tbuckley/cabot-search huggingface dataset:
Acute exacerbations of COPD: it's the weekend but it can't wait until Monday
Authors: Bram van den Borst, Geertjan Wesseling
Journal: European Respiratory Journal (2012)

Acute exacerbations of COPD: it's the weekend but it can't wait until MondayTo the Editors:In a large nationwide study in Spain, BARBA et al. [1] recently reported that patients admitted for treatment of an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) over a weekend showed poorer in-hospital survival compared to those admitted on weekdays.The data suggest that this effect is independent of confounders such as age, sex, comorbidity and respiratory failure.The authors elaborate on the possibility that limited healthcare availability during the weekends may be an explanation for their findings.
ANTERIOR INTERVENTRICULAR CORONARY SINUS VEIN AS THE ONLY SITE OF ORIGIN OF VENTRICULAR TACHYCARDIA AFTER ENDO-EPICARDIAL MAPPING
Authors: Luigi Di Biase, Pasquale Santangeli, J. David Burkhardt, Antonio Dello Russo, Gemma Pelargonio, Michela Casella, Pietro Santarelli, Javier E. Sanchez, Rodney Horton, Shane Bailey, J. Joseph Gallinghouse, Prasant Mohanty, Subba Reddy Vanga, Dhanunjay Lakkireddy, Rong Bai, Andrea Natale
Journal: Journal of the American College of Cardiology (2011)
Endothelin B Receptor Deficiency Predisposes to Pulmonary Edema Formation via Increased Lung Vascular Endothelial Cell Growth Factor Expression
Authors: Todd Carpenter, Stacey Schomberg, Wolfgang Steudel, John Ozimek, Kelley Colvin, Kurt Stenmark, D. Dunbar Ivy
Journal: Circulation Research (2003)

Endothelin (ET) may contribute to pulmonary edema formation, particularly under hypoxic conditions, and decreases in ET-B receptor expression can lead to reduced ET clearance. ET increases vascular endothelial cell growth factor (VEGF) production in vitro, and VEGF overexpression in the lung causes pulmonary edema in vivo. We hypothesized that pulmonary vascular ET-B receptor deficiency leads to increased lung ET, that excess ET increases lung VEGF levels, promoting pulmonary edema formation, and that hypoxia exaggerates these effects. We studied these hypotheses in ET-B receptor–deficient rats. In normoxia, homozygous ET-B–deficient animals had significantly more lung vascular leak than heterozygous or control animals. Hypoxia increased vascular leak regardless of genotype, and hypoxic ET-B–deficient animals leaked more than hypoxic control animals. ET-B–deficient animals had higher lung ET levels in both normoxia and hypoxia. Lung HIF-1α and VEGF content was greater in the ET-B–deficient animals in both normoxia and hypoxia, and both HIF-1α and VEGF levels were reduced by ET-A receptor antagonism. Both ET-A receptor blockade and VEGF antagonism reduced vascular leak in hypoxic ET-B–deficient animals. We conclude that ET-B receptor–deficient animals display an exaggerated lung vascular protein leak in normoxia, that hypoxia exacerbates that leak, and that this effect is in part attributable to an ET-mediated increase in lung VEGF content.
Sequence variants at CHRNB3–CHRNA6 and CYP2A6 affect smoking behavior
Authors: Thorgeir E Thorgeirsson, Daniel F Gudbjartsson, Ida Surakka, Jacqueline M Vink, Najaf Amin, Frank Geller, Patrick Sulem, Thorunn Rafnar, Tõnu Esko, Stefan Walter, Christian Gieger, Rajesh Rawal, Massimo Mangino, Inga Prokopenko, Reedik Mägi, Kaisu Keskitalo, Iris H Gudjonsdottir, Solveig Gretarsdottir, Hreinn Stefansson, John R Thompson, Yurii S Aulchenko, Mari Nelis, Katja K Aben, Martin den Heijer, Asger Dirksen, Haseem Ashraf, Nicole Soranzo, Ana M Valdes, Claire Steves, André G Uitterlinden, Albert Hofman, Anke Tönjes, Peter Kovacs, Jouke Jan Hottenga, Gonneke Willemsen, Nicole Vogelzangs, Angela Döring, Norbert Dahmen, Barbara Nitz, Michele L Pergadia, Berta Saez, Veronica De Diego, Victoria Lezcano, Maria D Garcia-Prats, Samuli Ripatti, Markus Perola, Johannes Kettunen, Anna-Liisa Hartikainen, Anneli Pouta, Jaana Laitinen, Matti Isohanni, Shen Huei-Yi, Maxine Allen, Maria Krestyaninova, Alistair S Hall, Gregory T Jones, Andre M van Rij, Thomas Mueller, Benjamin Dieplinger, Meinhard Haltmayer, Steinn Jonsson, Stefan E Matthiasson, Hogni Oskarsson, Thorarinn Tyrfingsson, Lambertus A Kiemeney, Jose I Mayordomo, Jes S Lindholt, Jesper Holst Pedersen, Wilbur A Franklin, Holly Wolf, Grant W Montgomery, Andrew C Heath, Nicholas G Martin, Pamela A F Madden, Ina Giegling, Dan Rujescu, Marjo-Riitta Järvelin, Veikko Salomaa, Michael Stumvoll, Tim D Spector, H-Erich Wichmann, Andres Metspalu, Nilesh J Samani, Brenda W Penninx, Ben A Oostra, Dorret I Boomsma, Henning Tiemeier, Cornelia M van Duijn, Jaakko Kaprio, Jeffrey R Gulcher, Mark I McCarthy, Leena Peltonen, Unnur Thorsteinsdottir, Kari Stefansson
Journal: Nature Genetics (2010)
Sniff nasal inspiratory pressure: what is the optimal number of sniffs?
Authors: F. Lofaso, F. Nicot, M. Lejaille, L. Falaize, A. Louis, A. Clement, J-C. Raphael, D. Orlikowski, B. Fauroux
Journal: European Respiratory Journal (2006)

Sniff nasal inspiratory pressure (SNIP) measurement is a volitional noninvasive assessment of inspiratory muscle strength. A maximum of 10 sniffs is generally used. The purpose of the present study was to investigate whether the maximum SNIP improved after the tenth sniff. In total, 20 healthy volunteers and 305 patients with various neuromuscular and lung diseases were encouraged to perform 40 and 20 sniffs, respectively. The best SNIP among the first 10 sniffs was lower than the best SNIP among the next 10 sniffs in the healthy volunteers and patients. The SNIP improvement after the twentieth sniff was marginal. In conclusion, a learning effect persists after the tenth sniff. The current authors suggest using 10 additional sniffs when the best result of the first 10 sniffs is slightly below normal, or when sniff nasal inspiratory pressure is used to monitor a progressive decline in inspiratory muscle strength.
“Treatment patterns in the newly diagnosed COPD patients in Catalonia between 2007-2012”
Authors: Miriam Barrecheguren, Mónica Monteagudo, Jaume Ferrer, Eulalia Borrell, Carles Llor, Marc Miravitlles
Journal: European Respiratory Journal (2014)

Introduction:Initial treatment patterns in the newly diagnosed COPD patient usually don´t follow current clinical guidelines.

Methods:Epidemiological study with data obtained from the Information System for Development in Research in Primary Care (SIDIAP), a population database that contains information of 5.8 million of habitants (80% of Catalonia´s population). Newly diagnosed COPD patients in 2007-2012 were identified through a diagnostic algorithm and information about the initial treatment patterns was collected.

Results:During the study period, 40863 patients were diagnosed of COPD with an incidence rate of 18 cases per 10000 person/year.32606 were men(79.8%) with a mean age of 66.05 years(SD 11.49).44% had spirometric confirmation. As a first treatment, 18575 (45.5%) were prescribed inhaled corticosteroids ICs, 17626 (42.1%) were on long acting b-adrenergic agonists (LABA), 11519 (28.2%) short acting b-adrenergic agonists (SABA), 10008 (24.5%) short acting muscarinic antagonists (SAMA), 9758 (23.9%) patients were treated with long acting muscarinic antagonists (LAMA), and. 7353 patients (18%) received no treatment after diagnosis.

Between 2007 and 2012 the use of bronchodilators (LAMA, LABA and LABA/LAMA) doubled (from 6% to 11.4%, 4.6% to 8.87% and from 1.06% to 3.73% respectively). There were little or no changes in the use of LABA + ICS (24.6% to 21.7%) and triple therapy (11.3% to 12%). Patients receiving no treatment decreased from 20.6% to 13.4%.

Conclusions:ICs are frequently prescribed as a first treatment for newly diagnosed COPD patients. The use of bronchodilators alone has increased but still represents a small part of initial treatments.

Study funded by Novartis Spain.
The history and evolution of sutures in pelvic surgery
Authors: Tyler M Muffly, Anthony P Tizzano, Mark D Walters
Journal: Journal of the Royal Society of Medicine (2011)

Summary The purpose of the study is to review the history and innovations of sutures used in pelvic surgery. Based on a review of the literature using electronic- and hand-searched databases we identified appropriate articles and gynaecology surgical textbooks regarding suture for wound closure. The first documented uses of suture are explored and then the article focuses on the use of knotted materials in pelvic surgery. The development of suture of natural materials is followed chronologically until the present time where synthetic suture is implanted during countless surgeries every day. This millennial history of suture contains an appreciation of the early work of Susruta, Celsus, Paré and Lister, including a survey of some significant developments of suture methods over the last 100 years. Most surgeons know little about the history and science of sutures. A retrospective view of suture is critical to the appreciation of the current work and development of this common tool.
The cost of tuberculosis sequelae
Authors: Alvaro Proaño, William Rudgard, Oscar Gayoso
Journal: European Respiratory Journal (2014)

hypertension due to hypoventilation or a patient with late diagnosed pulmonary arterial hypertension and consecutive respiratory failure.The treatment is different.Another open question is how to treat patients with hypoventilation due to hypoventilation and residual pulmonary hypertension following noninvasive positive-pressure ventilation.Is this a vascular abnormality with a prognostic impact?Perhaps a look at cardiac index might be helpful.For patients with pulmonary hypertension and lung disease, the current statement of the international conference on pulmonary hypertension recommends to separate patients with a predominantly exhausted circulatory or ventilatory reserve [4].This is difficult in patients with severe pulmonary hypertension and hypoventilation.As we showed, these patients present with a high minute ventilation/carbon dioxide output slope but low respiratory exchange ratio and increasing end-tidal carbon dioxide tension reflecting a pattern which is different to that seen in patients with pulmonary arterial hypertension and patients with pure ventilatory impairment [1].V. Cottin and co-workers encourage us to treat the underlying disease as stated in our study [1].However, we believe that an additional prospective study is needed in order to obtain a clear idea of how to manage these specific patients with residual pulmonary hypertension despite effective noninvasive positive-pressure ventilation.Effects of PH-specific drugs on persistent PH after effective NIPPV are unclear and should be studied prospectively http://ow.ly/xnN4k
Whole-mtDNA Genome Sequence Analysis of Ancient African Lineages
Authors: Mary Katherine Gonder, Holly M. Mortensen, Floyd A. Reed, Alexandra de Sousa, Sarah A. Tishkoff
Journal: Molecular Biology and Evolution (2006)

Studies of human mitochondrial (mt) DNA genomes demonstrate that the root of the human phylogenetic tree occurs in Africa. Although 2 mtDNA lineages with an African origin (haplogroups M and N) were the progenitors of all non-African haplogroups, macrohaplogroup L (including haplogroups L0–L6) is limited to sub-Saharan Africa. Several L haplogroup lineages occur most frequently in eastern Africa (e.g., L0a, L0f, L5, and L3g), but some are specific to certain ethnic groups, such as haplogroup lineages L0d and L0k that previously have been found nearly exclusively among southern African “click” speakers. Few studies have included multiple mtDNA genome samples belonging to haplogroups that occur in eastern and southern Africa but are rare or absent elsewhere. This lack of sampling in eastern Africa makes it difficult to infer relationships among mtDNA haplogroups or to examine events that occurred early in human history. We sequenced 62 complete mtDNA genomes of ethnically diverse Tanzanians, southern African Khoisan speakers, and Bakola Pygmies and compared them with a global pool of 226 mtDNA genomes. From these, we infer phylogenetic relationships amongst mtDNA haplogroups and estimate the time to most recent common ancestor (TMRCA) for haplogroup lineages. These data suggest that Tanzanians have high genetic diversity and possess ancient mtDNA haplogroups, some of which are either rare (L0d and L5) or absent (L0f) in other regions of Africa. We propose that a large and diverse human population has persisted in eastern Africa and that eastern Africa may have been an ancient source of dispersion of modern humans both within and outside of Africa.
Copy-Number Variation and False Positive Prenatal Aneuploidy Screening Results
Authors: Matthew W. Snyder, LaVone E. Simmons, Jacob O. Kitzman, Bradley P. Coe, Jessica M. Henson, Riza M. Daza, Evan E. Eichler, Jay Shendure, Hilary S. Gammill
Journal: New England Journal of Medicine (2015)

Investigations of noninvasive prenatal screening for aneuploidy by analysis of circulating cell-free DNA (cfDNA) have shown high sensitivity and specificity in both high-risk and low-risk cohorts. However, the overall low incidence of aneuploidy limits the positive predictive value of these tests. Currently, the causes of false positive results are poorly understood. We investigated four pregnancies with discordant prenatal test results and found in two cases that maternal duplications on chromosome 18 were the likely cause of the discordant results. Modeling based on population-level copy-number variation supports the possibility that some false positive results of noninvasive prenatal screening may be attributable to large maternal copy-number variants. (Funded by the National Institutes of Health and others.).
Oral versus i.v. antibiotics for community-acquired pneumonia in children: a cost-minimisation analysis
Authors: P. K. Lorgelly, M. Atkinson, M. Lakhanpaul, A. R. Smyth, H. Vyas, V. Weston, T. Stephenson
Journal: European Respiratory Journal (2009)

Community-acquired pneumonia represents a high financial burden to healthcare providers. This manuscript seeks to estimate and compare the costs of treating children hospitalised with community-acquired pneumonia, with oral and intravenous antibiotics, thus determining which treatment is cost minimising. A cost-minimisation analysis was undertaken alongside a randomised controlled non-blinded equivalence trial. 232 children (from eight paediatric centres in England) diagnosed with pneumonia, who required admission to hospital, were randomised to receive oral amoxicillin or i.v. benzyl penicillin. The analysis considered the cost to the health service, patients and society, from pre-admission until the child was fully recovered. Oral amoxicillin and i.v. benzyl penicillin have equivalent efficacy. Children treated with i.v. antibiotics were found to have significantly longer in-patient stays (3.12 versus 1.93 days; p&lt;0.001). i.v. treatment was found to be more expensive than oral treatment (£1,256 versus £769; difference £488; 95% CI: £233–£750), such that treatment of community-acquired pneumonia with oral amoxicillin would result in savings of between £473 and £518 per child (€545 and €596 per child) admitted. The findings demonstrate that oral amoxicillin is a cost-effective treatment for the majority of children admitted to hospital with pneumonia.
Antiviral agents and corticosteroids in the treatment of severe acute respiratory syndrome (SARS)
Authors: W C Yu
Journal: Thorax (2004)

Systematic evaluation of treatment modalities for SARS is still needed

The epidemic of severe acute respiratory syndrome (SARS) of 2003 caught the medical profession by surprise. The accumulated global total number of cases was 8098 with 774 deaths, a case-fatality ratio of 9.6%.1 Although the novel coronavirus (SARS-CoV) was discovered within weeks,2 treatment was inevitably empirical as controlled clinical trials were not possible during the epidemic of this new and serious illness. Many antiviral and immunomodulatory drugs, as well as other treatments such as convalescent patient plasma and traditional Chinese medicines, have been tried. Ribavirin and corticosteroids are by far the most widely used treatments for SARS. In the later phase of the epidemic lopinavir and ritonavir in combination were also used in Hong Kong.

### Ribavirin

Ribavirin is used extensively for the treatment of SARS and was given to over 90% of patients in Hong Kong. It is a nucleoside analogue that has activity against a number of DNA and RNA viruses in vitro.3 The mechanism of action of ribavirin has been studied for decades and is still under active debate.4 In early March 2003, before the isolation of the SARS-CoV, many experts believed that the mysterious severe illness was due to an unknown virus and ribavirin was empirically given because of its broad spectrum antiviral activity. Furthermore, corticosteroids were increasingly prescribed for the treatment of SARS and some believed that such treatment would be dangerous if not covered with an antiviral agent. The published reports on the effectiveness of ribavirin were mostly retrospective case series with intrinsic methodological issues and it is difficult to draw conclusions. The major side effect of ribavirin is anaemia which occurs in 27–59% …
Effects of Magnesium-Deficient Diet Upon Puppies
Authors: JOSEPH J. VITALE, EARL E. HELLERSTEIN, MOTOOMI NAKAMURA, BERNARD LOWN
Journal: Circulation Research (1961)

Diet-induced magnesium deficiency in male puppies resulted in lowered weight gain, hy perirritability, and convulsions. The histopathological changes consisted of calcification of the elastica and media of the aorta, of coronary and other peripheral arteries, and of the inner portion of the myocardium. Fibrous, virtually fat-free, plaques were seen in the coronary arteries. Magnesium deficiency had no effect on serum cholesterol, sodium, calcium, ortotal protein. Slight lowering of serum magnesium lacked statistical significance. There was a significant decrease in the serum-potassium concentration of these magnesium-deficient dogs. Electrocardiographic changes were noted.
Mutational analysis of an autoantibody: differential binding and pathogenicity.
Authors: J B Katz, W Limpanasithikul, B Diamond
Journal: The Journal of Experimental Medicine (1994)

We have used site-directed mutagenesis to change amino acid residues in the heavy chain of the pathogenic R4A anti-double-stranded DNA (dsDNA) antibody and have looked for resultant alterations in DNA binding and in pathogenicity. The data demonstrate that single amino acid substitutions in both complementarity determining and framework regions alter antigen binding. Changes in only a few amino acids entirely ablate DNA specificity or cause a 10-fold increase in relative binding. In vivo studies in mice of the pathogenicity of the mutated antibodies show that a single amino acid substitution leading to a loss of dsDNA binding leads also to a loss of glomerular sequestration. Amino acid substitutions that increase relative affinity for dsDNA cause a change in localization of immunoglobulin deposition from glomeruli to renal tubules. These studies demonstrate that small numbers of amino acid substitutions can dramatically alter antigen binding and pathogenicity, and that the pathogenicity of anti-DNA antibodies does not strictly correlate with affinity for DNA.
Chemopreventive Effect of Peroxisome Proliferator–Activated Receptor γ on Gastric Carcinogenesis in Mice
Authors: Jie Lu, Kazuhiro Imamura, Sachiyo Nomura, Ken-ichi Mafune, Atsushi Nakajima, Takashi Kadowaki, Naoto Kubota, Yasuo Terauchi, Genichiro Ishii, Atsushi Ochiai, Hiroyasu Esumi, Michio Kaminishi
Journal: Cancer Research (2005)

Abstract Peroxisome proliferator–activated receptor γ (PPARγ) is known to be expressed in several cancers, and the treatment of these cancer cells with PPARγ ligands often induces cell differentiation and apoptosis. Recently, the chemopreventive potential of PPARγ ligands on colon carcinogenesis was reported, although the effect of PPARγ on colon carcinogenesis and the mechanism of the effect remain controversial. In this study, we attempted to elucidate the role of PPARγ in gastric carcinogenesis and explored the possible use of PPARγ ligand as a chemopreventive agent for gastric cancer. N-methyl-N-nitrosourea (MNU, 240 ppm) was given in drinking water for 10 weeks to induce gastric cancer in PPAR wild-type (+/+) and heterozygous-deficient (+/−) mice, followed by treatment with PPARγ ligand [troglitazone, 0.15% (w/w) in powder food] or the vehicle alone for 42 weeks. At the end of the experiment, PPARγ (+/−) mice were more susceptible to MNU-induced gastric cancer than wild-type (+/+) mice (89.5%/55.5%), and troglitazone significantly reduced the incidence of gastric cancer in PPARγ (+/+) mice (treatment 55.5%/vehicle 9%) but not in PPARγ (+/−) mice. The present study showed that (a) PPARγ suppresses gastric carcinogenesis, (b) the PPARγ ligand troglitazone is a potential chemopreventive agent for gastric carcinogenesis, and (c) troglitazone's chemopreventative effect is dependent on PPARγ.
Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment
Authors: R. Leigh, M. M. M. Pizzichini, M. M. Morris, F. Maltais, F. E. Hargreave, E. Pizzichini
Journal: European Respiratory Journal (2006)

The role of inhaled corticosteroids in the management of chronic obstructive pulmonary disease (COPD) remains controversial. The purpose of this study was to evaluate whether sputum eosinophilia (defined as eosinophils > or = 3%) predicts clinical benefit from inhaled corticosteroid treatment in patients with smoking-related clinically stable moderate-to-severe COPD. Forty consecutive patients with effort dyspnoea (mean age 67 yrs; 52 pack-yr smoking history; post-bronchodilator forced expiratory volume in one second (FEV1) <60% predicted, consistent with moderate-to-severe smoking-related chronic airflow limitation) were enrolled. Subjects were treated with inhaled placebo followed by inhaled budesonide (Pulmicort Turbuhaler 1,600 microg.day(-1)), each given for 4 weeks. While the treatment was single-blind (subject level), sputum cell counts before and after treatment interventions were double-blind, thus removing bias. Outcome variables included spirometry, quality-of-life assessment and 6-min walk test. Sputum eosinophilia was present in 38% of subjects. In these, budesonide treatment normalised the eosinophil counts and, in comparison to placebo treatment, resulted in clinically significant improvement in the dyspnoea domain of the disease-specific chronic respiratory questionnaire (0.8 versus 0.3) and a small but statistically significant improvement in post-bronchodilator spirometry (FEV1 100 mL versus 0 mL; p<0.05). In conclusion, sputum eosinophilia predicts short-term clinical benefit from high-dose inhaled corticosteroid treatment in patients with stable moderate-to-severe chronic obstructive pulmonary disease.