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Biomedical subjects

D E Casey

Publications and source records attributed to D E Casey.

At least 109 records · Page 6Linked to original sources
PubMed1980

gamma-Acetylenic GABA in tardive dyskinesia.

Brain gamma-aminobutyric acid (GABA) has been proposed to play a role in the modulation of extrapyramidal motor function. The effects of increasing brain GABA with gamma-acetylenic GABA (GAG), a drug that inhibits GABA transaminase, were evaluated in ten patients with stable tardive dyskinesia during a blind placebo-controlled trial. Drug effects during active treatment and two placebo periods were evaluated by scoring randomly sequenced videotapes of tardive dyskinesia and parkinsonian symptoms recorded weekly during a standardized examination. Tardive dyskinesia was significantly reduced, and preexisting parkinsonism increased slightly. The largest decrease in tardive dyskinesia symptoms occurred in patients receiving higher neuroleptic doses, suggesting an interaction between GABA and dopamine. Prolactin values increased but growth hormone values were unchanged. Psychiatric symptoms were also unchanged during GAG treatment.

4-Aminobutyrate Transaminase↗
PubMed1980

Enkephalin, morphine, and naloxone in tardive dyskinesia.

Eight psychiatric patients with tardive dyskinesia (TD) were treated with single doses of the synthetic met-enkephalin analogue FK 33-824 (1, 2, and 3 mg IM) morphine (10 mg SC) and naloxone, an opiate receptor antagonist (0.8 mg IM). The drug effects were assessed by blind evaluation of randomly sequenced videotapes made before and during treatment. FK 33-824 (1, 2, and 3 mg IM) slightly reduced TD (P < 0.05) and increased preexisting bradykinesia. The effect on TD, however, was pronounced only in patients concurrently treated with neuroleptics in relatively high doses. Morphine had a similar although weaker antihyperkinetic effect, whereas naloxone had no effect. Side effects of FK 33-824 included dizziness, heaviness in the extremities, slurred speech, and dryness of mouth. Morphine caused drowsiness, dizziness, ataxia, and nausea, and naloxone had no side effects. The results do not point to a primary role of enkephalin in the pathophysiology of TD, but enkephalin may interact with dopamine functions and potentiate some of the effects of neuroleptic drugs.

Aged↗
PubMed1980

Dopamine, acetylcholine, and GABA effects in acute dystonia in primates.

Neurological side effects associated with neuroleptic drugs result from a complex interaction of multiple neurotransmitters. To clarify the etiology of neuroleptic-induced acute dystonic reactions, monkeys (Cercopithecus aethiops) were treated with haloperidol at doses sufficient to evoke dystonia, and the effects of agents that influenced dopaminergic, cholinergic, or GABAergic neurotransmitters were evaluated. Apomorphine, a dopamine (DA) agonist, and biperiden, an acetylcholine (ACh) antagonist, decreased acute dystonia, whereas alpha-methyl-p-tyrosine (AMPT), an inhibitor of DA synthesis, and physostigmine, an ACh agonist, agonist, increased the symptoms. Muscimol, a GABA agonist, increased the dystonias in a dose-dependent way, and GABA inhibition with picrotoxin also aggravated dystonia, complicated by systemic intoxication and seizures. The reciprocal interaction between DA and ACh influences is consistent with clinical findings and animal models of dyskinesias. Dystonia may also be modulated by GABAergic substrates, but the results suggest complex interactions among DA, ACh, and GABA neurotransmission. Symptoms involving the orofacial, limb, and trunk regions, and purposeless overactivity are discussed in comparison with acute and tardive neuroleptic-induced movement disorders.

Acetylcholine↗
PubMed1980

Oxiperomide in tardive dyskinesia.

Tardive dyskinesia can be suppressed by dopaminergic receptor blockers, but often at the cost of a reciprocal increase in Parkinsonism. Oxiperomide, a dopaminergic antagonist that has been shown to reduce levodopa-induced dyskinesias without producing an equal aggravation of Parkinsonism, was evaluated in a blind placebo-controlled trial in 10 patients with tardive dyskinesia. It decreased tardive dyskinesia significantly (p less than 0.01) without significantly provoking or increasing Parkinsonism. There was no relationship between either tardive dyskinesia or Parkinsonism and eye blinking rates. These results can be interpreted as additional evidence for the existence of more than one population of dopamine receptors involved in controlling extrapyramidal function. Although oxiperomide is only a palliative suppressing agent in tardive dyskinesia, as the symptoms returned when the drug was stopped, it is an interesting agent in the search for selective dopaminergic receptor blockers.

Aged↗
PubMed1980

Pharmacology of blepharospasm-oromandibular dystonia syndrome.

Blepharospasm and oromandibular dystonia are clinically similar to other hyperkinetic movement disorders. Dopaminergic antagonist (neuroleptic) and purported cholinergic agonist (deanol) treatment improved symptoms, whereas dopaminergic agonist (carbidopa/levodopa) and cholinergic antagonist (benztropine) drugs worsened symptoms in two patients. This suggested that the syndrome is also pharmacologically related to the hyperkinetic dyskinesias. Symptoms worsened substantially during carbidopa/levodopa but temporarily resolved in one patient and improved in another when the drug was discontinued. This suggests that the pathophysiology of these symptoms involves an idiopathic form of receptor hypersensitivity that can be modified by agonist treatment. The effect of cholinergic agents was less than the effect of dopaminergic drugs, implying that dopamine plays a predominant role in the pathophysiology.

Aged↗
PubMed1980

Gamma-Acetylenic GABA in tardive dyskinesia.

gamma-Acetylenic GABA, a drug that increases brain GABA via GABA transaminase inhibition, was evaluated in a blind placebo-controlled trial in 10 patients with stable tardive dyskinesia. Drug effects during active treatment (75 to 225 mg/day) and pre- and post-treatment placebo periods were determined by scoring TD and parkinsonian symptoms recorded weekly on videotape during standardized examinations. GAG significantly reduced TD (p < 0.01), although the effect was moderate, in patiens concurrently taking neuroleptics and increased preexisting parkinsonism. The greatest antihyperkinetic effects tended to occur in patients receiving higher neuroleptic doses, suggesting an interaction between GABA and dopamine. There was no effect of GAG on psychiatric symptoms. Further investigations with GAG and similar agents will be important tools for investigating GABA in movement disorders and other central nervous system dysfunctions.

Adult↗
PubMed1980

Watch it: a method to assist and simplify record keeping.

A quick inexpensive, reproducible method of recording changes in size of visible cutaneous or palpable subcutaneous lesions has been used for more than 10 years with satisfaction. Records are life-size and assist in treatment planning and patient acceptance.

Female↗
PubMed1979

Mood alterations during deanol therapy.

An imbalance between central cholinergic and adrenergic influences may affect mood disorders. Of 38 patients taking high doses of deanol, a putative acetylcholine precursor, eight developed changes in mood: five became depressed and three became hypomanic. A predisposition is suggested as seven of these eight patients had histories of affective symptoms. There was no relationship between the changes in dyskinesias and mood. These observations have both practical and heuristic implications for the management of patients and for further research into the pharmacology of affective disorders and deanol.

Affective Symptoms↗
PubMed1979

Sulpiride in tardive dyskinesia.

Tardive dyskinesia can be suppressed by drugs that block dopaminergic receptors, but often at the cost of a concomitant increase in parkinsonism. Sulpiride (400 -- 2100 mg/day), a selective type-2 dopamine receptor antagonist, was evaluated in a blind, placebo-controlled trial in 11 patients with tardive dyskinesia. It significantly (P less than 0.01) reduced tardive dyskinesia without significantly affecting parkinsonism, although three patients had a increase in preexisting parkinsonian hypokinesia and tremor. During the placebo phase, the tardive dyskinesia and parkinsonian scores returned to the pretreatment values. There was no relationship between either tardive dyskinesia or parkinsonism and eye blinking rates. These results are consistent with the hypothesis that more than one population of dopamine receptors are involved in controlling extrapyramidal function. Sulpiride is an important tool for elucidating both the practical and heuristic aspects of subtypes of dopamine receptors and is a lead in the search for compounds that selectively affect dopaminergic mechanisms.

Aged↗
PubMed1979

Neuroleptic-potentiating effect of alpha-methyl-p-tyrosine compared with haloperidol and placebo in a double-blind cross-over trial.

The hypothesis that schizophrenia results from overactive dopaminergic influences suggests that reducing dopamine synthesis may increase the clinical effects of dopamine receptor blocking neuroleptic drugs. The neuroleptic potentiating role of alpha-methyl-paratyrosine (AMPT), a tyrosine hydroxylase inhibitor, was compared with haloperidol and placebo in a double-blind cross-over trial. Both AMPT and haloperidol increased the anti-schizophrenic effect of neuroleptic treatment in reduced dose compared with placebo (P less than 0.05), though two patients relapsed during the AMPT period. Both drugs slightly increased extrapyramidal symptoms, but the effect was greater with haloperidol. The limited antipsychotic effect and the potential for aggravating neurological symptoms suggest that the combination of AMPT and neuroleptics does not offer a superior advantage to treating schizophrenia. AMPT, however, may still be used as a research tool in elucidating pathogenetic mechanisms.

Adult↗
PubMed1979

Sodium valproate in tardive dyskinesia.

Recent findings suggest that tardive dyskinesia may involve GABA-ergic influences in addition to dopaminergic receptor hypersensitivity and relative cholinergic hypofunction. Sodium valproate, which may increase brain GABA, moderately recuded tardive dyskinesia with doses of 900--3000 mg/day, as measured by a tremorgraph and rating scales. There was no correlation between dosage, blood levels, or clinical response. Although the symptoms were not completely controlled, valproate and other GABA-ergic agents may be useful compounds in studying and treating tardive dyskinesia.

Dose-Response Relationship, Drug↗
PubMed1978

Simultaneous metastatic epidermoid carcinoma and chronic granulocytic leukemia.

The second reported patient with simultaneous metastatic epidermoid carcinoma and chronic myelogenous leukemia is described. The difficulty of differentiating the leukemia from a leukemoid reaction is discussed. The incidence of, and importance of looking for, second primary cancers in patients known to have cancer is emphasized.

Carcinoma, Squamous Cell↗
PubMed1978

Tardive dyskinesia in an adolescent.

The frequent use of neuroleptic drugs in the treatment of disturbed children and adolescents demands that clinicians be aware of the danger of tardive dyskinesia in this age group. A case history of a 15-year-old boy who developed incapacitating tardive dyskinesia that resolved during treatment with deanol is presented. The recognition, differential diagnosis, and management of this syndrome in children are discussed. Lithium carbonate was a useful alternative to neuroleptics in managing the adolescent's disturbed behavior.

Adolescent↗