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Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 793 records · Page 44Linked to original sources
PubMed1982

Pergolide in late-stage Parkinson disease.

Twenty-six patients with late-stage Parkinson disease were given 0.4 to 15 mg of pergolide mesylate daily in addition to, or as replacement for, levodopa or bromocriptine therapy. Despite treatment with individually determined optimum doses of levodopa, bromocriptine, and anticholinergics, they had shown response failure or fluctuating response. Forty percent (11 patients) were unable to tolerate pergolide. Nausea and vomiting, somnolence, and psychiatric disturbances were the most frequent side effects. Eleven of the remaining patients improved on pergolide, 2 were unchanged, and 2 were slightly worse. Among the patients who benefited, pergolide improved dose-related response fluctuations more than non-dose-related fluctuations, with a reduction in number and duration of "off" periods and improvement in quality of sleep and early morning akinesia but little change in freezing episodes. Despite treatment failure in many cases, pergolide is at present the best available drug for specific late-stage management problems.

Bromocriptine↗
PubMed1982

Tryptamine-induced myoclonus in guinea-pigs pretreated with a monoamine oxidase inhibitor indicates pre- and post-synaptic actions of tryptamine upon central indoleamine systems.

Tryptamine (1-320 mg/kg) evoked only slight muscle jerking in naive guinea-pigs but, in animals pretreated with pargyline (75 mg/kg; 1 hr previously), tryptamine induced a dose-dependent (6-160 mg/kg) myoclonus. The myoclonus induced by tryptamine (40 mg/kg) plus pargyline (75 mg/kg) was differentially inhibited by the indoleamine receptor antagonists, methergoline (5 mg/kg) which was more potent than methysergide (10 mg/kg), mianserin (10 mg/kg) which was more potent that cyproheptadine (10 mg/kg) and propranolol (20 mg/kg) which was more potent than cinanserin (10 mg/kg). This rank order of potency differed from that observed for the order of potency of these drugs in inhibiting the myoclonus induced by L-5-hydroxytryptophan (5HTP) plus carbidopa in guinea-pigs (Luscombe, Jenner and Marsden, Neuropharmacology, 1981), perhaps indicating involvement of pharmacologically distinct indoleamine receptors. Manipulation of presynaptic function of 5-hydroxytryptamine (5HT) by tryptophan hydroxylase inhibition with p-chlorophenylalanine to produce depletion of cerebral 5HT, or by an L-tryptophan load to elevate 5HT in brain, suggested that the functional integrity of serotonergic neurones is required for the expression of myoclonus induced by tryptamine plus pargyline. A range of blockers of 5HT re-uptake did not alter the jerking produced by tryptamine (40 mg/kg) in guinea pigs pretreated with pargyline (75 mg/kg; 1 hr previously), or the threshold myoclonus induced by a smaller dose of tryptamine (10 mg/kg; plus pargyline 75 mg/kg). It is suggested that myoclonus induced by tryptamine in guinea pigs pretreated with pargyline involves activation of post-synaptic indoleamine receptors by tryptamine by a mechanism which requires intact presynaptic function of 5HT.

5-Hydroxytryptophan↗
PubMed1982

Anticholinergics in adult-onset focal dystonia.

Anticholinergics are one of the most common treatments used in adult-onset focal dystonias although their general efficacy has not been proven. We have investigated the effects of intravenous administration of atropine, benztropine and chlorpheniramine, in comparison to normal saline, in 20 patients with adult-onset focal dystonias (spasmodic torticollis (9), cranial dystonia (6), writer's cramp (5), and have retrospectively reviewed the notes of 78 patients (spasmodic torticollis (38), cranial dystonia (25), writer's cramp (15), who had received chronic oral anticholinergic therapy in varying doses at some time in the past. Patients with spasmodic torticollis and writer's cramp showed no consistent change with any of the intravenous drugs, while the few with cranial dystonia who improved usually did so at the expense of drug-induced sedation. The natural variability of these disorders was evident in the response to normal saline, which caused changes in the scores for severity of the involuntary movements of 20% or more in some patients. Only 8 of the patients who had received chronic oral therapy obtained more than mild benefit, and in 3 of them this improvement was transient. We conclude that cholinergic mechanism are not of general or prime importance in the pathogenesis of adult-onset focal dystonias. However, each new patient warrants a trial of chronic oral anticholinergic therapy in view of the occasional useful responses obtained with these drugs.

Administration, Oral↗
PubMed1982

Writers' cramp-a focal dystonia.

We have examined 29 subjects with writers' cramp (and 4 with typists' and one with pianists' cramp) and have noted two major groupings, simple and dystonic. We have observed spread from one to the other. We have seen repeatedly, in patients with isolated simple writers' cramp certain subtle physical signs which are found also in other basal ganglia diseases. We have noted also the frequent association of other features of segmental and generalized dystonia in patients with dystonic writers' cramp. We have demonstrated that patients with isolated writers' cramp have no higher an incidence of psychiatric disturbance, as judged by formal Present State Examination, than the normal population. We conclude that isolated writers' cramp is a physical illness rather than a psychological disturbance, and that it is a focal dystonia.

Adult↗
PubMed1982

Manual motor performance in a deafferented man.

We have studied manual motor function in a man deafferented by a severe peripheral sensory neuropathy. Motor power was almost unaffected. Our patients could produce a very wide range of preprogrammed finger movements with remarkable accuracy, involving complex muscle synergies of the hand and forearm muscles. He could perform individual finger movements and outline figures in the air with high eyes closed. He had normal pre- and postmovement EEG potentials, and showed the normal bi/triphasic pattern of muscle activation in agonist and antagonist muscles during fast limb movements. He could also move his thumb accurately through three different distances at three different speeds, and could produce three different levels of force at his thumb pad when required. Although he could not judge the weights of objects placed in his hands without vision, he was able to match forces applied by the experimenter to the pad of each thumb if he was given a minimal indication of thumb movement. Despite his success with these laboratory tasks, his hands were relatively useless to him in daily life. He was unable to grasp a pen and write, to fasten his shirt buttons or to hold a cup in one hand. Part of hist difficulty lay in the absence of any automatic reflex correction in his voluntary movements, and also to an inability to sustain constant levels of muscle contraction without visual feedback over periods of more than one or two seconds. He was also unable to maintain long sequences of simple motor programmes without vision.

Adult↗
PubMed1982

Alpha methylparatyrosine and tetrabenazine in movement disorders.

Clinical and experimental evidence suggests that alpha methylparatyrosine (AMPT), an inhibitor of tyrosine hydroxylase, can potentiate the effects of other dopamine antagonists. We therefore treated patients having various forms of dystonia and chorea with tetrabenazine (TBZ), and then added AMPT to determine if further improvement could be obtained. Side effects of both drugs were common, and they often necessitated withdrawal of the drug. Patients with Huntington's chorea and tardive dyskinesia were improved by TBZ. They obtained additional benefit from the combination of AMPT and TBZ. The results in the dystonia patients were disappointing with both drugs. Although a small number of patients did improve, and short- and long-term remissions occurred in a few, most patients with dystonia were not benefited by either drug.

Adult↗
PubMed1982

Concentrations of GABA and other amino acids in CSF from torsion dystonia patients.

Free amino acid concentrations were measured by conventional amino acid analysis, and gamma-aminobutyric acid (GABA) concentrations were determined, by an ion-exchange fluorometric technique, in CSF specimens from 16 patients with torsion dystonias and in CSF from a large number of control subjects. The mean CSF GABA concentration of the dystonia patients (97 +/- 11 nmol/L) did not differ significantly from the means for CSF GABA in two groups of adult control subjects. Mean concentrations of all commonly determined amino compounds were normal in the CSF of torsion dystonia patients, except for ornithine, which was modestly but significantly reduced.

Adolescent↗
PubMed1982

Are dopamine receptors present on human lymphocytes?

The characteristics of [3H] spiperone binding to human lymphocytes have been examined. The haloperidol displaceable component of [3H] spiperone binding to human lymphocytes was not saturable, and stereoselective displacement by the isomers of butaclamol was not observed. These was no correlation between the ability of known dopamine active drug to cause displacement of the ligand and their rank order of potency. Chloroquine, a drug with no dopaminergic action, was the most potent displacing agent examined. Fragmentation of the cells caused a marked decrease in the haloperidol displaceable component of [3H] spiperone binding, and saturable binding to the lymphocyte membrane fragments was not observed. lysis of cells after equilibrium incubation with [3H] spiperone caused a marked reduction in the haloperidol displaceable component of ligand binding. Association of [3H] spiperone with lymphocytes was unaffected by the metabolic inhibitor iodoacetate or by replacement of sodium ions by lithium ions in the incubation medium, suggesting that such association did no involve an active process. We cannot confirm the existence of dopamine receptors on the surface of human lymphocytes. We suggest that the apparent association of [3H] spiperone with lymphocytes is due to some passive uptake process causing accumulation of the ligand within the cells.

Binding, Competitive↗
PubMed1982

Accurate repositioning of the human thumb against unpredictable dynamic loads is dependent upon peripheral feed-back.

1. The strategy of accurate movement of the human thumb has been studied in nine subjects. An open-loop hypothesis, which states that a new final position is defined by re-setting the agonist/antagonist spring constants, was tested2. Subjects were trained to flex the top joint of the thumb rapidly through 20 deg in about a third of a second from a fixed starting position against a load. Occasionally, and unpredictably, the viscous friction of the load was altered prior to it's being moved. The spring hypothesis predicts that such a change in load should have no effect on final position accuracy.3. Under normal conditions no final position error developed when the viscous friction was increased. A small overshoot occurred when the viscous friction was decreased.4. The electromyogram recorded from surface electrodes over the belly of flexor pollicis longus in the forearm revealed an increase in activity in response to an increase in viscous friction and a decrease in activity when the viscous friction was reduced.5. When the joint and cutaneous afferents from the thumb were anaesthetized, the e.m.g. response to a change in viscous friction was severely attenuated and consistent final position errors developed.6. Even though the compensatory open-loop muscle properties went some way towards maintaining accuracy, the change in final position error that occurred as a result of thumb anaesthesia correlated well (r = 0.84) with the amount of muscle e.m.g. response that was lost.7. The latency of the e.m.g. response to a change in viscous friction was compared to that of a voluntary response by asking the subject to push down or let go upon perception of the load change. Approximately the first 100 ms of the e.m.g. response was unaffected by the voluntary intervention of the subject.8. We conclude that the spring hypothesis does not explain human thumb movement. It is argued that the long-latency stretch reflex machinery is responsible for some automatic compensation for unexpected interference with movement.

Adult↗
PubMed1982

Early onset of the "on-off" phenomenon in children with symptomatic Parkinsonism.

Many patients with idiopathic Parkinson's disease treated with levodopa for more than five years develop fluctuations in their clinical response to this drug. Such fluctuations may be unpredictable, but more commonly occur in a regular pattern related to the size and timing of the levodopa dosage. Theories as to their cause have emphasised both the progression of the underlying Parkinson's disease and the possibility of a late side-effect of levodopa. We report two children with Parkinsonism, one after recurrent obstructive hydrocephalus and the other following an encephalitic illness. Both patients had striking improvement with levodopa, but developed predictable and unpredictable dramatic response fluctuations within weeks of starting levodopa therapy. This suggests that neither the pathology of idiopathic Parkinson's disease, nor the long-term use of levodopa are essential for the development of predictable or unpredictable fluctuations in response to levodopa therapy.

Cerebrospinal Fluid Shunts↗
PubMed1982

Tardive dystonia: late-onset and persistent dystonia caused by antipsychotic drugs.

It is not widely recognized that antipsychotic drugs can cause late-onset and persistent dystonia. This dystonia, which we call tardive dystonia, is to be distinguished from acute dystonic reactions, which are transient, and from classic tardive dyskinesia, which is a choreic disorder that predominantly affects the oral region. We present 42 patients with tardive dystonia. The age of onset of dystonia was 13 to 60 years. Symptoms began after 3 days to 11 years of antipsychotic therapy. Younger patients tended to have more generalized dystonia. In a few patients, spontaneous remission occurred, but dystonia persisted for years in most. Therapy was rarely a complete success. The most frequently helpful medications were tetrabenazine (68% of patients improved) and anticholinergics (39% improved).

Adolescent↗