tbuckley/cabot-search huggingface dataset:
Genetic variant of the nicotinic receptor gene and the long term prognosis of smokers
Authors: Henna Kupiainen, Mikko Kuokkanen, Jukka Kontto, Veikko Salomaa, Jarmo Virtamo, Ingileif Jonsdottir, Tarja Laitinen
Journal: European Respiratory Journal (2013)

Study objective: Polymorphisms in the nicotinic acetylcholine receptor gene (CHRNA3/A5 locus) has been associated with several smoking related traits such as nicotine dependence, cigarette consumption, smoking cessation, lung cancer and the development of COPD. Our aim was to study one of the polymorphisms (rs1051730) in long term prognosis among smokers.  Subjects and methods: Genotyping was done in two longitudinal cohorts: Finnish COPD patients (N=575, 74% men) among which several clinical variables are available and among smoking men (N=1911) to whom only basic demographic information was available. The analyses were done using multivariate logistic regression model and Cox proportional hazards model. Additive model was used in all analyses and OR and HR values are given for minor homozygote. Finnish Health2000 population cohort (N=1728) was used for control for estimating the risk of COPD.  Results: The genetic variant increased the risk of COPD when compared to the Finnish population at large (OR=1.4, p=3.2 x 10-5). Among COPD patients the minor allele was associated with cancerous diseases (adjusted OR 2.4 CI 1.00-5.67), in smoking men with pack years (adjusted OR 1.4 CI 1.09-1.96) and in both cohorts with all-cause mortality. Adjusted hazards ratios for mortality in COPD patients and in smoking men were HR 2.2, CI 1.22-3.82 and HR 1.2, CI 1.09-1.50, respectively.  Conclusions: Genetic variance found in the CHRNA3/A5 locus may be associated with long-term prognosis among smokers.
High urine levels of interleukin-8 (IL-8) in patients with non-Hodgkin lymphoma (NHL)
Authors: Se-Woon Ha, Kong Sun-Young, Hye Lin Lee, Hyeon-Seok Eom, Tak Yun, Hyun-Ju Kim, Weon-Seo Park, Byung-Ho Nam, Moon-Woo Seung, Do Hoon Lee
Journal: Clinical Cancer Research (2007)

B54   Angiogenesis plays an important role in many types of cancer. IL-8 has been known a pro-inflammatory and pro-angiogenic cytokine and it has been reported the association with tumor progression, prognosis and survival in several cancers. However, the role of IL-8 in non-Hodgkin lymphoma (NHL) has not been fully elucidated. We aimed to evaluate the usefulness of serum and urine IL-8 in patients with NHL. We conducted reference intervals of serum and urine IL-8 in 131 controls. The patient’s samples were serially obtained during CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CHOP (rituximab and CHOP) chemotherapy. Clinical characteristics such as histologic type and international prognostic index (IPI) including age, performance, LDH, stage, extranodal involvement were evaluated. T-test was used to compare the levels of IL-8 in controls with those in patients. As a result, the reference intervals of serum and urine IL-8 were 15.9-430.3 and 0.0-61.5 pg/ml, respectively. The concentration of urine IL-8 in patients was significantly higher than those in controls (24.95±54.93 vs. 9.50±25.04 pg/ml;  P =0.007). However, serum IL-8 concentration did not show significant differences (159.21±40.37 vs. 99.60±107.12 pg/ml;  P =0.098). The receiver operating characteristic (ROC) analysis showed 0.74 and 0.43 ROC area for urine and serum IL-8, respectively. There was no correlation with the concentration of serum and urine IL-8 with clinical variables. This study indicated that the urine IL-8 is associated with NHL, however, there was no correlation with aggressiveness.
Functional decline in patients with cirrhosis awaiting liver transplantation: Results from the functional assessment in liver transplantation (FrAILT) study
Authors: Jennifer C. Lai, Jennifer L. Dodge, Saunak Sen, Kenneth Covinsky, Sandy Feng
Journal: Hepatology (2015)

Cirrhosis is characterized by sarcopenia and malnutrition, leading to progressive functional decline. We aimed to objectively measure functional decline in patients with cirrhosis awaiting liver transplantation and its association with waiting list mortality. Consecutive adults listed for liver transplantation with laboratory Model for End‐Stage Liver Disease (MELD) ≥12 at a single center underwent functional status assessments at every outpatient visit using the Short Physical Performance Battery (0 = impaired to 12 = robust), consisting of gait, chair stands, and balance tests. Joint linear time‐to‐event analyses modeled the simultaneous impact of the longitudinal trajectory of physical function on waiting list mortality (=death or delisted for being too sick for liver transplantation). Included were 309 liver transplantation candidates. Median laboratory MELD was 15, serum albumin was 3.0 g/dL, 28% had ascites, 18% had hepatic encephalopathy, and 83% were Child class B or C. At a median follow‐up of 14 months, 15% died or were delisted and 28% underwent liver transplantation. Average physical function worsened per 3 months on the waiting list: −0.38 kg in grip strength, −0.05 meters/second in gait, 0.03 seconds in chair stands, and −0.16 Short Physical Performance Battery points. In joint models of longitudinal trajectories of physical function and waiting list mortality adjusted for MELD‐Na, albumin, hepatocellular carcinoma, and baseline physical function, the longitudinal trajectories of each physical function measure were significantly associated with waiting list mortality: grip (hazard ratio = 0.89, 95% confidence interval 0.83‐0.95), gait (hazard ratio = 0.72, 95% confidence interval 0.62‐0.84), chair stands (hazard ratio = 1.17, 95% confidence interval 1.09‐1.25), and Short Physical Performance Battery &lt;10 (hazard ratio = 1.45, 95% confidence interval 1.15‐2.20). Conclusion : Liver transplantation candidates experience significant functional decline on the waiting list, despite modest wait time and low baseline MELD; decline in physical function is associated with an increased risk of death or delisting, independent of liver disease severity. (H epatology 2016;63:574–580)
Altered proliferation of alveolar epithelial cells is involved in progressive elastase-induced emphysema
Authors: Alexander Bohla, Katrin Kohse, Johannes Schwarz, Gerrit John, Oana Veronica Amarie, Oliver Eickelberg, Ali Oender Yildirim
Journal: European Respiratory Journal (2012)

RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized amongst others by development of emphysema. We showed that a single application of porcine pancreatic elastase (PPE) causes a severe progressing emphysema-like phenotype in C57BL/6 mice. Since the development of emphysema is apparently not completed after PPE application, we aimed to identify possible key mechanisms that drive this process even at late time points.  METHODS: Female C57BL/6 mice received a single oropharyngeal application of PPE or PBS, and lung function, histology and gene expression were analyzed on days 2, 28, 56, and 162. Fibroblasts of PPE treated mice were characterized analyzing mitochondrial membrane potential. Furthermore, LA-4 lung epithelial cells were treated with PPE and proliferative and apoptotic characteristics were measured using gene expression or wound healing assays.  RESULTS: PPE treated C57BL/6 mice develop progressive airway enlargement and impairment of pulmonary function during 23 weeks of analysis. Q-PCR revealed elevated expression of apoptosis markers, reduced proliferation and increased expression of matrix components. Lung fibroblasts of PPE treated mice show reduced proliferation and an altered mitochondrial membrane potential. Reduced proliferation was also found in PPE treated LA-4 cells.  CONCLUSION: Diminished proliferation in PPE treated lung epithelial cell lines as well as in lungs and primary fibroblasts of PPE treated mice could explain the persistent progression of PPE induced emphysema in mice.
Multimodality noninvasive imaging for assessing therapeutic effects of exogenously transplanted cell aggregates capable of angiogenesis on acute myocardial infarction
Authors: Chieh-Cheng Huang, Hao-Ji Wei, Kun-Ju Lin, Wei-Wen Lin, Ching-Wen Wang, Wen-Yu Pan, Shiaw-Min Hwang, Yen Chang, Hsing-Wen Sung
Journal: Biomaterials (2015)
Abstract 193: 18-HEPE, An EPA Metabolite Released By Macrophages, Prevents Against Pressure Overload-induced Cardiac Remodeling
Authors: Jin Endo, Motoaki Sano, Keiichi Fukuda, Makoto Arita
Journal: Circulation Research (2014)

N-3 polyunsaturated fatty acids (PUFAs) have potential cardiovascular benefit, although the mechanisms underlying this effect remain poorly understood. The present study investigated the impact of the enrichment of n-3 PUFAs in the setting of pressure overload induced cardiac hypertrophy using fat-1 mouse, a genetic model with elevated n-3 PUFA levels in tissues, as well as the possible cellular mechanism involved in such a role. The fat-1 mice subjected to pressure overload by transverse aortic constriction showed less infiltration of macrophages and decreased interstitial fibrosis, leading to the preserved cardiac function as compared to wild type (WT) mice. Bone marrow (BM) transplantation experiments revealed that fat-1 transgenic BM cells, but not fat-1 transgenic cardiac cells, contributed the anti-remodeling effect, which was comparable between fat-1 and WT mice transplanted with fat-1 transgenic BM, but was absent in fat-1 mice transplanted with WT BM. In the co-culture assay with cardiac fibroblasts, the fat-1 transgenic macrophages showed anti-inflammatory and anti-fibrotic activities. Lipidomic analysis revealed selective enrichment of eicosapentaenoic acid (EPA) in fat-1 transgenic bone marrow (BM) cells and an EPA-metabolite 18-hydroxyeicosapentaenoic acid (18-HEPE) in fat-1 transgenic macrophages. 18-HEPE-rich milieu in the fat-1 transgenic heart was generated by BM-derived cells, most likely macrophages. 18-HEPE inhibited macrophage-mediated proinflammatory activation of cardiac fibroblasts in culture, and in vivo administration of 18-HEPE significantly attenuated the inflammation and fibrosis of hypertrophied hearts, resulting in improvement of cardiac function. We found that the elevated n-3 PUFA level in BM-derived macrophages is responsible for cardiac protection, and 18-HEPE exhibited cardioprotective potential when administered in vivo.
Drug-resistant tuberculosis among foreign-born persons in Italy: Table 1–
Authors: Lanfranco Fattorini, Alessandro Mustazzolu, Giovanni Piccaro, Manuela Pardini, Perla Filippini, Federico Giannoni, Giovanni Battista Migliori, Giovanni Sotgiu, Emanuele Borroni, Daniela Maria Cirillo
Journal: European Respiratory Journal (2012)

test for smoking behaviour [2].Cotinine is specific to nicotine intake and has a half-life of 18 h, meaning results are indicative of smoking over a number of days.However, cotinine measurements are largely confined to sophisticated laboratory tests, which are expensive and time consuming.We would like to take this opportunity to describe a new point of care saliva test, which measures cotinine and the other nicotine metabolites.A previous colorimetric urine test [3] called SmokeScreen was modified.The same testing device was used, but the reagents were changed to improve sensitivity to detect the lower levels of cotinine found in saliva.The new, more sensitive assay based on the Ko ¨nig reaction has been developed and evaluated in the laboratory and then using a group of healthy volunteers (n5124, age range 21-67 yrs), including 61 smokers with a cigarette consumption of four or more cigarettes per day, (mean 16.6 cigarettes per day), 25% of whom smoked hand rolled cigarettes.Each provided a saliva sample using a manufactured collecting sponge and collecting bottle. 1 mL of saliva was eluted using the test's fixed-volume syringe.The sample was introduced onto freeze-dried reagents and quickly shaken.A sample positive for nicotine metabolites would be expected to turn pink within 1 min, but up to 10 min was allowed for full colour development.The resultant colour was compared with a four-point colour chart (i.e.1-4 point to represent weak to very intense colour) and the level of smoking recorded.Samples from nonsmokers remained unchanged.A positive colour change was obtained from 55 of the 61 smokers and a negative result from 62 of the 63 nonsmokers, giving a sensitivity of 90%, specificity of 98% and accuracy of 94% (p,0.05).There is a significant difference in saliva test results between the smoking and nonsmoking groups (Chi-squared test, p,0.01), indicating that the test is specific for screening smokers with a cigarette consumption of four or more cigarettes a day.The new test was found to have a sensitivity and specificity comparable with the other commercial point of care saliva cotinine test available [4], but was quicker and is less expensive.A dedicated colorimeter to quantify the result is under development.This test could be an important adjunct for identifying smokers and treating smoking-related diseases by providing instantaneous results at a fraction of the cost of laboratory cotinine analysis.
We must all act now
Authors: Alan Maryon-Davis, Ian Gilmore, Patricia Hamilton
Journal: BMJ (2007)

We select the letters for these pages from the rapid responses posted on bmj.com favouring those received within five days of publication of the article to which they refer.Letters are thus an early selection of rapid responses on a particular topic.Readers should consult the website for the full list of responses and any authors' replies, which usually arrive after our selection. cnri/spl Acute bronchiolitis risk of hyponatraemiaBush and Thomson stated that electrolytes should be determined only in infants with bronchiolitis who are dehydrated. 1 However hyponatraemia is seen in up to 33% of children in hospital with this disease. 2It is unrelated to dehydration and has been associated with administration of intravenous fluids together with increased antidiuretic hormone values. 3 4 It can cause generalised tonic-clonic seizures, 2 which may be refractory to anticonvulsants.The National Patient Safety Agency has issued an alert aimed at reducing the risk of hyponatraemia in children -electrolytes should be determined before starting intravenous fluids and at least daily afterwards. 5 Fluids should be restricted in children with hyponatraemia who are receiving intravenous 0.9% saline (with 5% dextrose) and who have high antidiuretic hormone concentrations.
Petrolatum: Barrier repair and antimicrobial responses underlying this “inert” moisturizer
Authors: Tali Czarnowicki, Dana Malajian, Saakshi Khattri, Joel Correa da Rosa, Riana Dutt, Robert Finney, Nikhil Dhingra, Peng Xiangyu, Hui Xu, Yeriel D. Estrada, Xiuzhong Zheng, Patricia Gilleaudeau, Mary Sullivan-Whalen, Mayte Suaréz-Fariñas, Avner Shemer, James G. Krueger, Emma Guttman-Yassky
Journal: Journal of Allergy and Clinical Immunology (2015)
Publication time for letters
Authors: P. Taylor, R. Smith, M. Mullner
Journal: BMJ (1999)

Editor—The delay between publication of articles and their commenting letters in the paper BMJ is now seriously interfering with the educative importance of the letters, which often radically alters the significance of the article to non-expert readers. Although I wrote this letter electronically, I read the paper journal, as I imagine do most of your readers.

The BMJ manages to have special issues such as the Christmas edition and the children's issue. I suggest it is time for a special letters issue. This would contain the entire backlog of letters for which publication is intended. After publication of this catch up issue an agreed minimum time lag could be introduced. The current lag is not acceptable.
Abstract 1737: A Strategy for Continuous ECG Recording in Patients Post Pulmonary Vein Isolation for Atrial Fibrillation
Authors: Andrew D Choi, Sandeep Joshi, Daniel Marrero, Farbod Raiszadeh, Apurva Badheka, Jonathan S Steinberg, Suneet Mittal
Journal: Circulation (2007)

Introduction : Following pulmonary vein isolation (PVI) for management of atrial fibrillation (AF), may centers obtain continuous ECG recordings for several weeks in order to detect early recurrences of AF. However, the implications of early AF following PVI in an individual patient are unknown as is the optimal duration of monitoring in these patients. Methods : We evaluated 72 pts (60 ± 11 yrs, 67% male, 67% paroxysmal AF) who underwent PVI and were followed for &gt;= 6 months. At hospital discharge, all pts were fitted with an external event loop recorder (LifeWatch AF Express) for 14 weeks for the continuous automatic detection of AF (defined as an episode lasting &gt;= 30 sec). Clinical follow-up occurred at 1, 3 and 6 months post-PVI; procedural success was defined by freedom from AF at the 6 month follow-up. Results : During the 14-week loop monitoring period, no AF was observed in 25 (35%) patients. Only 2 of these pts subsequently developed AF; in both cases, AF occurred 3– 6 months post-PVI. In contrast, 47 (65%) patients had at least 1 AF episode, most commonly (39/47 pts, 83%) within the first 2 weeks of PVI. In fact, absence of AF during the first 2-weeks of loop monitoring identified a cohort of patients with high likelihood of procedural success at 6 months (Figure ). Conclusions : Our data support a rationale for at least 2-weeks of continuous automatic loop ECG monitoring in all pts post-PVI. Patients without AF during this period can be expected to have excellent long-term outcome. Longer periods of ECG monitoring may be better limited to patients in whom AF is observed during initial 2-week monitoring.
Cardiovascular disease and mortality in patients with type 2 diabetes after bariatric surgery in Sweden: a nationwide, matched, observational cohort study
Authors: Björn Eliasson, Vasileios Liakopoulos, Stefan Franzén, Ingmar Näslund, Ann-Marie Svensson, Johan Ottosson, Soffia Gudbjörnsdottir
Journal: The Lancet Diabetes & Endocrinology (2015)
Abstract 6254: Nfkb Blockade Attenuates Cardiac Oxidative Stress And Improves Mitochondrial Function In Type II Diabetes
Authors: Nithya Mariappan, Srinivas Sriramula, Masudul Haque, Elizabeth McIlwain, Joseph Francis
Journal: Circulation (2008)

Type II diabetes is the most important predisposing factor for the development of cardiovascular disease. Recent findings from our lab suggest that cytokines and the nuclear transcription factor (NF-kB) contribute to oxidative stress and cardiac function. In this study, we determined the effect of NF-kB blockade on cardiac pathology in a mouse model of type II diabetes. Five week old obese db/db mice (control) and heterozygous lean mice (n = 8) were treated with PDTC (100mg/kg, orally) for 20 weeks. At the end of the study, left ventricular (LV) function was measured using echocardiography. Subsequently, mice were sacrificed and the LV was used for biochemical and mitochondrial assays. LV tissue and mitochondrial ROS and superoxide (O 2 − ) were measured using electron spin resonance spectroscopy. The structural integrity of the mitochondrial membrane was measured using swelling assay and TEM analysis. Fractional shortening was decreased (24.29 ± 0.48) in control db/db mice relative to that of db/db mice treated with PDTC (38.06 ± 1.3). Control db/db mice had enhanced tissue NFkB activity accompanied by increased production of ROS and O 2 − . These animals had increased expression of NF-kB, RAGE, and gp91 phox, contributing to increased oxidative stress. Obese db/db mice also showed increased mitochondrial damage and mitochondrial ROS production which was accompanied by decreased ATP production. In contrast, treatment with PDTC attenuated oxidative stress, protected against mitochondrial dysfunction and preserved cardiac function. This study demonstrates that PDTC, a NFkB blocker, can mitigate oxidative stress, and improve mitochondrial structural integrity directly, through down-regulation of increased oxygen free radicals by its superoxide scavenging activity, thereby increasing ATP synthesis and thus restoring cardiac function in type II diabetes.
Effects of dopamine on the elevated airway tone by histamine and methacholine in rabbits
Authors: Ferenc Petak, Gergely Fodor, Adam Balogh, Laszlo Fazekas, David Telegdi, Orsolya Ivánkovitsné Kiss, Barna Babik
Journal: European Respiratory Journal (2014)

The beneficial effects of dopamine (DA) on the cardiovascular system have been well established; however the potential mechanisms of how it alters the airway tone have not been clarified. Therefore, we aimed at characterizing the changes in the airway function following DA administrations, when the bronchial tone is elevated via stimulating the histaminic or the cholinergic pathway.  The input impedance of the respiratory system (Zrs) was measured in anaesthetized mechanically ventilated rabbits (n=10) under the control conditions, and during iv infusions of methacholine and histamine, in random sequence. After a stable level of bronchoconstriction has been reached, iv DA (5 and 15 µg/kg/min) was administered. Airway resistance (Raw) was determined from the Zrs spectra under each experimental condition by model fitting. The thermodilution method was used to measure cardiac index (CI).  The beneficial cardiovascular effect of DA was reflected in the increases in CI (14±10[SE]%, p=0.034). The bronchoconstriction induced by methacholine (55.6±8.6% increase in Raw) and histamine (58.4±8.4%) were significantly inhibited by DA (-9.4±3.2% and -11.0±2.9%; p  These findings indicate that the mechanism of how DA relaxes the elevated airway smooth muscle tone is independent of the mode of constrictor stimuli. This generalized beneficial profile of DA suggests the ability of this drug to provide an effective treatment of respiratory adverse events involving bronchoconstriction, besides its positive inotropic effects on the myocardial contractility.  Grant support: OTKA K81169, TAMOP 4.2.2.A-11/1/KONV-2012-0052.
Changes in epithelial lining fluid albumin associated with smoking and interstitial lung disease
Authors: CM Roberts, D Cairns, DH Bryant, WM Burke, M Yeates, H Blake, R Penny, L Shelley, JJ Zaunders, SN Breit
Journal: European Respiratory Journal (1993)

Albumin is an important plasma protein which is useful in the assessment of in vivo membrane permeability in the lung. In subjects with interstitial lung disease (ILD) the relationship between albumin recovered from bronchoalveolar lavage (BAL) and other markers of inflammatory activity may provide useful information of the pathogenesis of the disease process. Unfortunately, its measurement is hampered by the variable dilution in BAL fluid. In this study, urea was used as a marker of epithelial lining fluid (ELF) dilution allowing the calculation of an apparent epithelial lining fluid volume and adjusted albumin content. We examined the relationship between ELF albumin content and BAL cell counts, immunoglobulin content, respiratory function tests and gallium lung scans in both smokers and nonsmokers with and without interstitial lung disease. Forty seven subjects with connective tissue disease and interstitial lung disease and 51 subjects with either connective tissue disease but no pulmonary involvement or non pulmonary malignancy (18 current smokers) underwent BAL, gallium lung scans and respiratory function tests. The subjects with ILD were further subdivided into those with active ILD or bronchiolitis using cluster analysis. In smokers without ILD an increased ELF volume and a decrease in ELF albumin were found. Increased ELF albumin was related to increased age. In subjects with ILD, increased albumin was strongly correlated with increased BAL lymphocyte absolute and differential counts, which overwhelmed any age or smoking effect. These findings suggest a possible causal relationship between lung vascular permeability and lymphocyte numbers in subjects with interstitial lung disease and reinforce the need to consider smoking and age as confounding factors in BAL analysis.