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M Humbert

Publications and source records attributed to M Humbert.

At least 73 records · Page 4Linked to original sources
PubMed2003

[Pulmonary artery hypertension associated with connective tissue diseases].

MOST IMPORTANT: Pulmonary hypertension (PH) is a severe, potentially life-threatening complication of connective tissue diseases, among which scleroderma is first line. The aim of this paper was to review the literature and report our experience with this particular complication of connective tissue diseases. In our centre of pulmonary vascular diseases, connective tissue diseases represent the third cause of PH. RESULTS: Scleroderma and particularly its limited cutaneous variant, the CREST syndrome, is the most common connective tissue disease affected by pulmonary hypertension. It can be related to a specific lung parenchymal involvement (hypoxic PH), to an isolated pulmonary vascular involvement or to a cardiac dysfunction secondary to specific myocardial lesions. DIAGNOSIS: Echocardiography is an excellent examination to detect pulmonary hypertension. However, right heart catheterisation is necessary to confirm the diagnosis of pulmonary hypertension and to test vasoreactivity with a potent vasodilator such as nitric oxide (NO). REGARDING TREATMENTS: Oral calcium channel blockers are indicated in patients who are responders to acute NO tests. Treatment with continuous intravenous prostacylin is obviously an improvement, at least functionally, although it appears less effective than in primary PH. With the new subcutaneous, oral and inhaled vasodilatators (prostaglandin and endothelin receptor antagonists), a few cases of improvement of PH with intensive immunosuppressive therapy were observed, essentially during systemic lupus erythematosus and Sharp syndrome. IN PRACTICE: PH is a severe complication of connective tissue diseases. Early detection of this complication should allow an earlier and more aggressive therapeutic approach in these patients, before irreversible vascular lesions occur.

Adult↗
PubMed2003

[Pulmonary hypertension complicating systemic diseases other than connective tissue diseases].

A COMPLICATION OF CERTAIN SYSTEMIC DISEASES: Pulmonary hypertension (PH) can complicate the progression of certain systemic diseases such as sarcoidosis, histiocytosis X and some vasculites. The mechanisms at the origin of PH are varied and always require rigorous analysis in order to optimise treatment. DEPENDING ON THE DISEASE: PH associated with sarcoidosis is essentially related to specific lung parenchymal fibrosis and is poorly responder to corticosteroids. Other mechanisms may be more rarely incriminated (compressive andenopathies, mediastinal fibrosis, florid sarcoidosis concomitant to a pulmonary occlusive vascular disease...). During histiocytosis X, the ventilatory limitation of these patients does not always correlate with the severity of the respiratory failure, suggesting the existence of a pulmonary vascular disease progressing independently of the pulmonary parenchymal lesions. The pulmonary artery damage during Takayasu's arteritis and other auto-immune pulmonary arteritis may lead to potentially life-threatening complications, notably through stenosis and/or obstruction of the pulmonary arteries. Pulmonary hypertension is exceptional during Wegener's disease or periateritis nodosa. CONCLUSION: PH can complicate the progression of certain systemic diseases. The physiopathological mechanisms responsible are unclear (specific parenchymal fibrosis, isolated vascular involvement...). Globally, available treatments are disappointing.

Cardiac Catheterization↗
PubMed2003

Difficult asthma.

Explore the source record for details and available documents.

Anti-Asthmatic Agents↗
PubMed2003

Evaluation of CD4+ T cells proliferating to grass pollen in seasonal allergic subjects by flow cytometry.

Our objective was to characterize T-cell responses to Phleum pratense in grass pollen allergic individuals and healthy controls using the fluorescent dye PKH26. Peripheral blood mononuclear cells were stimulated with P. pratense, or with recall antigens, and CD3+/CD4+ and CD3+/CD8+ T-cells that had proliferated were analysed by flow cytometry. In the presence of P. pratense CD4+/CD3+ T-cells proliferated more in grass pollen sensitive atopic patients than in nonallergic controls or in nongrass pollen sensitive atopic subjects. PPD and TT recall antigens elicited uniformly high proliferation in all T-cell subsets. Only half of pollen sensitive patients also had an increased proliferation of CD3+/CD8+ T-cells in response to P. pratense. We determined precursor frequency of CD4+ T cells in the original population that responded to P. pratense and found values ranging from 1 x 10-3 to 0.6 x 10-1, in the same range as those measured for PPD and TT. In conclusion, grass pollen sensitive atopic patients show enhanced CD4+ T-cell reactivity to P. pratense, and this could be related to the presence of elevated numbers of circulating allergen-specific CD4+ T cells. This flow cytometric method should allow the identification of other phenotypic markers such as intracellular cytokines in allergen specific responding CD4+ T cells.

Allergens↗
PubMed2003

Inflammation in pulmonary arterial hypertension.

Inflammatory mechanisms appear to play a significant role in some types of pulmonary hypertension (PH), including monocrotaline-induced PH in rats and pulmonary arterial hypertension of various origins in humans, such as connective tissue diseases (scleroderma, systemic lupus erythematosus, mixed connective disease), human immunodeficiency virus infection, or plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal (M) protein and skin changes (POEMS) syndrome. Interestingly, some patients with severe pulmonary arterial hypertension associated with systemic lupus erythematosus have experienced significant improvements with immunosuppressive therapy, emphasising the relevance of inflammation in a subset of patients presenting with PH. Patients with primary PH (PPH) also have some immunological disturbances, suggesting a possible role for inflammation in the pathophysiology of this disease. A subset of PPH patients have been shown to have circulating autoantibodies, including antinuclear antibodies, as well as elevated circulating levels of the pro-infammatory cytokines, interleukins -1 and -6. Lung histology has also revealed inflammatory infiltrates in the range of plexiform lesions in patients displaying severe PPH, as well as an increased expression of the chemokines regulated upon activation, normal T-cell expressed and secreted (RANTES) and fractalkine. Further analysis of the role of inflammatory mechanisms is necessary to understand whether this component of the disease is relevant to its pathophysiology.

Animals↗
PubMed2003

[Intrinsic asthma].

Although asthma is often regarded as a manifestation of atopy, many asthmatics are not atopic. As compared to atopic ("extrinsic") asthma, nonatopic ("intrinsic") asthma occurs later in life, mostly in females, and nasal polyposis, aspirin sensitivity and steroid dependence are common. In this patient population, there is no history of allergy, skin prick testing is negative for all aeroallergens tested and total as well as specific immunoglobulin E serum levels are within the normal range. Epidemiological studies and analysis of bronchial mucosal expression of "pro-eosinophilic" and "pro-atopic" markers demonstrate that there are more similarities than differences in immunopathology between atopic and nonatopic asthma.

Adult↗
PubMed2002

Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension.

Primary pulmonary hypertension is a progressive and often fatal disorder in humans that results from an increase in pulmonary blood pressure associated with abnormal vascular proliferation. Dexfenfluramine increases the risk of pulmonary hypertension in humans, and its active metabolite is a selective serotonin 5-hydroxytryptamine 2B (5-HT(2B)) receptor agonist. Thus, we investigated the contribution of the 5-HT(2B)receptor to the pathogenesis of pulmonary hypertension. Using the chronic-hypoxic-mouse model of pulmonary hypertension, we found that the hypoxia-dependent increase in pulmonary blood pressure and lung remodeling are associated with an increase in vascular proliferation, elastase activity and transforming growth factor-beta levels, and that these parameters are potentiated by dexfenfluramine treatment. In contrast, hypoxic mice with genetically or pharmacologically inactive 5-HT(2B)receptors manifested no change in any of these parameters. In both humans and mice, pulmonary hypertension is associated with a substantial increase in 5-HT(2B) receptor expression in pulmonary arteries. These data show that activation of 5-HT(2B) receptors is a limiting step in the development of pulmonary hypertension.

Animals↗
PubMed2002

[Pulmonary hypertension associated with connective tissue diseases].

PURPOSE: Pulmonary hypertension is a rare but well-known life-threatening complication of connective tissue diseases. The aim of this article is to analyse the available literature and to report the experience of a pulmonary vascular diseases centre about this complication. CURRENT KNOWLEDGE AND KEY POINTS: Scleroderma and its limited variant, the CREST syndrome (calcification, Raynaud phenomenon, esophageal dysmotility, sclerodactily, telangiectasia), is the most common connective tissue disease affected by pulmonary hypertension. Dyspnea is the main symptom and is frequently severe. Echocardiography is an excellent exam to detect pulmonary hypertension. However, right heart catheterization is necessary to confirm the diagnosis of pulmonary hypertension and to test vasoreactivity with a potent vasodilator such as nitric oxide. Pulmonary hypertension is less severe in patients with connective tissue diseases perhaps because of an earlier diagnosis. A significantly lower proportion of patients presents an acute vasodilator response, suggesting an early constitution of irreversible pulmonary vascular lesions. Continuous intravenous epoprostenol therapy seems to be less effective as compared with patients with primitive pulmonary hypertension and does not improve survival. So, we observed dramatic improvement in rare cases after immunosuppressive therapy. FUTURE PROSPECTS AND PROJECTS: New treatments with oral, subcutaneous or inhaled stable prostacyclin analogs or with an endothelin receptor antagonist are currently being evaluated. The role of immunosuppressive therapy has to be defined.

Antihypertensive Agents↗
PubMed2002

Plasminogen activation by blood monocytes and alveolar macrophages in primary pulmonary hypertension.

The pathophysiology of primary pulmonary hypertension (PPH) remains poorly understood. Vascular wall remodeling and endothelial dysfunction reflected by modifications in plasma fibrinolytic proteins and von Willebrand factor have been well documented in PPH. We hypothesize that endothelial mediators, produced in excess in PPH patients, may stimulate migrating mononuclear cells and thereby modulate alveolar macrophage function; in particular, the plasminogen activation system. Components of the fibrinolytic system were therefore studied in plasma, blood monocytes and alveolar macrophages obtained from bronchoalveolar lavage in 10 patients with PPH and in four controls. Compared with controls, PPH patients had elevated plasma levels of tissue-type plasminogen activator (15.6 +/- 9.9 versus 5.5 +/- 3 ng/ml) and plasminogen activator inhibitor-1 (27.8 +/- 23 versus 16.4 +/- 12 ng/ml). In contrast, binding and activation of plasminogen by single-chain urokinase-type plasminogen activator (scu-PA) at the surface of blood monocytes and alveolar macrophages were not different from those of control values. Dissociation constants (K(d)) for binding of scu-PA and plasminogen to alveolar macrophages were similar in both PPH (4.7 +/- 1.5 and 0.88 +/- 0.3 micromol/l, respectively) and control (6.7 +/- 0.1 and 1.02 +/- 0.12 micromol/l, respectively) groups. These results indicate that in PPH patients the fibrinolytic activity of alveolar macrophages is normal, whereas endothelial fibrinolytic proteins are abnormally elevated in plasma.

Adult↗
PubMed2002

Pulmonary arterial hypertension and type-I glycogen-storage disease: the serotonin hypothesis.

A case of pulmonary arterial hypertension in a patient with type-Ia glycogen-storage disease, a rare autosomal recessive disorder caused by a deficiency of glucose-6-phosphatase is reported in this study. It has been suggested that the occurrence of pulmonary arterial hypertension in type-Ia glycogen-storage disease could be due to an abnormal production of vasoconstrictive amines such as serotonin. To test this hypothesis, plasma serotonin concentrations were prospectively measured in 13 patients with type-Ia glycogen-storage disease, one patient with severe pulmonary hypertension and type-Ia glycogen-storage disease, 16 patients displaying severe pulmonary arterial hypertension, and 26 normal healthy controls. Elevated plasma serotonin concentrations were found in patients with either severe pulmonary arterial hypertension (38.8+/-7.3 nmol x L(-1)) or type-Ia glycogen-storage disease (36.8+/-11.5 nmol x L(-1)), as compared with controls (8.8+/-0.6 nmol x L(-1), p<0.001). Plasma serotonin was dramatically elevated in the patient with type-Ia glycogen-storage disease and pulmonary arterial hypertension (113.4 nmol x L(-1)). It is concluded that type-Ia glycogen-storage disease may be another condition in which abnormal handling of serotonin is one event in a multistep process leading to severe pulmonary arterial hypertension.

Adolescent↗
PubMed2002

BMPR2 germline mutations in pulmonary hypertension associated with fenfluramine derivatives.

This study investigated whether patients developing pulmonary arterial hypertension (PAH) after exposure to the appetite suppressants fenfluramine and dexfenfluramine have mutations in the bone morphogenetic protein receptor 2 (BMPR2) gene, as reported in primary pulmonary hypertension. BMPR2 was examined for mutations in 33 unrelated patients with sporadic PAH, and in two sisters with PAH, all of whom had taken fenfluramine derivatives, as well as in 130 normal controls. The PAH patients also underwent cardiac catheterisation and body mass determinations. Three BMPR2 mutations predicting changes in the primary structure of the BMPR-II protein were found in three of the 33 unrelated patients (9%), and a fourth mutation was found in the two sisters. No BMPR2 mutations were identified in the 130 normal controls. This difference in frequency was statistically significant. Moreover, the mutation-positive patients had a somewhat shorter duration of fenfluramine exposure before illness than the mutation-negative patients, a difference that was statistically significant when the two sisters were included in the analysis. In conclusion, the present authors have detected bone morphogenetic protein receptor 2 mutations that appear to be rare in the general population but may combine with exposure to fenfluramine derivatives to greatly increase the risk of developing severe pulmonary arterial hypertension.

Adolescent↗
PubMed2002

Genetics of pulmonary hypertension: from bench to bedside.

Primary pulmonary hypertension has been described as either sporadic or clustered in families. Familial primary pulmonary hypertension segregates as an autosomal dominant trait with markedly reduced disease gene penetrance. Defects within bone morphogenetic protein receptor type II gene, coding for a receptor member of the transforming growth factor-beta family, underlie familial primary pulmonary hypertension. Several lines of evidence point to the potential requirement of additional factors, either environmental or genetic, in the pathogenesis of the disease. In addition, a proportion of so-called sporadic primary pulmonary hypertension turns out to have an inherited basis, as demonstrated by germline bone morphogenetic protein receptor type II gene mutations. Analysis of cases in association with hereditary haemorrhagic telangiectasia led to the demonstration that pulmonary arterial hypertension can involve activin-receptor-like kinase 1 mutations, a type I transforming growth factor-beta receptor. These findings emphasise the critical role of the transforming growth factor-beta signalling pathway in pulmonary arterial hypertension. While this achievement has generated extreme interest, the pathobiology of severe pulmonary arterial hypertension remains unclear and genomic approaches to pulmonary hypertension research may identify additional molecular determinants for this disorder. Finally, there is an urgent need to develop relevant guidelines for genetic counselling to assist patients, their relatives and pulmonary vascular specialists to utilise these recent observations.

Activin Receptors, Type I↗