Search

Background: Inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABAs) are used to treat moderate to severe chronic obstructive pulmonary disease (COPD). Objective: To determine whether long-term ICS therapy, with and without LABAs, reduces inflammation and improves pulmonary function in COPD. Design: Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00158847) Setting: 2 university medical centers in The Netherlands. Patients: 114 steroid-naive current or former smokers with moderate to severe COPD. Measurements: Cell counts in bronchial biopsies and sputum (primary outcome); methacholine responsiveness at baseline, 6, and 30 months; and clinical outcomes every 3 months. Intervention: Random assignment by minimization method to receive fluticasone propionate, 500 μg twice daily, for 6 months (n = 31) or 30 months (n = 26); fluticasone, 500 μg twice daily, and salmeterol, 50 μg twice daily, for 30 months (single inhaler; n = 28); or placebo twice daily (n = 29). Results: 101 patients were greater than 70% adherent to therapy. Fluticasone therapy decreased counts of mucosal CD3+ cells (-55% [95% CI, -74% to -22%]; P - 0.004), CD4- cells (-78% [CI, -88% to 60%]; P < 0.001), CD8+ cells (-57% [CI, -77% to -18%]; P = 0.010), and mast cells (-38% [CI, -60% to -2%]; P = 0.039) and reduced hyperresponsiveness (P = 0.036) versus placebo at 6 months, with effects maintained after 30 months. Fluticasone therapy for 30 months reduced mast cell count and increased eosinophil count and percentage of intact epithelium, with accompanying reductions in sputum neutrophil, macrophage, and lymphocyte counts and improvements in FEV1 decline, dyspnea, and quality of life. Reductions in inflammatory cells correlated with clinical improvements. Discontinuing fluticasone therapy at 6 months increased counts of CD3+ cells (120% [CI, 24% to 289%]; P = 0.007), mast cells (218% [CI, 99% to 407%]; P < 0.001), and plasma cells (118% [CI, 9% to 336%]; P = 0.028) and worsened clinical outcome. Adding salmeterol improved FEV1 level. Limitations: The study was not designed to evaluate clinical outcomes. Measurement of primary outcome was not available for 24% of patients at 30 months. Conclusion: ICS therapy decreases inflammation and can attenuate decline in lung function in steroid-naive patients with moderate to severe COPD. Adding LABAs does not enhance these effects. Primary Funding Source: Netherlands Organization for Scientific Research, Netherlands Asthma Foundation, GlaxoSmithKline of The Netherlands, University Medical Center Groningen, and Leiden University Medical Center.

Toll-like receptors (TLRs) participate in the defence against bacterial infections that are common in patients with Chronic Obstructive Pulmonary Disease (COPD). We studied all tagging SNPs in TLR2 and TLR4 and their associations with the level and change over time of both FEV1 and sputum inflammatory cells in moderate-to-severe COPD. Nine TLR2 SNPs and 17 TLR4 SNPs were genotyped in 110 COPD patients. Associations of SNPs with lung function and inflammatory cells in induced sputum were analyzed cross-sectionally with linear regression and longitudinally with linear mixed-effect models. Two SNPs in TLR2 (rs1898830 and rs11938228) were associated with a lower level of FEV1 and accelerated decline of FEV1 and higher numbers of sputum inflammatory cells. None of the TLR4 SNPs was associated with FEV1 level. Eleven out of 17 SNPs were associated with FEV1 decline, including rs12377632 and rs10759931, which were additionally associated with higher numbers of sputum inflammatory cells at baseline and with increase over time. This is the first longitudinal study showing that tagging SNPs in TLR2 and TLR4 are associated with the level and decline of lung function as well as with inflammatory cell numbers in induced sputum in COPD patients, suggesting a role in the severity and progression of COPD.

Several studies support the use of CT for diagnosing coronal fractures of the distal radius but the inter-observer reliability of these observations is less well studied. We tested the null hypothesis that radiographs alone and the combination of radiographs and two-dimensional computed tomography scans (2DCT) have the same inter-observer variation for the diagnosis of coronal articular fracture lines in the distal radius.Using a web-based survey, 63 surgeons were randomized to evaluate 16 fractures of the distal radius on radiographs alone or radiographs and 2DCT for the presence or absence of a coronal fracture line of the lunate facet and, if present, the stability of the fracture. The kappa multirater measure was calculated to estimate agreement between observers.The inter-observer variation in diagnosis of a coronal fracture line was fair with both radiographs and 2DCT, as was the diagnosis of instability of the volar lunate facet fracture when present.Two-dimensional computed tomography does not improve observer agreement on the diagnosis of coronal plane articular fracture lines in the lunate facet of the distal radius.

Background Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia. These features are partially attributed to activation of the epidermal growth factor receptor (EGFR). Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists. We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation. Methods 114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 ± 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV1 63 ± 9% predicted. Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue+) area (%), proliferating (Ki-67+) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies. Results Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression. Epithelial features were not different between short-term quitters ( Conclusion Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years). Trial registration NCT00158847

Chronic atrial fibrillation was induced in goats by electrical pacing. After 9 to 23 weeks of sustained atrial fibrillation, the morphology of the atrial structures was examined. The majority of the cardiomyocytes exhibited marked changes in their cellular substructures, with the replacement of sarcomeres by glycogen as the main characteristic. Using immuno-histochemical staining procedures, we assessed the expression and organization of contractile and cytoskeletal proteins in these cases and compared them with the expression and organization of these proteins in normal atria. Part of the atrial cardiomyocytes acquired a dedifferentiated phenotype, as deduced from the re-expression of alpha-smooth muscle actin, the disappearance of cardiotin, and the staining patterns of titin, which resembled those of embryonic cardiomyocytes. From these results we conclude that chronic atrial fibrillation induces myocardial dedifferentiation. This model of chronic atrial fibrillation in goats offers the possibility to study the time course of changes in cardiac structure during sustained atrial fibrillation and after cardioversion.

66 pág, 13 ilus, 8 tab, 30 ref The USTED methodology is a linear programming model, which supports land use planning as regional planning of agricultural lands. Although it is focused at the regional level, it does include the farm level as well and it will mainly concentrate on the definition of farm types. These farm types are generalizations of the relatively large number of farms in the study area and are determined by farm size and soil type. Actual land use can not be used for the determination of these farm types, because the output of the methodology comprises land use. Still it might be important to relate farm sizes and soil types to actual land use, so that decisions of farmers are also included in the methodology. So this thesis tries to define farm size classes, related to actual land use, in order to determine farm types for the farm typology to be used for the USTED methodology. To get an overview of actual land use in relation to farm size and soil types, an inventory is carried out for a limited number of farms, on the basis of interviews. The investigated area is a part of the Guanacaste province, which is situated in the nort-west of Costa Rica. In the farm typology all the farms which are grouped together in farm types are included. Due to the impossibility to incorporate all the farms of the study area, a stratified sampling is used to define farm size classes. To get a sample of farms with the greatest pilot areas are chosen, where interviews are held. To see if this sample is a representative sample of the study area, two distributions are compared, one from census and one from interviews. When it seems to be a representative sample, data from interviews can be used to obtain the following information: - Types of soils and variances in soils within one farm. - Relation between farm size and current land use. - Relation between soil type and current land use. - Relation between parcel sizes and farm sizes. - In case of cattle breeding details can be mentioned about different pasture systems in relation with farm sizes. To make farm size classes, seven soil clusters from the study area, are distinguished, which are associations of soil types between different soil groups or combinations within one soil group. Soil group characteristics, which determine land properties, are given together with land use requirements of the occurring crops and pasture types, in order to get information about soil suitabilities which finally can be used for a land evaluation. This land evaluation is used to compare the expected land use with actual land use. Beside using scientific names of soil types it also seems important to use local names (the way farmers call them), because the relation between soil type with local names and land use seems more clear than the relation with scientific names. When looking at the relation between farm size and current land use, six land use classes are distinguished: homegardens, crops, pasture, forest, tree plantation and fallow. When farm size classes were related with actual land use there was a relation, but because these farm size classes are arbitrarily chosen, they did not coincide with actual land use. To rectify this fault, individual farms, instead of farm classes, were plotted per different soil cluster. Looking at the relation between soil type and current land use. Homegardens, forest and fallow occur on mostly all soil clusters, crops on fertile soils, and tree plantation is mainly present on soils with steep slopes. Pasture occurs on all soil clusters and is often the main land use cover. Because pasture is very important in the study area, differences are made as well in pasture systems, like pasture without animals, beef cattle, breeding cattle, dairy cattle and double purpose are investigated. It could be concluded that pasture systems were related to agro-ecological zones, which means that theses systems are more or less related to soil types. A relation between parcel size and farm size could not be made. So each farmer determines his land use by the occurring soil types. For the farm typology it is recommendable to define farm size classes per soil type, for each soil type has its own land use. In this way farm size classes coincide with actual land use and farm types may be better classified than in the past.