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Biomedical subjects

D L Garver

Publications and source records attributed to D L Garver.

At least 91 records · Page 5Linked to original sources

Lithium response in good prognosis schizophrenia.

The authors report the results of a 2-week lithium trial using 31 patients meeting Research Diagnostic Criteria for schizophrenia or schizoaffective disorder who were also diagnosed according to DSM-III criteria. One-third of the patients showed reduction of their schizophrenic-like symptoms during the lithium trial. Seven of the 9 responders (78%) met DSM-III criteria not for schizophrenia but for a schizophreniform disorder. Such patients also met McCabe and associates' criteria for good prognosis schizophrenia. This study lends further support to the growing body of evidence which suggests that schizophreniform disorder and good prognosis schizophrenia may be affective disorders with atypical schizophrenic-like features. The authors cautiously suggest that a lithium trial may be indicated in this subgroup of patients.

Adult↗

Beta-adrenergic receptor function in affective illness.

In a study of beta-adrenergic receptor sensitivity, the authors determined the response of cyclic AMP synthesis to in vitro addition of norepinephrine (NE) and isoproterenol (IP) in leukocytes of patients with affective illness and schizophrenia and of normal controls. IP-stimulated increase in 3H-cyclic AMP synthesis in depressed patients was significantly lower than in normal subjects and schizophrenic patients. These results suggest that beta-adrenergic receptor sensitivity is reduced in depressive illness.

Adenylyl Cyclases↗

Phencyclidine-induced stereotyped behavior in monkeys: antagonism by pimozide.

The psychotomimetic substance, phencyclidine (PCP), was administered chronically to selected members of a primate social colony. PCP induced stereotyped behavior in all treated monkeys at each of three test doses. Furthermore, there was a significant increase in the amount of stereotypy seen during the second and third weeks of treatment compared to the first week. The dopamine receptor blocking agent pimozide antagonized PCP stereotypy. The results are discussed in terms of dopamine mediation of these responses.

Animals↗

Urinary cyclic AMP excretion by methadone subjects during gradual and acute withdrawal.

Laboratory and animal investigations have supported the hypothesis that levels of cyclic AMP are stable during tolerance to narcotic drugs and increased during withdrawal. In order to test this hypothesis, serial 24-h urinary excretion of cyclic AMP by long-term methadone addicts was determined during a period of stable methadone intake, a period of gradual withdrawal, and a period of acute withdrawal. Cyclic AMP excretion during stable methadone intake is identical to that of normal control subjects. Neither gradual nor acute withdrawal appears to affect the urinary excretion of cyclic AMP. These data agree with previous reports in the literature which suggest that cyclic AMP levels are not altered during tolerance to narcotics, but do not support the hypothesis that levels of the nucleotide might be increased during withdrawal.

Adult↗

Neuroleptic drug levels and therapeutic response: preliminary observations with red blood cell bound butaperazine.

The authors studied neuroleptic concentration-therapeutic response curves for butaperazine (BPZ), a piperazine phenothiazine, in 10 schizophrenic patients during the first 12 days of treatment. BPZ bound to red blood cells (RBC) was more strongly correlated with therapeutic response than was plasma BPZ. RBC BPZ concentrations could be used to define a "therapeutic window", an optimun concentration for therapeutic response, above and below which favorable response diminishes. The authors emphasize the preliminary nature of the data but suggest that levels of RBC-bound neuroleptic may provide an important guide for dosage regulation in schizophrenic patients.

Administration, Oral↗

Postsynaptic supersensitivity in schizophrenia.

In the context of the dopamine hypothesis of schizophrenia, the authors examined postsynaptic dopamine (DA) receptor sensitivity in schizophrenic patients by means of a neuroendocrine strategy using the DA receptor agonist apomorphine and growth hormone (GH) release as the measurable postsynaptic event. The activity of platelet adenylate cyclase, an enzyme intimately associated with catecholamine receptor activity, was also studied following stimulation by prostaglandin E1 (PGE1). Patients diagnosed as having acute schizophrenia had significantly higher GH responses and adenylate cyclase activity than normal control subjects and patients diagnosed as having chronic schizophrenia. Chronic schizophrenic patients with and without tardive dyskinesia showed GH responses slightly lower than but not significantly different from those of control groups.

Acute Disease↗

Dystonic reactions following neuroleptics: time course and proposed mechanisms.

The occurrence of acute dystonic reactions was studied relative to drug pharmacokinetic parameters following a single dose of the phenothiazine, butaperazine. Dystonias occurred more than one half-life from peak butaperazine levels, 23 to 56 h after drug administration. The authors postulate that the appearance of dystonias on falling plasma concentrations may be due to disruption of dopaminergic-cholinergic balance caused by differential antidopaminergic and anticholinergic potencies of the drug.

Acetylcholine↗

Pharmacokinetics of red blood cell phenothiazine and clinical effects. Acute dystonic reactions.

Pharmacokinetics of the phenothiazine, butaperazine, were studied in relationship to acute dystonic reactions. Dystonias appeared on falling drug concentrations, more than one half-life after plasma and red blood cell (RBC) peak butaperazine concentrations. Red blood cell butaperazine kinetics differentiated better than did plasma butaperazine levels those subjects in whom dystonias would develop from those in whom they did not. We conclude that RBC phenothiazine levels may more clearly reflect drug concentration at critical brain sites than do simple plasma drug levels. Furthermore, dystonic reactions may be the result of differential sensitivity of two or more receptor systems to receptor blockade by antischizophrenic agents.

Acute Disease↗

Behavioral changes in a juvenile primate social colony with chronic administration of d-amphetamine.

Three selected members of a stable juvenile primate social colony of six, peer-raised, one-year old Stumptail macaques received 0.5 mq/kg of d-amphetamine sulfate daily for four weeks. Amphetamine significantly reduced play activity to a minimum in the treated monkeys throughout the treatment period. These animals preferred huddling with eyes open, although no sedation was apparent. As the treatment period progressed, stereotyped behavior developed, rising significantly during the final week of treatment. This model may be useful in studying the seemingly "paradoxical" quietening effect of amphetamine in children.

Amphetamine↗

Monoamine distribution in primate brain. I Catecholamine-containing perikarya in the brain stem of Macaca speciosa.

The distribution of catecholamine-containing cell bodies was examined in the brain stem of Macaca speciosa using the Falck-Hillarp histofluorescence technique. Extensive accumulations of such cells were seen in the ventral tegmental area, locus coeruleus, mesencephalic reticular formation and ventrolateral reticular formation of pons and medulla. This distribution was compared to that previously reported in rat, cat, squirrel monkey and human brain. Apparent species dissimilarities and similarities are reported.

Animals↗

A schizophreniform behavioral psychosis mediated by dopamine.

The authors conducted a study in which schizophrenic-like behavioral disturbances were induced in members of a macaque social colony by the chronic administration of d-amphetamine. Animals given the drug showed hypervigilance, hyperactivity, fragmented and repetitive behaviors, and progressive social withdrawal as well as the development of solitary stereotypies. The syndrome was dissected pharmacologically with alpha-methyl-para-tyrosine, chlorpromazine, pimozide, and haloperidol. Based on the behavioral findings and the known mechanisms of action of these drugs, the authors conclude that the major elements of the psychotic-like behavior induced by d-amphetamine were mediated by dopamine systems.

Animals↗