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Biomedical subjects

G Simonneau

Publications and source records attributed to G Simonneau.

At least 73 records · Page 4Linked to original sources
PubMed2000

Thrombotic risk factors in pulmonary hypertension.

Thrombotic lesions are consistently observed in chronic thromboembolic pulmonary hypertension (CTEPH) and frequently found in primary pulmonary hypertension (PPH). It remains unknown, however, whether thrombosis is related to defects of the antithrombotic pathway or to previous vascular injury. This study therefore analysed the frequency of both hereditary and acquired thrombotic risk factors in CTEPH and PPH. One hundred and forty-seven consecutive patients with CTEPH investigated in the author's institution were compared to 99 consecutive patients with PPH. In 116 CTEPH patients and 83 PPH patients, phospholipid-dependent antibodies (antiphospholipid antibodies and lupus anticoagulant) were analysed by both immunological and clotting assays. In patients enrolled since 1994 (46 CTEPH and 64 PPH), hereditary thrombotic risk factors were also determined. Antithrombin, protein C and protein S activities were measured by functional assays. Mutations of factor V and factor II were identified by polymerase chain reaction. The prevalence of hereditary thrombotic risk factors was not increased in patients with either PPH or CTEPH. In contrast, a high frequency of phospholipid-dependent antibodies was observed in PPH (10%) and more notably in CTEPH (20%). Moreover, in PPH, antibodies were present only in low titre whereas in CTEPH, half of the patients with antiphospholipid antibodies had high titres. In addition, in CTEPH all but one of the patients with lupus anticoagulant also had antiphospholipid antibodies. The most striking finding of this study was the high prevalence of phospholipid-dependent antibodies but their clinical relevance appears to be different in primary pulmonary hypertension and chronic thromboembolic pulmonary hypertension. In primary pulmonary hypertension, these antibodies in low titre probably reflect endothelial dysfunction. In contrast, in chronic thromboembolic pulmonary hypertension the presence of antibodies in high titre associated with lupus anticoagulant, underlines the role of thrombosis in the pathogenesis of this condition.

Antibodies, Antiphospholipid↗
PubMed2000

Inhaled corticosteroids and Churg-Strauss syndrome: a report of five cases.

Churg-Strauss syndrome is an eosinophil-associated, small vessel granulomatous vasculitis, characterized by late onset asthma, upper airways disease, eosinophilia, and clinical manifestations of systemic vasculitis. Several cases of Churg-Strauss syndrome have been recognized in patients treated with cysteinyl leukotriene-receptor antagonists and weaned off systemic corticosteroids. These cases have led to a general warning on the possible development of Churg-Strauss syndrome after taking cysteinyl leukotriene-receptor antagonists. The authors report five cases of Churg-Strauss syndrome in severe steroid dependent asthmatics in whom inhaled corticosteroids allowed systemic corticosteroid withdrawal. It is concluded that physicians should monitor patients carefully when severe asthma is controlled with any substance allowing withdrawal from (or even avoidance) of systemic corticosteroids. Case-control studies should identify more precisely the risk factors of Churg-Strauss syndrome.

Administration, Inhalation↗
PubMed2000

Fine specificity of anti-fibrillin-1 autoantibodies in primary pulmonary hypertension syndrome.

Autoantibodies to fibrillin-1 (Fbn-1) have been found in systemic sclerosis (SSc), calcinosis, Raynaud's esophagael dysmotility, sclerodectyly, and telaengectasia (CREST) and mixed connective tissue disease (MCTD) diseases. The purpose of this study was to determine whether patients with primary pulmonary hypertension (PPH) and appetite-suppressant-associated PPH have anti-Fbn-1 autoantibodies. In addition we assessed the human leucocyte antigen (HLA) class II alleles (DRB1, 3, 4, 5 and DQB1) in these patients in order to determine whether the response is genetically restricted. The frequency of anti-Fbn-1 autoantibodies in patient groups was compared with that of a control group of 88 healthy patients, and HLA was correlated similarly with a group of 51 healthy subjects. Anti-Fbn-1 autoantibodies were found at high frequency in PPH: in 70 of 75 adults with PPH (93%), in 28 of 33 children with PPH (84.8) and in 12 of 18 (67%) patients with appetite-suppressant-associated PPH. Utilization of two Fbn-1 fusion proteins allowed us to determine the dominant determinant region, recognized by anti-Fbn-1 autoantibodies, which may be located on the N-terminal fragment of the Fbn-1 protein. No significant immunogenetic correlations were found when the PPH patient groups were compared with normal controls. This novel category of autoantibodies is found in diseases characterized by endothelial and extracellular matrix protein alterations and fibrosis.

Adult↗
PubMed2000

High plasma serotonin levels in primary pulmonary hypertension. Effect of long-term epoprostenol (prostacyclin) therapy.

Elevated plasma serotonin is associated with primary pulmonary hypertension (PPH). To test whether this elevation could be related to platelet activation, the 2 pools of blood serotonin (platelets and plasma) and plasma 5-hydroxyindoleacetic acid (5-HIAA) as well as markers of platelet activation (alpha(IIb)beta(3), CD36, P-selectin, and CD63 membrane epitopes) were measured in 16 patients with severe PPH (group 1) before and at days 10 and 40 of treatment with a continuous infusion of epoprostenol (prostacyclin). The same biological parameters were also measured in 19 healthy subjects (group 2) and in 10 patients after cardiovascular surgery with extracorporeal circulation (group 3), a condition known to profoundly activate the platelets. Twelve PPH patients showed hemodynamic and clinical improvement, 3 remained stable, and 1 had the treatment stopped because of clinical aggravation. At day 0, mean plasma serotonin (5-hydroxytryptamine [5-HT]) concentration was much higher in PPH patients than in normal subjects (34.4+/-21.2 versus 9.1+/-6.0 nmol/L, respectively; P:<0.001) and positively correlated with total pulmonary resistance. The mean platelet 5-HT content was not significantly different in PPH compared with normal individuals. Mean plasma 5-HIAA concentrations were much higher in PPH than in normal patients (162+/-57 versus 61+/-7 nmol/L, respectively; P<0.001). These parameters did not significantly change during epoprostenol treatment. There was no correlation between the changes in plasma 5-HT during treatment and clinical or hemodynamic improvement. In PPH patients, the mean platelet volume significantly decreased (ANOVA, P<0.01) during treatment. Positive correlations were evidenced between the size of platelets and the number of alpha(IIb)beta(3) and CD36 epitopes. When compared with control platelets, the number of alpha(IIb)beta(3) epitopes detected on PPH platelets at day 0 tended to be higher, but this difference did not reach a statistical significance (41 300+/-7140 for PPH patients versus 36 010+/-3930 for control subjects, P=0.069). The number of CD36 epitopes, in the range of controls at day 0 (11 590+/-5080 for PPH patients versus 11 900+/-1790 for control subjects), decreased during treatment (ANOVA, P=0.038) and became significantly low at day 40 (8660+/-3520, P<0.001). The number of CD63 epitopes was not elevated, and P-selectin was never detected at any time point on PPH platelets. This glycoprotein profile indicates that the platelets of PPH patients were not highly activated but had an accelerated turnover and returned to normal under epoprostenol treatment without change of the elevated plasma serotonin, characteristic of PPH. In conclusion, neither platelet activation nor a significant alteration of the 5-HT endothelial metabolism explains the high level of plasma 5-HT in PPH patients. The 5-HT plasma concentration is not a predictive marker of the severity of PPH, and its evolution is independent of the clinical and hemodynamic status. Treatment by a potent antiaggregating agent, epoprostenol, does not affect the increase of plasma 5-HT, despite a therapeutic benefit.

Adult↗
PubMed2000

Severe pulmonary hypertension in histiocytosis X.

Diminished exercise capacity in advanced pulmonary histiocytosis X does not appear to be related to ventilatory limitation but may be related to pulmonary vascular dysfunction. Pulmonary hemodynamics and respiratory function were studied in 21 consecutive patients with advanced pulmonary histiocytosis X, and compared with parameters of patients with other severe chronic lung diseases (29 patients with chronic obstructive pulmonary disease and 14 patients with idiopathic pulmonary fibrosis). All patients with pulmonary histiocytosis X displayed severe pulmonary hypertension: mean pulmonary arterial pressure, 59 +/- 4 mm Hg; cardiac index, 2.6 +/- 0.8 L/min/m(2); and total vascular pulmonary resistance, 25 +/- 3 IU/m(2) (p < 0.05, as compared with patients with other chronic lung diseases). Pa(O(2)) was similar in the three groups, whereas FEV(1) was lower in patients with other chronic lung diseases (p < 0.05). In contrast to other chronic lung diseases, the degree of pulmonary hypertension was not related to variables of pulmonary function in pulmonary histiocytosis X. Histopathology was available for 12 patients with pulmonary histiocytosis X and revealed proliferative vasculopathy involving muscular arteries and veins, with prominent venular involvement. Two consecutive lung samples (taken before and after the occurrence of pulmonary hypertension) were available for six patients with pulmonary histiocytosis X, and showed that pulmonary vasculopathy worsened, whereas parenchymal and bronchiolar lesions remained relatively unchanged. These results indicate that pulmonary hypertension in pulmonary histiocytosis X might be related to an intrinsic pulmonary vascular disease, in which the pulmonary circulation is involved independent of small airway and lung parenchyma injury.

Adult↗
PubMed2000

Nadroparin in the prevention of deep vein thrombosis in acute decompensated COPD. The Association of Non-University Affiliated Intensive Care Specialist Physicians of France.

Low molecular weight heparins are as effective as unfractionated heparin in deep-vein thrombosis (DVT) prophylaxis for major surgery. However, there is no evidence nor consensus for prophylaxis in medical patients. We compared the efficacy and safety of nadroparin calcium (nadroparin) with placebo in medical patients at high risk of DVT. A total of 223 patients mechanically ventilated for acute, decompensated chronic obstructive pulmonary disease, were randomized to treatment with subcutaneous nadroparin adjusted for body weight (0.4 ml, i.e., 3,800 AXa IU, or 0.6 ml, i.e., 5,700 AXa IU) or placebo. The average duration of treatment was 11 d. The incidence of DVT in patients receiving nadroparin was significantly lower than that in patients receiving placebo (15.5 versus 28.2%; p = 0.045). Although the incidence of adverse events was high in both groups, there were no significant differences between nadroparin and placebo for total adverse events (46.3 versus 39.8%; p = 0.33), serious adverse events (25.0 versus 19.5%; p = 0.32), or those resulting in early permanent discontinuation of treatment (12.0 versus 8.8%; p = 0.44). The most common adverse event was hemorrhage. There was the same number of deaths in both treatment groups. Subcutaneous nadroparin resulted in 45% decrease in incidence of DVT compared with placebo.

Aged↗
PubMed2000

Imbalance between platelet vascular endothelial growth factor and platelet-derived growth factor in pulmonary hypertension. Effect of prostacyclin therapy.

Focal vascular injury and impaired endothelial function are features of pulmonary hypertension (PH) that lead to enhanced platelet endothelial cell interactions. Vascular endothelial growth factor (VEGF) is contained in platelets and released at sites of vascular injury to promote endothelial repair and wound healing in combination with platelet-derived nonspecific mitogens such as platelet-derived growth factor (PDGF). The overall balance between platelet VEGF and PDGF was investigated in 21 patients with primary PH, 8 with secondary PH, and 27 with chronic hypoxemic lung disease (CHLD), as well as in 29 control subjects. Platelet VEGF content was increased in patients with primary and secondary PH as compared with control subjects (518 +/- 89, 675 +/- 156, and 166 +/- 29 fg/10(5) platelets, respectively; p < 0.01), whereas platelet PDGF content was similar in the three groups (31 +/- 2, 36 +/- 4, and 33 +/- 3 pg/10(5) platelets, respectively; NS). Patients treated with a continuous prostacyclin infusion had a higher platelet VEGF but a similar platelet PDGF content as compared with untreated patients. Moderate increases in platelet VEGF and PDGF contents were observed in the CHLD patients. We conclude that patients with primary or secondary PH have an increase in platelet VEGF content, but not in platelet PDGF content, and that their platelet VEGF content increases further in response to prostacyclin infusion. We suggest that imbalance between platelet VEGF and PDGF is beneficial to patients with PH.

Adolescent↗
PubMed1999

Angioscopic video-assisted pulmonary endarterectomy for post-embolic pulmonary hypertension.

OBJECTIVES: To assess whether the use of video-assisted angioscopy would increase the outcome of pulmonary thromboendarterectomy (PTE). METHODS: PTE included a median sternotomy, intrapericardial dissection of the superior vena cava, institution of cardiopulmonary bypass, deep hypothermia and sequential circulatory arrest periods. It was always performed through two separate arteriotomies on both main intrapericardial pulmonary arteries, into which a rigid 5 mm angioscope connected to a video camera was introduced to increase the visibility and endarterectomies. RESULTS: From January 1996 to July 1998, 68 consecutive patients (35 males and 33 females) aged 54.3 +/- 13.5 years underwent PTE. Patients were in New York Heart Association (NYHA) class II (n = 2), III (n = 43) or IV (n = 23) with the following hemodynamics: mean pulmonary arterial pressure (PAP) 54 +/- 13 mmHg; cardiac output (CO): 3.8 +/- 0.8 l/min, and total pulmonary resistance (TPR): 1207 +/- 416 dyne x s x cm(-5). The cumulated circulatory arrest time was 23 +/- 12 min and postoperative length of ventilatory support 10 +/- 12 days. Nine patients died, for an overall in-hospital mortality of 13.2%. The functional outcome in surviving patients was significantly improved (P < 0.0001) both clinically (NYHA class 3.2 +/- 0.5 vs. 1.3 +/- 0.6) and hemodynamically (PAP (mmHg) 53.1 +/- 13 vs. 30.2 +/- 11.8, CI (l/min per m2) 2.1 +/- 0.5 vs. 2.8 +/- 0.6, TPR (dyne x s x cm(-5)) 1174 +/- 416 vs. 519 +/- 250). CONCLUSIONS: Video-assisted angioscopy improves the quality and degree of pulmonary endarterectomy expanding the indications to include patients with previously inaccessible distal disease.

Adult↗
PubMed1999

Pulmonary arterial resistance: noninvasive measurement with indexes of pulmonary flow estimated at velocity-encoded MR imaging--preliminary experience.

Cardiac output and pulmonary vascular resistance (PVR) were measured in 19 patients by means of catheterization of the right side of the heart. Results were compared with the cardiac output and indexes of pulmonary arterial blood flow estimated with velocity-encoded magnetic resonance (MR) imaging. Correlations were good between estimates with right-sided heart catheterization and those with velocity-encoded MR imaging. By providing accurate pulmonary arterial blood flow measurements, velocity-encoded MR imaging allowed distinction of patients with high PVR from subjects with normal PVR.

Adult↗
PubMed1999

Short-term and long-term epoprostenol (prostacyclin) therapy in pulmonary hypertension secondary to connective tissue diseases: results of a pilot study.

Continuous intravenous epoprostenol improves exercise capacity, haemodynamics, and survival in severe primary pulmonary hypertension. Pulmonary hypertension can also be life-threatening in patients with connective tissue diseases. In a prospective open monocentre uncontrolled study, the effects of epoprostenol were evaluated in patients with severe pulmonary hypertension secondary to connective tissue diseases who were unresponsive to oral vasodilators (including calcium channel blockers) and continued to be in the New York Heart Association (NYHA) functional class III or IV despite conventional medical therapy. Seventeen patients received epoprostenol administered by a portable infusion pump associated with conventional therapy (oral anticoagulants, diuretics, supplemental oxygen). During the first six weeks of therapy, two (12%) patients died, of pulmonary oedema (n = 1) and severe sepsis (n = 1). In the fifteen remaining subjects, clinical and haemodynamic parameters improved significantly at six weeks. These patients were subsequently monitored for 80+/-48 (range 14-154) weeks after initiation of epoprostenol. Five (33%) patients died, of right heart failure (n = 2), severe sepsis (n = 2) or syncope (n = 1) and two patients were successfully transplanted 24 and 52 weeks after initiation of epoprostenol. Seven of the remaining eight patients had a persistent clinical improvement. Short-term epoprostenol therapy is effective in some patients with connective tissue diseases as demonstrated by better clinical status and haemodynamics at six weeks. However, this study reports several cases of early and late major complications including severe sepsis and pulmonary oedema. Additional information is needed to evaluate the benefit: risk ratio of long-term epoprostenol therapy in pulmonary hypertension secondary to connective tissue diseases.

Adult↗
PubMed1999

High prevalence of detectable deep venous thrombosis in patients with acute pulmonary embolism.

STUDY OBJECTIVES: Because specific studies are unavailable, the exact prevalence of detectable "residual" deep venous thrombosis (DVT) in patients with acute pulmonary embolism (PE) is unknown. DESIGN: Review of clinical records and radiologic documents of consecutive patients. SETTING: Pulmonary diseases and radiology departments at a university hospital. PATIENTS: All patients hospitalized in the Department of Pulmonary Diseases with a diagnosis of acute PE during a 5-year period (1984 to 1988). During this period, the diagnosis of PE was based exclusively on pulmonary angiography, and bilateral lower limb venography was routine in patients with proven acute PE. MEASUREMENTS AND RESULTS: Among 228 consecutive patients with angiography-proven PE, 213 underwent bilateral lower limb venography within 48 h of the diagnosis. Venography demonstrated DVT in 174 patients (81.7%; 95% confidence interval, 76.5 to 86.9%), including 128 patients (60%) with proximal DVT. Signs or symptoms of DVT were present in only 72 patients (42%) with DVT. The prevalence of detectable DVT was significantly lower in patients with recent pelvic surgery or delivery (6 of 12, 50%) than in the other patients, whatever their individual risk factors (p < 0.05). The mean pulmonary vascular obstruction was significantly lower in patients with normal venography than in patients with detectable DVT (37.6 +/- 20.9% vs 48.4 +/- 21.7%; p = 0.007). CONCLUSIONS: Lower limb venography demonstrates a high prevalence (82%) of residual DVT in patients with angiography-proven PE. These data should be taken into account in the diagnostic and therapeutic management of patients with suspected or proven PE.

Adolescent↗
PubMed1999

[Strategies for utilization of anticoagulants in pulmonary embolism].

Anticoagulant therapy significantly reduces the incidence of fatal recurrent thromboembolism and mortality. Today, initial anticoagulant therapy in acute pulmonary embolism mostly consists in the use of intravenous non fractioned heparin associated with simultaneous oral anticoagulation. Treatment with non fractioned heparin is continued until the INR is between 2 and 3 for 2 consecutive days. Long term therapy with antivitamin K should be continued for at least 3 months. It is recommended that patients with recurrent venous thromboembolism should be treated indefinitively. Long term anticoagulant therapy will be discussed individually in the presence of a persistent risk factor. Low molecular weight heparins have been evaluated in the initial treatment of patients with acute, hemodynamically stable pulmonary embolism and are as effective and safe as continuous intravenous non fractioned heparin. Low molecular weight heparins will probably replace non fractioned heparin in the initial treatment of acute hemodynamically stable pulmonary embolism, on a short term perspective.

Administration, Oral↗
PubMed1998

A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group.

BACKGROUND: The efficacy and safety of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis is still a matter of debate. METHODS: Using a two-by-two factorial design, we randomly assigned 400 patients with proximal deep-vein thrombosis who were at risk for pulmonary embolism to receive a vena caval filter (200 patients) or no filter (200 patients), and to receive low-molecular-weight heparin (enoxaparin, 195 patients) or unfractionated heparin (205 patients). The rates of recurrent venous thromboembolism, death, and major bleeding were analyzed at day 12 and at two years. RESULTS: At day 12, two patients assigned to receive filters (1.1 percent), as compared with nine patients assigned to receive no filters (4.8 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.22; 95 percent confidence interval, 0.05 to 0.90). At two years, 37 patients assigned to the filter group (20.8 percent), as compared with 21 patients assigned to the no-filter group (11.6 percent), had had recurrent deep-vein thrombosis (odds ratio, 1.87; 95 percent confidence interval, 1.10 to 3.20). There were no significant differences in mortality or the other outcomes. At day 12, three patients assigned to low-molecular-weight heparin (1.6 percent), as compared with eight patients assigned to unfractionated heparin (4.2 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.38; 95 percent confidence interval, 0.10 to 1.38). CONCLUSIONS: In high-risk patients with proximal deep-vein thrombosis, the initial beneficial effect of vena caval filters for the prevention of pulmonary embolism was counterbalanced by an excess of recurrent deep-vein thrombosis, without any difference in mortality. Our data also confirmed that low-molecular-weight heparin was as effective and safe as unfractionated heparin for the prevention of pulmonary embolism.

Aged↗
PubMed1998

[Pulmonary thromboendarterectomy with video-angioscopy and circulatory arrest: an alternative to cardiopulmonary transplantation and post-embolism pulmonary artery hypertension].

The best predictor of poor or suboptimum outcome from pulmonary thromboendarterectomy (PTE) is insufficient relief of obstruction, especially in the lower lobes. The aim of this study is to emphasize that the use of video-assisted angioscopy may increase the quality of PTE and thus improve outcome. PTE included a median sternotomy, intrapericardial dissection limited to the superior vena cava, institution of cardiopulmonary bypass, deep hypothermia and sequential circulatory arrest periods. PTE was always bilateral and performed through two separate arteriotomies of both main intrapericardial pulmonary arteries. A rigid 5 mm angioscope connected to a video camera was introduced through the arteriotomy into the lumen to increase the visibility and perform the video-assisted endarterectomies of all obstructed segmental branches, including normally inaccessible anterior segmental branches. Between January 1996 and December 1997, 48 patients with severe postembolic pulmonary hypertension had PTE. Patients were in New York Heart Association (NYHA) class II (n = 2), III (n = 28) or IV (n = 18) with the following hemodynamics: mean pulmonary arterial pressure (PAP) 53 +/- 13 mmHg, cardiac index 2.16 +/- 0.5 L/min/m2, pulmonary vascular resistances (PVR): 1,152 +/- 414 dyne.s-1.cm-5. Six patients died from alveolar hemorrhage (n = 1), high residual pulmonary pressure and rethrombosis (n = 4) and hypoxic cardiac arrest (n = 1). The functional outcome in surviving patients was as follows: (NYHA) class I (n = 24), II (n = 16) or III (n = 2) with improved hemodynamics: mean pulmonary arterial pressure: 30 +/- 9 mmHg, cardiac index: 2.78 +/- 0.5 L/min/m2, pulmonary vascular resistances (PVR): 484 +/- 159 dynes.s-1.cm-5. Video-assisted angioscopy allows much improved quality and degree of pulmonary endarterectomy. This expands the indications to include patients with previously inaccessible distal disease and candidates for heart-lung transplantation.

Adult↗
PubMed1998

Urinary cGMP concentrations in severe primary pulmonary hypertension.

BACKGROUND: Prognostic evaluation of patients with primary pulmonary hypertension (PPH) requires right heart catheterisation. The development of accurate non-invasive methods for monitoring these patients remains an important task. Cyclic guanosine monophosphate (cGMP) is an indicator of the action of natriuretic peptides and nitric oxide on target cells. Plasma and urinary cGMP concentrations are raised in patients with congestive heart failure in whom they correlate closely with haemodynamic parameters and disease severity. The aim of the present study was to determine whether the urinary concentration of cGMP could be used as a non-invasive marker of haemodynamic impairment in patients with severe PPH. METHODS: Urinary cGMP concentrations were measured in 19 consecutive patients with PPH, seven with acute asthma, and 30 normal healthy controls. RESULTS: Patients with PPH had higher urinary cGMP concentrations than asthmatic patients or normal healthy controls (p = 0.001). Urinary cGMP concentrations were higher in patients with severe haemodynamic impairment--that is, those with a cardiac index (CI) of < or = 2 l/min/m2 (p = 0.002)--and urinary cGMP concentrations were inversely correlated with CI (r = -0.69, p = 0.002) and venous oxygen saturation (r = -0.65, p = 0.003). CONCLUSION: Urinary cGMP concentrations may represent a non-invasive indicator of the haemodynamic status of patients with severe PPH.

Adult↗