The primary outcome was the rate of radiologically proven, symptomatic catheter- related thrombosis. Analysis was by intention to treat. This trial is 14 registered as an International Standard Randomised Controlled Trial, number I SRCTN 50312145.
Findings Compared with no warfarin (n=404), warfarin (n=408; 324 [79%] on fixed-dose and 84 [21%] on dose-adjusted) did not reduce the rate of catheter- check details related thromboses (24 [6%] vs 24 [6%]; relative risk 0 . 99, 95% Cl 0 . 57-1.72, p=0 . 98). However,
compared with fixed-dose warfarin (n=471), dose-adjusted warfarin (n=473) was superior in the prevention of catheter- related thromboses (13 [3%] vs 34 [7%]; 0 . 38, 0.20-0.71, p=0 . 002). Major bleeding events were rare; an excess was noted with warfarin compared with no warfarin (7 vs 1, p=0. 07) and with dose-adjusted warfarin compared with fixed-dose warfarin (16 vs 7, p=0.09). A combined endpoint of thromboses and major bleeding showed no difference between comparisons. We did not note a survival benefit in either comparison.
Interpretation The findings show that prophylactic warfarin compared with no warfarin is not associated with a reduction in symptomatic catheter- related or other thromboses in patients with cancer and therefore we should consider newer treatments.
Funding Medical Research Council and Cancer Research UK.”
“Fenamates
like flufenamic acid (FFA) are anti-inflammatory drugs known to alter ion fluxes through the plasma membrane. They are Foretinib mw for instance potent blockers of cation and anion channels and IFFA is now, commonly
used to block currents through TRP channels and receptor-operated channels. However, FFA exerts complex and multifaceted actions on ion transport systems and, in most instances, a molecular understanding of these FFA-dependent modulations is lacking. In addition, FFA is also to known to perturb the homeostasis of Ca(2+). In the present report, we investigated whether the IFFA-induced alterations of the Ca(2+) homeostasis could play a role in the FFA-dependent CHIR-99021 order modulation of transmembrane ion fluxes. Experiments performed with the Ca(2+) indicator Fluo-4 on cultured cortical neurons and HEK-293 cells showed that FFA increased the cytosolic concentration of Ca(2+) even in cells kept in a Ca(2+)-free medium or when the endoplasmic reticulum was depleted with thapsigargin. The FFA-dependent Ca(2+) responses were, however, strongly reduced by bongkrekic acid, a specific ligand of the mitochondrial ADP/ATP carrier which, in addition, inhibits the permeability transition pore. Like IFCCR FFA released Ca(2+) from isolated brain mitochondria and indirectly modulates store-operated Ca(2+) channels. We suggest that some of the effects of FFA on plasma membrane ion channels could be explained, at least partially, by its ability to modulate the mitochondrial Ca(2+) homeostasis. (C) 2009 Elsevier Ltd. All rights reserved.