bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased plasma levels of pentraxin 3 in patients with multiple sclerosis and neuromyelitis optica
Authors: Wang Honghao , Wang Kai , Wang Conghui , Zhong Xiaonan , Qiu Wei , Hu Xueqiang 
Published: September 2012

Background: Multiple sclerosis (MS) and neuromyelitis optica (NMO) are immune-mediated inflammatory diseases of the central nervous system. In the acute phase of these diseases, secondary ischemia due to inflammation-induced endothelial dysfunction may be an important pathological change. Pentraxin 3 (PTX3) is a pro-inflammatory protein and a novel biomarker of inflammatory vascular diseases. Objective: We aimed to determine whether PTX3 levels are elevated in MS and NMO patients. Methods: The concentrations of plasma PTX3 were measured using an enzyme-linked immunosorbent assay in 22 MS patients, 26 NMO patients, 15 acute cerebral infarction (CI) patients, 11 mild headache patients, and 14 volunteer controls. Results: During relapse, plasma PTX3 levels were higher in MS patients than in headache patients ( p=0.003) and controls ( p<0.001). Plasma PTX3 levels were also increased in NMO patients compared with CI patients ( p=0.011), headache patients ( p<0.001) and controls ( p<0.001). CI patients showed elevated PTX3 levels compared with controls ( p=0.008). MS and NMO patients showed a trend toward an increased disease disability with higher plasma PTX3 during relapse (MS: p=0.005; NMO: p<0.001). Plasma PTX3 levels were remarkably lower in remission than in the relapse stage (MS: p<0.001; NMO: p<0.001). Conclusion: Plasma PTX3 level is associated with inflammatory responses in MS and NMO.
Expanded functional coupling of subcortical nuclei with the motor resting-state network in multiple sclerosis
Authors: Dogonowski Anne-Marie , Siebner Hartwig R , Sørensen Per Soelberg , Wu Xingchen , Biswal Bharat , Paulson Olaf B , Dyrby Tim B , Skimminge Arnold , Blinkenberg Morten , Madsen Kristoffer H 
Published: September 2012

Background: Multiple sclerosis (MS) impairs signal transmission along cortico-cortical and cortico-subcortical connections, affecting functional integration within the motor network. Functional magnetic resonance imaging (fMRI) during motor tasks has revealed altered functional connectivity in MS, but it is unclear how much motor disability contributed to these abnormal functional interaction patterns. Objective: To avoid any influence of impaired task performance, we examined disease-related changes in functional motor connectivity in MS at rest. Methods: A total of 42 patients with MS and 30 matched controls underwent a 20-minute resting-state fMRI session at 3 Tesla. Independent component analysis was applied to the fMRI data to identify disease-related changes in motor resting-state connectivity. Results: Patients with MS showed a spatial expansion of motor resting-state connectivity in deep subcortical nuclei but not at the cortical level. The anterior and middle parts of the putamen, adjacent globus pallidus, anterior and posterior thalamus and the subthalamic region showed stronger functional connectivity with the motor network in the MS group compared with controls. Conclusion: MS is characterised by more widespread motor connectivity in the basal ganglia while cortical motor resting-state connectivity is preserved. The expansion of subcortical motor resting-state connectivity in MS indicates less efficient funnelling of neural processing in the executive motor cortico-basal ganglia-thalamo-cortical loops.
Scoring treatment response in patients with relapsing multiple sclerosis
Authors: Sormani MP , Rio J , Tintorè M , Signori A , Li D , Cornelisse P , Stubinski B , Stromillo ML , Montalban X , De Stefano N 
Published: September 2012

Background: We employed clinical and magnetic resonance imaging (MRI) measures in combination, to assess patient responses to interferon in multiple sclerosis. Objective: To optimize and validate a scoring system able to discriminate responses to interferon treatment in patients with relapsing–remitting multiple sclerosis (RRMS). Methods: Our analysis included two large, independent datasets of RRMS patients who were treated with interferons that included 4-year follow-up data. The first dataset (“training set”) comprised of 373 RRMS patients from a randomized clinical trial of subcutaneous interferon beta-1a. The second (“validation set”) included an observational cohort of 222 RRMS patients treated with different interferons. The new scoring system, a modified version of that previously proposed by Rio et al., was first tested on the training set, then validated using the validation set. The association between disability progression and risk group, as defined by the score, was evaluated by Kaplan Meier survival curves and Cox regression, and quantified by hazard ratios (HRs). Results: The score (0–3) was based on the number of new T2 lesions (>5) and clinical relapses (0,1 or 2) during the first year of therapy. The risk of disability progression increased with higher scores. In the validation set, patients with score of 0 showed a 3-year progression probability of 24%, while those with a score of 1 increased to 33% (HR = 1.56; p = 0.13), and those with score greater than or equal to 2 increased to 65% (HR = 4.60; p < 0.001). Conclusions: We report development of a simple, quantitative and complementary tool for predicting responses in interferon-treated patients that could help clinicians make treatment decisions.
Improved ability to work after one year of natalizumab treatment in multiple sclerosis. Analysis of disease-specific and work-related factors that influence the effect of treatment
Authors: Wickström Anne , Nyström Josefina , Svenningsson Anders 
Published: September 2012

Background: Multiple sclerosis (MS) constitutes one of the major diseases that leads to neurological impairment and as a consequence also reduces ability to work. Objectives: The purpose of this study was to analyze possible effects on work ability resulting from highly active anti-inflammatory treatment in MS. Methods: We analyzed the effects of introducing an anti-inflammatory treatment, natalizumab, in MS, on factors related to work ability. This was done through a comprehensive questionnaire distributed to all patients in Sweden starting on natalizumab treatment between June 2007 and May 2008, identified via the Swedish National MS registry. Results: MS patients who were receiving sickness benefit and were treated with natalizumab approximately doubled their working ability in relation to their total employment rate. We also documented a significant improvement of their ability to cope with work-related requirements after one year of natalizumab treatment, an improvement which was independent of the previous level of employment. Predictors of a positive effect on work ability were short disease duration, younger age and lower Expanded Disability Status Scale (EDSS) grade at treatment onset. Conclusions: Our data support the notion that early inflammatory control in MS is essential to preserve a healthy state in MS that counteracts the negative consequences of the disease both at a personal and at a societal level.
Nocturnal Asthma and Domestic Exposure to Fungi
Authors: Terčelj Marjeta , Salobir Barbara , Narancsik Zoltan , Kriznar Kristina , Grzetic-Romcevic Tanja , Matos Tadeja , Rylander Ragnar 
Published: September 2012

Fungal growth indoors is a common problem both in older and modern buildings. Numerous studies demonstrate a deterioration of asthma in environments with fungal growth but precise estimates of exposure levels have not been reported. This study was carried out to investigate whether levels of airborne fungi were higher in homes of subjects with nocturnal asthma as compared to controls. Subjects with nocturnal asthma (n = 42) and non-nocturnal asthma (n = 14) were recruited from an outpatient department. Subjects without disease or respiratory symptoms (n = 24) served as controls. Among the asthmatics, determinations were made of pulmonary function before and after treatment with bronchodilatators. The subjects were equipped with a pump and a filter and instructed to sample air in their bedroom. The filters were analysed for the content of N-acetylhexosaminidase (NAHA) as a marker of fungal cell biomass. In some houses the number of colony forming units was also determined. Patients with asthma had significantly higher activities of NAHA in their bedrooms as compared to controls (31.2 vs. 12.5 U m−3, p = 0.004). When the material was divided according to the 2nd quartile of NAHA (14.0 U m−3), 29 out of 42 subjects with nocturnal asthma had high values compared to 5 out of 24 for the controls (p<0.0001). The results support the hypothesis that patients with nocturnal asthma have high levels of fungi in their homes. This provides a basis for treatment and exposure diminution. Whether that exposure is causative for their disease; or if it aggravates already existing airway symptoms remains to be elucidated.
Aclidinium inhibits cigarette smoke-induced lung fibroblast-to-myofibroblast transition
Authors: Milara Javier , Serrano Adela , Peiró Teresa , Artigues Enrique , Gavaldà Amadeu , Miralpeix Montse , Morcillo Esteban J. , Cortijo Julio 
Published: September 2012

Cigarette smoking contributes to lung remodelling in chronic obstructive pulmonary disease (COPD). As part of this remodelling, peribronchiolar fibrosis is observed in the small airways of COPD patients and contributes to airway obstruction. Fibroblast-to-myofibroblast transition is a key step in peribronchiolar fibrosis formation.Thisin vitrostudy examined the effect of cigarette smoke on bronchial fibroblast-to-myofibroblast transition, and whether aclidinium bromide inhibits this process. Human bronchial fibroblasts were incubated with aclidinium bromide (10−9–10−7M) and exposed to cigarette smoke extract. Collagen type I and α-smooth muscle actin (α-SMA) expression were measured by real-time PCR and Western blotting, as myofibroblast markers. Intracellular reactive oxygen species, cyclic AMP (cAMP), extracellular signal-regulated kinase (ERK)1/2 and choline acetyltransferase were measured as intracellular signalling mediators.Cigarette smoke-induced collagen type I and α-SMA was mediated by the production of reactive oxygen species, the depletion of intracellular cAMP and the increase of ERK1/2 phosphorylation and choline acetyltransferase. These effects could be reversed by treatment with the anticholinergic aclidinium bromide, by silencing the mRNA of muscarinic receptors M1, M2 or M3, or by the depletion of extracellular acetylcholine by treatment with acetylcholinesterase.A non-neuronal cholinergic system is implicated in cigarette smoke-induced bronchial fibroblast-to-myofibroblast transition, which is inhibited by aclidinium bromide.
Expression of the nuclear factor-κB inhibitor A20 is altered in the cystic fibrosis epithelium
Authors: Kelly Catriona , Williams Mark T. , Mitchell Kathryn , Elborn J. Stuart , Ennis Madeleine , Schock Bettina C. 
Published: September 2012

A20 is a lipopolysaccharide (LPS)-inducible, cytoplasmic zinc finger protein, which inhibits Toll-like receptor-activated nuclear factor (NF)-κB signalling by deubiquitinating tumour necrosis factor receptor-associated factor (TRAF)-6. The action of A20 is facilitated by complex formation with ring finger protein (RNF)-11, Itch and TAX-1 binding protein-1 (TAX1BP1). This study investigated whether the expression of A20 is altered in the chronically inflamed cystic fibrosis (CF) airway epithelium.Nasal epithelial cells from CF patients (F508del homozygous), non-CF controls and immortalised epithelial cells (16HBE14o- and CFBE41o-) were stimulated with LPS. Cytoplasmic expression of A20 and expression of NF-κB subunits were analysed. Formation of the A20 ubiquitin editing complex was also investigated.In CFBE41o-, peak LPS-induced A20 expression was delayed compared with 16HBE14o- and fell significantly below basal levels 12–24 h after LPS stimulation. This was confirmed in primary CF airway cells. Additionally, a significant inverse relationship between A20 and p65 expression was observed. Inhibitor studies showed that A20 does not undergo proteasomal degradation in CFBE41o-. A20 interacted with TAX1BP1, RNF11 and TRAF6 in 16HBE14o- cells, but these interactions were not observed in CFBE41o-.The expression of A20 is significantly altered in CF, and important interactions with complex members and target proteins are lost, which may contribute to the state of chronic NF-κB-driven inflammation.
Childhood tuberculosis in Israel: epidemiological trends and treatment outcomes, 1999–2010
Authors: Mor Zohar , Cedar Noa , Pinsker Galia , Bibi Haim , Grotto Itamar 
Published: September 2012

Childhood tuberculosis (TB) poses a high risk for morbidity and death. This study describes the characteristics of childhood TB in Israel and examines treatment outcomes. Data sources were the National TB Registry and the National Civil Census.Between 1999 and 2010, 416 children (aged <18 years) had TB, averaging 1.5 per 100 000 children (range 0.6–3.2), demonstrating a declining trend. The average proportion of all TB cases reported annually that were in children was 8.4% (range 5.4–11.8%). Most (n=320, 79%) of the childhood TB cases were pulmonary. TB rates were highest for the 0–4-year age group and lowest for the 10–14-year age group.Of all childhood TB cases, 236 (56.7%) were born in countries with high prevalence of TB: 214 were Israeli citizens who were Ethiopian-born and 22 were non-Israeli citizens. The overall childhood TB incidence in 2010 was 1.05 cases per 100 000 children. The incidence of TB for Israeli-born children, children whose parents were Ethiopian-born and children of migrant workers was 0.55 per 100 000, 7.5 per 100 000 and 50–100 per 100 000, respectively. Cultures were taken from 60% of all childhood TB cases. Most children (97.8%) achieved treatment success, while three children (0.7%) died.Overall, rates of childhood TB rates in Israel are decreasing. However, children of parents born in countries with a high prevalence of TB are still at high risk of developing TB. Bacteriological confirmation should be encouraged to improve control of childhood TB.
Survival of lung adenocarcinoma patients with malignant pleural effusion
Authors: Wu Shang-Gin , Yu Chong-Jen , Tsai Meng-Feng , Liao Wei-Yu , Yang Chih-Hsin , Jan I-Shiow , Yang Pan-Chyr , Shih Jin-Yuan 
Published: September 2012

In the era of targeted therapy, the association between lung adenocarcinoma patient survival and malignant pleural effusions (MPEs) remains unclear. This study investigated the clinical characteristics, survival and epidermal growth factor receptor (EGFR) gene (EGFR) mutation status of lung adenocarcinoma patients with MPE.From June 2005 to December 2010, consecutive pleural effusions were collected prospectively. Patient clinical characteristics,EGFRmutation status, and overall survival were analysed.We collected MPEs from 448 patients in stage IV lung adenocarcinoma at initial diagnosis. Median overall survival for patients with MPEs at initial diagnosis and following disease progression were 14.3 months and 21.4 months, respectively (p=0.001). There were 296 (66.1%) patients harbouringEGFRmutations, the mutation rates among patients with an MPE at initial diagnosis and one following disease progression were 68.2% and 56.6%, respectively (p=0.044); the L858R mutation rate was also higher among the former (32.6%versus18.1%; p=0.009). Multivariate analysis revealed that patients who: developed MPEs following disease progression, harbouredEGFRmutations, and received EGFR-tyrosine kinase inhibitor therapy, had longer overall survival. Patients in stage IV lung adenocarcinoma with MPEs at initial diagnosis have shorter overall survival and higherEGFRmutation rate, especially for L858R, than patients who develop MPEs following disease progression.
Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis: a phase II randomised study
Authors: Wilson Robert , Welte Tobias , Polverino Eva , De Soyza Anthony , Greville Hugh , O'Donnell Anne , Alder Jeff , Reimnitz Peter , Hampel Barbara 
Published: September 2012

This phase II, randomised, double-blind, multicentre study (NCT00930982) investigated the safety and efficacy of ciprofloxacin dry powder for inhalation (DPI) in patients with non-cystic fibrosis bronchiectasis.Adults who were culture positive for pre-defined potential respiratory pathogens (includingPseudomonas aeruginosaandHaemophilus influenzae) were randomised to ciprofloxacin DPI 32.5 mg or placebo administered twice daily for 28 days (with 56 days of follow-up). Bacterial density in sputum (primary end-point), pulmonary function tests, health-related quality of life and safety were monitored throughout the study.60 subjects received ciprofloxacin DPI 32.5 mg and 64 received placebo. Subjects on ciprofloxacin DPI had a significant reduction (p<0.001) in total sputum bacterial load at the end of treatment (-3.62 log10CFU·g−1(range -9.78–5.02 log10CFU·g−1)) compared with placebo (-0.27 log10CFU·g−1(range -7.96–5.25 log10CFU·g−1)); the counts increased thereafter. In the ciprofloxacin DPI group, 14 (35%) out of 40 subjects reported pathogen eradication at end of treatmentversusfour (8%) out of 49 in the placebo group (p=0.001). No abnormal safety results were reported and rates of bronchospasm were low.Ciprofloxacin DPI 32.5 mg twice daily for 28 days was well tolerated and achieved significant reductions in total bacterial load compared with placebo in subjects with non-cystic fibrosis bronchiectasis.
Pulmonary hypertension in COPD: results from the ASPIRE registry
Authors: Hurdman Judith , Condliffe Robin , Elliot Charlie A. , Swift Andrew , Rajaram Smitha , Davies Christine , Hill Catherine , Hamilton Neil , Armstrong Iain J. , Billings Catherine , Pollard Lauren , Wild Jim M. , Lawrie Allan , Lawson Rod , Sabroe Ian , Kiely David G. 
Published: September 2012

The phenotype and outcome of severe pulmonary hypertension in chronic obstructive pulmonary disease (COPD) is described in small numbers, and predictors of survival are unknown. Data was retrieved for 101 consecutive, treatment-naïve cases of pulmonary hypertension in COPD.Mean±sdfollow-up was 2.3±1.9 years. 59 patients with COPD and severe pulmonary hypertension, defined by catheter mean pulmonary artery pressure ≥40 mmHg, had significantly lower carbon monoxide diffusion, less severe airflow obstruction but not significantly different emphysema scores on computed tomography compared to 42 patients with mild–moderate pulmonary hypertension. 1- and 3-year survival for severe pulmonary hypertension, at 70% and 33%, respectively, was inferior to 83% and 55%, respectively, for mild–moderate pulmonary hypertension. Mixed venous oxygen saturation, carbon monoxide diffusion, World Health Organization functional class and age, but not severity of airflow obstruction, were independent predictors of outcome. Compassionate treatment with targeted therapies in 43 patients with severe pulmonary hypertension was not associated with a survival benefit, although improvement in functional class and/or fall in pulmonary vascular resistance >20% following treatment identified patients with improved survival.Standard prognostic markers in COPD have limited value in patients with pulmonary hypertension. This study identifies variables that predict outcome in this phenotype. Despite poor prognosis, our data suggest that further evaluation of targeted therapies is warranted.
Obstructive sleep apnoea: longer respiratory event lengths in patients with heart failure
Authors: Efken Christina , Bitter Thomas , Prib Natalie , Horstkotte Dieter , Oldenburg Olaf 
Published: September 2012

This study investigated the effect of heart failure on respiratory patterns in patients with obstructive sleep apnoea (OSA).39 patients with established OSA (apnoea/hypopnoea index (AHI) >10 events·h−1) and either with heart failure (New York Heart Association (NYHA) class II and III, left ventricular-ejection fraction (LVEF) ≤40%; n=26, age mean±sd67±9 years) or without heart failure (LVEF ≥50%, N-terminal pro-brain naturic peptide <400 pg·mL−1; n=13, age 73±6 years) underwent simultaneous right- and left-heart catheterisation within 12 h of cardiorespiratory polygraphy recording.Respiratory patterns of OSA were significantly longer in OSA patients with heart failureversuswithout heart failure, including mean±sdcycle length (46.0±10.0versus37.8±10.6 s; p=0.024), ventilation length (25.4±6.3versus21.3±7.1 s; p=0.044), apnoea length (20.5±4.9versus16.5±3.9 s; p=0.013), time-to-peak ventilation (10.6±3.0versus8.3±2.5 sc; p=0.021) and circulatory delay (28.5±7.5versus22.6±3.7 s; p=0.005). Positive and robust correlations were found between some of these parameters and the degree of congestion in heart failure: cycle length (r=0.53; p=0.006), ventilation length (r=0.55; p=0.004) and time-to-peak ventilation (r=0.47; p=0.015) all increased with a rise in pulmonary capillary wedge pressure.Respiratory patterns in OSA appear to be dependent on cardiac function, with an increase in event lengths as cardiac function decreases. In patients with heart failure, some of these events correlate with the degree of pulmonary congestion.
The Study to Understand Mortality and Morbidity in COPD (SUMMIT) study protocol
Authors: Vestbo Jørgen , Anderson Julie , Brook Robert D. , Calverley Peter M.A. , Celli Bartolome R. , Crim Courtney , Haumann Brett , Martinez Fernando J. , Yates Julie , Newby David E. 
Published: September 2012

Chronic obstructive pulmonary disease (COPD) often coexists with other chronic diseases and comorbidities that can markedly influence patients' health status and prognosis. This is particularly true for cardiovascular disease (CVD). However, there have been no trials assessing the effect of COPD medications on CVD in patients with both diseases.The “Study to Understand Mortality and Morbidity in COPD” (SUMMIT) aims at determining the impact of fluticasone furoate/vilanterol combination and the individual components on the survival of patients with moderate COPD and either a history of CVD or at increased risk for CVD.SUMMIT is a multicentre, randomised, double-blind, parallel-group, placebo-controlled trial of 16 000 patients with moderate COPD randomly assigned to once daily treatment with fluticasone furoate/vilanterol (100/25 μg), fluticasone furoate (100 μg), vilanterol (25 μg) or matched placebo; mortality is the primary end-point. The study is an event-driven trial powered by the comparison of furoate/vilanterolversusplacebo. Secondary end-points are decline in forced expiratory volume in 1 s and effect on a composite cardiovascular end-point. This article describes the design of the SUMMIT study.
Imaging the inflammatory activity of sarcoidosis
Authors: Keijsers Ruth G.M. , van den Heuvel Daniel A.F. , Grutters Jan C. 
Published: September 2012

Accurate assessment of pulmonary and extrapulmonary organ involvement in sarcoidosis is one of the great challenges for clinicians. This assessment includes the evaluation of symptoms and of sarcoidosis activity in a specific organ and its functional consequences.In this review, radiological and nuclear techniques to image the inflammatory activity of sarcoidosis are described, in particular18F-FDG positron emission tomography/computed tomography. The current use of this technique in clinical practice is explained, particularly in patients with persistent symptoms, stage IV disease and cardiac sarcoidosis.