Search PubMed⌕ Search

Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 523 records · Page 29Linked to original sources
PubMed1988

Levels of Met-enkephalin, Leu-enkephalin, substance P and cholecystokinin in the brain of the common marmoset following long term 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine treatment.

Common marmosets were treated daily with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 7-9 mg/kg i.p.) for 25 days, and then kept out of drug for three months before biochemical measurements in various brain areas. This treatment induced a dramatic fall (-80%) in dopamine, homovanillic acid and dihydroxyphenylacetic acid levels in the putamen and caudate nucleus, and a significant but less pronounced reduction (less than or equal to 50%) in the levels of these compounds in the nucleus accumbens. In contrast, the concentrations of four neuropeptides: met-enkephalin, leu-enkephalin, substance P, and cholecystokinin, remained unaltered in all brain areas examined in MPTP-treated marmosets. Therefore the neuropeptide alterations previously reported in Parkinson's disease are probably not secondary to the severe lesion of dopaminergic neurones, but constitute another intrinsic feature of the disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Depression and disability in Parkinson's disease: a follow-up of 132 cases.

Patients with Parkinson's disease, 132 in number, were followed up after approximately one year, and measures of depression and disability re-administered. Depression was common on both occasions, and was characterized by dysphoria, pessimism and somatic symptoms, but not guilt or self-blame. Depression and disability were associated on both occasions. The relationship between changes in disability and depression across time was complex. In trying to understand changes in depression, the absolute change in disability may be less important than the relative change and rate of change. The results were discussed in relation to findings from other disease groups, and the implications for the clinical management of depression in Parkinson's disease.

Activities of Daily Living↗
PubMed1988

Personality in torticollis: a controlled study.

The Eysenck Personality Questionnaire, the trait scales of the Leyton Obsessional Inventory, the Spielberger State Trait Anxiety Inventory, and a questionnaire assessing marital status and harmony were completed by 100 torticollis patients and a control group of 49 cervical spondylosis sufferers. Information regarding employment status, and events preceding onset of their complaint was also obtained. The two groups did not differ in terms of any of the personality dimensions evaluated, or in their self-reports of events prior to onset of their illness. The groups differed significantly with regards to marital status (a higher proportion of the torticollis patients were single) but not marital harmony. A significantly higher proportion of the torticollis patients were in the permanently sick category of employment status. Findings of previous studies evaluating personality in torticollis and in sufferers of other disabling physical conditions are considered, and the results are discussed in terms of the effects of disabling chronic physical disorders.

Cervical Vertebrae↗
PubMed1988

Depression in torticollis: a controlled study.

Eighty-five patients with idiopathic, persistent spasmodic torticollis were compared to a control group of 49 patients with cervical spondylosis to assess (1) the prevalence of psychiatric disorder prior to and following the onset of their physical complaint, and (2) to establish the effect of torticollis on self-reports of depression on the Beck Depression Inventory, and self-rated hopelessness on the Hopelessness Scale. The prevalence of psychiatric disorder in the two groups did not differ. The torticollis patients had significantly higher mean scores on the Beck Depression Inventory, but did not differ from the control group in terms of hopelessness. Self-referent negative cognitions such as self-blame, self-accusation, self-punitive thoughts, and negative body-image emerged as the prominent component of depression in torticollis, which has implications for the management of depression in torticollis.

Adolescent↗
PubMed1988

The significance of ophthalmological symptoms in idiopathic blepharospasm.

Two hundred and seventy-two patients with idiopathic blepharospasm were reviewed to establish the role of local eye disease in their illness. The majority of patients (57%) had symptoms at the onset of their illness such as dryness of the eyes, grittiness, irritation or photophobia suggesting eye lid or ocular surface disease. Detailed ophthalmological examination at the time of presentation had been carried out in 170 of the 272 cases; 64% of these patients had ocular symptoms, and 40% had demonstrable ocular surface or eye lid pathology. Such pathology was usually bilateral, chronic and resistant to local treatment. Blepharospasm developed in these patients after a long latent period, often of many years. Unilateral pathology was acute, normally responded well to local treatment, but was followed by the development of bilateral blepharospasm usually within six months. Amongst all 272 patients, those without ocular symptoms at presentation rarely developed them subsequently; if they did, there were no abnormal signs. The data suggest that ophthalmological disorders may trigger idiopathic blepharospasm in a substantial proportion of cases predisposed to develop this condition.

Adolescent↗
PubMed1988

The coexistence of bradykinesia and chorea in Huntington's disease and its implications for theories of basal ganglia control of movement.

Investigation of motor function in a group of 17 patients with Huntington's disease reveals that, in addition to the chorea that many patients exhibit, defects in voluntary motor performance also are evident. Fast simple wrist flexion movements to 15 degrees or 60 degrees were slower, and individual movements showed greater variability than seen in normal subjects. This bradykinesia was most pronounced in those patients who were akinetic and rigid, but also was seen in those with chorea alone; bradykinesia was independent of the drug treatment that the patients were receiving (and was therefore not due to drug-induced parkinsonism). The electromyographic activity of the agonist muscles during such simple but slow movement differed from that seen in Parkinson's disease. The performance of complex movements revealed further deficits. Some patients were unable to combine two movements in a simultaneous or sequential movement task of squeezing the hand and flexing the elbow. Those who could perform these complex movements exhibited slowing of the velocity of the movement and prolongation of the interval between movements. These abnormalities were present in patients with chorea who were not taking neuroleptic drugs. It is argued that they represent an abnormality of motor programming of complex movements, over and above the defect in executing simple movements. The long latency stretch reflexes in wrist flexor muscles and flexor pollicis longus were reduced or absent, but this did not correlate with changes in motor performance, or with the reduced size of the early components of cortical sensory evoked potentials. Bradykinesia is thus shown to be an integral component of the motor disorder of Huntington's disease, in addition to the chorea. The coexistence of bradykinesia and chorea in this illness is compatible with current theories of the role of the basal ganglia in the control of movement.

Adult↗
PubMed1988

'Frontal' cognitive function in patients with Parkinson's disease 'on' and 'off' levodopa.

A wide range of cognitive impairments can be observed in patients with Parkinson's disease. A close parallel exists between these deficits and those found following damage to prefrontal cortex. Anatomical evidence is reviewed which reveals a complex pattern of neuronal circuits connecting the frontal cortex and basal ganglia. All these circuits are in some way dependent upon dopamine, suggesting that changes in the levels of dopamine stimulation may alter performance on 'frontal' tests. To test this hypothesis, a group of patients with Parkinson's disease were assessed both on and off levodopa treatment, on a range of tests selected from the human and animal experimental literature as being sensitive to disruption of prefrontal cortex. A variable pattern of results was obtained. On one test, a measure of verbal fluency, patients were impaired, compared with normal controls, only when off levodopa. On two measures, associative conditional learning and subject-ordered pointing, patients were impaired only when on levodopa, while on the final measures, the Wisconsin Card Sorting Test, patients were impaired both on and off levodopa. Two mechanisms are discussed to explain these results, one based on the effects of dopamine depletion, and the other based on the adverse effects of dopamine overstimulation. The results suggest that different areas of prefrontal cortex are involved in the tasks employed, and that functional levels of dopamine in separate areas of cortex and caudate may differ crucially in Parkinson's disease.

Aged↗
PubMed1988

Internal versus external cues and the control of attention in Parkinson's disease.

In recent years, several attempts have been made to characterize the nature of the cognitive deficits shown by patients with Parkinson's disease. It has been suggested variously that they have difficulty in switching cognitive set, in performing effortful (or controlled) as opposed to automatic tasks, or that their impairment is found in tasks which maximize the amount of 'self-directed task specific planning'. It is proposed that this latter distinction may be reformulated in terms of the degree of internal versus external attentional control which is required by the task. An experiment is described which attempted to manipulate this parameter. A version of the Stroop colour-word test was used, in which the words 'red' and 'green' were presented in the complementary coloured 'ink'. Subjects responded either to the colour of the ink in which the word was written or the colour named by the word. The relevant attribute changed at intervals during the course of the experiment. In one condition, the relevant stimulus attribute was cued before each trial. In another condition, subjects had to remember which attribute was currently relevant. Results revealed that patients with Parkinson's disease were impaired mainly on the second version of the task which required internal attentional control. The results are discussed in relation to the models of Working Memory (Baddeley, 1986), and attentional control (Norman and Shallice, 1980). Exploration of these models leads to the formulation of a theory in which the crucial determinant of cognitive impairment in Parkinson's disease is reduced resources in the Supervisory Attentional System. Provided the demands of the task are within the patient's available attentional resources the patient may not show any deficit. If, however, the attentional demands exceed available resources, as in tasks which depend upon internal cues, then deficits will be observed.

Attention↗
PubMed1988

Piracetam in the treatment of different types of myoclonus.

Forty patients with different clinical and electrophysiological types of myoclonus were treated with piracetam (18-24 g per day, p.o.) alone, or with other drugs (clonazepam, sodium valproate, and primidone) in different combinations. Piracetam in monotherapy improved the electrophysiological abnormalities in patients with cortical reflex myoclonus, but had no useful clinical effect. Sixteen patients obtained benefit from piracetam when given in combination with other antimyoclonic drugs; improvement was dramatic in two patients, moderate in seven and mild in seven. All patients showing some response to piracetam had myoclonus of cortical origin; however, five other patients with similar cortical myoclonus failed to improve when piracetam was added. Tolerance was excellent and side effects were minimal and transient. It is concluded that piracetam probably has an antimyoclonic action, but its potential value as a therapeutic tool for disabling myoclonus requires further study.

Adolescent↗
PubMed1988

The interaction of substituted benzamides with brain benzodiazepine binding sites in vitro.

1. The interaction of substituted benzamides with brain benzodiazepine (BDZ) binding sites was examined by their ability to displace [3H]-flunitrazepam ([3H]-FNM) from specific binding sites in bovine cortical membranes in vitro. 2. Clebopride, Delagrange 2674, Delagrange 2335 and BRL 20627 displayed concentration-dependent displacement of [3H]-FNM with IC50 values of 73 nM, 132 nM, 7.7 microM and 5.9 microM, respectively. Other substituted benzamides including metoclopramide, sulpiride, tiapride, sultopride and cisapride were inactive at 10(-5) M. 3. Inhibition by clebopride and Delagrange 2674 of [3H]-FNM binding was apparently competitive and readily reversible. 4. In the presence of gamma-aminobutyric acid (GABA), the ability of diazepam and Delagrange 2674 to displace [3H]-Ro 15-1788 binding was increased 3.6 and 1.6 fold respectively, compared to the absence of GABA, while ethyl beta-carboline-3-carboxylate (beta CCE) and clebopride were less potent in the presence of GABA. 5. Diazepam was 30 fold less potent at displacing [3H]-Ro 15-1788 in membranes that had been photoaffinity labelled with FNM than in control membranes, whereas the potency of beta CCE did not differ. Clebopride and Delagrange 2674 showed a less than two fold loss of potency in photoaffinity labelled membranes. 6. The pattern of binding of clebopride and Delagrange 2674 in these in vitro tests is similar to that found previously with partial agonists or antagonists at BDZ binding sites. 7. Clebopride and Delagrange 2674 inhibited [3H]-FNM binding with similar potency in rat cerebellar and hippocampal membranes, suggesting they have no selectivity for BDZ1 and BDZ2 binding sites. 8. Clebopride and Delagrange 2674 are structurally dissimilar to other BDZ ligands and represent another chemical structure to probe brain BDZ binding sites.

Affinity Labels↗
PubMed1988

Definition of the in-vivo accumulation of [3H]spiperone in brain using haloperidol and sulpiride to determine functional dopamine receptor occupation.

The in-vivo administration of [3H]spiperone caused an accumulation of radioactivity in the substantia nigra, tuberculum olfactorium, nucleus accumbens, striatum and frontal cortex when compared with cerebellar levels. Haloperidol (0.01-1.0 mg kg-1 i.p.) dose-dependently prevented the accumulation of [3H]spiperone in the substantia nigra, tuberculum olfactorium, striatum and nucleus accumbens. Sulpiride (10-160 mg kg-1 i.p.) dose-dependently prevented the accumulation of [3H]spiperone only in the substantia nigra. The effects of sulpiride on other areas were not consistent; there was a suggestion of a reduction in the accumulation of [3H]spiperone in tuberculum olfactorium and striatum, but not in nucleus accumbens. Neither haloperidol (0.01-1.0 mg kg-1 i.p.) nor sulpiride (10-160 mg kg-1 i.p.) caused displacement of [3H]spiperone from the frontal cortex. Both haloperidol (0.01-0.5 mg kg-1) and sulpiride (10-80 mg kg-1) increased striatal and mesolimbic HVA concentrations. Haloperidol potently blocked apomorphine-induced stereotypy but sulpiride was only effective at the highest dose employed. The functional effect produced by haloperidol correlated with its ability to define [3H]spiperone binding in-vivo to dopamine receptors in the substantia nigra, striatum and tuberculum olfactorium. In contrast, there was no correlation between functional effect of sulpiride and its ability to define [3H]spiperone binding in-vivo.

Animals↗
PubMed1988

Comparison of the in-vitro receptor selectivity of substituted benzamide drugs for brain neurotransmitter receptors.

The in-vitro selectivity of a group of substituted benzamide drugs for brain neurotransmitter receptors was determined to assess the most appropriate drugs for use in human PET studies. All substituted benzamide drugs studied inhibited [3H]haloperidol and [3H]spiperone binding to rat striatal membranes. The most potent compounds were YM 09151-2, clebopride and raclopride. However, these substances also interacted in differing degrees with alpha-1, alpha-2, beta-adrenergic, 5-HT-1, 5-HT-2, and opiate sites. Sulpiride, alizapride, SL 74205, TER 1546 and tiapride were specific for D-2 receptors, but these drugs were active only in the 10(-7)-10(-6) M range. Raclopride, amisulpiride and sultopride showed a 100-1000 differentiation between action on dopamine sites compared with other neurotransmitter receptors. No such selectivity was observed for clebopride or YM 09151-2. Specific substituted benzamides such as alizapride, may be appropriate in high concentrations for defining the interaction of PET ligands with brain dopamine receptors. More potent, but selective, drugs such as raclopride and amisulpiride, may be effective in low concentrations as ligands for labelling dopamine receptor sites. However, the ability of these various substituted benzamide drugs to penetrate into brain and in-vivo to identify dopamine receptors in all brain areas must be assessed.

Animals↗
PubMed1988

Percutaneous electrical stimulation of lumbosacral roots in man.

High voltage percutaneous electrical stimulation over the lumbosacral spinal column was used to assess conduction in the cauda equina of 13 normal subjects. Electromyographic activity elicited by such stimulation was recorded from various muscles of the lower limbs. The stimulating cathode was placed over the spinous process of each vertebral body and the anode kept on the iliac crest contralateral to the studied limb. Shifting the cathode in a rostro-caudal direction shortened the response latency in quadriceps, tibialis anterior and extensor digitorum brevis muscles. At moderate intensities (60% maximum), this occurred abruptly when the cathode was placed at levels corresponding to the exit sites from the spinal canal of the roots innervating these muscles. At these intensities, the size of the response in each muscle was largest when the cathode was placed over the conus medullaris or at or below the exit of the motor roots from the spine. Latencies were always equal to or shorter than those obtained with F-wave measurements, suggesting that peripheral motor axons, rather than intraspinal structures were activated by the stimulus. Collision experiments demonstrated that activation occurred at two sites: near the spinal cord and at the root exit site in the vertebral foramina. Recordings made from soleus indicated that larger diameter proprioceptive afferent fibres also could be activated. This technique might have useful clinical applications in the study of both proximal and distal lesions of the cauda equina and provide a non-invasive method of localising such lesions electrophysiologically.

Adult↗
PubMed1988

Blepharospasm: a review of 264 patients.

The natural history and response to different treatments have been evaluated in 264 patients with blepharospasm. The mean age of onset was 55.8 years and there was a female preponderance of 1.8 to 1. Dystonia elsewhere was found in 78% of patients, usually in the cranial-cervical region, and appeared to follow a somatotopic progression. A family history of blepharospasm or dystonia elsewhere was found in 9.5% of cases, which suggests a genetic predisposition. Ocular lesions preceded the onset of blepharospasm in 12.1% of cases. The response to drugs was inconsistent, although initial improvement was experienced by one fifth of patients treated with anticholinergics. Twenty-nine bilateral facial nerve avulsion operations were performed with benefit in 27 cases; but recurrences appeared in 22, on average one year after surgery. Botulinum toxin injections were performed in 151 patients. Significant improvement was achieved in 118 cases. Mean duration of benefit was 9.2 weeks. Transient ptosis and diplopia were the commonest side effects.

Adolescent↗
PubMed1988

Leukocyte glutamate dehydrogenase activity in patients with degenerative neurological disorders.

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 39 normal subjects, 32 neurological controls, 66 patients with progressive ataxic disorders, 32 with multiple system atrophy, 40 with Parkinson's disease, eight with Steele-Richardson-Olszewski syndrome, eight with juvenile Parkinsonism and four with the dystonia-Parkinsonism syndrome. GDH activity was reproducible to within 10% in leukocyte pellets stored at -70 degrees C for up to 9 months, and did not vary with sex or age in control subjects. There was marked variation in the relative proportions of heat stable and heat labile forms of GDH between control subjects and on repeated assay in the same subject. Total leukocyte GDH activity was similar in normal subjects and neurological controls. Mean total GDH activity was reduced in all patient groups by between 15 to 29% compared with controls. Fourteen patients had total GDH activity below 50% of the control mean, but low values were not specific for any one disease (five had ataxic disorders, four Parkinson's disease, three multiple system atrophy, one juvenile Parkinsonism, and one dystonia-Parkinsonism). The heat labile fraction of GDH represented about 20% of total activity in control subjects, and 27% in the patients with reduced total GDH activity. Thus low GDH activity was not disease-specific in this study, and the heat-labile GDH fraction was not selectively affected. "Reduced" leucocyte GDH activity in some patients may represent no more than the lower end of a normal distribution.

Adult↗
PubMed1988

Botulinum toxin in spasmodic torticollis.

Ten patients with spasmodic torticollis were treated by injection of a total dose of 30 ng of botulinum toxin type A into the affected sternomastoid and posterior cervical muscles. Nine patients reported improvement in head position and control, which was confirmed in seven cases by clinical assessment and "blind" videotape ratings before and 6 weeks after injection. Five patients who had pain reported relief. Seven patients had mild transient dysphagia after injection; two who were given a more concentrated solution of the toxin developed more severe dysphagia, but this also recovered. Other minor transient side effects included weakness of the voice and local pain. The beneficial effects of botulinum toxin injections lasted some 2 to 3 months. A slight reduction in the total dose of toxin injected avoided the main side effects, and this method of treatment appears to offer successful control of head position and pain in the majority of patients with torticollis.

Adult↗