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Biomedical subjects

D Chadwick

Publications and source records attributed to D Chadwick.

33 records · Page 2Linked to original sources
PubMed1977

Clinical, biochemical, and physiological features distinguishing myoclonus responsive to 5-hydroxytryptophan, tryptophan with a monoamine oxidase inhibitor, and clonazepam.

Fifteen patients with a variety of myoclonic syndromes were studied clinically, pharmacologically, and physiologically. CSF tryptophan, 5HIAA, and HVA were also measured. Of these patients, 8 were improved to varying degrees by therapy with 5HTP, tryptophan in combination with MAOI (but not tryptophan alone), and clonazepam. This group included 6 cases of post-anoxic myoclonus, one case of post-traumatic myoclonus and one undiagnosed case of non-progressive focal myoclonus and epilepsy. In this group low levels of CSF 5HIAA were found compared to non-responsive cases and controls. Two cases of dysynergia cerebellaris myoclonica, 2 cases of undiagnosed aetiology, 2 cases of essential myoclonus, and one case of palatal myoclonus failed to respond to drug therapy. However, even amongst the responsive group the improvement varied. The most dramatic responses were seen in those patients in whom physiological study suggested that myoclonus was mediated by brain-stem structures. Less dramatic responses were seen in patients in whom the myoclonus appeared to originate from cortical structures. The neurochemical basis of myoclonus responding to 5HT precursors and clonazepam is discussed. It is suggested that such myoclonus arises from a relative hypoactivity of the 5HT neuronal system which results in a release of abnormal responses to sensory stimuli which characterize this type of myoclonus.

5-Hydroxytryptophan↗
PubMed1977

Reticular reflex myoclonus: a physiological type of human post-hypoxic myoclonus.

A patient with post-hypoxic myoclonus, sensitive to therapy with 5-hydroxytryptophan and clonazepam, was subjected to detailed electrophysiological investigation. Brief generalised jerks followed the critical stimulus of muscle stretch. The electroencephalogram showed generalised spikes that were associated with, but not time locked to, the myoclonus. The cranial nerve nuclei were activated upward. Analysis of the findings suggests that the mechanism of the myoclonus is hyperactivity of a reflex mediated in the reticular formation of the medulla oblongata.

5-Hydroxytryptophan↗
PubMed1976

One drug (phenytoin) in the treatment of epilepsy.

Thirty-one, previously untreated, adult outpatients with idiopathic or focal grand-mal and/or focal minor seizures were treated initially with phenytoin. Serum-phenytoin concentrations were monitored to achieve an optimum range of 10-20 mug/ml if necessary. With a mean duration of follow-up of 14-7 months, only three (10%) patients have required the addition of a second drug, although without the guidance of serum concentrations sixteen (54%) might have been treated with a further drug. In the optimum serum-phenytoin range only 1 grand-mal attack occurred in this series, compared with a mean pre-treatment grand-mal seizure-rate of 1-1/month. Serum phenytoin declined slowly in fourteen (45%) patients. These observations suggest that many epileptic patients could be satisfactorily treated with one drug instead of the polypharmacy which they usually receive.

Adolescent↗
PubMed1976

Anticonvulsant-induced dyskinesias: a comparison with dyskinesias induced by neuroleptics.

Anticonvulsants cause dyskinesias more commonly than has been appreciated. Diphenylhydantoin (DPH), carbamazepine, primidone, and phenobarbitone may cause asterixis. DPH, but not other anticonvulsants, may cause orofacial dyskinesias, limb chorea, and dystonia in intoxicated patients. These dyskinesias are similar to those caused by neuroleptic drugs and may be related to dopamine antagonistic properties possessed by DPH.

Adolescent↗
PubMed1975

Manipulation of brain serotonin in the treatment of myoclonus.

The response of myoclonus to oral and intravenous L-5-hydroxytryptophan (5-H.T.P.) in combination with a peripheral decarboxylase inhibitor (carbidopa) and to clonazepam has been examined in 9 patients. Moderate improvement or complete cessation of myoclonus followed treatment with one or both of these regimens in 5 patients, 1 of whom also responded to the concurrent administration of L-tryptophan and a monoamineoxidase inhibitor. The remaining 4 patients were at best only slightly improved by either 5-H.T.P. or clonazepam. The responsive group consisted of 3 patients with a history of anoxia, 1 patient with non-history of severe head injury, and 1 patient with non-progressive focal myoclonus and epilepsy. This group had low levels of 5-hydroxyindole acetic acid in the lumbar cerebrospinal fluid. It is suggested that 5-H.T.P. plus carbidopa, L-tryptophan plus a monoamine-oxidase inhibitor, and clonazepam may all act by elevating brain levels of serotonin (5-H.T.) and that some human myoclonic syndromes may be specifically related to a cerebral deficiency of 5-H.T.

5-Hydroxytryptophan↗
PubMed1975

Amines, anticonvulsants, and epilepsy.

Concentrations of 5-hydroxyindoleacetic acid (5-H.I.A.T.) in cerebrospinal fluid (C.S.F.) were significantly raised in twenty-seven anticonvulsant-treated epileptic patients compared with fifteen untreated epileptics and twenty-two neurological controls. This rise was not seen until therapeutic blood-levels of phenobarbitone and diphenylhydantoin had been achieved, and was most striking in clinically intoxicated patients. Similar trends were seen in C.S.F. homovanillic acid (H.V.A). There was a close correlation between C.S.F. 5-H.I.A.A. and H.V.A., especially in the treated epileptics. These findings have implications for the antiepileptic and toxic effects of anticonvulsant drugs.

Adolescent↗
PubMed1975

Folate and monoamine metabolism in epilepsy.

In 27 drug-treated epileptics there was a significant fall in serum, red cell and CSF folate levels compared with 15 untreated epileptics and 22 neurological controls. The 3 folate parameters were positively correlated with each other and negatively correlated with serum phenobarbitone, diphenylhydantoin and primidone. There was also a significant elevation of CSF 5-hydroxyindoleacetic acid (5HIAA) in the drug-treated epileptics; but this was not seen until "therapeutic" serum levels of phenobarbitone and diphenylhydantoin had been achieved and was most marked in clinically intoxicated patients. Similar trends were observed in CSF homovanillic acid (HVA). CSF 5HIAA and HVA were positively correlated with each other, especially in the drug-treated patients, in whom both amine metabolites were also negatively correlated with CSF folate. A possible relationship between folate and monoamine metabolism is discussed with particular reference to the antiepileptic and toxic effects of phenobarbitone, diphenylhydantoin and primidone.

Adolescent↗
PubMedDate not supplied

Psychosocial outcomes of antiepileptic drug discontinuation. The Medical Research Council Antiepileptic Drug Withdrawal Study Group.

The MRC Antiepileptic Drug Withdrawal Study compared seizure control and the risk of relapse resulting from policies of slow discontinuation and routine maintenance of antiepileptic drug (AED) treatment in patients seizure-free for > or = 2 years. Because the decision to discontinue AEDs can have important psychosocial as well as medical consequences, we also sought to examine the psychosocial outcomes of the alternative policies Questionnaires were sent to eligible adults 2 years after their randomization. The response rate was 85%. There was little evidence of substantial effects of treatment policy on psychosocial outcomes, but seizure recurrence since randomization was associated with increased distress on several measures. However, receiving AEDs to control seizures was also associated with increased distress. Among patients for whom the risk of relapse after discontinuation appears low, the psychosocial benefits of discontinuation may be considerable.

Activities of Daily Living↗