Improved ventricular function during inhalation of PGI(2) aerosol partly relies on enhanced myocardial contractility

Inhaled prostacyclin (PGI(2)) aerosol induces selective pulmonary vasodilation. Further, it improves right ventricular ( RV) function, which may largely rely on pulmonary vasodilation, but also on enhanced myocardial contractility. We investigated the effects of the inhaled PGI(2) analogs epoprostenol (EPO) and iloprost (ILO) on RV function and myocardial contractility in 9 anesthetized pigs receiving aerosolized EPO (25 and 50 ng center dot kg(-1) center dot min(-1)) and, consecutively, ILO (60 ng center dot kg(-1) center dot min(-1)) for 20 min each. We measured pulmonary artery pressure ( PAP), RV ejection fraction (RVEF) and RV end-diastolic-volume (RV-EDV), and left ventricular end-systolic pressure-volume-relation (end-systolic elastance, E-es). EPO and ILO reduced PAP, increased RVEF and reduced RVEDV. E-es was enhanced during all doses tested, which reached statistical significance during EPO25ng and ILO, but not during EPO50ng. PGI(2) aerosol enhances myocardial contractility in healthy pigs, contributing to improve RV function. Copyright (C) 2005 S. Karger AG, Basel

MicroRNA-196a & microRNA-101 expression in Barrett's oesophagus in patients with medically and surgically treated gastro-oesophageal reflux

<p>Abstract</p> <p>Background</p> <p>Proton pump inhibitor (PPI) medication and surgical fundoplication are used for the control of gastro-oesophageal reflux in patients with Barrett's oesophagus, but differ in their effectiveness for both acid and bile reflux. This might impact on the inflammatory processes that are associated with progression of Barrett's oesophagus to cancer, and this may be evident in the gene expression profile and microRNA expression pattern in Barrett's oesophagus mucosa. We hypothesised that two miRNAs with inflammatory and oncogenic roles, miR-101 and miR-196a, are differentially expressed in Barrett's oesophagus epithelium in patients with reflux treated medically vs. surgically.</p> <p>Findings</p> <p>Mucosal tissue was obtained at endoscopy from patients with Barrett's oesophagus whose reflux was controlled by proton pump inhibitor (PPI) therapy (n = 20) or by fundoplication (n = 19). RNA was extracted and the expression of miR-101 and miR-196a was measured using real-time reverse transcription - polymerase chain reaction. There were no significant differences in miR-101 and miR-196a expression in Barrett's oesophagus epithelium in patients treated by PPI vs. fundoplication (p = 0.768 and 0.211 respectively). Secondary analysis showed a correlation between miR-196a expression and Barrett's oesophagus segment length (p = 0.014).</p> <p>Conclusion</p> <p>The method of reflux treatment did not influence the expression of miR-101 and miR-196a in Barrett's oesophagus. This data does not provide support to the hypothesis that surgical treatment of reflux better prevents cancer development in Barrett's oesophagus. The association between miR-196a expression and Barrett's oesophagus length is consistent with a tumour promoting role for miR-196a in Barrett's oesophagus.</p

Worldwide Esophageal Cancer Collaboration : clinical staging data

Peer reviewe

Designing programmes of physical activity through sport: Learning from a widening participation intervention, 'City of Football'

Background: Implementation profoundly influences how well new audiences engage with sport-based physical activity programmes. Recognising that effective implementation relies on concurrently generating supportive contexts, systems and networks for the least engaged ‘target’ groups; this paper aims to address what underpins children’s (non) engagement with football-based physical activity. Methods: An observational research design, using a non-probability sample of N=594 primary and secondary schoolchildren assessed outcomes of a three-year ‘City of Football’ (CoF) programme. Pupils self-reported football participation, personal friendship networks and exposure to six concurrent sources of influence (SoI). A 2-step hierarchical cluster analysis and univariate analyses assessed between-cluster differences. Results: Girls played football least regularly (χ2 [4] = 86.722, p = 0.000). Overall, participation was significantly associated with personal networks engaged in football. Boys’ personal networks were more stable and structurally effective. Football participation was also positively and linearly association with SoI scores. Girls and pupils with no personal networks around football reported the lowest SoI scores. Three clusters emerged, dominated by social network influences. The Traditional Market (n=157, 27.7%) comprised 81.7% boys; they regularly played football, had the most effective network structure and scored highly across all six domains of SoI. The Sporadically Engaging Socialisers (n=190, 33.5%) comprised 52.9% girls who rarely played football, reported low SoI scores and an inferior network structure. In the Disconnected cluster (n=220, 38.8%), 59.3% were non-footballing girls who reported the lowest motivation and ability SoI scores; and no personal networks engaged in football. Conclusions: This study reveals new insights about the primacy of social network effects for engaging children in football-based physical activity programmes. With little or no attention to these social-oriented issues, such interventions will struggle to attract ‘target’ children, but will readily engage already well-connected, experienced football-playing boys. The challenge for drawing non-footballing children into football-based interventions lies with engaging children – especially girls - whose social networks are not football-focused, while they also find football neither personally motivating nor easy to do

Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals

We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was "pinched," with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved

Recommendations for neoadjuvant pathologic staging (ypTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals

We report analytic and consensus processes that produced recommendations for neoadjuvant pathologic stage groups (ypTNM) of esophageal and esophagogastric junction cancer for AJCC/UICC cancer staging manuals, 8(th) edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data for 22,654 patients with epithelial esophageal cancers; 7,773 had pathologic assessment after neoadjuvant therapy. Risk-adjusted survival for each patient was developed. Random Forest analysis identified data-driven neoadjuvant pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. An additional analysis produced data-driven anatomic neoadjuvant pathologic stage groups based only on ypT, ypN, and ypM categories. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus neoadjuvant pathologic stage groups. Grade and location were much less discriminating for stage grouping ypTNM than pTNM. Data-driven stage grouping without grade and location produced nearly identical groups for squamous cell carcinoma and adenocarcinoma. However, ypTNM groups and their associated survival differed from pTNM. The need for consensus process was minimal. The consensus groups, identical for both cell types were as follows: ypStage I comprised ypT0-2N0M0; ypStage II ypT3N0M0; ypStage IIIA ypT0-2N1M0; ypStage IIIB ypT3N1M0, ypT0-3N2, and ypT4aN0M0; ypStage IVA ypT4aN1-2, ypT4bN0-2, and ypTanyN3M0; and ypStage IVB ypTanyNanyM1. Absence of equivalent pathologic (pTNM) categories for the peculiar neoadjuvant pathologic categories ypTisN0-3M0 and ypT0N0-3M0, dissimilar stage group compositions, and markedly different early- and intermediate-stage survival necessitated a unified, unique set of stage grouping for patients of either cell type who receive neoadjuvant therapy