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Pulmonary arterial hypertension

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https://www.readbyqxmd.com/read/29453947/evaluation-of-the-effects-of-rp5063-a-novel-multimodal-serotonin-receptor-modulator-as-single-agent-therapy-and-co-administrated-with-sildenafil-bosentan-and-treprostinil-in-a-monocrotaline-induced-pulmonary-arterial-hypertension-rat-model
#1
Laxminarayan Bhat, Jon Hawkinson, Marc Cantillon, Dasharatha G Reddy, Seema R Bhat, Charles-E Laurent, Annie Bouchard, Marzena Biernat, Dany Salvail
Pulmonary arterial hypertension (PAH), a condition that is defined by pulmonary vasculature constriction and remodeling, involves dysfunctional signaling of the serotonin (5-HT) receptors, 5-HT 2/2B/7 . In a rat model of monocrotaline (MCT)-induced PAH, the effectiveness of RP5063 (RP), a dopamine and 5-HT receptor modulator, was evaluated as monotherapy and as an adjunct to standard PAH treatments. After a single 60mg/kg dose of MCT, rats received vehicle (MCT+Veh; gavage twice-daily [b.i.d.]), RP (10mg/kg; gavage b...
February 14, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29453476/postoperative-outcome-in-patients-with-pulmonary-hypertension-undergoing-elective-non-cardiac-surgery
#2
Vikas Pathak, Kriti Suwal
INTRODUCTION: The impact of pulmonary artery hypertension on post-operative outcome in elective, non-cardiac surgery is incompletely understood. This study was designed to evaluate the post-operative outcome of patients undergoing elective, non-cardiac surgery with and without pulmonary hypertension. METHODS: The study was conducted in an inner-city hospital in Bronx, New York. A retrospective chart review was conducted on all patients who underwent elective, non- cardiac surgery from January 2000 to December 2010 and had echocardiogram within 30 days of surgery...
October 2017: JNMA; Journal of the Nepal Medical Association
https://www.readbyqxmd.com/read/29449428/a-novel-piperidine-identified-by-stem-cell-based-screening-attenuates-pulmonary-arterial-hypertension-via-regulating-bmp2-and-ptgs2-levels
#3
Yanjiang Xing, Shuang Zhao, Qingxia Wei, Shiqiang Gong, Xin Zhao, Fang Zhou, Rafia Ai-Lamki, Daniel Ortmann, Mingxia Du, Roger Pedersen, Guangdong Shang, Shuyi Si, Nicholas W Morrell, Jun Yang
Genetic defects in bone morphogenetic protein type-II receptor (BMPRII) signalling and inflammation contribute to the pathogenesis of pulmonary arterial hypertension (PAH). The receptor is activated by BMP ligands, which also enhance BMPR2 transcription. A small molecule BMP upregulator with selectivity on vascular endothelium would represent a desirable therapeutic intervention for PAH.We assayed compounds identified in the screening of BMP2 upregulators for their ability to increase expression of Inhibitor of DNA binding 1 (Id1), using a dual reporter driven specifically in human embryonic stem cell (hESC)-derived endothelial cells (ECs)...
February 15, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29447737/pulmonary-arterial-hypertension-related-morbidity-is-prognostic-for-mortality
#4
Vallerie V McLaughlin, Marius M Hoeper, Richard N Channick, Kelly M Chin, Marion Delcroix, Sean Gaine, Hossein-Ardeschir Ghofrani, Pavel Jansa, Irene M Lang, Sanjay Mehta, Tomás Pulido, B K S Sastry, Gérald Simonneau, Olivier Sitbon, Rogério Souza, Adam Torbicki, Victor F Tapson, Loïc Perchenet, Ralph Preiss, Pierre Verweij, Lewis J Rubin, Nazzareno Galiè
BACKGROUND: Registry data suggest that disease progression in pulmonary arterial hypertension (PAH) is indicative of poor prognosis. However, the prognostic relevance of PAH-related morbidity has not been formally evaluated in randomized controlled trials. OBJECTIVES: The purpose of these analyses was to assess the impact of morbidity events on the risk of subsequent mortality using the landmark method and data from the SERAPHIN and GRIPHON studies. METHODS: For each study, the risk of all-cause death up to the end of the study was assessed from the landmark time point (months 3, 6, and 12) according to whether a patient had experienced a primary endpoint morbidity event before the landmark...
February 20, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29447389/survival-of-adults-with-systemic-autoimmune-rheumatic-diseases-and-pulmonary-arterial-hypertension-after-lung-transplantation
#5
Elana J Bernstein, Joan M Bathon, David J Lederer
Objectives: Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality in adults with systemic autoimmune rheumatic diseases (ARDs). The aim of this study was to determine whether adults with ARDs and PAH on right-sided heart catheterization (ARD-PAH) have increased mortality following lung transplantation compared with those with PAH not due to an ARD. Methods: We conducted a retrospective cohort study of 93 adults with ARD-PAH and 222 adults with PAH who underwent lung transplantation in the USA between 4 May 2005 and 9 March 2015 using data from the United Network for Organ Sharing...
February 13, 2018: Rheumatology
https://www.readbyqxmd.com/read/29446818/heart-involvement-in-systemic-sclerosis
#6
Ihsen Zairi, Lilia Baili, Khadija Mzoughi, Manel Dridi, Zouhaier Jnifene, Fatma Boussema
INTRODUCTION: Primary and secondary heart involvement in systemic sclerosis are important mortality predictors. Aim of this study was to investigate by standard echocardiography associated to pulsed-tissue Doppler imaging, six-minute walk test (6MWT) and BNP level cardiac manifestation in 30 patients with ScS and to establish a strategy to detect and to evaluate this complication. METHODS: This was a cross-sectional study conducted over a period of 16 months: a total of 30 consecutive patients with ScS diagnosed as proposed by the American college of Rheumatology and the European League Against Rheumatism 2013 and who were hospitalized in Internal Medicine department of Habib Thameur hospital underwent cardiac assessment...
March 2017: La Tunisie Médicale
https://www.readbyqxmd.com/read/29446710/early-versus-late-cardiac-remodelling-during-right-ventricular-pressure-load-and-impact-of-preventive-versus-rescue-therapy-with-endothelin-1-receptor-blockers
#7
Sara Roldan Ramons, Guido Ehrenfried Pieles, Mei Sun, Cameron Slorach, Wei Hui, Mark K Friedberg
BACKGROUND: Pulmonary artery banding (PAB) causes right ventricular (RV) dysfunction, biventricular fibrosis and apoptosis which are attenuated by endothelin-1 (ET1) receptor blockade (ERB). Little is known about the time-course of remodelling and whether early versus late ERB confers improved outcome. MATERIALS AND METHODS: PAB was performed in 5-groups of rabbits: Shams, 3W (3-weeksPAB), 6W (6-weeksPAB), 6WERB1 (6-weeksPAB+ERB from day-1) and 6WERB21 (6-weeksPAB+ERB from day-21)...
February 15, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29445936/pulmonary-arterial-hemodynamic-assessment-by-a-novel-index-in-systemic-sclerosis-patients-pulmonary-pulse-transit-time
#8
Mehmet Dogan, Tolga Han Efe, Tolga Cimen, Cem Ozisler, Mehmet Ali Felekoglu, Ahmet Goktug Ertem, Mehmet Erat, Omer Yiginer, Murat Tulmac
OBJECTIVES: Systemic sclerosis (SSc) is a chronic, inflammatory, and autoimmune connective tissue disease that is associated with vascular lesions, and fibrosis of the skin and visceral organs. Cardiac complications may occur as a secondary effect of SSc as a result of pulmonary arterial hypertension and interstitial lung disease. The objective of this study was to assess whether the pulmonary pulse transit time (pPTT) could serve as a diagnostic marker for pulmonary arterial alterations in patients with SSc, prior to development of pulmonary hypertension...
February 14, 2018: Lung
https://www.readbyqxmd.com/read/29445095/granzyme-b-deficiency-promotes-osteoblastic-differentiation-and-calcification-of-vascular-smooth-muscle-cells-in-hypoxic-pulmonary-hypertension
#9
Min Mao, Min Zhang, Anqi Ge, Xin Ge, Rui Gu, Chen Zhang, Yao Fu, Jiayin Gao, Xiaoying Wang, Yang Liu, Daling Zhu
Calcification is a major risk factor for vascular integrity. This pathological symptom and the underlying mechanisms in hypoxic pulmonary artery hypertension remain elusive. Here we report that pulmonary vascular medial calcification is elevated in pulmonary artery hypertension models as a result of an osteoblastic phenotype change of pulmonary arterial smooth muscle cells induced by hypoxia. Notably, inhibiting store-operated calcium channels significantly decreased osteoblastic differentiation and calcification of pulmonary arterial smooth muscle cells under hypoxia...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29444988/nmda-type-glutamate-receptor-activation-promotes-vascular-remodeling-and-pulmonary-arterial-hypertension
#10
Sébastien J Dumas, Gilles Bru-Mercier, Audrey Courboulin, Marceau Quatredeniers, Catherine Rücker-Martin, Fabrice Antigny, Morad K Nakhleh, Benoit Ranchoux, Elodie Gouadon, Maria-Candida Vinhas, Matthieu Vocelle, Nicolas Raymond, Peter Dorfmüller, Elie Fadel, Frédéric Perros, Marc Humbert, Sylvia Cohen-Kaminsky
Background -Excessive proliferation and apoptosis resistance in pulmonary vascular cells underlie vascular remodeling in pulmonary arterial hypertension (PAH). Specific treatments for PAH exist, mostly targeting endothelial dysfunction, but high pulmonary arterial pressure still causes heart failure and death. Pulmonary vascular remodeling may be driven by metabolic reprogramming of vascular cells to increase glutaminolysis and glutamate production. The N-methyl-D-aspartate receptor (NMDAR), a major neuronal glutamate receptor, is also expressed on vascular cells, but its role in PAH is unknown...
February 14, 2018: Circulation
https://www.readbyqxmd.com/read/29444925/increasing-incidence-and-prevalence-of-world-health-organization-groups-1-to-4-pulmonary-hypertension-a-population-based-cohort-study-in-ontario-canada
#11
D Thiwanka Wijeratne, Katherine Lajkosz, Susan B Brogly, M Diane Lougheed, Li Jiang, Ahmad Housin, David Barber, Ana Johnson, Katharine M Doliszny, Stephen L Archer
BACKGROUND: The World Health Organization recognizes 5 groups of pulmonary hypertension (PH), categorized by pathogenesis or comorbidity: 1-pulmonary arterial hypertension 2-left-heart disease, 3-lung disease and hypoxia 4-chronic thromboembolic disease, and 5-miscellaneous. The epidemiology of PH, apart from group 1, is largely unknown. METHODS AND RESULTS: We describe incidence, prevalence, comorbidities, mortality and prescribing patterns for groups 1 to 4 PH from 1993 to 2012...
February 2018: Circulation. Cardiovascular Quality and Outcomes
https://www.readbyqxmd.com/read/29444773/lung-function-inflammation-and-endothelin-1-in-congenital-heart-disease-associated-pulmonary-arterial-hypertension
#12
Andrew Low, Sarah George, Luke Howard, Nicholas Bell, Ann Millar, Robert M R Tulloh
BACKGROUND: Breathlessness is the most common symptom in people with pulmonary arterial hypertension and congenital heart disease (CHD-APAH), previously thought to be caused by worsening PAH, but perhaps also by inflammation and abnormalities of lung function. We studied lung function and airway inflammation in patients with CHD-APAH and compared the results with controls. METHODS AND RESULTS: Sixty people were recruited into the study: 20 CHD-APAH, 20 CHD controls, and 20 healthy controls...
February 14, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29442198/hgf-reduces-disease-severity-and-inflammation-by-attenuating-the-nf-%C3%AE%C2%BAb-signaling-in-a-rat-model-of-pulmonary-artery-hypertension
#13
Ying Pang, Ming-Ting Liang, Ying Gong, Yong Yang, Pei-Li Bu, Mei Zhang, Heng-Chen Yao
The purpose of the present study was to investigate the anti-inflammatory effect of hepatocyte growth factor (HGF) on pulmonary artery hypertension (PAH) in a rat model and underlying mechanisms. Wistar rats were treated with monocrotaline intravenously to induce PAH and then treated with vehicle or HGF for 2 weeks, respectively. The mean pulmonary artery pressure (mPAP), the index of right heart ventricular hypertrophy (RHVI), pathological changes, and inflammation in the lungs of individual rats were measured...
February 13, 2018: Inflammation
https://www.readbyqxmd.com/read/29441403/sex-differences-in-hemodynamic-responses-and-long-term-survival-to-optimal-medical-therapy-in-patients-with-pulmonary-arterial-hypertension
#14
Katsuya Kozu, Koichiro Sugimura, Tatsuo Aoki, Shunsuke Tatebe, Saori Yamamoto, Nobuhiro Yaoita, Toru Shimizu, Kotaro Nochioka, Haruka Sato, Ryo Konno, Kimio Satoh, Satoshi Miyata, Hiroaki Shimokawa
It is widely known that the incidence of pulmonary arterial hypertension (PAH) is higher in female, whereas prognosis is poorer in male patients. However, sex differences in hemodynamic response to and long-term prognosis with PAH-targeted treatment in the modern era remain to be fully elucidated. We examined the long-term prognosis of 129 consecutive PAH patients (34 males and 95 females) diagnosed in our hospital from April 1999 to October 2014, and assessed hemodynamic changes in response to PAH-targeted therapy...
February 13, 2018: Heart and Vessels
https://www.readbyqxmd.com/read/29440197/assessing-prognosis-of-pulmonary-arterial-hypertension-in-the-therapeutic-era-importance-of-serial-hemodynamic-measurements
#15
EDITORIAL
Lewis J Rubin
No abstract text is available yet for this article.
February 13, 2018: Circulation
https://www.readbyqxmd.com/read/29438624/lessons-from-cancer-subcellular-drug-targeting-of-mitochondrial-hsp90-in-pulmonary-arterial-hypertension
#16
Wolfgang M Kuebler
No abstract text is available yet for this article.
February 13, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29438559/oxidative-stress-increases-m1dg-a-major-peroxidation-derived-dna-adduct-in-mitochondrial-dna
#17
Orrette R Wauchope, Michelle M Mitchener, William N Beavers, James J Galligan, Jeannie M Camarillo, William D Sanders, Philip J Kingsley, Ha-Na Shim, Thomas Blackwell, Thong Luong, Mark deCaestecker, Joshua P Fessel, Lawrence J Marnett
Reactive oxygen species (ROS) are formed in mitochondria during electron transport and energy generation. Elevated levels of ROS lead to increased amounts of mitochondrial DNA (mtDNA) damage. We report that levels of M1dG, a major endogenous peroxidation-derived DNA adduct, are 50-100-fold higher in mtDNA than in nuclear DNA in several different human cell lines. Treatment of cells with agents that either increase or decrease mitochondrial superoxide levels leads to increased or decreased levels of M1dG in mtDNA, respectively...
February 9, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29438213/new-no-donor-ncx-1443-therapeutic-effects-on-pulmonary-hypertension-in-the-sad-mouse-model-of-sickle-cell-disease
#18
Shariq Abid, Kanny Kebe, Amal Houssaïni, Françoise Tomberli, Elisabeth Marcos, Emilie Bizard, Marielle Breau, Aurelien Parpaleix, Claire-Marie Tissot, Bernard Maitre, Larissa Lipskaia, Genevieve Derumeaux, Elena Bastia, Armand Mekontso-Dessap, Serge Adnot
Nitric oxide (NO) donors may be useful for treating pulmonary hypertension (PH) complicating sickle cell disease (SCD), as endogenous NO is inactivated by hemoglobin released by intravascular hemolysis. Here, we investigated the effects of the new NO donor NCX1443 on PH in transgenic SAD mice, which exhibit mild SCD without severe hemolytic anemia. In SAD and wild-type (WT) mice, the pulmonary pressure response to acute hypoxia was similar and was abolished by 100 mg/kg NCX1443. The level of PH was also similar in SAD and WT mice exposed to chronic hypoxia (9% O2) alone or with SU5416, and was similarly reduced by daily NCX1443 gavage...
February 8, 2018: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29436381/subcutaneous-treprostinil-in-congenital-heart-disease-related-pulmonary-arterial-hypertension
#19
Nika Skoro-Sajer, Christian Gerges, Olga Hajnalka Balint, Dora Kohalmi, Monika Kaldararova, Iveta Simkova, Johannes Jakowitsch, Harald Gabriel, Helmut Baumgartner, Mario Gerges, Roela Sadushi-Kolici, David S Celermajer, Irene Marthe Lang
OBJECTIVE: To assess the efficacy and safety of subcutaneous treprostinil in adult patients with congenital heart disease (CHD)-associated pulmonary arterial hypertension (PAH) after 12 months of treatment. METHODS: Consecutive adult patients with CHD-PAH received subcutaneous treprostinil to maximum tolerated doses in an observational study. RESULTS: Advanced CHD-PAH patients with WHO class III or IV disease (n=32, age 40±10 years, 20 females) received treprostinil for suboptimal response to bosentan (n=12), WHO functional class IV disease (FC, n=7) or prior to bosentan approval (n=13)...
February 7, 2018: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/29436260/treatment-patterns-and-associated-health-care-costs-before-and-after-treatment-initiation-among-pulmonary-arterial-hypertension-patients-in-the-united-states
#20
Charles D Burger, A Burak Ozbay, Howard M Lazarus, Ellen Riehle, Leslie B Montejano, Gregory Lenhart, R James White
BACKGROUND: Despite multiple treatment options, the prognosis of pulmonary arterial hypertension (PAH) remains poor. PAH patients experience a high economic burden due to comorbidities, hospitalizations, and medication costs. Although combination therapy has been shown to reduce hospitalizations, the relationship between treatment, health care utilization, and costs remains unclear. OBJECTIVE: To provide a characterization of health care utilization and costs in real-world settings by comparing periods before and after initiating PAH-specific treatment...
February 13, 2018: Journal of Managed Care & Specialty Pharmacy
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