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Biomedical subjects

J F Lipinski

Publications and source records attributed to J F Lipinski.

At least 19 recordsLinked to original sources
PubMed1992

Polysomnographic characteristics of young manic patients. Comparison with unipolar depressed patients and normal control subjects.

Although sleep disturbance is a prominent feature of mania, its polysomnographic (PSG) features have received little study. To investigate more systematically the PSG characteristics of sleep in mania, all-night PSG evaluations were performed for two to four consecutive nights in 19 young manic patients (age range, 18 to 36 years), 19 age-matched patients with major depression, and 19 age-matched normal control subjects. Manic and depressed patients displayed nearly identical profiles of PSG abnormalities compared with normal control subjects, including disturbed sleep continuity, increased percentage of stage 1 sleep, shortened rapid eye movement latency, and increased rapid eye movement density. These results are similar to those reported in previous studies of major depression, and they are consistent with the possibility that the sleep disturbance in mania and major depression is caused by the same mechanism.

Adolescent↗
PubMed1992

Quantitative assessment of psychomotor activity in patients with neuroleptic-induced akathisia.

1. An ambulatory activity monitor with solid-state memory was employed to obtain 24-hour activity data in 29 neuroleptic-treated hospitalized patients and 9 normal controls. 2. The activity monitor is a piezoelectric device which was strapped to the non-dominant ankle. Activity was recorded in 5-minute epochs throughout the 24-hour period. 3. In contrast to patients with mania (N = 15) and schizophrenia (N = 4), depressed patients (N = 9) had higher clinical ratings of akathisia and lower levels of daytime activity. 4. Manic and depressed patients showed a delay of peak activity (= acrophase). 5. Quantifiable alterations in rest-activity rhythms may occur in neuroleptic-induced akathisia but measurement of activity may be complicated by the patient's psychiatric disorder.

Adolescent↗
PubMed1991

Polysomnographic characteristics of neuroleptic-induced akathisia.

To investigate nocturnal leg movement activity and other polysomnographic features in patients with neuroleptic-induced akathisia (NIA), all-night polysomnography was performed in nine patients with NIA and compared with nine healthy individuals and eight unmedicated patients with depression. Patients with NIA displayed a pattern of leg movement activity during sleep similar to healthy individuals and depressed patients. In addition, eight of nine patients with NIA exhibited 10- to 40-second bursts of increased leg muscle tone before sleep onset. Although the significance of this finding is unclear, it is possible that it may be a pathophysiological correlate of NIA.

Adult↗
PubMed1991

Lack of efficacy of d-propranolol in neuroleptic-induced akathisia.

d-Propranolol lacks clinically significant beta-adrenergic receptor blocking properties, but has the same membrane stabilizing effects as racemic (d,l) propranolol. To assess the role of beta-blockade versus membrane stabilization or other shared nonspecific effects in the therapeutic action of propranolol in neuroleptic-induced akathisia (NIA) we treated 11 patients with NIA in a crossover, double-blind study of d-propranolol versus placebo. Akathisia scores were unchanged after both d-propranolol and placebo. Eight patients were subsequently treated in a nonblind manner with racemic propranolol, with a significant reduction in akathisia scores. These findings suggest that beta-blockade, not membrane stabilization or other shared nonspecific effects, contributes to the efficacy of propranolol in NIA.

Adult↗
PubMed1989

A fixed dose study of the plasma concentration and clinical effects of thioridazine and its major metabolites.

Fifty-three patients in an acute episode or exacerbation of psychosis were given thioridazine 200 or 400 mg daily for 2 weeks. Thioridazine and its active metabolites, mesoridazine and sulforidazine, were estimated in plasma by high performance liquid chromatography (HPLC) and radioreceptor assay (RRA). One week after institution of treatment, plasma concentrations of drug were stable in the morning 12h after dosing. Drug levels varied widely between patients, but in all patients the relative level of thioridazine to mesoridazine was about one half and thioridazine to sulforidazine was about two fold. Estimates of neuroleptic activity by RRA and the weighted sum of thioridazine, mesoridazine and sulforidazine by HPLC were very similar. Plasma concentration of parent compound, metabolites, or the sum of active substances as estimated by HPLC or RRA, showed only modest correlations (rs = 0.10-0.22, all NS) to the degree of improvement as measured by change on the Brief Psychiatric Rating Scale. Significant correlations were observed between plasma concentrations of drug and side effects, including dry mouth, blurred vision, or total rating on the Somatic Symptoms Scale. Even patients receiving the lowest dose and achieving the lowest plasma concentrations of drug showed considerable improvement. There was suggestive evidence that the patients achieving the highest plasma levels of drug did not have the best clinical outcome. These and similar observations from other studies suggest that currently used doses of neuroleptics may be excessive. Optimal drug effects as well as stronger relationships between dose, drug concentration, and clinical therapeutic effects might best be sought at doses below those in common use.

Adolescent↗
PubMed1989

Fluoxetine-induced akathisia: clinical and theoretical implications.

Five patients receiving fluoxetine for the treatment of obsessive compulsive disorder or major depression developed akathisia. The typical fluoxetine-induced symptoms of restlessness, constant pacing, purposeless movements of the feet and legs, and marked anxiety were indistinguishable from those of neuroleptic-induced akathisia. Three patients who had experienced neuroleptic-induced akathisia in the past reported that the symptoms of fluoxetine-induced akathisia were identical, although somewhat milder. Akathisia appeared to be a common side effect of fluoxetine and generally responded well to treatment with the beta-adrenergic antagonist propranolol, dose reduction, or both. The authors suggest that fluoxetine-induced akathisia may be caused by serotonergically mediated inhibition of dopaminergic neurotransmission and that the pathophysiology of fluoxetine-induced akathisia and tricyclic antidepressant-induced "jitteriness" may be identical.

Adolescent↗
PubMed1988

Beta-adrenergic antagonists in psychosis: is improvement due to treatment of neuroleptic-induced akathisia?

Van Putten and colleagues have reported an association between akathisia and exacerbations of psychosis in schizophrenic patients treated with neuroleptic drugs. They noted that treatment with an anticholinergic drug, biperiden, led to prompt improvement in both conditions. Recent reports suggest that beta-adrenergic antagonists may be effective in the treatment of akathisia. Based on these observations, we surveyed studies in which beta-adrenergic antagonists were administered as putative antipsychotic agents in order to determine whether reports of improvement may actually have reflected successful treatment of underlying neuroleptic-induced akathisia. Though inferential, the results of this review support this hypothesis. It is possible that the mechanism of action for the anti-akathisia and antipsychotic effects of beta-adrenergic antagonists may be due to enhancement of the firing rate of dopamine neurons in the ventral tegmental area, with subsequent increased release of dopamine and decreased interference with dopaminergic neurotransmission.

Adrenergic beta-Agonists↗
PubMed1987

Adrenoceptors and the pharmacology of affective illness: a unifying theory.

Based on recent clinical and preclinical research, it is theorized that antimanic and antidepressant effects of clinically available drugs can be produced through their actions on alpha-1 adrenoreceptor-mediated neurotransmission in the central nervous system. The theory suggests that final effects on alpha-1 mediated neurotransmission may be produced not only by drugs which have direct effects on the alpha-1 receptor or its second messenger, but also by drugs having effects on neurotransmitter systems such as acetylcholine, GABA, and serotonin, among others, which modulate the activity of central norepinephrine neurons or, via feedback mechanisms, by drugs having effects on adrenergic receptors other than the alpha-1 receptor itself.

Adrenergic alpha-Agonists↗
PubMed1986

In vivo potencies of antipsychotic drugs in blocking alpha 1 noradrenergic and dopamine D2 receptors: implications for drug mechanisms of action.

In addition to being dopamine antagonists, all antipsychotic drugs are potent antagonists of alpha-1 noradrenergic receptors. Nevertheless, the contribution of alpha blockade to the clinical therapeutic effects of the antipsychotic drugs has never attracted extensive study. In particular, the relative alpha-1 noradrenergic antagonist potency of antipsychotic drugs has rarely been determined in vivo during extended treatment, although such treatment would provide a better model of clinical drug effects than the determination of potencies in in vitro systems, such as assays of competition for binding sites in tissue homogenates, as is most often done. To estimate the physiological efficacy of antipsychotic drugs as dopamine and alpha adrenergic antagonists, we treated rats for four weeks with daily IP injections of the following antipsychotic drugs: Fluphenazine, 1 mg/kg; haloperidol, 1 mg/kg; chlorpromazine, 25 mg/kg; thioridazine, 25 mg/kg; and clozapine, 25 mg/kg. Effective antagonism should lead to an increase in density of the relevant receptors. After two drug-free days, rats were sacrificed and the affinity and density of dopamine D2 and alpha-1 noradrenergic receptors were determined in striatum and brain exclusive of striatum, respectively. Alpha 1 noradrenergic receptor density but not dopamine receptor density was increased after all treatments. Thus, preliminary experiments with this in vivo model suggest that all antipsychotic drugs are effective antagonists at alpha 1 noradrenergic receptors, while not all are effective antagonists at dopamine D2 receptors.

Animals↗
PubMed1979

Methylation hypothesis.

L-Methionine had no behavioral effects in normal humans and failed to increase concentrations of S-adenosylmethionine (methyl donor) in human or rat blood, while increasing rat liver levels more than fivefold. Methionine or S-adenosylmethionine in very high doses had almost no effect on methylation of tritiated levodopa in rodent tissues; various "methyl acceptor" molecules, including nicotinamide, guanidineacetic acid, and estradiol similarly had little effect. In rabbit lung, methionine and S-adenosylmethionine not only failed to increase production of dimethyltryptamine, but actually decreased it, possibly due to end-product inhibition by S-adenosylhomocysteine, which also strongly inhibited methylation of dopa in rat. These results fail to support several predictions of the "methylation hypothesis" concerning the pathophysiology and potential treatment of idiopathic psychotic disorders and leave the consistent clinical worsening effects of methionine in schizophrenia unexplained.

Adult↗
PubMed1978

Diagnosis in schizophrenia and manic-depressive illness: a reassessment of the specificity of 'schizophrenic' symptoms in the light of current research.

Present clinical and research methods of differential diagnosis of schizophrenia and affective psychoses rely very heavily on presenting symptoms and signs, especially in acute psychosis. We have reviewed studies bearing on this issue, including studies of the phenomenology of psychotic illness, outcome, family history, response to treatment with lithium carbonate, and cross-national and historical diagnostic comparisons. We conclude that most so-called schizophrenic symptoms, taken alone and in cross section, have remarkably little, if any, demonstrated validity in determining diagnosis, prognosis, or treatment response in psychosis. In the United States, particularly, overreliance on such symptoms alone results in overdiagnosis of schizophrenia and underdiagnosis of affective illnesses, particularly mania. This compromises both clinical treatment and research.

Bipolar Disorder↗
PubMed1978

Activities of types A and B MAO and catechol-o-methyltransferase in blood cells and skin fibroblasts of normal and chronic schizophrenic subjects.

We assayed activities of monoamine oxidase (MAO) type B in blood platelets and type A (and B) in fibroblasts cultured from punch biopsy specimens of skin, as well as of catechol-O-methyltransferase (COMT) in erythrocytes and fibroblasts. Fibroblasts contained moderate amounts of both forms of MAO (types A and B) found in human brain and large amounts of COMT activity. Activities of both enzymes correlated poorly between fibroblasts and blood cells. Comparing carefully diagnosed chronic schizophrenics with age-matched normal young men, we found no difference in these biochemical variables, nor could we distinguish patients with paranoid symptoms. In contrast, we confirmed markedly lower MAO activities in platelet samples from chronic patients provided by colleagues at the National Institute of Mental Health. Results concerning MAO and COMT activities are now sufficiently inconsistently characteristic of schizophrenics as to question their clinical applicability and to indicate a need for further critical evaluation, with special attention to diagnosis, matching of subjects, and effects of possible spurious environmental variables.

Adolescent↗