed rhythmic activity over the supination phase of RAM in the majority of the parkinsonian patients, whereas continuous activity was evident in most normal subjects. Similar phenomena were observed when single movements were executed in response to visual or kinesthetic signals. Rhythmic activity could be triggered without any external displacements by voluntarily initiated supination of a previously quiescent limb even before actual movement of the limb occurred. Voluntary pronation (involving biceps inactivation) did not trigger any rhythmic biceps activity. The results are interpreted to support the hypothesis that parkinsonian patients have action tremor because voluntarily initiated activity leads to oscillations in internal feedback circuit involving descending pathways from motor cortex to spinal cord, and ascending pathways from the spinal cord back to the motor cortex.

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