6,963 publications from this institution
The first clinical study of paclitaxel-eluting stent for de novo lesions showed promising results. We performed the TAXUS III trial to evaluate the feasibility and safety of paclitaxel-eluting stent for the treatment of in-stent restenosis (ISR).The TAXUS III trial was a single-arm, 2-center study that enrolled 28 patients with ISR meeting the criteria of lesion length < or =30 mm, 50% to 99% diameter stenosis, and vessel diameter 3.0 to 3.5 mm. They were treated with one or more TAXUS NIRx paclitaxel-eluting stents. Twenty-five patients completed the angiographic follow-up at 6 months, and 17 of these underwent intravascular ultrasound (IVUS) examination. No subacute stent thrombosis occurred up to 12 months, but there was one late chronic total occlusion, and additional 3 patients showed angiographic restenosis. The mean late loss was 0.54 mm, with neointimal hyperplasia volume of 20.3 mm3. The major adverse cardiac event rate was 29% (8 patients; 1 non-Q-wave myocardial infarction, 1 coronary artery bypass grafting, and 6 target lesion revascularization [TLR]). Of the patients with TLR, 1 had restenosis in a bare stent implanted for edge dissection and 2 had restenosis in a gap between 2 paclitaxel-eluting stents. Two patients without angiographic restenosis underwent TLR as a result of the IVUS assessment at follow-up (1 incomplete apposition and 1 insufficient expansion of the stent).Paclitaxel-eluting stent implantation is considered safe and potentially efficacious in the treatment of ISR. IVUS guidance to ensure good stent deployment with complete coverage of target lesion may reduce reintervention.
Despite astounding advances in our understanding and treatment of asthma, patients still die. Indeed, mortality from asthma in several countries, including the United States, continues to rise, unlike mortality from other common treatable conditions1. The majority of deaths from asthma are avoidable if patients are adequately treated. Most deaths follow a period of unstable and deteriorating control of asthma, and pathological examination of the lungs shows an intense inflammatory response with widespread mucous plugging2. This finding suggests that therapeutic intervention -- in particular, an increase in glucocorticoid therapy -- is possible. A small proportion of patients, however, die . . .
<b>Rationale:</b> The commonest cause of hospitalizations is exacerbations of COPD, with ~50% attributed to bacterial infection. Epithelial cells are able to internalise bacteria, which remain viable after antibiotic treatment and can recolonize following airway damage by oxidants or viruses. This is possibly via a phosphoinositide-3- kinase-dependent mechanism. To explore this, BEAS-2B bronchial epithelial cells were treated with a PI3K inhibitor and uptake of <i>Haemophilus influenzae</i> compared with effects of naturally occurring stilbenes resveratrol and isorhapontigenin, which also inhibit this pathway. <b>Methods:</b> BEAS-2B cells were pre-treated for 1h with resveratrol, isorhapontigenin (30μM), or the PI3K inhibitor LY29400 (10μM), prior to 48h exposure to fluorescently-labelled heat-killed <i>H. influenzae</i> (n=4). Extra-cellular fluorescence was quenched by Trypan blue and internal fluorescence measured fluorometrically. Cell viability was measured by MTT assay. <b>Results:</b> BEAS-2B cells ingested <i>H. influenzae</i> in a time-dependent manner (Fig. 1), with significant inhibition by all three compounds at 24 and 48h. There was no significant effect on cell viability at these time points. <b>Conclusion:</b> PI3K inhibition disrupts the ability of cells to engulf <i>H. influenzae</i> with similar effects seen with resveratrol and isorhapontigenin. Reducing bacterial uptake using natural products may be a useful novel therapy to reduce repeat exacerbations.
The modulatory effect of bradykinin on excitatory nonadrenergic noncholinergic (e-NANC) neural constrictor responses was examined in anesthetized guinea pig airways in vivo. e-NANC responses were obtained by bilateral vagal stimulation in the presence of atropine (1 mg/kg i.v.) and propranolol (1 mg/kg i.v.). Indomethacin (5 mg/kg i.v.) and captopril (1 mg/kg i.v.) were pretreated to avoid the indirect effects of bradykinin by producing prostaglandins and to prevent endogenous breakdown of bradykinin, respectively. Bradykinin (0.01-1 nmol/kg i.v.) potentiated e-NANC responses in a dose-dependent manner. The potentiation was significant with 0.1 and 1 nmol/kg of bradykinin, 22.7 +/- 3.2% (mean +/- S.E.; P < .01) and 34.5 +/- 4.7% (P < .01), respectively), compared with that in sham-injected control animals (-4.7 +/- 3.6%). The potentiation of e-NANC responses by bradykinin (1 nmol/kg i.v.) was abolished by the subsequent administration of a bradykinin B2 receptor antagonist, HOE140 (0.1 mumol/kg i.v.), that was without effect on e-NANC responses by itself. The contraction induced by exogenous administration of substance P (1 nmol/kg i.v.) was not affected by the same dose of i.v. bradykinin; the change in substance P-induced bronchoconstriction was 9.2 +/- 8.3% with and 3.2 +/- 3.6% without bradykinin (P > .05). These results suggest that bradykinin potentiates e-NANC responses in guinea pig airways in vivo via B2 receptors which are possibly on prejunctional sites.
BACKGROUND--Inhaled frusemide inhibits airway responses to sodium metabisulphite and other indirect bronchial challenges in asthma by undetermined mechanisms which may relate to its ability to stimulate prostaglandin release. Inhalation of sodium metabisulphite provokes indirect bronchoconstriction, possibly by activating sensory nerves. To investigate the role of cyclooxygenase products in the airway actions of frusemide and sodium metabisulphite, the effects of a potent cyclooxygenase inhibitor, flurbiprofen, alone and in combination with frusemide were investigated against airway responsiveness to sodium metabisulphite. METHODS--In a double blind double placebo controlled study, 12 mild asthmatic subjects attended on four occasions to undergo three inhalation challenges with sodium metabisulphite. A baseline challenge was performed one hour before oral intake of flurbiprofen 200 mg or matched placebo, and two hours before inhalation of frusemide 40 mg or matched placebo. A second challenge was performed immediately after inhalation of frusemide (two hours after flurbiprofen) with a further challenge three hours later. The log concentration provoking a 20% fall in FEV1 (log PC20) was used to assess airway responsiveness to sodium metabisulphite. RESULTS--Frusemide caused an immediate 1.9 doubling dose protection and a lesser 0.7 doubling dose protection at three hours. This protection was enhanced by flurbiprofen at both time points to 2.7 (early) and 1.9 (late) doubling doses. In addition, flurbiprofen alone significantly reduced airway responsiveness to sodium metabisulphite by 1.1 doubling doses at both two and five hours. CONCLUSIONS--The generation of bronchoprotective prostaglandins is unlikely to underlie the inhibitory action of frusemide against airway responsiveness to sodium metabisulphite. Endogenous contractile prostaglandins within the airways may be involved in the bronchoconstrictor response to sodium metabisulphite.
No abstract is provided for this article.
With the growing use of stainless steel in the construction and offshore industries, there is an increasing interest and need to study the performance of stainless structures at elevated temperatures. The behavior and design of stainless steel I-section beam-columns in fire is investigated in this paper, addressing a scarcity of previous research on this topic. Finite element (FE) models of stainless steel beam-columns, able to replicate their response at elevated temperatures, are created and validated; the validated models are then used to perform parametric studies to generate extensive benchmark structural performance data. The design rules set out in the European structural steel fire design standard EN 1993-1-2 are assessed and shown to provide rather inaccurate and often unsafe ultimate strength predictions for stainless steel I-section beam-columns in fire. New fire design rules for stainless steel beam-columns are put forward. It is shown that the new proposals are able to offer improved accuracy and design efficiency relative to the EN 1993-1-2 beam-column design rules. The reliability of the proposed design rules is also verified on the basis of the fire design reliability criteria set out by Kruppa [Eurocodes–Fire parts: Proposal for a methodology to check the accuracy of assessment methods, CEN TC 250, Horizontal Group Fire, Document no: 99/130 (1999)], thereby demonstrating the suitability of the proposed design rules for inclusion in the upcoming revised version of EN 1993-1-2.
In order to study the mechanism of airway narrowing after inhaled platelet-activating factor (PAF) we measured concomitant changes in lung resistance (Rl) and in airway microvascular leakage in anesthetized guinea pigs. Rl and its recovery after hyperinflation at 5 min were measured until 6 min after PAF aerosol (0.1, 0.3, 1, and 3 mM), and in the case of 3 mM PAF also until 10 min. Microvascular leakage in trachea, main bronchi, and proximal and distal intrapulmonary airways was determined by measurement of extravasated Evans blue dye content. For comparison, the responses to inhaled histamine (3 mM) and 5-hydroxytryptamine (5HT) (3 mM), which act directly on airway smooth muscle, were also examined. Inhaled PAF increased Rl dose-dependently, with a maximal response (peak Rl) at 4 min after the inhalation, whereas the response to histamine or 5HT was maximal within a few seconds after the inhalation. Peak Rl (cm H2O/ml/s) was significantly less after PAF (1.03 ± 0.09) than after histamine (8.39 ± 1.07) or 5HT (18.3 ± 6.48), although there was no significant difference in Rl after hyperinflation (recovery Rl). No additional increase in Rl was seen between 5 and 10 min after exposure. PAF caused a dose-dependent increase in Evans blue dye extravasation; 3 mM PAF induced significantly higher leakage than did histamine or 5HT at all airway levels at 6 min. PAF did not cause any additional extravasation of Evans blue dye at 10 min compared with that at 6 min after exposure. After PAF, recovery Rl, as well as peak Rl, correlated significantly with the degree of Evans blue dye extravasation at all airway levels. PAF was comparably more potent than histamine and 5HT in inducing airway microvascular leakage than in causing increase in Rl. These data suggest that airway edema resulting from airway microvascular leakage is an important component of airway narrowing induced by inhalation of PAF.
