Double-blind controlled trial of flumazenil in patients who underwent upper gastrointestinal endoscopy

The antisedative effect of flumazenil, a benzodiazepine antagonist, was studied in a double-blind placebo controlled trial in 61 patients who underwent upper gastrointestinal endoscopy and sedation with benzodiazepines. The efficacy of flumazenil in reversing the effect of both benzodiazepines, diazepam and midazolam, was significantly higher than placebo (p less than 0.0001). The effect of flumazenil was prompt and was clearly noticed at the first assessment, 5 min after its administration. In none of the patients was a relapse of the sedative effect of the benzodiazepines noticed. The administration of flumazenil was free of major side effects. Flumazenil administration permits an earlier discharge of patients following endoscopy. Its availability in the endoscopy suite may improve the outcome of serious but rare side effects related to benzodiazepines.     

MF tricyclic and sulindac retard tumor formation in an animal model

New selective cyclooxygenase-2 inhibitors offer the benefit of cancer protection with less gastrointestinal toxicity associated with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). We hypothesize that MF tricyclic and sulindac can retard all stages of tumor formation in nude mice. In a blinded placebo controlled study, 3 types of experiments were performed: 1) 2.5 x 10(6) cells were injected into 2 flanks of nude mice subcutaneously, as a model for in situ cancer (n = 192); 2) 1 x 10(6) cells were injected into the cecum of mice as a model for in situ colorectal cancer (n = 78) and 3) 0.5 x 10(6) cells were implanted into the splenic subcapsule to establish a colorectal cancer liver metastasis model (n = 78). The animals were fed with standard chow containing either placebo, MF tricyclic (67 mg/kg of chow) or sulindac (150 mg/kg of chow). Mice that were given MF tricyclic or sulindac, at clinical anti-inflammatory plasma concentrations, were significantly more tumor free and had significantly smaller primary tumors and fewer metastases, as compared to mice that consumed placebo. The mortality and the latency period were significantly better in the treatment groups. These findings suggest that selective COX-2 inhibitors may serve as an adjunct to standard therapy in colorectal cancer.     

Quantitative SPECT/CT reconstruction for (177)Lu and (177)Lu/(90)Y targeted radionuclide therapies

We investigated the quantitative accuracy of SPECT/CT imaging studies as would be performed before and after targeted radionuclide therapy (TRT) using phantom experiments with (i) (99m)Tc, (ii) (177)Lu and (iii) (90)Y/(177)Lu. While the experiment with (99m)Tc imitated a diagnostic scan, the experiments with (177)Lu and (90)Y/(177)Lu modeled post-therapy acquisitions. At the next stage, we reconstructed images from pre- and post-therapy patient studies. The data were first reconstructed using two methods with limited corrections for the physics effects. Then, to generate quantitatively accurate absolute activity distributions, we applied a hybrid (model-based and window-based) reconstruction strategy where some of the physics effects were accurately modeled while corrections for other effects were empirical and based on information obtained from the projection data. The accuracies of absolute activity recovered by the hybrid method from the six phantom experiments were very similar to each other and acceptable for potential use in TRT. When measured in identical regions of interest, the (99m)Tc activity was reconstructed with errors ranging between?-3.3% and 2.9%, while the (177)Lu activity was reconstructed from experiments with (177)Lu and (90)Y/(177)Lu with errors ranging between?-1.6% and 1.6%. The reconstruction algorithms with limited corrections led to larger and case-specific errors as might have been expected. From a clinical prospective, our results showed that physics-based reconstructions improved resolution of images corresponding to both diagnostic scans with (99m)Tc and post-therapy scans with (177)Lu. Our analysis of patient study demonstrated that lack of corrections led to overestimation of activities in organs and tumor by 29-39% for the diagnostic scan with (99m)Tc and by 105-218% for post-therapy scan with (177)Lu.     

Renal effects of the serine protease inhibitor aprotinin in healthy conscious mice

Treatment with aprotinin,a broad-spectrum serine protease inhibitor with a molecular weight of 6512 Da,was associated with acute kidney injury,which was one of ...     

Determinants of mortality in patients with type 2 diabetes: a review

We aimed to review and summarize the evidence from accomplished trials analyzing factors influencing mortality in patients with T2DM and to provide some recommendations for targets and treatment in the European region. The following databases were searched for relevant trials: PubMed and the Cochrane Library. Of 3.806 citations, 134 trials met our inclusion criteria. Results: The reduction in lifetime for 65 + ?years-old patients having less than 10 years T2DM amounts to 1.8 years. Having T2DM for more than 10 years lifetime will be reduced by 2.7 years. However, the lifetime shortening factor of T2DM will even be stronger for 40 + ?years-old patients at onset. Males will lose 11.6 years of life and 18.6 QUALYs. T2DM among females will reduce life by 14 QUALYs by 22 years. From a statistical point of view, the highest mortality rate will occur in an over 55-years-old European smoking and non-compliant diabetic woman with alcohol abuse living in a rural area with a low level of education and a low socio-economic status. Furthermore, other co-morbidities such as cardiovascular diseases, gout, and depression affect mortality. Additionally, mortality will increase with a BMI over 35 and also with a BMI under 20–25. This refers to the obesity paradox indicating a higher mortality rate among normal weight patients with T2DM compared to overweight patients with T2DM. HbA1c-levels between 6.5 % and 7 % are associated with the lowest impact on mortality.