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Biomedical subjects

J Hirschowitz

Publications and source records attributed to J Hirschowitz.

At least 19 recordsLinked to original sources
PubMed1992

Nocturnal growth hormone secretion in schizophrenic patients and healthy subjects.

Plasma growth hormone concentrations were measured at hourly intervals between 10 p.m. and 8 a.m. the next morning in 15 drug-free chronic schizophrenic male inpatients and 14 healthy males. Growth hormone secretion was significantly lower in the patients as compared with the controls. Growth hormone release peaked around 1 a.m. in the controls, but a growth hormone peak was absent in the patient group. Increased dopamine activity, increased serotonin activity, or both could explain the absence of a nocturnal growth hormone surge in the schizophrenic patients.

Adult↗
PubMed1991

A new approach to dose reduction in chronic schizophrenia.

The bromocriptine growth hormone test (BGHT) was used to monitor D2 receptor activity in a group of 16 chronic schizophrenics who during the baseline phase were receiving greater than or equal to 20 mg/day haloperidol. In all subjects at baseline, the rise in plasma GH in response to the oral administration of bromocriptine (50 micrograms/kg) was blocked. The dose of haloperidol was then gradually reduced; the BGHT was repeated as each new dose was established. No escape from blockade of the GH response was observed until the dose of haloperidol was lowered to 10 mg/day (3 of 16 subjects escaped from blockade). At this dose the average plasma haloperidol level was 4 ng/ml. Two additional subjects escaped as the dose was reduced to 5 mg/day and six more escaped as the dose was reduced to 2.5 mg/day. The average haloperidol plasma level at 5 and 2.5 mg/day was 1.6 and 1.2 ng/ml respectively. The remaining five subjects escaped from blockade as the dose was reduced to 0 mg/day. In five subjects, escape from blockade was associated with a significant decrease in positive psychotic symptoms; in these subjects reestablishing the "just" blockade dose of haloperidol did not increase psychotic symptoms. In nine subjects escape from blockade was associated with an increase of positive psychotic symptoms; in six of these patients, reestablishing the "just" blockade dose of haloperidol attenuated psychotic symptoms to near baseline levels. We conclude that the GH challenge test is a useful adjunct to dose-reduction in the chronic patient. Furthermore, for some patients the "just" blockade dose appears to be near the minimum dose with the maximum therapeutic effect.

Adult↗
PubMed1990

Single- vs multiple-dose pharmacokinetics of clozapine in psychiatric patients.

Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose-multiple dose-single dose). Each patient received a single 75-mg dose (3 x 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple-dose regimen was started, consisting of an initial dose escalation period followed by dosing at a constant regimen for at least 6 days. After the last dose, serial plasma samples were again obtained over 72 hr. Drug was then withheld for at least 7 days, a final single 75-mg dose was given, and plasma sampling was repeated. A subset of the patient population (N = 7) was used to test for a food effect during the single-dose treatments. The pharmacokinetic parameters between the initial and the final single dose periods were not significantly different. Similarly, there were no differences within patients when given the dose after fasting (fed 1 hr after dose) or with a meal. In contrast, the terminal elimination rate differed between the single-dose and the multiple-dose treatments (t1/2 m3 = 7.9 hr single dose and 14.2 hr multiple dose) (P less than 0.05) and the dose-normalized area under the plasma concentration/time curves increased 27% with multiple dosing. Since a previous study in patients (Choc et al., Pharm. Res. 4:402-405, 1987) showed dose proportionality of clozapine plasma concentrations during multiple-dose regimens, the present results cannot be described by Michaelis-Menten kinetics.

Adult↗
PubMed1989

RBC lithium transport in the psychoses.

In vitro and in vivo red blood cell (RBC) lithium (Li+) intracellular/extracellular ratios were determined in 93 DSM-III schizophrenics (SCZ) in 47 DSM-III schizophreniform disorder patients (SF), in 22 DSM-III bipolar manics (M), in 15 affective disorders patients with mood-incongruent psychotic features (AD-MIP), and in 40 normal controls. There were no significant differences among groups in the in vitro Li+ ratio. Similarly, there was no significant difference among patient groups in the in vivo Li+ ratio. Furthermore, there was no significant difference in the mean Li+ ratios between the Li+-responsive and nonresponsive schizophrenic-like subjects. However, the distribution of Li+ ratios (both in vitro and in vivo) in the Li+-responsive group was significantly abnormal, showing more ratios in the extremes of the distribution (a platykurtic distribution).

Bipolar Disorder↗
PubMed1989

Lithium antagonism of ethanol-induced intoxication: relationship to intracellular lithium levels.

Seventeen detoxified chronic alcoholics participated in a double-blind trial comparing placebo and lithium (Li+) effects on acute ethanol (1 g/kg) intoxication. In a repeated measures, split-half crossover design, subjects were maintained for 7 days on Li+ or placebo before the ethanol challenge. Plasma Li+ levels on day 7 averaged 1.3 +/- 0.3 mM. Li+ was not more effective than placebo in attenuating ethanol effects across the subjective dimensions of intoxication, desire to drink, and control of drinking and across the cognitive dimensions measured by Trail Making A, Speed of Closure, and the Minnesota Clerical Test. Li+ was not significantly more effective than placebo in preventing the ethanol-induced rise in plasma prolactin. Subjects were divided according to high and low red blood cell (RBC) Li+ intracellular/extracellular Li+ ratios. In a comparison of the Li+ to placebo arms of the trial, the high ratio subjects (n = 9) showed a significant 44% decrease in ethanol-induced intoxication, while the low ratio subjects (n = 8) showed a 15% increase. Furthermore, the high ratio subjects performed better than the low ratio subjects, independent of the ethanol effect, on all tests of cognitive performance. These preliminary data suggest that the Li+ ratio may be a useful tool in defining unique subgroups of alcoholic patients.

Adult↗
PubMed1989

Clonazepam treatment of five lithium-refractory patients with bipolar disorder.

The authors describe the first five patients enrolled in an open clinical trial of clonazepam as a maintenance treatment in lithium-refractory bipolar disorder. All patients relapsed quickly after taking clonazepam (one within 2 weeks and four within 10-15 weeks), and the study was prematurely terminated. The results cast doubt over the usefulness of clonazepam as a prophylaxis in lithium-resistant bipolar patients who have histories of psychotic mania or delusional depression.

Adult↗
PubMed1988

Lithium transport in human fibroblasts: relationship to RBC lithium transport and psychiatric diagnoses.

Cultured fibroblasts were prepared from six normal controls, five DSM-III manic patients, and six DSM-III schizophrenic patients. Lithium (Li+) uptake, 24-hour Li+ ratios, and steady-state membrane potential were measured in these cell lines. The uptake of 10 mM Li+ reached maximum at 2 hours, with an intracellular concentration of approximately 15 mM. No significant difference in uptake was found among subject groups. Twenty-four hour Li+ (ratio of intracellular/extracellular Li+) ratios were determined by incubating the cell lines for 24 hours in the presence of 2 mM Li+. No significant difference was observed among groups; nor was there any significant correlation between the fibroblast 24-hour ratios and 24-hour in vitro ratios determined in donor red cells. The relationship between membrane potential and the 24 hour Li+ ratio in fibroblasts was determined. The average potential in these cell lines was -56 mV and was not affected by Li+ treatment. No correlation between the Li+ ratio and membrane potential was found.

Adult↗
PubMed1988

Drug response patterns as a basis of nosology for the mood-incongruent psychoses (the schizophrenias).

Interaction of therapeutic drugs with a series of different biopathological substrates of psychosis might be expected to generate a series of different response patterns. Herein the authors suggest that multi-modal response patterns following lithium and neuroleptic treatment of psychotic patients may aid in resolving the heterogeneity of psychotic disorders and lead to a new nosology of the psychoses.

Haloperidol↗
PubMed1987

Growth hormone response to apomorphine and family patterns of illness.

Sixty-five psychotic probands were divided into three groups (low, intermediate, and high) on the basis of the GH response to the dopamine receptor agonist apomorphine. Two hundred and sixty-five first-degree relatives of the probands were diagnosed according to SADS-DSM-III methods, and the relatives of the three groups of probands were compared so as to detect familial differences in the incidence of DSM-III Axis I disorders, schizotypal personality disorder, and antisocial personality. Although the morbid risk of schizophrenic spectrum disorder was only 3.1% in the relatives of the high GH probands, the morbid risk for disorders of the schizophrenic spectrum was 17.0% and 10.7% in the relatives of the intermediate and low GH probands, respectively. These data provide preliminary evidence that there may be a psychotic subtype that is characterized by supersensitivity of the dopamine system that is familially, and perhaps genetically, distinct from the bulk of the schizophrenias.

Adolescent↗
PubMed1986

Relation of clinical symptoms to apomorphine-stimulated growth hormone release in mood-incongruent psychotic patients.

The relationship between dopamine receptor agonist (apomorphine hydrochloride)-stimulated growth hormone (GH) release and psychotic symptoms was examined in 138 schizophrenic or schizoaffective inpatients (Research Diagnostic Criteria) and ten healthy normal volunteers. Patients were divided into three groups: those demonstrating an abnormally large GH response, an average GH response (mean GH response), or an abnormally low GH response. Abnormally large GH responses were associated with higher total psychosis scores. The increased psychosis scores observed in this group were due primarily to an increased incidence of thought disorder. Further analysis revealed a strong, positive correlation between thought disorder and the GH response. The apomorphine-stimulated GH response was also significantly related to duration of illness, an effect independent of age. Consistent with this last result, patients with a diagnosis of a DSM-III schizophreniform disorder demonstrated an elevated GH response.

Adolescent↗
PubMed1986

Fluphenazine activity and antipsychotic response.

Plasma fluphenazine levels and plasma total neuroleptic activity (as quantitated by the neuroleptic receptor binding assay) were related to therapeutic response in 15 DSM-III schizophrenic patients who received a predetermined, fixed dose of fluphenazine for 14 days. Mean neuroleptic activity of the plasma was 84% greater than can be accounted for by the parent fluphenazine alone, and varied widely between patients. A sigmoidal relationship between total neuroleptic activity of plasma and response was found, with a continued plateau of response at higher total neuroleptic levels. Furthermore, the RBA data suggested (P less than 0.002) that two populations of drug-responsive schizophrenics exist which may be discriminated by the total D2 binding activity of plasma required for response.

Chromatography, Gas↗
PubMed1986

Growth hormone response to apomorphine and diagnosis: a comparison of three diagnostic systems.

Our study takes a further look at the apomorphine test in the psychoses and affective disorders, with special reference to the use of different diagnostic systems. Patients meeting Research Diagnostic Criteria (RDC) for schizophrenia, schizoaffective disorder, or manic disorder were included. In addition to the RDC, diagnosis was also made using the DSM-III and ICD-9. All patients underwent an evaluation of peak GH response to apomorphine administration. The results show that RDC and ICD-9 are similar, in that for both systems, a high GH response correlates with a schizoaffective disorder and distinguishes those patients significantly from manic patients. The DMS-III brings in some new dimensions, in that schizophreniform disorder (6-month cut-off) is distinguished from schizophrenia. In addition, patients with affective symptoms and mood-incongruent psychoses are more closely related to schizophreniform disorder than to classical manic disorder.

Adult↗
PubMed1986

Relationship of psychotic symptom clusters in schizophrenia to neuroleptic treatment and growth hormone response to apomorphine.

The authors propose an alternative model for relating clinically rated psychotic symptoms to biological measures in schizophrenic patients. They suggest that clinical presentation in schizophrenic patients comprises at least four distinct psychotic symptom clusters and that at most one or two of the symptom clusters are closely associated with central dopamine (DA) activity as measured by growth hormone (GH) response to apomorphine. Factor and cluster analytic techniques both identified the same four psychotic symptom clusters, three of which were similar to the major subtypes of schizophrenia: paranoid delusions (paranoid type), thought disorder (disorganized type), and catatonia (catatonic type). The fourth psychotic symptom cluster was auditory hallucinations, a prominent clinical feature of schizophrenia. The authors compared clinical symptom cluster scores to apomorphine-induced GH response by creating a new data set containing the output of the factor analysis of each patient's symptoms and GH response, and performing regression modeling of the patient's symptom cluster scores on GH response. Patients with elevated thought disorder cluster scores also had elevated GH responses to apomorphine, suggesting an association between thought disorder and central DA receptor supersensitivity. A fixed-dose neuroleptic trial showed that thought disorder and auditory hallucinations respond rapidly to treatment with a DA receptor blocker (haloperidol), while no significant effect on other symptom cluster scores occurred during the initial 2 weeks of treatment. These data suggest that two of the identified symptom clusters, thought disorder and auditory hallucinations, may be preferentially associated with central DA hyperactivity.

Adolescent↗
PubMed1986

Comparative effects of limbitrol and amitriptyline on sleep efficiency and architecture.

Chlordiazepoxide-amitriptyline (Limbitrol) has been shown to be more rapidly effective than amitriptyline alone for treating depression. A double-blind, randomized study was designed to compare the effects of Limbitrol and amitriptyline on insomnia, anxiety, and depression. The rate of improvement of symptoms was faster with Limbitrol. No differences were noted between groups in the degree or rate of improvement of the sleep laboratory parameters nor in sleep Stages 1 to 4. Percentages of rapid eye movement (REM) sleep and REM latency were similarly affected by the drugs, but REM density showed a significantly greater decrease with Limbitrol. Phasic REM factors may be crucial in the role of REM sleep and depression.

Adult↗
PubMed1986

Possible efficacy of alprazolam in restless leg syndrome.

Restless leg syndrome is a frequently misdiagnosed and often misunderstood condition contributing to a complaint of insomnia in geriatric patients. Various pharmacologic agents used to treat the condition are often ineffective and have not consistently provided relief for the majority of patients with this condition. Our recent experience with Xanax suggests its possible effectiveness in controlling symptoms of the restless leg syndrome. Further, more controlled double blind studies--especially comparing other benzodiazepines at appropriate dosages--are called for.

Aged↗
PubMed1986

Morning amnestic effects of triazolam.

The effects of triazolam on immediate and delayed recall were evaluated in a double-blind placebo controlled study in 22 normal volunteers. Subjects were randomized to receive triazolam or a placebo as a single dose administered at bedtime. Immediate and delayed recall are tested using a modified version of the "Williams Word Memory Task" before and at .5, 8, and 14 hours after drug administration. Delayed recall was evaluated at the 14 hour time point for words recalled at the pre drug and 1/2 and 8 hour time points. No significant difference was noted between the triazolam and placebo group with regard to their immediate recall ability at any of the time points. The placebo group demonstrated no decrease in their delayed recall ability during any of the various post drug time points. However, when evaluating delayed recall in the triazolam group, a statistically significant (p less than .05) decrease compared to baseline in their recall ability of words remembered at the .5 and 8 hour time points was noted. This study suggests that triazolam's amnestic effect may extend beyond the duration of its generally accepted hypnotic efficacy. This is consistent with the hypothesis that amnestic potency among the benzodiazepines is related to benzodiazepine receptor binding affinity and lipophilicity.

Adult↗
PubMed1985

Characteristics of phospholipid methylation in human erythrocyte ghosts: relationship(s) to the psychoses and affective disorders.

Recent studies have shown that patients with a schizophrenic-like illness have a significant deficit in erythrocyte ghost membrane (EGM) phosphatidylcholine (PC); patients with the most severe deficiency showed a marked decrease in Na+-Li+ counterflow activity (Hitzemann et al. 1984a and b). The present study was undertaken to see if the decrement in PC is associated with a decrease in phospholipid methylation activity. Phospholipid methylation in human EGMs is distinctly different from that in rat EGMs (Hirata and Axelrod 1980) in that the human activity is not Mg++-dependent, and apparent methyltransferase I activity is located in the external membrane surface. The patient population consisted of 20 DSM-III schizophrenics (SCZ), 13 DSM-III schizophreniform (SF) disorder patients, and 11 DSM-III manics (M). Twelve age- and sex-matched controls were used for the comparison group. Methylation activity was significantly decreased in all three patient groups, although the M group had significantly higher activity than the SF group. Twenty-four of the SCZ and SF patients entered a Li+ trial. The Li+ responder group (n = 8) showed significantly lower activity than the nonresponder group (n = 16). Overall, we conclude that the decrement in phospholipid methylation activity partially contributes to the decrement in PC levels.

Adult↗