Publications

The "edge effect," late lumen loss at the margins of the treated segment, has become an important issue in the field of coronary brachytherapy. The aim of the present study was to assess the edge effect in noninjured margins adjacent to the irradiated segments after catheter-based intracoronary beta-irradiation.Fifty-three vessels were assessed by means of 3-dimensional intravascular ultrasound after the procedure and at 6- to 8-month follow-up. Fourteen vessels (placebo group) did not receive radiation (sham source), whereas 39 vessels were irradiated. In the irradiated group, 48 edges (5 mm in length) were identified as noninjured, whereas 18 noninjured edges were selected in the placebo group. We compared the volumetric intravascular ultrasound measurements of the noninjured edges of the irradiated vessels with the fully irradiated nonstented segments (IRS, n=27) (26-mm segments received the prescribed 100% isodose) and the noninjured edges of the vessels of the placebo patients. The lumen decreased (6 mm(3)) in the noninjured edges of the irradiated vessels at follow-up (P:=0. 001). We observed a similar increase in plaque volume in all segments: noninjured edges of the irradiated group (19.6%), noninjured edges of the placebo group (21.5%), and IRS (21.0%). The total vessel volume increased in the IRS in the 3 groups. No edge segment was subject to repeat revascularization.The edge effect occurs in the noninjured margins of radiation source train in both irradiated and placebo patients. Thus, low-dose radiation may not play an important role in this phenomenon, whereas nonmeasurable device injury may be considered a plausible alternative explanation.

Responsabilidad: Las Guías de Práctica Clínica recogen la opinión de la ESC y se han elaborado tras una consideración minuciosa de las evidencias disponibles en el momento en que fueron escritas. Se anima a los profesionales de la sanidad a que las tengan en plena consideración cuando ejerzan su juicio clínico. No obstante, las Guías de Práctica Clínica no deben invalidar la responsabilidad individual de los profesionales de la salud a la hora de tomar decisiones adecuadas a las circunstancias individuales de cada paciente, consultando con el propio paciente y, cuando sea necesario y pertinente, con su tutor o representante legal. También es responsabilidad del profesional de la salud verificar las normas y los reglamentos que se aplican a los fármacos o dispositivos en el momento de la prescripción. El contenido de las Guías de Práctica Clínica de la Sociedad Europea de Cardiología (ESC) ha sido publicado para uso exclusivamente personal y educacional. No está autorizado su uso comercial. No se autoriza la traducción o reproducción en ningún formato de las Guías de la ESC ni de ninguna de sus partes sin un permiso escrito de la ESC. El permiso puede obtenerse enviando una solicitud por escrito a Oxford University Press, la empresa editorial de European Heart Journal y representante autorizada de la ESC para gestionar estos permisos. © The European Society of Cardiology 2010. Reservados todos los derechos. Para la solicitud de permisos, diríjase por correo electrónico a: journals.permissions@ oxfordjournals.org Los comentarios-anotaciones (*) incluidos en esta traducción de la Guía han sido realizados por el Dr. José López-Sendón (Madrid, España).

Emergency stent implantation appears to be an effective method for restoring antegrade flow in case of an abrupt coronary occlusion during percutaneous transluminal coronary angioplasty (PTCA). In this case report, hemodynamic and metabolic changes throughout abrupt coronary closure and stent implantation were followed in order to study the efficacy of this bail out technique in restoring metabolic and hemodynamic disturbances due to acute coronary occlusion.

Eosinophils play a central role in asthma. The present study was performed to investigate the effect of tumour necrosis factor-α (TNF-α) on longevity of isolated human eosinophils. In contrast to Fas, TNF-α inhibited eosinophil apoptosis as evidenced by a combination of flow cytometry, DNA fragmentation assay and morphological analyses. The effect of TNF-α on eosinophil apoptosis was reversed by a TNF-α neutralising antibody. The anti-apoptotic effect of TNF-α was not due to autocrine release of known survival-prolonging cytokines interleukins 3 and 5 or granulocyte-macrophage-colony-stimulating factor as their neutralisation did not affect the effect of TNF-α. The anti-apoptotic signal was mediated mainly by the TNF-receptor 1. TNF-α induced phosphorylation and degradation of IκB and an increase in NF-κB DNA-binding activity. The survival-prolonging effect of TNF-α was reversed by inhibitors of NF-κB pyrrolidinedithiocarbamate and gliotoxin and by an inhibitor of IκB kinase, BMS-345541. TNF-α induced also an increase in AP-1 DNA-binding activity and the antiapoptotic effect of TNF-α was potentiated by inhibitors of AP-1, SR 11302 and tanshinone IIA and by an inhibitor of c-jun-N-terminal kinase, SP600125, which is an upstream kinase activating AP-1. Our results thus suggest that TNF-α delays human eosinophil apoptosis via TNF-receptor 1 and the resulting changes in longevity depend on yin-yang balance between activation of NF-κB and AP-1.

Gene expression, at least in part, is regulated by changes in histone acetylation status induced by activation of the proinflammatory redox-sensitive transcription factors activator protein-1 (AP-1) and nuclear factor-κB (NF-κB). Hyperacetylated histone is associated with open actively transcribed DNA and enhanced inflammatory gene expression. In contrast, hypoacetylated histone is linked to a closed repressed DNA state and a lack of gene expression. The degree of inflammatory gene expression is a result of a balance between histone acetylation and histone deacetylation. One of the major mechanisms of glucocorticoid function is to recruit histone deacetylase enzymes to the site of active gene expression, thus reducing inflammation. Oxidative stress can enhance inflammatory gene expression by further stimulating AP-1- and NF-κB-mediated gene expression and elevating histone acetylation. In addition, oxidants can reduce glucocorticoid function by attenuating histone deacetylase activity and expression. Thus, oxidant stress, acting through changes in chromatin structure, can enhance inflammation and induce a state of relative glucocorticoid insensitivity. This may account for the lack of glucocorticoid sensitivity in patients with chronic obstructive pulmonary disease. Antioxidants should reduce the inflammation and restore glucocorticoid sensitivity in these subjects. Antioxid. Redox Signal. 7, 144–152.

By combining two surveys covering a large fraction of the molecular material in the Galactic disk we investigate the role the spiral arms play in the star formation process. We have matched clumps identified by ATLASGAL with their parental GMCs as identified by SEDIGISM, and use these giant molecular cloud (GMC) masses, the bolometric luminosities, and integrated clump masses obtained in a concurrent paper to estimate the dense gas fractions (DGF$_{\rm gmc}=\sum M_{\rm clump}/M_{\rm gmc}$) and the instantaneous star forming efficiencies (i.e., SFE$_{\rm gmc} = \sum L_{\rm clump}/M_{\rm gmc}$). We find that the molecular material associated with ATLASGAL clumps is concentrated in the spiral arms ($\sim$60% found within $\pm$10 km s$^{-1}$ of an arm). We have searched for variations in the values of these physical parameters with respect to their proximity to the spiral arms, but find no evidence for any enhancement that might be attributable to the spiral arms. The combined results from a number of similar studies based on different surveys indicate that, while spiral-arm location plays a role in cloud formation and HI to H$_2$ conversion, the subsequent star formation processes appear to depend more on local environment effects. This leads us to conclude that the enhanced star formation activity seen towards the spiral arms is the result of source crowding rather than the consequence of a any physical process.

The purpose of this study was to compare the mid‐term clinical outcome of sirolimus‐eluting stent (SES) implantation and vascular brachytherapy (VBT) for in‐stent restenosis (ISR). We assessed the 9‐month occurrence of major adverse cardiac events (MACE) in 44 consecutive patients with ISR treated with SES implantation and 43 consecutive patients treated with VBT in the period immediately prior. Baseline clinical and angiographic characteristics of the two groups were similar. During follow‐up, three patients (7%) died in the VBT group and none in the SES group. The incidence of myocardial infarction was 2.3% in both groups. Target lesion revascularization was performed in 11.6% of the VBT patients and 16.3% of the SES patients ( P = NS). The 9‐month MACE‐free survival was similar in both groups (79.1% VBT vs. 81.5% SES; P = 0.8 by log rank). The result of this nonrandomized study suggests that sirolimus‐eluting stent implantation is at least as effective as vascular brachytherapy in the treatment of in‐stent restenosis. Catheter Cardiovasc Interv 2004;62:283–288. © 2004 Wiley‐Liss, Inc.

Electrical impedance measurements were performed on 13 atherosclerotic human aortic segments at 67 measuring spots in order to determine whether or not on the basis of these data a distinction can be made between atherosclerotic lesions and normal tissue. Stenosis localization and guidance of interventional techniques could be among the applications of an impedance measuring technique implemented on a catheter system. The experimental results, obtained with a two-electrode measuring technique, show that the apparent resistivity of an atherosclerotic spot does not necessarily deviate much from the resistivity of normal tissue. This is clarified by histology which shows that the majority of lesions has a surface layer of connective, fibrous tissue having almost similar conducting properties as the normal arterial wall. For gaining a deeper understanding of the way in which the measured data come about, a physical model of an atherosclerotic lesion is presented and confronted with the data. Both experimental data and theoretical considerations lead to the conclusion that only when the superficial fibrous layer is absent or very thin in relation to the size of the measuring electrode, the measured resistivity at a lesion is much higher than at normal spots. This occurs as a consequence of the high ohmic properties of the calcified or lipid deposits in the atherosclerotic lesion.

The effects of the inhaled neuropeptides, neurokinin A (NKA) and substance P (SP) on lung resistance (R L ) and airway microvascular permeability were studied in anaesthetized guinea‐pigs. Single doses of inhaled NKA (3 × 10 −5 , 1 × 10 −4 , 3 × 10 −4 m ; 45 breaths) and SP (1 × 10 −4 , 3 × 10 −4 , 1 × 10 −3 ; 45 breaths) caused a dose‐dependent increase in both R L and airway microvascular leakage, assessed as extravasation of the albumin marker, Evans blue dye. NKA at 1 × 10 −4 and 3 × 10 −4 m resulted in a significantly higher increase in R L than SP at the same doses. Inhaled SP (3 × 10 −4 m ; 45 breaths) caused significantly higher Evans blue dye extravasation in main bronchi and proximal intrapulmonary airways compared to the same dose of NKA. Pretreatment with the specific inhibitor of neural endopeptidase (NEP24.11), phosphoramidon, caused an approximately 100 fold leftward shift of the R L responses to inhaled NKA and SP. Phosphoramidon significantly potentiated both NKA‐ and SP‐induced airway microvascular leakage at proximal intrapulmonary airways, but not at any other airway level. Inhibition of NEP24.11 potentiate both the SP‐ or NKA‐induced airflow obstruction to a larger extent than the induced airway microvascular leakage, suggesting that NEP24.11 is more important in the modulation of the airflow obstruction observed after these mediators.