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Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 775 records · Page 43Linked to original sources
PubMed1983

Neuromelanin and Parkinson's disease.

Neuromelanin is closely linked to Parkinson's disease, but is it the cause of the illness? The main pathology of Parkinson's disease is a loss of pigmented brain-stem neurones, and neuromelanin or its precursors might be cytotoxic. However, the cellular marker of Parkinsonian pathology, the Lewy body, is not confined to neurones containing neuromelanin. There are areas of the brain, of which the substantia innominata is a good example, which contain no neuromelanin or catecholaminergic neurones, but whose cells are packed with Lewy bodies and die. It is concluded that it is not neuromelanin, but the Lewy body which holds the key to Parkinson's disease.

Animals↗
PubMed1982

Scope of a technique for electrical stimulation of human brain, spinal cord, and muscle.

Brief high-voltage electrical shocks from a special low-output-resistance stimulator, delivered through electrodes on the skin, can excite human muscle directly (not by way of the nerves) and can also excite the motor cortex, the visual cortex, and the spinal cord. Possible applications of the technique include measurement in muscle disorders of the latency relaxation and of the excitability and contractility of muscle without the interposition of nerve fibres or the neuromuscular junction; measurement of conduction velocity in the pyramidal tract; and the detection of neuropathy in the nerves to the external sphincter ani.

Action Potentials↗
PubMed1982

Complicated response fluctuations in Parkinson's disease: response to intravenous infusion of levodopa.

The cause(s) of response fluctuations in patients with Parkinson's disease treated chronically with levodopa is unknown. In some subjects it is difficult to establish a clear relation between levodopa dosage and timing and the resultant clinical effects. This may be due to variation in the degree of absorption of the drug, and in the latency from ingestion to peak plasma level and from plasma peak to central action. In one patient illustrated, careful analysis of "on-off" charts reveals an underlying pattern of end-of-dose deterioration at a time when history alone suggested a completely random response to levodopa. In three patients replacement of oral treatment by continuous intravenous infusion of levodopa, with oral administration of decarboxylase inhibitor, produced a prolonged and stable clinical response, even when ambulant. This response was maintained not only in one subject showing predictable fluctuations, but also in two subjects with unpredictable response to oral treatment. The addition of intravenous levodopa infusion to the usual oral regimen of the first patient when she was experiencing prolonged "off" periods despite generous doses of oral levodopa with decarboxylase inhibitor also produced stable clinical benefit. These results suggest that, even in patients with complicated response swings, central dopamine receptors remain available for stimulation providing levodopa can be delivered at a constant rate and in an adequate quantity to the brain.

Administration, Oral↗
PubMed1982

Increased striatal acetylcholine after 14 months cis-flupenthixol treatment in rats suggests functional supersensitivity of dopamine receptors.

Rats received continuous administration of cis-flupenthixol (0.8-1.2 mg/kg/day) or trans-flupenthixol (0.9-1.2 mg/kg/day) in drinking water for 14 months. The administration of cis-flupenthixol, but not trans-flupenthixol, caused apparent cerebral dopamine receptor supersensitivity. Thus, animals receiving cis-flupenthixol, but not trans-flupenthixol, showed enhanced apo-morphine-induced stereotyped behaviour. Dopamine concentration in striatum was not altered by drug treatment but striatal HVA and DOPAC concentrations were reduced in animals receiving cis-flupenthixol, but not trans-flupenthixol. No consistent change in Bmax of KD for specific striatal 3H-spiperone binding was observed after 14 months drug intake. However, in cis-flupenthixol treated animals a 40% increase in Bmax was observed following 2 weeks drug withdrawal. Continuous cis-flupenthixol intake increased striatal acetylcholine concentrations; trans-flupenthixol was without effect. This suggests the apparent increase in cerebral dopamine receptor supersensitivity caused by continuous long-term cis-flupenthixol administration is of functional importance in the intact animal.

Acetylcholine↗
PubMed1982

Myoclonus in guniea pigs is induced by indole-containing but not piperazine-containing 5HT agonists.

L-5-Hydroxytryptophan (5HTP) induces in guinea pigs a myoclonic jerking which is dependent upon stimulation of brainstem 5-hydroxytryptamine (5HT) receptors. We have investigated the ability of 5HT precursors and a range of synthetic 5HT agonists to produce myoclonus. The 5HT precursors and 5HT agonists containing an indole nucleus induced dose-dependent jerking in guinea pigs. In contrast, 5HT agonists possessing a piperazine moiety induced occasional jerking only at toxic doses, but not a those doses normally associated with 5HT agonist activity. The difference in activity between the indole-containing compounds and piperazine-containing 5HT agonists suggests that myoclonus is due to activation of an indole-selective brainstem 5HT receptor and provides further evidence for multiple cerebral 5HT receptors.

Animals↗
PubMed1982

Repeated administration of sulpiride for three weeks produces behavioural and biochemical evidence for cerebral dopamine receptor supersensitivity.

Administration of sulpiride (2 X 100 mg/kg i.p.) or haloperidol (5 mg/kg i.p.) to rats for 3 weeks with subsequent withdrawal for 3 or 4 days induced cerebral dopamine receptor supersensitivity. Apomorphine-induced stereotyped behaviour after drug withdrawal was enhanced by pretreatment with either haloperidol or sulpiride both of which increased the number of specific striatal binding sites (Bmax) for [3H]spiperone, [3H]N,n-propylnorapomorphine and [3H]sulpiride. Neither drug altered the dissociation constant (KD) for the ligand binding assays. Striatal dopamine sensitive adenylate cyclase activity was unaltered by such a pretreatment with either haloperidol or sulpiride. The data show that sulpiride, like haloperidol, is capable of inducing behavioural and biochemical supersensitivity of cerebral dopamine receptors.

Adenylyl Cyclases↗