Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review.

According to current guidelines, pulmonary arterial hypertension (PAH) is diagnosed when mean pulmonary arterial pressure (Ppa) exceeds 25 mmHg at rest or 30 mmHg during exercise. Issues that remain unclear are the classification of Ppa values <25 mmHg and whether Ppa >30 mmHg during exercise is always pathological. We performed a comprehensive literature review and analysed all accessible data obtained by right heart catheter studies from healthy individuals to determine normal Ppa at rest and during exercise.

Stress Doppler echocardiography in relatives of patients with idiopathic and familial pulmonary arterial hypertension: results of a multicenter European analysis of pulmonary artery pressure response to exercise and hypoxia.

Background: This large, prospective, multicentric study was performed to analyze the distribution of tricuspid regurgitation velocity (TRV) values during exercise and hypoxia in relatives of patients with idiopathic and familial pulmonary arterial hypertension (PAH) and in healthy control subjects. We tested the hypothesis that relatives of idiopathic/familial PAH patients display an enhanced frequency of hypertensive TRV response to stress and that this response is associated with mutations in the bone morphogenetic protein receptor II (BMPR2) gene.

Methods And Results: TRV was estimated by Doppler echocardiography during supine bicycle exercise in normoxia and during 120 minutes of normobaric hypoxia (FIO(2)=12%; approximately 4500 m) in 291 relatives of 109 PAH patients and in 191 age-matched control subjects.

Inhaled iloprost for the treatment of pulmonary hypertension.

Prostacyclin and its analogues (prostanoids) are potent vasodilators, and exhibit antithrombotic, antiproliferative and anti-inflammatory properties. Pulmonary arterial hypertension (PAH) is characterised by vasoconstriction, thrombosis and proliferation, and is associated with reduced synthesis of endogenous prostacyclin. This provides a strong rationale for the use of prostanoids to treat PAH, a concept that is now supported by more than two decades of clinical research and experience.

Endothelin-1 inhibits background two-pore domain channel TASK-1 in primary human pulmonary artery smooth muscle cells.

Endothelin (ET)-1 causes long-lasting vasoconstriction and vascular remodeling by interacting with specific G-protein-coupled receptors in pulmonary artery smooth muscle cells (PASMCs), and thus plays an important role in the pathophysiology of pulmonary arterial hypertension. The two-pore domain K(+) channel, TASK-1, controls the resting membrane potential in human PASMCs (hPASMCs), and renders these cells sensitive to a variety of vasoactive factors, as previously shown. ET-1 may exert its vasoconstrictive effects in part by targeting TASK-1.

Nuclear and cytoplasmic death receptor 5 as prognostic factors in patients with non-small cell lung cancer treated with chemotherapy.

Background: Death receptor 4 (DR4) and death receptor 5 (DR5) are tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) receptors that activate apoptosis via the extrinsic apoptosis pathway. DcR1 and DcR2 are decoy receptors for TRAIL that act antagonistically. Intracellular trafficking of TRAIL receptors has been described, but the role of the subcellular localization of TRAIL receptors in non-small cell lung cancer (NSCLC) progression is unclear.

Metered dose inhaler delivery of treprostinil for the treatment of pulmonary hypertension.

Background: The stable prostanoid analogue treprostinil is approved as continuous infusion for treatment of pulmonary arterial hypertension. Unique drug characteristics may render this prostanoid feasible for inhalation therapy with a metered dose inhaler.

Methods And Results: Randomised open label investigation of acute haemodynamic effects, safety and tolerability of inhaled treprostinil delivered in seconds by a metered dose inhaler (MDI-TRE).

The emerging role of magnetic resonance imaging in the diagnosis and management of pulmonary hypertension.

Pulmonary hypertension is a life-threatening chronic disorder of the pulmonary circulation. Elevated pressure and resistance in the pulmonary vessels lead to progressive right heart failure which results in functional limitations and ultimately the death of most patients. Thus, the monitoring of right ventricular (RV) function is of great importance.

[Dana Point: what is new in the diagnosis of pulmonary hypertension?].

The hemodynamic definition of pulmonary hypertension (PH) has not been evidence-based. Normal individuals have a pulmonary pressure of about 14 mm Hg. The respective normal range is up to 20 mm Hg.

Ambrisentan therapy in patients with pulmonary arterial hypertension who discontinued bosentan or sitaxsentan due to liver function test abnormalities.

Background: Some endothelin receptor antagonists (ERAs) are associated with liver function test (LFT) result abnormalities. However, ambrisentan has an incidence of serum aminotransferase levels more than three times the upper limit of normal (ULN), similar to that observed in PAH patients who are not receiving ERAs. Because ambrisentan may provide benefits in PAH patients who have discontinued ERA therapy due to LFT abnormalities, we evaluated the safety and efficacy of ambrisentan in this patient population.

Acute effects of the combination of sildenafil and inhaled treprostinil on haemodynamics and gas exchange in pulmonary hypertension.

Background: Inhaled treprostinil was recently developed for the treatment of pulmonary arterial hypertension (PAH). We investigated the safety and acute haemodynamic effects of the combination oral sildenafil and inhaled treprostinil in an open label study in patients with precapillary pulmonary hypertension.

Methods And Patients: Inhaled nitric oxide (20ppm; n=50), sildenafil (50mg; n=50) and inhaled treprostinil (15microg; n=25 or 30microg; n=25) were applied in subsequent order during right heart catheter investigation to consecutive patients with pulmonary arterial hypertension (PAH; n=28), non-operable chronic thromboembolic pulmonary hypertension (CTEPH; n=17) and pulmonary fibrosis associated pulmonary hypertension (n=5).

Magnetic resonance-derived 3-dimensional blood flow patterns in the main pulmonary artery as a marker of pulmonary hypertension and a measure of elevated mean pulmonary arterial pressure.

Background: Pulmonary hypertension is a disease characterized by an elevation in pulmonary arterial pressure that is diagnosed invasively via right heart catheterization. Such pathological altered pressures in the pulmonary vascular system should lead to changes in blood flow patterns in the main pulmonary artery.

Methods And Results: Forty-eight subjects (22 with manifest pulmonary hypertension, 13 with latent pulmonary hypertension, and 13 normal control subjects) underwent time-resolved 3D magnetic resonance phase-contrast imaging of the main pulmonary artery.

Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2.

Background: Ambrisentan is a propanoic acid-based, A-selective endothelin receptor antagonist for the once-daily treatment of pulmonary arterial hypertension.

Methods And Results: Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Study 1 and 2 (ARIES-1 and ARIES-2) were concurrent, double-blind, placebo-controlled studies that randomized 202 and 192 patients with pulmonary arterial hypertension, respectively, to placebo or ambrisentan (ARIES-1, 5 or 10 mg; ARIES-2, 2.5 or 5 mg) orally once daily for 12 weeks.

Oral and intestinal Candida colonization in patients undergoing hematopoietic stem-cell transplantation.

We investigated (1) the prevalence and quantity of, as well as risk factors for, orointestinal Candida colonization in patients undergoing hematopoietic stem-cell transplantation (HSCT) and (2) the genetic relatedness of colonizing C. albicans strains. Mouth-wash and stool samples were collected from 77 patients before they underwent HSCT and on days 1, 8, and 15 and were quantitatively cultured.

Prostacyclin therapies for the treatment of pulmonary arterial hypertension.

Prostacyclin and its analogues (prostanoids) are potent vasodilators and possess antithrombotic, antiproliferative and anti-inflammatory properties. Pulmonary hypertension (PH) is associated with vasoconstriction, thrombosis and proliferation, and the lack of endogenous prostacyclin may considerably contribute to this condition. This supports a strong rationale for prostanoid use as therapy for this disease.

Pulmonary histoplasmosis in three Austrian travelers after a journey to Mexico.

Three Austrian travelers (a 37-year-old woman, a 47-year-old woman and a 47-year-old man) presented with fever, dyspnea, thoracodynia, cephalea, arthralgia and fatigue 4 weeks after visiting a bat cave in Mexico. Computed tomography of the lungs showed bilateral nodular infiltrates in all three patients and enlarged mediastinal lymph nodes in two patients. In all patients, specific IgM antibodies against Histoplasma capsulatum could be detected.

Effect of sildenafil on hypoxia-induced changes in pulmonary circulation and right ventricular function.

Hypoxia leads to pulmonary vasoconstriction in healthy men. However, the consequences on right ventricular function are not known. The effects of hypoxia on systolic pulmonary artery pressure (sPAP) and right ventricular function index (TEI) were assessed by Doppler echocardiography.

Long-term treatment with sildenafil in chronic thromboembolic pulmonary hypertension.

For chronic thromboembolic pulmonary hypertension not amenable to pulmonary endarterectomy, effective medical therapy is desired. In an open-label uncontrolled clinical trial, 104 patients (mean +/- sem age 62 +/- 11 yrs) with inoperable chronic thromboembolic pulmonary hypertension were treated with 50 mg sildenafil t.i.

Delayed processing of blood samples influences time to positivity of blood cultures and results of Gram stain-acridine orange leukocyte Cytospin test.

We investigated in vitro whether storage of blood samples influences the time to positivity used for the calculation of the differential time to positivity (DTP) and the results of the Gram stain-acridine orange leukocyte Cytospin (AOLC) test. A 24-hour storage of blood samples at room temperature may lead to false-negative DTP and false-positive Gram stain-AOLC test results, whereas storage at 4 degrees C does not.

Treprostinil potentiates the positive inotropic effect of catecholamines in adult rat ventricular cardiomyocytes.

Background And Purpose: Prostanoids have been shown to improve exercise tolerance, hemodynamics and quality of life in patients with pulmonary arterial hypertension (PAH). We investigated whether treprostinil exerts direct contractile effects on cardiomyocytes that may explain partly the beneficial effects of these drugs.

Experimental Approach: Ventricular cardiomyocytes from adult rats were paced at a constant frequency of 0.

Aspergillus oryzae peritonitis in CAPD: case report and review of the literature.

Fungal peritonitis is a rare, but serious, complication of continuous ambulatory peritoneal dialysis (CAPD). We report a case of peritonitis caused by Aspergillus oryzae in a man on CAPD therapy who was treated successfully with amphotericin B and caspofungin, followed by itraconazole and removal of the peritoneal catheter. A oryzae was identified by using sequence analysis of the ribosomal DNA genes.

Effect of inhaled iloprost during off-medication time in patients with pulmonary arterial hypertension.

Background: Iloprost is a stable prostacyclin analogue that is associated with a longer duration of vasodilatation and has been approved for inhalative use with 6 or 9 inhalations during the daytime and a night pause. It is not known if during the night pause rebound pulmonary hypertension occurs. The aim of this study was to assess the hemodynamics in iloprost-treated patients during the daytime and at night.

[Current recommendations for the diagnosis and treatment of pulmonary hypertension].

Spiroergometry and Doppler stress echocardiography are recommended in cases of suspected but unproven pulmonary hypertension (PHT). Treatment of the underlying disease is indicated when there is pulmonary hypertension associated with disease of the left heart or the lungs. Surgery is indicated if there if the PHT is caused by chronic thromboembolism.