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.     

Massive haemoptysis death and other morbidity associated with high dose rate intraluminal radiotherapy for carcinoma of the bronchus

Fluctuation analysis allows for the determination of mutation rates in cell cultures in vitro. As originally described by Luria and Delbruck and extended by Lea and Coulson and by Capizzi and Jameson, this analysis has been useful in estimating mutation rates in cultured cells where the frequency of mutational events is low. However. in cultures where high mutation rates and multiple independent mutation events occur, leading to the accumulation of many mutant cells, these standard methods may not apply. Here, we present a new method for the estimation of mutation rates based on the assumption that multiple events may contribute to the accumulation of mutant cells. We compared mutation rates determined by Lea and Coulson's and by Capizzi and Jameson's methods with those determined by our method using experimental and stimulated data from our studies of immunoglobulin gene mutation and isotype switching in B lymphocyte cultures. The three methods resulted in very different calculated rates when many mutants were present in the culture, such as when mutation rates were high, while only small differences in calculated rates were found when mutants were rare. Unlike previous fluctuation analysis calculations, our method is applicable for the estimation of both low and high rates.     

A TORSION-BENDING LOADING FRAME FOR A UNIAXIAL FATIGUE TEST MACHINE

Abstract— A novel mixed-mode loading frame has been designed to fit a uniaxial servo-hydraulic test machine. The frame allows fatigue tests to be performed on circurnferentially slit round bars under combined in-phase torsion and bending loads at positive mean stresses. The growth of fatigue cracks was monitored using a direct current potential drop technique. An empirical equation relating crack depth and voltage is presented.     

Forskolin stimulation of water and cation permeability in aquaporin 1 water channels

Aquaporin 1, a six-transmembrane domain protein, is a water channel present in many fluid-secreting and -absorbing cells. In Xenopus oocytes injected with aquaporin 1 complementary RNA, the application of forskolin or cyclic 8-bromo- adenosine 3',5'-monophosphate increased membrane permeability to water and triggered a cationic conductance. The cationic conductance was also induced by direct injection of protein kinase A (PKA) catalytic subunit, reduced by the kinase inhibitor H7, and blocked by HgCl2, an inhibitor of aquaporin 1. The cationic permeability of the aquaporin 1 channel is activated by a cyclic adenosine monophosphate-dependent mechanism that may involve direct or indirect phosphorylation by PKA.     

Chemokine-induced fever: intracerebroventricular actions of MIP-1 and MIP-1 alpha in rats

The central pyrogenic actions in the rat of doublet macrophage inflammatory protein-1 (MIP-1) and MIP-1 alpha were determined by their intracerebroventricular infusion. Doses of 560 pg and 11.2 ng of MIP-1 or 10.0 ng MIP-1 alpha infused into the third cerebral ventricle induced a long lasting fever. However, MIP-1 alpha was much less potent than MIP-1 in terms of intensity and longer latency. Overall, these cytokines are pyrogenic when acting on the walls of the third ventricle; however, a dose 10 times greater than that injected directly into the anterior hypothalamus is required to evoke fever, as based on earlier experiments. Finally, circulating MIP-1 could act centrally by its entry through the choroid plexus into the ventricular system of the brain.     

A genetic screen for aminophospholipid transport mutants identifies the phosphatidylinositol 4-kinase, STT4p, as an essential component in phosphatidylserine metabolism

In an effort to understand molecular mechanisms of intracellular lipid transport, we have focused upon specific events required for de novo aminophospholipid synthesis in the yeast Saccharomyces cerevisiae. A genetic system for examining the steps between phosphatidylserine (PtdSer) synthesis in the endoplasmic reticulum and its transport to and decarboxylation by PtdSer decarboxylase 2 in the Golgi/vacuole has been developed. We have isolated a mutant, denoted pstB1, that accumulates PtdSer and has diminished phosphatidylethanolamine formation despite normal PtdSer decarboxylase 2 activity. The lesion in PtdSer metabolism is consistent with a defect in interorganelle lipid transport. A genomic DNA clone that complements the mutation was isolated, and sequencing revealed that the clone contains the STT4 gene, encoding a phosphatidylinositol 4-kinase. The pstB1 mutant exhibits a defect in Stt4p-type phosphatidylinositol 4-kinase activity, and direct gene replacement indicates that STT4 is the defective gene in the mutant. Creation of an STT4 null allele (stt4Delta::HIS3) demonstrates the gene is essential. These results provide evidence that implicates phosphoinositides in the regulation of intracellular aminophospholipid transport.     

Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial

CONTEXT: Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures. OBJECTIVE: To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures. DESIGN: Randomized, blinded, placebo-controlled trial. SETTING: Eleven community-based clinical research centers. SUBJECTS: Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later). INTERVENTION: All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial. MAIN OUTCOME MEASURES: Clinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry. RESULTS: Alendronate increased BMD at all sites studied (P<.001) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group, but not significantly so (14% reduction; relative hazard [RH], 0.86; 95% confidence interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by 36% in women with baseline osteoporosis at the femoral neck (>2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects. CONCLUSIONS: In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD.