Association study of BCL9 gene polymorphism rs583583 with schizophrenia and negative symptoms in Japanese population.

B-cell CLL/lymphoma 9 (BCL9) is located within the schizophrenia (SCZ) suspected locus chr1q21.1. A recent study reported that a single nucleotide polyphormism (SNP) within BCL9 (rs583583) is associated with negative symptoms of Schizophrenia, as measured by the Positive and Negative Syndrome Scale (PANSS), in the Caucasian population. We therefore investigated genetic association of rs583583, and its effect on negative symptoms in the Japanese patients. For association analysis, we used a Japanese sample set comprising 1089 SCZ and 950 controls (CON). Analysis of the effect of rs586586 on negative symptoms as examined by PANSS was investigated using 280 SCZ. Furthermore, for analysis of cognitive performance, we investigated 90 SCZ and 51 CON using the Continuous Performance Test (CPT-IP) and the Wisconsin Card Sorting Test (WCST) Keio version. We did not detect association between rs583583 and SCZ. Furthermore, rs583583 was not associated with PANSS negative scores or with CPT-IT or WCST cognitive tests. Considering the results of our previous study, combined with the results of the current study of rs583583, we argue that BCL9 most likely does not harbor a common genetic variant that can increase the risk for SCZ in the Japanese population.

Wisconsin Card Sorting Test scores and clinical and sociodemographic correlates in Schizophrenia: multiple logistic regression analysis.

OBJECTIVES: This study investigated what clinical and sociodemographic factors affected Wisconsin Card Sorting Test (WCST) factor scores of patients with schizophrenia to evaluate parameters or items of the WCST. DESIGN: Cross-sectional study. SETTING: Patients with schizophrenia from three hospitals participated. PARTICIPANTS: Participants were recruited from July 2009 to August 2011. 131 Japanese patients with schizophrenia (84 men and 47 women, 43.5±13.8 years (mean±SD)) entered and completed the study. Participants were recruited in the study if they (1) met DSM-IV criteria for schizophrenia; (2) were physically healthy and (3) had no mood disorders, substance abuse, neurodevelopmental disorders, epilepsy or mental retardation. We examined their basic clinical and sociodemographic factors (sex, age, education years, age of onset, duration of illness, chlorpromazine equivalent doses and the positive and negative syndrome scale (PANSS) scores). PRIMARY AND SECONDARY OUTCOME MEASURES: All patients carried out the WCST Keio version. Five indicators were calculated, including categories achieved (CA), perseverative errors in Milner (PEM) and Nelson (PEN), total errors (TE) and difficulties of maintaining set (DMS). From the principal component analysis, we identified two factors (1 and 2). We assessed the relationship between these factor scores and clinical and sociodemographic factors, using multiple logistic regression analysis. RESULTS: Factor 1 was mainly composed of CA, PEM, PEN and TE. Factor 2 was mainly composed of DMS. The factor 1 score was affected by age, education years and the PANSS negative scale score. The factor 2 score was affected by duration of illness. CONCLUSIONS: Age, education years, PANSS negative scale score and duration of illness affected WCST factor scores in patients with schizophrenia. Using WCST factor scores may reduce the possibility of type I errors due to multiple comparisons.

Evaluation of factors affecting continuous performance test identical pairs version score of schizophrenic patients in a Japanese clinical sample.

Aim. Cognitive impairment in schizophrenia strongly relates to social outcome and is a good candidate for endophenotypes. When we accurately measure drug efficacy or effects of genes or variants relevant to schizophrenia on cognitive impairment, clinical factors that can affect scores on cognitive tests, such as age and severity of symptoms, should be considered. To elucidate the effect of clinical factors, we conducted multiple regression analysis using scores of the Continuous Performance Test Identical Pairs Version (CPT-IP), which is often used to measure attention/vigilance in schizophrenia. Methods. We conducted the CPT-IP (4-4 digit) and examined clinical information (sex, age, education years, onset age, duration of illness, chlorpromazine-equivalent dose, and Positive and Negative Symptom Scale (PANSS) scores) in 126 schizophrenia patients in Japanese population. Multiple regression analysis was used to evaluate the effect of clinical factors. Results. Age, chlorpromazine-equivalent dose, and PANSS-negative symptom score were associated with mean d' score in patients. These three clinical factors explained about 28% of the variance in mean d' score. Conclusions. As conclusion, CPT-IP score in schizophrenia patients is influenced by age, chlorpromazine-equivalent dose and PANSS negative symptom score.

Common variants in MAGI2 gene are associated with increased risk for cognitive impairment in schizophrenic patients.

Schizophrenia is a complex psychiatric disorder characterized by positive symptoms, negative symptoms, and cognitive impairment. MAGI2, a relatively large gene (∼1.5 Mbps) that maps to chromosome 7q21, is involved in recruitment of neurotransmitter receptors such as AMPA- and NMDA-type glutamate receptors. A genetic association study designed to evaluate the association between MAGI2 and cognitive performance or schizophrenia has not been conducted. In this case-control study, we examined the relationship of single nucleotide polymorphism (SNP) variations in MAGI2 and risk for schizophrenia in a large Japanese sample and explored the potential relationships between variations in MAGI2 and aspects of human cognitive function related to glutamate activity. Based on the result of first schizophrenia genome-wide association study in a Japanese population (JGWAS), we selected four independent SNPs and performed an association study using a large independent Japanese sample set (cases 1624, controls 1621). Wisconsin Card Sorting Test (WCST) was used to evaluate executive function in 114 cases and 91 controls. We found suggestive evidence for genetic association of common SNPs within MAGI2 locus and schizophrenia in Japanese population. Furthermore in terms of association between MAGI2 and cognitive performance, we observed that genotype effect of rs2190665 on WCST score was significant (p = 0.034) and rs4729938 trended toward significance (p = 0.08). In conclusion, although we could not detect strong genetic evidence for association of common variants in MAGI2 and increased schizophrenia risk in a Japanese population, these SNPs may increase risk of cognitive impairment in schizophrenic patients.

The Effects of Percutaneous Endoscopic Gastrostomy on Quality of Life in Patients With Dementia.

BACKGROUND: To examine the effects of percutaneous endoscopic gastrostomy (PEG) on quality of life (QOL) in patients with dementia. METHODS: We retrospectively included 53 Japanese community and tertiary hospitals to investigate the relationship between the newly developed PEG and consecutive dementia patients with swallowing difficulty between Jan 1st 2006 and Dec 31st 2008. We set improvements in 1) the level of independent living, 2) pneumonia, 3) peroral intake as outcome measures of QOL and explored the factors associated with these improvements. RESULTS: Till October 31st 2010, 1,353 patients with Alzheimer's dementia (33.1%), vascular dementia (61.7%), dementia with Lewy body disease (2.0%), Pick disease (0.6%) and others were followed-up for a median of 847 days (mean 805 ± 542 days). A total of 509 deaths were observed (mortality 59%) in full-followed patients. After multivariate adjustments, improvement in the level of independent living was observed in milder dementia, or those who can live independently with someone, compared with advanced dementia, characterized by those who need care by someone: Odds Ratio (OR), 3.90, 95% confidence interval (95%CI), 1.59 - 9.39, P = 0.003. Similarly, improvement of peroral intake was noticed in milder dementia: OR, 2.69, 95%CI, 1.17 - 6.17, P = 0.02. Such significant associations were not observed in improvement of pneumonia. CONCLUSIONS: These results suggest that improvement of QOL after PEG insertion may be expected more in milder dementia than in advanced dementia.

Sexual dysfunction and hyperprolactinemia in Japanese schizophrenic patients taking antipsychotics.

This study aimed to estimate the prevalence of sexual dysfunction, evaluated by the Nagoya Sexual Function Questionnaire (NSFQ), and hyperprolactinemia in patients with schizophrenia and examine a relationship between sexual dysfunction and serum prolactin levels. This cross-sectional, comparative study was performed using a sample comprising 195 Japanese schizophrenic in- and outpatients treated with antipsychotics (117 males and 78 females). Data were collected from October 2009 to January 2010 using single, cross-sectional ratings of sexual function assessed by the NSFQ and concurrent measurement of serum prolactin levels. The prevalence of sexual dysfunction in patients with schizophrenia was high (males 66.7%; females 79.5%). Hyperprolactinemia (>25ng/ml) was highly prevalent among schizophrenia patients, affecting 53.8% of females and 51.3% of males. Among female patients, 16.7% had prolactin levels>100ng/ml. There was no relationship between sexual dysfunction and serum prolactin levels. The present study demonstrated a higher prevalence of sexual dysfunction and hyperprolactinemia in Japanese schizophrenia patients. Clinicians should keep these problems in mind and discuss potential solutions with patients to improve patients' quality of life and adherence to therapy.

A case control association study and cognitive function analysis of neuropilin and tolloid-like 1 gene and schizophrenia in the Japanese population.

BACKGROUND: Using a knock-out mouse model, it was shown that NETO1 is a critical component of the NMDAR complex, and that loss of Neto1 leads to impaired hippocampal long term potentiation and hippocampal-dependent learning and memory. Moreover, hemizygosity of NETO1 was shown to be associated with autistic-like behavior in humans. PURPOSE OF THE RESEARCH: We examined the association between schizophrenia and the neuropilin and tolloid-like 1 gene (NETO1). First, we selected eight single nucleotide polymorphisms (SNPs) within the NETO1 locus, based on the Japanese schizophrenia genome wide association study (JGWAS) results and previously conducted association studies. These SNPs were genotyped in the replication sample comprised of 963 schizophrenic patients and 919 healthy controls. We also examined the effect of associated SNPs on scores in the Continuous Performance Test and the Wisconsin Card Sorting Test Keio version (schizophrenic patients 107, healthy controls 104). RESULTS: There were no significant allele-wise and haplotype-wise associations in the replication analysis after Bonferroni correction. However, in meta-analysis (JGWAS and replication dataset) three association signals were observed (rs17795324: p = 0.028, rs8098760: p = 0.017, rs17086492: p = 0.003). These SNPs were followed up but we could not detect the allele-specific effect on cognitive performance measured by the Continuous performance test (CPT) and Wisconsin Card Sorting test (WCST). MAJOR CONCLUSIONS: We did not detect evidence for the association of NETO1 with schizophrenia in the Japanese population. Common variants within the NETO1 locus may not increase the genetic risk for schizophrenia in the Japanese population. Additionally, common variants investigated in the current study did not affect cognitive performance, as measured by the CPT and WCST.

[Drug resistance of Pseudomonas aeruginosa in four community hospitals: influence of antimicrobial use density].

We investigated the relation between hospital antimirobial use density (AUD) and minimum inhibitory concentrations (MIC) for Pseudomonas aeruginosa in four community hospitals. Subjects were a total of 476 strains isolated from urine, sputum, and pus during a total of seven years since 2002, for which 50- and 90-percentile MICs were analyzed. Hospitals A, B, and C moved in 2000, 2005, and 2009, respectively, but MIC50 and MIC90 were stable. MIC values showed significance in five drugs, in which Hospital B showed maximal values in five and Hospital D showed minimal values in four drugs. AUD values were different in nine drugs, Hospital B showing the highest data in meropenem, flomoxef, and sulbactam/cefoperazone while Hospital D having the lowest data in meropenem, ceftazidime, cefotaxime, and sulbactam/cefoperazone. Thus MIC for P aeruginosa may show resistance in the presence of high AUD with wide antimicrobial spectrum.

Reliability and validity of a new sexual function questionnaire (Nagoya Sexual Function Questionnaire) for schizophrenic patients taking antipsychotics.

OBJECTIVE: This study aims to validate a new user-friendly sexual function questionnaire (Nagoya Sexual Function Questionnaire [NSFQ]) for schizophrenic patients taking antipsychotics. METHODS: Schizophrenic outpatients (men = 30, women = 30) were asked to fill out the NSFQ at initial entry into the research program (Time1) and again 1 to 2 weeks later (Time2). To assess the convergent validity of the NSFQ, at Time1, subjects were asked to fill out the Japanese version of the Udvalg for Kliniske Undersogekser Side Effect Rating Scale (UKU). To assess the discriminant validity of the NSFQ, at Time1, subjects were also asked to fill out the Japanese version of Epworth Sleepiness Scale. RESULTS: Results from Cronbach's alpha analysis indicated that the NSFQ demonstrated excellent internal consistency and scale reliability. The NSFQ also demonstrated strong test-retest reliability. The NSFQ total score was highly correlated with the UKU total score. The NSFQ was shown to have good convergent validity with the UKU. The NSFQ total score was not correlated with the Japanese version of Epworth Sleepiness Scale total score. CONCLUSIONS: This study revealed the internal consistency, test-retest reliability, and convergent and discriminant validities of the NSFQ.

Survival of geriatric patients after percutaneous endoscopic gastrostomy in Japan.

AIM: To examine the long term survival of geriatric patients treated with percutaneous endoscopic gastrostomy (PEG) in Japan. METHODS: We retrospectively included 46 Japanese community and tertiary hospitals to investigate 931 consecutive geriatric patients (≥ 65 years old) with swallowing difficulty and newly performed PEG between Jan 1st 2005 and Dec 31st 2008. We set death as an outcome and explored the associations among patient's characteristics at PEG using log-rank tests and Cox proportional hazard models. RESULTS: Nine hundred and thirty one patients were followed up for a median of 468 d. A total of 502 deaths were observed (mortality 53%). However, 99%, 95%, 88%, 75% and 66% of 931 patients survived more than 7, 30, 60 d, a half year and one year, respectively. In addition, 50% and 25% of the patients survived 753 and 1647 d, respectively. Eight deaths were considered as PEG-related, and were associated with lower serum albumin levels (P = 0.002). On the other hand, among 28 surviving patients (6.5%), PEG was removed. In a multivariate hazard model, older age [hazard ratio (HR), 1.02; 95% confidence interval (CI), 1.00-1.03; P = 0.009], higher C-reactive protein (HR, 1.04; 95% CI: 1.01-1.07; P = 0.005), and higher blood urea nitrogen (HR, 1.01; 95% CI: 1.00-1.02; P = 0.003) were significant poor prognostic factors, whereas higher albumin (HR, 0.67; 95% CI: 0.52-0.85; P = 0.001), female gender (HR, 0.60; 95% CI: 0.48-0.75; P < 0.001) and no previous history of ischemic heart disease (HR, 0.69; 95% CI: 0.54-0.88, P = 0.003) were markedly better prognostic factors. CONCLUSION: These results suggest that more than half of geriatric patients with PEG may survive longer than 2 years. The analysis elucidated prognostic factors.

Electrohydrodynamic effect on phase separation morphology in polymer blend films.

We have investigated the effect of electrohydrodynamic (EHD) convection on the domain structure in a polystyrene (PS)/polyvinyl acetate (PVA) blend film to demonstrate the feasibility of using the EHD effect as a means of mixing and morphology control in a polymer blend film prepared by solvent evaporation. Here, polymers-toluene solutions were spread on a glass substrate with patterned electrodes to apply a dc electric field, and well-defined structures of EHD convection were formed in the polymer solutions. As a result, regular patterns were formed in the PS/PVA polymer blend film in which PVA-rich domains were confined within each unit of patterned electrodes, i.e., between positive and negative electrodes, at an appropriate electric voltage. In addition, it was demonstrated that such novel morphology is not due to the wetting/dewetting effect of polymer components to the Pt electrodes deposited on the glass substrate, by experiments with a SiO2-covered substrate.

[A case of recurrent gastric cancer that responded dramatically to docetaxel and 5'-DFUR combination chemotherapy].

A 54-year-old man suffering from Borrmann type 4 advanced gastric cancer with pancreatic invasion and paraaortic lymph node metastases underwent a total gastrectomy, which was a radical C operation. From postoperative month 4, he visited our hospital with multiple liver metastases and increased lymph node metastases. After chemotherapy with CDDP and 5-FU, CDDP and UFT was administered on an outpatient basis. The effect of this therapy was PD, therefore, docetaxel and 5'-DFUR combination chemotherapy was performed as second line therapy. After 2 courses of this therapy, the size of liver and lymph node metastases was reduced and the effect of this therapy was PR. The patient has undergone 4 courses of this therapy and is maintaining a clinical PR. It is conceivable that docetaxel and 5'-DFUR combination chemotherapy is useful for patients with advanced and recurrent gastric cancer, even if they had been treated with 5-FU administration as first line therapy.

[Weekly administration of low-dose paclitaxel for advanced or metastatic breast cancer].

The activity and toxicity of a weekly infusion of low-dose paclitaxel was studied. Twelve patients with metastatic or advanced breast cancer received paclitaxel (80 mg/m2 over 1 h) every week. Administration was continued for 6 weeks with two weeks rest until disease progression or limiting toxicity. Dexamethasone 20 mg, diphenhydramine 50 mg, and ranitidine 50 mg were given prior to each dose of paclitaxel. Six patients had received prior standard CMF therapy, and four patients had received CMF and docetaxel therapy. Two patients had not received prior therapy. The overall response rate was 58% with 17% complete responses and 42% partial responses. Responses were observed in both patients without prior therapy, and in five of 10 (50%) with prior therapy. Grade 3/4 neutropenia occurred in one patient; febrile neutropenia was not observed. There was no neuropathy or hypersensitivity. Weekly paclitaxel is active and well tolerated in patients with metastatic or advanced breast cancer. This schedule allows a high cumulative dose of paclitaxel without major myelo- or neurotoxicity. This weekly regimen deserves further exploration.