Search PubMed⌕ Search

Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 469 records · Page 26Linked to original sources
PubMed1989

Oxyferriscorbone elevates the total iron content of blood but not brain.

Following the intravenous infusion of oxyferriscorbone into the tail vein of the rat, the blood and brain metal ion content was measured over the following 72 h period. Administration of oxyferriscorbone increased the total iron content of blood for up to 24 h following intravenous infusion. In contrast, there was no increase in the total iron content of the cerebellum or striatum. Overall, there was no change in total zinc or copper content of the blood or brain following oxyferriscorbone administration. The effect of oxyferriscorbone in Parkinson's disease may not be related to any alteration in total iron content of the brain.

2,3-Diketogulonic Acid↗
PubMed1989

Antiparkinsonian activity of CY 208-243, a partial D-1 dopamine receptor agonist, in MPTP-treated marmosets and patients with Parkinson's disease.

The effect of stimulation of cerebral dopamine D-1 receptors by CY 208-243 on motor disability was tested in MPTP-treated parkinsonian marmosets and patients with Parkinson's disease. CY 208-243 (0.5-1.25 mg/kg s.c.) produced a dose-related reversal of akinesia and rigidity in the marmosets, lasting some 2 h. Single morning doses of CY 208-243 (5-40 mg) were compared with the usual morning dose of levodopa in eight patients with Parkinson's disease on long-term levodopa therapy who had developed motor fluctuations from immobility with akinesia and rigidity (off) to mobility often with dyskinesias (on). CY 208-243 alone was capable of switching such patients from off to on; five of the eight patients responded to the highest dose (40 mg), sometimes with dyskinesias. The response to CY 208-243 was comparable to that produced by levodopa in these cases. Drugs designed to stimulate both dopamine D1 and D2 receptors in the brain may improve the therapy of Parkinson's disease.

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

Assessment of the muscarinic receptor subtype involved in the mediation of pilocarpine-induced purposeless chewing behaviour.

Purposeless chewing behaviour in rats was enhanced by intraperitoneal administration of the muscarinic agonists pilocarpine (1.0-8.0 mg/kg), RS 86 (0.5-0.8 mg/kg), oxotremorine (1-2 mg/kg) and arecoline (2-32 mg/kg), but not by nicotine (0.1-3.2 mg/kg). Chewing behaviour was also induced by the ICV administration of the muscarinic agonists carbachol (12.5-100 micrograms) and pilocarpine (50-200 micrograms), but not by the putative M-1 receptor agonist McN-A-343 (50-200 micrograms) or AH 6405 (100-200 micrograms). The muscarinic receptor antagonists scopolamine (0.01-0.1 mg/kg SC), benzhexol (0.075-2.5 mg/kg SC), secoverine (1-10 mg/kg SC), and dicyclomine (1.25-10 mg/kg SC) antagonised purposeless chewing behaviour induced by pilocarpine (4 mg/kg IP). AF-DX 116 (2.5-100 mg/kg SC), an M-2 antagonist, partially inhibited the actions of pilocarpine (4 mg/kg IP). Based on ED40 values the rank order of potency following IP administration was scopolamine greater than benzhexol greater than secoverine greater than dicyclomine greater than AF-DX 116. The ICV administration of the muscarinic antagonists N-methylscopolamine (2.5-10 micrograms) and oxyphenonium (10-40 micrograms) antagonised chewing behaviour induced by pilocarpine (4 mg/kg IP) in a dose-related manner. The M-2 antagonist 4-DAMP (40-160 micrograms ICV), as well as AF-DX 116 (40-160 micrograms ICV), also inhibited the effects of pilocarpine (40-160 micrograms ICV). The putative M-1 receptor antagonist pirenzepine (80-320 micrograms ICV) did not antagonise chewing behaviour induced by pilocarpine (4 mg/kg IP).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Further treatment with MPTP does not produce parkinsonism in marmosets showing behavioural recovery from motor deficits induced by an earlier exposure to the toxin.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), or 0.9% saline, was administered to a group of common marmosets initially treated with the toxin 12-18 months previously. Initial treatment had consisted of a cumulative dose of 6-22 mg/kg (i.p.) which caused marked parkinsonism. Subsequently, the animals gradually recovered normal motor function. Further treatment consisted of a cumulative dose of MPTP of 78-83 mg/kg (i.p.) but this produced only modest akinesia. At 12-18 months after the initial treatment with MPTP, the content of dopamine, HVA and DOPAC in the caudate and putamen was markedly reduced. However, levels of dopamine, HVA and DOPAC in the nucleus accumbens were normal. Three months after the second treatment with MPTP there was no further decrease in the content of dopamine in the caudate-putamen. However, in the nucleus accumbens the content of dopamine, HVA and DOPAC was now reduced. The initial treatment with MPTP substantially decreased the binding of [3H]mazindol in the caudate-putamen but less so in the nucleus accumbens. Only a small additional decrease occurred upon further treatment with MPTP. The density of tyrosine hydroxylase (TH) immunoreactive cells in substantia nigra was reduced after the initial treatment with MPTP. However, the cell loss was far less marked than the decrease in terminal density, assessed by the binding of [3H]mazindol. Subsequent treatment with MPTP caused a small further loss of tyrosine hydroxylase-positive cells. Initial treatment with MPTP may kill the majority of MPTP-sensitive dopamine cells in the nigra. Compensation by the remaining nigrostriatal neurones may account for the behavioural recovery observed.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Behavioural and morphological changes following treatment with GM-1 ganglioside of rats with an electrolytic lesion of the substantia nigra.

The effects of daily treatment with GM-1 ganglioside (30 mg/kg i.p.) or saline (1 ml/kg i.p.) in rats with discrete unilateral electrolytic lesions of the dorsal substantia nigra were investigated. Treatment with GM-1 ganglioside, beginning 3 days prior to surgery and continuing for 33 days post-operatively, caused reductions in the total ipsilateral turns and peak turning rates induced by apomorphine (0.75 mg/kg s.c.) between 7 and 31 days post-operatively, without altering the time course of the effect of apomorphine. No effects of GM-1 on lesion-induced changes in synaptosomal uptake of [3H]dopamine, dopamine, serotonin in the striatum or corresponding levels of metabolites were found. Treatment with GM-1 ganglioside had no effect on the rostrocaudal extent of the electrolytic lesion, but caused morphological changes at the site of the lesion, including a reduction in the density of glial cells. Treatment with GM-1 ganglioside resulted in a relative preservation of cell bodies, staining immunocytochemically for tyrosine hydroxylase, in the substantia nigra pars compacta (expressed as a percentage of the intact side), when compared with saline-treated rats. The results showed that GM-1 ganglioside promoted a partial functional recovery from apomorphine-induced circling, which may be due in part to a reduction in the extent of damage at the lesion site.

Animals↗
PubMed1989

Treatment with a selective MAO B inhibitor prevents loss of dopamine in the nucleus accumbens of MPTP-treated common marmosets.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets induced motor deficits, associated with a marked decrease in the uptake of [3H]dopamine into synaptosomes in the putamen and a reduction in the content of dopamine in both caudate nucleus and nucleus accumbens. Histological analysis showed a marked loss of dopamine-containing cells in the zona compacta of the substantia nigra and less loss in the ventral tegmental area. Treatment of animals with the selective monoamine oxidase (MAO) B inhibitor, MDL 72145 (0.5 or 2.0 mg/kg) prior to, during and following administration of MPTP partially protected animals from the motor abnormalities induced by administration of MPTP alone. Both doses inhibited the onset of akinesia but only the large dose of MDL 72145 prevented the occurrence of other motor abnormalities. Moreover, while MDL 72145 (2.0 mg/kg) prevented the loss in uptake of [3H]dopamine into synaptosomes of the putamen, this was only partly prevented using the smaller dose. Similarly, while MDL 72145 (2.0 mg/kg) prevented loss of dopamine in the caudate, only partial protection was afforded by the smaller dose. However, in the nucleus accumbens, both doses of MDL 72145 prevented the depletion of dopamine, occurring in this region. Histological examination of the substantia nigra showed little or no cell loss in animals receiving the larger dose of MDL 72145 but a moderate cell loss in animals receiving the smaller dose. No damage was observed in the ventral tegmental area of animals treated with MDL 72145 (2.0 mg/kg) and only mild cell loss in those receiving the smaller dose.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Sequence ability in parkinsonians, patients with frontal lobe lesions and patients who have undergone unilateral temporal lobectomies.

Patients in the early stages of Parkinson's disease were compared with patients who had sustained damage specific to either the frontal or temporal lobes and normal controls on a number of sequencing tests. These tests involved the reproduction of sequences of hand gestures, sequences tapped out on blocks, and sequences of digits. Only the groups with frontal lobe lesions or right temporal lobectomies were impaired on any of these tasks, though no group was impaired on all of the sequencing tasks.

Adolescent↗
PubMed1989

The performance on learning tasks of patients in the early stages of Parkinson's disease.

It is known that in animals learning is disrupted by caudate lesions; but there has been no agreement about whether pathology in the basal ganglia causes a similar impairment in man. Nineteen patients in the early stages of Parkinson's disease were tested on two associative learning tasks and on the Wisconsin Card Sorting Task; and their performance was compared with that of patients with frontal or temporal lobe lesions. On the two associative learning tasks there was no overall difference between the Parkinsonian group and the controls. However, a minority of the Parkinsonian patients performed very poorly on these tasks; and it was noted that these tended to be the older patients.

Adult↗
PubMed1989

Interruption of motor programmes by electrical or magnetic brain stimulation in man.

These experiments describe the effect on voluntary movement of an electrical or magnetic stimulus delivered to the brain through the scalp. Subjects were trained to flex or extend their wrists as rapidly as possible in response to an auditory tone. A single brain stimulus delivered after the tone, and before the usual time of onset of the voluntary reaction, could delay the movement for up to 150 ms, without affecting the pattern of agonist and antagonist EMG bursts. Movement was not delayed when similar experiments were performed with supramaximal stimulation of the median nerve instead of the brain stimulus. The delay following a cortical shock was not due to spinal motoneurones being inaccessible to input during the delay, since H-reflexes given in the middle of the delay period were capable of activating the muscle. Neither could the delay be explained by the brain stimulus altering the time of the subject's intention to respond, since a stimulus delivered to one hemisphere prior to an attempted simultaneous bilateral wrist movement produced a far greater delay on the contralateral than the ipsilateral side. We suggest that the brain stimulus delayed movement by inhibiting a group of strategically placed neurones in the brain (probably in the motor cortex) which made them unresponsive for a brief period to the command signals which initiate agonist and antagonist muscle activity.

Cerebral Cortex↗
PubMed1989

The Bereitschaftspotential is abnormal in Parkinson's disease.

The average Bereitschaftspotential (BP) preceding a rapid, self-paced voluntary extension movement of the index finger was recorded from 6 scalp locations in 14 patients with Parkinson's disease who had been withdrawn from their normal drug therapy for at least 12 h before testing. The amplitude of the potential was measured at the peak negativity (N1) and 650 ms prior to this (NS1), and compared with that recorded in a group of 12 age-matched control subjects. The N1 amplitude was the same as in the normals, but the NS1 component was smaller in the patients, especially in midline leads. As a result, the rise in the BP between the peak NS1 and N1 component (termed NS2) was larger in the patient group. The NS1 component of the BP is thought to reflect preparatory activity in the supplementary motor area (SMA) of cortex. Since the basal ganglia provide a major source of afferent input to SMA, the reduction in NS1 in the patients probably results from inadequate basal ganglia activation of SMA. The larger NS2 component may reflect extra activity in other brain areas to compensate for the reduced SMA activity.

Aged↗
PubMed1989

Delay in the execution of voluntary movement by electrical or magnetic brain stimulation in intact man. Evidence for the storage of motor programs in the brain.

Experiments were undertaken to study the effect on voluntary movement of an electrical or magnetic stimulus delivered to the brain through the scalp. Subjects were trained to flex or extend their wrist rapidly in response to an auditory tone. A single brain stimulus (electrical or magnetic) delivered after the tone and before the usual time of onset of the voluntary reaction could delay the execution of the movement for up to 150 ms, without affecting the pattern of the agonist and antagonist EMG bursts. The delay increased with increasing stimulus intensity and with stimuli which were applied nearer to the usual time of onset of the voluntary reaction. A stimulus given after the onset of the first voluntary agonist EMG burst only delayed the onset of the first antagonist and later EMG bursts. Movement was not delayed when similar experiments were performed with supramaximal stimulation of the median nerve instead of the brain stimulus. The delay following a cortical shock was not due to spinal motoneurons being inaccessible to descending input during the delay period since a second brain stimulus, given in the middle of the delay period, was capable of producing a direct muscle response. Neither could the delay be explained by the brain stimulus altering the time of the subject's intention to respond since a stimulus delivered to one hemisphere before an attempted simultaneous bilateral wrist movement produced a far greater delay of the contralateral than the ipsilateral movement. We suggest that the brain stimulus delayed movement by inhibiting a group of strategically placed neurons in the brain (probably in the motor cortex) which made them unresponsive for a brief period to the command signals they receive which initiate the motor program of agonist and antagonist muscle activity. The results have implications for the issues of the storage of motor programs, internal monitoring of central movement commands and the site of organization of the antagonist EMG burst.

Adult↗
PubMed1989

Reciprocal inhibition between forearm muscles in patients with writer's cramp and other occupational cramps, symptomatic hemidystonia and hemiparesis due to stroke.

Reciprocal inhibition of H reflexes in the forearm flexor muscles was examined in a group of 16 patients with writer's and other occupational cramps. The early disynaptic phase of reciprocal inhibition was normal. However, there was a reduction in the amount of later, presynaptic inhibition, when compared with age-matched normal subjects. Similar findings were seen in 2 patients with symptomatic hemidystonia in whom structural brain lesions were present. However, this reduction in presynaptic inhibition was not specific to patients with dystonia. In a further group of 13 patients with hemiparesis or hemiplegia due to stroke, abnormalities of both early and later phases of reciprocal inhibition were found. The patients with spasticity exhibited less disynaptic inhibition than those with normal tone or flaccid limbs. The changes in the presynaptic phase of reciprocal inhibition did not correlate with the clinical signs of spasticity and increased muscle tone. These results provide objective evidence of a physiological basis for the action or task-specific focal dystonias such as writer's cramp.

Adolescent↗
PubMed1989

The treatment of severe action myoclonus.

Ten patients with severe disabling myoclonus were treated with clonazepam, sodium valproate, primidone and piracetam alone, or in different combinations. Electrophysiological assessment indicated a cortical origin for the myoclonus in every case. Considerable improvement of myoclonus was achieved with combinations of these drugs in all patients, but this was not possible with monotherapy. In one patient two drugs were necessary (clonazepam and piracetam); in the others more than two drugs were required. The combination of sodium valproate, clonazepam and primidone (3 patients), or piracetam, clonazepam and primidone (3 patients), or the four drugs together (3 patients) was necessary to provide substantial relief of myoclonus. Such polytherapy generally was tolerated well. The benefits of treatment continued for more than 1 year in all cases, although progressive underlying pathology often caused other increasing disability.

Adolescent↗
PubMed1989

Corticobasal degeneration.

Three patients with clinical and pathological features of corticobasal degeneration are described. They presented with a progressive disease bearing some clinical resemblance to Steele-Richardson-Olszewski syndrome and displaying some pathological features of Pick's disease. Their illness began at the age of 59 to 66 yrs with focal dystonia and myoclonus of an arm, the 'alien hand' sign, or an akinetic-rigid syndrome. They developed a supranuclear gaze palsy, parkinsonian features and mild cerebellar signs. Two patients showed constructional dyspraxia when using the arms. The duration of disease to death was 4 to 6 yrs. Pathological examination showed frontoparietal atrophy with cortical cell loss, gliosis and Pick cells, but there was no significant hippocampal disease or Pick bodies in this region. There was nerve cell loss and gliosis in the thalamus, lentiform nucleus, subthalamic nucleus, red nucleus, midbrain tegmentum, substantia nigra and locus coeruleus. Neuronal inclusions in the substantia nigra, termed corticobasal inclusions, were reminiscent of the globose neurofibrillary tangle of Steele-Richardson-Olszewski syndrome, and other pale inclusions resembled the pale body of Parkinson's disease, but Lewy bodies and neurofibrillary tangles were generally absent. Some nigral inclusions were similar to those in Pick's disease. Despite some pathological similarities to Pick's disease we suggest that the distribution of nerve cell loss and the corticobasal inclusion are unique to corticobasal degeneration.

Aged↗
PubMed1989

The antiparkinsonian activity of CQA 206-291, a new D2 dopamine receptor agonist.

CQA 206-291, a new D2 dopamine receptor agonist with a biphasic dopaminergic profile, was given to six patients with idiopathic Parkinson's disease after overnight drug withdrawal. With incremental single oral doses of CQA, a dose-related, clinically significant, and prolonged antiparkinsonian effect was observed. Most subjects experienced drowsiness after the drug while a minority of subjects experienced nausea and/or vomiting or postural hypotension. Further study of this drug in humans is indicated.

Aged↗
PubMed1989

The value of urethral sphincter electromyography in the differential diagnosis of parkinsonism.

A series of 54 patients presenting with parkinsonism underwent clinical assessment and urethral sphincter electromyography (EMG). After clinical assessment, 26 were thought to be suffering from probable multiple system atrophy (MSA), 15 were thought to have possible MSA and 13 were diagnosed as having probable idiopathic Parkinson's disease (IPD). Of those with probable MSA, 16 were found to have an abnormal urethral sphincter EMG. In the group with possible MSA, only 5 patients had an abnormal EMG while in the group with probable IPD, only 1 patient had an abnormal EMG. It was concluded that urethral sphincter electromyography provides a useful method of distinguishing between idiopathic Parkinson's disease and multiple system atrophy. It also provides a means of identifying those patients with parkinsonism whose incontinence may well be worsened, or in whom incontinence may develop following lower urinary tract surgery.

Aged↗