The sensitization of glioma cells to cisplatin and tamoxifen by the use of catechin.

Telomerase expression strongly correlates with the grade of malignancy in glioma with inhibition illustrating a definite increase in chemosensitivity. This study was designed to investigate the effects of a green tea derivative, epigallocatechin-3-gallate (EGCG); together with either cisplatin or tamoxifen in glioma, and to investigate whether these effects are mediated through telomerase suppression. EGCG showed a significant cytotoxic effect on 1321N1 cells after 24 h and on U87-MG cells after 72 h (P < 0.001) without significantly affecting the normal astrocytes. Treatment with EGCG inhibited telomerase expression significantly (P < 0.01) and enhanced the effect of cisplatin and tamoxifen in both 1321N1 (P < 0.01) and U87-MG (P < 0.001) cells. EGCG, as a natural product has enormous potential to be an anti-cancer agent capable of enhancing tumour cell sensitivity to therapy.

Empirical Vancomycin Dosing in Pediatric Patients with Congenital Heart Disease and the Impact of Cardiopulmonary Bypass on Trough Concentrations.

OBJECTIVES: To determine the optimal vancomycin dosing regimen to achieve empirical goal trough concentrations in pediatric patients with congenital heart disease and to examine the impact of cardiopulmonary bypass on vancomycin dosing requirements. METHODS: Patients younger than 18 years admitted to the pediatric cardiovascular intensive care unit (CVICU) at our institution from October 1, 2012-December 31, 2014, who received at least one dose of vancomycin, were reviewed retrospectively. Included patients had a steady-state vancomycin trough concentration drawn during the study period. The first steady-state vancomycin trough drawn after being initiated on empirical vancomycin therapy was analyzed for each patient. Excluded patients were those who received mechanical circulatory support, any form of renal replacement therapy, or had a serum creatinine result greater than 1.0 mg/dl on the day of vancomycin initiation. RESULTS: Overall, 77 patients met inclusion criteria, of which 57.1% had undergone cardiopulmonary bypass (CPB) before CVICU admission. Median age was 62 days (interquartile range [IQR] 8.3-176 days). Median daily vancomycin dose was 36.25 mg/kg/day (IQR 29-40 mg/kg/day), resulting in a median steady-state trough of 10.0 µg/ml (IQR 6.3-12.9 µg/ml). Therapeutic troughs occurred in 50.6% of patients; supratherapeutic and subtherapeutic concentrations were attained in 18.2% and 31.2% of patients, respectively. A subgroup analysis of patients who were post-CPB revealed that the only additional variable to affect vancomycin trough concentrations was aortic cross-clamp time (median 56 min, IQR 0-123.3 min, p=0.02). CONCLUSIONS: Empirical vancomycin dosing to achieve troughs of 8-15 µg/dl in patients with congenital heart disease without evidence of significant acute kidney injury should be 30 mg/kg/day for neonates, 35-40 mg/kg/day for infants, and 45 mg/kg/day in children, with adjustments required for patients with elevated creatinine or significant aortic cross-clamp time. The receipt and duration of CPB did not affect total daily vancomycin dose requirements.

Racial differences are seen in blood pressure response to fosinopril in hypertensive children.

BACKGROUND: Few antihypertensive therapies have been systematically studied in children and dosages for many agents are either extrapolated from adult studies or obtained from small homogenous pediatric populations. It is well established that adult patients of different races show disparate response to angiotensin-converting enzyme (ACE) inhibitors, however no such studies have been performed in children. METHODS: Two hundred fifty three children ages 6-16 with hypertension or with high normal blood pressure with an associated medical condition requiring antihypertensive therapy were enrolled at 78 clinical sites in the US, Russia, and Israel in a double blind study to evaluate the efficacy of fosinopril compared to placebo. RESULTS: The racial composition of the cohort included 60.1% white (152/253), 20.6% black (52/253), 13.8% Hispanic (35/253), 2.0% Asian (5/253), 0.4% Native American (1/253), and 3.2% (8/253) children classified as other or of mixed race. After adjusting for baseline blood pressure and body surface area (BSA) there was no significant dose response seen in non-black patients. Non-blacks randomized to the low, medium, and high dosages of fosinopril all had a mean decrease of 12 mm Hg in their sequential systolic BP (SBP). Blacks, however, demonstrated a significant dose response to fosinopril; those who received the low dosage had a 5 mm Hg decrease in SBP, and those who received the high dosage had a mean 13 mm Hg decrease in SBP. CONCLUSIONS: Fosinopril was effective in treating hypertension, but black children required a higher dose per body weight in order to achieve adequate control. This suggests that black children treated with fosinopril for hypertension on average require higher doses to achieve adequate systolic blood pressure control that non-black children.