One hundred and ten patients with acute proximal deep-vein thrombosis were randomized in a sequential dose-finding design, to receive continuous intravenous infusion of napsagatran, a novel synthetic ...thrombin-inhibitor, at a fixed dose of 5 mg/h (n = 37) or 9 mg/h (n = 26), or APTT-adjusted unfractionated heparin (n = 47). Oral anticoagulants were started on the 2nd day and the study drug was discontinued from the 5th treatment day, as soon as the International Normalized Ratio was above 2. Control venogram (97 venogram pairs evaluable) after 5-8 days of treatment showed improvement in 3 napsagatran-treated patients (versus none in heparin-treated patients) and worsening in 4 napsagatran-treated patients (versus 2 in heparin-treated patients). The venographic Marder's score did not change among the treatment groups. New lung scan perfusion defects (99 scintigram pairs evaluable) occurred in 4 (11%), 4 (21%), and 4 (10%) patients in the napsagatran (5 mg/h) group, in the napsagatran (9 mg/h) group, and in the heparin control group, respectively. There was no statistically significant difference in any of these endpoints between the 3 groups. No major bleeding was observed and the rare minor bleedings occurred at a similar rate in the three treatment groups. In conclusion, the ADVENT trial has shown data that suggest comparable efficacy and safety of a synthetic, direct thrombin inhibitor (napsagatran) and conventional heparin therapy for treatment of proximal DVT. These results suggest that synthetic direct thrombin inhibitors are a promising class of antithrombotic agents which deserves further development in this field.
The pharmacokinetics of pentoxifylline were investigated in six healthy volunteers and in 10 patients with alcoholic cirrhosis. After a 100 mg intravenous infusion, pentoxifylline elimination ...half‐life was prolonged in cirrhotic patients (2.12 ± 1.22 hours versus 0.83 ± 0.29 hours, p < 0.05) because of a decrease in its plasma clearance (1.44 ± 0.46 L · hr−1 · kg−1 in patients with cirrhosis versus 3.62 ± 0.75 L · hr−1 · kg−1 in volunteers, p < 0.001). The elimination half‐life of the metabolite (5‐hydroxypentoxifylline) was similar to that of the parent compound. After oral administration of a 400 mg sustained‐released tablet, absolute bioavailability of pentoxifylline increased in cirrhotic patients (0.71 ± 0.24 versus 0.33 ± 0.13, p < 0.01). Although plasma concentrations of pentoxifylline and hydroxypentoxifylline were significantly increased in cirrhotic patients, the AUCpentoxifylline/AUChydroxypentoxifylline ratio remained unchanged in both groups after either intravenous or oral administration. These findings show that liver cirrhosis profoundly alters the pharmacokinetics of pentoxifylline. However the formation of hydroxypentoxifylline is not modified in these patients, suggesting an extrahepatic metabolism.
Clinical Pharmacology and Therapeutics (1990) 47, 354–359; doi:10.1038/clpt.1990.39
The present study was undertaken to clarify if needle positioning in percutaneous partial rhizotomy in the thoracic area based on bony landmarks and guided by fluoroscopic control leads to adequate ...placement in or at the targeted nervous tissue, i.e., the dorsal root ganglion (DRG), and to determine if needle localization by CT is more reliable than by fluoroscopic control. An investigation was performed in 2 cadavers, simulating the clinical setting as much as possible. At the levels T1-T8 a drill hole was made in the vertebral arc with a Kirschner wire. At the levels T9-T12 the "classic" dorsolateral technique was used. In 46 procedures the position of the needle tips was compared using hard copies of the fluoroscopic images, CT images at 1.5 mm intervals, surface photographs, and stained 25 microns sections obtained by a multirange heavy duty cryomicrotome. The position of the DRG in the foramen, and its size, were measured. In the sections, considered as the "golden standard", in 28 cases (60.9%) the needle tip was found in the DRG and in the extradural dorsal root in 14 cases (30.4%). In 4 cases (8.7%) no nervous tissue was encountered. In 8 of 32 "drill hole procedures" the facet joint was pierced. No accidental pleural puncture occurred in any of the procedures. The needle position was imaged more accurately by fluoroscopy. It is concluded that fluoroscopic control is a reliable guide to needle placement in percutaneous partial rhizotomy and permits standardization of the technique with the help of bony landmarks.
Uranium decay daughters from isolated mines: Accumulation and sources Cuvier, A; F. PanzaauthorIRSN/Ple Radioprotection, Environnement, Dchets et Crises, Service d'Intervention et d'Assistance en Radioprotection (SIAR), 92262 Fontenay aux Roses Cedex, France; L. PourcelotauthorIRSN/PRP-ENV/SESURE/Laboratoire d'tudes Radiocologiques en milieu Continental et Marin, BP 1 13108 Saint Paul Lez Durance Cedex, France ...
2015
Journal Article
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