Citations

Identifying biomarkers that distinguish Parkinson's disease (PD) from normal control (NC) individuals has the potential to increase diagnostic sensitivity for the detection of early-stage PD. A previous proteomic study identified potential biomarkers in postmortem ventricular cerebrospinal fluid (V-CSF) from neuropathologically diagnosed PD subjects lacking Alzheimer's disease (AD) neuropathology. In the present study, we assessed these biomarkers as well as p-tau 181 , Aβ42, and S100B by ELISA in PD (n = 43) and NC (n = 49) cases. The p-tau 181 /Aβ42 ratio and ApoA-1 showed statistically significant differences between groups. Multiple regression analysis demonstrated that p-tau 181 /Aβ42 had a significant odds ratio: OR = 1.42 (95% confidence interval [CI], 1.12–1.84), P = 0.006. Among the molecules investigated, intriguing correlations were observed that require further investigation. Our results suggest coexistent AD CSF biomarkers within the PD group notwithstanding that it was selected to minimize AD neuropathological lesions.

Objective: To expand the adverse events associated with metronidazole to include nonconvulsive status epilepticus (NCSE). Design: Observational single case report of a rare association. Setting: Hospitalized lung transplant recipient treated with metronidazole for prevention of infection. Patient: A 56-year-old man with systemic symptoms, peripheral neuropathy, generalized seizure, and a subsequent acute deterioration of mental status due to NCSE. Interventions: Administration of midazolam was successful in terminating status epilepticus. Main Outcome Measures: Abrupt termination of NCSE was evident on continuous bedside electroencephalogam associated with clinical resolution of mental status. Results: Recovery occurred from NCSE eventually deteriorating to a fatal outcome. Conclusions: Metronidazole may be associated with successfully treated NCSE.

Objective Identify novel prognostic factors for patients with peripartum cardiomyopathy (PPCM). Design and setting Prospective cohort study conducted in a single tertiary care centre in South Africa. Patients 176 African women with newly diagnosed PPCM were studied. Interventions Clinical assessment, echocardiography and laboratory results were obtained at baseline and at 6 months. Main outcome measures Poor outcome was defined as the combined end point of death, left ventricular (LV) ejection fraction (LVEF) < 35%, or remaining in New York Heart Association (NYHA) functional class III/IV at 6 months. Complete LV recovery was defined as LVEF ≥55% at 6 months. Results Forty-five (26%) patients had a poor outcome. Multiple logistic regression analysis revealed that, after adjustment for age, NYHA functional class, LVEF and systolic blood pressure, increased left ventricular end systolic dimension (LVESD), lower body mass index (BMI) and lower total cholesterol at baseline were independent predictors of poor outcome (adjusted OR 1.09, 95% CI 1.04 to 1.15, p=0.001; OR 0.89, 95% CI 0.83 to 0.96, p=0.004, and OR 0.50, 95% CI 0.34 to 0.73, p=0.0004, respectively). Thirty (21%) of the 141 surviving patients with echocardiographic follow-up recovered LV function at 6 months. Multiple logistic regression analysis revealed that, after adjustment for NYHA functional class, LVEF and left ventricular end diastolic dimension, older age and smaller LVESD at baseline were predictors of LV recovery (OR 1.08, 95% CI 1.01 to 1.17, p=0.02 and OR 0.92, 95% CI 0.86 to 0.98, p=0.007, respectively). Conclusions This study suggests that increased LVESD, lower BMI and lower serum cholesterol at baseline may be independent predictors of poor outcome in patients with PPCM, while older age and smaller LVESD at baseline appear to be independently associated with a higher chance of LV recovery.

Abstract SHP2 is a protein tyrosine phosphatase encoded by the PTPN11 gene. SHP2 is normally auto-inhibited by its regulatory N-SH2 domain. It is activated by several receptor tyrosine kinases and positively regulates the RAS/ERK and other signaling pathways by mechanisms that remain incompletely defined. Furthermore, gain-of-function activating SHP2 mutants have been found in human hematologic malignancies and solid tumors, including lung, colon, and prostate cancer. Previous studies have demonstrated the oncogenic activity of gain-of-function SHP2 mutants in the hematopoietic system. To investigate the biological functions of mutant SHP2 in vivo, we generated transgenic mice harboring a tetO-SHP2E76K transgene for tetracycline-inducible expression of the constitutively active SHP2E76K mutant. This allows us to examine the roles of the cancer-associated, Glu-76 mutant SHP2 in various tissues in bitransgenic mice. tetO-SHP2E76K mice were crossed with CCSP-rtTA or SPC-rtTA mice for inducible expression of SHP2E76K in the lung type II pneumocytes. Elevated levels of active Erk1/2 and Src were detected in the lungs of bitransgenic mice induced with doxycycline. Focal hyperplasia of bronchioloalveolar epithelial cells was observed within one month of doxycycline induction in bitransgenic mice, which progressed to more extensive atypical adenomous hyperplasia and adenoma after six months. These results suggest that Shp2 is a proto-oncogene of lung carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4005. doi:1538-7445.AM2012-4005