BACKGROUND It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82). CONCLUSIONS Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized.

3D-transit is a well-tolerated and minimal invasive ambulatory method for assessment of GI motility. By providing both total and regional transit times, the 3D-Transit system holds great promise for future clinical studies of GI function in health and disease.

Fluorescence photodetection (PD) and photodynamic therapy (PDT) are techniques currently under clinical assessment for both visualization and local destruction of malignant tumours and premalignant lesions. One drawback of these methods found with some photosensitizers is a more or less long-term cutaneous photosensitivity (Wagnières et al, 1998;Dougherty et al, 1990). A more recent strategy for administering photosensitizers involves the application of 5-aminolaevulinic acid (ALA) in order to stimulate the formation of protoporphyrin IX (PpIX) in situ. The exogenous ALA bypasses the negative feedback control from haem to ALA synthase that catalyses the condensation of glycine and succinyl-coenzyme A (CoA). Given in excess, exogenous ALA thus can result in a temporary accumulation of PpIX, in particular, in cells with higher metabolic turnover. Since PPIX has fairly good photosensitizing properties (Cox et al, 1982;Kennedy et al, 1990) proposed ALA as a possible photodynamic agent. Following this pioneering work, this treatment modality has been widely studied for various cancers (Kennedy et al, 1992;Peng et al, 1992;Svanberg et al, 1994).As well as for the PDT of malignant or premalignant lesions, ALA-induced PpIX is now being used for the detection of such lesions. This technique has been shown to work, among other applications, in urology, where easy instillation in the bladder, combined with the fact that this organ is readily accessible endoscopically, makes it an ideal object. Alongside classical techniques such as cytology or white light examination, fluorescence PD by ALA-induced PpIX provides some advantages (Leveckis et al, 1994;Kriegmair et al, 1996;Jichlinski et al, 1997). This inspection modality allows an exact mapping which pinpoints, with a high level of sensitivity and specificity, the locations of carcinoma in situ (CIS) as well as early stages of cancer-like dysplasias, which are normally difficult to recognize under white light examination.However, when using topically instilled ALA for the PDT of CIS and precancerous lesions, this modality appears to be limited by the amount of ALA that enter the target cells or by the tissue penetration and the distribution of the resulting PpIX in the targeted tissue. Almost all of these possible disadvantages accompanying the use of ALA can be ascribed to the physical-chemical properties of the molecule itself. Applied under physiological conditions, ALA is a zwitterion (Novo et al, 1996). Because the lipid bilayer of biological membranes is relatively impermeable to charged molecules, the cellular uptake of ALA is shallow. Consequently, in order to increase the transport across cellular membranes, fairly high drug doses and increased administration times have to be used. This deficiency results in a low penetration depth (Warloe et al, 1992;Loh et al, 1993;Peng et al, 1995) and an ALA-induced PpIX distribution, which is not optimized for the PDT of the deep layers of nodular lesions in the urothelium (Iinuma et al, 1995;Chang et al, 1996) after topical A...

Duchenne muscular dystrophy is a frequent muscular disorder caused by mutations in the gene encoding dystrophin, a cytoskeletal protein that contributes to the stabilization of muscle fiber membrane during muscle activity. Affected individuals show progressive muscle wasting that generally causes death by age 30. In this study, the dystrophic mdx(5Cv) mouse model was used to investigate the effects of green tea extract, its major component (-)-epigallocatechin gallate, and pentoxifylline on dystrophic muscle quality and function. Three-week-old mdx(5Cv) mice were fed for either 1 or 5 wk a control chow or a chow containing the test substances. Histological examination showed a delay in necrosis of the extensor digitorum longus muscle in treated mice. Mechanical properties of triceps surae muscles were recorded while the mice were under deep anesthesia. Phasic and tetanic tensions of treated mice were increased, reaching values close to those of normal mice. The phasic-to-tetanic tension ratio was corrected. Finally, muscles from treated mice exhibited 30-50% more residual force in a fatigue assay. These results demonstrate that diet supplementation of dystrophic mdx(5Cv) mice with green tea extract or (-)-epigallocatechin gallate protected muscle against the first massive wave of necrosis and stimulated muscle adaptation toward a stronger and more resistant phenotype.

The Magnet Tracking System (MTS) is a minimally-invasive technique of continuous evaluation of gastrointestinal motility. In this study, MTS was used to analyse colonic propulsive dynamics and compare the transit of a magnetic pill with that of standard radio-opaque markers. MTS monitors the progress in real time of a magnetic pill through the gut. Ten men and 10 women with regular daily bowel movements swallowed this pill and 10 radio-opaque markers at 8 pm. Five hours of recordings were conducted during 2 following mornings. Origin, direction, amplitude and velocity of movements were analysed relative to space-time plots of the pill trajectory. Abdominal radiographs were taken to compare the progress of both pill and markers. The magnetic pill lay idle for 90% of its sojourn in the colon; its total retrograde displacement accounted for only 20% of its overall movement. Analysis of these movements showed a bimodal distribution of velocities: around 1.5 and 50 cm min(-1), the latter being responsible for 2/3 of distance traversed. There were more movements overall and more mass movements in males. Net hourly forward progress was greater in the left than right colon, and greater in males. The position of the magnetic pill correlated well with the advancement of markers. MTS showed patterns and propulsion dynamics of colonic segments with as yet unmet precision. Detailed analysis of slow and fast patterns of colonic progress makes it possible to specify the motility of colonic segments, and any variability in gender. Such analysis opens up promising avenues in studies of motility disorders.