A longitudinal study of cortical changes and their cognitive correlates in patients followed up after first-episode psychosis.

BACKGROUND: Loss of cortical volume in frontotemporal regions occurs in patients with first-episode psychosis (FEP) and longitudinal studies have reported progressive brain volume changes at different stages of the disease, even if cognitive deficits remain stable over time. We investigated cortical changes in patients over the 2 years following their FEP and their associations with clinical and cognitive measures. METHOD: Twenty-seven patients after their FEP (20 with schizophrenia, seven with schizo-affective disorder) and 25 healthy controls matched for age and gender participated in this study. Magnetic resonance imaging (MRI) was performed on a 1.5-T scanner both at baseline and after 2 years. Area and thickness of the cortex were measured using surface-based morphometry (SBM). Patients also underwent neuropsychological testing at these two time points. RESULTS: Progressive cortical thinning in the superior and inferior frontal and, to a lesser extent, superior temporal cortex was observed in patients. Cortical area remained constant. Cortical thinning was associated with duration of treatment at a trend level and was predicted by baseline measures of IQ and working memory. Cortical thinning occurred in the absence of clinical or cognitive deterioration. CONCLUSIONS: The clinical implications of these cortical changes remain uncertain, but patients with less cognitive reserve may be more vulnerable to developing cortical abnormalities when exposed to medication or other disease-related biological factors.

Metronomic gemcitabine suppresses tumour growth, improves perfusion, and reduces hypoxia in human pancreatic ductal adenocarcinoma.

BACKGROUND: The current standard of care for pancreatic cancer is weekly gemcitabine administered for 3 of 4 weeks with a 1-week break between treatment cycles. Maximum tolerated dose (MTD)-driven regimens as such are often associated with toxicities. Recent studies demonstrated that frequent dosing of chemotherapeutic drugs at relatively lower doses in metronomic regimens also confers anti-tumour activity but with fewer side effects. METHODS: Herein, we evaluated the anti-tumour efficacy of metronomic vs MTD gemcitabine, and investigated their effects on the tumour microenvironment in two human pancreatic cancer xenografts established from two different patients. RESULTS: Metronomic and MTD gemcitabine significantly reduced tumour volume in both xenografts. However, K(trans) values were higher in metronomic gemcitabine-treated tumours than in their MTD-treated counterparts, suggesting better tissue perfusion in the former. These data were further supported by tumour-mapping studies showing prominent decreases in hypoxia after metronomic gemcitabine treatment. Metronomic gemcitabine also significantly increased apoptosis in cancer-associated fibroblasts and induced greater reductions in the tumour levels of multiple pro-angiogenic factors, including EGF, IL-1alpha, IL-8, ICAM-1, and VCAM-1. CONCLUSION: Metronomic dosing of gemcitabine is active in pancreatic cancer and is accompanied by pronounced changes in the tumour microenvironment.

Translation and validation of Arthritis Impact Measurement Scales 2 into Chinese: CAIMS2.

OBJECTIVE: To evaluate the validity, reliability, and cultural relevance of the Arthritis Impact Measurement Scales 2 (AIMS2) as a health assessment tool for Chinese-speaking patients with arthritis. METHODS: The cultural relevance, language equivalency, and content validity of the AIMS2, Chinese version (CAIMS2) were evaluated by an expert panel. Measurement performance was tested on 240 subjects (rheumatoid arthritis = 81, osteoarthritis = 77, healthy = 82). Subjects (n = 175) were retested within 2 weeks for testing of reliability. RESULTS: Three items were modified and 2 items were added, as suggested by the expert panel. Interitem reliability was satisfactory (intraclass correlation coefficient 0.8552-0.9594). Test-retest reliability of the CAIMS2 subscales ranged from 0.770 to 0.952 in subjects in whom the CAIMS2 was self administered. Significant score differences between patients with arthritis and healthy subjects were found in all 12 subscales, except for the support from family and friends and tension subscales. CAIMS2 subscale scores correlated with clinical and laboratory measures of disease activity and patients' perceived quality of life as measured using the Chinese version of the World Health Organization Quality of Life instrument. CONCLUSION: Empirical data support CAIMS2 is a valid and reliable health status measure for Chinese speaking patients with arthritis.