6,963 publications from this institution
Aims:The Xeltis aortic valve leaflets are made from a bioabsorbable supramolecular polymer that guides the tissue to restoring itself.It is mounted on a self-expanding nitinol frame that includes three feelers and a native leaflet clipping mechanism.We sought to investigate the acute valve performance in a preclinical setting.
Background Current ESC guidelines recommend the use of intra-coronary pressure guidewires for functional assessment of intermediate-grade coronary stenoses. Angiography-derived quantitative flow ratio (QFR) is a novel method of assessing these stenoses, and guiding percutaneous coronary intervention (PCI). Methods/Design The PIONEER IV trial is a prospective, all-comers, multi-center trial, which will randomize 2,540 patients in a 1:1 ratio to PCI guided by angiography-derived physiology or usual care, with unrestricted use in both arms of the Healing-Targeted Supreme sirolimus-eluting stent (HT Supreme). The stent's fast, biologically healthy, and robust endothelial coverage allows for short dual-antiplatelet therapy (DAPT); hence the antiplatelet regimen of choice is 1-month DAPT, followed by ticagrelor monotherapy. In the angiography-derived physiology guided arm, lesions will be functionally assessed using on-line QFR, with stenting indicated in lesions with a QFR ≤0.80. Post-stenting, QFR will be repeated in the stented vessel(s), with post-dilatation or additional stenting recommended if the QFR<0.91 distal to the stent, or if the delta QFR (across the stent) is >0.05. Usual care PCI is performed according to standard clinical practice. The primary endpoint is a non–inferiority comparison of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, any myocardial infarction, or any clinically, and physiologically driven revascularization with a non–inferiority risk-difference margin of 3.2%, at 1-year post-procedure. Clinical follow-up will be up to 3 years. Summary The PIONEER IV trial aims to demonstrate non–inferiority of QFR-guided PCI to usual care PCI with respect to POCE at 1-year in patients treated with HT Supreme stents and ticagrelor monotherapy. Clinical Trial Registration ClinicalTrials.gov Unique Identifier NCT04923191 Classifications Interventional Cardiology
A range of low molecular weight chemicals have been developed to antagonise the eotaxin receptor, cysteine-cysteine chemokine receptor-3 (CCR3), with the aim of selectively inhibiting eosinophil recruitment into tissue sites. However, the results of recent clinical trials with monoclonal antibodies directed against interleukin-5 (IL-5) question the role of eosinophils in mediating the symptoms of asthma and allergic disease. For this reason, the plans for clinical development of certain CCR3 antagonists have been halted. However, eotaxin 1-3 and a variety of other chemokines interact with CCR3; and this receptor is expressed not only on eosinophils but also on basophils, mast cell subpopulations, activated Th2 cells, macrophages, and airway epithelial cells. Hence, CCR3 is closely associated with asthma and allergy and blockade of this receptor may have pronounced beneficial effects in these diseases. We consider the chemical structures of CCR3 antagonist molecules from a range of pharmaceutical companies, and present an early clinical development plan for a hypothetical CCR3 antagonist. CCR3 antagonists are likely to be safe and effective therapies for allergic diseases, and their clinical pharmacology can readily be defined within phase I/II studies in patients with allergy and asthma.
No abstract is provided for this article.
Introducción y objetivos La relación entre las dimensiones del lumen medidas por ecografía intravascular (IVUS) y tomografía de coherencia óptica (OCT) en arterias coronarias humanas no es bien conocida. Los objetivos son comparar las dimensiones del lumen en IVUS, OCT e histología en arterias coronarias humanas ex vivo, y comparar in vivo las dimensiones del lumen obtenidas en pacientes con IVUS, OCT con oclusión y OCT sin oclusión. Métodos Estudio ex vivo: el área luminal se midió en secciones anatómicas correspondientes en IVUS, OCT e histología en arterias coronarias humanas. Estudio in vivo: el área luminal se midió en regiones correspondientes en IVUS y OCT con y sin oclusión. Resultados Ex vivo: en las 8 muestras estudiadas, el área del lumen fue más grande en IVUS y OCT que en histología –diferencia media, 0,8±1mm2 (28%) para OCT y 1,3±1,1mm2 (40%) para IVUS–. In vivo: en los cinco vasos analizados las dimensiones del lumen fueron más grandes en IVUS que en OCT –diferencia area media del lumen, 1,67±0.54mm2 (33,7%) para IVUS y OCT con oclusión y 1,11±0.53mm2 (21,5%) para IVUS y OCT sin oclusión–. Las dimensiones del lumen fueron más grandes en OCT sin oclusión que en OCT con occlusion –diferencia media, 0,61±0,23mm2 (13%). Conclusiones En arterias coronarias humanas fijadas, IVUS y OCT sobrestimaron el área del lumen en comparación con la histología. In vivo, las dimensiones del lumen fueron más grandes en IVUS que en OCT con o sin oclusión. La técnica de adquisición de OCT (con o sin oclusión) influye en las dimensiones del lumen. Introduction and objectives The relationship between the lumen dimensions obtained in human coronary arteries using intravascular ultrasound (IVUS) and those obtained using optical coherence tomography (OCT) is not well understood. The objectives were to compare the lumen measurements obtained ex vivo in human coronary arteries using IVUS, OCT and histomorphometry, and in vivo in patients using IVUS and OCT with and without balloon occlusion. Methods Ex vivo study: the lumen areas of matched anatomical sections of human coronary arteries were measured using IVUS, OCT and histology. In vivo study: the lumen areas in matched sections were measured using IVUS and OCT with and without occlusion. Results Ex vivo: in the eight specimens studied, the lumen area obtained using OCT and IVUS was larger than that obtained using histomorphometry: mean difference 0.8±1mm2 (28%) for OCT and 1.3±1.1mm2 (40%) for IVUS. In vivo: in the five vessels analyzed, the lumen area obtained using IVUS was larger than that obtained using OCT: mean difference 1.67±0.54mm2 (33.7%) for IVUS relative to OCT with occlusion and 1.11±0.53mm2 (21.5%) relative to OCT without occlusion. The lumen area obtained using OCT without occlusion was larger than that obtained using OCT with occlusion: mean difference 0.61±0.23mm2 (13%). Conclusions In fixed human coronary arteries, both IVUS and OCT overestimated the lumen area compared with histomorphometry. In vivo the lumen dimensions obtained using IVUS were larger than those obtained using OCT, with or without occlusion. Moreover, the OCT image acquisition technique (i.e. with or without occlusion) also had an impact on lumen measurement.
Cigarette smoke induces plasma exudation in the airways of rodents by activation of capsaicin‐sensitive ‘sensory‐efferent’ nerves. The response is mediated predominantly by substance P (SP) and the magnitude of exudation is regulated by neutral endopeptidase (NEP). The component(s) of the smoke responsible for the activation of the nerves may be reactive oxygen radicals. We investigated the effect of the hydroxyl radical scavenger dimethylthiourea (DMTU), a regulator of superoxide anion, superoxide dismutase (SOD), and a regulator of hydrogen peroxide, catalase, on plasma exudation (measured using Evans blue dye) induced by cigarette smoke in guinea‐pig main bronchi in vivo . The effect of DMTU on plasma exudation and non‐cholinergic bronchoconstriction (measured as pulmonary insufflation pressure, PIP) induced by electrical stimulation of the vagus nerves was also assessed. Interaction between hydroxyl radicals and NEP was assessed with the NEP inhibitor phosphoramidon. In each of the experiments, cigarette smoke increased plasma exudation by ∼200% above air‐exposed controls. Acute administration of DMTU (1.5 g kg −1 , i.v. for 20 min) significantly reduced cigarette smoke‐induced plasma exudation by 69%. In contrast, neither SOD (240,000 u kg −1 , i.v.) nor catalase (400,000 u kg −1 , i.v.) significantly affected the exudative response. Chronic pretreatment with DMTU (1.25 g kg −1 over 4 days) significantly reduced bronchial plasma exudation induced by cigarette smoke by 72%. Phosphoramidon (1.5 mg kg −1 , i.v.) completely reversed the inhibition by DMTU of cigarette smoke‐induced plasma exudation. Vagal stimulation increased plasma exudation by ∼200% and PIP by ∼250%. Acute treatment with DMTU had no significant inhibitory effect on these responses, whereas chronic pretreatment inhibited them by ∼80%. Phosphoramidon reversed the inhibition by chronic DMTU. SP (1 nmol kg −1 ) increased plasma exudation by ∼250%, a response which was not inhibited by either acute or chronic DMTU. We conclude that hydroxyl radicals, rather than superoxide anion or hydrogen peroxide, are involved in the induction of neurogenic plasma exudation and bronchoconstriction induced by cigarette smoke or by electrical stimulation of the vagus nerves. These radicals also affect the activity of NEP. Acute DMTU may affect directly the neural actions of hydroxyl radicals contained in the cigarette smoke. Chronic pretreatment with DMTU may inhibit the neurogenic airway responses by effects on tachykinin biosynthesis and/or axonal transport.
