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Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 631 records · Page 35Linked to original sources
PubMed1986

Hysteria--a neurologist's view.

Hysterical symptoms are defined as complaints that are not fully explained by organic or functional neurological disease. Hysterical symptoms are common in neurological practice, accounting for about 1% of neurological diagnoses. Of those with neurological hysterical symptoms, about 80% will not have the hysterical personality, and about 80% will not have Briquet's hysteria. Some 60% will have a physical disease and perhaps as many as 50% will have recognizable psychiatric illness, particularly depression. Others may have unrecognized physical or psychiatric illness. Many hysterical symptoms may be understood in terms of abnormal illness behaviour.

Adolescent↗
PubMed1986

Performance of simultaneous movements in patients with Parkinson's disease.

Ten right-handed patients with Parkinson's disease and 9 normal subjects performed five different types of movements as rapidly as possible in their own time: isotonic elbow flexion through an angle of 15 deg ('flex'); isometric squeezing of a force transducer between thumb and fingers ('squeeze'); isotonic finger flexion ('cut'); simultaneous performance of both 'flex' and 'squeeze'; simultaneous performance of 'flex' and 'cut'. The patients performed the separate movements of 'flex', 'squeeze' and 'cut' more slowly than normals. However, a more striking deficit was seen when a 'flex' and a 'squeeze' had to be performed at the same time, and with the same arm. There was an additional increase in movement times over and above that seen in the separate movements alone. If the patients used both arms ('flex' with the right, 'squeeze' with the left), rather than one, or when a 'flex' and a 'cut' had to be combined in the same arm, only a slight increase in movement times was observed. In normals, however, the speed of individual movements of 'flex', 'squeeze' or 'cut' was the same irrespective of whether they were performed separately or simultaneously. In any one subject, movement times for the separate components of 'flex' and 'squeeze' varied independently during the performance of the simultaneous movement. Because they remain independent, we suggest that when 'flex' and 'squeeze' are performed at the same time, two separate motor programmes are superimposed to produce the combined movement. In Parkinson's disease there may be a deficit in superimposing two separate motor programmes which leads to the pronounced slowness of simultaneous movements with the same arm. Comparison of movement times for a 'flex' (but not for a 'squeeze') in the separate and simultaneous movements showed that the degree of clinical akinesia was more closely related to the additional slowness in simultaneous movements than to the slowness seen when the movements were performed separately. The degree of disturbance in superimposing separate motor programmes may determine the amount of clinical akinesia in patients with Parkinson's disease.

Adult↗
PubMed1986

Visuospatial function in Parkinson's disease.

Previous research on visuospatial function in Parkinson's disease is reviewed. The present experiment was designed to test two fundamental aspects of spatial ability, namely right-left discrimination and the manipulation of those concepts in different spatial perspectives. Measures of accuracy and reaction time were taken. The performance of patients with Parkinson's disease did not differ from that of normal subjects in the spatial components of the task. Neither a review of the literature, nor the results of the present study, give support to the idea of a generalized visuospatial deficit in Parkinson's disease.

Female↗
PubMed1986

Repeated levodopa infusions in fluctuating Parkinson's disease: clinical and pharmacokinetic data.

The short-term efficacy of continuous intravenous infusions of levodopa (with oral peripheral decarboxylase inhibitor) in abolishing or reducing "on-off" fluctuations in patients with Parkinson's disease is well established. However, there are suggestions that clinical response may be less good with longer infusions, or infusions on consecutive days. We therefore gave intravenous infusions of levodopa to three such subjects on five consecutive days (6 h on day 1, 12 h/day on days 2 to 5). One subject's symptoms were perfectly controlled, one experienced one "off" period per day, and the third developed one or two off-periods per day. Nevertheless, clinical control in all three subjects was superior with levodopa infusions to that seen on optimum oral therapy. Plasma levodopa concentrations during the infusions could be correlated with off to on, and with on to off switches. In general, subjects needed higher plasma levodopa levels to turn "on" than to keep them mobile once on, and the threshold levels below which off-periods supervened were lower still. These experiments show that repeated intravenous infusions of levodopa are very effective in some parkinsonian subjects, who may be suitable candidates for prolonged parenteral treatment with alternative, more highly soluble, dopaminergic drugs.

Drug Administration Schedule↗
PubMed1986

Differential alterations in striatal acetylcholine function in rats during 12 months' continuous administration of haloperidol, sulpiride, or clozapine.

Rats were treated continuously for 12 months with therapeutically equivalent doses of either haloperidol (1.4-1.6 mg/kg/day), sulpiride (102-109 mg/kg/day), or clozapine (24-27 mg/kg/day). After treatment for 3 and 12 months with haloperidol or clozapine but not sulpiride, striatal acetylcholine levels were increased. Striatal choline acetyltransferase activity was not altered by any drug treatment. Vmax for striatal acetylcholinesterase activity during the course of 12 months' treatment with haloperidol or clozapine, but not with sulpiride, tended to increase; Km was not altered by any drug treatment. Bmax for specific striatal [3H]quinuclidinyl benzilate binding was not altered by haloperidol or sulpiride treatment but was transiently elevated after 6 months of clozapine treatment, thereafter returning to control levels. Kd was not altered by any drug treatment. These findings indicate that alterations in striatal acetylcholine content caused by chronic treatment with some but not all neuroleptics are due to changes in cholinergic neuronal activity rather than neurotransmitter synthesis or destruction. The effects of haloperidol but not those of clozapine may be related to the emergence of functional striatal dopamine receptor supersensitivity. Since haloperidol (which is associated with a high prevalence of tardive dyskinesias) but not clozapine (which is not) had similar effects on striatal cholinergic function, the latter may not be related to the emergence of tardive dyskinesias during chronic therapy.

Acetylcholine↗
PubMed1986

Lack of change in basal ganglia neuropeptide content following subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of the common marmoset.

Treatment of common marmosets with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 1-4 mg/kg for up to 4 days) caused a profound parkinsonian state. Ten days from the start of MPTP treatment, all animals showed marked motor impairment, consisting of bradykinesia and akinesia, limb rigidity, postural abnormalities, loss of vocalisation and blink reflex, and, on occasions, postural tremor. Measurement of caudate-putamen monoamine content at this time showed a profound loss in 3,4-dihydroxyphenylethylamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid concentrations. Measurement of neuropeptide concentrations in the caudate-putamen, internal and external segments of the globus pallidus, nucleus accumbens, substantia nigra, frontal cortex, and hippocampus showed met-enkephalin, leu-enkephalin, and cholecystokinin (CCK-8) concentrations to be unaffected by MPTP treatment. There was a small decrease in the substance P content of frontal cortex, but otherwise the content of this neuropeptide was unaltered. Parkinsonism in the marmoset, induced by MPTP treatment 10 days earlier, does not alter neuropeptide concentrations in the manner observed in Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Specific [3H]piflutixol binding to CHAPS-solubilised rat striatal preparations involves dopamine D-2 but not D-1 binding sites.

[3H]Piflutixol binding to rat striatal membrane preparations identifies both D-1 and D-2 sites. We used [3H]piflutixol to characterise those binding sites present in 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS)-solubilised rat striatal preparations. The specific binding of [3H]piflutixol, as defined using cis-flupenthixol, to CHAPS-solubilised rat striatal tissue was saturable and of high affinity. Specific [3H]piflutixol binding to the solubilised preparations was displaced stereoselectively by the isomers of butaclamol and to an equal extent by both cis-flupenthixol and (+/-)-sulpiride. A positive correlation was found between the capacity of a range of drugs to displace [3H]piflutixol binding and the displacement of [3H]spiperone to the same preparations. The Bmax of [3H]piflutixol binding was not different from that of [3H]spiperone binding to the same preparation. These studies suggest that, in contrast to specific binding of membrane preparations, the specific binding of [3H]piflutixol to CHAPS-solubilised preparations involves mainly D-2 sites. Specific [3H]piflutixol binding, in contrast to [3H]spiperone binding, showed only slow dissociation from soluble preparations. The binding of [3H]piflutixol to CHAPS-solubilised preparations was retained during passage through a gel filtration column. This prelabelling of solubilised striatal preparations using [3H]piflutixol may aid in the purification of CHAPS-solubilised rat striatal D-2 sites.

Animals↗
PubMed1986

A comparison of motor behaviours in groups of rats distinguished by their climbing response to apomorphine.

Administration of apomorphine hydrochloride (0.5 mg kg-1 s.c.) to adult male or female Wistar rats previously acclimatized to the test environment induced climbing behaviour in approximately 50% of animals examined. The proportion of animals climbing was related to age, being maximal at 8-9 weeks. Those animals showing an initial climbing response to apomorphine (0.5 mg kg-1 s.c.), climbed when challenged with this dose of apomorphine on subsequent occasions. In 'climbing' animals the intensity of response was related to the dose of apomorphine administered; no dose-response relationship was observed in 'non-climbing' animals. No overall differences in the spontaneous motor behaviour of 'climbing' and 'non-climbing' animals were apparent as assessed by measurement of spontaneous climbing behaviour, by holeboard activity, and by locomotor activity measured in either photocell cages or in a treadwheel. There was no overall difference in the ability of apomorphine to induce locomotor activity or stereotyped behaviour in 'climbing' and 'non-climbing' animals. However, the administration of apomorphine induced rearing and treadwheel activity only in those animals classified as 'climbers'. There was no difference between the number (Bmax) of specific [3H]-spiperone binding sites or the dissociation constant (KD) in striatal or mesolimbic tissue preparations for 'climbing' and 'non-climbing' rats. The ability of an animal to climb in response to apomorphine appears to be dependent on an ability to orient vertically, since this is a component of behaviour common to climbing, rearing, and treadwheel activity. The ability to climb does not appear to be related to differences in dopamine receptor numbers in brain or to the penetration of apomorphine into brain.

Age Factors↗
PubMed1986

[3H]SCH 23390 identifies D-1 binding sites in rat striatum and other brain areas.

The specific in-vitro binding of [3H]SCH 23390 has been characterized and its use in the identification of D-1 sites in various brain regions examined. At a single ligand concentration (0.4 nM) the specific binding of [3H]SCH 23390 to striatal membranes was routinely 98% of total binding as defined using 10(-5) M cis-flupenthixol. Specific binding at 37 degrees C reached equilibrium at 15 min and was reversible with a t1/2 for dissociation of 14 min. Specific binding of [3H]SCH 23390 over a range of concentrations (0.01-3.5 nM) was saturable (Bmax 73 pmol g tissue-1) of high affinity (Kd 0.36 nM) and to a single population of binding sites. Specifically bound [3H]SCH 23390 (0.4 M) was stereo selectively displaced by the isomers of butaclamol and flupenthixol but not by the D-2 selective antagonist, sulpiride. 5-HT, noradrenaline and cinanserin caused little or no displacement. Specific binding of [3H]SCH 22390 (0.4 nM; as defined using 10(-5) M cis-flupenthixol) showed marked regional variation. Specific binding was highest in the striatum; high levels were also observed in the mesolimbic area and substantia nigra. Lower specific binding was found in the frontal cortex and superior colliculus with the lowest levels in cerebellar preparations. The inclusion of 3 X 10(-7) M cinanserin did not alter the extent of specific binding observed in any brain region. The properties of [3H]SCH 23390 suggest it to be an excellent ligand for identification of D-1 sites in a variety of brain regions.

Animals↗
PubMed1986

[125I]Spiperone is not a useful ligand for studying the CHAPS solubilized dopamine D-2 receptor from rat striatum.

The interaction of [125I]spiperone and [3H]spiperone with CHAPS solubilized preparations of rat striatal tissue has been compared. Only about 15% of [125I]spiperone binding was displaced by sulpiride compared with about 67% of [3H]spiperone binding. In the presence of (+)-butaclamol the displacement of [125I]spiperone was twice that found with sulpiride suggesting an interaction with sites other than D-2 receptors. The specific binding of [125I]spiperone was not saturable within the maximum concentration range that could be employed and its affinity for soluble preparations was far lower than that of [3H]spiperone. Despite its very high specific activity [125I]spiperone offers no advantage over [3H]spiperone in the identification of dopamine receptors in soluble tissue preparations.

Animals↗
PubMed1986

Scaling of the size of the first agonist EMG burst during rapid wrist movements in patients with Parkinson's disease.

Rapid wrist flexion movements were studied in a group of 10 patients with Parkinson's disease both on and off their normal drug therapy, and were compared with the same movements made by a group of eight normal individuals. When normal subjects made movements through 60 degrees, the first agonist burst of EMG activity in the wrist flexor muscles was longer and larger than that seen in movements of 15 degrees. If a large opposing load of 2.2 Nm was added, this also increased the size and duration of the first agonist EMG burst. Although the movements made by the patients were slower than those of normals, the size and duration of the first agonist EMG burst changed with movement size and added load in the normal way. This shows that patients can produce large, long bursts of EMG activity, but that there is a failure to match these parameters appropriately to the size of movement required. The effect of levodopa therapy on the movements was not dramatic. Although patients produced faster wrist movements when on medication than when off, the change was relatively small compared with the change seen in their overall clinical rating. Changes in the velocity of movements at a single joint are not a good reflection of the overall clinical state of patients with Parkinson's disease.

Adult↗
PubMed1986

Associated postural adjustments in Parkinson's disease.

Postural activity in muscles of the back and legs associated with voluntary forward elevation of the arm at the shoulder with the subject standing was examined in 14 patients with Parkinson's disease and nine normal individuals. The time of onset of EMG activity in each of the postural muscles, relative to the onset of activity in the prime mover, was the same for both patient and normal groups and did not depend on load. The amplitude of the EMG bursts and their frequency of occurrence, was less in patients off drug treatment and immobile, than when mobile on therapy. We conclude that the timing of associated postural adjustments is normal in Parkinson's disease, although their size may be decreased.

Adult↗
PubMed1986

A method of monitoring function in corticospinal pathways during scoliosis surgery with a note on motor conduction velocities.

Spinal cord potentials produced by high voltage electrical stimulation of the scalp over the motor cortex were recorded intraoperatively from bipolar electrodes inserted into the epidural space of eleven patients undergoing corrective surgery for scoliosis. Responses to single stimuli could be recorded from the cord at all levels from cervical to low thoracic regions. The potentials were larger in the cervical than in the thoracic region and sometimes were followed by later waves at high stimulation intensities. Conduction velocity in large corticomotoneuron fibres was estimated to be between 50-74 ms-1 in different patients. This technique for monitoring motor tract function may be a useful adjunct to conventional monitoring of the sensory pathways during surgery.

Adolescent↗
PubMed1986

Depression in Parkinson's disease: a quantitative and qualitative analysis.

Depression is a common feature of Parkinson's disease, a fact of both clinical and theoretical significance. Assessment of depression in Parkinson's disease is complicated by overlapping symptomatology in the two conditions, making global assessments based on observer or self-ratings of doubtful validity. The present study aimed to provide both a quantitative and qualitative description of the nature of the depressive changes found in Parkinson's disease as compared with normal elderly subjects and arthritis patients. As with previous studies, the patients with Parkinson's disease scored significantly higher than normal controls on various self-ratings of depression and anxiety but, in this study, did not differ from those with arthritis. Qualitatively, both the Parkinson's disease and the arthritis groups had depression characterised by pessimism and hopelessness, decreased motivation and drive, and increased concern with health. In contrast, the negative affective feelings of guilt, self-blame and worthlessness were absent in both patient groups. This pattern of depression was significantly associated with severity of illness and functional disability. However, these factors account for only a modest proportion of the variability in test scores. Probable unexplored factors are individual differences in coping style and availability of support.

Aged↗
PubMed1986

Familial dystonia and visual failure with striatal CT lucencies.

A unique disorder is described in seven members of two families in whom dystonia was variably associated with subacute visual loss or asymptomatic optic atrophy, and striking bilateral symmetrical lucencies on CT scan, especially involving the putamen. It is possible that this is a variant of Leigh's disease. However, there were considerable differences between these patients and those with pathologically proven Leigh's disease. This condition must be excluded in all patients thought to have idiopathic dystonia, subacute visual failure similar to Leber's optic neuropathy, or a combination of these disorders.

Adolescent↗
PubMed1986

Focal dystonia of the jaw and the differential diagnosis of unilateral jaw and masticatory spasm.

The clinical features, differential diagnosis and treatment of unilateral spasms of the jaw and masticatory muscles are discussed and illustrated by eight cases of unilateral jaw spasms of various aetiologies. These include focal dystonia of the jaw, hemimasticatory spasm with and without facial hemiatrophy, paroxysmal events in multiple sclerosis and tetany. Attention is particularly drawn to four cases of unilateral dystonia of the jaw which has not been described before.

Adult↗