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Pulmonary hypertension treatment

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https://www.readbyqxmd.com/read/27932335/multicentre-randomised-placebo-controlled-trial-of-oral-anticoagulation-with-apixaban-in-systemic-sclerosis-related-pulmonary-arterial-hypertension-the-sphinx-study-protocol
#1
Alicia Calderone, Wendy Stevens, David Prior, Harshal Nandurkar, Eli Gabbay, Susanna M Proudman, Trevor Williams, David Celermajer, Joanne Sahhar, Peter K K Wong, Vivek Thakkar, Nathan Dwyer, Jeremy Wrobel, Weng Chin, Danny Liew, Margaret Staples, Rachelle Buchbinder, Mandana Nikpour
INTRODUCTION: Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12-15% of patients with SSc and accounts for 30-40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH...
December 8, 2016: BMJ Open
https://www.readbyqxmd.com/read/27929408/a-review-of-targeted-pulmonary-arterial-hypertension-specific-pharmacotherapy
#2
REVIEW
Ali Ataya, Jessica Cope, Hassan Alnuaimat
Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the treatment of this complex disease state. In this manuscript, we provide a comprehensive review of the current Food and Drug Administration (FDA)-approved pulmonary arterial hypertension-specific therapies, and their supporting evidence for adults, targeting the nitric oxide, soluble guanylate cyclase, endothelin, and prostacyclin pathways...
December 6, 2016: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/27927914/tryptophan-hydroxylase-1-tph1-inhibition-impacts-pulmonary-vascular-remodeling-in-two-rat-models-of-pulmonary-hypertension
#3
Robert J Aiello, Patricia-Ann Bourassa, Qing Zhang, Jeffrey Dubins, Daniel R Goldberg, Stephane De Lombaert, Marc Humbert, Christophe Guignabert, Maria A Cavasin, Timothy A McKinsey, Vishwas Paralkar
Pulmonary arterial hypertension (PAH) is a progressive disease defined by a chronic elevation in pulmonary arterial pressure with extensive pulmonary vascular remodeling and perivascular inflammation characterized by an accumulation of macrophages, lymphocytes, dendritic cells and mast cells. While the exact etiology of the disease is unknown, clinical as well as pre-clinical data strongly implicate a role for serotonin (5 HT) in the process. Here, we investigated the chronic effects of pharmacological inhibition of tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in peripheral 5 HT biosynthesis, in two pre-clinical models of pulmonary hypertension (PH), the monocrotaline (MCT) rat and the SU5416 (SUGEN)-hypoxia rat...
December 7, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27927014/genetic-modification-of-the-lung-directed-toward-treatment-of-human-disease
#4
Dolan Sondhi, Katie Stiles, Bishnu P De, Ronald G Crystal
Genetic modification therapy is a promising therapeutic strategy for many diseases of the lung intractable to other treatments. Lung gene therapy has been the subject of numerous preclinical animal experiments and human clinical trials, for targets including genetic diseases such as cystic fibrosis and α1-antitrypsin deficiency, complex disorders such as asthma, allergy and lung cancer, infections such as respiratory syncytial virus and Pseudomonas, as well as pulmonary arterial hypertension, transplant rejection and lung injury...
December 7, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27919727/patent-ductus-arteriosus-in-cats-felis-catus-50-cases-2000-2015
#5
A Bascuñán, K M Thieman Mankin, A B Saunders, J M Bright, V Scharf, A Singh, L O'Sullivan, B Brisson, A H Estrada, S P Tou, C Ruoff
OBJECTIVES: To describe signalment, clinical characteristics, diagnostic, treatment, and outcome data in a large case series of cats with patent ductus arteriosus (PDA). ANIMALS: Fifty cats with confirmed PDA. METHODS: Retrospective review of medical records from five referral veterinary hospitals for cats with PDA between 2000 and 2015. Cats were included if a PDA was visualized echocardiographically, during surgery, or on post-mortem examination...
December 2, 2016: Journal of Veterinary Cardiology: the Official Journal of the European Society of Veterinary Cardiology
https://www.readbyqxmd.com/read/27919660/a-comparison-of-vasodilation-mode-among-selexipag-ns-304-2-4-5-6-diphenylpyrazin-2-yl-isopropyl-amino-butoxy-n-methylsulfonyl-acetamide-its-active-metabolite-mre-269-and-various-prostacyclin-receptor-agonists-in-rat-porcine-and-human-pulmonary-arteries
#6
Chiaki Fuchikami, Kohji Murakami, Koyuki Tajima, Junko Homan, Keiji Kosugi, Kazuya Kuramoto, Michiko Oka, Keiichi Kuwano
Selexipag (NS-304; [2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N- (methylsulfonyl)acetamide]) is a novel, orally available non-prostanoid prostacyclin receptor (IP receptor) agonist that has recently been approved for the treatment of pulmonary arterial hypertension (PAH). We examined the effect of the active metabolite of selexipag, MRE-269, and IP receptor agonists that are currently available as PAH therapeutic drugs on the relaxation of rat, porcine and human pulmonary artery. cAMP formation in human pulmonary artery smooth muscle cells was induced by all test compounds (MRE-269, epoprostenol, iloprost, treprostinil and beraprost sodium) and suppressed by IP receptor antagonists (CAY10441 and 2-[4-(1H-indol-4-yloxymethyl)-benzyloxycarbonylamino]-3-phenyl-propionic acid)...
December 2, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27919605/not-all-patients-with-critical-limb-ischaemia-require-revascularisation
#7
T B Santema, R M Stoekenbroek, J van Loon, M J W Koelemay, D T Ubbink
OBJECTIVES: International guidelines recommend revascularisation as the preferred treatment for patients with critical limb ischaemia (CLI). Most contemporary research focuses on the outcome of invasive procedures for CLI, but little is known about the outcome of conservative management. Amputation free survival (AFS) and overall survival (OS) was investigated in patients with CLI who did or did not receive revascularisation, and characteristics associated with clinical outcomes were explored...
December 2, 2016: European Journal of Vascular and Endovascular Surgery
https://www.readbyqxmd.com/read/27918213/percutaneous-therapies-for-tricuspid-regurgitation
#8
Erin A Fender, Rick A Nishimura, David R Holmes
Chronic tricuspid valve regurgitation is usually associated with left-sided heart disease or pulmonary hypertension. Although severe tricuspid valve regurgitation carries a poor prognosis, isolated surgery is rarely performed due to high in-hospital mortality and an unclear impact on long term survival. The lack of adequate surgical treatment has resulted in a large population of patients with an unmet clinical need. Areas Covered: Transcatheter therapies have revolutionized the management of high risk patients with left-sided valvular disease, and have sparked interest in translating minimally invasive therapies to the tricuspid valve...
December 5, 2016: Expert Review of Medical Devices
https://www.readbyqxmd.com/read/27916062/-perioperational-management-of-gynecological-cancer-patients-with-severe-internal-medical-complications-a-serial-of-37-clinical-cases
#9
J Hu, W Q Lyu, Y L Guo, H W Wen, H Qiao, Y Qu
Objective: To evaluate the effectiveness and safety of perioperational management of gynecological cancer patients with severe internal medical complications. Methods: We collected 37 cases of gynecological cancer patients with severe internal medical complications who were hospitalized in Peking University First Hospital from Jan. 2010 to Nov. 2014. All of the cases were planned to move to ICU right after operation based on the preoperational assessment of anesthetist and physician. The median age was 69.4 years, and 25 cases (68%,25/37) of them were over 70 years old...
November 25, 2016: Zhonghua Fu Chan Ke za Zhi
https://www.readbyqxmd.com/read/27915426/impact-of-a-medication-therapy-management-service-on-the-clinical-status-of-patients-with-chronic-obstructive-pulmonary-disease
#10
Kirla B Detoni, Isabela V Oliveira, Mariana M G Nascimento, Thaís R Caux, Mateus R Alves, Djenane Ramalho-de-Oliveira
Background At this moment, there is no information in the literature showing the impact of comprehensive medication management (CMM) service delivered to patients with chronic obstructive pulmonary disease. Objective This study aims to present the clinical outcomes of this service provided to patients with chronic obstructive pulmonary disease. Settings Public specialty pharmacy where high cost drug treatments are provided for medical conditions not covered by the primary care such as COPD, located in Minas Gerais State, Brazil...
December 3, 2016: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/27915325/possible-role-of-sildenafil-citrate-in-the-recurrence-of-neovascularization-in-laser-regressed-aggressive-posterior-rop
#11
Chaitra Jayadev, Phanibhushan Ramasastry, Alia Gul, Anand Vinekar
BACKGROUND: Systemic diseases and their treatment influence aggressive posterior retinopathy of prematurity. CASE CHARACTERISTICS: A premature infant with aggressive posterior retinopathy of prematurity underwent laser treatment with a favourable outcome. She was started on oral sidenafil citrate for pulmonary hypertension. Ten days later she developed neovascularization within the lasered retina. INTERVENTION/OUTCOME: Considering the possible role of sildenafil in this unusual development, the drug was withdrawn resulting in regression of the neovascularization...
November 7, 2016: Indian Pediatrics
https://www.readbyqxmd.com/read/27913560/cohort-profile-the-diabetes-tuberculosis-treatment-outcome-ditto-study-in-pakistan
#12
Fatima Mukhtar, Zahid A Butt
PURPOSE: Pakistan is faced with an increasing prevalence of diabetes in addition to its existing high burden of tuberculosis (TB). Diabetes has a detrimental effect on treatment outcomes of patients with TB, which may hinder achieving the goals of the End-TB strategy by 2030. We conducted a prospective cohort study to determine difference between treatment outcomes among patients with diabetes and new pulmonary tuberculosis (PTB) and patients without diabetes and new PTB. This would help generate contextual and valid scientific evidence from a developing country like Pakistan with its unique interplay of sociocultural, economic and health system factors to inform policy and practice...
December 2, 2016: BMJ Open
https://www.readbyqxmd.com/read/27913498/long-term-risk-of-second-malignancy-and-cardiovascular-disease-after-hodgkin-lymphoma-treatment
#13
Flora E van Leeuwen, Andrea K Ng
Long-term survivors of Hodgkin lymphoma (HL) experience several late adverse effects of treatment, with second malignant neoplasms (SMNs) and cardiovascular diseases (CVDs) being the leading causes of death in these patients. Other late effects have also been identified, such as pulmonary dysfunction, endocrinopathies (thyroid dysfunction, infertility), neck muscle atrophy, and persistent fatigue. HL survivors have two- to fourfold increased risks to develop SMNs and CVD compared with the general population...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913427/intermittent-hypoxia-during-recovery-from-neonatal-hyperoxic-lung-injury-causes-long-term-impairment-of-alveolar-development-a-new-rat-model-of-bpd
#14
Anastasiya Mankouski, Crystal Kantores, Mathew J Wong, Julijana Ivanovska, Amish Jain, Eric J Benner, Stanley N Mason, A Keith Tanswell, Richard L Auten, Robert P Jankov
Bronchopulmonary dysplasia (BPD) is a chronic lung injury characterized by impaired alveologenesis that may persist into adulthood. Rat models of BPD using varying degrees of hyperoxia to produce injury either cause early mortality or spontaneously recover following removal of the inciting stimulus, thus limiting clinical relevance. We sought to refine an established rat model induced by exposure to 60% O2 from birth by following hyperoxia with intermittent hypoxia (IH). Rats exposed from birth to air or 60% O2 until day 14 were recovered in air with or without IH (FiO2 = 0...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27913300/suppression-of-nadph-oxidase-attenuates-hypoxia-induced-dysfunctions-of-endothelial-progenitor-cells
#15
Bin Liu, Kai-Di Ren, Jing-Jie Peng, Tao Li, Xiu-Ju Luo, Chengming Fan, Jin-Fu Yang, Jun Peng
NADPH oxidases (NOX) - derived reactive oxygen species (ROS) contribute to oxidative injury in hypoxia-induced pulmonary arterial hypertension. This study aims to evaluate the status of NOX in endothelial progenitor cells (EPCs) under hypoxic condition and to determine whether NOX inhibitors could attenuate hypoxia-induced dysfunctions of EPCs. EPCs were isolated from peripheral blood of SD rats and subjected to hypoxia (O2/N2/CO2, 1/94/5) for 24 h. The cells were collected for β-galactosidase or Hoechst staining, or for functional analysis (migration, adhesion and tube formation)...
November 29, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27912147/inhibition-of-endocan-attenuates-monocrotaline-induced-connective-tissue-disease-related-pulmonary-arterial-hypertension
#16
Haiyan Zhao, Yunxin Xue, Yun Guo, Yue Sun, Dongmei Liu, Xiaofei Wang
Connective tissue disease related pulmonary arterial hypertension (CTD-PAH) is characterized by vascular remodeling, endothelial dysfunction and inflammation. Endocan is a novel endothelial dysfunction marker. The aim of the present study was to investigate the role of endocan in CTD-PAH. Monocrotaline (MCT)-induced PAH rats were used as the CTD-PAH model. Short hairpin RNA packed in a lentiviral vector used to inhibit endocan expression was intratracheally instilled in rats prior to the MCT injection. Endocan was found to be increased in the serum and lung of MCT-induced PAH rats...
November 29, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27910060/microrna-delivery-strategies-to-the-lung-in-a-model-of-pulmonary-hypertension
#17
Lin Deng, Andrew H Baker, Angela C Bradshaw
Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation of pulmonary artery smooth muscle cells and endothelial cells associated with obliteration of small pulmonary arterioles and formation of plexiform lesions. To date, no curative treatments have been identified for pulmonary arterial hypertension. There are various therapeutic options, including conventional medical therapies and oral, subcutaneous, intravenous, and inhalation delivery. We have previously shown that miR-143/145 knockout can prevent the development of chronic hypoxia-induced pulmonary hypertension (PH) in mice...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27903664/practical-considerations-for-therapies-targeting-the-prostacyclin-pathway
#18
REVIEW
Harrison W Farber, Wendy Gin-Sing
Therapies that target the prostacyclin pathway play a key role in the treatment of both early- and late-stage pulmonary arterial hypertension, and provide significant clinical benefits for patients. A number of agents have been approved, which are administered via intravenous, subcutaneous, inhaled or oral routes. The use of these therapies is associated with practical challenges, relating to the need for up-titration and their routes of administration. We discuss here a number of measures that can be taken to support patients and healthcare professionals in order to address the complexities of using these therapies and to encourage compliance...
December 2016: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/27903663/beyond-a-single-pathway-combination-therapy-in-pulmonary-arterial-hypertension
#19
REVIEW
Olivier Sitbon, Sean Gaine
There is a strong rationale for combining therapies to simultaneously target three of the key pathways implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Evidence to support this strategy is growing, and a number of studies have demonstrated that combination therapy, administered as either a sequential or an initial regimen, can improve long-term outcomes in PAH. Dual combination therapy with a phosphodiesterase-5 inhibitor and an endothelin receptor antagonist is the most widely utilised combination regimen...
December 2016: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/27903661/risk-assessment-in-pulmonary-arterial-hypertension
#20
REVIEW
Amresh Raina, Marc Humbert
Regular patient assessment is essential for the management of chronic diseases, such as pulmonary arterial hypertension (PAH). Comprehensive patient assessment and risk stratification in PAH are important to guide treatment decisions and to monitor disease progression as well as patients' response to treatment. Approaches for assessing risk in PAH patients include the use of risk variables, as recommended in the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension (PH) guidelines, and the application of risk equations and scores, such as the French registry risk equation and the REVEAL registry risk score...
December 2016: European Respiratory Review: An Official Journal of the European Respiratory Society
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