Biomedical subjects

A Weizman

Publications and source records attributed to A Weizman.

At least 19 recordsLinked to original sources

PubMed1999

Low platelet-poor plasma concentrations of serotonin in patients with combat-related posttraumatic stress disorder.

BACKGROUND: Combat-related posttraumatic stress disorder (CR-PTSD) is associated with a dysregulation of various neurotransmitter systems. METHODS: We assessed levels of platelet-poor plasma (PPP) norepinephrine (NE), and serotonin (5-HT), and 24-hour urinary excretion of NE, dopamine (DA), and homovanillic acid (HVA) in 17 male outpatients with untreated chronic CR-PTSD (age, 33.1 +/- 7.4 years) and 10 normal control subjects (age, 35.8 +/- 2.7 years). RESULTS: Compared with the control subjects, the PTSD patients showed significantly lower PPP 5-HT levels, elevated PPP NE levels, and significantly higher mean 24-hour urinary excretion of all three catecholamines (NE, DA, and HVA). The 24-hour urinary HVA values of the CR-PTSD patients correlated significantly and positively with the total Impact of Event Scale scores and the avoidance symptoms cluster scores, and the PPP 5-HT levels correlated negatively with the Hamilton Anxiety Rating Scale scores. The PPP NE/5-HT ratio was significantly higher in the study group than in the control subjects. CONCLUSIONS: We believe this combined enhanced noradrenergic activity and diminished 5-HT activity may be relevant to the neurobiology of CR-PTSD.

Adult↗

PubMed1999

Clinical characteristics of schizophrenia associated with velo-cardio-facial syndrome.

Velo-cardio-facial syndrome (VCFS) is caused by a microdeletion in the long arm of chromosome 22 and is associated with an increased frequency of schizophrenia and bipolar mood disorder. The purpose of this study was to investigate the genetic, physical, developmental and psychiatric features of schizophrenic patients with VCFS microdeletion. It describes the clinical findings in four schizophrenic inpatients with the characteristic chromosomal deletion. The four patients displayed delayed motor development, language deficits, learning disabilities, mental retardation, early age of onset, chronic and disabling course of illness and poor response to classical neuroleptic drugs and electroconvulsive therapy. Two patients benefited from treatment with clozapine. We suggest that schizophrenic patients with a history of delayed motor development, early onset of the disorder, history of learning disability, mental retardation, congenital cardiac anomalies and/or hypernasal speech should be screened for the velo-cardio-facial syndrome deletion. The implications of this study for psychiatric phenotype, nosology, disease mechanism, and possible new treatments in the future are discussed.

Abnormalities, Multiple↗

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

Involvement of tumor necrosis factor alpha and interleukin-1beta in enhancement of pentylenetetrazole-induced seizures caused by Shigella dysenteriae.

Neurologic manifestations, mainly convulsions, are the most frequent extraintestinal complications of shigellosis. We used an animal model to study the roles of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) in Shigella-related seizures. Administration of Shigella dysenteriae 60R sonicate enhanced the sensitivity of mice to the proconvulsant pentylenetetrazole (PTZ) within 7 h. This was indicated by a significantly higher mean convulsion score and an increased number of mice responding with clonic-tonic seizures in the Shigella-pretreated group. Preinjection of mice with anti-murine TNF-alpha (anti-mTNF-alpha) or anti-murine IL-1beta (anti-mIL-1beta) 30 min prior to administration of Shigella sonicate abolished their enhanced response to PTZ at 7 h. Mean convulsion scores were reduced by anti-mTNF-alpha from 1.2 to 0.8 (P = 0.017) and by anti-mIL-1beta from 1.3 to 0.7 (P = 0.008). Preinjection of anti-mTNF-alpha also reduced the percentage of mice responding with clonic-tonic seizures, from 48 to 29% (P = 0.002), and preinjection of anti-mIL-1beta reduced it from 53 to 21% (P = 0. 012). Neutralization of TNF-alpha or IL-1beta did not protect the mice from death due to S. dysenteriae 60R. These findings indicate that TNF-alpha and IL-1beta play a role in the very early sensitization of the central nervous system to convulsive activity after S. dysenteriae administration. Similar mechanisms may trigger neurologic disturbances in other infectious diseases.

Animals↗

PubMed1999

Intramuscular flunitrazepam versus intramuscular haloperidol in the emergency treatment of aggressive psychotic behavior.

OBJECTIVE: The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or aggressive behavior in acutely psychotic patients. METHOD: Twenty-eight actively psychotic inpatients, aged 20-60 years, who were under treatment with neuroleptic agents were selected for the study. Each was randomly assigned on a double-blind basis to receive either 5 mg i.m. of haloperidol (N=13) or 1 mg i.m. of flunitrazepam (N=15) during an aggressive event. Verbal and physical aggression was measured over time with the Overt Aggression Scale. Patients were also rated with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale. RESULTS: Both flunitrazepam and haloperidol exhibited acute antiaggressive activity. This beneficial effect, as assessed by the Overt Aggression Scale, was obtained within 30 minutes. CONCLUSIONS: Intramuscular flunitrazepam may serve as a convenient, rapid, safe, and effective adjunct to neuroleptics in reducing aggressive behavior in emergency psychiatric settings.

Acute Disease↗

PubMed1998

Antiproliferative and differentiating effects of benzodiazepine receptor ligands on B16 melanoma cells.

In this study, we evaluated the effect of several ligands active at the central-type and peripheral-type benzodiazepine receptor (BzR) (clonazepam, diazepam, PK11195 and Ro5-4864) on the growth and differentiation of B16 melanoma cells. All tested BzR ligands were able to suppress proliferation of the cells at the micromolar range and in a concentration-dependent manner. However, agents selectively active at the peripheral-type BzR (PK11195 and Ro5-4864) exhibited more potent antiproliferative activity. In addition, the BzR ligands were demonstrated to affect the cell cycle by reducing the percent of cells in the S phase and increasing the percent in the G2/M phase. BzR ligands induced cellular phenotypic alterations, which have been previously shown to be associated with melanoma cell differentiation. These alterations included: marked morphological changes, enhancement of melanogenesis, lipid accumulation and increase in the activity of gamma glutamyl transpeptidase. All BzR ligands induced a marked reduction in the concentration of UTP and most of them did the same in GTP and CTP, while ATP levels were not significantly altered. In summary, BzR ligands (clonazepam, diazepam, PK11195 and Ro5-4864) were found to exert antitumor effects in B16 melanoma cells. These findings encourage further studies of a possible therapeutic potential of BzR ligands in treatment of melanoma.

Animals↗

PubMed1998

The antinociceptive effect of moclobemide in mice is mediated by noradrenergic pathways.

Moclobemide is an antidepressant which affects the monoaminergic neurotransmitter system through a reversible inhibition of monoamine oxidase (MAO), preferentially type A. We examined the antinociceptive effects of moclobemide alone and in conjunction with specific opioid, adrenergic and serotonergic antagonists, using the mouse-tail flick test. Intraperitoneal moclobemide produced a dose-dependent antinociceptive effect with an ED50 of 69.1 mg/kg. Tests with selective antagonists yielded positive results only for yohimbine (P < 0.001), implying a noradrenergic mechanism of action in the moclobemide antinociceptive effect. This was confirmed by the coadministration of moclobemide with inactive doses of prototype agonists of the opioid, adrenergic and serotonergic systems. Only clonidine, an alpha2 agonist, significantly shifted (8-fold) the dose response curve of moclobemide. We conclude that there is a selective involvement of the alpha2 adrenergic pathways in the moclobemide-induced antinociceptive effect and a lesser involvement (if any) of the opioid, serotonergic and alpha1 adrenergic mechanisms. More research is needed to establish a possible role for moclobemide in pain management.

Analgesics↗

PubMed1998

Bone age in adolescents with schizophrenia and obsessive-compulsive disorder.

The bone age (BA), height and weight of 20 adolescents with schizophrenia and 21 matched adolescents with obsessive-compulsive disorder (COD) were measured. The BA of the schizophrenic patients was significantly higher than their chronological age (CA)(p < 0.05), while the OCD subjects' BA was non-significantly lower than their CA. In addition, the difference between CA and BA (delta ages) in the schizophrenic adolescents was significantly different from the delta ages of the OCD adolescents (p , 0.05). Gender did not significantly affect BA or delta ages. A positive correlation (r = 0.5, p < 0.01) was obtained between CA and delta ages in the schizophrenic patients but not in the OCD patients. Both groups were within the normal range of weight and height percentiles.

Adolescent↗

PubMed1998

Linkage disequilibrium of common Gaucher disease mutations with a polymorphic site in the pyruvate kinase (PKLR) gene.

Gaucher disease (GD), caused by a deficiency of the lysosomal enzyme glucocerebrosidase (GBA), is the most common human glycolipid storage disease. The incidence of the disease is particularly high in the Ashkenazi Jewish population, with a carrier frequency of 0.068. The 1226A-->G and 84GG mutations are the two predominant disease-causing alleles. We investigated the association of various mutations in the GBA gene with different alleles of a highly polymorphic site in the adjacent pyruvate kinase (PKLR) gene. Ninety-seven unrelated type I GD patients of various genotypes were studied to determine their genotype for the PKLR gene trinucleotide repeat polymorphism. One hundred out of 104 (96%) alleles carrying the 1226G mutation also carried the A1 allele of the PKLR gene, which is present in only 6.7% of the control population. The calculated linkage disequilibrium between 1226G and the A1 allele of the PKLR gene is 0.957. Mutation 84GG was found to be uniquely associated with the PKLR A6 allele, with a linkage disequilibrium of 1.00. The association of several less frequent GD mutations with PKLR alleles was also studied. These results support the hypothesis that the 1226G and 84GG mutations in the Ashkenazi Jewish population each originated in a single founder. Further studies of the association of the 1226G and 84GG mutations with PKLR alleles in European non-Jewish GD patients could help in the study of the chronological order of these mutations and may shed light on the history of the Ashkenazi Jews in the past two millennia.

Alleles↗

PubMed1998

Regulation of rat brain vesicular monoamine transporter by chronic treatment with ovarian hormones.

Ovarian steroids play an important role in neuroregulation and in the pathophysiology of various neuropsychiatric disorders. Most of the studies focused on the impact of gonadal steroids on post-synaptic receptors and plasma membrane transporters. In the present study, we evaluated the effect of chronic treatment with ovarian steroids on the expression of rat brain vesicular monoamine transporter (VMAT2). Ovariectomized rats were treated for 21 days with estradiol, progesterone or both. VMAT2 gene expression was assessed on the protein level by high affinity [3H]dihydrotetrabenazine ([3H]TBZOH) binding using autoradiography and on the mRNA level by in situ hybridization. Progesterone administration led to a decrease in [3H]TBZOH binding in the middle striatum and in the nucleus accumbens and to a parallel decrease in VMAT2 mRNA level in the substantia nigra pars compacta and dorsal raphè nuclei. Chronic estradiol treatment reduced VMAT2 mRNA level in the dorsal raphè and [3H]TBZOH binding in middle part of the striatum and nucleus accumbens but did not affect VMAT2 mRNA level in the substantia nigra pars compacta. Simultaneous administration of both ovarian steroids did not modulate VMAT2 mRNA in the substantia nigra pars compacta as well as [3H]TBZOH binding in the striatum or the nucleus accumbens but reduced VMAT2 mRNA level in the dorsal raphè. It appears that ovarian steroids may play a crucial role in the regulation of VMAT2 gene expression in the dopamine and serotonin systems. This modulatory activity may be relevant to synaptic and neuronal plasticity as well as to the molecular and cellular pathophysiology of gender-specific neuropsychiatric disorders.

Animals↗

PubMed1998

Recurrence pattern of serum creatine phosphokinase levels in repeated acute psychosis.

BACKGROUND: Elevated serum creatine phosphokinase (CPK)MM level is frequently found in acute psychosis. Theories relate this CPKemia to psychomotor agitation and medication. We hypothesized that psychosis-related CPKemia observed in individual patients is relatively consistent. METHODS: Ninety psychotic patients were studied; 83% were schizophrenics (Brief Psychiatric Rating Scale scores > or = 40) whose serum CPKMM levels were recorded during two or more different acute psychoses. The serum CPKMM levels used were the maximal levels monitored during the beginning of each hospitalization. The last CPK measurement in a circumscribed period was defined as the index serum CPK level (IndCPK). The mean of all other individual maximal CPK measurements during other psychotic episodes was defined as the average CPK (AvgCPK). RESULTS: Multiple linear regression analysis showed a significant correlation of natural logarithm (Ln) of (IndCPK with Ln(AvgCPK), as well as with gender (coefficient = .65 and .63, p < .0001 and p < .01, respectively). There were significantly higher IndCPK levels among male patients than among female patients (p < or = .001). A relatively consistent individual pattern of serum CPKMM levels during repeated acute psychotic episodes was observed. CONCLUSIONS: Serum CPKMM levels and gender were found to be good predictors of maximal serum CPKMM levels during every repeated acute psychotic episode. High IndCPK levels are probably risk factors for neuroleptic malignant syndrome.

Acute Disease↗

PubMed1998

Interventional catheterization decreases plasma levels of atrial natriuretic peptide (ANP) in children with congenital heart defects.

Atrial natriuretic peptide (ANP) is one of the cardiac peptides implicated in volume and sodium homeostasis. We investigated the effect of interventional catheterization on plasma levels of ANP, aldosterone, and cortisol in 28 children with various congenital heart defects (CHD). Patients were divided by age into two groups: group A--infants and children over 3 months of age (n = 22), and group B--newborns (n = 6). These were compared to age-matched control groups. In group A, interventions included pulmonic valvotomy (n = 8), aortic valvotomy (n = 4), balloon angioplasty of native coarctation of the aorta (n = 3), balloon dilatation of the mitral valve (n = 1), and Rashkind double umbrella closure of patent ductus arteriosus (n = 6). Group B interventions included pulmonic valvotomy (n = 3), aortic valvotomy (n = 1), and balloon atrial septosomy (n = 2). In group A, mean ANP levels were markedly higher than in age-matched controls (125.2+/-15.8 vs. 24.6+/-4.6 pg/ml) (P <0.0001), and decreased immediately after intervention (75.6+/-11.4 pg/ml, P <0.02), and more markedly on follow-up (42.9+/-5.0 pg/ml, P < 0.0001). In group B (newborns), mean basal plasma levels were high before and after intervention and were not different from age-matched controls (243+/-42.1 vs. 220.8+/-16.2 pg/ml). There was a significant decrease on follow-up measurement (62.1+/-12.7 pg/ml, P < 0.005). In both groups, plasma cortisol levels increased significantly immediately following catheterization (P < 0.02), and normalized on follow-up. Basal aldosterone levels were normal in group A and high in Group B (9.9+/-3.8 vs. 167.6+/-16.9 ng/dl) (P < 0.001). It is suggested that plasma ANP levels are increased in children with CHD, without overt heart failure, and decrease significantly following successful intervention. In newborns with CHD, the physiological high ANP levels obscure the effect of the CHD.

Aldosterone↗

PubMed1998

The suicide brain: a review of postmortem receptor/transporter binding studies.

The present review summarizes the last 15 years of research involving postmortem receptor/transporter binding studies on brains of suicide victims. It is our working hypothesis, on the basis of psychological, behavioral and epidemiological studies, that suicidal behavior is an independent unique behavioral entity with specific neurochemical characteristics. This review tries to test this hypothesis at the level of neurotransmitter receptors by using a different approach to data analysis. We suggest that this statistical approach, involving multivariate analyses, can contribute to the formulation of new hypotheses at the level of molecular biology and genetics. Such studies if undertaken in the future, would help define suicidal behavior as a psycho-neuro-pathological entity.

Brain↗

PubMed1998

Psychiatric and polysomnographic evaluation of sleep disturbances.

BACKGROUND: We evaluated psychiatrically 100 subjects, who were referred to a sleep laboratory in a general hospital because of sleep complaints. METHODS: All subjects were interviewed using a Structured Clinical Interview for DSM-III-R and underwent one night of standard polysomnography (PSG) examination. RESULTS: Forty three percent of the population had at least one Axis I DSM-III-R disorder. High rate of depressive mood disorder (24%) was observed in our sample, in contrast to low prevalence of alcohol and drug abuse (4%). Our results of a Israeli population are different from the United States studies in respect to alcohol and drug abuse. Furthermore, 11% of patients with PSG diagnosis exhibited comorbid psychiatric disorder. CONCLUSION: it appears that individuals with sleep complaints have high rate of psychiatric morbidity, especially mood disorders. LIMITATION: The rapid eye movement (REM) latency, a biological marker for depression, was not investigated. CLINICAL RELEVANCE: it seems that both PSG and psychiatric evaluation of sleep disturbance are of importance for appropriate therapeutic strategy for individuals with sleep complaints, especially in those with features of suspected depressive mood disorders.

Adult↗

PubMed1998

Elevated adhesiveness/aggregation of peripheral blood leukocytes in patients with major depression.

A simple slide test was used to determine the effects of major depression (MD) and heterocyclic antidepressants on leukocyte adhesiveness/aggregation (LAA) in the peripheral blood. Eighty subjects were categorized into four equal groups: untreated-MD patients, treated-MD patients, nondepressed patients treated with antidepressants and healthy controls. Significantly higher LAA values were observed both in untreated- and treated-MD patients, 13.8+/-1.7% and 13.5+/-1.9% respectively, compared to nondepressed-treated patients and healthy controls, 5.4+/-0.9% and 6.4+/-0.7% respectively (P < 0.0001). Increased LAA was associated with the depressive episode, was not affected by antidepressants and may potentially serve as a useful laboratory state marker for MD.

Adult↗

PubMed1998

Lateral preference in post-traumatic stress disorder.

BACKGROUND: We assessed lateral preference in 80 male patients with combat-related post-traumatic stress disorder (PTSD) and in 100 healthy age-matched male controls. METHODS: Hand, foot, eye and ear preferences were examined, using the Edinburgh Handedness Inventory-Modified and the Coren Inventory of Lateral Preference. RESULTS: Mixed lateral preference was noted in significantly more PTSD patients than controls (65 v. 43%, P < 0.005). CONCLUSIONS: These results indicate a possible hemispheric imbalance (less lateralization) in PTSD patients, with the right hemisphere playing a more active role in perceptual and cognitive processing and in the regulation of biological responses in these patients. This imbalance may be relevant to the pathophysiology of PTSD.

Adult↗

PubMed1998

Vitamin E (alpha-tocopherol) in the treatment of tardive dyskinesia: a statistical meta-analysis.

Tardive dyskinesia is an involuntary movement disorder developing following treatment with neuroleptics. As many as 50% of chronic psychotic patients develop this disabling condition. No treatment has been found effective for tardive dyskinesia. This study was undertaken to meta-analyze the effects of vitamin E (alpha-tocopherol) reported in the last decade. All studies published since 1987, focusing on vitamin E and tardive dyskinesia are reviewed. Double-blind studies are analyzed using measures of effect and variance as described by secondary analysis of magnitude of effects in pooled data. A total of 223 patients received vitamin E treatment (400-1600 IU/day) for tardive dyskinesia, in 12 studies. A significant subgroup (28.3%) showed a modest improvement. Vitamin E was well tolerated, and only rarely did side effects occur-of no clinical significance. Vitamin E is a safe, well-tolerated compound that may provide some beneficial effects in patients suffering from neuroleptic-induced tardive dyskinesia.

Adult↗

PubMed1998

Reliability and validity of the Family Eating and Activity Habits Questionnaire.

OBJECTIVE: The purpose of this work was to develop and test an instrument that will identify the factors that facilitate childhood obesity and monitor the environmental changes and family behavior modifications associated with weight loss. DESIGN AND METHODS: The relevant factors that affect obesity and weight loss in children were divided into four scales: activity level, stimulus exposure, eating related to hunger, and eating style. We designed a questionnaire to be completed by the parents of the obese child aged 6-11 years. Scores accumulated were calculated separately for each member of the family. Higher numerical scores reflected less appropriate eating patterns. The questionnaire reliability (test-retest), internal consistency and ability to discriminate obese vs normal-weight children's behaviors was tested using a pilot population of 40 mothers not enrolled in a formal weight loss program. The questionnaire reliability (parents' report and spouse report) and predictive validity was tested using a selective population: 60 parents of obese children enrolled in a clinical intervention intended to treat childhood obesity with an environmental approach vs a dietary approach. RESULTS: The content validity of the questionnaire was evaluated by a team of ten experts. Cronbach's alpha was calculated to test internal consistency. Mean r was 0.83. Pearson's correlation coefficients were computed between test and retest scores for individual items and for the total score, and ranged from 0.78 to 0.90 (median 0.84) (P < 0.01 for all). Total score test-retest r was 0.85 (P < 0.01). The total family score was also higher in the families with an obese child compared to families with a normal-weight child, P < 0.01. No significant differences were noted between parent report and spouse report scores. The construct validity of the questionnaire was also supported by its high sensitivity to weight loss treatment. Weight loss in the child correlated highly with improvement in questionnaire score. CONCLUSIONS: The Family Activity and Eating Habits Questionnaire is reliable and internally consistent, and it is useful as an optional tool for planning an intervention program for childhood obesity.

Behavior↗