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Biomedical subjects

A Weizman

Publications and source records attributed to A Weizman.

At least 109 records · Page 6Linked to original sources
PubMed2000

Heat intolerance in patients with chronic schizophrenia maintained with antipsychotic drugs.

OBJECTIVE: Schizophrenia may be associated with hyperthermic syndromes such as febrile catatonia, neuroleptic malignant syndrome, and heatstroke. The authors hypothesized that an exercise-heat tolerance test would disclose abnormal thermoregulation in schizophrenic patients. METHOD: Seven male schizophrenic outpatients in remission maintained on depot antipsychotic treatment and eight healthy comparison subjects completed a heat tolerance test that consisted of two 50-minute bouts of walking a motor-driven treadmill at 40xC (relative humidity=40%). RESULTS: A significantly higher rise in rectal and skin temperatures was observed in the patient group. No differences in heart rate, blood pressure, or perspiration were detected. CONCLUSIONS: Schizophrenic patients maintained on antipsychotic drugs exhibit impaired heat tolerance. Possible explanations are a reduced ability to convey heat from the body's core to the periphery with or without excessive heat production. The hyperthermic response to the heat tolerance test may reflect a dysfunction associated with schizophrenia, a neuroleptic-induced side effect, or both.

Adult↗
PubMed2000

Neuroendocrinological response to standardized mixed meal in female anorectic patients during active and refeeding phases.

To evaluate the neuroendocrinological dysfunction in anorexia nervosa, plasma somatostatin, glucose, insulin, and growth hormone were monitored in ten patients with anorexia nervosa in the active and refeeding (remission) phases of the disorder and in nine age-matched healthy control subjects. Somatostatin levels were significantly higher in the anorectic patients in both the active and refeeding phases than in the controls at baseline (mean+/-SD 27.4 +/-5.5 and 31.1+/-2.6 vs 21.3+/-1.9 pg/ml; p<0.001), and significantly higher in the anorectic patients in the active phase compared to the refeeding phase and to the controls in response to a mixed meal (p<0.05). Insulin levels were significantly lower in the anorectic patients in both the active and refeeding phases compared to the controls at baseline (9.3+/-1.1, 7.6+/-1.0 vs 14.7+/-3.5 microU/ml; p<0.0001) and after a mixed meal (p<0.05). An attenuated glucose response discriminated the anorectic patients in the active state from the same patients in the refeeding state and the controls (p<0.0001). There was no significant difference in growth hormone response between the anorectic patients and the controls. These findings suggest that there is an augmented response of somatostatin and an attenuated response of insulin to mixed meal stimulation in active anorexia. The diminished insulin response persists during the refeeding phase. It seems that central and peripheral alterations in endocrine function occur in anorexia nervosa.

Adolescent↗
PubMed2000

Serotonin transporter polymorphism and response to SSRIs in major depression and relevance to anxiety disorders and substance abuse.

The selective serotonin re-uptake inhibitors (SSRIs) which modulate serotonergic activity are effective in the treatment of serotonin-related mental disorders, such as depression and anxiety. These agents bind to the serotonin transporter (5-HTT) and inhibit its capacity to transport serotonin (5-hydroxytryptamine; 5-HT). A functional polymorphism in the promoter region of 5-HTT (5-HTTLPR) has been described. The insertion variant of this polymorphism (long allele) is associated with higher expression of brain 5-HTT compared to the deletion variant (short allele). An association between the 5-HTTLPR polymorphism and mental disorders has been reported by some, but not all, investigators. In addition, the 5-HTT gene polymorphisms were found to be associated with a better and faster response to SSRIs with or without pindolol augmentation in depressed patients. Further studies are needed to clarify the relationship between the 5-HTT genotype, the susceptibility to mental disorders, the response to serotonergic agents and the side effect profile.

Antidepressive Agents↗
PubMed2000

Is melatonin treatment effective for tardive dyskinesia?

BACKGROUND: Tardive dyskinesia is a severe and disabling side effect of conventional antipsychotic treatment, with incidence rates reaching a high of 50% in chronically institutionalized populations. On the basis of recent studies showing some benefit of antioxidants, we evaluated the effect of melatonin, the most potent naturally occurring antioxidant, on tardive dyskinesia in patients with chronic schizophrenia. METHOD: Nineteen patients (8 men, 11 women), aged a mean +/- SD 74.0+/-9.5 years with chronic DSM-IV schizophrenia of 31.3+/-7.0 years' duration, were randomly assigned in a double-blind, placebo-controlled, crossover trial to receive slow-release melatonin, 2 mg/day, or placebo for 4 weeks. After a 2-week washout period, the patients were switched to the other treatment arm for an additional 4 weeks. The Abnormal Involuntary Movement Scale (AIMS) was administered at baseline, 4 weeks, 6 weeks, and 10 weeks. Regular administration of antipsychotic and other medications was kept unchanged throughout the study. RESULTS: Mean AIMS scores did not change significantly from baseline in either treatment arm. All patients completed the study, and there were no side effects or adverse events. CONCLUSION: Supraphysiologic doses of melatonin do not positively affect tardive dyskinesia. Considering that melatonin is a safe drug, further studies are needed of higher doses and in patients with shorter disease duration before its use in the treatment of tardive dyskinesia is ruled out.

Aged↗
PubMed2000

Induction of mRNA for tumor necrosis factor-alpha and interleukin-1 beta in mice brain, spleen and liver in an animal model of Shigella-related seizures.

BACKGROUND: The pathogenesis of neurological symptoms, the most common extraintestinal complication of childhood shigellosis, is unclear. To elucidate the mechanisms involved, we developed an animal model and demonstrated that TNF alpha and IL-1 beta play a role. OBJECTIVES: To determine whether TNF alpha and IL-1 beta genes are expressed in the brain following peripheral administration of Shigella dysenteriae 60R. METHODS: Expression of mRNA for TNF alpha and IL-1 beta was examined in the brain structures (hypothalamus and hippocampus) and peripheral organs by reverse transcriptase polymerase chain reaction, at different time points after intraperitoneal injection of S. dysenteriae sonicate. RESULTS: In our animal model of Shigella-related seizures, TNF alpha and IL-1 beta mRNA were induced in the brain, spleen and liver already 1 hour after injection of S. dysenteriae sonicate. The expression of TNF alpha and IL-1 beta mRNA in spleen, hippocampus and hypothalamus decreased after 6 h and increased again at 18 h post-injection. CONCLUSIONS: Local production of TNF alpha and IL-1 beta in the brain may be involved in the enhanced seizure response of mice after administration of S. dysenteriae. It is possible that intracerebral production of TNF alpha and IL-1 beta plays a role in neurological disturbances of human shigellosis.

Animals↗
PubMed2000

[Oral rehydration in acute gastroenteritis in infants and children--advantages of a standardized protocol].

Oral rehydration (OR) for acute gastroenteritis in infants and children has been shown to be as effective as IV therapy, with less discomfort and lower costs. In this retrospective study we compared 2 pediatric wards, in 1 of which only a standardized, simplified, bedside protocol, based on American Academy of Pediatrics guidelines, was used. There were no significant clinical characteristics in the 208 patients. In the ward which used the above protocol, OR utilization was significantly more frequent than in the other ward (48% versus 15%), thus saving equipment costs of nearly $1,000/3 months. There were no significant differences in outcome between the wards. We conclude that introducing a standardized management protocol may increase OR utilization in hospitalized children with acute diarrhea.

Acute Disease↗
PubMed1999

Mutations uncouple human fibroblast growth factor (FGF)-7 biological activity and receptor binding and support broad specificity in the secondary receptor binding site of FGFs.

The fibroblast growth factor (FGF) family plays a key role in a multitude of physiological and pathological processes. The activities of FGFs are mediated by a family of tyrosine kinase receptors, designated FGFRs. The mechanism by which FGFs induce receptor activation is controversial. Despite their structural similarity, FGFs display distinct receptor binding characteristics and cell type specificity. Previous studies with FGF-2 identified a low affinity receptor binding site that is located within a loop connecting its 9th and 10th beta-strands. The corresponding residues in the other family members are highly variable, and it was proposed that the variability might confer on FGFs unique receptor binding characteristics. We studied the role of this loop in FGF-7 by both site-directed mutagenesis and loop replacement. Unlike the other members of the FGF family, FGF-7 recognizes only one FGFR isoform and is, therefore, ideal for studies of how the specificity in the FGF-FGFR interaction is conferred at the structural level. Point mutations in the loop of FGF-7 did not change receptor binding affinity but resulted in reduced mitogenic potency and reduced ability to induce receptor-mediated phosphorylation events. These results suggest that the loop of FGF-7 fulfills the role of low affinity binding site required for receptor activation. The observation that it is possible to uncouple FGF-7 receptor binding and biological activity favors a bivalent model for FGFR dimerization, and it may be clinically relevant to the design of FGF-7 antagonists. Reciprocal loop replacement between FGF-7 and FGF-2 had no effect on their known receptor binding affinities nor did it alter their known specificity in eliciting a mitogenic response. In conclusion, these results suggest that, despite the diversity in the loop structure of FGF-2 and FGF-7, the loop has a similar function in both growth factors.

3T3 Cells↗
PubMed1999

Effects of psychotropic drugs on cell proliferation and differentiation.

Some of the psychotropic agents widely used for the amelioration of anxiety, depression, and psychosis also show an effect at the cellular proliferation level. Surprisingly little research, however, has been directed to the antitumoral potential of these drugs, alone or in combination with established cancer treatments. Our review of the literature to date has yielded some promising early findings. Ligands active at the benzodiazepine (BZ) receptors have been studied the most extensively and were found to have differential, concentration-dependent effects on the growth and proliferation of both normal and cancer cells. Of the phenothiazines tested, chlorpromazine (CPZ) and perphenazine (PPZ) had the most potent cytotoxic action on fibroblasts and glioma cells. Antiproliferative effects also were noted by these and other agents in leukemic and breast cancer cell lines. Additional psychotropic drugs studied include the atypical antipsychotics, antidepressants, and mood stabilizers, especially lithium. Most of the reported activities were observed in in vitro studies and were achieved at high pharmacological concentrations. Further in vivo studies in well-designed animal models are warranted to determine whether these well-tolerated, relatively inexpensive, and widely available drugs or their derivatives may be added in the future to the armamentarium of cancer pharmacotherapy.

Anticonvulsants↗
PubMed1999

Decreased platelet peripheral-type benzodiazepine receptors in adolescent inpatients with repeated suicide attempts.

BACKGROUND: Peripheral-type benzodiazepine receptors (PBR) are responsible for mitochondrial cholesterol uptake, the rate limiting step of steroidiogenesis. They have been shown to be increased after acute stress, and decreased during exposure to chronic stressful conditions, and in patients with generalized anxiety disorder and post-traumatic stress disorder. In view of the proven connection between adolescent suicidal behavior and stress, we hypothesized that PBR may be decreased in the suicidal adolescent population. METHODS: We measured [3H] PK 11195 binding to platelet membrane in nine adolescent (age 13-20 years) inpatients with a history of at least three suicidal attempts and ten age-matched psychiatric inpatients with no history of suicide attempts. Suicidality was assessed with the Suicide Risk Scale (SRS), and symptom severity with the Beck Depression Inventory, State-Trait Anxiety Inventory (STAI), Overt Aggression Scale (OAS), and Impulsivity Scale (IS). RESULTS: Suicide Risk Scale scores were significantly higher in the suicidal group. The suicidal group showed a significant decrease in platelet PBR density (-35%) compared to the controls (p < 0.005). CONCLUSIONS: Our results of PBR depletion in adolescent suicide are in accordance with the findings in patients with generalized anxiety disorder and posttraumatic stress disorder and lend further support to the role of PBR in human response to chronic stress in adolescent suicide.

Adolescent↗
PubMed1999

Serum cholesterol, suicidal tendencies, impulsivity, aggression, and depression in adolescent psychiatric inpatients.

BACKGROUND: This study was undertaken to examine the relationship between serum cholesterol levels and suicidal behaviors in adolescent psychiatric inpatients. Any association between serum cholesterol and measures of suicidal behavior, impulsivity, aggression, anxiety, and depression was also examined. METHODS: Consecutive admissions (n = 152) to an adolescent psychiatric inpatient unit were assessed using measures of suicidal behavior, violence, impulsivity, and depression. Serum cholesterol was compared between those admitted for reasons of suicidal tendencies and those for other reasons. Correlation between serum cholesterol and measures of suicidal behavior, violence, impulsivity, and depression were examined. RESULTS: Serum cholesterol levels were significantly higher in adolescent patients who were currently suicidal than in nonsuicidal adolescents. Within the suicidal group, but not in the total inpatient group, serum cholesterol correlated negatively with the degree of suicidal behavior. No correlation between serum cholesterol levels and depression, violence, and impulsivity were detected. No significant differences were found in serum cholesterol levels between diagnoses or between suicidal and nonsuicidal patients within each diagnostic group. CONCLUSIONS: The association between cholesterol and suicidal tendencies remains complex and may depend on several variables within the population studied. Its usefulness as a biologic risk factor in clinical samples remains to be determined.

Adolescent↗
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

Impact of treatment for childhood obesity on parental risk factors for cardiovascular disease.

BACKGROUND: Family-based approaches using the parents as agents of change to treat childhood obesity are superior to programs targeting only children in achieving weight reduction and have a lower dropout rate. OBJECTIVE: The aim of this study was to compare the impact of two behavioral approaches (parents only vs children only) for the treatment of childhood obesity on parental weight, eating, and activity habits as well as cardiovascular risk factors. DESIGN: A randomized 1-year clinical intervention study was performed. METHODS: Sixty obese children (>/=20% over ideal weight for age, height, and sex), ages 6-11 years, were randomly allocated to the experimental (parents as sole agents of change) or conventional groups (children as sole agents of change). Fourteen (1-h-long) support/educational sessions were conducted by a clinical dietitian for the parents in the experimental group and 30 sessions for children in the conventional group. Anthropometric and biochemical measurements were determined at the start and end of the program. RESULTS: The experimental approach, when compared to the conventional intervention, was found to be superior in the reduction of fathers overweight (P < 0.05). The former approach resulted also in improved profile of risk factors for cardiovascular disease in both parents. These changes could be ascribed to a greater improvement in eating and activity behaviors observed in parents belonging to the experimental intervention group who participated in a family-based intervention to treat their children's obesity. CONCLUSIONS: Treatment of childhood obesity targeting the parents as the sole agent of change, which is more effective for the treatment of childhood obesity when compared to a children-oriented program, may in addition award parents with the benefit of changing their own eating and activity patterns, thus making this program ideal for treatment of obesity in children and their overweight parents.

Adult↗
PubMed1999

Elevated cellular immune response to human heat-shock protein-60 in schizophrenic patients.

Heat shock protein-60 (HSP60) is implicated in several autoimmune diseases as a triggering antigen. Based on the autoimmune hypothesis of schizophrenia, we examined cellular and humoral responses against HSP60 and a series of its peptide fragments with peripheral blood samples of schizophrenic patients and healthy subjects each of group size between 12 to 32 participants. The average stimulation indices of peripheral blood mononuclear cells (PBMC) to HSP60 were 3.17 +/- 0.36 (mean +/- SE) for schizophrenic patients and 2.23 +/- 0.24 (mean +/- SE) for healthy subjects, with a significant difference between the groups (P = 0.0457). In parallel, 38 synthetic peptide fragments of HSP60, each of 18-21 amino acids, were tested for in vitro sensitization of PBMC. With one peptide (p32) the average stimulation index of PBMC from schizophrenic patients was significantly higher than that obtained for PBMC of control subjects (P = 0.0006). Comparing the cellular immune response to p32 between patients who were distinctive responders (n = 10) or non-responders (n = 10) to neuroleptic treatment indicated a similar elevation of cellular response in these groups. Antibodies against HSP60 were screened by dot-blot and ELISA in the sera of the above blood samples. Titers of IgG and IgM against HSP60 were found to be of similar magnitude in schizophrenic patients and in controls. Titers of IgA against HSP60 were somewhat higher in the sera of schizophrenic patients in comparison to sera of control subjects (P = 0.0605).

Adult↗
PubMed1999

Montelukast, a leukotriene receptor antagonist, reduces the concentration of leukotrienes in the respiratory tract of children with persistent asthma.

BACKGROUND: Leukotrienes are bronchoactive mediators secreted by inflammatory cells in the respiratory mucosa on exposure to asthma triggers. OBJECTIVE: We investigated the effect of montelukast, a leukotriene receptor antagonist, on the release of leukotrienes in the respiratory mucosa of children with persistent asthma. METHOD: Twenty-three children aged 6 to 11 years with moderately severe asthma were treated in a cross-over design starting, after a 2-week run in period, with either montelukast (n = 12) or cromolyn (n = 11) for 4 weeks with a 2-week washout period between treatments. Twelve of them were then treated with either montelukast or beclomethasone for 6 months. The use of beta(2)-agonists was recorded on a diary card. The concentration of leukotriene C(4) (LTC(4)) was measured by HPLC in nasal washes obtained before and at the end of each treatment period. Eosinophilic cationic protein (ECP) was measured in the nasal washes by RIA. RESULTS: The LTC(4) concentration significantly decreased in the children treated for the first 4 weeks with montelukast, from 5.03 +/- 1.17 to 1.42 +/- 0.33 ng/mL (P <.005), and a nonsignificant increase was noted in children treated with cromolyn, from 3.37 +/- 1.11 to 5.88 +/- 2.17 ng/mL (P =.17). ECP concentration also decreased in the children receiving montelukast (P =.12). The concentration of LTC(4) remained low after 3 and 6 months of treatment with montelukast (0.8 +/- 0.7 and 1.0 +/- 0.3 microg/mL) and was lower than with beclomethasone. Children treated with montelukast required significantly fewer beta(2)-agonists (P <.04), CONCLUSION: Montelukast reduces the concentration of leukotrienes in the respiratory tract of children with persistent asthma parallel to reduction in ECP and clinical improvement. This effect was not observed when the same children were treated with cromolyn.

Acetates↗