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Biomedical subjects

Y Barak

Publications and source records attributed to Y Barak.

At least 19 recordsLinked to original sources

Suicidality and second generation antipsychotics in schizophrenia patients: a case-controlled retrospective study during a 5-year period.

RATIONALE: Rates of attempted suicide for individuals with schizophrenia are approaching 30%. Attempted suicide is among the most potent predictors of subsequent suicide. Several studies suggest that suicide is more likely to occur in patients who are not being adequately treated or not being treated at all. An effort was made in the last decade to evaluate the antisuicide effects of pharmacological treatment in schizophrenia with emphasis on the role of the newer second-generation antipsychotics (SGA). OBJECTIVE: The aim of the present study was to assess in a large cohort of schizophrenia patients the effects of exposure to SGA on suicidality of patients suffering from schizophrenia or schizoaffective disorder. The study is a retrospective case-controlled evaluation over a 5-year period undertaken in a large university affiliated tertiary care psychiatric hospital. METHODS: Between January 1998 and December 2002, all records of admissions of schizophrenia or schizoaffective disorder patients (ICD-10) were assessed. Data as to age, gender, diagnosis, suicide attempt prior to admission, treatment with antipsychotic medication, dose and duration of treatment (mg daily, duration) with SGA was extracted from patients' files. All patients who had attempted suicide prior to admission were defined as the index group. The case-controlled group was comprised of the next admission of a patient suffering from schizophrenia (or schizoaffective disorder), matched for gender and age, who did not attempt suicide. RESULTS: Records of 756 patients (4486 admissions for said period) were analyzed (56.6% male, mean age 39.1+/-13.5 years). Amongst 378 patients who attempted suicide (index group), 16.1% were exposed to SGA while 37% were exposed in the control group (P=0.0001). The protective effect (odds ratio) of treatment by SGA was 3.54 (95%CI: 2.4-5.3). Risperidone was more frequently prescribed in the control group (54.3%) and had a larger effect-size than olanzapine (3.16 versus 1.76), although not statistically significant. Clozapine was prescribed only to a few patients. CONCLUSIONS: Schizophrenia patients exposed to both risperidone and olanzapine may gain protection from suicidality. The antisuicide effects seem to differ between SGAs. The long duration and large sample size support this finding, despite the retrospective nature of this study.

Adult↗

T cell vaccination in multiple sclerosis relapsing-remitting nonresponders patients.

Myelin autoreactive T cells are involved in the pathogenesis of multiple sclerosis (MS) and lead to propagation of the disease. We evaluated the efficacy of T cell vaccination (TCV) therapy for patients with aggressive relapsing-remitting MS who failed to respond to immunomodulatory treatments. Twenty nonresponders relapsing-remitting MS patients were immunized with autologous attenuated T cell lines after activation with synthetic myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) encephalitogenic peptides. Each patient received three vaccinations in 6- to 8-week intervals. Annual relapse rate decreased from 2.6 to 1.1, P = 0.026. Neurological disability stabilized as compared with the 2- and 1-year pretreatment progression rates. Significant reduction in the number and volume of active lesions, as well as reduction in T2 lesion burden, was demonstrated by quantitative MRI analysis. No serious adverse events were observed. Our findings suggest that TCV has beneficial clinical effects in MS patients who, in spite of immunomodulatory treatments, continue to deteriorate. TCV could serve as a potential alternative therapy for this subgroup of nonresponders patients.

Adult↗

Effects of discontinuation of long-term anticholinergic treatment in elderly schizophrenia patients.

Anticholinergic medication (ACM) is frequently used in psychiatry to treat the side-effects of D2 blocking agents. However, ACM is not without adverse effects and, in the elderly, cognitive and memory impairments have been emphasized. The aim of this study was to evaluate the effects of discontinuation of ACM on cognitive functions in a group of elderly chronic schizophrenia patients. Twenty-seven elderly patients (age 60 years or older), who were diagnosed as suffering from schizophrenia (DSM-IV) and receiving ACM in addition to antipsychotic treatment, were enrolled. Before and after ACM was discontinued, the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) subscale was administered. Twenty-one patients completed the study. All were receiving Akineton (biperiden), 2-6 mg daily before the study. Significant improvement in the ADAS-Cog total score was demonstrated (P < 0.03), as well as in the ideational praxia and orientation subscales. Improvement was correlated with the previous dose of biperidin. No adverse events or emergent extrapyramidal symptoms were noted. Discontinuation of ACM may be warranted in chronic schizophrenia patients since it may improve cognitive functioning with no adverse effects.

Aged↗

Cognitive impairment in probable multiple sclerosis.

OBJECTIVES: To evaluate and characterise cognitive impairment in the very early stage of multiple sclerosis (MS), in which patients are still diagnosed as suffering from probable MS. METHODS: The Brief Repeatable Battery-Neuropsychological (BRB-N) that has been validated for MS patients was used. Abnormal performance was defined as one standard deviation below the mean reported for healthy age matched subjects. Neurological disability and brain magnetic resonance imaging (MRI) were performed for all patients. Correlation coefficients were calculated between disease burden variables and performance on the BRB-N. RESULTS: Sixty seven patients with probable MS were evaluated within a mean of one month of the onset of new neurological symptoms. Evidence for the presence of cognitive impairment was shown in 53.7% of patients. Verbal abilities and attention span were most frequently affected. Impairment was not correlated with neurological disability or MRI disease burden. CONCLUSION: Prevalent cognitive impairment already exists at onset of MS.

Adolescent↗

Estimation of autonomic response based on individually determined time axis.

The analysis of the time-dependence of autonomic response requires: 1. A reliable procedure for the quantification of autonomic activity under nonsteady conditions, such as an algorithm for time-frequency decomposition (ex. SDA. Wigner-Ville, or others). 2. The choice of an adequate time scale for focusing on the data: (a) the regular, universal time scale, independent of the unsteady physiological conditions, or (b) a time axis defined by specific events related to an applied perturbation, as the indicators of specific experimental or physiological conditions, so that each individual is considered according to his own intrinsic time scale. The alignment of the various subjects according to their intrinsic time scale, reflecting their individual response mechanisms, may help to disclose a common pattern of autonomic function. Using an absolute time scale to align and average results for different subjects may obscure the underlying mechanisms. Several examples of autonomic challenges are presented, in which the use of an individual time scale contributes to unveil a typical response pattern: tilt test in vasovagal syncope, the autonomic effect of active standing on hypertension, and the autonomic response to acute hypoxia.

Autonomic Nervous System↗

In vitro effects of recombinant TNF-alpha binding protein (rTBP-1) on hematopoiesis of HIV-infected patients.

Tumor necrosis factor-alpha (TNF-alpha) is believed to contribute to the hematopoietic failure often observed in patients with AIDS. Soluble TNF receptors (sTNFR) compete for TNF-alpha with cell surface receptors and thus may block its activity. The effect of the p55 sTNFR (recombinant TNF-binding protein-1 [rTBP-1]) on the clonogenic growth of hematopoietic progenitor cells from 27 HIV-infected patients was evaluated in comparison with 11 normal study subjects. Peripheral blood-derived, myelopoietic (i.e., granulomonocytic colony-forming cells [GM-CFC]) and erythropoietic (i.e, burst-forming unit, erythroid [BFU-E]) colonies were grown in 10-day semisolid cultures with increasing concentrations of rTBP-1. Significantly, dose-dependent increases occurred in GM-CFC from 17 of 21 AIDS patients and 12 of 21 in BFU-E at rTBP-1 concentrations of 1microg/ml to 25 microg/ml. In contrast, rTBP-1 failed to induce any appreciably increased colony formation in normal cell cultures. In 6 patients treated with highly active antiretroviral treatment (HAART), TBP-1 alone did not demonstrate the in vitro hematopoiesis-enhancing effect. This study may provide an initial step in development of therapeutic use of TBP as a TNF-alpha antagonist in HIV-infected patients who do not benefit sufficiently from antiretroviral treatment, and in other conditions in which increased levels of TNF-alpha may contribute to hematopoietic deficiencies.

Acquired Immunodeficiency Syndrome↗

Melatonin treatment for tardive dyskinesia: a double-blind, placebo-controlled, crossover study.

BACKGROUND: Antipsychotics remain the mainstay of drug intervention in the management of schizophrenia. However, long-term treatment with antipsychotics is associated with a variety of movement disorders, the most disabling of which is tardive dyskinesia (TD), which occurs in up to 50% of patients hospitalized with chronic schizophrenia. The pathophysiology of TD is still unclear and no definite treatment exists. Both dopamine receptor supersensitivity and oxidative stress-induced neurotoxicity in the nigrostriatal system are apparently implicated. The pineal hormone melatonin is a potent antioxidant and attenuates dopaminergic activity in the striatum and dopamine release from the hypothalamus. Thus, it may have a beneficial effect for both the treatment and prevention of TD. METHODS: Using a double-blind, placebo-controlled, crossover study, we evaluated the efficacy of 10 mg/d of melatonin for 6 weeks in 22 patients with schizophrenia and TD. The primary outcome measure was the change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. RESULTS: The decrease (mean +/- SD) in AIMS score was 2.45 +/- 1.92 for the melatonin and 0.77 +/- 1.11 for the placebo treatment groups (P<.001). No adverse events or side effects were noted. CONCLUSION: This is the first clinical evidence for efficacy of melatonin in the treatment of TD.

Adult↗

Survey of patient satisfaction in adult psychiatric outpatient clinics.

A client satisfaction survey was undertaken in two adult psychiatric outpatient clinics. The anonymous self-report questionnaire covering demographic, setting and satisfaction with service variables was endorsed by 203 participants. The mean age of the subjects was 42.5 +/- 19 years, with a small majority (58.6%) of females. Overall satisfaction with psychiatric care was high (79.8%). None of the demographic or setting variables correlated significantly with satisfaction. Psychoeducation was significantly correlated with level of satisfaction with services. These findings further emphasize the importance of psychoeducation by service providers in mental health.

Adult↗

A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis.

Previous work has implicated PPAR gamma in the regulation of CD36 expression and macrophage uptake of oxidized LDL (oxLDL). We provide evidence here that in addition to lipid uptake, PPAR gamma regulates a pathway of cholesterol efflux. PPAR gamma induces ABCA1 expression and cholesterol removal from macrophages through a transcriptional cascade mediated by the nuclear receptor LXR alpha. Ligand activation of PPAR gamma leads to primary induction of LXR alpha and to coupled induction of ABCA1. Transplantation of PPAR gamma null bone marrow into LDLR -/- mice results in a significant increase in atherosclerosis, consistent with the hypothesis that regulation of LXR alpha and ABCA1 expression is protective in vivo. Thus, we propose that PPAR gamma coordinates a complex physiologic response to oxLDL that involves particle uptake, processing, and cholesterol removal through ABCA1.

ATP Binding Cassette Transporter 1↗

PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is highly expressed in lipid-accumulating macrophages of the coronary artery. In light of this, the wide-spread clinical use of thiazolidinediones (TZDs) in the treatment of type II diabetes raises concerns about the role of PPAR-gamma in macrophage function and disease progression. To define the role of PPAR-gamma in macrophage biology, we used homologous recombination to create embryonic stem cells that were homozygous for a null mutation in the PPAR-gamma gene. We demonstrate here that PPAR-gamma is neither essential for nor substantially affects the development of the macrophage lineage both in vitro and in vivo. In contrast, we show it is an important regulator of the scavenger receptor CD36, which has been genetically linked to lipid accumulation in macrophages. Both 15-deoxy-Delta12,14prostaglandin J2 and thiazolidinediones have anti-inflammatory effects that are independent of PPAR-gamma. We show that PPAR-gamma is required for positive effects of its ligands in modulating macrophage lipid metabolism, but that inhibitory effects on cytokine production and inflammation may be receptor independent.

3T3 Cells↗

Late-onset multiple sclerosis.

OBJECTIVE: The onset of multiple sclerosis (MS) after age 50 is infrequent and presents a diagnostic challenge. The purpose of the present study was to review the prevalence, presentation, and clinical characteristics of late-onset MS. DESIGN: A retrospective chart review. SETTING: The Multiple Sclerosis Center at Sheba Medical Center, Israel. PARTICIPANTS: 640 patients with a definite diagnosis of MS. MEASUREMENTS: Diagnosis of MS was established according to Poser criteria and confirmed by brain magnetic resonance imaging (MRI) using our unit's computerized database. Late-onset MS was defined as the first presentation of clinical symptoms after the age of 50 years. For each patient, age, gender, clinical presentation, disease course, neurological involvement, disease duration, neurological disability assessed, and Progression Index (PI) were analyzed. All patients were interviewed using the structured clinical interview for DSM-IV, SCID-lifetime Hebrew version. RESULTS: Of 640 MS patients, 30 (4.6%) were diagnosed as suffering from late-onset MS. Mean age at onset was 53.5 +/- 3.1, range 50 to 62 years. Female to male ratio was 1.73:1. Mean disease duration was 7.6 years, range 2 to 11 years. In 50% of patients the disease course was relapsing-remitting. Motor symptoms were the most common neurological presentation at onset (63.3%). Major depressive episode was diagnosed in 6 out of 30 patients (20%) in the two years prior to the diagnosis of MS. After a mean disease duration of 7.6 years there was a marked increase in sphincteric and cerebellar involvement. In addition 7 out of 30 patients had suffered a major depressive episode within 4 years of diagnosis. Mean PI was 0.81, suggesting rapid neurological deterioration. CONCLUSIONS: Late-onset MS is not rare and may present as major depression and, although neurological presentation at onset is similar to that of young adults, progression to disability is more rapid and a primary progressive course is more prevalent.

Activities of Daily Living↗

A physiological replacement for polyvinylpyrrolidone (PVP) in assisted reproductive technology.

The technique of intracytoplasmic sperm injection (ICSI) requires mechanical immobilization of the sperm that are to be injected; damage thus caused to the sperm membrane is considered to be necessary to activate the sperm for fertilization. Mechanical immobilization and the injection procedure are facilitated by introducing the sperm into a viscous medium that will hinder motility: a solution of polyvinylpyrrolidone (PVP) has been used successfully for this purpose. PVP is an artificial polymer, which has been regarded as chemically inert, although adverse effects have been reported as a result of its use both in vivo and in vitro. Therefore, the use of hyaluronate, the natural component of the extracellular matrix of the cumulus-oocyte complex, was investigated as a replacement for PVP during ICSI. A solution of hyaluronate was found to be as effective as PVP in facilitating the injection procedure, its effect on sperm motility was readily reversible, and its use did not affect the outcome of the treatment cycles in terms of fertilization, pregnancy and live birth rates. Every attempt should be made to eliminate artificial factors in assisted reproductive procedures. Hyaluronate, a natural and readily degradable glycosaminoglycan can be used as a substitute for the artificial PVP polymer without jeopardising the outcome of the treatment cycle.

Adult↗

Autonomic response to hypobaric hypoxia assessed by time-dependent frequency decomposition of heart rate.

BACKGROUND: Acute hypoxia tolerance varies substantially among healthy individuals. We hypothesized that this variability results from a difference in autonomic (ANS) response to hypoxic stress. METHODS: Peripheral oxygen saturation, respiration and ECG were recorded from 21 healthy subjects (age, 29 +/- 7 yr) in an altitude chamber during normoxia, severe hypoxia (282 mm Hg), and mild hypoxia (360 mm Hg). Cardiovascular control was assessed by time-frequency decomposition of the heart rate signal applying the Selective Discrete Transform Algorithm (SDA). This procedure uses a variable time window, thus providing reliable physiological data even during transient states. Autonomic activity was quantified by power spectral density integrals over a 3-dimensional time-dependent spectral distribution of heart rate fluctuations. RESULTS: Subjects who had slower peripheral oxygen desaturation during severe hypoxia onset (mean 92.9 vs. 58.4 s) were those who displayed higher ANS activity in all ambient states, namely normoxia and hypoxia. These same subjects withstood hypoxia for significantly longer time periods (mean 313 vs. 244 s). CONCLUSION: Improved hypoxia tolerance is linked to enhanced autonomic activity, involving a better management of peripheral blood flow.

Adult↗

Animal-assisted therapy for elderly schizophrenic patients: a one-year controlled trial.

Animal-assisted therapy (AAT) has been used as a therapeutic tool in various psychiatric populations, but there have been no published studies with elderly schizophrenic patients. The authors evaluated, in a blinded, controlled manner, the effects of AAT in a closed psychogeriatric ward over 12 months. Subjects were 10 elderly schizophrenic patients and 10 matched patients (mean age: 79.1+/-6.7 years). The outcome measure was the Scale for Social Adaptive Functioning Evaluation (SAFE). AAT was conducted in weekly 4-hour sessions. Treatment encouraged mobility, interpersonal contact, and communication and reinforced activities of daily living (ADLs), including personal hygiene and independent self-care, through the use of cats and dogs as "modeling companions." The SAFE scores at termination showed significant improvement compared with baseline scores and were significantly more positive for the AAT group on both Total SAFE score and on the Social Functions subscale. AAT proved a successful tool for enhancing socialization, ADLs, and general well-being.

Activities of Daily Living↗

Stem cell transplantation in patients with severe congenital neutropenia without evidence of leukemic transformation.

Severe congenital neutropenia (CN) (Kostmann syndrome) is a hematologic disorder characterized by a maturation arrest of myelopoiesis at the promyelocyte/myelocyte stage of development. This arrest results in severe neutropenia leading to absolute neutrophil counts (ANC) below 0.2 x 10(9)/L associated with severe bacterial infections from early infancy. Data on over 300 patients with CN collected by the Severe Chronic Neutropenia International Registry (SCNIR) beginning in 1994 indicate that more than 90% of these patients respond to recombinant human granulocyte-colony stimulating factor (r-HuG-CSF) treatment with an ANC greater than 1. 0 x 10(9)/L. For patients who are refractory to r-HuG-CSF treatment and continue to have severe and often life-threatening bacterial infections, hematopoietic stem cell transplantation is the only currently available treatment. We report on a total of 11 patients with CN reported to the SCNIR who underwent transplantation for reasons other than malignant transformation between 1976 and 1998. Of these patients, 8 were nonresponders or showed only partial response to r-HuG-CSF treatment with ongoing infections. Results from these patients suggest that transplantation of stem cells from an HLA-identical sibling is beneficial for patients refractory to r-HuG-CSF. (Blood. 2000;95:1195-1198)

Adolescent↗

Multiple sclerosis-from probable to definite diagnosis: a 7-year prospective study.

OBJECTIVES: To investigate the rate of progression from probable to clinically definite multiple sclerosis (MS) and to define patients who had rapidly (within 1 year) progressed to a definite diagnosis. DESIGN: A 7-year prospective study. PATIENTS: A group of 163 patients experiencing their first episode of neurologic symptoms suggestive of MS. All patients had brain magnetic resonance imaging that demonstrated at least 3 demyelinating lesions at onset. RESULTS: Within the follow-up period (mean, 42 months; range, 13-84 months), 136 patients (83.4%) had an additional relapse and were thus defined as having clinically definite MS, whereas 27 patients (16.6%) were defined as having clinically probable MS. Most of the 136 patients with clinically definite MS (57.6%, 94 patients) experienced the additional relapse within 1 year. Demographic and clinical parameters at presentation were analyzed to identify variables predictive of rapid progression (within 1 year) to clinical definite MS. Motor involvement at onset was the only clinical parameter associated with rapid progression to a definite diagnosis. Survival curves demonstrated that polysymptomatic involvement and higher Extended Disability Status Scale score at presentation correlated with rapid progression to definite diagnosis. CONCLUSION: Most patients with a diagnosis of probable MS and positive brain magnetic resonance imaging will progress rapidly to clinically definite MS.

Adolescent↗