Biomedical subjects

Moshe Kotler

Publications and source records attributed to Moshe Kotler.

87 records · Page 5Linked to original sources

PubMed2002

Human immunodeficiency virus type 1 Vif binds the viral protease by interaction with its N-terminal region.

The vif gene, one of the six auxiliary genes of human immunodeficiency virus (HIV), is essential for virus propagation in peripheral blood lymphocytes and macrophages and in certain T-cell lines. Previously, it was demonstrated that Vif inhibits the autoprocessing of truncated HIV type 1 (HIV-1) Gag-Pol polyproteins expressed in bacterial cells, as well as the protease-mediated cleavage of synthetic peptides in vitro. Peptides derived from the aa 78-98 region in the Vif molecule specifically inhibit and bind the HIV-1 protease in vitro and arrest the production of infectious viruses in HIV-1-infected cells. This study demonstrates that (i) purified recombinant Vif protein and HIV-1 but not avian sarcoma leukaemia virus protease specifically bind each other and (ii) the interaction between these two proteins takes place at the N terminus of the protease (aa 1-9) and the central part of Vif (aa 78-98). The data presented in this report suggest a model in which Vif interacts with the dimerization sites of the viral protease.

Binding Sites↗

PubMed2002

Vitamin B6 as add-on treatment in chronic schizophrenic and schizoaffective patients: a double-blind, placebo-controlled study.

BACKGROUND: Vitamin B6, or pyridoxine, plays an intrinsic role in the synthesis of certain neurotransmitters that take part in development of psychotic states. Several reports indicate that vitamin B6 may be a factor in a number of psychiatric disorders and related conditions, such as autism, Alzheimer's disease, hyperactivity, learning disability, anxiety disorder, and depression. Moreover, there are anecdotal reports of a reduction in psychotic symptoms after vitamin B6 supplementation of psychopharmacologic treatment of patients suffering from schizophrenia or organic mental disorder. The aim of this study was to examine whether vitamin B6 therapy influences psychotic symptoms in patients suffering from schizophrenia and schizoaffective disorder. METHOD: The effects of the supplementation of vitamin B6 to antipsychotic treatment on positive and negative symptoms in 15 schizophrenic and schizoaffective patients (DSM-IV criteria) were examined in a double-blind, placebo-controlled, crossover study spanning 9 weeks. All patients had stable psychopathology for at least 1 month before entry into the study and were maintained on treatment with their prestudy psychoactive and antiparkinsonian medications throughout the study. All patients were assessed using the Positive and Negative Syndrome Scale (PANSS) for schizophrenia on a weekly basis. Patients randomly received placebo or vitamin B6, starting at 100 mg/day in the first week and increasing to 400 mg/day in the fourth week by 100-mg increments each week. RESULTS: PANSS scores revealed no differences between vitamin B6- and placebo-treated patients in amelioration of their mental state. CONCLUSION: Further studies with larger populations and shorter duration of illness are needed to clarify the question of the possible efficacy of vitamin B6 in treatment of psychotic symptoms in schizophrenia.

Adult↗

PubMed2002

[False memory syndrome: state of the art].

The review describes the heated dispute on the present state of recovered traumatic memories. There are two main schools concerning the status of recovered memories of child abuse. One school believes in their authenticity unconditionally. Those who oppose the authenticity claim False Memory Syndrome's existence. They describe it as "a serious form of psychopathology characterized by strongly believed pseudomemories of childhood sexual abuse" and "condition in which a person's identity and interpersonal relationships are centered around a memory of traumatic experience which is objectively false but in which the person strongly believes". This review presents the allegations of both sides involved in the dispute, with updates of scientific and judicial references and relevant recommendations to care takers.

Child↗

PubMed2001

Electronic Transduction of Polymerase or Reverse Transcriptase Induced Replication Processes on Surfaces: Highly Sensitive and Specific Detection of Viral Genomes Parts of this research are supported by the Israel Ministry of Science as an Infrastructure Project in Biomicroelectronics and as an Israel-Japan cooperation. M.K. acknowledges the support of the American Foundation for Aids Research, AmfAR (grant No. 02730-28-RG).

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Journal Article↗

PubMed2001

Plasma serotonin response to carbohydrate-rich food in chronic schizophrenic patients: clozapine versus classic antipsychotic agents.

Researchers have reported a stimulatory effect of carbohydrate-rich intake on platelet-poor plasma (PPP) serotonin (5-HT) levels in healthy human subjects. Dietary manipulation may serve as a safer and less invasive means than pharmacologic challenge to provoke serotonergic responsivity in studies of schizophrenia. In the present study, we used the carbohydrate-rich meal test as an indicator of 5-HT activity in 12 patients with chronic schizophrenia maintained for at least 6 months on clozapine. PPP 5-HT levels were measured at baseline and at 1, 2 and 3 h after administration of the test. Findings were compared with those in schizophrenic patients treated with classic antipsychotic agents for the same duration. The maximal PPP 5-HT response was reached 120 min after meal administration in the clozapine-treated group and 60 min after in the classic antipsychotic-treated group (P<0.05 vs baseline for both). The 5-HT level (as percentage of baseline) at 60 min was significantly lower in the clozapine-treated group (P<0.02), as were individual PPP 5-HT peak values (P<0.05). The individual time to reach the peak response was similar in the two groups. Our results indicate that in patients with chronic schizophrenia 5-HT responsivity to the natural challenge of carbohydrate-rich meals is lower in those treated with clozapine than in those given classic antipsychotic agents. Values in both groups were lower than those in an appropriate historical comparative group of healthy subjects. We suggest that both clozapine and classic antipsychotic agents suppress serotonergic system sensitivity, but to a different degree. Copyright 2001 John Wiley & Sons, Ltd.

Journal Article↗

PubMed2001

Extended nucleocapsid protein is cleaved from the Gag-Pol precursor of human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 Gag and Gag-Pol precursors are translated from an mRNA which is indistinguishable from the full-length genomic RNA. The ratio of Gag to Gag-Pol polyproteins is approximately 20:1 and is controlled by a frameshift of the reading frame, which takes place downstream of the p7 nucleocapsid (NC) in the N terminus of the p1 peptide. The viral precursors Gag and Gag-Pol are cleaved by the virus-encoded protease (PR) into the structural proteins, and into p6(Pol), PR, reverse transcriptase and integrase. Due to the frameshift event, the cleavage site at the C terminus of NC coded in the Gag frame (ERQAN-FLGKI) changes either to ERQANFLRED or ERQANFFRED. The results presented in this report demonstrate that the NC released from the Gag-Pol precursor is 8 amino acid residues longer than the NC cleaved from the Gag polyprotein. Our results also show that truncated Gag-Pol precursors bearing cleavage site mutation at the NC/p6(Pol), and/or p6(Pol)/PR junctions, undergo autoprocessing in bacterial and eukaryotic cells, indicating that PR is active when part of the precursor.

Animals↗

PubMedDate not supplied

The Positive and Negative Symptoms Questionnaire: a self-report scale in schizophrenia.

The assessment of various symptoms in schizophrenia has received much interest, although few studies have compared evaluations by clinicians to those of their patients. Self-report tools may improve service delivery, data collection, and possibly also treatment adherence. We constructed the Positive and Negative Symptoms Questionnaire (PNS-Q), a self-report measure, after items from the Scale for Assessment of Positive Symptoms (SAPS) and the Scale for Assessment of Negative Symptoms (SANS). The PNS-Q contained 68 items and was administered to 61 schizophrenic inpatients. We examined its psychometric properties and utility as a self-report tool in schizophrenia. The PNS-Q exhibited high internal consistency for both its positive and negative subscales. External validity with the SAPS and SANS was low. The positive symptoms subscale correlated significantly with the SAPS ( r = .341, P < .01), whereas the negative symptoms subscale did not correlate at all with the SANS ( r = -0.086, P > .1). The correlation between patients' insight and scores of the PNS-Q was mixed. A partial correlation analysis failed to confirm a relationship between the rating of the patients' level of insight (measured by the Amador Scale to Assess Unawareness of Mental Disorders [SUMD]) and the disparity between the PNS-Q and the SAPS and SANS. However, the PNS-Q correlated highly with McEvoy's Vignettes, a measure of self-perception of symptoms. The results of this study are discussed in light of current research and methodologic issues. The PNS-Q reflects schizophrenics' self-perception, an important, yet neglected, aspect of schizophrenia. Using this new measure, we believe that clinicians and researchers will be able to gain insight to the inner world of these patients and improve their condition, as well as enhance patients' involvement in treatment planning.

Adult↗

PubMedDate not supplied

Treatment of eating disorders improves eating symptoms but not alexithymia and dissociation proneness.

BACKGROUND: Eating disorders have been reported to increase in frequency, but it is yet unclear what psychological characteristics increase the proneness toward the development of eating disorders. Alexithymia (AL; a difficulty in awareness to one's emotions) and dissociation proneness are 2 such plausible features. METHOD: In this study, we evaluated the efficacy of a combined intervention (group therapy, individual therapy, and pharmacologic therapy) in a group of soldiers with eating disorders (n = 30) in the Israel Defense Forces. Moreover, we examined whether AL and dissociation proneness were frequent in this group and whether clinical improvement was associated with an improvement in these factors as well. RESULTS: High scores on the AL and dissociation measures were noted. The intervention was associated with a 50% decrease in the Eating Attitudes Test and Eating Disorders Inventory scores, consistent with our clinical impression of improvement in the eating symptoms. However, the decrease observed on the Dissociative Experiences Scale and Toronto Alexithymia Scale scores was minimal. CONCLUSIONS: The combined intervention was efficient in our sample of patients with eating disorder despite the small sample size. The aforementioned specific psychometric change may be indicative of the lack of importance of changes in AL or dissociation proneness in the short-term improvement in patients with eating disorder.

Adolescent↗

PubMedDate not supplied

Beneficial effect of donepezil augmentation for the management of comorbid schizophrenia and dementia.

Comorbid schizophrenia and dementia is a common clinical phenomenon; however, management of the coexisting illnesses remains incomplete. Donepezil, a cholinesterase inhibitor, may be beneficial for the management of symptoms of Alzheimer's disease, a disease in which cholinergic pathways in the cerebral cortex and basal forebrain are well known to be compromised. Furthermore, impaired cognition in elderly schizophrenic patients has been observed to be more than two thirds; however, there are no published controlled studies reporting the use of cholinesterase inhibitors in the management of schizophrenia in patients with associated dementia. In this study, six patients with chronic schizophrenia and comorbid dementia were administered donepezil, 5 mg, in single-blind fashion as augmentation to their standard antipsychotic medication for a 4-week period. Patients were evaluated with the Mini Mental State Examination (MMSE); Alzheimer's Disease Assessment Scale, Cognitive subscale; Positive and Negative Symptom Scale (PANSS); and the Clinical Global Impression (CGI) scales. A significant improvement was noted in MMSE scores (P < 0.01) and for CGI scores (P < 0.01). In addition, three patients demonstrated improvement on the PANSS. Donepezil appears to be an effective treatment for the management of symptoms of dementia accompanying patients with comorbid schizophrenia and dementia. Since cholinergic dysfunction may be present in some patients with schizophrenia, the authors' findings further demonstrate the possibility that this disorder may be managed with cholinergic medications as augmenting agents, at least in this specific subpopulation of patients with comorbid dementia. To confirm the findings of this preliminary trial, further investigation is mandated with a larger sample of subjects in the context of a double-blind medication trial.

Aged↗

PubMedDate not supplied

Treatment of neuroleptic-induced akathisia with the 5-HT2A antagonist trazodone.

Akathisia is a common and distressful extrapyramidal adverse side effect usually resulting from the use of antipsychotic medications. Early management of akathisia is important because it may be associated with poor treatment response and medication noncompliance. Unfortunately many patients fail to respond to standard management of akathisia. In addition to dopaminergic mechanisms, it has been hypothesized that serotonin may play a prominent role in the pathophysiology of akathisia. Trazodone is an antidepressant agent demonstrating prominent serotonergic antagonistic properties. This open-label pilot study investigates the efficacy of trazodone in the management of akathisia. Nine female patients with a score of at least "mild akathisia" on the Barnes Akathisia Scale, and receiving a stable dose of antipsychotic medication, were administered trazodone, titrated up to a dosage of 100 mg/day over a period of 5 days. The patients demonstrated marked improvement in symptoms of akathisia. In addition, some improvement was noted in symptomatology of anxiety, depression, and psychosis. These observations suggest the use of trazodone as a beneficial and relatively safe medication for the treatment of antipsychotic medication-induced akathisia. Further study in the context of a double-blind, placebo-controlled trial is mandated to substantiate these preliminary findings.

Adult↗

PubMedDate not supplied

Topiramate versus fluvoxamine in the treatment of pathological gambling: a randomized, blind-rater comparison study.

Pathologic gambling (PG) is a highly prevalent and disabling impulse control disorder. Recent studies have demonstrated that PG patients respond well to treatment with SSRIs, mood stabilizers, and opioid antagonists. These findings support the idea that PG and other disorders of impulse control may be conceptualized as part of the obsessive-compulsive spectrum disorders. Pilot studies have shown topiramate to be effective in the treatment of specific disorders of impulse control. The aim of the study is to compare the effectiveness of topiramate versus fluvoxamine in the treatment of PG. Thirty-one male PGs were assigned in a randomized fashion to receive either topiramate (15/31) or fluvoxamine (16/31) pharmacotherapy for 12 weeks. A comprehensive psychiatric diagnostic evaluation was performed on all patients, and all patients were evaluated for symptoms of gambling, depression, and anxiety using the South Oaks Gambling Screen, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Yale-Brown Obsessive Compulsive Symptoms Scale, and the Clinical Global Impression-Improvement Scale. The rating scales were administered at baseline and at the 12-week endpoint. In addition, the patients completed self-report questionnaires about their demographic status. Twelve of the 15 patients from the topiramate group completed the 12-week treatment. Nine of the 12 topiramate completers reported full remission of gambling behavior, and 3 completers had a partial remission. The CGI-improvement score was significantly better for the topiramate group at the 12-week visit as compared with baseline (F = 10.5, P < 0.01, df = 2.31). In the fluvoxamine treatment group 8/16 patients completed the study, and 6/8 fluvoxamine completers reported a full remission, and the remaining 2/8 fluvoxamine completers reported a partial remission. The fluvoxamine group showed improvement in the CGI-improvement score at week 12, although this difference was not significant (F = 3.7, P < 0.08, df = 2.31). Topiramate and fluvoxamine monotherapy may be effective in the treatment of pathologic gambling.

Adolescent↗

PubMedDate not supplied

Hormonal profile effects following dehydroepiandrosterone (DHEA) administration to schizophrenic patients.

Dehydroepiandrosterone (DHEA) is an important neurosteroid and has demonstrated efficacy in the improvement of mood and energy. The authors previously reported the efficacy of DHEA augmentation in the management of negative, depressive, and anxiety symptoms of schizophrenia. To characterize further the effects of DHEA administration and to describe any hormonal effects following DHEA augmentation of antipsychotic medication, several hormones were measured (TSH, prolactin, testosterone, insulin, and estradiol) in 27 chronic schizophrenic inpatients receiving DHEA or placebo augmentation for 6 weeks. No significant changes in hormonal blood measures were noted. At the study end point, an association was noted between DHEA-S and TSH levels (P < 0.05) as well as a change in DHEA-S and insulin levels (P < 0.001). A modest nonsignificant decrease in plasma testosterone was observed following DHEA treatment. In subjects receiving DHEA, change in testosterone levels was associated with improvement in anxiety (P < 0.05) and illness severity (P < 0.05). Findings in this preliminary study demonstrate minimal effects on hormonal profiles despite the theoretic possibility that DHEA may elevate various hormones (eg, testosterone) with potential long-term adverse effects. DHEA's clinical efficacy appears to be mediated by other mechanisms, including direct effects on membrane channel-coupled receptors.

Adjuvants, Immunologic↗

PubMedDate not supplied

Recurrence of panic disorder during pregnancy: a 7-year naturalistic follow-up study.

OBJECTIVES: The aim of this naturalistic follow-up study was to examine the effect of pregnancy as a predicting factor of relapse in patients with panic disorder (PD). METHODS: Eighty-five female patients with PD (between the ages of 20 and 35 years) were included in this study. They were divided into 2 groups based on whether the onset of PD had been during pregnancy (PD-pregnancy [PD-P]) or whether the onset of PD had been while not pregnant (PD-nonpregnant [PD-NP]). Patients were treated with paroxetine up to 40 mg/day for 12 months, and the full responders were tapered off their medication and were monitored for an additional 6 years. Treatment response was assessed using the Panic Self-Questionnaire (PSQ) with full response being defined as "0" panic attacks. Assessments using the PSQ were made at baseline and every 4 weeks for the first twelve months. During the 6-year drug-free follow-up period, patients were assessed using the PSQ every 3 months. Relapse was defined as the occurrence of a panic attack in any phase of the study. The effect of group membership (PD-P vs. PD-NP) and new pregnancies as risk factors for relapse were explored. RESULTS: Sixty-eight patients completed the 6-year follow-up, and each of the study groups (PD-P and PD-NP) was composed of 34 patients. Twenty-six of 34 (76.6%) patients in the PD-P group had another pregnancy, and 15/26 (57%) in this group experienced a relapse during the subsequent pregnancy. Three of 8 (37%) PD-P patients experienced a relapse without pregnancy. Among the second group (PD-NP), 18/34 (52.9%) became pregnant and 8/18 (44.4%) experienced a relapse at the time of pregnancy, whereas 4/16 (25%) experienced a relapse while not pregnant. Patients who relapsed during pregnancy had a more severe relapse (as defined by the severity of the PSQ score) compared with nonpregnant relapsers. CONCLUSIONS: Our naturalistic follow-up study demonstrated that pregnancy might confer an increased risk of relapse in PD. Moreover, when compared with patients who develop PD while not pregnant (PD-NP), patients who develop PD during pregnancy (PD-P) appear to have a higher risk of relapse at the time of a subsequent pregnancy (P < 0.001).

Adult↗

PubMedDate not supplied

Increased suicidal risk among smoking schizophrenia patients.

INTRODUCTION: Schizophrenia patients display a high suicidal risk, although this risk is difficult to predict. One of the variables associated with increased suicide risk is smoking. In the present study, we assessed the suicidal risk in schizophrenia patients, smokers and nonsmokers. We also evaluated the impact of various variables such as psychotic symptoms, impulsivity, and extra-pyramidal side effects on suicidal risk. METHODS: Sixty-one schizophrenia patients responded to a battery of measures, including the suicidal risk scale (SRS), the positive and negative syndrome scale (PANSS), the impulsivity control scale, and the Simpson Angus Scale for extrapyramidal side effects. The effect of smoking on the various measures, especially suicidal risk, was examined. RESULTS: Schizophrenia patients who smoke obtained higher PANSS scores (both total score and positive and negative subscales), but did not differ on the Simpson Angus scale of extrapyramidal side effects. They also exhibited higher suicide risk as reflected by higher scores on the SRS, and a trend for higher impulsivity as measured by the impulsivity control scale. Women that smoked had higher SRS scores as compared with female nonsmokers, and also higher than in males, smokers and nonsmokers. Smoking and a history of suicide attempt predicted in our regression analysis a higher SRS score. When conducting separate analyses for the male and female patients, the significant contributors were the PANSS total score among the males and the number of pack-years among the female patients. CONCLUSIONS: Despite hints toward the role of smoking in suicidal behavior in Schizophrenia, especially among female patients, more studies are needed to elucidate the association between smoking and suicidality in schizophrenia patients.

Female↗

PubMedDate not supplied

Sildenafil citrate for the sexual dysfunction in antidepressant-treated male patients with posttraumatic stress disorder. A preliminary pilot open-label study.

BACKGROUND: Previous studies have suggested that posttraumatic stress disorder (PTSD) may be associated with pervasive sexual dysfunction. Sildenafil citrate was established as a highly effective and well-tolerated oral agent for the treatment of sexual dysfunction of various etiologies. There are no studies that have examined the efficacy of oral sildenafil in PTSD patients with sexual dysfunction. OBJECTIVE: The current study evaluated the impact of sildenafil added to an ongoing antidepressive treatment in male PTSD patients. METHODS: Ten consecutive male PTSD patients who complained of sexual dysfunction were enrolled in an open-label 4-week fixed-dose study of sildenafil citrate 50 mg/day p.r.n. Patients were evaluated at baseline and after treatment with the Clinician-Administered PTSD Scale (CAPS); sexual function assessments were performed using the International Index of Erectile Function. RESULTS: All patients completed the study and statistically significant improvement was observed in all evaluated domains of sexual functioning: erectile function (53.5%), orgasmic function (40.3%), sexual desire (53%), intercourse satisfaction (82%) and overall satisfaction (57.4%). Oral sildenafil treatment appeared to be well tolerated and no single patient stopped the treatment. Improvements in various CAPS subscales were also obtained; however, there was no significant correlation between improvement in sexual functioning and the changes in CAPS subscale scores. CONCLUSION: Sildenafil seems to be an efficacious, safe and well-tolerated treatment of sexual dysfunction in antidepressant-treated male PTSD patients.

Adult↗