Biomedical subjects

A Weizman

Publications and source records attributed to A Weizman.

At least 127 records · Page 7Linked to original sources

PubMed1999

Is there sexual dimorphism in obsessive-compulsive disorder?

The present review addresses the question of sexual dimorphism in obsessive-compulsive disorder. It enumerates examples that could be interpreted to suggest the existence of such dimorphism from the fields of epidemiology, phenomenology, pharmacology, neuropsychology, neuroimaging and genetics. We conclude that data, at this point, are too scarce to warrant a firm conclusion. On the contrary it seems that there are enough indications in the literature that hint at the possibility of sexual dimorphism to stimulate further research in the field.

Female↗

PubMed1999

Platelet peripheral-type benzodiazepine in pregnancy and lactation.

The aim of the present study was to investigate the impact of hormonal changes during pregnancy and lactation on the expression of peripheral-type benzodiazepine receptors in platelet membranes. Platelet peripheral benzodiazepine receptor binding characteristics, Hamilton anxiety and depression rating Scores, and progesterone and prolactin (PRL) levels were evaluated during pregnancy and lactation in 17 pregnant women [first (n = 9) and third (n = 8) trimesters], 10 lactating women, and 8 nonpregnant women. A significant decrease (38-41%) in peripheral benzodiazepine receptor density was observed in women during the third trimester of pregnancy when compared to nonpregnant controls and women in their first trimester of pregnancy. The decrease is peripheral benzodiazepine receptors was parallel to the peak in progesterone and PRL secretion. The reduction in peripheral benzodiazepine receptor expression is hormone-dependent and may play a regulatory role geared to prevent pregnancy-related overactivity of the hypothalamic-pituitary-ovarian, hypothalamic-pituitary-adrenal, and hypothalamic-PRL axes.

Adolescent↗

PubMed1999

Homicide by schizophrenic patients in Israel.

Thirty-three schizophrenic inpatients aged 45.3 +/- 13.5 years who had been found not guilty of homicide by reason of insanity were compared with 28 schizophrenic patients matched for age, sex and duration of disease who had not committed any crime. Statistical analysis revealed a high rate in the study group of individual factors associated with aggression, such as alcohol abuse, previous contact with the police, aggressive behavior and threats (P < 0.05). Significantly more of them were also immigrants (P < 0.05). There was no between-group difference in familial factors. These findings support earlier studies indicating that schizophrenic patients with the profile of alcoholism, aggressiveness and foreign country of origin are at high risk of homicidal behavior.

Adolescent↗

PubMed1999

The effect of vitamin E addition to acute neuroleptic treatment on the emergence of extrapyramidal side effects in schizophrenic patients: an open label study.

The anti-oxidant vitamin E has been reported to be effective in the treatment of tardive dyskinesia. The present open label study examined the effect of supplemental therapy with vitamin E on acute extrapyramidal symptoms and cell enzymes in patients receiving neuroleptic drugs. Thirty-nine hospitalized schizophrenic patients were randomly assigned to two groups: group 1 (n = 20) was treated with neuroleptics, and group 2 (n = 19) with neuroleptics combined with a fixed dose of vitamin E (600 IU/day), administered for two weeks. All patients were assessed with the Simpson-Angus Rating Scale (Simpson and Angus, 1970) for neuroleptic induced Parkinsonism (NIP), Barnes' Akathisia Scale (Barnes, 1989), and Brief Psychiatric Rating Scale: laboratory parameters included serum creatine kinase (CK) activity, serum glutamate oxaloacetic transaminase (SGOT) and white blood cell count (WBC). The addition of vitamin E to neuroleptic agents was associated with a trend (p = 0.08) towards prevention of the emergence of NIP compared to neuroleptic treatment alone. Addition of vitamin E to neuroleptics may reduce the severity of acute NIP in schizophrenic patients.

Adult↗

PubMed1999

Orbitofrontal cortex dysfunction in obsessive-compulsive disorder? II. Olfactory quality discrimination in obsessive-compulsive disorder.

BACKGROUND: Olfactory quality discrimination is a putative marker of orbitofrontal cortex function in mammals. As this portion of the cerebral cortex was repeatedly implicated in the pathophysiology of obsessive-compulsive disorder (OCD) this study was designed in an attempt to quantify this behavioural function in OCD patients. METHODS AND RESULTS: Olfactory quality discrimination was compared in OCD patients and healthy controls. Thirty two subjects participated in the study: 16 (13 women and 3 men) medication free OCD outpatients and 16 sex and age matched healthy controls. Olfactory tests consisted of determination of detection thresholds to isoamyl acetate, and a three way forced choice quality discrimination task, using isoamyl acetate, citral and eugenol as stimuli. No significant differences in sensitivity and performance of the quality discrimination task between the two groups were found. Within the OCD group the more severely affected patients (Y-BOCS>29) performed significantly better than the less severely affected (Y-BOCS<30) patients on the more difficult part of the quality discrimination task. Within this subgroup of patients the correlation between performance on the olfactory task and a previously reported alternation task tended to be negative as compared to a significantly positive correlation in the control group. CONCLUSIONS: It seems that olfactory quality discrimination may prove to be a useful noninvasive marker of prefrontal cortex function in OCD. Furthermore, the organization of functional modules within the orbitofrontal cortex, rather than a simple dysfunction, may prove to characterize OCD.

Adolescent↗

PubMed1999

Orbitofrontal cortex dysfunction in obsessive-compulsive disorder? I. Alternation learning in obsessive-compulsive disorder: male-female comparisons.

BACKGROUND: We have previously reported a significant negative correlation between severity of symptoms and performance of an alternation learning task in female obsessive-compulsive disorder (OCD) patients. The present study was aimed at exploring this relationship between alternation learning and OCD symptom severity in male OCD patients. METHODS AND RESULTS: Eighteen female obsessive-compulsive disorder patients and 14 male non-depressed, drug free, OCD patients participated in the study. Measures of dorsolateral prefrontal function (Wisconsin Card Sorting Test) and orbitofrontal cortex function (object alternation learning) showed no significant differences between the sexes. The relationship between orbitofrontal cortex function and severity of OC symptoms was significantly different between the sexes (z=2.44. P=0.007). While this correlation was negative in the females it was positive in the males. CONCLUSIONS: These results may indicate sexual dimorphism in OCD.

Adult↗

PubMed1999

Autistic subjects with comorbid epilepsy: a possible association with viral infections.

This study evaluates the comorbidity of epilepsy as a variable supporting a viral hypothesis in Autism. Data covering a 30-year period (1960-1989), including general population live births, autistic births, and incidence of viral encephalitis and viral meningitis, were collected for Israel. 290 autistic births were evaluated. The annual birth pattern of subjects with comorbid epilepsy fit the seasonality of viral meningitis. These findings support the role of viral C.N.S. infections in the causality of this disorder.

Adolescent↗

PubMed1999

Insulin-like-growth-factor-I (IGF-I) antagonizes apoptosis induced by serum deficiency and doxorubicin in neuronal cell culture.

We evaluated the effect of insulin-like growth factor (IGF)-I on neuronal cell viability and apoptosis induced by exposure to serum-free (SF) medium and to doxorubicin. In primary neuronal culture, IGF-I (0.5-2.0 microg/ml) slightly increased basal cell viability; SF medium tended to decrease viability (20-27%), and addition of IGF-I significantly antagonized this decrease (P< 0.05). In neuroblastoma (NB) SK-N-SH cell culture, IGF-I significantly increased viability (0.05-1.25 microg/ml) (P< 0.005); SF medium decreased it by 75%, and this decrease was prevented by IGF-I (0.5-1. 0 microg/ml) (P< 0.005). Flow cytometry studies showed an increased apoptosis on exposure to SF medium (88.8 vs 10.2%), which was suppressed to 38.3% by addition of IGF-I. Growth hormone (1-10 microU/ml) did not modify basal cell viability in either culture, and SF-induced cell death in NB cells. Doxorubicin (1-100 microM) caused neurotoxicity in primary and NB cultures (66-39% and 39-10% of controls, respectively), and increased apoptosis in NB cells (73. 8 vs 20.1%). IGF-I antagonized these neurotoxic/apoptotic effects (P< 0.05). This study suggests that IGF-I possesses a potent neuroprotective activity which may be involved in the resistance to doxorubicin.

Animals↗

PubMed1999

Biophysical shunt theory for neuropsychopathology: biphasal homeostatic dysregulation.

OBJECTIVE: We challenge Freud's psychodynamic theory using a systematic modus operandi which has been outlined in detail in a succession of articles. Here, we deal with Freud's first assumption of human psychological primacy in forming goal-directed behavior. According to our theory, biphasal homeostatic dysregulation is the underlying mechanism of clinical phenomenology. MODEL: Evolutionary neurobiology has provided humans with a precise technical solution for optimal organismic survival. Humans are armed with an accurate negative feedback mechanism that operates within the alternating upper and lower thresholds of biphasal homeostatic maintenance and is coupled with a basal indicator of individual sensation of the degree of the given organismic well-being in any unit of time. This originates the organismic pleasure principle (OPP). The latter is achieved by a straightforward quantal injection of endorphins according to one of eight possible body operational regimens. Thanks to the essential duality of the dynamic interactions, stipulated by the complex harmonics of term-dependent and event-dependent adaptation when one or more of the essential elements for homeostasis goes above or below its predetermined threshold, certain branches of the organismic defense system (ODS) are 'turned on' in the second phase of homeostasis. The individual then adapts behavioral modifications directed toward a long-lasting search for the optimal resources needed for normal survival. This evolutionary biphasal homeostatic design has an intrinsic, methodical expression that confirms changes and correctly informs the individual about them, further imposing behavioral modifications, when necessary. In cases of a homeostatic derangement, the OPP is replaced by an erratic inclusion of pain, tension or depression, all components of the alarm system of the ODS, which may lead to disordered behavioral patterns. CONCLUSIONS: The underlying biological mechanism of goal-directed assignments for biphasal homeostatic maintenance is described. The intrinsic rules and regulations that guide both normal and abnormal survival may be clinically manifest. Normal survival behavior is necessary to regain organismic homeostasis.

Biophysical Phenomena↗

PubMed1999

Biophysical shunt theory for neuropsychopathology: neuroimmunological causality for the suicide condition.

This article describes a working hypothesis of the nature of the 'suicide condition' (SC). The authors contend that the SC emerges as a specialized result of two-phase impairment in the neuroimmunological 'inherited schematic representation' (ISR) involving: (a) the formation of a 'microcellular suicide' phenomenon; and (b) the establishment of a 'macro-organismic suicide' program. Our hypothesis, unlike earlier ones, is based on scientific evidence spanning diverse clinical diagnostic areas indicating that the SC is induced by a local histoincompatibility across distinct tissue structures and/or a remodeling of one or more neurimmunological ISR designs due to biophysical ion shunt bypass and neglect, whereas a normal neuroimmunological ISR complex produces an all-embracing organismic histocompatible tissue-syntonic-to-ego-syntonic expression. The presence of abnormal 'microcellular suicide' assemblies leads to cell syntonic-to-cell dystonic transformation and initiates the first modification phase by contaminating certain neurimmunological ISR programs which in turn trigger the onset of partial ego syntonic-to-ego-dystonic conversion. This is translated by the self-conscious experience as partial self-to-alien tissue translocation. These formations accumulate at a rate, arriving at the second phase in SC establishment when they reach a magnitude resolution that surpasses the organismic suicide threshold level and increase the amount of ego-syntonic-to-ego-dystonic inclusion. This is then translated by the self-conscious experience as a 'foreseeable and inescapable death' that is based on severe self-to-alien multiorgan substitution. The latter overcomes the rules and regulations prescribed by impulse-induced inner events, regardless of outer psychosocial events, and leads to an irrevocable drive to suicide.

Humans↗

PubMed1999

Biophysical shunt theory for neuropsychopathology: pentaphasic lipid-induced model for schizophrenia.

We propose a five-phase model for schizophrenia: (A) Imperfect diet-induced fatty acid combinations are mobilized from reservoirs during stress exposure into the bloodstream; (B) Increased brain-blood barrier permeability, with a further penetration of fat into the brain matter; (C) Rearrangement in the regional neuronal membrane fatty acids with a further physical compression of the adjacent membrane protein structures causing conformational alterations; (D) Cytokines generate further physical changes, impairing single- or multi-dispersed ion channels placed on the same neuron; (E) Ion channels are blocked, with a subsequent biophysical ion shunt-to-ion flow propagation, which results in neuronal misfiring and the appearance of schizophrenic signs and symptoms.

Biophysical Phenomena↗

PubMed1999

Fluvoxamine treatment of obsessive-compulsive symptoms in schizophrenic patients: an add-on open study.

Obsessive-Compulsive (OC) symptoms are observed in a substantial proportion of schizophrenic patients and pose a significant therapeutic challenge. Based on findings of the benefit of the anti-obsessive agent clomipramine, we designed an open-label study to examine the effect of adding the serotonin-selective reuptake inhibitor (SSRI) fluvoxamine to the ongoing antipsychotic regimen of schizo-obsessive patients. The study population consisted of ten neuroleptic-stabilized chronic schizophrenic patients with OC symptoms. Fluvoxamine (up to 150 mg/day) was added to the ongoing antipsychotic treatment, which remained unchanged for the entire 12-week trial period. The patients were evaluated before the trial and at weeks 1, 2, 4, 6, 8 and 12 (end point) with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Schedule for Assessment of Positive Symptoms and the Schedule for Assessment of Negative Symptoms. The results showed a significant improvement in obsessions (P < 0.02) (but not compulsions) and both positive (P < 0.01) and negative (P < 0.05) schizophrenic symptoms. By the end of the trial, three patients showed a more than 50% reduction in the Y-BOCS score, with complete amelioration of the OC symptoms in one of them. Three patients were dropped from the study during the first 4 weeks, two because of aggressiveness and one because of psychotic exacerbation. No exacerbation or new onset of extrapyramidal side-effects (EPS), as measured by the Barnes Akathisia Scale (BARS) and the Simpson-Angus Scale (SAS), was noted during the course of the trial and there were no other significant clinical side-effects of fluvoxamine addition. We conclude that fluvoxamine may be an effective adjunctive agent in some schizo-obsessive patients.

Adult↗

PubMed1999

The effect of long-term antipsychotic treatment on the body weight of patients suffering from chronic schizophrenia: clozapine versus classical antipsychotic agents.

The aim of this study was to evaluate the effect of long-term clozapine treatment on body weight changes in neuroleptic-resistant chronic schizophrenic patients and to compare it with that of classical antipsychotic agents. The body mass index (BMI) of 96 neuroleptic-resistant chronic schizophrenic patients was calculated before the beginning and after long-term (mean +/- SD 1.7 +/- 1.3 years) clozapine treatment. These data were compared to the BMI of 98 chronic schizophrenic patients maintained on classical antipsychotic agents for a similar duration (mean +/- SD 1.9 +/- 1.6 years). A significant elevation in BMI was detected in both groups during these periods (P < 0.0001 versus baseline, for both groups). The change in BMI (delta BMI) was similar in both groups (P < 0.9). We conclude that the increase in body weight caused by long-term (> 6 months) clozapine treatment is comparable to that obtained following long-term classical antipsychotic agents treatment.

Adult↗

PubMed1999

Lack of efficacy of the 5-HT3 receptor antagonist granisetron in the treatment of acute neuroleptic-induced akathisia.

The specific mechanism underlying the apparent involvement of the serotonergic (5-HT) system in the pathophysiology of extrapyramidal side-effects, particularly neuroleptic-induced akathisia (NIA), remains unknown. We hypothesized that the 5-HT3 receptor subtype may play a role in the light of the moderate-to-high affinity to this receptor of some of the atypical antipsychotic agents which have a low propensity to cause akathisia, as well as our earlier findings with the 5-HT2/5-HT3 antagonist mianserin. In an open-label pilot study, we administered the selective 5-HT3 antagonist granisetron (fixed dose, 2 mg/day) for 4 days to 10 neuroleptic-treated patients with acute NIA. Three patients discontinued granisetron because of a lack of response. The remainder showed no significant change in score on the Barnes Akathisia Scale during the trial. NIA symptoms remained unchanged or worsened in five patients (71.4%) and improved to a certain degree in only two. It seems that the 5-HT3 subtype of serotonergic receptor is not involved in the development of NIA, and 5-HT3 antagonists are ineffective in the serotonin-related pharmacotherapy of NIA.

Acute Disease↗

PubMed1999

Ondansetron treatment in patients with Tourette's syndrome.

Ondansetron, a selective 5-HT3 antagonist, may lower mesolimbic dopaminergic hyperactivity. The present open-label pilot study evaluated the effect of ondansetron in Tourette's syndrome. Six Tourette's syndrome men aged 14-48 years resistant to haloperidol participated in the study. Assessments included the Yale Global Tic Severity Scale (YGTSS), Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and Tourette's syndrome-Clinical Global Impression (TS-CGI) scale. The maximal ondansetron dosage (8-16 mg per day) was given for 3 weeks. Ondansetron treatment was associated with a significant decrease in the severity of tics. Two patients showed a definite response (score improvement of 40% or more), and two showed a probable response (> 25%). Two patients did not improve. Side-effects were transient and included abdominal pain (n = 5) and constipation (n = 2). Ondansetron may possess anti-tic effects in some Tourette's syndrome patients.

Adolescent↗

PubMed1999

Lack of association between suicide attempt and a polymorphism at the dopamine receptor D4 locus.

Dopaminergic neurotransmission has been implicated in suicidal behaviour. The 48 bp-repeat polymorphism in the gene coding for dopamine receptor D4 was investigated in a sample of suicide attempters (n = 165) and healthy control subjects (n = 99). No association between suicide attempts and this polymorphism was observed. Neither did any significant differences emerge in comparison with control subjects when the suicide attempters were grouped into different diagnostic categories: unipolar (n = 45), anxiety (n = 23), adjustment (n = 37) and personality disorders, cluster B (n = 36). The results suggest that alleles defined by the investigated polymorphism do not have a major impact on suicidal behaviour.

Adjustment Disorders↗

PubMed1999

Circulatory levels of catecholamines, serotonin and lipids in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) may be associated with a dysregulation of the catecholaminergic and serotonergic systems. Furthermore, ADHD is frequently complicated by aggressive impulsive behaviour, which is suggested to be related to low serum cholesterol levels. We examined the relationship between blood serotonin, norepinephrine, dopa and lipid levels and the degree of hyperactivity, impulsiveness, lack of concentration, and aggressiveness in boys with ADHD of low and high severity as determined by a specially designed formulated scale based on the DSM-IV criteria for ADHD. No differences were noted between the groups in any of the peripheral biological parameters except blood serotonin, for which a tendency (P=0.08) towards lower levels was observed in the children with more severe disorder. We conclude that children with severe ADHD may have a different serotonin turnover compared to children with mild ADHD. These results may have implications for our understanding of the pathogenesis of ADHD, at least the more severe type.

Adolescent↗

PubMed1999

Role of nitric oxide in the enhancement of pentylenetetrazole-induced seizures caused by Shigella dysenteriae.

Convulsions and encephalopathy are frequent complications of childhood shigellosis. We studied the role of nitric oxide (NO) in Shigella-related seizures in an animal model. Pretreatment of mice with Shigella dysenteriae 60R sonicate elevated serum NO levels and enhanced the convulsive response to pentylenetetrazole (PTZ), as indicated by a higher mean convulsion score and a higher number of mice responding with seizures. Treatment of the mice with S-methylisothiourea sulfate (SMT), a potent inhibitor of inducible NO synthase (NOS), prevented the elevation of serum NO levels and concomitantly reduced the enhanced response to PTZ. The mean convulsion scores were 0.7, 0.7, 1.3, and 0.8 for mice treated with saline, saline and SMT, S. dysenteriae 60R sonicate, and S. dysenteriae 60R sonicate with SMT, respectively (P = 0.001 for 60R sonicate versus saline and P = 0.013 for 60R sonicate versus 60R sonicate with SMT). The corresponding seizure rates were 40, 44, 75, and 47% for saline, saline with SMT, S. dysenteriae 60R sonicate, and S. dysenteriae 60R sonicate with SMT, respectively (P = 0.0004 for 60R sonicate versus saline and P = 0.005 for 60R sonicate versus 60R sonicate with SMT). In contrast, injection of N-nitro-L-arginine, a selective inhibitor of constitutive NOS, neither abolished the elevation of serum NO nor attenuated the enhancement of seizures. These findings indicate that NO, induced by S. dysenteriae 60R sonicate, is involved in enhancing the susceptibility to seizures caused by S. dysenteriae.

Animals↗