Isolated rat hepatocyte couplets were used to perform the comparative study of two widely used immunosuppressors, cyclosporin A (CsA) and tacrolimus (FK506) on hepatocanalicular function. We assessed canalicular function by counting the percentage of couplets that were able to accumulate the fluorescent cholephile, cholyl-lysyl-fluorescein (CLF), into the canalicular vacuole between the two cel...

BACKGROUND Venous gangrene complicating deep vein thrombosis in the context of anticoagulation use in patients with gynecologic malignancy is rarely reported. We report an unusual presentation of venous gangrene of the lower limbs associated with warfarin therapy in a 53-year-old woman from the Cook Islands with an occult ovarian cancer. CASE PRESENTATION A 53-year-old woman of Cook Islands o...

Purpose of the study Lersivirine (LRV) is a next-generation NNRTI currently under investigation in two Phase IIb studies at doses of 500 1000 mg QD. In vitro analyses suggest that LRV is a weak Ikr and CA 2+ channel blocker. However, doseranging Phase I studies have not shown prolongation of QTc interval to date. This study was performed to investigate the effect of a supratherapeutic dose of L...

In this issue of Blood, Warkentin et al describe a novel clinical syndrome of warfarin-associated severe venous limb ischemia occurring in a series of 10 patients with malignancy after initiating treatment of deep venous thrombosis. Patients in this series also demonstrated a decline in platelet counts after stopping heparin, warfarin-associated supratherapeutic international normalized ratios ...

BACKGROUND Myocardial effects of propofol have been previously investigated but most studies have been performed in healthy hearts. This study compared the cardiac effects of propofol on isolated normal and hypertrophic rabbits hearts. METHODS The effects of propofol (10-1,000 microM) on myocardial contractility, relaxation, coronary flow and oxygen consumption were investigated in hearts fro...

Two studies (ROADMAP and ORIENT) evaluating the renoprotective effects of olmesartan medoxomil (OM) in patients with type 2 diabetes suggested OM is associated with increased cardiovascular mortality. We conducted a thorough QTc study to evaluate the effects of OM on cardiac repolarization. A randomized, double-blind, phase 1 study was conducted per E14 Guidance to assess the effects of single ...

Tafenoquine is being developed for relapse prevention in Plasmodium vivax malaria. This Phase I, single-blind, randomized, placebo- and active-controlled parallel group study investigated whether tafenoquine at supratherapeutic and therapeutic concentrations prolonged cardiac repolarization in healthy volunteers. Subjects aged 18-65 years were randomized to one of five treatment groups (n = 52 ...

BACKGROUND Iris vascular tufts are rare iris stromal vascular hamartomas. Patients with iris vascular tufts generally remain asymptomatic until presenting with a spontaneous hyphaema or with mild intraoperative pupil margin haemorrhage during anterior segment surgery. This is the first reported case of spontaneous hyphaema from iris vascular tuft related to a documented supratherapeutic Interna...