Current Issue : April - June Volume : 2015 Issue Number : 2 Articles : 7 Articles
Abstract\nBackground: This study evaluated the effects of aclidinium bromide, a long-acting muscarinic antagonist indicated\nfor maintenance treatment of chronic obstructive pulmonary disease (COPD), on exercise endurance, dyspnea, lung\nhyperinflation, and physical activity.\nMethods: In this randomized, double-blind, crossover study, patients with stable COPD and moderate-to-severe\nairflow limitation received aclidinium 400 ?g twice daily or placebo via Genuair�®/Pressair�®a for 3 weeks (2-week\nwashout between treatment periods). The primary endpoint was change from baseline to Week 3 in endurance\ntime, measured by constant work rate cycle ergometry testing at 75% peak incremental work rate. Changes from\nbaseline in intensity of exertional dyspnea (Borg CR10 Scale�®) and trough inspiratory capacity were secondary\nendpoints. Additional endpoints included changes from baseline in other spirometric, plethysmographic, and physical\nactivity (assessed by objective accelerometer measurement) parameters. Efficacy endpoints were analyzed using an\nanalysis of covariance model.\nResults: In total, 112 patients were randomized and treated (mean age 60.3 years; mean post-bronchodilator\nforced expiratory volume in 1 s 1.7 L [56.7% predicted]; mean endurance time 485.7 s). After 3 weeks, endurance\ntime was significantly increased with aclidinium versus placebo (treatment difference 58.5 s; p < 0.05). At Week 3,\naclidinium significantly reduced dyspnea intensity at isotime during exercise (treatment difference ?0.63; p < 0.05)\nand improved trough inspiratory capacity (treatment difference 78 mL; p < 0.05) versus placebo. Significant\nimprovements in spirometric, plethysmographic, and some physical activity parameters were observed with aclidinium\nversus placebo.\nConclusions: These results suggest that aclidinium significantly improves exercise endurance, exertional dyspnea,\nhyperinflation, and physical activity in patients with COPD....
Background: Delirium is an acute change in cognition and concentration that complicates the postoperative course.\nPatients who suffer delirium after surgery have an increased risk of persistent cognitive impairment, functional decline,\nand death. Postoperative delirium is also associated with an increased length of hospital stay and higher costs. With the\ngoal of preventing delirium in postoperative patients, we organized a medical team from the Delirium Management\nand Assessment Center (D-mac) at Okayama University Hospital in January 2012. The team members consisted of\nphysicians, pharmacists, nurses, and clinical psychologists.\nMethods: We retrospectively reviewed the medical records of patients with delirium to examine risk factors related to\nthe patients� background.\nResults: Fifty-nine postoperative patients with lung or esophageal cancer were investigated; 25% exhibited delirium\nduring hospitalization. Multiple logistic regression analysis showed significant associations between the presence of\ndelirium and a past history of delirium (odds ratio, 4.22; 95% CI, 1.10-16.2; p = 0.09) and use of benzodiazepine\nreceptor agonists (odds ratio, 3.97; 95% CI, 1.09-14.5; p = 0.03). Intervention by the D-mac significantly reduced the\nrate of delirium episodes in lung cancer patients (p =0.01). Notably, prior to intervention, the incidence of delirium\nwas 100% when three high-risk factors for delirium were present. In contrast, the incidence of delirium in patients\nwith three high-risk factors decreased following implementation of the D-mac intervention.\nConclusions: These findings suggest that active participation by various staff in the medical team managing delirium\nhad a marked therapeutic impact....
Background An imbalance between proteolytic enzymes\nand their inhibitors is thought to be involved in the pathogenesis\nof chronic obstructive pulmonary disease. Matrix\nmetalloproteinase-1, also known as interstitial collagenase,\nhas been implicated as a potentially important proteinase in\nthe genesis of chronic obstructive pulmonary disease and,\nmore specifically, emphysema.\nMethods We performed quantitative immunohistochemical\nassessment of matrix metalloproteinase-1 expression in\nthe resected lung of 20 smokers/ex-smokers who had varying\nseverity of airflow obstruction and emphysema and\ncompared this with the lungs of 5 nonsmokers. Emphysema\nwas measured using a morphometric measure of the lungs�\nsurface area/volume ratio and with qualitative and quantitative\ncomputed tomography (CT) measures of emphysema.\nResults There were significantly more matrix metalloproteinase-\n1-expressing alveolar macrophages and type II\npneumocytes as well as a greater percentage of small airways\nthat stained positively for matrix metalloproteinase-1\nin the lungs of smokers than in those of nonsmokers\n(p\\0.0001, p\\0.0001, and p = 0.0003, respectively).\nThe extent of staining of type II pneumocytes and airways\nfor matrix metalloproteinase-1 was significantly related to\nthe extent of smoking (p = 0.012 and p = 0.013, respectively).\nIn addition, the extent of matrix metalloproteinase-\n1 staining of alveolar macrophages was related to the lung\nsurface area/volume ratio and to qualitative estimates of\nemphysema on CT.\nConclusion These findings suggest that cigarette smoking\nincreases expression of matrix metalloproteinase-1 in\nalveolar macrophages as well as in alveolar and small\nairway epithelial cells. Smokers who develop emphysema\nhave increased alveolar macrophage expression of matrix\nmetalloproteinase-1....
Objectives We conducted a study on usefulness of the\ntuberculin skin test (TST) and the Quantiferon-TB Gold IT\n(QFT) tests as predictors of radiological changes after\ncontact with tuberculosis.\nMaterials and Methods The study group consisted of TBexposed\nHCWs working in the Military Institute of Medicine\n(Warsaw, Poland). The usefulness of TST, QFT, and\na combination of both tests was assessed for prediction of\nsilent radiological findings.\nResults 83 previously TB-exposed participants were\nrecruited. None of the participants had a history of active\ntuberculosis. Positive TST results were reported in 72\n(86.8 %) participants, and positive QFTs were observed in\n27 (32.5 %) cases. Chest radiographs revealed 23 findings\nspecific for non-active tuberculosis in 18 (21.7 %) participants.\nThe results of the QFTs were associated with the\nhighest negative predictive value, positive predictive value,\nand positive likelihood ratio of silent chest X-ray findings\nsuggestive of latent tuberculosis infection. Positive QFT\nwas the only statistically significant variable that increases\nthe odds ratio (ORââ?¬â??8.3) of the presence of typical of\ntuberculosis radiological changes in the lung.\nConclusion A positive QFT result in an individual with\nno TB history who was exposed to tuberculosis in the past\nis associated with a significantly higher risk of clinically\nsilent parenchymal lesions in lungs suggestive of previous\ntuberculosis....
Introduction. Epidermal growth factor receptor (EGFR) mutations are known as oncogene driver mutations and with EGFR\nmutations exhibit good response to the EGFR tyrosine kinase inhibitor Gefitinib. Some studies have shown that activation of\nestrogen and estrogen receptor ???? or ???? (ER????/????) promote adenocarcinoma.We evaluated the relationship between the two receptors\nand the potential therapeutic benefit with Gefitinib and Tamoxifen. Methods.We assessed the association between EGFRmutations\nas well as ER????/???? expression/location and overall survival in a cohort of 55 patients with LAC from a single hospital. PC9 (EGFR\nexon 19 deletion mutant; Gefitinib-vulnerable cells) and A549 (EGFR wild type; Gefitinib-resistant cells) cancer cells were used\nto evaluate the in vitro therapeutic benefits of combining Gefitinib and Tamoxifen. Results. We found that the cytosolic but not\nthe nuclear expression of ER???? was associated with better OS in LAC tumors but not associated with EGFRmutation. The in vitro\nstudy showed that combined Gefitinib and Tamoxifen resulted in increased apoptosis and cytosolic expression of ER????. In addition,\ncombining both medications resulted in reduced cell growth and increased the cytotoxic effect of Gefitinib. Conclusion. Tamoxifen\nenhanced advanced LAC cytotoxic effect induced by Gefitinib by arresting ER???? in cytosol....
Acute lung injury (ALI) occurs frequently in patients with severe traumatic brain injury (TBI) and is associated with a poor clinical\noutcome. Aquaporins (AQPs), particularly AQP1 and AQP4, maintain water balances between the epithelial and microvascular\ndomains of the lung. Since pulmonary edema (PE) usually occurs in the TBI-induced ALI patients, we investigated the effects of\na thaliporphine derivative, TM-1, on the expression of AQPs and histological outcomes in the lung following TBI in rats. TM-1\nadministered (10mg/kg, intraperitoneal injection) at 3 or 4 h after TBI significantly reduced the elevated mRNA expression and\nprotein levels of AQP1 and AQP4 and diminished the wet/dry weight ratio, which reflects PE, in the lung at 8 and 24 h after TBI.\nPostinjury TM-1 administration also improved histopathological changes at 8 and 24 h after TBI. PE was accompanied with tissue\npathological changes because a positive correlation between the lung injury score and the wet/dry weight ratio in the same animal\nwas observed. Postinjury administration of TM-1 improved ALI and reduced PE at 8 and 24 h following TBI. The pulmonaryprotective\neffect of TM-1 may be attributed to, at least in part, downregulation of AQP1 and AQP4 expression after TBI....
Purpose: To investigate the influence of induction chemotherapy (ICT) on dosimetric outcomes in patients with\ninoperable non-small cell lung cancer (NSCLC) treated with definitive chemoradiation (CRT).\nMaterials and methods: 30 patients with inoperable stage II-III NSCLC treated with 2ââ?¬â??4 cycles of ICT followed by\ndefinitive CRT to ? 60 Gy were selected. Tumor response to chemotherapy was scored by RECIST criteria. Treatment\nplans based on tumor extent prior to chemotherapy were generated based on equivalent planning constraints and\ntechniques as the original post-chemotherapy plans. Dosimetric parameters predictive of toxicity for lung, esophagus,\nheart, and spinal cord were compared amongst the pre- and post-ICT plans.\nResults: The majority of patients (70%) experienced an overall reduction in GTV size between the pre-ICT imaging and\nthe time of simulation. Comparing pre-and post-ICT diagnostic imaging, 5 patients met the RECIST criteria for response,\n23 were classified as stable, and 2 experienced disease progression on diagnostic imaging. Despite a significantly\nreduced GTV size in the post-ICT group, no systematic improvements in normal tissue doses were seen amongst the\nentire cohort. This result persisted amongst the subgroup of patients with larger pre-ICT GTV tumor volumes (>100 cc3).\nAmong patients with RECIST-defined response, a significant reduction in lung mean dose (1.9 Gy absolute, median 18.2\nGy to 16.4 Gy, p = 0.04) and V20, the percentage of lung receiving 20 Gy (3.1% absolute, median 29.3% to 26.3%, p = 0.04)\nwas observed. In the non-responding group of patients, an increased esophageal V50 was found post-chemotherapy\n(median 28.9% vs 30.1%, p = 0.02).\nConclusions: For patients classified as having a response by RECIST to ICT, modest improvements in V20 and mean\nlung dose were found. However, these benefits were not realized for the cohort as a whole or for patients with larger\ntumors upfront. Given the variability of tumor response to ICT, the a priori impact of induction chemotherapy to\nreduce RT dose to normal tissue in these patients is minimal in the setting of modern treatment planning...
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