tbuckley/cabot-search huggingface dataset:
Vasodilators in the treatment of primary pulmonary hypertension
Authors: EK Weir, B Schremmer
Journal: European Respiratory Journal (1998)

be identified? There is nothing in the duration of their symptoms, clinical presentation or baseline haemodynamics to indicate which patients will respond. In a paper in this issue of the European Respiratory Journal, SITBON et al. [14] report a comparison of the acute haemodynamic responses to inhaled nitric oxide and to high-dose oral CCB (nifedipine or diltiazem) in 33 consecutive PPH patients. Of these patients, ten showed a fall in both mean pulmonary artery pressure and total pulmonary resistance of >20% after inhaled nitric oxide. Nine of the 10 patients also responded acutely to CCB. The other 23 patients failed to respond to either nitric oxide or CCB. Consequently in this series, there were no patients who responded to CCB who did not also respond to nitric oxide. If this is confirmed in a larger series, nitric oxide will be the agent of choice to determine which patients would be candidates for long-term CCB treatment. The administration of nitric oxide (10 parts per million (ppm)) is fast and relatively inexpensive compared to prostacyclin. The same group has reported that the acute responses of pulmonary artery pressure and resistance to nitric oxide and prostacyclin are closely correlated [15]. In that study of 35 PPH patients, 13 patients (37%) had a fall in total pulmonary resistance >30% in response to both drugs, while 22 were nonresponders to both. Although occasional patients who respond to prostacyclin may fail to respond to nitric oxide, the key conclusion from the present paper [14] is that nitric oxide testing identifies most, or possibly all, of those who might benefit from long-term oral CCB. If nitric oxide can be relied upon to do this, then an acute trial with high-dose oral CCB, which carries the greatest risk of side-effects in nonresponders, will not be necessary. It is interesting that 38% of the nonresponders suffered serious side-effects from the acute trial of CCB (shock, prolonged hypotension or severe vomiting), compared to 6% in an earlier study [10]. It is possible that the preceding trial of nitric oxide initiated some longer-lasting changes in vascular smooth muscle physiology, which rendered the patients more susceptible to CCB-induced hypotension. The problem with CCB is that they are not selective for the voltage-gated, L-type calcium channels in pulmonary vascular smooth muscle and consequently can precipitate systemic hypotension. Potassium channels are largely responsible for the control of vascular smooth muscle membrane potential and thus can determine the gating of the L-type calcium channel. Given the greater number of potassium channels and the diversity of their expression in different blood vessels [16, 17], it may be possible to develop potassium channel agonists that cause only pulmonary vasodilatation. Other new approaches to the treatment of PPH include nebulizing prostacyclin or its stable analogue iloprost [18]. This mode of delivery may be more convenient, induce
Telemedicine enhances quality of forced spirometry in primary care
Authors: Felip Burgos, Carlos Disdier, Elena Lopez de Santamaria, Batxi Galdiz, Núria Roger, Maria Luisa Rivera, Ramona Hervàs, Enric Durán-Tauleria, Judith Garcia-Aymerich, Josep Roca
Journal: European Respiratory Journal (2011)

Forced spirometry is pivotal for diagnosis and management of respiratory diseases, but its use in primary care is suboptimal. The aim of the present study was to assess a web-based application aiming at fostering high-quality spirometry in primary care. This was a randomised controlled trial with 12 intervention primary care units (PCi) and six control units (PCc) studied over 12 months. All 34 naïve nurses (PCi and PCc) received identical training. The PCi units had access to educational material and remote expert support. Quality of spirometry and usability of the web application were assessed. We included 4,581 patients (3,383 PCi and 1,198 PCc). At baseline, quality was similar (PCi 71% and PCc 67% high-quality tests). During the study, PCi showed higher percentage (71.5%) of high-quality tests than PCc (59.5%) (p&lt;0.0001). PCi had 73% more chance of high-quality performance than PCc. The web application was better for assessing quality of testing than the automatic feedback provided by the spirometer. Healthcare professionals’ satisfaction and usability were high. The web-based remote support for primary care by specialists generated a sustained positive impact on quality of testing. The study expands the potential of primary care for diagnosis and management of patients with pulmonary diseases.
S135 Does Cd248 Have A Role In Ipf?
Authors: L. Crowley, D. Bartis, L. Borthwick, A. Fisher, D. Thickett
Journal: Thorax (2014)

<h3></h3> Idiopathic pulmonary fibrosis (IPF) has a complex pathophysiology withepithelial-mesenchymal transition (EMT) thought to be important to the pathogenesis of fibrotic lesions. CD248 is a membrane bound receptor that has collagen and lectins as ligands and is a stromal cell marker, whose expression is up-regulated post-natally during tissue inflammation andre-modelling. A role of CD248 is emerging in kidney fibrosis, but its function in the lung is unknown. We hypothesised that CD248 is a mesenchymal marker of IPF severity and that CD248 contributes to IPF pathogenesis. <h3>Methods</h3> CD248 expression was investigated in 23 IPF patient lung samples using immunohistochemistry (IHC) and qualitatively scored. Expression was assessed in cultured normal human lung fibroblasts (NHLFs), A549 cells, IPF derived fibroblasts and normal human primary ATIIs, treated with or without TGF-β1 and PDGF-BB, using flow cytometry and qRT-PCR. siRNA CD248 knock down (KD) on NHLF mesenchymal marker expression and proliferation was evaluated using qRT-PCR and BrdU assays. <h3>Results</h3> IHC revealed strong CD248 expression by fibroblasts in both fibrotic areas and physiological structures of IPF lung tissue (pericytes and pleural tissue). Expression was greatest in samples from lung transplant explants. <i>In vitro</i>, CD248 protein levels were significantly greater in IPF derived lung fibroblasts vs NHLFs (p &lt; 0.01). CD248 KD significantly reduced proliferation of control, PDGF-BB and/or TGF-β1 treated NHLFs (p &lt; 0.001), but collagen and αSMA mRNA levels were unaffected (p &gt; 0.05). The alveolar epithelium did not express CD248 on the protein level and minimal CD248 mRNA levels were detected in cultured A549 cells and ATIIs, which remained unchanged during TGF-β1 induced EMT. <h3>Summary</h3> CD248 expression is elevated in the lungs of IPF patients especially in severe disease. CD248 expression appears specific for fibroblasts compared to epithelial cells and does not change during EMT. CD248 KD reduced fibroblast proliferation, but not myofibroblast differentiation. We conclude that CD248 over-expression is involved in the pathogenesis of IPF – and that it has potential as a marker of mesenchymal/fibroblast lineage. Given that CD248 ligands are collagen type I, IV and fibronectin, we hypothesise that CD248 signalling represents a novel matrix-fibroblast interaction that may be a potential therapeutic target in IPF.
Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial
Authors: Derek J Hausenloy, Peter K Mwamure, Vinod Venugopal, Joanne Harris, Matthew Barnard, Ernie Grundy, Elizabeth Ashley, Sanjeev Vichare, Carmelo Di Salvo, Shyam Kolvekar, Martin Hayward, Bruce Keogh, Raymond J MacAllister, Derek M Yellon
Journal: The Lancet (2007)
Magnetic resonance imaging of the thorax in the evaluation of asbestosis
Authors: SI Bekkelund, U Aasebo, C Pierre-Jerome, J Holmboe
Journal: European Respiratory Journal (1998)

The purpose of the study was to evaluate the accuracy of magnetic resonance imaging (MRI) in detecting subclinical morphological changes caused by asbestos exposure. Conventional chest radiographs according to the International Labour Organisation (ILO) categories 0-11 and spirometric data were compared with MRI in 17 men with mean (+/-2SD) asbestos exposure time of 24.6+/-13.0 yrs. Mean age was 62.0+/-9.4 yrs. The inclusion criterion was an ILO score of 2 or more. Electrocardiographic registrations and antirespiratory movement artefact techniques were used in all MRI examinations to avoid movement artefacts. Mean ILO grading was found to be 7.7+/-3.8 on chest radiography and 9.8+/-2.0 with MRI (p=0.01). Five patients had a higher ILO stage as evaluated by MRI, but in nine patients the staging remained unchanged. MRI revealed mediastinal adenopathy in four patients. Forced expiratory volume in one second (expressed as a percentage of the predicted value) was negatively correlated with ILO score as assessed by MRI (r=-0.4, p=0.032). Magnetic resonance imaging seems to be more sensitive than conventional radiographs in detecting subclinical fibrosis as well as the extent of pleural asbestosis.
Paradoxical Immune Reconstitution Inflammatory Syndrome Associated With Rituximab-Containing Regimen in a Patient With Lymphoma
Authors: Jonathan Canaani, Sharon Amit, Jonathan Ben-Ezra, Mehrzad Cohen Pour, Nadav Sarid, Hedva Lerman, Chava Perry, Aaron Polliack, Elizabeth Naparstek, Yair Herishanu
Journal: Journal of Clinical Oncology (2013)
Tendon graft revitalization using adult anterior cruciate ligament (ACL)-derived CD34+ cell sheets for ACL reconstruction
Authors: Yutaka Mifune, Tomoyuki Matsumoto, Koji Takayama, Satoshi Terada, Naosumi Sekiya, Ryosuke Kuroda, Masahiro Kurosaka, Freddie H. Fu, Johnny Huard
Journal: Biomaterials (2013)
Brief episode of ischemia activates protective genetic program in rat heart: a gene chip study
Authors: B SIMKHOVICH, P MARJORAM, C POIZAT, L KEDES, R KLONER
Journal: Cardiovascular Research (2003)

Objective: Brief episodes of ischemia of 20 min or less have the potential to protect the heart. Such episodes are associated primarily with reversible ischemic injury yet they induce changes in gene expression. The purpose of the study was to determine whether activation of protective genes takes place within 4 h following a brief episode of ischemia that would mimic angina pectoris. Methods: Three groups of rats were studied. In the control (Ctrl) group, hearts were immediately excised following anesthesia; in the sham-operated (SO) group, opened-chest rats received 4 h and 20 min of no intervention; and in the group subjected to ischemia (SI) hearts received 20 min of proximal coronary occlusion followed by 4 h of reperfusion. Hearts from the SI group were divided into nonischemic (NI) and ischemic (Isc) areas. Changes in gene expression pattern were analyzed by using Affymetrix Gene Chips. Results: Ischemia led to strong upregulation of mRNA transcripts for heat shock proteins 70, 27, 105, 86 and 40 kDa, vascular endothelial growth factor, brain-derived neurotrophic factor, plasminogen activator inhibitor-1, activating transcription factor 3, B-cell translocation gene 2, and growth arrest and DNA damage inducible 45 α protein compared to the NI tissue. The majority of mRNAs whose levels increased following brief ischemia were of a protective nature. Conclusion: Genetic reprogramming emerging during or following brief episodes of ischemia that simulate angina, can be characterized as protective in nature. Developing new therapeutic strategies aimed to promote this protective response represents a legitimate target for future research.
Prostate-Specific Antigen and Prostate-Specific Antigen Velocity as Threshold Indicators in 11C-Acetate PET/CTAC Scanning for Prostate Cancer Recurrence
Authors: Reginald W. Dusing, Warner Peng, Sue-Min Lai, Gordon L. Grado, Jeffrey M. Holzbeierlein, J. Brantley Thrasher, Jacqueline Hill, Peter J. Van Veldhuizen
Journal: Clinical Nuclear Medicine (2014)

The aim of this study was to identify which patient characteristics are associated with the highest likelihood of positive findings on 11C-acetate PET/computed tomography attenuation correction (CTAC) (PET/CTAC) scan when imaging for recurrent prostate cancer.From 2007 to 2011, 250 11C-acetate PET/CTAC scans were performed at a single institution on patients with prostate cancer recurrence after surgery, brachytherapy, or external beam radiation. Of these patients, 120 met our inclusion criteria. Logistic regression analysis was used to examine the relationship between predictability of positive findings and patients' characteristics, such as prostate-specific antigen (PSA) level at the time of scan, PSA kinetics, Gleason score, staging, and type of treatment before scan.In total, 68.3% of the 120 11C-acetate PET/CTAC scans were positive. The percentage of positive scans and PSA at the time of scanning and PSA velocity (PSAV) had positive correlations. The putative sensitivity and specificity were 86.6% and 65.8%, respectively, when a PSA level greater than 1.24 ng/mL was used as the threshold for scanning. The putative sensitivity and specificity were 74% and 75%, respectively, when a PSAV level greater than 1.32 ng/mL/y was used as the threshold. No significant associations were found between scan positivity and age, PSA doubling time, Gleason score, staging, or type of treatment before scanning.This retrospective study suggests that threshold models of PSA greater than 1.24 ng/mL or PSAV greater than 1.32 ng/mL per year are independent predictors of positive findings in 11C-acetate PET/CTAC imaging of recurrent prostate cancer.
Mechanisms underlying increased right ventricular conduction sensitivity to flecainide challenge
Authors: R. Veeraraghavan, S. Poelzing
Journal: Cardiovascular Research (2007)

The cardiac sodium current (I(Na)) is a major determinant of conduction. Mechanisms underlying regionally heterogeneous conduction slowing secondary to reduced I(Na) in diseases such as the Brugada syndrome and heart failure remain incompletely understood. Right precordial electrophysiological manifestations during flecainide challenge suggest a decreased right ventricular depolarization reserve. We hypothesized that heterogeneous cardiac sodium channel (Na(v)1.5) distribution between ventricles causes interventricular depolarization heterogeneities.Western blotting analysis revealed Na(v)1.5, and Kir2.1 protein expressions were 18.2 and 12.0% lower, respectively, in the guinea pig right ventricle (RV) compared with the left ventricle (LV). Conduction velocity (theta) heterogeneities were quantified by optical mapping during LV or RV pacing. Although RV transverse theta((thetaT)) was significantly greater than LV (thetaT) by 33.09 +/- 1.38% under control conditions, there were no differences in longitudinal theta. During partial sodium channel blockade (flecainide, 0.5 microM), RV theta decreased by 35.3 +/- 1.3%, whereas LV theta decreased by 29.2 +/- 1.0%. These data demonstrate that the RV has an increased conduction dependence on sodium channel availability. Partial blockade of the inward rectifier potassium current (I(K1)) by BaCl(2) (10 microm) significantly increased theta in both ventricles under control conditions. However, BaCl(2) only increased conduction dependence on sodium channel availability in the LV. This suggests that the LV may have an increased depolarization reserve compared with the RV, but the larger I(K1) depresses control LV theta.Interventricular I(K1) heterogeneities may underlie conduction heterogeneities observed under control conditions. However, under conditions where I(Na) is functionally reduced in disease or during pharmacological sodium channel blockade, the heterogeneity in Na(v)1.5 expression may become a significant determinant of conduction heterogeneities.
Role of an Electrogenic Na <sup>+</sup> -HCO <sub>3</sub> <sup>−</sup> Cotransport in Determining Myocardial pH <sub>i</sub> After an Increase in Heart Rate
Authors: María C. Camilión de Hurtado, Bernardo V. Alvarez, Néstor G. Pérez, Horacio E. Cingolani
Journal: Circulation Research (1996)

The contribution of electrogenic Na + -HCO 3 − cotransport to pH i regulation during changes in heart rate was explored in cat papillary muscles loaded with BCECF-AM in bicarbonate-free (HEPES) medium and in CO 2 /HCO 3 − -buffered medium. Stepwise increments in the frequency of contraction from 15 to 100 bpm induced a reversible increase in the pH i from 7.13±0.03 to 7.36±0.03 ( P &lt;.05, n=5) in the presence of CO 2 /HCO 3 − buffer. The same increase in the frequency of stimulation, however, decreased pH i from 7.10±0.02 to 6.91±0.06 ( P &lt;.05, n=5), in the absence of bicarbonate. Moreover, in CO 2 /HCO 3 − -superfused muscles pretreated with SITS (0.1 mmol/L), this effect of increasing the contraction frequency was reversed, and a decrease of pH i from 7.03±0.04 to 6.88±0.06 ( P &lt;.05, n=4) was observed when the pacing rate was increased stepwise from 15 to 100 bpm. High [K + ] o –induced depolarization of cell membrane alkalinized myocardial cells in the presence of HCO 3 − ions, whereas acidification was observed as a consequence of hyperpolarization induced by low external [K + ] o . Myocardial resting membrane potential became hyperpolarized upon exposure to HCO 3 − -buffered media. This HCO 3 − -induced hyperpolarization was not blocked by the inhibition of Na + ,K + -ATPase activity by ouabain (0.5 μmol/L) but was prevented by SITS. The results suggested that membrane depolarization during cardiac action potential causes an increase in electrogenic Na + -HCO 3 − cotransport. Such depolarizations occurring as a consequence of increases in heart rate would thus, by means of elevated bicarbonate influxes, substantially increase the myocardial cell's ability to recover from an enhanced proton production.
The role of iron redox state in the genotoxicity of ultrafine superparamagnetic iron oxide nanoparticles
Authors: Neenu Singh, Gareth J.S. Jenkins, Bryant C. Nelson, Bryce J. Marquis, Thierry G.G. Maffeis, Andy P. Brown, Paul M. Williams, Chris J. Wright, Shareen H. Doak
Journal: Biomaterials (2011)
Nanoparticles encapsulating hepatitis B virus cytosine-phosphate-guanosine induce therapeutic immunity against HBV infection
Authors: Shujuan Lv, Jun Wang, Shuang Dou, Xianzhu Yang, Xiang Ni, Rui Sun, Zhigang Tian, Haiming Wei
Journal: Hepatology (2013)

Infection with hepatitis B virus (HBV) is the most common cause of liver disease worldwide. However, because the current interferon (IFN)-based treatments have toxic side effects and marginal efficacy, improved antivirals are essential. Here we report that unmethylated cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) from the HBV genome (HBV-CpG) induced robust expression of IFN-α by plasmacytoid dendritic cells (pDCs) in a Toll-like receptor 9 (TLR9)-dependent manner. We also identified inhibitory guanosine-rich ODNs in the HBV genome (HBV-ODN) that are capable of inhibiting HBV-CpG-induced IFN-α production. Furthermore, nanoparticles containing HBV-CpG, termed NP(HBV-CpG), reversed the HBV-ODN-mediated suppression of IFN-α production and also exerted a strong immunostimulatory effect on lymphocytes. Our results suggest that NP(HBV-CpG) can enhance the immune response to hepatitis B surface antigen (HBsAg) and skew this response toward the Th1 pathway in mice immunized with rHBsAg and NP(HBV-CpG). Moreover, NP(HBV-CpG)-based therapy led to the efficient clearance of HBV and induced an anti-HBsAg response in HBV carrier mice. Conclusion : Endogenous HBV-CpG ODNs from the HBV genome induce IFN-α production so that nanoparticle-encapsulated HBV-CpG may act as an HBsAg vaccine adjuvant and may also represent a potent therapeutic agent for the treatment of chronic HBV infection. (Hepatology 2014;59:385–394)
Caffeine ameliorates hemodynamic derangements and portosystemic collaterals in cirrhotic rats
Authors: Shao‐Jung Hsu, Fa‐Yauh Lee, Sun‐Sang Wang, I‐Fang Hsin, Te‐Yueh Lin, Hui‐Chun Huang, Ching‐Chih Chang, Chiao‐Lin Chuang, Hsin‐Ling Ho, Han‐Chieh Lin, Shou‐Dong Lee
Journal: Hepatology (2014)

Portal hypertension (PH), a pathophysiological derangement of liver cirrhosis, is characterized by hyperdynamic circulation, angiogenesis, and portosystemic collaterals. These may lead to lethal complications, such as variceal bleeding. Caffeine has been noted for its effects on liver inflammation, fibrogenesis, and vasoreactiveness. However, the relevant influences of caffeine in cirrhosis and PH have not been addressed. Spraque‐Dawley rats with common bile duct ligation–induced cirrhosis or sham operation received prophylactic or therapeutic caffeine treatment (50 mg/kg/day, the first or 15th day since operation, respectively) for 28 days. Compared to vehicle (distilled water), caffeine decreased cardiac index, increased systemic vascular resistance, reduced portal pressure (PP), superior mesenteric artery flow, mesenteric vascular density, portosystemic shunting (PSS), intrahepatic angiogenesis, and fibrosis without affecting liver and renal biochemistry. The beneficial effects were reversed by selective adenosine A1 agonist N6‐cyclopentyladenosine (CPA) or A2A agonist GCS21680. Both prophylactic and therapeutic caffeine treatment decreased portal resistance and PP in thioacetamide (200mg/kg, thrice‐weekly for 8 weeks)‐induced cirrhotic rats. Caffeine down‐regulated endothelial nitric oxide synthase, vascular endothelial growth factor (VEGF), phospho‐VEGFR2, and phospho–Akt mesenteric protein expression. Caffeine adversely affected viability of hepatic stellate and sinusoidal endothelial cells, which was reversed by CPA and GCS21680. On the other hand, caffeine did not modify vascular response to vasoconstrictors in splanchnic, hepatic, and collateral vascular beds. Conclusions : Caffeine decreased PP, ameliorated hyperdynamic circulation, PSS, mesenteric angiogenesis, hepatic angiogenesis, and fibrosis in cirrhotic rats. Caffeine may be a feasible candidate to ameliorate PH‐related complications in cirrhosis. (H epatology 2015;61:1672‐1684)
Loss of p16 Protein Defines High-Risk Patients with Gastrointestinal Stromal Tumors: A Tissue Microarray Study
Authors: Regine Schneider-Stock, Carsten Boltze, Jerzy Lasota, Brigitte Peters, Chris L. Corless, Petra Ruemmele, Luigi Terracciano, Matthias Pross, Luigi Insabato, Dolores Di Vizio, Igor Iesalnieks, Stefan Dirnhofer, Arndt Hartmann, Michel Heinrich, Markku Miettinen, Albert Roessner, Luigi Tornillo
Journal: Clinical Cancer Research (2005)

Despite clearly defined histologic criteria, the prediction of tumor behavior for patients with gastrointestinal stromal tumors (GIST) still poses a challenge to pathologists. Therefore, searching for alternative markers that allow for better prognostic evaluation is an important task. To determine the practicability of immunohistochemical staining for p16 in clinical cases, we examined p16 protein expression in a group of 284 GISTs, a subset of which had long-term follow-up (median, 45 months; range, 1-204 months). P16 protein expression was ascertained on tissue microarrays as well as on standard sections. Survival analyses were carried out in 157 patients. P16 loss was found in 50% of GISTs, there being no correlation with age, sex, histologic subtype, signs of necrosis, or metastases. Patients having p16-negative tumors had a worse prognosis than those with p16-positive tumors (P = 0.012) with a 2.3-fold relative increased risk of dying of disease. P16 loss identified a subgroup of gastric tumors with a worse prognosis (P = 0.03). The multivariate configural frequency analysis identified two "antitypes," whose observed frequency was found to be significantly lower than the expected frequency [i.e., marker combinations: p16 positive, no metastases, and death of disease and p16 loss, metastases, and still alive]. The "type" whose observed frequency was significantly higher than the expected frequency consisted of the following marker pattern: p16 loss, necrosis, and death of disease (P < 0.001). In the multivariate Cox regression analysis, p16 loss, necrosis, and metastases each had independent prognostic value. P16 loss is a common molecular abnormality in GISTs and might be used in routine diagnosis to identify patients with high-risk tumors.