tbuckley/cabot-search huggingface dataset:
Effects of Phenoxybenzamine on Bladder Neck Opening<sup>1</sup>
Authors: N B Waterfall, Grant Williams
Journal: Journal of the Royal Society of Medicine (1980)

A study of the effects of the action of phenoxybenzamine on bladder neck opening during micturition is reported. Twenty patients with symptoms of prostatism but minimal prostatic enlargement were studied. Bladder neck opening was measured radiographically. Phenoxybenzamine was shown to increase bladder neck opening by an average of 30% and give symptomatic relief. Minimal side effects were noted.
Clinical course of patients with bronchiolitis obliterans after hematopoietic stem cell transplantation
Authors: Makiko Yomota, Yoshiro Nakahara, Yusuke Okuma, Yusuke Takagi, Shinichiro Mikura, Yukio Hosomi, Jum Aoki, Kazuteru Ohashi, Tatsuru Okamura
Journal: European Respiratory Journal (2014)

Introduction: Bronchiolitis obliterans (BO) is thought to be a rare complication with poor prognosis after hematopoietic stem cell transplantation (HSCT).

Method: We analyzed 825 patients who received HSCT between 2003 and 2013 at our hospital. Diagnosis of BO was made according to the NIHdefinition in 12 patients (1.5%).

Result: The 12 patients with BO included six males (50%), and median age was 41 years (range, 18–63 years). The medium period from HSCT to diagnosis of BO was 21 months. Mean values for %FEV1, FEV1%, %RV/TLC and %PEFR were 43%, 48.7%, 140.2% and 42%, respectively, at the time of diagnosis. In seven cases, declines in pulmonary function tests (PFT) antecedent to the appearance of findings on computed tomography (CT) were detected. In all cases, dose of systemic corticosteroid was increased after onset of BO. Bronchodilators were used in 10 patients, inhaled corticosteroids in 10, and oral macrolides in five. After the start of treatment, FEV1% improved in five patients, and the mean difference in FEV1.0% between pre- and post-treatment was +3.7%. Median survival time from diagnosis of BO was 33.7 months. The 2- and 5-year survival rates were 58% and 25%, respectively. The most common cause of death was respiratory infection (five cases), followed by carcinoma in another organ (two cases) and unknown (two cases). All three patients who survived less than 1 year died of infection (two with bacterial pneumonia, one with pulmonary aspergillosis).

Conclusion: Early detection of BO may be achieved by PFT, although whether early initiation of treatment can improve outcomes remains unclear. Patients with adequate management of infection could become long-term survivors.
Abstract 8893: High Purity Eicosapentaenoic Acid in Addition to a Strong Statin Makes Regression of Coronary Plaque in Patients with Angina Pectoris
Authors: Yoshinori Wakita, Yasushi Wakida, Takahumi Itou, Rika Mizuno
Journal: Circulation (2011)

Background: Japan EPA Lipid Intervention Study ( JELIS ) indicated the efficacy of EPA in addition to the first generation statin for coronary events. However, there are few studies on the efficacy of additional EPA to a strong statin in a manner of randomized controlled study. Objective: To evaluate the efficacy of additional EPA for coronary plaque volume ( CPV ) using intracoronary ultrasound ( IVUS ). Methods: Forty patients ( mean age 70 yo ) with angina pectoris who underwent percutaneous coronary intervention ( PCI ) and were administrated 2mg/day of pitavastatin were randomly assigned to EPA-group ( n=20 ) and non-EPA-group ( n=20 ). The patients in EPA-group were additionally administered 1800mg/day of EPA for more than 6 months. In all patients IVUS was performed at the day of PCI and average 8 months later. CPV were obtained at the site with apparent plaque but without clinically significant stenosis. At the same timing, pulse wave velocity ( PWV ) and carotid echography were recorded. Results: There were no significant changes in lipids profile, PWV and carotid echography index after randomization between 2 groups. There was significant reduction of CPV in EPA-group compared with non-EPA-group ( -21.9% vs -1.5% for total atheroma volume and -10.9% vs 4.4% for percent change in percent atheroma volume, respectively; P&lt;0.01 ). EPA/AA ratio was increased in EPA-group ( 0.4±0.3 to 1.2±0.5; p&lt;0.01 ). Conclusion: EPA reduced CPV even under the strong statin administration.
Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684.
Authors: J M Kirkwood, M H Strawderman, M S Ernstoff, T J Smith, E C Borden, R H Blum
Journal: Journal of Clinical Oncology (1996)

PURPOSE Interferon alfa-2b (IFN alpha-2b) exhibits antitumor activity in metastatic melanoma and on this basis has been evaluated as an adjuvant therapy following surgery for deep primary (T4) or regionally metastatic (N1) melanoma. METHODS A randomized controlled study of IFN alpha-2b (Schering-Plough, Kenilworth, NJ) administered at maximum-tolerated doses of 20 MU/m2/d intravenously (i.v.) for 1 month and 10 MU/m2 three times per week subcutaneously (SC) for 48 weeks versus observation, was conducted by the Eastern Cooperative Oncology Group (ECOG) in 287 patients. RESULTS A significant prolongation of relapse-free survival (P = .0023, one-sided) and prolongation of overall survival (P = .0237, one-sided) was observed with IFN alpha-2b therapy in this trial, which is now mature with a median follow-up time of 6.9 years. The impact of treatment on relapse rate is most pronounced early during the treatment interval. The overall benefit of treatment in this trial was analyzed stratified by tumor burden and the presence or absence of microscopic nonpalpable and palpable regional lymph node metastasis. The benefit of therapy with IFN alpha-2b was greatest among node-positive strata. Toxicity of IFN alpha-2b required dose modification in the majority of patients, but treatment at &gt; or = 80% of the scheduled dose was feasible in the majority of patients through the IV phase of treatment, and for more than 3 months of SC maintenance therapy. Discontinuation of treatment due to toxicity was infrequent after the fourth month of therapy. CONCLUSION IFN alpha-2b prolongs the relapse-free interval and overall survival of high-risk resected melanoma patients. The increment in median disease-free survival (from 1 to 1.7 years) and overall survival (from 2.8 to 3.8 years) that results from this therapy is associated with a 42% improvement in the fraction of patients who are continuously disease-free after treatment with IFN (from 26% to 37%) in comparison to observation. IFN alpha-2b is the first agent to show a significant benefit in relapse-free and overall survival of high-risk melanoma patients in a randomized controlled trial.
Sequence of the ebgA gene of Escherichia coli: comparison with the lacZ gene.
Authors: H W Stokes, P W Betts, B G Hall
Journal: Molecular Biology and Evolution (1985)

We have sequenced the ebgA (evolved beta-galactosidase) gene of Escherichia coli K12. The sequence shows 50% nucleotide identity with the E. coli lacZ gene, demonstrating that the two genes are related by descent from a common ancestral gene. Comparison of the two sequences suggests that the ebgA gene has recently been under selection. A significant excess of identical, rather than synonymous, codons used to encode identical amino acids at the same positions in the aligned sequences implies that some form of selection is operating directly at the DNA level. This selection is independent of, and in addition to, selection based on codon usage or on function of the gene products.
P-080 Staging echoendoscopy in esophagogastric cancer patients ongoing surgery
Authors: A. Villaescusa, M.T. Delgado Urena, B. Gonzalez-Astorga, F. Galvez Montosa, M. Yelamos Vargas, C.J. Rodriguez Gonzalez, J.M. Jurado Garcia
Journal: Annals of Oncology (2015)
Evaluation of asthma patients using the control of allergic rhinitis and asthma test (CARAT)
Authors: Ana Sofia Santos, Ricardo Coelho, Sofia Granadeiro, Raquel Rosa, Nicole Murinello, Rita Gerardo, Madalena Emiliano, Alexandra Borba, Luísa Semedo, Maria João Gomes, João Cardoso
Journal: European Respiratory Journal (2012)

Introduction: Asthma and allergic rhinitis are diseases often associated. According to international guidelines a combined approach of both conditions is recommended. The Asthma Control Test (ACT) is the most commonly used test to assess asthma control, but lacks an evaluation of the upper airway disease component. Recently a new test was created to assess the control of both components – the CARAT.

Aim: To evaluate asthma control in patients with associated rhinitis, by using ACT and CARAT tests, and compare results.

Methods: We performed a prospective study with a group of consecutive adult patients with allergic rhinitis and asthma from our outpatient clinic. The control of the disease was assessed using both ACT and CARAT tests.

Results: Forty patients were evaluated (mean age 53, 70% female). 17% of the patients had ACT controlled asthma and 45% had ACT uncontrolled asthma. In both groups CARAT results were equivalent.

In the 38% patients with ACT partially controlled asthma, CARAT results were as follow: 26% had a controlled CARAT test; 27% had an uncontrolled CARAT test due only to an uncontrolled upper airway component; 13% had only uncontrolled lower airway component and 27% had both airway components uncontrolled.

Conclusions: A tool able to assess both asthma and allergic rhinitis control was lacking. In our patients, using the CARAT was useful mainly in the partially controlled asthma population by helping to differentiate those in whom uncontrolled rhinitis was the main cause of the uncontrolled asthma.
The sedentary office: an expert statement on the growing case for change towards better health and productivity
Authors: John P Buckley, Alan Hedge, Thomas Yates, Robert J Copeland, Michael Loosemore, Mark Hamer, Gavin Bradley, David W Dunstan
Journal: British Journal of Sports Medicine (2015)

An international group of experts convened to provide guidance for employers to promote the avoidance of prolonged periods of sedentary work. The set of recommendations was developed from the totality of the current evidence, including long-term epidemiological studies and interventional studies of getting workers to stand and/or move more frequently. The evidence was ranked in quality using the four levels of the American College of Sports Medicine. The derived guidance is as follows: for those occupations which are predominantly desk based, workers should aim to initially progress towards accumulating 2 h/day of standing and light activity (light walking) during working hours, eventually progressing to a total accumulation of 4 h/day (prorated to part-time hours). To achieve this, seated-based work should be regularly broken up with standing-based work, the use of sit–stand desks, or the taking of short active standing breaks. Along with other health promotion goals (improved nutrition, reducing alcohol, smoking and stress), companies should also promote among their staff that prolonged sitting, aggregated from work and in leisure time, may significantly and independently increase the risk of cardiometabolic diseases and premature mortality. It is appreciated that these recommendations should be interpreted in relation to the evidence from which they were derived, largely observational and retrospective studies, or short-term interventional studies showing acute cardiometabolic changes. While longer term intervention studies are required, the level of consistent evidence accumulated to date, and the public health context of rising chronic diseases, suggest initial guidelines are justified. We hope these guidelines stimulate future research, and that greater precision will be possible within future iterations.
Pulmonary distribution and localization of pirfenidone in animal models of IPF by MS/MS
Authors: Isis Fernandez, Na Sun, Mian Wei, Michaela Aichler, Axel Walch, Oliver Eickelberg
Journal: European Respiratory Journal (2014)

Idiopathic Pulmonary Fibrosis (IPF) represents a life-threatening disease with poor prognosis and limited treatment options. Pirfenidone is the only drug approved in for the treatment of IPF, although its precise mechanism of action remains unclear. The presence and distribution of Pirfenidone within different compartments, and whether its administration routs has any metabolic effect during treatment is unknown.  10 week old mice were treated with pirfenidone or control orally for 10, 30, 45, 60, 90, and 180 min (n=4). Fibrosis was induced by bleomycin, at day 7 mice were treated orally with 500mg/kg of Pirfenidone daily, and harvested 7 days later. Tissue was snap frozen and used for in-situ identification of targets via MALDI-imaging.  In-situ distribution of pirfenidone and its relevant metabolites: 5-hydroxymethyl pirfenidone and 5-carboxylic acid pirfenidone was successfully achieved and analyzed qualitatively and quantitatively. Exhaustive kinetics allowed us detail quantification and organ specific drug and metabolites distribution from the initial peaks (30min) to complete excretion. Different administration routs (PO vs IT) showed distinct metabolite dynamics and distribution to the liver. Endogenous metabolic pathways (e.g. Purine and Pyrimidine biosynthesis, Glycolysis) alterations were detected in fibrotic vs healthy lung (e.g. Glutathione).  Our results are helping us to gain more insight in drug distribution and destination in fibrotic tissue, further experiments of in-situ correlation with ECM niches and cell-type specific compartments are ongoing. This will help us improving the current available therapy, and develop high-tech methods for up-coming drugs.
Is heart rate a risk marker in patients with chronic heart failure and concomitant atrial fibrillation? Results from the <scp>MAGGIC</scp> meta‐analysis
Authors: Joanne Simpson, Davide Castagno, Rob N. Doughty, Katrina K. Poppe, Nikki Earle, Iain Squire, Mark Richards, Bert Andersson, Justin A. Ezekowitz, Michel Komajda, Mark C. Petrie, Finlay A. McAlister, Greg D. Gamble, Gillian A. Whalley, John J.V. McMurray
Journal: European Journal of Heart Failure (2015)
Dismantling Limb-Girdle Muscular Dystrophy
Authors: Pushpa Narayanaswami
Journal: JAMA Neurology (2015)

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TNF-α, IL-8, IL-6 levels in serum of sarcoidosis patients with different clinical course
Authors: Olga Denisova, Kseniya Egorova, Georgy Chernogoryuk
Journal: European Respiratory Journal (2013)

Background: Although researchers have demonstrated systemic inflammation in sarcoidosis, the prognostic significance of various cytokines is yet unknown.  Methods: Levels of TNF-α, IL-8, IL-6 were determined by by ELISA s in blood serum of 41 patients with sarcoidosis onset (stage II) and 18 healthy controls. According to the 1-3year period of observation (without systemic corticosteroid treatment) sarcoidosis group was divided into 3 groups: spontaneous regression, progression and stabilization.  Results: Progression group is characterized by the highest levels of blood TNF-α, IL-6. Their values were significantly higher compared to regression group. IL-8, IL-6 levels were significantly higher in blood of progression group patients compared to control. The group of spontaneous regression expressed the highest level of IL-8. In contrast, TNF-α, IL-8, IL-6 levels was significantly reduced in Healthy control. Cytokine levels in the group with stabilization were not significantly different. Increased serum IL-6 level was associated with reduced FVC in sarcoidosis patients (r = -0.6; p   Conclusions: Serum TNF-α, IL-8, IL-6 appears to have a predictive value for sarcoidosis.
Time course effects of exercise training on pulmonary injury induced by exposure to cigarette smoke in mice
Authors: Alessandra C. Toledo-Arruda, Flávia Guarnier, Camila L. Suehiro, Francine Almeida, Clarice Olivo, Fernanda Lopes, Rodolfo Vieira, José Carlos Silva Camargo-Filho, Rubens Cecchini, Chin Lin, Mílton A. Martins
Journal: European Respiratory Journal (2013)

Rationale:  Experimental study recently developed by our group showed that the regular physical training attenuated the pulmonary injury in an experimental model of chronic exposure to cigarette smoke (CS).  Objective : The goal of this study was to evaluate the time course effects of the mechanisms related to the exercise protection.  Methods : Male C57BL/6 mice were divided into four groups: control, exercise, smoke and smoke+exercise. Exposure to CS and treadmill training were carried out: 5 days/week for 4, 8 and 12 weeks. We evaluated lung mechanics by using a FlexiVent ventilator (Scireq, Montreal, Canada); the number of total and differentials cells in bronchoalveolar lavage fluid (BALF); mean linear intercept (LM); TNFα, IL-1β, IL6, IL10, TBARS, antioxidant enzymes (SOD, Gpx and TRAP) in the lung tissue.  Results:  Exercise protected mice exposed to CS from the: reduction on tissue damping and tissue elastance (p Conclusion:  Exercise protection in mice exposed to CS is more pronounced after 12 weeks and the mechanisms involved include anti-inflammatory mediators and antioxidants enzymes that have an important role in COPD development.  .
The effects of short-term CPAP withdrawal on myocardial perfusion in OSA - A randomised placebo-controlled trial
Authors: Esther I. Schwarz, Christian Schlatzer, Julia Stehli, Philipp A. Kaufmann, Konrad E. Bloch, John R. Stradling, Malcolm Kohler
Journal: European Respiratory Journal (2014)

Background   Obstructive sleep apnoea (OSA) is a risk factor for hypertension and associated with increased cardiovascular risk. Continuous positive airway pressure (CPAP) is presumed to be an everyday therapy and has been shown to reduce blood pressure and improve other measures of vascular risk. It is not known whether short-term CPAP withdrawal results in impaired myocardial perfusion and thus, might increase the risk for myocardial ischemia.   Objective   We assessed the effect of a short-term CPAP withdrawal on myocardial perfusion in patients with OSA.   Methods   45 patients with moderate to severe OSA, currently on CPAP, were randomised to either continue or withdraw CPAP (subtherapeutic CPAP) for two weeks. Sleep studies and cardiac positron emission tomography to assess myocardial perfusion were performed at baseline and at two weeks.   Results   CPAP withdrawal led to a recurrence of OSA (mean difference in AHI between groups +39.7/h, 95%CI 32.7 to 46.7/h, pl0.001). In comparison to continuing CPAP, subtherapeutic CPAP led to a statistically significant increase in morning blood pressure; mean difference in systolic blood pressure +10.8mmHg (95%CI 5.2 to 16.4mmHg) and diastolic blood pressure +7.5mmHg (95%CI 3.5 to 11.5mmHg, both pl0.001), but was not associated with deterioration of myocardial perfusion (mean difference in hyperaemic myocardial blood flow -0.09ml/min/g, 95%CI -0.17 to -0.36ml/min/g, p=0.907).   Conclusions   Although short-term CPAP therapy withdrawal leads to a considerable increase in blood pressure, it is not associated with impaired myocardial perfusion. Thus, short-term discontinuation of CPAP does not seem to increase the risk of myocardial ischemia.
Systemic inflammation is enhanced by acute hyperglycaemia and suppressed by insulin in COPD
Authors: John Archer, Emma Baker
Journal: European Respiratory Journal (2011)

Introduction: Over half of COPD patients hospitalised for exacerbations have elevated blood glucose. Acute hyperglycaemia is associated with increased risk of death and prolonged hospital stay [Baker et al Thorax;61:284-9]. We investigated the effect of acute hyperglycaemia and insulin therapy on systemic inflammation.

Methods: 8 stable COPD patients (4male, 66±8yrs, FEV1 44±16%predicted) and 8 volunteers (8male, 24±5yrs, FEV1 89±12%) with fasting glucose <7mM received an octreotide infusion to inhibit pancreatic function. Glucose and insulin were infused for 4 consecutive 60min periods to achieve: Low glucose (fasting), low insulin (0.3mU.kg-1.min-1); high glucose (10mM above fasting levels), low insulin; high glucose, high insulin (1.5mU.kg-1.min-1); low glucose, high insulin. Cytokines were measured in blood sampled at the end of each 60min period using a Bio-Plex system (Bio-Rad).

Results: In COPD, high glucose, low insulin increased IP10 by 48 (12-181)% (median (interquartile range)), TNFa by 28 (8-54)% and IL-12 by 16 (2-34)% from low glucose, low insulin (p<0.05). IP10 increased significantly more in COPD than in volunteers (p=0.009). Subsequently, low glucose, high insulin suppressed IP10, TNFa and IL-12 to starting concentrations (p<0.05). Additionally low glucose, high insulin suppressed IL-1a, IL-1b, IL-16 and IL-4 by 4 to 26% (p<0.05). Suppression of IP10 and TNFa was significantly greater in COPD patients than in volunteers (p=0.038).

Conclusion: Acute hyperglycaemia amplifies systemic inflammation in COPD, which could be detrimental during exacerbations. The anti-inflammatory potential of blood glucose control with insulin for exacerbations requires further investigation.
ALX-0962, an anti-IgE Nanobody® with a dual mode of action
Authors: Manuela Rinaldi, Tinneke Denayer, Sophie Thiolloy, Luis C. Perez Tosar, Marie-Ange Buyse, Philip De Decker, Emilie De Witte, Peter Meerts, Judith Baumeister, Josefin-Beate Holz
Journal: European Respiratory Journal (2013)

Background   The interaction of IgE with its high affinity receptor FceRI on mast cells and basophils is essential to induce an allergic response. Omalizumab, a competitive inhibitor of circulating IgE, is used to treat allergic asthma. However, the dissociation of IgE-FceRI complexes is very slow and this interaction is not influenced by Omalizumab. Here we describe ALX-0962, a bispecific Nanobody (Nb) (single variable domain of antibody) targeting IgE as well as human serum albumin to obtain plasma half-life extension.  Aim  The aim of this study was to explore the IgE-Nb complex formation and establish the mode of action (MoA) of ALX-0962.  Methods   The IgE-Nb complex was investigated using surface plasmon resonance (SPR) and electrochemiluminescence (ECL), while the MoA was explored with SPR and with XCELLigence using human FceRI transfected rat basophil cells in a degranulation assay.  Results   SPR and ECL indicated the occurrence of 1:2 IgE-Nb complex, with at least one Nb binding site preventing the interaction with the FceRI epitope. Next, investigation of the MoA demonstrated a dual functionality of the Nb:1) neutralization of soluble IgE with a higher potency than Omalizumab 2) binding and displacement of preformed IgE-FceRI complexes on basophils.The displacement by ALX-0962 was verified in the cell based assay, demonstrating a significant decrease in degranulation for Nb at nM range, while no decrease was observed for Omalizumab.  Conclusion   Our results show that ALX-0962 has a dual mode of action: it neutralizes soluble IgE and displaces preformed IgE-FceRI complexes as shown  in vitro .This could lead to a faster onset of action compared to Omalizumab, potentially resulting in an earlier clinical improvement in asthma.