tbuckley/cabot-search huggingface dataset:
Oxidative stress, obesity and chronic inflammation in smokers according to smoking duration and heaviness
Authors: Velin Startev, Mariana Jordanova, Jordan Petev
Journal: European Respiratory Journal (2011)

Background:  Smoking and obesity are rising worldwide in an epidemic manner being common risk factors associated with the increase in the overall mortality. Smoking generates oxidative stress and chronic inflammation in the lungs, and the same mechanisms are involved in the pathogenesis of obesity.   Aim:  To assess the relationship between cigarette smoking, spirometry parameters and some anthropometric and inflammatory variables, as well as their association with the levels of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx).   Methods:  We performed a cross-sectional study of 94 smokers without any chronic diseases (mean age 52.7±6.4 years), divided into four groups according to their pack years. We performed a questionnaire, anthropometry, spirometry and biochemical tests. The erythrocyte activities of cellular SOD and GPx were measured.   Results:  We found that pack years correlated positively with body mass index (BMI) (p=0.002, r=0.323), waist circumference (WC) (p 1  (p=0.047, r= -0.205). BMI and WC were significantly associated with CRP. GPx concentrations were influenced by BMI (p=0.017, β= -0.358) and the number of cigarettes smoked per day (p=0.025, β= -0.398). SOD was also negatively influenced by BMI and WC (p 1  was related negatively with WC (p=0.047, β= -0.31).   Conclusion:  There is an increased oxidative stress and chronic inflammation in heavy smokers with long smoking history. These processes are closely linked with obesity, which along with smoking increase the risk of early decline in lung function.
Effects of Bu-Zhong-Yi-Qi-Tang (Hochuekkito: TJ-41) on the inflammatory responses in alveolar macrophages of hyperglycemic mice
Authors: Masayuki Nakayama, Hideaki Yamasawa, Manabu Soda, Naoko Mato, Tatsuya Hosono, Masashi Bando, Yukihiko Sugiyama
Journal: European Respiratory Journal (2011)

This study examines the influence of  Bu-Zhong-Yi-Qi-Tang  ( Hochuekkito ; TJ-41) on the inflammatory response in alveolar macrophage in hyperglycemic mice. BALB/c mice (males, six to eight weeks old) were divided into three groups: A, B, and C. From the outset, group A and B were fed an ordinary diet, whereas TJ-41 was given to group C. After the initiation of these diets, intraperitoneal injection of streptozotocin (STZ), 250mg/g in mice of groups B and C. Four weeks after the start of these diets, blood-glucose levels were measured, and bronchoalveolar lavage (BAL) was performed. Alveolar macrophages were sampled, and those demonstrating blood-glucose levels of more than 200 mg/dL were selected for use. Toll-like receptor (TLR) ligands (TLR2: peptidoglycan [PGN], TLR4: LPS, TLR5: flagellin [FLG]) were employed to stimulate pulmonary-alveolar macrophages, and ELISA was used to measure TNF-a production. TLR expression on pulmonary-alveoli surface was evaluated on the basis of the emergence of each TLR mRNA in alveolar macrophages. In mice given STZ, stimulus with TLR2, 5 ligands significantly inhibited TNF-a production. But in mice given a diet including TJ-41 inhibition of TNF-a production improved significantly. No differences were observed in the expression of TLR mRNA in pulmonary-alveolar macrophages and on cell surfaces. These results suggests the possibility that TJ-41 may enhance inhibition of pulmonary-alveolar macrophage inflammation response to TLR-ligands stimulus in conditions of high blood glucose.
The impact of paramedics' education on controlled oxygen prescribing for patients with acute exacerbations of COPD during ambulance transfers on outcomes
Authors: Emma Johnston, Tessa Coulson, Mark Newton, Ronan O'Driscoll, Nawar Diar Bakerly
Journal: European Respiratory Journal (2012)

Introduction   Oxygen is a drug and should be administered with caution and only when indicated using the principle of target oxygen saturation (British Thoracic Society-BTS emergency oxygen guidelines, 2008) particularly in those at risk of Type 2 Respiratory Failure (T2 RF) like COPD patients.   Aims   To reduce complications of excessive use of oxygen during ambulance transfer in patients with acute exacerbation of COPD.   Methods   Ambulance paramedics within Salford, UK were offered education on the BTS acute oxygen therapy guidelines that included lectures and written material with supplementary access to on-line training. The education focused on the principle of using target O2 saturations and controlled oxygen delivery to guide oxygen therapy in patients transferred to hospital with suspected exacerbation of COPD.   Results   Total of 63 paramedics were trained. Over the 3 months evaluation period post training, 75 (21 males) patients with COPD exacerbations were transferred by ambulance to the local hospital, 10 of whom were transferred by trained paramedics. No differences were noted between the 2 groups of patients in relation to first blood gas results (PH, PCO2, PO2), length of stay and number of 30 days readmissions. Fewer patients in the trained paramedics group needed NIV within 24 hours of admission, were admitted to ITU, or died in hospital.   Conclusions   A simple programme of paramedics9 education on the appropriate use of oxygen in patients at risk of T2RF according to guidelines may have a favourable impact on important patients9 safety and outcomes like in-hospital death, admission to ITU or the need for NIV.
Registry and conformity of endotracheal tube tip distance from carina at a large tertiary hospital
Authors: Leda Tomiko Yamada da Silveira, Aline Costa Lopes, Rodrigo Marques Di Gregorio, Carolina Fu
Journal: European Respiratory Journal (2011)

Physiotherapists are part of the Intensive Care Unit (ICU) team, although their role varies. In Brazil, they participate in endotracheal tube (ETT) management. Artificial airway management is an important part of routine ICU patient care. However, there are few studies about this subject.  Objectives were to find out: if ICU staff registered the measured mark of ETT at the lips (ETT mark); if registry was in accordance with real ETT mark; if a specific field for ETT mark registry influenced the filling of patient9s file; and if ETT tip distance from carina (ETT-carina distance) was correct according to thorax radiography.  199 cases of patients intubated for over 24 hours, from seven ICUs of Clinical Hospital of Medicine School of University of Sao Paulo, were included. Data observed: ETT mark, ETT-carina distance, ETT mark registry at patient9s files.  We found that there was no ETT mark registry neither on medical nor nursing records. Physiotherapists registered it in 55.8% of the cases. ETT mark registry was in accordance with observed in 82 cases (73.9%). Among the cases in which ETT mark was not registered, in most of them (72%) there was not a specific field. ETT-carina distance was correct (from 2.5 to 4.0 cm) in 60.8% of the cases.  In the ICUs analyzed, only physiotherapists registered ETT mark. In an expressive percentage (44.2%) there was no registry of this important information at all. The presence of a specific field may have positively influenced the filling of patient9s files. In a significant number of cases (39.2%) ETT-carina distance was incorrect, propitiating risk for intubated ICU patients. Perhaps ETT positioning has not been given the necessary attention.
Effect of baseline eosinophil count on response to CYT003-QbG10 in patients with persistent allergic asthma
Authors: Ian Pavord, Philipp Mueller, Cheryl Lassen, Thomas Casale, Kai-Michael Beeh
Journal: European Respiratory Journal (2013)

Background  The novel TLR-9 agonist CYT003-QbG10 (CYT003) has clinical activity in persistent allergic asthma thought to be mediated via inhibition of TH2 immune response.   Aims  This post-hoc analysis of a proof-of-concept randomised phase IIa study in mild-to-moderate controlled asthma tested the effect of CYT003 vs placebo on treatment response markers by TH2 status assessed by baseline blood eosinophil count (bEos).   Methods  63 patients received 7 doses of CYT003 (n=33) or placebo (n=30) over 12 weeks, with controlled ICS withdrawal in the last 8 weeks. Findings were stratified by an approximate median split of bEos.   Results  Mean (SE) bEos were 0.087 (0.01) in the lower (≤0.1 cells/nL) and 0.310 (0.03) in the higher bEos group. In higher bEos, ACQ increased significantly (p=0.002) from baseline with placebo (n=17) compared with CYT003 (n=16). This effect was evident before ICS withdrawal but was more obvious after (figure). There was no significant ACQ difference in patients with lower bEos (n=13 [placebo] and n=17 [CYT003]). FeNO (p=0.041) and FEV 1  deteriorated significantly with placebo compared with CYT003 (p=0.006) in patients with higher, but not lower, bEos.   Conclusions  Efficacy of CYT003 was most obvious in patients with evidence of TH2 activation. The effect persisted during ICS withdrawal, consistent with an inhibitory effect on TH2 immune responses. These findings warrant further investigation.
Activin-A expression in COPD exacerbations: Local index of airway inflammation? Preliminary results
Authors: Î‘rgyro Chatziantoniou, Î•irini Apostolou, Nikolaos Soulitzis, Eirini Neofytou, Eugenia Synolaki, Katerina M. Antoniou, Nikolaos Tzanakis, Paschalis Sideras, Nikolaos M. Siafakas
Journal: European Respiratory Journal (2014)

Background: Activin-A, a member of the TGF-β superfamily, is a widely expressed protein that can induce or inhibit inflammation, depending on cellular type and the stage of the host9s immune response. Activin-A also plays a key role in airway remodelling and its production is increased in several acute and chronic respiratory conditions.  Aim: To measure Activin-A levels at serum and sputum samples of COPD patients with exacerbations, in order to indentify its role as pro- or anti-inflammatory biomarker.  Methods: Serum blood and sputum specimens from 12 COPD current smokers [Age: 69.3±9.7 years; pack-years: 83±46; FEV 1  (%pred.): 50.2±29.7 and FEV 1 /FVC (%pred.): 54.2±12.0] were collected at three different time points for each patient: the first day of hospitalization (t 1 ), the day of discharge from the hospital (t 2 ) and one month after hospitalization (t 3 ). Activin-A levels were measured using an ELISA assay.  Results: A statistical significant decrease in Activin-A sputum levels was observed from hospitalization up to one month after exacerbation (t 1 : 545±101 pg/ml, t 2 : 481±115 pg/ml, t 3 : 217±98 pg/ml, p=0.043). In contrast, no significant differences were detected in Activin-A levels in patients9 serum (t 1 : 1006±307 pg/ml, t 2 : 933±324 pg/ml, t 3 : 1060±394 pg/ml, p=0.95).  Conclusion: These preliminary results suggest that sputum Activin-A levels could be a reliable progression index of airway inflammation. Further studies are needed to verify our findings.
Intravascular and Extravascular Microvessel Formation in Chronic Total Occlusions
Authors: Nigel R. Munce, Bradley H. Strauss, Xiuling Qi, Max J. Weisbrod, Kevan J. Anderson, General Leung, John D. Sparkes, Julia Lockwood, Ronen Jaffe, Jagdish Butany, Aaron A. Teitelbaum, Beiping Qiang, Alexander J. Dick, Graham A. Wright
Journal: JACC. Cardiovascular imaging (2010)
Evaluation of left ventricular function in patients with COPD – A mono centric retrospective study
Authors: Sreejita Bhowmick, Subhasis Ghosh
Journal: European Respiratory Journal (2011)

The functional abnormalities of right ventricle in long standing chronic obstructive pulmonary disease (COPD) have been well documented. Derangement of the left ventricular (LV) function in such patients, in the absence of other disorders affecting the LV, has not been clearly established.  This study has been designed to provide more definitive information concerning left ventricular function in patients with COPD primarily to ascertain the involvement of left ventricle in stable COPD patients in whom other sources of diastolic dysfunction has been systematically excluded which the previous studies had failed to do.  The aim of the study was to evaluate LV function in COPD patients.  To assess LV function in COPD patients, 30 patients with COPD without additional cardiac diseases and 30 age and sex-matched healthy subjects were enrolled into the study. We defined COPD by GOLD criteria. Well Investigated parameters of Left ventricular diastolic functions like E/A (peak velocity of early E wave (E)/peak velocity of early A wave (A) transmitral flow), IVRT (Isovolumetric relaxation time), MPI (Myocardial Performance Index) were used for the evaluation of LV diastolic function.  The study shows that 30% i.e. 9 out of the 30 patients admitted to the hospital with COPD had left ventricular diastolic dysfunction and that the risk of association with Left ventricular diastolic dysfunction is 6 times more in COPD patients than in a normal individual.  In COPD patients, LV diastolic function is significantly impaired and its magnitude is related with the severity of COPD as well as the increase in pulmonary artery pressure. This is in spite of preserved LV systolic function
Virtually all methicillin-resistant Staphylococcus aureus (MRSA) infections in the largest Portuguese teaching hospital are caused by two internationally spread multiresistant strains: the ‘Iberian’ and the ‘Brazilian’ clones of MRSA
Authors: D. Oliveira, I. Santos-Sanches, R. Mato, M. Tamayo, G. Ribeiro, D. Costa, H. de Lencastre
Journal: Clinical Microbiology and Infection (1998)
The STAT3 Inhibitor Galiellalactone Effectively Reduces Tumor Growth and Metastatic Spread in an Orthotopic Xenograft Mouse Model of Prostate Cancer
Authors: Giacomo Canesin, Susan Evans-Axelsson, Rebecka Hellsten, Olov Sterner, Agnieszka Krzyzanowska, Tommy Andersson, Anders Bjartell
Journal: European Urology (2015)
Prenatal exposure to DDE and PCB153 and infant's respiratory health: A European study
Authors: Mireia Gascon, Jordi Sunyer, Cécile Chevrier, Merete Eggesbo, Eva Govarts, Monika Kasper-Sonnenberg, Lubica Palkovicova, Maties Torrent, Maria Vassilaki, Martine Vrijheid
Journal: European Respiratory Journal (2013)

Epidemiological data suggest adverse effects of early-life exposure to persistent organic pollutants on the immune and respiratory systems, but evidence is still limited. The aim was to study the association between prenatal exposure to DDE and PCB153 and occurrence of respiratory symptoms in children from 10 European birth cohorts. A total of 4483 children with information on exposure and at least one respiratory health outcome were included: bronchitis, wheeze and acute otitis media (  2 years). We performed random effects meta-analyses using Poisson regression models. Exposure was introduced as a continuous variable (log transformed) and comparing high versus low (tertile) categories. DDE and PCB153 exposure as continuous were associated with bronchitis [RR per log unit increase of ng/L exposure (95%CI)=1.08 (1.00,1.16) and 1.09 (1.01,1.18), respectively]. Similar results were found when comparing high versus low exposure groups. However, in this case the risk of wheeze
Prediction of therapeutic effectiveness of nocturnal oxygen supplementation in Cheyne-Stokes breathing
Authors: Mihaela Hubatsch
Journal: European Respiratory Journal (2014)

Objective :Based on the clinical observation that many patients with Cheyne-Stokes breathing (CSB) exhibiting hypocapnia due to hyperventilation will normalise their PaCO2 value under treatment, we looked for a method to determine therapy's efficiency based on the changes of PaCO2 level in patients who underwent nightly O2 supplementation.

Design/subjects : Prospective intervention study of 55 consecutive patients with predominant CSB identified from 1457 patients referred for suspected sleep apnea syndrome. The mean age was 73.04 yrs. (SD=9.17), six were women.

Setting/Methods: Sleep Lab, Klinik Lowenstein, Germany. Overnight polysomnography was performed without and with O2 supplementation, respectively. Additionally, blood gases analysis was performed before and during O2 supply.

Results: The mean central apnoea-hypopnea index (AHI) was 35.65/h (SD=18.25), after O2 therapy it was reduced to 11.27/h (SD= 13.88) (p<0.0001). Therapy effectiveness is defined as the reduction of AHI under 5/h. O2 therapy proved to be effective in 67.27%. Although in the subgroups of effective and ineffective O2 therapy, AHI and nocturnal hypoxia (T85% and T90%) were decreased in a highly significant manner, only in the first subgroup these parameters were in therapeutic range. Regarding the gas exchange, statistically significant increase in PaO2 and fall in pH (p<0.0001) was noted. Highly significant increase in PaCO2 with a mean difference of 3.31 mmHg was noted in the first subgroup (p<0.0001), but only of 1.4 mmHg (p=0.49) in the therapy ineffective subgroup.

Conclusion : Certain increase in PaCO2 value irrespective of eu- or hypocapnia at baseline, could predict nocturnal O2 therapeutic efficacy.
Targeting a Novel ER/HOXB7 Signaling Loop in Tamoxifen-Resistant Breast Cancer
Authors: Marinus R. Heideman, Anna Frei, Nancy E. Hynes
Journal: Cancer Discovery (2015)

Abstract Summary: The majority of patients with breast cancer present with an estrogen receptor–positive (ER+) tumor, and the endocrine agent tamoxifen is a mainstay for their treatment. Unfortunately, however, resistance remains a major problem because most patients who respond eventually have a recurrence. Thus, an enduring challenge in the breast cancer field is to identify mechanisms underlying tamoxifen resistance. Jin and colleagues describe a novel ER/HOXB7 signaling loop in tamoxifen-resistant breast cancer models. Importantly, they reveal that targeting this signaling loop has great promise as an approach to treat patients with tamoxifen-resistant breast cancer. Cancer Discov; 5(9); 909–11. ©2015 AACR. See related article by Jin et al., p. 944.
Immunization with recombinant MAGE-A3 protein combined with adjuvant systems AS15 or AS02B in patients with unresectable and progressive metastatic cutaneous melanoma: A randomized open-label phase II study of the EORTC Melanoma Group (16032- 18031)
Authors: W. H. Kruit, S. Suciu, B. Dreno, V. Chiarion-Sileni, L. Mortier, C. Robert, M. Maio, V. G. Brichard, F. Lehmann, U. Keilholz
Journal: Journal of Clinical Oncology (2008)

9065 Background: The MAGE-A3 antigen, expressed in ±60% of metastatic melanomas, is a target of anti-tumor CD4+ and CD8+ T-cells. Previous data showed a few clinical responses of MAGE-A3 Antigen-Specific Cancer Immunotherapeutic in melanoma. This study was designed to evaluate MAGE-A3 recombinant protein combined with different Adjuvant Systems (AS). Methods: Patients (pts) with measurable metastatic MAGE-A3 (+) cutaneous melanoma (unresectable or in transit stage III or stage IV M1a) were randomized between immunization with MAGE-A3 protein combined with AS15 (CpG/MPL/QS21) or with AS02B (MPL/QS 21) as 1st line metastatic treatment. Pts received immunizations every 2 weeks for 6 doses. Those with clinical benefit received additional maintenance treatment for up to 4 yrs. Primary endpoints were CTC grade III/IV toxicity, objective response rate; secondary endpoints were immune response, progression- free survival. Planned sample size was 68 pts. Results: 91 out of 165 screened (55%) had MAGE-A3 (+) tumor biopsies and 75 pts were randomized. Among 72 eligible pts median age: 66 y (range 29–866 y), male: 36%, ECOG = 0: 93%, stage III in-transit: 26%, unresectable stage III: 46%, stage IV M1a: 28%. Toxicity in both treatment arms was comparable, mainly grade I/II with injection site reaction and constitutional symptoms (96%), rarely grade III/IV. Median number of immunizations was 9 (range 2–22). Objective responses (CR, PR) were reported in 3 pts (11, 23+, 24+ mns), 1 pt (5 mns) (AS15) and 0, 1 pt (6 mns) (AS02B). Stable disease (SD) > 16 wk was reported in 6 vs 5 pts in the 2 arms respectively. Anti-MAGE-3 antibody titers were higher in AS15 arm than in AS02B arm. CD4+ T-cell responses were observed in 72% (AS15) versus 36% (AS02B). Conclusions: The combination of MAGE-A3 + AS15 yielded higher specific Ab titers, more robust T-cell induction and long-lasting clinical responses or SD in metastatic melanoma. This warrants further development. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline
A simulation comparison of phylogeny algorithms under equal and unequal evolutionary rates.
Authors: Mary K. Kuhner, Joseph Felsenstein
Journal: Molecular Biology and Evolution (1994)

Using simulated data, we compared five methods of phylogenetic tree estimation: parsimony, compatibility, maximum likelihood, Fitch-Margoliash, and neighbor joining. For each combination of substitution rates and sequence length, 100 data sets were generated for each of 50 trees, for a total of 5,000 replications per condition. Accuracy was measured by two measures of the distance between the true tree and the estimate of the tree, one measure sensitive to accuracy of branch lengths and the other not. The distance-matrix methods (Fitch-Margoliash and neighbor joining) performed best when they were constrained from estimating negative branch lengths; all comparisons with other methods used this constraint. Parsimony and compatibility had similar results, with compatibility generally inferior; Fitch-Margoliash and neighbor joining had similar results, with neighbor joining generally slightly inferior. Maximum likelihood was the most successful method overall, although for short sequences Fitch-Margoliash and neighbor joining were sometimes better. Bias of the estimates was inferred by measuring whether the independent estimates of a tree for different data sets were closer to the true tree than to each other. Parsimony and compatibility had particular difficulty with inaccuracy and bias when substitution rates varied among different branches. When rates of evolution varied among different sites, all methods showed signs of inaccuracy and bias.
Clinical response to ertapenem in severe community-acquired pneumonia: a retrospective series in an elderly population
Authors: J.M. Murcia, J. González-Comeche, A. Marín, J. Barberán, J.J. Granizo, L. Aguilar, J. González-Moreno, B. González-Pina, M. López-Dupla, J. Irurzun
Journal: Clinical Microbiology and Infection (2009)