tbuckley/cabot-search huggingface dataset:
<i>N</i>‐acetylcysteine reduces chemokine release<i>via</i>inhibition of p38 MAPK in human airway smooth muscle cells
Authors: W.A. Wuyts, B.M. Vanaudenaerde, L.J. Dupont, M.G. Demedts, G.M. Verleden
Journal: European Respiratory Journal (2003)

Reactive oxygen species are involved in the activation of several mitogen-activated protein kinases (MAPKs), key-players in the production of several cytokines. Therefore the current study investigated whether N ‐acetylcysteine (NAC), an antioxidative agent, inhibits the interleukin (IL)‐1β‐induced expression and production of eotaxin and monocyte chemotactic protein (MCP)‐1 in human airway smooth muscle cells (HASMC). NAC (10 mM) decreased the expression of eotaxin and MCP‐1, by 46±11% (n=7) and 87±4% (n=6), respectively; the eotaxin release was inhibited by 75±5% (n=7), whereas the MCP‐1 release was decreased by 69±4% (n=10). NAC (1 mM) also decreased the IL‐1β‐induced activation of p38 MAPK. Compared with unstimulated cells, a four-fold increase in 8‐isoprostane production in IL‐1β‐stimulated HASMC was observed, which could be inhibited by NAC in a concentration-dependent way, with a maximum inhibition of 39±12% with 1 mM NAC. The present study demonstrated that N ‐acetylcysteine inhibits the interleukin‐1β‐induced eotaxin and monocyte chemotactic protein 1 expression and production due to a decreased activation of p38 mitogen-activated protein kinase. This study has also shown that N ‐acetylcysteine decreases the interleukin‐1β‐induced production of reactive oxygen species, as suggested by a reduction in the 8‐isoprostane production.
Association of Serum Interleukin 6 and C-Reactive Protein in Childhood With Depression and Psychosis in Young Adult Life
Authors: Golam M. Khandaker, Rebecca M. Pearson, Stanley Zammit, Glyn Lewis, Peter B. Jones
Journal: JAMA Psychiatry (2014)

Longitudinal studies have linked the systemic inflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP) with the risk of developing heart disease and diabetes mellitus, which are common comorbidities for depression and psychosis. Recent meta-analyses of cross-sectional studies have reported increased serum levels of these inflammatory markers in depression, first-episode psychosis, and acute psychotic relapse; however, the direction of the association has been unclear.
Internal market rules OK
Authors: J. Le Grand
Journal: BMJ (1994)

When the internal market was introduced into the NHS health economists pointed out that it would have to meet several conditions if it was to achieve the ends that its promoters hoped.1 Analysis of its early operation by the King's Fund and others suggested that it was more successful than might have been expected in meeting most of these conditions.2 However, several unresolved issues remained, particularly regarding the competitive structure of the market. Economists at the Department of Health became increasingly aware of these problems as the market evolved, and they have used the experience of the past four years of market operations to develop a set of guidelines, or rules, for operating the internal market.

These guidelines, The Operation of the Internal Market: Local Freedoms, National Responsibilities, were published earlier this week.3 They concern four areas: mergers between providers and joint ventures; mergers between purchasers; managing change when providers are in difficulty (a euphemism for reconfiguring hospitals, including closures); and collusion between providers and purchasers, or between providers.

Mergers between providers present difficulties for markets. On the one hand, the creation of bigger units may result in efficiency savings through economies of scale. On the other hand, these large units may monopolise the market, operating against the interests of purchasers and hence ultimately of patients.

The guidelines propose that, in general, mergers will not be challenged by the NHS Executive so long as they do not require existing trusts to be dissolved and the resulting …
Observational trials in pulmonary arterial hypertension: low scientific evidence but high clinical value
Authors: M. M. Hoeper
Journal: European Respiratory Journal (2007)

In this issue of the European Respiratory Journal , Mathai et al . 1 (from Johns Hopkins University, Baltimore, MD, USA) report on their experience with the use of sildenafil, a phosphodiesterase-5 inhibitor, in patients with pulmonary arterial hypertension (PAH) who failed monotherapy with bosentan, an endothelin receptor antagonist. Within a 4-yr period, 82 patients with either idiopathic PAH (IPAH) or PAH associated with systemic sclerosis (PAH-SSc) were treated with bosentan. Among those, 13 IPAH patients and 12 PAH-SSc patients showed signs of clinical worsening such that sildenafil was added to bosentan. Although haemodynamic parameters were similar at baseline, the median time from initiation of bosentan treatment to clinical worsening was 792 days in the IPAH group but only 458 days in the PAH-SSc group. The clinical response to combination therapy was mixed: in IPAH patients, the 6-min walk distance improved by 47±77 m, whereas in PAH-SSc patients the 6-min walk distance deteriorated by -7±40 m. During follow-up, only one IPAH patient needed additional therapy (intravenous treprostinil), whereas five PAH-SSc patients required further escalation of treatment by addition of either inhaled or intravenous prostanoids. Death occurred in one IPAH patient (from gastro-intestinal bleeding unrelated to PAH) and in four patients with PAH-SSc. Mathai et al . 1 thus concluded that addition of sildenafil to bosentan was more effective in patients with IPAH than in patients with PAH-SSc and that additional studies are needed to assess safety and efficacy of this combination in the latter group of patients.

Although this study is limited by its small sample size and the lack of a control group, it has some …
The association between early life lung function and wheezing during the first 2 yrs of life
Authors: S Young, J Arnott, PT O'Keeffe, PN Le Souef, LI Landau
Journal: European Respiratory Journal (2000)

Reports have suggested that certain infants are predisposed to wheezing in the first 2 yrs of life due to abnormal lung function, prior to the first wheezing illness. The authors investigated the association between infant lung function and wheeze during the first 2 yrs of life. A cohort of 253 infants was evaluated. Respiratory function assessment was performed at 1, 6, and 12 months of age. Parental history of asthma, atopy, and maternal antenatal smoking habits were recorded. An infant was identified as having wheezed on the basis of parental report and, where possible, physician diagnosis. One hundred and sixty infants (63%) had complete diary and questionnaire information on wheeze available for analysis. Of these: 79 infants (50%) had never wheezed (NW) during the first 2 yrs of life and 81 had reported wheeze (W) (50%). Of those with a report of wheeze, the distribution through the first 2 yrs of life was; 28 during the first year of life only (Y1), 21 in the second year of life only (Y2), and 32 wheezed in both the first and second years of life (Y1&amp;2). At the age of 1 month, prior to any lower respiratory illness, the W group had impaired lung function in comparison to the NW group. In Y1 infants, the neonatal lung function differences resolved by 12 months of age. In Y2 and Y1&amp;2 infants lung function differences persisted throughout the first year of life. Prevalence of parental asthma and maternal antenatal smoking was increased in the W group p=0.001, p=0.008, respectively), in comparison to the NW infants. Maternal antenatal smoking prevalence was increased in the Y2 and Y1&amp;2 infants in comparison to the NW group (p=0.04), (p=0.01), respectively. Wheezing during the first year of life is often a transient condition which improves with time. It appears to be related to early life reduced small airway calibre. Wheezing that begins or persists into the second year of life is usually associated with a different abnormality of the airways. Commencement or persistence of wheeze into the second year of life may be part of the clinical entity recognized as asthma.
Salmonella Manipulation of Host Signaling Pathways Provokes Cellular Transformation Associated with Gallbladder Carcinoma
Authors: Tiziana Scanu, Robbert M. Spaapen, Jeroen M. Bakker, Chandra Bhan Pratap, Lin-en Wu, Ingrid Hofland, Annegien Broeks, Vijay Kumar Shukla, Mohan Kumar, Hans Janssen, Ji-Ying Song, E. Andra Neefjes-Borst, Hein te Riele, David W. Holden, Gopal Nath, Jacques Neefjes
Journal: Cell Host & Microbe (2015)
Systematic Review: The Relationship between Clinical Experience and Quality of Health Care
Authors: Niteesh K. Choudhry, Robert H. Fletcher, Stephen B. Soumerai
Journal: Annals of Internal Medicine (2005)

Background: Physicians with more experience are generally believed to have accumulated knowledge and skills during years in practice and therefore to deliver high-quality care. However, evidence suggests that there is an inverse relationship between the number of years that a physician has been in practice and the quality of care that the physician provides. Purpose: To systematically review studies relating medical knowledge and health care quality to years in practice and physician age. Data Sources: English-language articles in MEDLINE from 1966 to June 2004 and reference lists of retrieved articles. Study Selection: Studies that provided empirical results about knowledge or a quality-of-care outcome and included years since graduation or physician age as explanatory variables. Data Extraction: We categorized studies on the basis of the nature of the association between years in practice or age and performance. Data Synthesis: Overall, 32 of the 62 (52%) evaluations reported decreasing performance with increasing years in practice for all outcomes assessed; 13 (21%) reported decreasing performance with increasing experience for some outcomes but no association for others; 2 (3%) reported that performance initially increased with increasing experience, peaked, and then decreased (concave relationship); 13 (21%) reported no association; 1 (2%) reported increasing performance with increasing years in practice for some outcomes but no association for others; and 1 (2%) reported increasing performance with increasing years in practice for all outcomes. Results did not change substantially when the analysis was restricted to studies that used the most objective outcome measures. Limitations: Because of the lack of reliable search terms for physician experience, reports that provided relevant data may have been missed. Conclusions: Physicians who have been in practice longer may be at risk for providing lower-quality care. Therefore, this subgroup of physicians may need quality improvement interventions.
Revascularization for Coronary Artery Disease: Stents Versus Bypass Surgery
Authors: Spencer B. King, John Jeffrey Marshall, Pradyumna E. Tummala
Journal: Annual Review of Medicine (2009)

Coronary artery disease (CAD) is one manifestation of ischemic heart disease, which is the leading cause of mortality in the world. In addition to preventive medical therapy and lifestyle changes, consideration of revascularization of obstructed arteries to reduce ischemia, alleviate angina, and improve quality of life is a mainstay of current practice. However, the benefits of different methods of revascularization in particular patient populations are debated. Percutaneous coronary intervention (PCI), which involves placement of intracoronary stents in most patients, is a less invasive procedure than coronary artery bypass graft (CABG) surgery. Although it is generally accepted that patients with single-vessel obstructive CAD are best treated with PCI, patients with multivessel CAD have a higher ischemia burden, a greater risk for developing recurrent ischemic events, and a higher mortality. It is in this patient population where the debate over revascularization with stents versus surgery continues.
Diabetic Nephropathy in Type 2 Diabetes Prevention and Patient Management
Authors: Gunter Wolf, Eberhard Ritz
Journal: Journal of the American Society of Nephrology (2003)

It is an irony of medical progress that the renal involvement in diabetes mellitus type 2 had been considered twenty years ago ([1][1]) as a benign condition for the kidney without causing renal function loss greater than expected from the "normal" aging process. In contrast, today it has become
Slower Metabolism and Reduced Intake of Nicotine From Cigarette Smoking in Chinese-Americans
Authors: N. L. Benowitz, E. J. Perez-Stable, B. Herrera, P. Jacob
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Lung cancer rates are lower in Asians and Latinos than in whites. Ethnic differences in nicotine metabolism might explain, in part, ethnic differences in cigarette consumption and/or nicotine intake per cigarette and resultant tobacco-related cancer risk. We compared the rate of nicotine metabolism and the intake of nicotine per cigarette smoked among smokers of different ethnicities. Methods: Healthy volunteer smokers, including 37 Chinese-Americans, 40 Latinos, and 54 whites, received simultaneous infusions of deuterium-labeled nicotine and cotinine, a metabolite of nicotine. From blood and urine measurements, the disposition kinetics and daily intake of nicotine from smoking were determined. All statistical tests were two-sided. Results: Total and nonrenal clearance of nicotine and cotinine and metabolic clearance of nicotine via the cotinine pathway were similar in Latinos and whites and statistically significantly lower in Chinese-Americans. Intake of nicotine per cigarette by Chinese-Americans (0.73 mg; 95% confidence interval [CI] = 0.53 to 0.94 mg) was statistically significantly lower than that by Latinos (1.05 mg; 95% CI = 0.85 to 1.25 mg) or whites (1.10 mg; 95% CI = 0.91 to 1.30 mg; P = .039). Among all of the participants, there was a statistically significant positive correlation between nicotine clearance and daily intake of nicotine from cigarette smoking and between nicotine clearance and nicotine intake per cigarette (r = .41 and r = .39, respectively) (P<.001 for both). Conclusions: The lower nicotine (and, therefore, tobacco smoke) intake per cigarette and the fewer cigarettes smoked per day, which may result, in part, from slower clearance of nicotine, may explain lower lung cancer rates in Chinese-Americans. Lower lung cancer rates among Latinos compared with whites, given their similar nicotine intake per cigarette, are probably due to smoking fewer cigarettes. The results with Chinese-Americans may have implications for dosing with nicotine medications to aid smoking cessation in Chinese- American smokers and perhaps in other Asian smokers.
Proton Therapy in Clinical Practice: Current Clinical Evidence
Authors: Michael Brada, Madelon Pijls-Johannesma, Dirk De Ruysscher
Journal: Journal of Clinical Oncology (2007)

Article Tools Review Articles Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2006.10.0131 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 17350945 Proton Therapy in Clinical Practice: Current Clinical Evidence Michael BradaxMichael BradaSearch for articles by this author , Madelon Pijls-JohannesmaxMadelon Pijls-JohannesmaSearch for articles by this author , Dirk De RuysscherxDirk De RuysscherSearch for articles by this author Show More From The Institute of Cancer Research and The Royal Marsden National Health Service Foundation Trust, Sutton, Surrey, United Kingdom; and Department of Radiation Oncology, Maastricht Radiation Oncology, Research Institute Growth and Development, University Hospital Maastricht, Maastricht, the Netherlands https://doi.org/10.1200/JCO.2006.10.0131 First Page Full Text PDF Figures and Tables © 2007 by American Society of Clinical Oncology
Diagnosing pneumonia in patients with acute cough: clinical judgment compared to chest radiography
Authors: Saskia F. van Vugt, Theo J.M. Verheij, Pim A. de Jong, Chris C. Butler, Kerenza Hood, Samuel Coenen, Herman Goossens, Paul Little, Berna D.L. Broekhuizen
Journal: European Respiratory Journal (2013)

Pneumonia is often diagnosed and treated empirically. We set out to determine the diagnostic accuracy of clinical judgment based on signs and symptoms to detect radiographic pneumonia in patients presenting with acute cough in primary care. In 2810 European patients with acute cough, general practitioners (GPs) recorded whether they considered pneumonia to be present (“yes” or “no”) immediately after history and physical examination. Chest radiography was performed within 1 week by local radiologists blind to other patient characteristics. 140 patients had radiographic pneumonia (5%), of whom 41 (29%) had been diagnosed as such. 31 (1%) patients had a clinical diagnosis that was not confirmed by radiography (n=2670). In clinically suspected pneumonia, 57% of subjects were subsequently diagnosed with radiographic pneumonia. Negative predictive value (NPV), sensitivity and specificity of GPs’ clinical judgment were 96%, 29% and 99%, respectively. Compared to patients with a clinical diagnosis of pneumonia, less severe symptoms were found in radiographic pneumonia cases not suspected clinically (p&lt;0.05). The predictive values of GPs’ clinical judgment, particularly the high NPVs, are helpful in routine care. Nonetheless, the majority of diagnoses of radiographic pneumonias was not suspected on clinical grounds. There is a need to further support the detection of clinically relevant pneumonia in primary care.
IgE to Gly m 5 and Gly m 6 is associated with severe allergic reactions to soybean in Japanese children
Authors: Komei Ito, Sigrid Sjölander, Sakura Sato, Robert Movérare, Akira Tanaka, Lars Söderström, Magnus Borres, Maryam Poorafshar, Motohiro Ebisawa
Journal: Journal of Allergy and Clinical Immunology (2011)
Genetic instability occurs in the majority of young patients with colorectal cancer
Authors: Bo Liu, Susan M. Farrington, Gloria M. Petersen, Stanley R. Hamilton, Ramon Parsons, Nickolas Papadopoulos, Takato Fujiwara, Jin Jen, Kenneth W. Ainzler, Andrew H. Wyllie, Bert Vogelstein, Malcolm G. Dunlop
Journal: Nature Medicine (1995)
958 DIAGNOSIS OF BENIGN HEPATOCELLULAR TUMORS/VALUE OF A SIMPLE ALGORITHM BASED ON SPECIFIC HISTOCHEMICAL MARKERS PERFORMED ON LIVER BIOPSIES, COMPARED WITH SURGICAL SPECIMEN
Authors: P. Bioulac-Sage, G. Cubel, B. Le Bail, G. Couchy, C. Balabaud, J. Zucman-Rossi
Journal: Journal of Hepatology (2011)
Neutral protease secretion by human monocytes. Effect of surface-bound immune complexes.
Authors: C G Ragsdale, W P Arend
Journal: The Journal of Experimental Medicine (1979)

The effect of surface-bound immune complexes on the secretion of neutral proteases by human peripheral monocytes was examined. Monocytes cultured on 125I-fibrin secreted plasminogen activator in a continuous fashion. Monocytes incubated on 125I-fibrin with surface-bound immune complexes displayed a burst of plasminogen-independent fibrinolytic activity, whereas no release of plasminogen activator was observed through 21 h. The plasminogen-independent fibrinolytic enzymes were derived from monocytes and not from lymphocytes or contaminating polymorphonuclear neutrophils. The effects of various protease inhibitors on the secretion of plasminogen-dependent and independent enzymes were determined. Chymostatin selectively inhibited the monocyte-derived plasminogen activators. Similar effects of chymostatin were observed on human urokinase in the absence of cells. The predominant protease producing plasminogen-independent fibrinolysis exhibited responses to inhibitors characteristic of leukocyte elastase. When monocytes were cultured on 125I-fibrin with adherent immune complexes approximately equal to 40% of the solubilized radioactivity represented deiodination and not proteolysis. It was concluded that culture of human monocytes on surface-bound immune complexes stimulates the secretion of plasminogen-independent fibrinolytic proteases, primarily elastase, and of deiodinating enzymes. Under these conditions, plasminogen activator secretion is inhibited. Neutral proteases secreted from newly recruited monocytes may contribute to tissue injury in human diseases characterized by the presence of adherent immune complexes.
Duration of symptoms of respiratory tract infections in children: systematic review
Authors: M. Thompson, T. A. Vodicka, P. S. Blair, D. I. Buckley, C. Heneghan, A. D. Hay
Journal: BMJ (2013)

<b>Objective</b> To determine the expected duration of symptoms of common respiratory tract infections in children in primary and emergency care. <b>Design</b> Systematic review of existing literature to determine durations of symptoms of earache, sore throat, cough (including acute cough, bronchiolitis, and croup), and common cold in children. <b>Data sources</b> PubMed, DARE, and CINAHL (all to July 2012). <b>Eligibility criteria for selecting studies</b> Randomised controlled trials or observational studies of children with acute respiratory tract infections in primary care or emergency settings in high income countries who received either a control treatment or a placebo or over-the-counter treatment. Study quality was assessed with the Cochrane risk of bias framework for randomised controlled trials, and the critical appraisal skills programme framework for observational studies. <b>Main outcome measures</b> Individual study data and, when possible, pooled daily mean proportions and 95% confidence intervals for symptom duration. Symptom duration (in days) at which each symptom had resolved in 50% and 90% of children. <b>Results</b> Of 22 182 identified references, 23 trials and 25 observational studies met inclusion criteria. Study populations varied in age and duration of symptoms before study onset. In 90% of children, earache was resolved by seven to eight days, sore throat between two and seven days, croup by two days, bronchiolitis by 21 days, acute cough by 25 days, common cold by 15 days, and non-specific respiratory tract infections symptoms by 16 days. <b>Conclusions</b> The durations of earache and common colds are considerably longer than current guidance given to parents in the United Kingdom and the United States; for other symptoms such as sore throat, acute cough, bronchiolitis, and croup the current guidance is consistent with our findings. Updating current guidelines with new evidence will help support parents and clinicians in evidence based decision making for children with respiratory tract infections.