Demographic correlates of psychotic-like experiences in young Australian adults

Objective: Psychotic‐like experiences (PLE) in the general community are common. The aims of this study were to examine the prevalence and demographic correlates of PLE in young adults. Method: The sample consisted of 2441 subjects aged 18–23 years. Subjects completed the Composite International Diagnostic Interview (CIDI) and the 21‐item Peters Delusional Inventory (PDI). Associations between age, gender, hallucinations and delusions were examined using logistic regression. Results: Both CIDI hallucinations and delusions predicted high scores on the PDI. Younger age was significantly associated with endorsement of CIDI delusions [odds ratio (OR) = 0.66, 95% confidence interval (CI) 0.48–0.92) and with PDI total scores (OR = 0.68, 95% CI 0.55–0.83). Women were significantly more likely to endorse items related to hallucinations (OR = 1.49, 95% CI 1.14–1.95) but not delusions. Conclusion: PLE are common in young adults. The mechanisms underpinning the age and gender gradients in PLE may provide clues to the pathogenesis of psychotic disorders.     

The antecedents of schizophrenia: a review of birth cohort studies

Background: Birth cohort (BC) studies demonstrate that individuals who develop schizophrenia differ from the general population on a range of developmental indices. The aims of this article were to summarize key findings from BC studies in order to identify areas of convergence and to outline areas requiring further research. Method: We define BC studies as studies based on general population BCs where data are collected prospectively from birth or childhood and which identify schizophrenia or related disorders as an outcome. To identify such studies, we searched various electronic databases using the search parameters (schizo* OR psych*) AND (birth cohort). We also checked the references of relevant articles and previous reviews. Results: We identified 11 BCs from 7 countries that have examined schizophrenia as an outcome in adulthood. There is relatively consistent evidence that, as a group, children who later develop schizophrenia have behavioral disturbances and psychopathology, intellectual and language deficits, and early motor delays. Evidence with respect to alterations in language, educational performance, and physical growth has also been identified in some studies. BC studies have also contributed evidence about a wide range of putative risk factors for schizophrenia. Conclusions: BC studies have provided important, convergent insights into how the developmental trajectory of individuals who develop schizophrenia differs from their peers. The combination of new paradigms and larger cohorts, with the tools of modern epidemiology and biomedical science, is advancing our understanding of the developmental pathways to schizophrenia.     

Population pharmacokinetics of enfuvirtide in HIV-1-infected pediatric patients over 48 weeks of treatment

The objective of this study was to characterize the population pharmacokinetics of enfuvirtide in HIV-1-infected children and adolescents. HIV-infected patients received combination antiretroviral therapy, including enfuvirtide 2.0 mg/kg subcutaneously, twice daily. Serial and trough blood samples were collected up to 48 weeks. NONMEM was used for population pharmacokinetic analysis. Enfuvirtide exposure was calculated from individual parameter estimates derived from the final model. A total of 218 samples from 43 patients were included in the analysis. Enfuvirtide plasma concentration-time data were described by a 1-compartment model with first-order absorption and elimination. The addition of each subject's actual body weight as a covariate affected CL/F but not V/F or K(a). The population CL/F, V/F, and K(a) for a 33-kg reference patient was 1.31 L/h, 2.31 L, and 0.105 h(-1), respectively. The final model was CL/F (L/h) = 1.31 . (body weight/33 [kg])(0.721). Age did not affect enfuvirtide exposure. These results confirm the appropriateness of body weight-based pediatric enfuvirtide dosing.     

The antecedents of non‐affective psychosis in a birth‐cohort,with a focus on measures related to cognitive ability,attentional dysfunction and speech problems

Welham J, Scott J, Williams GM, Najman JM, Bor W, O’Callaghan M, McGrath J. The antecedents of non‐affective psychosis in a birth‐cohort, with a focus on measures related to cognitive ability, attentional dysfunction, and speech problems. Objective: Adults with non‐affective psychosis show subtle deviations in a range of developmental trajectories as children and adolescents. Method: Based on a birth‐cohort (n = 3801), we examined the Peabody Picture Vocabulary Test (PPTV) at age 5, and Raven’s Standard Progressive Matrices (RSPM) and Wide Range Achievement Test reading scale (WRAT‐R) at age 14. Items related to speech problems and attentional dysfunction were available from maternal‐ or self‐report. At age 21, we identified 60 cohort members who were screen‐positive for non‐affective psychosis (SP‐NAP). Results: Impaired performance on the PPVT and RSPM (but not WRAT‐R) predicted SP‐NAP for males only. Male cohort members in the highest quartile for attentional dysfunction at ages 5 and 14 were about 5–8 times more likely to develop SP‐NAP. SP‐NAP in males was significantly associated with speech problems at age 14. Conclusion: Males who develop non‐affective psychoses have subtle impairments in cognitive capacity prior to the development of their psychotic disorder.     

The proteomic analysis of cisplatin resistance in breast cancer cells

Resistance to cisplatin represents a major obstacle in the effective management of many cancers, including metastatic breast cancer. We aimed to gain further understanding of the mechanisms underlying development of cisplatin resistance using an in vitro cell line model. The MCF-7 breast cancer cell line and a novel derivative displaying significant resistance to cisplatin were analyzed using two-dimensional gel electrophoresis. The protein profiles were compared and 15 differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The downregulation of beta-tubulin type 3, cytokeratin 17, tropomyosin 1-alpha, peroxiredoxin 4, heat shock 27-kDa protein 1, glutathione-S-transferase mu 3, ribosomal protein P0, isocitrate dehydrogenase 3, and peptidyl-prolyl isomerase A isoform 1 was associated with cisplatin-resistant cells. In contrast, the expression of hydroxyprostaglandin dehydrogenase 15-(NAD), matrix metalloproteinase 9, heterogeneous nuclear ribonucleoprotein A3, proteasome beta 1 subunit, electron transfer flavoprotein beta-polypeptide isoform 1, and peptidyl-propyl isomerase B precursor was upregulated in cisplatin-resistant cells. The downregulation (at least twofold) of glutathione-S-transferase mu 3, cytokeratin 17, and peroxiredoxin 4 was confirmed by Western blotting. We have identified alterations in the expression levels of several proteins that may be associated with cisplatin resistance and are candidates for further validation in clinical samples.     

Cardiac performance and myocardial blood flow in pigs with compensated right ventricular hypertrophy

Compensated right ventricular hypertrophy (RVH), defined by a greater than 100% RV weight increase compared to 17 normal animals, was created in 17 young pigs by pulmonary arterial banding. RVH was associated with significant elevations (p less than 0.001) in RV peak dP/dt, RV stroke work, RV minute work and RV rate-pressure product compared to normal animals matched by body weight. RV peak dP/dt showed a positive correlation (p less than 0.001) with RV peak systolic pressure in normals; however, this relationship was lost in banded animals since progressively higher RV pressures were not associated with concomitant increases in RV peak dP/dt, thus, suggesting an intrinsic difference between right and left ventricles when working at systemic arterial pressures. Time to RV peak dP/dt became progressively longer (p less than 0.05) as RV weight increased in the RVH animals. When indices of cardiac work were normalized for RV weight, the RVH group could not be distinguished from normals suggesting that the performance per unit weight of RV muscle in RVH was unchanged. Total RV blood flow, measured by radioactive microspheres, closely followed (p less than 0.001) increases in RV mass in banded animals. Blood flow . g-1 muscle in RV and septal right side were unaltered in RVH; however, regional perfusion of the left ventricle (p less than 0.001) and septal right side were unaltered in RVH; however, regional perfusion of the left ventricle (p less than 0.001) and septal left side (p less than 0.02) increased significantly. There were regional variations in RV perfusion which were maintained in compensated RVH; stress (isoprenaline infusion) caused significant increases in blood flow to all regions of the heart in normal and RVH animals (p less than 0.001), but relative regional distribution was maintained. Our observations suggest a relationship between myocardial work and blood flow in RVH such that RV perfusion . g-1 is elevated to meet haemodynamic requirements once RV regional work . g-1 become greater than normal.     

NEW INVESTIGATOR AWARD FINALISTSNIA0001Induction of differentiation in human preadipocytes may contribute to adipogenic effect of human adenovirus Ad-36

Human adenovirus Ad-36 causes adiposity in animal models and shows association with human obesity. The mechanism involved is unknown. We previously reported that Ad-36 enhances differentiation of 3T3-L1 preadipocytes and E4orf-1 gene of the virus is responsible for the adipogenic effect in the rodent cell line. We undertook a three-step approach to investigate the role of preadipocyte differentiation in adipogenic effect of Ad-36. First, we showed that the viral mRNA is expressed in adipose-derived stem cells (ASC) of animals experimentally infected with Ad-36. Infection of rats with Ad-36 resulted in increased epididymal fat pad weight and the expression of Ad-36 E4orf-1 mRNA was detected in ASC isolated from the fat pads. Next, we determined if humans naturally infected with Ad-36 will show greater preadipocyte differentiation. Subcutaneous adipose-tissue samples from 33 Pima Indian subjects were screened by nested-PCR specific for Ad-36 DNA. Nine subjects (27%) had Ad-36 DNA. A blinded comparison of their ASC showed greater differentiation to adipocytes for the Ad-36 DNA positive subjects ( P =  0.06) compared to the Ad-36 DNA negative group. Finally, we used a direct approach. Human-ASC when infected with Ad-36 showed spontaneous replication, differentiation, and lipid accumulation, which was significantly greater than the uninfected controls ( P  < 0.01). Ad-36 induced lipid accumulation in human-ASC increased in response to the viral load and the lipogenic response was observed regardless of the donor gender and over an age range of 22–57 years. These results suggest that ability of Ad-36 to induce preadipocyte differentiation may play a role in human adiposity.     

高位胸段硬膜外麻醉下清醒病人的冠状动脉搭桥手术

目的　了解在高位胸段硬膜外麻醉下避免全麻行非体外循环心脏跳动下冠状动脉搭桥手术的可行性。方法　硬膜外麻醉下对 2 5例清醒病人行非体外循环心脏跳动下冠状动脉搭桥手术 ,没有气管插管全麻 ,所有病人在手术前晚行硬膜外置管。结果　总共搭桥 71支 (1支 11例 ,2支 5例 ,3支 6例 ,4支 3例 )。除 1例因为术中出现室颤转为全麻和体外循环外 ,2 4例在硬外麻作为唯一麻醉下完成非体外循环心脏跳动下冠状动脉搭桥手术。除 2例行左胸小切口外其余行正中切口 ;其中 6例为再次手术 ;平均每例搭桥2 8支 ,没有手术死亡。术后在复苏室和病房住院时间分别为 (16 2± 4 2 )h和 (3 2 4± 1 2 )d。结论　本组的早期经验提示在没有气管插管全麻、病人清醒下可以行多支冠状动脉搭桥术