Effect of polytetrafluoroethylene covering of Palmaz stents on the development of intimal hyperplasia in human iliac arteries

PURPOSE: The occurrence of neointimal hyperplasia within a stent may result in restenosis with recurrent symptoms of end-organ ischemia. This study evaluated the potential of a nonporous covering of a stent to function as a barrier to the formation of intrastent neointimal hyperplasia. MATERIALS AND METHODS: Twelve endovascular stent grafts were used to treat 12 high-risk patients with limb-threatening ischemia secondary to long-segment iliac artery occlusion. A 6-mm, thin-walled polytetrafluoroethylene graft was inserted and anchored to the common iliac artery with use of Palmaz stents. Each stent was covered by graft material over one-half of its length. Control angiograms obtained immediately after graft insertion were compared with follow-up angiograms obtained between 4 and 6 months after the initial procedure. On each angiogram, the region of the stent was magnified by 20x to permit computerized luminal diameter measurements. RESULTS: The mean luminal diameter within the stent was significantly greater on the covered (7.7 mm +/- 0.33 standard deviation) compared with the uncovered (6.7 mm +/- 0.85 standard deviation) portions (P < .01). CONCLUSIONS: Partially covered stents are a unique model for assessing the effects of an extrinsic stent covering on arterial healing and myointimal hyperplasia. These data suggest that a relatively nonporous covering of polytetrafluoroethylene may inhibit stent-related restenosis in iliac arteries.     

Elongation of the N-acyl side chain of sialic acids in MDCK II cells inhibits influenza A virus infection

The internal areas and the position of integration of the glycopeptide resistance element Tn1546 were characterized by using PCR fragment length polymorphism, sequencing, and DNA hybridization techniques with 38 high-level vancomycin-resistant Enterococcus faecium isolates of human and animal origins from Europe and the United States. Only minor variations in the coding regions within Tn1546 were found, suggesting high genetic stability. The isolates originated from broilers (n = 5), a chicken (n = 1), a duck (n = 1), a turkey (n = 1), pigs (n = 8), a pony (n = 1), and humans (n = 23). A total of 13 different types were defined based on a single-nucleotide difference in the vanX gene, the presence of insertion sequences, and hybridization patterns. For some types more than one isolate were found. For type 1, 10 isolates of both human and animal origins were found. All were indistinguishable from the reference strain, BM4147. For type 2, 11 isolates of human and animal origins were found. Six human isolates from England were all of type 3. Two human isolates from the United States, indistinguishable from each other, were type 9. These results showed that vancomycin-resistant E. faecium of animal and human origins can contain indistinguishable genetic elements coding for vancomycin resistance, indicating either horizontal gene transfer between E. faecium organisms of human and animal origins or the existence of a common reservoir for glycopeptide resistance.     

Empirical scoring functions. II. The testing of an empirical scoring function for the prediction of ligand-receptor binding affinities and the use of Bayesian regression to improve the quality of the model

This paper tests the performance of a simple empirical scoring function on a set of candidate designs produced by a de novo design package. The scoring function calculates approximate ligand-receptor binding affinities given a putative binding geometry. To our knowledge this is the first substantial test of an empirical scoring function of this type on a set of molecular designs which were then subsequently synthesised and assayed. The performance illustrates that the methods used to construct the scoring function and the reliance on plausible, yet potentially false, binding modes can lead to significant over-prediction of binding affinity in bad cases. This is anticipated on theoretical grounds and provides caveats on the reliance which can be placed when using the scoring function as a screen in the choice of molecular designs. To improve the predictability of the scoring function and to understand experimental results, it is important to perform subsequent Quantitative Structure-Activity Relationship (QSAR) studies. In this paper, Bayesian regression is performed to improve the predictability of the scoring function in the light of the assay results. Bayesian regression provides a rigorous mathematical framework for the incorporation of prior information, in this case information from the original training set, into a regression on the assay results of the candidate molecular designs. The results indicate that Bayesian regression is a useful and practical technique when relevant prior knowledge is available and that the constraints embodied in the prior information can be used to improve the robustness and accuracy of regression models. We believe this to be the first application of Bayesian regression to QSAR analysis in chemistry.