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We use a novel technique that allows for closed recirculation of vector genomes in the cardiac circulation using cardiopulmonary bypass, referred to here as molecular cardiac surgery with recirculating delivery (MCARD). We demonstrate that this platform technology is highly efficient in isolating the heart from the systemic circulation in vivo. Using MCARD, we compare the relative efficacy of single-stranded (ss) adeno-associated virus (AAV)6, ssAAV9 and self-complimentary (sc)AAV6-encoding enhanced green fluorescent protein, driven by the constitutive cytomegalovirus promoter to transduce the ovine myocardium in situ. MCARD allows for the unprecedented delivery of up to 48 green fluorescent protein genome copies per cell globally in the sheep left ventricular (LV) myocardium. We demonstrate that scAAV6-mediated MCARD delivery results in global, cardiac-specific LV gene expression in the ovine heart and provides for considerably more robust and cardiac-specific gene delivery than other available delivery techniques such as intramuscular injection or intracoronary injection; thus, representing a potential, clinically translatable platform for heart failure gene therapy. [ABSTRACT FROM AUTHOR]

Background: Little is known about the extent of heterogeneity of symptomatology in treated early-onset psychosis. The current study aims to quantify the extent of heterogeneity in trajectories of treated symptom severity in early-episode psychosis and their antecedents. Methods: Data were from 491 persons with early-episode psychosis from a clinical trial of haloperidol and risperidone. Positive and Negative Syndrome Scale (PANSS) administrations were used to measure symptom severity trajectories for (a) rapid treatment response scores over 4 weeks and (b) medium-term course over 24 weeks. Baseline antecedents included sex, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis, age of onset, the Premorbid Adjustment Scale, and a cognitive test battery. Symptom severity trajectories were calculated with mixed mode latent class regression modeling from which groups were derived. Results: Five groups based on PANSS scores over time were identified. Over 4 weeks, 3 groups with varied baseline PANSS scores (54–105) did not surpass 30% PANSS improvement. Another group improved and then was stable (n = 76,15.3%), and another showed marked improvement (n = 94,18.9%). Logistic regression showed that membership in the best response trajectory was associated with not having a diagnosis of schizophrenia, good premorbid functioning, and higher cognitive functioning, whereas membership in the poor response trajectory was associated with earlier age of onset and poorer cognitive functioning. Conclusion: Amelioration generally characterizes treated symptom severity. Age of onset, diagnosis, cognitive functioning, and premorbid functioning have prognostic value in predicting treatment response trajectories. [ABSTRACT FROM PUBLISHER]

Objectives: To examine the effect of risperidone on specific behavioral and psychological symptoms of dementia (BPSD) among patients with psychosis of Alzheimer's disease (AD).Methods: Post hoc exploratory analysis of data on 479 nursing-home patients with psychosis of AD from three 12-week, double-blind, placebo-controlled clinical trials. Criteria for psychosis of AD were a diagnosis of AD or mixed dementia and a rating of >/= 2 on any delusion or hallucination item of the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale when entering the trial. Mean changes from baseline to endpoint were examined for items on the Cohen-Mansfield Agitation Inventory (CMAI) and BEHAVE- AD.Results: On the CMAI, risperidone was significantly more effective than placebo in treating cursing or verbal aggression (p = 0.004), hitting (p < 0.001), performing repetitious mannerisms (p < 0.001), pacing, aimless wandering (p = 0.017), hoarding things (p = 0.02), hiding things (p = 0.02) and repetitive sentences or questions (p = 0.025). On the BEHAVE-AD, risperidone was significantly more effective than placebo in treating physical threats and/or violence (p = 0.001), agitation (other) (p = 0.001) and verbal outbursts (p = 0.026). Although analysis on individual hallucination and delusional items did not demonstrate specific responses, analyses of a composite of delusional items revealed significant drug-placebo differences.Conclusions: These data indicate that risperidone is effective in treating a variety of symptoms associated with psychosis of AD. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The goals of this study were to determine 1) the occurrence of various dissociative phenomena in patients with somatization disorder, 2) the occurrence of six different types of childhood interpersonal trauma in these patients, and 3) the nature of these patients' early family environment. METHOD: Twenty-two patients with somatization disorder and 19 medical comparison subjects completed the Structured Clinical Interview for DSM-IV Dissociative Disorders, the Childhood Trauma Interview, and the Family Functioning Scale. RESULTS: The somatization disorder patients reported significantly higher level of dissociative amnesia than the comparison subjects. The two groups reported similar levels of depersonalization, derealization, identity confusion, and identity alteration. Somatization disorder patients reported significantly greater childhood emotional abuse and more severe forms of physical abuse, relative to the comparison subjects, with chronic emotional abuse being the best predictor of unexplained symptoms. Childhood sexual abuse, separation/loss, and witnessing violence were equally common in the two groups. The somatization disorder group reported significantly more family conflict and less family cohesion. CONCLUSIONS: Only some types of dissociation are more severe in patients with somatization disorder, relative to medical comparison subjects. Many patients with somatization disorder are raised in an emotionally cold, distant, and unsupportive family environment characterized by chronic emotional and physical abuse. Sexual abuse is not a necessary prerequisite for the disorder. [ABSTRACT FROM AUTHOR]

Weiser M, Reichenberg A, Rabinowitz J, Knobler HY, Lubin G, Yazvitzky R, Nahon D, Gur RC, Davidson M. Cognitive performance of male adolescents is lower than controls across psychiatric disorders: a population-based study.Acta Psychiatr Scand 2004: 1–5.© Blackwell Munksgaard 2004.Psychiatric patients, as well as humans or experimental animals with brain lesions, often concurrently manifest behavioral deviations and subtle cognitive impairments. This study tested the hypothesis that as a group, adolescents suffering from psychiatric disorders score worse on cognitive tests compared with controls.As part of the assessment for eligibility to serve in the military, the entire, unselected population of 16–17-year old male Israelis undergo cognitive testing and screening for psychopathology by the Draft Board. We retrieved the cognitive test scores of 19 075 adolescents who were assigned any psychiatric diagnosis, and compared them with the scores of 243 507 adolescents without psychiatric diagnoses.Mean test scores of cases were significantly poorer then controls for all diagnostic groups, except for eating disorders. Effect sizes ranged from 0.3 to 1.6.As group, adolescent males with psychiatric disorders manifest at least subtle impairments in cognitive functioning. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to compare the rehospitalization rates of patients discharged from the hospital while being treated with risperidone, olanzapine, or conventional antipsychotics.Method: By using Israel's National Psychiatric Hospitalization Case Registry, rehospitalization status was monitored for all patients with schizophrenia who were discharged from any inpatient psychiatric facility in Israel while taking risperidone (N=268) or olanzapine (N=313) between Jan. 1, 1998, and Dec. 31, 1998, and a group of patients discharged during that time who were treated with conventional antipsychotics (N=458). Time to readmission over the course of 2 years was measured by the product-limit (Kaplan-Meier) formula.Results: The readmission rate for patients discharged while taking conventional antipsychotics was higher than the rates for patients treated with either risperidone or olanzapine. At 24 months, 67% of the risperidone-treated patients and 69% of the olanzapine-treated patients remained in the community, as compared to 52% of the patients treated with conventional antipsychotics.Conclusions: This study suggests that the rehospitalization rates of patients taking the novel antipsychotics risperidone and olanzapine are not different from each other and are considerably lower than the rate for patients treated with conventional antipsychotics. The results confirm findings of previous studies suggesting that the levels of overall effectiveness of risperidone and olanzapine are not very different and offers evidence that these drugs are more effective in preventing rehospitalization than conventional antipsychotic drugs. [ABSTRACT FROM AUTHOR]

Background: The extent of premorbid changes associated with the onset of schizophrenia are debated.Aims: The study examined cognitive and behavioural functioning prior to, and after, first hospitalisation for schizophrenia.Method: Data from the Israeli Draft Board Register of intelligence, social functioning and behaviour testing for all Israeli males aged 16-17 was linked with data from the National Psychiatric Hospitalisation Case Register. This identified 692 men who had been admitted to hospital for schizophrenia. Cases and non-cases matched on age and school were compared, as were cases aggregated by the time that had elapsed between testing and first admission to hospital.Results: Cases performed worse than non-cases on all measures. On Social Functioning and on Raven's Progressive Matrices-R, differences between cases and non-cases were progressively greater for cases admitted closer to the time of testing. These differences were greatest for persons tested after first psychiatric hospitalisation.Conclusions: The results confirm premorbid deficits associated with schizophrenia and support the hypothesis that decline is progressive. [ABSTRACT FROM AUTHOR]

Background: This study examined prevalence of perceived need for mental health assistance, characteristics of people with a perceived need, and how persons with a need who sought help were different from those who did not.Methods: A national random phone survey (n = 1,394) was conducted in Israel, which included questions about (1) perceived need for mental health assistance and (2) help seeking.Results: Prevalence of life-time and recent perceived need for males was 21% and 10.7%, and for females 31% and 15.1%. Of those with a perceived need, 31.4% of males and 41.6% of females had gone for help. Based on logistic regression models, the variables associated with need were being female, divorced, having a chronic physical disease, and low income (for males only), while predictors of help seeking were living in a big city and not being a recent immigrant. The major sources of help in descending order were: mental health professionals (46%), family physician (25%), family or friends (19%), and other (10%).Conclusions: A majority of people who feel that they need help for mental health problems do not get help. [ABSTRACT FROM AUTHOR]

We attempted to predict revolving door (RD) patterns of admission (four or more admissions with less than 2.5 years between consecutive admissions) in a random sample of 10% of all first admissions to psychiatric hospitals and psychiatric wards of general hospitals in Israel from 1983 to 1990 with follow-up into 1993. This included 4570 hospitalizations of 2220 patients. Data were extracted from the National Psychiatric Case Registry of the Ministry of Health. Almost 59% of the sample had only one admission, 41% had two or more, 23% had three or more, and 14% had four or more admissions. Patients with four or more admissions were all RD patients. They had an average of 200 days between admissions. The average number of admissions for RD patients was 6.17, and the average number of years between the first admission and the last admission was 3.28 years. Using discriminant analysis we correctly predicted 73.9% of the non-RD group (about chance level since 80% of the cases were non-RD) and 71.2% of the RD group (considerably better than chance, only 12.0% of the sample were RD). The main predictors of RD in descending order were not being married at the time of first hospitalization, unemployment and more severe initial diagnosis. The minor predictors were older age, more education and longer first admission. Substance abuse, patients ability to care for their affairs, voluntary status of first admission and suicide attempts did not predict RD.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

We studied the effects of escalating doses of recombinant human IL-1β in patients receiving high-dose chemotherapy and ABMT for metastatic breast cancer or malignant melanoma. Sixteen patients received IL-1β, 4 to 32 ng/kg/day administered subcutaneously for 7 days beginning 3 h after bone marrow infusion. Three patients at the highest dose level also received G-CSF following completion of IL-1β. All patients completed the 7 days of therapy. The majority of patients experienced chills and fever following one or more injections, and seven had severe pain at the injection site. There was one episode of hypotension and one episode of transient confusion at the highest dose level; other significant toxicity was not identified. Recovery of neutrophils to >0.5 × 109/l and platelet transfusion independence occurred at a median of 23 and 22 days, respectively, which was comparable to historical controls. The mean number of bone marrow colony-forming unit granulocyte–macrophage (CFU-GM) per 105 mononuclear cells on day +21 post-ABMT was more than twice that of control patients or patients receiving G-CSF or GM-CSF. A linear correlation was found between the dose of IL-1β and endogenous concentrations of several cytokines. These patients also displayed significantly higher concentrations of endogenous G-CSF compared to historical controls receiving GM-CSF. While IL-1β was moderately toxic and had no effect on recovery of peripheral blood counts after ABMT, the increased number of bone marrow CFU-GM suggests that the addition of G- or GM-CSF to a short course of IL-1β may accelerate hematologic recovery. [ABSTRACT FROM AUTHOR]

Background: Clozapine's effectiveness in reducing symptoms and facilitating discharge among patients with chronic schizophrenia who were resistant to neuroleptics was studied.Method: All 169 such patients in a public psychiatric hospital were given clozapine. BPRS ratings (0-5 scale) were completed before treatment and 21 months later. Patients were followed for about 2.5 years.Results: Clozapine was discontinued in 37.8% of cases due to non-compliance, non-response, or side-effects. At follow-up 41% of clozapine recipients and 25.9% of the drop-outs were discharged and remained so, and 33% of recipients and 24.1% of drop-outs were being prepared for discharge. Longer treatment was associated with more improvement. Decline in average BPRS total scores of recipients was significantly more than drop-outs (32.7, s.d. 16.8 v. 12.1, s.d. 14.1, d.f. = 155, t = 7.5, P = 0.000).Conclusions: Clozapine appears to be effective for treating some chronic neuroleptic nonresponding schizophrenic patients. [ABSTRACT FROM AUTHOR]

This study explores the extent to which primary care physicians serve as gatekeepers for the treatment of psychosocial problems and the extent to which they have contact with social workers. We also attempted to identify physician variables related to gatekeeping and amount of contact with social workers. Data from a national study of the role of primary care physicians in Israel were used. About one-third of the physicians had regular contact with social workers, one-quarter had contact less often, and about one-third almost never had contact. Variables associated with gatekeeping for psychosocial problems included having a large caseload, specializing in family medicine, practicing in a rural location, and being under age 55. Variables associated with social work contact were affiliation with the largest health maintenance organization and specialization in family medicine. [ABSTRACT FROM AUTHOR]

A 47-year-old patient presented with a chylous knee effusion and traumatic infected skin lacerations. The diagnosis of septic arthritis was considered because of purulent looking joint fluid, spuriously high synovial fluid white cell count, and signs of acute knee synovitis. Synovial fluid lipid analysis showed increased total lipids due to high concentration of neutral lipids, mainly triglycerides, and repeated knee radiographs showed a small fracture of the tibial spine. Joint trauma with subchondral fracture can be associated with frank chylous effusion, which may mimic acute septic arthritis. [ABSTRACT FROM PUBLISHER]

We describe three women with unexplained acute monoarthritis and birefringent lipid spherules or lipid liquid crystals in their synovial fluid. Synovial fluid aspirated within 24 hours of onset showed leucocyte counts ranging from 10 X 10(9) to 46 X 10(9)/1 with 91-95% polymorphonuclear cells. Numerous positively birefringent 2-6 micron microspherules were seen inside and outside polymorphonuclear cells. These were dissolved in alcohol-ether but were not digested by uricase. Other non-birefringent globules of similar size that stained with Sudan black B were also seen. Transmission electron microscopy identified osmiophilic homogeneous or multilamellated material in phagocytic vacuoles. Serum lipids, lipase, and repeated joint radiographs were normal. Arthritis subsided completely after treatment with colchicine in one patient and nonsteroidal anti-inflammatory agents in two. Thus birefringent microspherules can be found in association with acute, otherwise unexplained, arthritis. It seems possible that certain lipid liquid crystals may induce synovial inflammation similar to inflammation seen in other crystal induced arthritides. [ABSTRACT FROM PUBLISHER]

Chondrosarcoma is a primary malignant tumor arising rarely in the axial skeleton. It usually presents as a destructive lesion with diffuse mottled calcification. We report three patients with chondrosarcoma of the spine. Each patient was evaluated by conventional radiographic technique, computed tomography, and myelography. All of them show radiographically a purely destructive process of the body and in one case the body and lamina. This pattern remains to be documented in the radiologic literature. [ABSTRACT FROM AUTHOR]

The catfish, Ictalurus punctatus is an important model system for the study of the biochemical mechanisms of taste reception. A detailed lipid analysis of epithelial tissue from the taste organ (barbel) of the catfish has been performed. Polar lipids account for 62±1% of the total, neutrals for 38±1%. Phosphatidyl-cholines, serines and ethanolamines are the major constitutents of the polar fraction. Plasmalogen concentration is high relative to that of non-neural tissues. [C]-Acetate is incorporated into cell lipid fractions after incubation of barbel tissue at 37°C for 60 min. Percentage amounts of most lipids change with time during this in vitro incubation. The phospholipids are the most metabolically active fractions. This work yields information for continuing reconstitution experiments and indicates that the taste epithelium of this important model system is a metabolically active tissue capable of supporting lipid turnover/synthesis. [ABSTRACT FROM AUTHOR]

Presents a study which examined sodium octanate-induced coma in primate. Overview of studies on the elevation of serum levels of octanate in hepatic encephalopathy; Materials and methods used; Result of polygraphs in Macaca mulatta; Arterial and venous concentrations in cirrhotic patients.

The thermal transformations in phosphorites during flash calcination were investigated by FT-IR spectroscopy, X-ray diffraction and chemical analyses. During flash calcination changes occur, both in the composition of the phosphorite and in the crystallochemistry of the fluor-carbonate-apatite (francolite). The former changes include: decomposition of a great part of the calcite in the rock and oxidation of organic matter. The latter changes include: partial removal of the structural carbonate; partial relocation of the remaining carbonate ions in the apatite structure; a new arrangement of hydroxyl groups and fluorine on the hexagonal axis; partial condensation of the orthophosphate groups and increase of crystallite sizes. Isomorphous substitution of PO in apatite by SO and SiO may take place. [ABSTRACT FROM AUTHOR]