Search PubMed⌕ Search

Biomedical subjects

Moshe Kotler

Publications and source records attributed to Moshe Kotler.

At least 37 records · Page 2Linked to original sources
PubMed2006

Analysis of clinical characteristics and antipsychotic medication prescribing practices of first-episode schizophrenia in Israel: a naturalistic prospective study.

BACKGROUND: Investigation of the clinical presentation and treatment of first-episode psychosis is important in order to exclude effects of age, chronic illness, long-term treatment and institutionalization. The aim of this descriptive study was to investigate the management practices of first-episode schizophrenia in a cohort of patients in Israel and to document use of the various "typical" or "atypical" antipsychotic agents. METHOD: Fifty-one consecutive patients (26 M, 25 F) with first-episode psychosis were recruited for study participation and were administered either typical or atypical antipsychotic medications in a naturalistic manner. RESULTS: While an approximately equal number of subjects received typical and atypical medications at illness onset, a prominent shift to atypical antipsychotic treatment occurred over the study course; 18 subjects had medication class shifts: 17 from typical to atypical, and one from atypical to typical. Negative symptoms did not affect length of hospitalization, but were associated with aggression. Higher depression rates were noted in patients with long hospitalizations who received typical antipsychotic medications. Immigrants were admitted at an age approximately four years older than native-born Israelis. CONCLUSIONS: The prominent shift from "typical" to "atypical" antipsychotic medications may indicate sensitivity of first-episode psychotic patients to side-effects of "typical" medications and prominence of use of atypical medications in this patient subpopulation be it due to improved efficacy over time or successful marketing. Unique cultural and population characteristics may contribute to the manifestation of first-episode psychosis and suggest the importance of more effective outreach to the immigrant population in order to manage an apparent treatment delay.

Adolescent↗
PubMed2005

Analysis of an association between the COMT polymorphism and clinical symptomatology in schizophrenia.

Based on their metabolic inactivation of dopamine and norepinephrine, genes encoding the catechol-O-methyltransferase (COMT) enzyme are appropriate candidates to consider in the pathogenesis of schizophrenia. COMT enzyme activity is regulated by a common polymorphism causing substantial variations in enzymatic activity, and evidence for allelic or genotypic association with cognitive and behavioral features of schizophrenia has been noted. Since the role of COMT in schizophrenia remains inconclusive, we determined whether any association exists between COMT genotypes and clinical symptomatology in a large cohort of schizophrenia subjects. DNA was extracted from peripheral blood in 111 patients with DSM-IV criteria schizophrenia (77 M, 34 F) and genotyped for COMT polymorphisms. Subjects were also were rated by means of the PANSS and the CGI. No association was found between COMT genotype or allele frequency and gender. No associations were observed between COMT and CGI or PANSS scores. Our findings do not support hypotheses regarding associations between COMT polymorphisms and clinical state in schizophrenia, contrary to other studies suggesting involvement of the COMT polymorphism with schizophrenia phenotype. Thus, while speculative, it may be suggested that a modifying gene may be required in order for the COMT polymorphism to manifest at the clinical level in schizophrenia with one set of susceptibility genes being more sensitive to COMT enzyme variability than others.

Adult↗
PubMed2005

Improvement of extrapyramidal symptoms following dehydroepiandrosterone (DHEA) administration in antipsychotic treated schizophrenia patients: a randomized, double-blind placebo controlled trial.

Recent investigation in schizophrenia indicated dehydroepiandrosterone (DHEA) levels to be inversely correlated with extrapyramidal symptomatology (EPS). This study thus investigates the effect of DHEA administration on medication-induced EPS. Inpatients with schizophrenia or schizoaffective disorder were randomized in double-blind fashion to receive either 100 mg DHEA or placebo in addition to a constant dosage of antipsychotic medication. Parkinsonism showed a favorable effect of DHEA with a significant time effect (p < 0.0001), as well as a significant group by time interaction (p < 0.05) and with no change noted on akathisia. Change of DHEA blood levels was negatively associated with change of Parkinsonism (p < 0.05) as well as with change of total EPS ratings (p < 0.05). DHEA appears to demonstrate a significant effect on EPS, with improvement observed particularly in Parkinsonian symptoms.

Adult↗
PubMed2005

Protection of cultured Cyprinus carpio against a lethal viral disease by an attenuated virus vaccine.

Massive mortality of koi and common carp--Cyprinus carpio species--has been observed since 1998 in many countries worldwide, resulting in severe economic losses. The cause of the disease is an as yet unclassified large DNA virus, designated carp nephritis gill necrosis virus (CNGV) or koi herpes virus (KHV). Previously, we demonstrated that the wild type CNGV lost its pathogenecity following serial transfer in cell culture, and that clones isolated from the attenuated population can be used as a prophylactic vaccine. Here, we describe the basic conditions required for proper fish immunization so that a protection protocol may be devised. We demonstrated that carps are very sensitive to the pathogenic and the attenuated viruses, and short immersion of fish in water containing the viruses is sufficient for infection. The infection of fish with the pathogenic and the attenuated viruses is temperature-restricted; fish held at the non-permissive temperature, immediately following infection, were not affected by the pathogenic virus, and were not rendered resistant to the disease. Thus, propagation of the virus in the fingerlings is a pre-requisite for immunization. In order to increase the number of random mutations in the genome of the attenuated virus, and thus, reduce the possibility of the attenuated virus reverting to pathogenic, we irradiated it and selected additional clones appropriate for vaccination. The results of our study suggest that a safe and efficient prophylactic vaccine can be developed by selecting an appropriate attenuated virus.

Animals↗
PubMed2005

Reduced platelet vesicular monoamine transporter density in smoking schizophrenia patients.

Brain vesicular monoamine transporter 2 (VMAT2) has a critical role in the regulation of monoaminergic neurotransmission. In our previous study we have found decreased platelet VMAT2 density in healthy habitual smokers. Schizophrenia is associated with high rate of cigarette smoking. In the present study we assessed platelet VMAT2 pharmacodynamic characteristics in a population of medicated schizophrenia patients (n=36) comparing smokers (n=23) vs. non-smokers (n=13). A significant decrease in platelet VMAT2 density (24%, p=0.005) was found in the smokers compared to the non-smokers . This decrease was not ascribed to the pharmacotherapy. An inverse correlation was found in the smokers between the platelet VMAT2 density and the severity of schizophrenia as assessed by the positive and negative syndrome scale (PANSS). Our observation in schizophrenia patients is consistent with that found in healthy smokers. The complex relationship between VMAT2 expression, cigarette smoking and schizophrenia merits a further large scale study.

Adult↗
PubMed2005

Sustained-release bupropion versus naltrexone in the treatment of pathological gambling: a preliminary blind-rater study.

BACKGROUND: Pathological gambling (PG) is a relatively common and highly disabling impulse control disorder. A range of psychotherapeutic agents, including selective serotonin reuptake inhibitors, mood stabilizers, and opioid antagonists, has been shown to be effective in the treatment of PG. The use of selective serotonin reuptake inhibitors and opioid antagonists for PG is consistent with the observation that PG shares features of both the obsessive-compulsive spectrum disorders and addictive disorders. The aim of the study is to compare the effectiveness of sustained-release bupropion versus naltrexone in the treatment of PG. METHODS: Thirty-six male pathological gamblers were enrolled in our study. A comprehensive psychiatric diagnostic evaluation was performed at baseline on all patients, and patients were screened for symptoms of gambling, depression, and anxiety using the South Oaks Gambling Screen, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression-Severity Scale. In addition, the patients completed self-report questionnaires about their demographic status. Patients were randomized in 2 groups and received either naltrexone (n = 19) or sustained-release bupropion (n = 17) for 12 weeks in a parallel fashion. Treatment response was monitored using the Clinical Global Impression-Improvement Scale which was performed at weeks 2, 4, 8, and 12. Patients were also assessed for the presence of gambling behavior via an unstructured interview, which was also performed at weeks 2, 4, 6, 8, and 12. Raters were blind to the study treatment. RESULTS: The majority of patients responded well to the drug treatment. Twelve of 17 patients in the sustained-release bupropion group completed the 12-week study, and 13 of 19 naltrexone patients completed the study. Nine (75%) of the 12 completers were rated as full responders in the sustained-release bupropion group versus 10 (76%) of 12 in the naltrexone group. Three (25%) of 12 completers in the bupropion group were rated as partial responders. In the naltrexone group, 3 (23%) of 13 completers were rated as partial responders. Full response was defined as the absence of gambling for a 2-week duration together with improvement on the Clinical Global Impression-Improvement Scale. Partial response was defined as a decrease in the frequency of gambling behavior and a decrease in the amount of money spent on gambling. CONCLUSION: This preliminary study shows that sustained-release bupropion may be effective as naltrexone in the treatment of PG. Further studies are needed to confirm our findings.

Adult↗
PubMed2005

Detection of carp interstitial nephritis and gill necrosis virus in fish droppings.

Carp interstitial nephritis and gill necrosis virus (CNGV) is an unclassified large DNA virus that morphologically resembles members of the Herpesviridae but contains a large (ca. approximately 280-kbp) linear double-stranded DNA. This virus has also been named koi herpesvirus, koi herpes-like virus, and cyprinid herpesvirus 3. CNGV is the cause of a lethal disease that afflicts common carp and koi. By using immunohistochemistry, molecular analysis, and electron microscopy we previously demonstrated that this virus is present mainly in the intestine and kidney of infected fish. Based on these observations, we postulated that viruses and/or viral components may appear in droppings of infected carp. Here we report that (i) by using PCR we demonstrated that fish droppings contain viral DNA, (ii) fish droppings contain viral antigens which are useful for CNGV diagnosis, and (iii) fish droppings contain active virus which can infect cultured common carp brain cells and induce the disease in naïve fish following inoculation. Thus, our findings show that CNGV can be identified by using droppings without taking biopsies or killing fish and that infectious CNGV is present in the stools of sick fish. The possibility that fish droppings preserve viable CNGV during the nonpermissive seasons is discussed.

Animals↗
PubMed2005

Description of an as yet unclassified DNA virus from diseased Cyprinus carpio species.

Numerous deaths of koi and common carp (Cyprinus carpio) were observed on many farms throughout Israel, resulting in severe financial losses. The lethal viral disease observed is highly contagious and extremely virulent, but morbidity and mortality are restricted to koi and common carp populations. Diseased fish exhibit fatigue and gasping movements in shallow water. Infected fish had interstitial nephritis and gill necrosis as well as petechial hemorrhages in the liver and other symptoms that were not consistent with viral disease, suggesting a secondary infection. Here we report the isolation of carp nephritis and gill necrosis virus (CNGV), which is the etiologic agent of this disease. The virus propagates and induces severe cytopathic effects by 5 days postinfection in fresh koi or carp fin cell cultures (KFC and CFC, respectively), but not in epithelioma papillosum cyprini cells. The virus harvested from KFC cultures induced the same clinical signs, with a mortality of 75 to 95%, upon inoculation into naive koi and common carp. Using PCR, we provide final proof that the isolated virus is indeed the etiologic agent of food and ornamental carp mortalities in fish husbandry. Electron microscopy revealed viral cores with icosahedral morphology of 100 to 110 nm that resembled herpesviruses. Electron micrographs of purified pelleted CNGV sections, together with viral sensitivities to ether and Triton X-100, suggested that it is an enveloped virus. However, the genome of the isolated virus is a double-stranded DNA (dsDNA) molecule of 270 to 290 kbp, which is larger than known herpesviruses. The viral DNA seems highly divergent and bears only small fragments (16 to 45 bp) that are similar to the genomes of several DNA viruses. Nevertheless, amino acid sequences encoded by CNGV DNA fragments bear similarities primarily to members of the Poxviridae and Herpesviridae and to other large dsDNA viruses. We suggest, therefore, that the etiologic agent of this disease may represent an as yet unclassified virus species that is endemic in C. carpio (carp).

Animals↗
PubMed2005

Video testimony of long-term hospitalized psychiatrically ill Holocaust survivors.

OBJECTIVE: Many Holocaust survivors who have both psychotic disorders and residual symptoms of posttraumatic stress disorder (PTSD) remain chronically hospitalized in psychiatric institutions. This study investigated the clinical benefits of a therapeutic process facilitating a detailed videotaped account of traumatic experience (testimony method) in elderly long-term hospitalized Holocaust survivors. METHOD: Twenty-four schizophrenia patients (mean age=72.2 years) who were chronically hospitalized in Israeli state psychiatric hospitals underwent assessment by blind rating with a battery of psychiatric rating scales before and 4 months after extensive videotaped interview. The rating scales included the Positive and Negative Syndrome Scale; Clinical Global Impression (CGI); Mini-Mental State Examination (MMSE); Clinician-Administered PTSD Scale, Form 2; and Structured Interview for Disorders of Extreme Stress. Full pre- and postinterview data were available for 21 patients. RESULTS: Thirty-eight percent of the patients met the criteria for PTSD at the first interview, compared with only 19% at the second interview. The patients had significant reductions in functional impairment and in the severity and intensity of all posttraumatic symptom clusters (intrusion, avoidance, hyperarousal); the avoidance cluster showed the most reduction. Eleven subjects had an improvement of 30% or more in total posttraumatic severity score. No differences in Positive and Negative Syndrome Scale, MMSE, Structured Interview for Disorders of Extreme Stress, and CGI total scores were noted postinterview or between the two preinterview evaluation batteries in the comparison group. Female patients had a higher prevalence of PTSD symptoms. Total Clinician-Administered PTSD Scale, Form 2, scores and total Positive and Negative Syndrome Scale scores were inversely correlated both at baseline and at follow-up. CONCLUSIONS: Study observations suggest clinical benefits of the testimony method in the alleviation of many posttraumatic symptoms, but not psychosis, in a cohort of psychiatrically ill Holocaust survivors, despite an interval of as many as 60 years since the traumatic events. The findings have implications for care and rehabilitation of patients many years after acute traumatic events.

Aged↗
PubMed2005

Prenatal exposure to influenza and the risk of subsequent development of schizophrenia.

Various events occurring during pregnancy might influence the normal neurogenesis of fetus brain, including exposure to the influenza virus. Several studies have attempted to find a relationship between exposure to influenza virus and the onset of schizophrenic behavior in childhood or adulthood, however results remain contradictory. In this review we describe several animal and human studies that show or do not show a relationship between exposure to the influenza virus during pregnancy and the subsequent development of schizophrenia.

Animals↗
PubMed2005

[Reform in mental health services--from whence and to where].

For years the subject of mental health has been neglected in Israel, and reform of mental health services is now of paramount importance. Psychiatric medicine has altered considerably over the years, and emphasis is shifting from treatment in mental health institutions to treatment at the community level. This transition is the result of the awakening of groups in our society advocating civil rights for the mentally ill and their integration into the community. This process is also bolstered by the advent of new anti-psychotic drugs. However, the social and medical infrastructure set up to deal with these issues has been found lacking. Over the past few years the Minister of Health has appointed a number of committees to address this issue, and they have all recommended extensive reform of mental health services in Israel. The recommendations handed down by the committees are for: (1) Restructure of mental health services, with emphasis on community services and gradual reduction of psychiatric beds; (2) Allocation of additional funding specifically ear-marked for the mentally challenged, enabling transfer of stabilized patients out of the hospital setting and often lengthy and unnecessary hospitalization, into community rehabilitation centers; (3) Transfer of responsibility for health insurance for mentally ill people from the State to the Health Funds, enabling integration of psychiatric treatment into the general treatment framework. The reform has already been initiated. This body of work will review the stages, processes and the difficulties that preceded the reform.

Community Mental Health Services↗
PubMed2005

Psychiatric admissions and hospitalization in Israel: an epidemiologic study of where we stand today and where we are going.

BACKGROUND: Analysis of the trends in psychiatric admissions and discharges is necessary to correctly plan and distribute resources, especially given the current international climate of "deinstitutionalization." Israel, too, is implementing "reform" in the national psychiatric system - to transfer psychiatric treatment from a hospital to a community setting. OBJECTIVES: To analyze admission and discharge patterns, explore trends in psychiatric hospital length of stay, and compare these characteristics between first-episode and chronic patients, between children, youth and adults, and between hospitals. METHODS: All admissions and discharges from inpatient psychiatric wards between the years 2000 and 2004 were analyzed and characterized according to age, length of hospitalization, legal status, and nature of admitting institution (state hospital, health fund, general hospital). RESULTS: Mean length of stay in adults decreased during the 5 year study period, from 37.6 days in 2000 to 36.4 days in 2004. In years with higher admissions, hospital stay was shorter (P < 0.05). Length of stay in psychiatric wards in general hospitals was shorter than in state hospitals (P < 0.001). In contrast to adults and children, length of stay among adolescents showed a gradual increase (P < 0.05). Involuntary hospitalization comprised 25.3% of all admissions, and 16.8% of discharged patients were re-admitted within 30 days. A dramatic decrease (24.3%) in the number of chronic hospitalizations was noted. CONCLUSIONS: Various factors may account for these developments. Protracted hospitalizations may be reduced through changes in various aspects of treatment planning and psychiatric care continuum. The decrease in number of admissions, length of stay and number of chronically admitted patients remains in line with international practices. Particular attention needs to be devoted to planning and funding so that availability of community services matches reduction in psychiatric hospitalization.

Adolescent↗
PubMed2005

Psychiatric inpatients' reactions to the SARS epidemic: an Israeli survey.

BACKGROUND: The threat of the potential spreading of the SARS epidemic caused significant stress to many individuals from non-affected countries. In this study, we investigated whether the SARS threat affected the subjective mood and behavior of Israeli patients with schizophrenia and compared their reactions with those noted in their clinical staff. METHODS: Subjects were evaluated with a specially designed questionnaire and a modified form of the Spielberger Scale for State Anxiety. RESULTS: As compared to staff, patients had higher scores on the Modified Spielberger State Anxiety Scale. However, many responses (e.g., dysphoria) to the SARS threat did not differ from staff. Patients felt more protected by the authorities and some perceived the epidemic in a psychotic manner. CONCLUSIONS: It seems that patients attempt to reduce the effect of external stressors by living in an "autistic bubble" (in which outside threats cannot enter) or by denying the significance of these stressors and over-emphasizing the power of medical authorities to protect them. On the other hand, some patients also psychotically interpreted these stressors.

Adult↗
PubMed2004

Abrogation of Vif function by peptide derived from the N-terminal region of the human immunodeficiency virus type 1 (HIV-1) protease.

The human immunodeficiency virus type 1 (HIV-1) auxiliary gene vif is essential for virus propagation in peripheral blood lymphocytes, macrophages, and in some T-cell lines. Previously, it was demonstrated that Vif inhibits the autoprocessing of truncated HIV-1 Gag-Pol polyproteins expressed in bacterial cells, and that purified recombinant Vif and Vif-derived peptides inhibit and bind HIV-1 protease (PR). Here we show that Vif interacts with the N-terminal region of HIV-1 PR, and demonstrate that peptide derived from the N-terminal region of PR abrogates Vif function in non-permissive cells. Specifically, we show that (i) Vif protein binds HIV-1 PR, but not covalently linked tethered PR-PR; (ii) the four amino acids residing at the N terminus of HIV-1 PR are essential for Vif/PR interaction; (iii) synthetic peptide derived from the N terminus of HIV-1 PR inhibits Vif/PR binding; and (iv) this peptide inhibits the propagation of HIV-1 in restrictive cells. Based on these data, we suggest that Vif interacts with the dimerization sites of the viral protease, and that peptide residing at the N terminus of PR abrogates Vif function(s).

Base Sequence↗
PubMed2004

Increased circulatory dehydroepiandrosterone and dehydroepiandrosterone-sulphate in first-episode schizophrenia: relationship to gender, aggression and symptomatology.

Dehydroepiandrosterone (DHEA) is a major circulating neurosteroid in humans and its administration has demonstrated efficacy in the improvement of mood, with increased energy, interest, confidence and activity levels. Since recent findings have suggested the role of neurosteroids in general, and DHEA in particular, in the symptomatology and pharmacotherapy of schizophrenia patients with chronic illness, we investigated DHEA and DHEA-S blood levels in individuals in their first-episode of psychosis in order to exclude effects of age, chronic illness, long-term treatment and institutionalization. Blood levels for DHEA, DHEA-S and cortisol were obtained for 37 first-episode schizophrenia subjects and 27 normal age- and sex-matched controls and correlated with a range of clinical and side-effect rating scales. Baseline DHEA and DHEA-S levels were significantly higher in schizophrenia patients (p<0.05 and p<0.001, respectively). No gender differences were noted in DHEA levels; however, DHEA-S levels were significantly higher in male patients. DHEA-S levels inversely correlated with severity of illness (p<0.05) and aggressive behavior (p<0.05). Patients with higher DHEA-S levels tended to have shorter hospitalizations. Results suggest that individuals in their first-episode of schizophrenia psychosis may develop a neurosteroid response to the first onset of psychosis, which may be associated with a reduction in various adverse clinical features including aggression. Such a putative mechanism may become desensitized with the onset of chronic illness. While preliminary, these results further imply the role of these neurosteroids in the pathophysiology and management of schizophrenia.

Adult↗
PubMed2004

Amplified detection of telomerase activity using electrochemical and quartz crystal microbalance measurements.

Telomerase is considered as an important biomarker for cancer cells. Two different methods for the amplified electrochemical and microgravimetric quartz-crystal-microbalance detection of telomerase activity originating from HeLa cancer cells are described. One method involves the telomerization of a primer (1) linked to the electrode, in the presence of telomerase from HeLa cell extract and dNTP, followed by the hybridization of a biotin-labeled nucleic acid (2) that is complementary to the telomere repeat units. The subsequent binding of an avidin-alkaline phosphatase conjugate (3) that catalyzes the oxidative hydrolysis of 5-bromo-4-chloro-3-indolyl phosphate (4) results in the precipitation of the insoluble product (5) on the electrode. The second method involves the telomerization of the primer (1) associated with the electrode, in the presence of the telomerase-containing HeLa cell extract and the dNTP nucleotide mixture that includes biotin-labeled dUTP. The telomerization leads to the labeling of the telomeres with biotin labels. The association of the avidin-alkaline phosphatase conjugate (3) to the biotin labels results in the biocatalyzed transformation of (4) to (5) and the formation of a precipitate on the electrode or the Au-quartz crystal. As numerous precipitate molecules are formed as a result of the formation of a single telomere, the methods represent routes for the amplified detection of telomerase activity. The formation of the precipitate on the respective transducers is probed by following the changes in the electrode resistance using chronopotentiometry, or by following the frequency changes of the piezoelectric quartz crystals. The amount of precipitate generated on the electrodes is controlled by the concentration of the HeLa cancer cells. The methods enable the detection of telomerase activity that is extracted from 1000 HeLa cancer cells.

Biomarkers, Tumor↗
PubMed2004

Electronic transduction of HIV-1 drug resistance in AIDS patients.

A drug composition consisting of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) is commonly used in AIDS therapy. A major difficulty encountered with the therapeutic composite involves the emergence of drug-resistant viruses, especially to the PIs, regarded as the most effective drugs in the composition. We present a novel bioelectronic means to detect the appearance of mutated HIV-1 exhibiting drug resistance to the PI saquinavir. The method is based on the translation of viral RNA, the association of cleaved or uncleaved Gag polyproteins at an electrode surface functionalized with the respective antibodies, and the bioelectronic detection of the Gag polyproteins associated with the surface. The bioelectronic process includes the association of anti-MA or anti-CA antibodies, the secondary binding of an antibody-horseradish peroxidase (HRP) conjugate, and the biocatalyzed precipitation of an insoluble product on the electronic transducers. Faradaic impedance measurements and quartz crystal microbalance analyses are employed to follow the autoprocessing of the Gag polyproteins. The method was applied to determine drug resistance in infected cultured cells and also in blood samples of consenting AIDS patients. The method described here is also applicable to the determination of drug effectiveness in AIDS patients and to screening of the efficiency of newly developed drugs.

Anti-HIV Agents↗