Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
Novel therapy for idiopathic pulmonary arterial hypertension: Can hepatocyte growth factor be beneficial?
Ying-Hua Guo,Long-Xiang Su,Na Guo,Chang-Ting Liu
老年心脏病学杂志(英文版) , 2012,
Long term combination treatment for severe idiopathic pulmonary arterial hypertension  [cached]
Flora Affuso,Plinio Cirillo,Antonio Ruvolo,Guido Carlomagno
World Journal of Cardiology , 2010,
Abstract: We report the long-term follow-up of 3 cases of severe idiopathic pulmonary arterial hypertension, in whom tadalafil plus sitaxentan combination therapy improved the clinical condition and exercise performance without any relevant adverse event.
Upregulated Genes In Sporadic, Idiopathic Pulmonary Arterial Hypertension
Alasdair J Edgar, Matilde R Chacón, Anne E Bishop, Magdi H Yacoub, Julia M Polak
Respiratory Research , 2006, DOI: 10.1186/1465-9921-7-1
Abstract: Peripheral lung samples were obtained immediately after removal from patients undergoing lung transplant for IPAH without familial disease, and control tissues consisted of similarly sampled pieces of donor lungs not utilised during transplantation. Pools of lung mRNA from IPAH cases containing plexiform lesions and normal donor lungs were used to generate the tester and driver cDNA libraries, respectively. A subtracted IPAH cDNA library was made by SSH. Clones isolated from this subtracted library were examined for up regulated expression in IPAH using dot blot arrays of positive colony PCR products using both pooled cDNA libraries as probes. Clones verified as being upregulated were sequenced. For two genes the increase in expression was verified by northern blotting and data analysed using Student's unpaired two-tailed t-test.We present preliminary findings concerning candidate genes upregulated in IPAH. Twenty-seven upregulated genes were identified out of 192 clones examined. Upregulation in individual cases of IPAH was shown by northern blot for tissue inhibitor of metalloproteinase-3 and decorin (P < 0.01) compared with the housekeeping gene glyceraldehydes-3-phosphate dehydrogenase.Four of the up regulated genes, magic roundabout, hevin, thrombomodulin and sucrose non-fermenting protein-related kinase-1 are expressed specifically by endothelial cells and one, muscleblind-1, by muscle cells, suggesting that they may be associated with plexiform lesions and hypertrophic arterial wall remodelling, respectively.In pulmonary hypertension (PAH), the mean resting pulmonary arterial pressure is greater than 25 mm Hg in contrast to the normal adult pulmonary circulation which has little resting vascular tone. The disease is also characterised by an absence of a significant pulmonary vasodilator response [1]. Many precapillary pulmonary arteries are affected by plexiform lesions, medial hypertrophy, intimal fibrosis and microthrombosis. PAH is a rare, often fatal cond
The importance of echocardiography in diagnostics of idiopathic pulmonary arterial hypertension: A case report
Stojkovi? Gabrijela,Mladenov Sun?ica,Jovanovi? Dimitrije,Stankovi? Aleksandar
Srpski Arhiv za Celokupno Lekarstvo , 2011, DOI: 10.2298/sarh1106376s
Abstract: Introduction. Idiopathic pulmonary arterial hypertension (IPAH) is rare and difficult progressive disease with prevalence of approximately 15 cases per million residents, with predominant female cases. Case Outline. A 47-year-old female presented with symptoms and signs of the right heart chambers failure. Over prior seven years the patient had the feeling of suffocation and fatigue when walking, and received treatment for bronchial asthma. Physical examination revealed a marked loud second heart sound over the pulmonary artery. Electrocardiogram: right ventricular hypertrophy. Spirometric (pulmonary capacity) test, cardiac perfusion scan and spiral CT scanning excluded secondary pulmonary arterial hypertension. Blood testing for connective tissue diseases and HIV were within normal reference limits. Transthoracic colour Doppler echocardiography demonstrated a mild tricuspid regurgitation with high values of estimated maximal and middle systolic pressure of the right ventricle (135/110 mm Hg), and excluded previous heart disease. Cardiac catheterization confirmed IPAH diagnosis, with systolic right ventricular pressure of 101/47/66 mm Hg and pulmonary capillary pressure of 30/13/10 mm Hg. Basic therapy with sildenafil, nevertheless, considerable limitations of strain tolerance was still present. Conclusion. IPAH is a severe heart disease with non-specific signs and symptoms. Screening for IPAH is transthoracic colour Doppler echocardiography shows high correlation with cardiac catheterization.
Pulmonary veno-occlusive disease misdiagnosed as idiopathic pulmonary arterial hypertension
M. Palazzini,A. Manes
European Respiratory Review , 2009,
Abstract: A 27-yr-old female with a 6-month diagnosis of idiopathic pulmonary arterial hypertension (PAH) confirmed elsewhere was referred to our centre with worsening dyspnoea. On examination, the patient had low systemic oxygen saturation despite high oxygen flow and reduced exercise capacity. Haemodynamics were indicative of severe pre-capillary PAH. High-resolution computed tomography revealed diffuse ground-glass opacity with thickening interlobular septa, and haemosiderin-laden macrophages were identified by bronchoalveolar lavage. Based on clinical and diagnostic findings, the patient was re-diagnosed with pulmonary veno-occlusive disease (PVOD). Treatment with high-dose diuretics and the endothelin-receptor antagonist bosentan improved the patient's exercise capacity, haemodynamics and quality of life. However, 1 yr later there was a progressive, slow deterioration in the patient's functional capacity and oxygen saturation, and inhaled prostanoid and oxygen therapy were initiated. Despite some subjective improvements, the patient's haemodynamics and oxygen saturation continued to decline and she underwent lung transplantation. This case emphasises that PVOD is an under-recognised and often misdiagnosed form of pulmonary hypertension. Therefore, accurate diagnosis of PVOD requires comprehensive clinical and diagnostic work-up. While lung transplantation remains the treatment of choice for patients with PVOD, targeted therapies for PAH in addition to high doses of diuretics merit evaluation.
Risk Factors for Hemoptysis in Idiopathic and Hereditary Pulmonary Arterial Hypertension  [PDF]
Darryl Tio, Edward Leter, Bart Boerrigter, Anco Boonstra, Anton Vonk-Noordegraaf, Harm Jan Bogaard
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0078132
Abstract: Introduction When hemoptysis complicates pulmonary arterial hypertension (PAH), it is assumed to result from bronchial artery hypertrophy. In heritable PAH, the most common mutation is in the BMPR2 gene, which regulates growth, differentiation and apoptosis of mesenchymal cells. The aim of this study is to determine the relationship in PAH between the occurrence of hemoptysis, and disease progression, bronchial artery hypertrophy, pulmonary artery dilation and BMPR2 mutations. Methods 129 IPAH patients underwent baseline pulmonary imaging (CT angio or MRI) and repeated right-sided heart catheterization. Gene mutations were assessed in a subset of patients. Results Hemoptysis was associated with a greater presence of hypertrophic bronchial arteries and more rapid hemodynamic deterioration. The presence of a BMPR2 mutation did not predispose to the development of hemoptysis, but was associated with a greater number of hypertrophic bronchial arteries and a worse baseline hemodynamic profile. Conclusion Hemoptysis in PAH is associated with bronchial artery hypertrophy and faster disease progression. Although the presence of a BMPR2 mutation did not correlate with a greater incidence of hemoptysis in our patient cohort, its association with worse hemodynamics and a trend of greater bronchial arterial hypertrophy may increase the risk of hemoptysis.
Nuclear Factor κ-B Is Activated in the Pulmonary Vessels of Patients with End-Stage Idiopathic Pulmonary Arterial Hypertension  [PDF]
Laura C. Price, Gaetano Caramori, Frederic Perros, Chao Meng, Natalia Gambaryan, Peter Dorfmuller, David Montani, Paolo Casolari, Jie Zhu, Konstantinos Dimopoulos, Dongmin Shao, Barbara Girerd, Sharon Mumby, Alastair Proudfoot, Mark Griffiths, Alberto Papi, Marc Humbert, Ian M. Adcock, S. John Wort
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075415
Abstract: Objectives To assess activation of the inflammatory transcription factor NF-kappa B (NF-κB) in human idiopathic pulmonary arterial hypertension (PAH). Background Idiopathic PAH is a severe progressive disease characterized by pulmonary vascular remodeling and excessive proliferation of vascular cells. Increasing evidence indicates that inflammation is important in disease pathophysiology. Methods NF-κB-p65 and CD68, CD20 and CD45 were measured by immunohistochemistry and confocal microscopy on lung specimens from patients with idiopathic PAH (n = 12) and controls undergoing lung surgery (n = 14). Clinical data were recorded for all patients including invasive pulmonary hemodynamics for the PAH patients. Immunohistochemical images were analyzed by blinded observers to include standard pulmonary vascular morphometry; absolute macrophage counts/mm2 and p65-positivity (p65+) using composite images and image-analysis software; and cytoplasmic:nuclear p65+ of individual pulmonary arterial endothelial and smooth muscle cells (PASMC) in 10–20 pulmonary arteries or arterioles per subject. The expression of ET-1 and CCL5 (RANTES) in whole lung was determined by RT-qPCR. Results Macrophage numbers were increased in idiopathic PAH versus controls (49.0±4.5 vs. 7.95±1.9 macrophages/100 mm2, p<0.0001): these macrophages demonstrated more nuclear p65+ than in macrophages from controls (16.9±2.49 vs. 3.5±1.25%, p<0.001). An increase in p65+ was also seen in perivascular lymphocytes in patients with PAH. Furthermore, NF-κB activation was increased in pulmonary arterial endothelial cells (62.3±2.9 vs. 14.4±3.8, p<0.0001) and PASMC (22.6±2.3 vs. 11.2±2.0, p<0.001) in patients with PAH versus controls, with similar findings in arterioles. Gene expression of both ET-1 mRNA ((0.213±0.069 vs. 1.06±0.23, p<0.01) and CCL5 (RANTES) (0.16±0.045 vs. 0.26±0.039, p<0.05) was increased in whole lung homogenates from patients with PAH. Conclusions NF-κB is activated in pulmonary macrophages, lymphocytes, endothelial and PASMC in patients with end-stage idiopathic PAH. Future research should determine whether NF-κB activation is a driver or bystander of pulmonary vascular inflammation and if the former, its potential role as a therapeutic target.
t-plasminogen activator inhibitor-1 polymorphism in idiopathic pulmonary arterial hypertension  [cached]
Katta Sujana,Vadapalli Shivani,Sastry BKS,Nallari Pratibha
Indian Journal of Human Genetics , 2008,
Abstract: Aim: The aim of the present study was to identify the possible genotypic association of 3′UTR Hind III polymorphism of Plasminogen activator Inhibitor-1 (PAI-1) gene with idiopathic pulmonary arterial hypertension (IPAH). Background: IPAH is a disorder with abnormally raised mean pulmonary arterial pressure and increase in the resistance to blood flow in pulmonary artery. One of the pathological features seen is development of intraluminal thrombin deposition leading to thrombosis. Plasminogen activator inhibitor-1 is an important inhibitor of the fibrinolytic system; its up-regulation may suppress fibrinolysis and result in an increased risk of thrombosis. Method: Blood samples from 54 IPAH patients and 100 healthy voluntary donors were analyzed by PCR-RFLP method for 3′UTR Hind III polymorphism. Results and Disscussion: A significant association of Hd2 allele with the disease was observed. Raised mean level of right ventricular systolic pressure was observed in the Hd2/Hd2 genotypic patients, strengthening the role of Hd2 allele in the disease progression. Our data suggests an association of Hd2/Hd2 genotype, which may lead to the up-regulation of PAI-1 gene leading to increased levels of PAI-1, which is seen in IPAH. PAI-1 competes with plasminogen activators and hinders the normal mechanism of plasminogen activation system and leads to thrombosis and formation of plexiform lesions in the lung tissue, further strengthening its role in tissue remodeling and disease progression.
Increased CD39 Nucleotidase Activity on Microparticles from Patients with Idiopathic Pulmonary Arterial Hypertension  [PDF]
Scott H. Visovatti, Matthew C. Hyman, Diane Bouis, Richard Neubig, Vallerie V. McLaughlin, David J. Pinsky
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0040829
Abstract: Background Idiopathic pulmonary arterial hypertension (IPAH) is a devastating disease characterized by increased pulmonary vascular resistance, smooth muscle and endothelial cell proliferation, perivascular inflammatory infiltrates, and in situ thrombosis. Circulating intravascular ATP, ADP, AMP and adenosine activate purinergic cell signaling pathways and appear to induce many of the same pathologic processes that underlie IPAH. Extracellular dephosphorylation of ATP to ADP and AMP occurs primarily via CD39 (ENTPD1), an ectonucleotidase found on the surface of leukocytes, platelets, and endothelial cells [1]. Microparticles are micron-sized phospholipid vesicles formed from the membranes of platelets and endothelial cells. Objectives: Studies here examine whether CD39 is an important microparticle surface nucleotidase, and whether patients with IPAH have altered microparticle-bound CD39 activity that may contribute to the pathophysiology of the disease. Methodology/ Principal Findings Kinetic parameters, inhibitor blocking experiments, and immunogold labeling with electron microscopy support the role of CD39 as a major nucleotidase on the surface of microparticles. Comparison of microparticle surface CD39 expression and nucleotidase activity in 10 patients with advanced IPAH and 10 healthy controls using flow cytometry and thin layer chromatograph demonstrate the following: 1) circulating platelet (CD39+CD31+CD42b+) and endothelial (CD39+CD31+CD42b?) microparticle subpopulations in patients with IPAH show increased CD39 expression; 2) microparticle ATPase and ADPase activity in patients with IPAH is increased. Conclusions/ Significance We demonstrate for the first time increased CD39 expression and function on circulating microparticles in patients with IPAH. Further research is needed to elucidate whether these findings identify an important trigger for the development of the disease, or reflect a physiologic response to IPAH.
Long-term effects of intravenous iloprost in patients with idiopathic pulmonary arterial hypertension deteriorating on non-parenteral therapy
Lars Knudsen, Alexander Schurawlew, Nils Nickel, Henning Tiede, Hossein A Ghofrani, Heinrike Wilkens, Ralf Ewert, Michael Halank, Hans Klose, Carlos B?zner, Jürgen Behr, Marius M Hoeper
BMC Pulmonary Medicine , 2011, DOI: 10.1186/1471-2466-11-56
Abstract: In this retrospective, multicentre study we collected data from consecutive IPAH patients receiving intravenous iloprost in addition to optimized non-parenteral therapy between Jan 2002 and Dec 2009. Analyses included 6 min walk distance (6MWD), functional class, need for transplantation, and survival.During the observation period, 50 patients were treated with intravenous iloprost in addition to non-parenteral therapy; 44% of the patients were on dual combination therapy and 52% on triple combination. Three months after initiation of iloprost, functional class had improved in 24% of the patients and the median 6MWD had increased from 289 m to 298 m (n.s.). During the observation period, 22 patients (44%) died and 14 (28%) underwent lung transplantation. The probabilities of LuTx-free survival at 1, 3 and 5 years following iloprost initiation were 38%, 17% and 17%, respectively. A 6MWD < 300 m and persistent functional class IV at 3 months after initiation of intravenous iloprost were predictors of an adverse outcome.In essence, late initiation of intravenous iloprost in IPAH patients who previously failed to respond to non-parenteral therapies appears to be of limited efficacy in the majority patients. Alternative therapeutic options are currently not available, underlying the need for the development of new drugs.Less than 10 years ago, intravenous epoprostenol was the standard treatment for patients with idiopathic pulmonary arterial hypertension (IPAH). The first intravenous prostanoid studied in patients with IPAH, epoprostenol is still the only drug for which improved survival in treatment-naive patients with advanced IPAH has been demonstrated [1]. Newer prostanoids used for intravenous therapy are treprostinil and iloprost [2-5]. It is unclear whether the efficacy of both drugs is comparable to epoprostenol as this has not yet been formally evaluated in randomized placebo controlled or head-to-head comparison trials. The need for parenteral administration, h
Page 1 /100
Display every page Item

Copyright © 2008-2017 Open Access Library. All rights reserved.