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Biomedical subjects

J Hirschowitz

Publications and source records attributed to J Hirschowitz.

At least 37 records · Page 2Linked to original sources
PubMed1985

Down-regulation of central dopamine receptors in schizophrenia.

CSF homovanillic acid (HVA) levels reflecting central dopamine release and apomorphine-stimulated human growth hormone (HGH) secretion reflecting central dopamine receptor activity were concomitantly determined in 20 schizophrenic patients. There was a strong negative correlation between HVA and HGH levels: high dopamine release was associated with lower HGH responses to dopamine receptor activation by apomorphine. Studies are reviewed which suggest that the presently observed relationship reflects release-mediated down-regulation of central D2 receptors, the dopamine receptor subtype associated with the antipsychotic properties of neuroleptic medication.

Adolescent↗
PubMed1985

Lack of amnestic effects of clorazepate on geriatric recall.

Significant amnestic effects in young adults have been found with the short-acting sedative-hypnotic triazolam and the intermediate-acting lorazepam, but not with the longer-acting clorazepate. The effects of placebo and clorazepate 3.75 and 7.5 mg were compared in 43 nonanxious geriatric subjects. Results were consistent with earlier studies, and no significant impairment of immediate or delayed recall was found.

Aged↗
PubMed1985

The effects and effectiveness of gamma-hydroxybutyrate in patients with narcolepsy.

Thirty patients with polysomnographically confirmed narcolepsy were treated with GHB (gamma-hydroxybutyrate) for up to 30 weeks. The number of nightly awakenings significantly decreased, while Stages 3 and 4 sleep substantially increased. The clinical symptoms of cataplexy, sleep paralysis, hypnogogic hallucinations, daily naps, and sleep attacks all showed significant improvements. Daytime sleepiness, while not completely eliminated, was controlled with lower doses of stimulant medication than patients were taking before the study. No patient developed tolerance to the drug, and no serious side effects were noted.

Adult↗
PubMed1984

Lithium ratio in vitro. Diagnosis and lithium carbonate response in psychotic patients.

The distribution of RBC lithium ratios in vitro in a recently hospitalized psychiatric population was found to be multimodal. Psychotic patients who had an antipsychotic response during open trials of lithium carbonate alone were identified with high sensitivity (89%), but low specificity (51%) before drug treatment, by lithium ratios that were in the extreme modes of the distribution (less than 0.30 or greater than 0.38). Diagnostic efficiency of the test was 61%. The DSM-III diagnosis of schizophreniform disorder demonstrated 90% diagnostic efficiency in predicting response/nonresponse during treatment with lithium carbonate alone. A subgroup of the psychotic disorders was similar to affective disorders with respect to course of illness, biological characteristics, and response to lithium carbonate.

Clinical Trials as Topic↗
PubMed1984

Combined thioridazine and desipramine: early antidepressant response.

The authors examined the effect of combined thioridazine (THI) and desipramine (DMI) for an early antidepressant response in 14 patients with a DSM III diagnosis of major depressive disorder with melancholia. All 14 patients received a constant dose of 200 mg DMI/day for 21 days while 7 patients received 100 mg THI/day for only the first 7 days. A significantly greater improvement from baseline Hamilton Depression Scale (HDS) scores occurred during the first 7 days in patients receiving both drugs. Possible mechanisms for this early antidepressant action are discussed.

Adult↗
PubMed1984

Dopamine and non-dopamine psychoses.

The time course of antipsychotic response following the initiation of an antipsychotic drug and functional dopamine receptor sensitivity were explored in a cohort of recently admitted psychotic (mood-incongruent) patients. The distribution of the latencies of antipsychotic response suggested at least two populations. Rapid responders (RRs) had 60% reduction of baseline psychotic symptoms by a mean of 5.5 days of drug treatment. Delayed/nonresponders required 2-7 weeks for a similar reduction of psychotic symptoms. The sensitivity of postsynaptic dopamine receptors was explored using a neuroendocrine probe: growth hormone response to the dopamine agonist, apomorphine (AP). RRs had an exaggerated growth hormone response to AP in comparison to delayed/nonresponders (P less than 0.05). Exaggerated sensitivity of postsynaptic dopamine receptors and rapid antipsychotic response following dopamine receptor blockade in RRs suggest a true functional dopamine hypersensitivity disorder in the RR group. In contrast, lower postsynaptic receptor sensitivity (as reflected by lower growth hormone response to AP) and failure of early response following dopamine receptor blockade focus attention away from dopamine hyperactivity as a relevant etiologic mechanism in delayed/nonresponders. Response rates to neuroleptic drugs and neuroendocrine probes of receptor sensitivity may separate two or more etiologically distinct diseases with schizophrenic-like symptoms.

Antipsychotic Agents↗
PubMed1984

Membrane abnormalities in the psychoses and affective disorders.

Erythrocyte ghost phospholipid data were collected on 67 psychotic and/or manic patients and compared to a group of 35 age and sex matched controls. Patients meeting DSM-III criteria for schizophreniform disorder or schizophrenia but not mania showed a small but significant decrease in membrane phosphatidylcholine (PC). In 53 of the patients data were available on lithium transport across red cell membranes. Patients in the upper quartile of the PC distribution showed a significant (-47%) decrease in the 24 h in vitro lithium ratio as compared to patients in the lower PC quartile. This difference was due to an increase in Na-Li+ counterflow activity in the upper PC quartile and not to a change in passive lithium leak. These data illustrate one example of a possible relationship between membrane composition and a membrane function, counterflow activity, which has been associated with the underlying mechanism(s) of lithium action.

Adult↗
PubMed1984

Mood-incongruent versus mood-congruent psychosis: differential antipsychotic response to lithium therapy.

The authors previously reported that a subgroup of schizophrenic-like patients respond favorably to lithium (Li) therapy, as do patients with a classical manic illness. In the present study, the time course of psychotic and affective symptom remission after Li therapy was examined in these two groups of patients. Li responsive patients with a mood-incongruent psychosis (schizophrenic-like illness) demonstrated a rapid antipsychotic response to Li therapy, showing a 50% improvement during the first 7 days, while no improvement in affective symptoms was seen until week 2 or 3 of treatment. Alternatively, patients with a mood-congruent psychosis (where mania is the primary diagnosis) demonstrated no antipsychotic response to Li therapy during the first 2 weeks of treatment, while some improvement in manic symptoms occurred during treatment week 2. The present study demonstrates that Li therapy differentially affects psychotic symptoms in mood-incongruent as opposed to mood-congruent psychosis. Further, the growth hormone (GH) response to apomorphine administration differentiated these two groups of Li responsive patients. Patients with a Li responsive mood-incongruent psychosis demonstrated over a seven-fold greater GH response than mood-congruent psychotic patients. The present data suggest that mood-incongruent and mood-congruent psychoses may represent two biologically distinct psychotic processes separable by both medication response and central dopamine function.

Apomorphine↗
PubMed1984

Platelet monoamine oxidase activity in the psychoses: relationship to symptoms and lithium response.

The kinetics of platelet monoamine oxidase (MAO) were studied in 100 psychotic and manic patients and 36 controls. No relationship was found between MAO activity and response to lithium in the schizophrenic-like illnesses. However, the data do suggest there is an association between enzyme affinity (Km) and specific symptom clusters. Patients with the low Km variant of platelet MAO are enriched in depressive symptoms, while those with the high Km variant are enriched in manic symptoms.

Adult↗
PubMed1984

Lithium response and psychoses: a double-blind, placebo-controlled study.

Lithium-associated remission of psychosis has been described in schizophreniform disorders and in psychotic patients with variants of the red blood cell (RBC)/lithium ratio. To determine whether such remissions are the consequence of lithium treatment rather than spontaneous in nature, a double-blind, placebo-controlled study was undertaken in 16 psychotic patients preselected for the variant of RBC/lithium ration and/or DSM-III schizophreniform diagnosis. Essentially full and sustained remission of psychosis began during periods of lithium treatment in 4 of 15 of the study patients. Improvement was significantly greater during lithium treatment periods than in counterbalanced placebo treatment conditions in these four subjects (p less than 0.02). Fifteen of the same 16 study patients failed to initiate sustained improvement either spontaneously or while on placebo during the initial 14-day treatment period. In this preselected psychotic population, sustained response to lithium occurred at a rate at least four times greater than that which could be attributed to spontaneous remission.

Affective Disorders, Psychotic↗
PubMed1984

Membranes, methylation and lithium responsive psychoses.

Data are presented showing that the erythrocyte ghost membranes of lithium-responsive and non-responsive schizophrenic-like patients are different from control membranes. In both groups of patients there was a significant decrement of phosphatidylcholine (PC) which was largely compensated for by an increase in sphingomyelin. The decrement in PC may in part be associated with a decrease in phospholipid methylation which converts phosphatidylethanolmine (PE) to PC. Interestingly, in the lithium-responsive but not the non-responsive patients, lithium stimulates methylation activity. This stimulation may affect a variety of membrane functions, e.g. adenyl cyclase activity, which would be involved in lithium's therapeutic actions.

Blood Platelets↗
PubMed1984

Impact of lithium therapy on core psychotic symptoms of schizophrenia.

The authors have previously reported that a sub-group of schizophrenic-like patients respond favorably to lithium therapy: furthermore, psychotic patients who respond to lithium demonstrate appreciable improvement during the first seven days of treatment. The present study investigated which symptoms of schizophrenia improved quickly during lithium treatment. We found that patients who do respond to lithium show significant improvement in the core symptoms of psychosis--hallucinations, delusions and formal thought disorder--during the first seven days of treatment, thus allowing early identification of 88 per cent of schizophrenic patients who ultimately respond to lithium and 91 per cent of those who do not.

Delusions↗
PubMed1984

Fluphenazine plasma levels and clinical response.

Plasma levels of fluphenazine and clinical response were examined in 19 inpatient schizophrenics (DSM-III diagnoses) using a constant dose, steady-state methodology. A significant curvilinear correlation was demonstrated between clinical response and steady-state plasma levels of fluphenazine (p less than .05). A therapeutic range of plasma fluphenazine is suggested in the range of .13-.70 ng/ml. The lowest plasma level detected (.13 ng/ml) appeared to be well within the therapeutic range. The 9 patients with plasma fluphenazine levels in this range demonstrated a mean clinical improvement of 59% compared to 34% for patients with plasma levels above .70 ng/ml (p less than .01).

Administration, Oral↗
PubMed1984

Haloperidol plasma and red blood cell levels and clinical antipsychotic response.

Two investigators have recently suggested therapeutic ranges for plasma haloperidol in the treatment of schizophrenia. An apparent optimal therapeutic range of red blood cell haloperidol as early as day 7 of the drug trial is described in this article. With continued treatment, an optimal plasma haloperidol range for response could be observed by day 14 of treatment. The previously described correlation between response at day 7 and plasma/red blood cell haloperidol ratio was confirmed but was found not to predict response at day 14 of drug treatment in this cohort of DSM-III schizophrenic patients.

Erythrocytes↗
PubMed1984

Clinical relevance of thiothixene plasma levels.

The authors examined plasma levels of thiothixene and clinical response in 19 DSM-III diagnosed inpatient schizophrenics, using an improved methodology. A significant curvilinear correlation was demonstrated between clinical response and plasma levels for thiothixene (p less than 0.02). Optimal clinical response to thiothixene appears to be associated with plasma levels from 2.0 to 15.0 ng/ml (p less than 0.05). These findings suggest that laboratory measurement of thiothixene levels may assist in determining the minimum effective dose for individual patients.

Humans↗