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Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 451 records · Page 25Linked to original sources
PubMed1990

Cutaneous effects on presynaptic inhibition of flexor Ia afferents in the human forearm.

1. In six subjects, H reflexes obtained in the flexor muscles in the forearm were inhibited by single motor threshold shocks to the radial nerve in the spiral groove. The first two phases of the inhibitory time course were studied: with intervals between the radial and median nerve shocks of -1 to +1 ms, and +5 to +30 ms. These two phases are thought to be due respectively to disynaptic inhibition between radial Ia afferents and flexor alpha-motoneurones, and to presynaptic inhibition of flexor Ia afferents. 2. Single or short trains (10 ms, 400 Hz) of cutaneous stimuli to the dorsal or palmar aspect of the proximal phalanx of the index finger or to the superficial radial nerve at the wrist, reduced the amount of presynaptic inhibition by 10-20%, but had no effect on the earlier disynaptic inhibition. Single stimuli to either side of the index finger or trains of stimuli to the ventral side, had no effect on the size of control H reflexes elicited alone. 3. Effects of cutaneous nerve shocks on presynaptic inhibition could be seen with stimuli as small as 1.5 x perceptual threshold. 4. Anaesthesia of the hand in one subject reversibly increased the amount of presynaptic inhibition and decreased the amount of disynaptic inhibition. 5. We conclude that, as in the cat, cutaneous input can modulate transmission in presynaptic inhibitory pathways in man.

Adult↗
PubMed1990

Nasogastric and intravenous infusions of (+)-4-propyl-9-hydroxynaphthoxazine (PHNO) in Parkinson's disease.

(+)-4-propyl-9-hydroxynaphthoxazine (PHNO) is a new dopamine agonist which is capable of producing a sustained response in parkinsonian patients with "on-off" fluctuations when given as a continuous infusion either nasogastrically or intravenously. These data suggest that a sustained release formulation of PHNO may provide a significant, new treatment for patients with "on-off" fluctuations.

Adult↗
PubMed1990

Sexual function in patients with Parkinson's disease and their partners.

Sexual function in patients with Parkinson's disease has received virtually no attention. There are many reasons (physical, psychological and social), why such patients might experience problems within their sexual relationships. A group of patients and their partners completed a series of self-report measures, aimed at assessing sexual function and a range of factors which might be associated with any difficulties. The results revealed a high level of dysfunction, not just in the patients but also in their partners. Most effected were the couples in which the patient was male. A range of problems were reported by both patients and their partners. These were, in turn, associated with a range of variables relating to the disease, psychological and social factors. No simple causal model was suggested, and a multimodal therapeutic approach might be expected to have most benefit.

Activities of Daily Living↗
PubMed1990

Saccadic function in spasmodic torticollis.

Twelve patients with idiopathic spasmodic torticollis were compared with 19 normal controls on tests of saccadic eye movements thought to depend upon normal basal ganglia function. The patients were able to make random, predictive, remembered, and self-paced saccades equally as well as control subjects. This suggests that those parts of the basal ganglia which may be damaged in spasmodic torticollis, are separate from pathways responsible for the normal initiation and execution of saccades.

Adult↗
PubMed1990

Dystonia in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy.

Adult-onset dystonia-parkinsonism is a syndrome in search of a pathology. We therefore reviewed the literature on dystonic manifestations in autopsy-proven cases of multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and idiopathic Parkinson's disease (PD). Only 6 of 140 autopsy reports of MSA remarked on the presence of dystonia in life, but personal observations suggest prominent antecollis may develop at some stage in up to 1/2 of sufferers. Similarly, very few (15/118) clinicopathologic observations on PSP included convincing dystonic manifestations, in contrast to some clinical reports where blepharospasm and early limb dystonia were prominent. Virtually any form of focal and segmental dystonia may sometimes occur with clinically diagnosed PD, with occasional descriptions of hemidystonia-hemiparkinsonism. However, there is pathologic confirmation of this diagnosis in only 1 case. With many patients thought clinically to have PD proving pathologically to have another cause for their parkinsonism, the true frequency and the range of dystonic manifestations acceptable in PD remain unknown.

Brain Diseases↗
PubMed1989

Transient depletion of nucleus accumbens dopamine content may contribute to initial akinesia induced by MPTP in common marmosets.

Acute treatment of common marmosets with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused an initial profound akinesia and other motor deficits. However, over the following months akinesia gradually disappeared although the animals remained clumsy and poorly coordinated. At 10 days following MPTP treatment there was a profound decrease in the dopamine, HVA and DOPAC content of the caudate nucleus, putamen and nucleus accumbens. By 3-4 months following MPTP treatment the animals had largely recovered from their akinesia, but the caudate nucleus and putamen dopamine, HVA and DOPAC content remained low. In contrast, the dopamine content of the nucleus accumbens had returned towards normal and the metabolite levels were higher than at 10 days. No overall alterations in 5HT or 5HIAA levels were observed at either time point. The transient and reversible nature of dopamine loss in the nucleus accumbens may contribute to the initial profound akinesia exhibited by common marmosets treated with MPTP. The restoration of dopamine levels in the nucleus accumbens may be partially responsible for the subsequent recovery of motor function that occurs in MPTP-treated marmosets.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Stereoselective reversal of MPTP-induced parkinsonism in the marmoset after dermal application of N-0437.

The selective dopamine D-2 receptor agonist N-0437 produced a rapid and dose-dependent reversal of motor deficits lasting 90-120 min following i.p. or oral administration of the racemate to MPTP-treated common marmosets. In contrast, topical application of (+/-)-, (+)- or (-)-N-0437 to the skin of MPTP-treated animals did not alter locomotor activity in the initial 4 h although other motor disabilities were reduced. However, 24 h following application of the racemate or the (-) enantiomer both locomotor activity and the other motor deficits induced by MPTP were improved. The increase in locomotor activity returned to basal values by 48-52 h following application of the racemate to the skin and by 72-76 h following administration of (-)-N-0437; the other motor deficits induced by MPTP were reduced for up to 72-76 h by both (+/-)- and (-)-N-0437. Application to skin of the (+) enantiomer produced no behavioural improvement or stimulation of locomotor activity. Transdermal administration of the active enantiomer of N-0437 may be of value in producing a prolonged reversal of parkinsonian motor deficits in man.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Increased caudate dopamine turnover may contribute to the recovery of motor function in marmosets treated with the dopaminergic neurotoxin MPTP.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets initially impaired motor function, but a partial recovery occurred over the following weeks. At both 10 days and 4-6 weeks following MPTP treatment, [3H]dopamine ([3H]DA) uptake into synaptosomal preparations of putamen was markedly decreased. At 10 days and 4-6 weeks following MPTP treatment DA, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the caudate nucleus and nucleus accumbens were substantially reduced. However, the levels of HVA and DOPAC in caudate nucleus were higher at 4-6 weeks than at 10 days. The ratio of (DOPAC + HVA)/DA in caudate nucleus was elevated at 10 days following MPTP treatment and even more so at 4-6 weeks. No change in Bmax or Kd values for [3H]spiperone binding to caudate preparations were observed. The recovery of motor function in marmosets observed following MPTP treatment may result partially from a compensatory increase in caudate DA turnover by remaining neurones.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Induction of purposeless chewing behaviour in rats by 5-HT agonist drugs.

The 5-HT agonist m-chlorophenylpiperazine (m-CPP; 1-16 mg/kg i.p. or s.c.), trifluoromethylphenylpiperazine (TFMPP; 2-16 mg/kg i.p.) and quipazine (2.5-20 mg/kg i.p.) increased purposeless chewing behaviour in rats. However, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.025-4 mg/kg s.c.) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT; 0.25-8 mg/kg s.c.) were without effect on chewing behaviour. Chewing behaviour induced by m-CPP (6 mg/kg s.c.) was antagonised by pretreatment with the 5-HT antagonists methiothepin and mianserin, but not by ketanserin or spiperone, or ICS 205-930. m-CPP (6 mg/kg s.c.)-induced chewing behaviour was also antagonised by pretreatment with (-)-propranolol (20 mg/kg). Pretreatment with the anticholinergic drugs benzhexol (2.5 mg/kg), and scopolamine (1 mg/kg) antagonised m-CPP (6 mg/kg s.c.)-induced chewing behaviour, but methylscopolamine (1 mg/kg) had no effect. These data support the role of 5-HT receptors in the mediation of purposeless chewing behaviour and suggest an interaction between brain 5-HT and acetylcholine systems.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Accuracy of self-reported disability in patients with parkinsonism.

For the patient, the most important aspect of parkinsonism is the degree to which the disease interferes with daily living. The patient's self-report may be the only way in which such information can be obtained. Depression and cognitive impairment, however, may influence that self-report. In the present study, three ratings of disability, from the patient, a relative, and an independent observer, showed high levels of agreement. The patients' cognitive function made a small but significant contribution to the accuracy of their self-report judged against the relative's rating. Depression, however, played no role. Agreement between patients and relatives for individual items on the disability questionnaire was reasonably high. The results suggest that patients with parkinsonism can provide accurate self-report of their level of disability, even in the presence of depression and cognitive impairment.

Activities of Daily Living↗
PubMed1989

The evolution and distribution of morphological changes in the nervous system of the common marmoset following the acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Six young adult marmosets received 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in multiple doses (total 8-16 mg/kg over 2-13 days) sufficient to produce a parkinsonian syndrome and were killed up to 3.5 months later. Cellular changes were found in the substantia nigra, ventral tegmental area, and hypothalamus. The earliest histological abnormalities were axonal swellings in proximal parts of nigrostriatal axons. Subsequent changes in the substantia nigra were reduced Nissl staining, reduced cell volume, and aggregation and loss of melanin granules. Other effects were reduced nuclear and nucleolar volumes, depletion of cells, and hyperplasia of glial cells. Shrunken cytoplasm and nuclei stained uniformly with eosin, and no cells showed cytoplasmic swellings or inclusions. These cellular alterations, with nuclear changes resembling karyolysis, do not occur in Parkinson's disease, which is characterised by Lewy body inclusions and signs of chromatolysis. The rapid appearance of axonal swellings, disruption of Nissl substance, and cell shrinkage suggest an insult to energy producing mechanisms. In this study, the absence of histological evidence of toxicity in the locus coeruleus and also in the substantia innominata and in serotonergic cell groups is unlike the more widespread degenerative changes of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Pure akinesia due to lewy body Parkinson's disease: a case with pathology.

The case of a patient with levodopa-responsive pure akinesia and freezing of gait for 17 years, whose brain showed the classical changes of Lewy body Parkinson's disease at postmortem is presented. A short trial of DL-threo-DOPS was ineffective. Intellectual function was preserved despite the presence of Lewy bodies and mild cell loss in subcortical cholinergic nuclei. Pure akinesia is likely to be a heterogeneous condition, with most cases having little or no response to levodopa therapy. However, this case demonstrates that this clinical picture may be caused by Lewy body Parkinson's disease.

Antiparkinson Agents↗
PubMed1989

The antiparkinsonian actions and pharmacokinetics of transdermal (+)-4-propyl-9-hydroxynaphthoxazine (+PHNO): preliminary results.

(+)-4-Propyl-9-hydroxynaphthoxazine (+PHNO) is a potent dopamine agonist that has been administered transdermally to four patients with Parkinson's disease and "on-off" fluctuations. Skin patches of increasing size were used to treat these patients, who also received infrequent doses of oral levodopa if required. The effect of +PHNO was measured as an increased duration of action of individual levodopa doses. The clinical effect measured in this way was directly proportional to the plasma concentrations of +PHNO achieved. The plasma concentrations of +PHNO began to rise 4-6 h after patch application and reached a steady state by 24 h. The final plasma concentration of +PHNO was proportional to the area of skin covered.

Administration, Cutaneous↗