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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary arterial hypertension is characterised by the presence of pulmonary hypertension (mean pulmonary artery pressure >25 mmHg at rest or >30 mmHg during exercise ) and normal pulmonary wedge pressure (<12 mmHg). Several risk factors for pulmonary arterial hypertension have been described. In the absence of any factor or condition suspected to play a causal or facilitating role in the process, pulmonary hypertension is "unexplained" (primary pulmonary hypertension, PPH). PPH is a rare condition, with an estimated incidence of 2 per million people. Recent genetic studies have identified mutations in the bone morphogenetic protein receptor-II (BMPR-II) gene, a receptor member of the transforming growth factor-beta family, in a majority of familial cases of PPH. Interestingly, 25% of patients displaying sporadic PPH may also have mutations in the BMPR-II gene, emphasising the relevance of genetic susceptibility for this severe condition. Other molecular and biochemical processes behind the complex vascular changes associated with pulmonary arterial hypertension are currently investigated. Type 1a glycogen storage disease caused by a deficiency of glucose-6-phosphatase has an estimated incidence of 1 per 100000 with a few reported cases of unexplained severe pulmonary hypertension. The occurrence of pulmonary arterial hypertension in type 1a glycogen storage disease could be due to vasoconstrictive amines such as serotonin, a pulmonary vasoconstrictor and growth factor for vascular smooth muscle cells stored in platelets.
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PMID:Severe pulmonary arterial hypertension in type 1 glycogen storage disease. 1237 80

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of primary pulmonary hypertension characterized by thin-walled microvessels infiltrating the peribronchial and perivascular interstitium, the lung parenchyma, and the pleura. These proliferating microvessels are prone to bleeding, resulting in accumulation of hemosiderin-laden macrophages in alveolar spaces. Here we report 2 cases of PCH with pulmonary hypertension, 1 of them associated with mechanical intravascular hemolysis, a feature previously reported in other hemangiomatous diseases, but not in PCH. Case 2 was diagnosed by pulmonary biopsy; to our knowledge the patient is the second adult to be treated with interferon alpha-2a. Review of the literature identified 35 patients with PCH and pulmonary hypertension. The prognosis is poor and median survival was 3 years from the first clinical manifestation. Dyspnea and right heart failure are the most common findings of the disease. Hemoptysis, pleural effusion, acropachy, and signs of pulmonary capillary hypertension are less common. Chest X-ray or computed tomography scan usually shows evidence of interstitial infiltrates, pulmonary nodules, or pleural effusion. Hemodynamic features include normal wedge pressures. Radiologic and hemodynamic findings are undifferentiated from those of pulmonary veno-occlusive disease but differ from other causes of primary pulmonary hypertension. Epoprostenol therapy, considered the treatment of choice in patients with primary pulmonary hypertension, may produce pulmonary edema and is contraindicated in patients with PCH. Regression of lesions was reported in 1 patient treated with interferon therapy and 2 other patients stabilized, including our second patient. PCH was treated successfully by lung transplantation in 5 cases. Early recognition of PCH in patients with suspected primary pulmonary hypertension is possible based on clinical and radiologic characteristics. Diagnosis by pulmonary biopsy is essential for allowing appropriate treatment.
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PMID:Pulmonary capillary hemangiomatosis associated with primary pulmonary hypertension: report of 2 new cases and review of 35 cases from the literature. 1244 98

Epoprostenol has markedly improved the treatment of pulmonary arterial hypertension, although predictors of outcome with epoprostenol are not well characterized. From June 1995 through August 2001, 91 patients with pulmonary arterial hypertension were treated with epoprostenol at our institution. We analyzed the effects of long-term epoprostenol treatment to determine features associated with outcome. Predictors of worse outcome included older age of disease onset (hazard ratio 3.2, 95% confidence interval 1.32-7.76 for patients above the median age of 44 years), World Health Organization functional Class IV, either at baseline or follow-up, (3.07, 1.42-6.62 compared with functional Class I, II, and III), and scleroderma spectrum of disease (2.32, 1.08-4.99). There were no baseline or follow-up hemodynamic factors predictive of outcome. Our results indicate that treatment with epoprostenol improves survival in patients with Primary Pulmonary Hypertension compared with that predicted by the National Institutes of Health Primary Pulmonary Hypertension Registry's survival equation and that their survival is significantly better than that of patients with scleroderma spectrum of disease (p = 0.001). Older patients treated with epoprostenol have significantly shorter survival, regardless of etiology.
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PMID:Outcome in 91 consecutive patients with pulmonary arterial hypertension receiving epoprostenol. 1244 66

For physicians to admit that a group of patients remains for whom no cure is available in modern medicine is intellectually unsatisfying. Pulmonary arterial hypertension is a rare condition. Because the symptoms are nonspecific and the physical finding can be subtle, the disease is often diagnosed in its later stages. The natural history of pulmonary arterial hypertension is usually progressive and fatal. At the 1998 Primary Pulmonary Hypertension World Symposium, clinical scientists from around the world gathered to review and discuss the future of pulmonary arterial hypertension. Bringing together experts from a variety of disciplines provided the opportunity for a better understanding of the pathology, pathobiology, risk factors, genetics, diagnosis and treatment for pulmonary arterial hypertension. Remarkable progress has been made in the field of pulmonary arterial hypertension over the past several decades. The pathology is now better defined and significant advances have occurred in understanding the pathobiological mechanisms. Risk factors have been identified and the genetics have been characterised. Advances in technology allow earlier diagnosis as well as better assessment of disease severity. Therapeutic modalities such as new drugs, e.g. epoprostenol, treprostinil and bosentan, and surgical interventions, e.g. transplantation and blade septostomy, which were unavailable several decades ago, have had a significant impact on prognosis and outcome. Thus, despite the inability to really cure pulmonary arterial hypertension, therapeutic advances over the past two decades have resulted in significant improvements in the outcome for children with various forms of pulmonary arterial hypertension. This review of pulmonary arterial hypertension will highlight the key features of pulmonary hypertension in infants and children and the current understanding of pulmonary arterial hypertension with specific recommendations for current practice and future directions.
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PMID:Pulmonary arterial hypertension in children. 1257 Jan 25

Pulmonary hypertension (PH) occurs frequently in parenchymal lung disease and is usually correlated with increased mortality. Thus, the treatment of PH in patients with lung disease has been an active area of interest. Secondary pulmonary hypertension (SPH), whether from parenchymal lung disease or other etiologies, is more common than primary pulmonary hypertension (PPH). In 2002, two new medications, oral bosentan and subcutaneous treprostinil, were released for the treatment of pulmonary arterial hypertension (PAH). These new agents are not restricted to use in PPH, as they are approved for use in PAH in general. It is reasonable to consider the use of these medications in select patients with SPH caused by parenchymal lung disease, although these groups have not yet been studied in clinical trials. The initial hemodynamic evaluation of SPH patients, the potential use of these new medications in the context of standard care, and the assessment of response to therapy are discussed in this update. A relevant case report is used to illustrate use of these new agents in SPH, and ongoing clinical trials are reviewed. The available treatment options for patients with SPH are rapidly improving.
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PMID:Advances in the treatment of secondary pulmonary hypertension. 1257 94

Endothelins are powerful vasoconstrictor agents produced by endothelial cells and identified by Yanagisawa et al. in 1988. Two types of receptors for endothelins have been identified: ET(A) receptors are located on smooth muscle cells of the vascular wall and are responsible for endothelin-induced vasoconstriction while ET(B) receptors are located on endothelial cells and induce these cells to release NO and prostacyclin. Moreover, these peptides not only cause a potent and prolonged vasoconstriction but are also known to enhance cell proliferation and to stimulate extracellular matrix accumulation. High levels of plasma or tissue endothelins have been found in patients with heart failure, diabetes, stroke, primary pulmonary hypertension, liver cirrhosis and other diseases. Given these effects of endothelins, blocking their receptors might be a new way to reduce blood pressure and to treat other illnesses. Accordingly, many endothelin antagonists have been developed and evaluated in animals and humans. Enrasentan is a mixed ET(A) and ET(B) receptor antagonist with a higher affinity for ET(A) receptors, although it cannot be considered a selective antagonist. In an animal model of hypertension and cardiac hypertrophy the drug has reduced blood pressure, prevented cardiac hypertrophy and preserved myocardial function. In rats with hyperinsulinemia and hypertension enrasentan normalized blood pressure and prevented cardiac and renal damage. In rats with stroke the drug reduced the ischemic area in the brain. Enrasentan has been added to conventional treatment in patients with heart failure (NYHA Class 2-3) and no addictive effect of the drug has been observed. This is in contrast with results obtained in animal models and still has not been explained. In conclusion, many possible clinical applications can be suggested for this drug, but further studies are necessary to better evaluate its therapeutic efficacy.
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PMID:Enrasentan, an antagonist of endothelin receptors. 1259 14

We report a large monocentric case series of 82 patients with human immunodeficiency virus-associated pulmonary arterial hypertension (PAH). No germline mutations of the PPH1 gene (bone morphogenetic protein receptor-II) were found in any of the 19 patients tested. PAH was the direct cause of death in 72% of cases. Survival rates of the overall population at 1, 2, and 3 years were 73, 60, and 47%, respectively. Survival was significantly poorer in patients in New York Heart Association functional class III-IV at the time of diagnosis, as compared with those in functional class I-II with respective rates of 60, 45, and 28% versus 100, 90, 84% at 1, 2, and 3 years (p < 0.0001). Subsequently, we analyzed prognostic factors in patients in functional class III-IV. Univariate analysis indicated that CD4 lymphocyte count of more than 212 cells mm(-3), the use of combination antiretroviral therapy (CART), and epoprostenol infusion were related with a better survival. On multivariate analysis only CD4 lymphocyte count was an independent predictor of survival, presumably because CART and epoprostenol infusion were strongly linked in our patient population. These results suggest that patients with severe human immunodeficiency virus-associated PAH should be considered for long-term epoprostenol infusion in association with CART.
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PMID:Prognostic factors for survival in human immunodeficiency virus-associated pulmonary arterial hypertension. 1261 32

Liver disease affects the lungs. The majority of patients exhibit mild to moderate arterial hypoxaemia essentially attributable to an alteration in ventilation/perfusion matching and limited by an increase in ventilation. A minority (some 10%) of patients exhibit a "hepatopulmonary syndrome" defined by severe hypoxaemia with arterial PO2 below 60 mm Hg, dyspnoea, cyanosis, digital clubbing, orthodeoxia, platypnoea and demonstrable pulmonary vascular dilatations causing a true pulmonary shunt and a diffusion/perfusion imbalance. The hepatopulmonary syndrome is incurable but resolves over time after liver transplantation. An even lower proportion of patients, approximately 1%, develop pulmonary hypertension. Clinically this "portopulmonary hypertension" resembles primary pulmonary hypertension, with dyspnoea and fatigue as the main symptoms, histopathology and response to prostacyclin therapy. Portopulmonary hypertension is irreversible. Liver transplantation mortality in patients with portopulmonary hypertension ranges from 50 to 100%. The common cause of the hepatopulmonary syndrome and portopulmonary hypertension is portal hypertension and portosystemic shunting, indicating that vasoactive and angiogenetic factors originating from the liver normally control the pulmonary circulation.
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PMID:Hepatopulmonary syndrome and portopulmonary hypertension. 1271 85

Pulmonary Arterial Hypertension (PAH) is a term which has been recently defined at the WHO-meeting in Evian and includes Primary Pulmonary Hypertension (PPH), as well as PAH related to specific pathological conditions. The poor prognosis of the disease seems to be related to a peculiar pathological anatomy, consisting of characteristic lesions of small, muscular pulmonary arteries. In addition to common hypertrophy of the tunica media, other proliferative lesions such as intimal thickening or plexiform lesions are summarized under the term of plexogenic arteriopathy. Moreover, in situ thrombosis and rarely isolated pulmonary arteritis can be observed in lungs of patients displaying PAH. Different pathomechanisms explaining these morphological changes of pulmonary vasculature have been discussed in the past, including endothelial and thrombocytic dysfunction, deregulated vasoconstriction, coagulation abnormalities, or cancer-like growth. Furthermore, latest studies on the importance of inflammatory mediators, so-called chemokines, in the lungs of PAH patients have brought a possible inflammatory component of the disease into consideration. Finally, recent identification of responsible gene mutations in subgroups of patients, as well as latest developments in genetic screening have shed some light into the modus of inheritance. Nevertheless, the role and impact of these different pathomechanisms have yet to be better defined.
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PMID:Pathology and aspects of pathogenesis in pulmonary arterial hypertension. 1273 75

In recent years, the better understanding of the pathobiology and pathogenesis of pulmonary arterial hypertension (PAH) has led to the development of new drugs for its treatment. Epoprostenol, which was the first drug approved for PAH, has shown an improvement in the survival at 3 years in patients with primary pulmonary hypertension. Recently, the Food and Drug Administration has approved two new compounds, Bosentan (an oral, non-selective endothelin receptor blocker) and Treprostinil (a subcutaneous prostacyclin analog). At least three multicenter, international studies are currently in progress. These studies include the use of a diet supplement rich in arginine (nitric oxide precursor), the evaluation of an endothelin A-receptor blocker (Sitaxsentan), and the evaluation of Sildenafil (a 5-phosphodiesterase inhibitor). As long as research continues to scrutinize the pathogenesis of this disease, clues to possible new therapies are warranted.
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PMID:[What is new in the treatment of pulmonary artery hypertension?]. 1296 61


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