Search PubMed⌕ Search

Biomedical subjects

M Humbert

Publications and source records attributed to M Humbert.

At least 55 records · Page 3Linked to original sources
PubMed2005

Reversibility of pulmonary arterial hypertension in HIV/HHV8-associated Castleman's disease.

The present study describes a case of pulmonary arterial hypertension (PAH) associated with multicentric Castleman's disease in a patient infected with HIV type 1 and human herpes virus 8. Therapy included highly active antiretroviral therapy, warfarin, diuretics, continuous i.v. epoprostenol and 12-monthly pulses of cyclophosphamide. The patient's condition improved dramatically with complete reversibility of PAH, allowing weaning of continuous i.v. epoprostenol therapy. After 5 yrs, both Castleman's disease and PAH have not relapsed. This supports the hypothesis that control of inflammation and retroviral replication may be of interest in the context of PAH, complicating the course of an inflammatory condition associated with viral infection. In conclusion, further studies should help in characterising the best candidates for anti-inflammatory treatment in the setting of pulmonary arterial hypertension.

Adult↗
PubMed2005

Which anaesthesia should be recommended for prostate biopsy?

OBJECTIVE: Although transrectal ultrasound-guided prostatic biopsies are associated with significant discomfort and pain, most urologists do not use any kind of anaesthesia. We therefore compared the efficacy of two local anaesthetics, namely, the rectal administration of lidocaine gel and lidocaine periprostatic infiltration prior to biopsies. DESIGN AND METHODS: Three hundred and fifty-six randomized patients received either 15 mL of 2% lidocaine gel administered intrarectally ten minutes before prostate biopsies in group 1 (180 patients) or 10 mL of 1% lidocaine given under ultrasound guidance in two periprostatic injections of 5 mL, four minutes before the biopsies in group 2 (176 patients). A visual analogue scale (VAS) was used to assess the pain score during anaesthesia (VAS 1), during the biopsies (VAS 2) and 30 minutes after them (VAS 3). RESULTS: Patients receiving lidocaine gel experienced statistically less pain than the lidocaine injection group for mean VAS 1 (0.1 vs 1.4, p < 0.0001) and mean VAS 3 (0.8 vs 1.4, p < 0. 001) but VAS 2 showed no statistically significant difference (2.0 vs 2.1). No major morbidity was noted with either anaesthetic. CONCLUSION: Rectal administration of lidocaine gel is both safe, simple and effective and results are more satisfactory than with lidocaine periprostatic infiltration.

Administration, Rectal↗
PubMed2004

[Pulmonary arterial hypertension in systemic sclerosis: definition of a screening algorithm for early detection (the ItinérAIR-Sclérodermie Study)].

PURPOSE: Pulmonary arterial hypertension (PAH) is a severe complication of scleroderma. Its prevalence varies from 5% to 35% in the literature. A systematic yearly screening is recommended for early detection and management of PAH, but no precise algorithm is yet available. METHODS: From literature analysis as well as evaluation of medical needs and practices, a multidisciplinary board of experts proposed an algorithm for the screening of PAH in scleroderma. RESULTS: This algorithm is based on a precise Doppler echocardiography methodology for the purpose of screening scleroderma patients for PAH. Patients are considered as being at high or low risk of PAH depending on the maximal tricuspid regurgitation velocity. High-risk patients undergo right heart catheterization for confirmation of the diagnosis of PAH. A French multicenter transversal observational study ("ItinérAIR Sclérodermie") will be conducted in 21 hospital centers in France and involved 100 investigators organized as multidisciplinary networks. FUTURE PROSPECTS: Final results will provide confirmation that the screening algorithm is applicable in a real world setting, as well as a better knowledge of the prevalence of PAH in the various sub-groups of scleroderma patients, of the risk profile for PAH and of the value of DLCO as a predictive factor for PAH, and will support elaboration of precise screening guidelines.

Algorithms↗
PubMed2004

[Treatments for pulmonary arterial hypertension].

PURPOSE: Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, in situ thrombosis and vascular remodeling of small pulmonary arteries inducing a fixed pulmonary arterial obstruction and persistent elevation of pulmonary arterial resistance. Conventional treatment is based on simple measures (exercise limitation) and non-specific drugs (warfarine, diuretics, oxygen). CURRENT KNOWLEDGE AND KEY POINTS: Pure vasodilators like calcium channel antagonists have little or no effect on the vast majority of patients, presumably because fixed pulmonary arteriopathy predominate over vasoconstriction. Intravenous prostacyclin (epoprostenol) and endothelin receptor antagonists have vasodilator and antiproliferative properties. Epoprostenol therapy has resulted in significant improvements in prognosis of this disease and this drug remains the first-line treatment of the most severe patients. Bosentan is an interesting first-line treatment for NYHA functional class III patients. Availability of novel specific drugs (endothelin receptor type A antagonists, prostacyclin analogues, type 5 phosphodiesterase inhibitors) open new perspectives in treatment of PAH. The long-term benefit of these drugs remains to be evaluated and their respective place in treatment of these patients is still uncertain. We here present the different therapeutic alternatives available in the PAH and propose an algorithm for treatment of these patients. FUTURE PROSPECTS AND PROJECTS: The evolution of therapy from vasodilators to antiproliferative agents reflects the advancement in our understanding of the mechanisms mediating pulmonary arterial hypertension.

Algorithms↗
PubMed2004

[Pulmonary hypertension: from genetics to treatments].

Pulmonary hypertertension (PHT) is a rare disease defined by increased resistance of the pulmonary arteries inevitably leading to right heart failure if specific treatment is not given. This disease can occur sporadically (idiopathic or primary PHT), within a familial context (familial PHT, BMPR2 gene mutation), or occur as a complication of other diseases (connective tissue disease, congenital cardiomyopathy, human immunodeficiency virus infection, portal hypertension, use of anorexigenic agents). The incidence of primary PHT is 2 million cases per year, probably an underestimation due to the low specificity of clinical signs, predominantly exercise-induced dyspnea. Recent therapeutic advances (prostacyclin and endothelin receptor antagonists administered in continuous infusion) have improved the prognosis of this orphan disease. Inhaled iloprost and type 5 phosphodiesterase inhibitors should be evaluated for this indication. Lung transplantation is reserved for patients unresponsive to medical treatment.

Bone Morphogenetic Protein Receptors, Type II↗
PubMed2004

[Surgical treatment of post-embolism pulmonary hypertension].

Pulmonary hypertension is a serous condition which, after a long history as an orphan disease, has raised renewed interest due to the development of efficacious therapeutic options including lung transplantation and continuous infusion of prostacycline. Bilateral endarteriectomy of the pulmonary arteries is another possibility for post-embolism pulmonary hypertension. The procedure is complex and must be performed in conditions of cardiac arrest and deep hypothermia but, unlike transplantation, provides definitive cure. Recognizing the post-embolic nature of pulmonary hypertension is not simple because old episodes of venous thrombosis or embolus migration are not found in 50% of patients. Segmentary defects on the perfusion scintigraphy contrasting with the homogeneous respiratory scintigraphy is the primary diagnostic feature. Lesions must be located in a main trunk or at the origin of lobular or segmentary branches to be accessible to endarteriectomy. An antero-posterior and lateral angiogram of each lung and a multiple-array helicoidal angioscan performed with a precise protocol by an experienced team are needed to identify the localization of the lesions. If the pulmonary resistance determined at right catheterism is correlated with anatomic obstruction, the risk of mortality of pulmonary endarteriectomy is low, offering patients a significant chance for normal or nearly normal cardiorespiratory function.

Endarterectomy↗
PubMed2004

[Clinical, haemodynamic and genetic features of familial pulmonary arterial hypertension].

INTRODUCTION: Pulmonary arterial hypertension (PAH) is defined by a raised pressure in the pulmonary arterial circulation associated with small vessel narrowing due to proliferation of the endothelium and vascular smooth muscle. Idiopathic PAH should be distinguished from PAH associated with a causal disease. One familial type (familial PAH), gathered from one family, has recently been linked to a mutation of the BMPR 2 (bone morphogenetic protein receptor 2) gene. It seems important to compare the idiopathic form of PAH with these familial forms to confirm that the same diagnostic and therapeutic principles can be applied to familial PAH. MATERIAL AND METHODS: The demographic, clinical, haemodynamic and prognostic data from 34 cases of familial PAH were compared with those of 451 cases of idiopathic PAH. The genetic characteristics of the familial forms were also defined. RESULTS: Familial PAH presented at a younger age than idiopathic PH (31 +/- 15 vs. 45 +/- 18 years p=0.002) without any other demographic difference (sex-ratio 2.09/1 et 1.42/1 p=NS). There was no difference in exercises tolerance (6 minute walking test 341 +/- 98 and 289 +/- 135 metres p=NS), in haemodynamic parameters (mean PAP 65 +/- 12 and 62 +/- 15 mmHg, p=NS), or in prognosis, with the exception of an absence of a vasodilator response in the familial group to nitric oxide challenge. We found the BMPR 2 gene mutation to be quantitatively and qualitatively comparable to previously published data. CONCLUSION: The only difference between these two forms of this illness were of a younger age at presentation and an absent vasodilator response in the familial PAH group. We do not propose that familial PAH should be treated any differently from the idiopathic form. Genetic counselling will need to be developed in line with the progress being made in the understanding of this condition.

Adult↗
PubMed2004

[Biomarkers as prognostic factors in pulmonary arterial hypertension. Rationale and study design].

CURRENT SITUATION: Pulmonary arterial hypertension (PAH) is a serious disease. Its prognostic is based on the functional status quantified by the NYHA class and the 6-min walking test, and the hemodynamic data. The algorithms of treatment are solely based on the hemodynamic data and the functional status. The main objective is to test whether basal concentrations of isoprostanes, Big endotheline 1, ADMA, high sensitivity CRP, NT-Pro-BNP and cardiac troponin T are a 3-year prognostic factor in PAH using a combined criterion: death from any cause and pulmonary or cardiopulmonary transplantation. MATERIALS AND METHODS: This is a multicenter, prospective, prognostic, single blinded study (plasma and urinary samples being blinded). The study started in november 2003, running for 2 years, with a 3 year follow-up for each patient. The main inclusion criterion is PAH. The data analysis will use a multivariable Cox model, taking into account the functional and hemodynamic parameters. EXPECTED RESULTS: This study will determine whether any of the biomarkers tested provides additional prognostic information in PAH in addition to the functional and hemodynamic parameters.

Biomarkers↗
PubMed2004

[Choroidal metastases in lung cancer].

INTRODUCTION: Ocular metastases are rare and their diagnosis can be difficult, being dependent on a combination of clinical examination of the eye, ultrasound, angiography and magnetic resonance imaging. CLINICAL CASE: We describe two cases of cases of choroidal metastases in patients with a bronchogenic carcinoma. In both cases the metastases presented at a late stage in the disease and occurred in association with cerebral metastases. One patient had an epidermoid tumour the other a small cell carcinoma. Loss of visual acuity, which was slowly progressive in the first case and abrupt in the second, led to the diagnosis of choroidal metastases. Following radiotherapy in a dose of 30 Gray delivered to the posterior segment of the eye, both patients' visual acuity recovered to near normal within a few weeks. CONCLUSION: If patients with lung cancer develop visual disturbance the possibility of choroidal metastases should be considered. Ocular radiotherapy can often ameliorate disabling visual disturbance, significantly improving quality of life.

Adult↗
PubMed2004

Epigenetic inheritance of fetal genes in allergic asthma.

Asthma has been associated with an exaggerated T-helper type 2 (Th2) over Th1 responses to allergic and nonallergic stimuli, which leads to chronic airway inflammation and airway remodeling. In the present article, we propose that many of the genes involved in IgE synthesis and airways (re)modeling in asthma are persistent or reminiscent fetal genes which may not be silenced during early infancy (or late pregnancy). Genes of the embryologic differentiation of ectodermic and endodermic tissues may explain some of the patterns of airway remodeling in asthma. In utero programming leads to gene expression, the persistence of which may be associated with epigenetic inheritance phenomena induced by nonspecific environmental factors. Clear delineation of these issues may yield new information on the mechanisms of asthma and new targets for therapeutic intervention and primary prevention.

Asthma↗
PubMed2004

Control and exacerbation of asthma: a survey of more than 3000 French physicians.

BACKGROUND: Asthma control and prevention of exacerbations are primary objectives for asthma care. However there is a lack of universal definition of these notions which may therefore have a different meaning according to the physician's practice. METHODS: In the present survey, 1805 general practitioners, 551 pulmonologists, 176 allergologists and 470 resuscitation/emergency care physicians were randomly selected in fall 2001 and asked to answer one question on asthma control and three questions on asthma exacerbation. RESULTS: Regarding asthma control, the presence of minimum symptoms was the primary criterion for asthma specialists (pulmonologists and allergologists), while a normal respiratory function was first considered by nonspecialist physicians (general practitioners and emergency care physicians). The first criterion of mild exacerbation for asthma specialists was the occurrence during at least 2 days of an increase in the frequency of dyspnoea and/or the use of short-acting bronchodilators. For nonspecialist physicians, dyspnoea affecting daily activities and/or sleeping was the preferred notion. Hospitalization was unanimously recognized as the first criterion for severe exacerbations. A decrease in peak expiratory flow of more than 30% below the baseline value on two consecutive days and an episode requiring systemic corticosteroids were the next criteria. CONCLUSIONS: This survey emphasizes the complexity of the notions of asthma control and exacerbation and provides novel informations to orient continuing education programmes.

Asthma↗
PubMed2004

Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with concomitant allergic asthma and persistent allergic rhinitis: SOLAR.

BACKGROUND: Anti-IgE therapy could be particularly beneficial for patients with concomitant disease as it targets a common factor in both diseases. The aim of this study was to evaluate the efficacy and safety of omalizumab in patients with concomitant moderate-to-severe asthma and persistent allergic rhinitis. METHODS: This multicentre, randomized, double-blind, parallel-group, placebo-controlled trial evaluated the safety and efficacy of omalizumab. A total of 405 patients (12-74 years) with a stable treatment (>/= 400 microg budesonide Turbuhaler) and >/= 2 unscheduled medical visits for asthma during the past year or >/= 3 during the past 2 years were enrolled. Patients received omalizumab (>/= 0.016 mg/kg/IgE [IU/ml] per 4 weeks) or placebo for 28 weeks. RESULTS: Fewer patients treated with omalizumab experienced asthma exacerbations (20.6%) than placebo-treated patients (30.1%), P = 0.02. A clinically significant (>/= 1.0 point) improvement in both Asthma Quality of Life Questionnaire and Rhinitis Quality of Life Questionnaire occurred in 57.7% of omalizumab patients compared with 40.6% of placebo patients (P < 0.001). Omalizumab reduced Wasserfallen symptom scores for asthma (P = 0.023), rhinitis (P < 0.001) and the composite asthma/rhinitis scores (P < 0.001) compared with placebo. Serious adverse events were observed in 1.4% of omalizumab-treated patients and 1.5% of placebo-treated patients. CONCLUSION: Omalizumab is well tolerated and effective in preventing asthma exacerbations and improving quality of life in patients with concomitant asthma and persistent allergic rhinitis.

Adolescent↗
PubMed2004

Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2.

The efficacy and safety of combining bosentan, an orally active dual endothelin receptor antagonist and epoprostenol, a continuously infused prostaglandin, in the treatment of pulmonary arterial hypertension (PAH) was investigated. In this double-blind, placebo-controlled prospective study, 33 patients with PAH started epoprostenol treatment (2 ng.kg(-1)min(-1) starting dose, up to 14+/-2 ng.kg(-1)min(-1) at week 16) and were randomised for 16 weeks in a 2:1 ratio to bosentan (62.5 mg b.i.d for 4 weeks then 125 mg b.i.d) or placebo. Haemodynamics, exercise capacity and functional class improved in both groups at week 16. In the combination treatment group, there was a trend for a greater (although nonsignificant) improvement in all measured haemodynamic parameters. There were four withdrawals in the bosentan/epoprostenol group (two deaths due to cardiopulmonary failure, one clinical worsening, and one adverse event) and one withdrawal in the placebo/epoprostenol group (adverse event). This study showed a trend but no statistical significance towards haemodynamics or clinical improvement due to the combination of bosentan and epoprostenol therapy in patients with pulmonary arterial hypertension. Several cases of early and late major complications were reported. Additional information is needed to evaluate the risk/benefit ratio of combined bosentan-epoprostenol therapy in pulmonary arterial hypertension.

Antihypertensive Agents↗
PubMed2004

Chronic thromboembolic pulmonary hypertension.

Pulmonary arterial hypertension is a severe disease that has been ignored for a long time. However, over the past 20 yrs chest physicians, cardiologists and thoracic surgeons have shown increasing interest in this disease because of the development of new therapies, that have improved both the outcome and quality of life of patients, including pulmonary transplantation and prostacyclin therapy. Chronic thromboembolic pulmonary arterial hypertension (CTEPH) can be cured surgically through a complex surgical procedure: the pulmonary thromboendarterectomy. Pulmonary thromboendarterectomy is performed under hypothermia and total circulatory arrest. Due to clinically evident acute-pulmonary embolism episodes being absent in > 50% of patients, the diagnosis of CTEPH can be difficult. Lung scintiscan showing segmental mismatched perfusion defects is the best diagnostic tool to detect CTEPH. Pulmonary angiography confirms the diagnosis and determines the feasibility of endarterectomy according to the location of the disease, proximal versus distal. The technique of angiography must be perfect with the whole arterial tree captured on the same picture for each lung. The lesions must start at the level of the pulmonary artery trunk, or at the level of the lobar arteries, in order to find a plan for the endarterectomy. When the haemodynamic gravity corresponds to the degree of obliteration, pulmonary thromboendarterectomy can be performed with minimal perioperative mortality, providing definitive, excellent functional results in almost all cases.

Chronic Disease↗
PubMed2004

Prevention of hepatopulmonary syndrome and hyperdynamic state by pentoxifylline in cirrhotic rats.

Inhibition of tumour necrosis factor-alpha (TNF-alpha), levels of which are increased in the blood of cirrhotic rats, prevents hyperdynamic circulatory state, mainly by decreasing the vascular overproduction of nitric oxide. Hepatopulmonary syndrome, which is characterised by intrapulmonary vascular dilatation and increased alveolar to arterial oxygen tension difference (PA-a,O2), is mainly related to pulmonary over-production of NO by macrophages accumulated in lung vessels. Since TNF-alpha is a potent activator of macrophagic inducible nitric oxide synthase (NOS), the aim of this study was to investigate whether TNF-alpha inhibition prevented hepatopulmonary syndrome and hyperdynamic circulatory state in rats with cirrhosis. TNF-alpha was inhibited by 5 weeks of pentoxifylline (10 mg x kg body weigh(-1) x day(-1)) in rats with cirrhosis induced by common bile duct ligation. Cardiac output, pulmonary and systemic vascular resistance, PA-a,O2 and cerebral uptake of intravenous technetium-99m-labelled albumin macroaggregates (which reflects intrapulmonary vascular dilatation) were similar in sham- and pentoxifylline-treated cirrhotic rats. Blood TNF-alpha concentrations and pulmonary intravascular macrophage sequestration, as assessed by morphometric analysis and radioactive colloid uptake, were decreased with pentoxifylline. Pentoxifylline also prevented increases in aorta and lung NOS activities and inducible NOS expression. Thus pentoxifylline prevents development of hyperdynamic circulatory state and hepatopulmonary syndrome, probably by inhibiting the effects of tumour necrosis factor-alpha on vascular nitric oxide synthase and intravascular macrophages. These results support an important role for tumour necrosis factor-alpha in the genesis of hepatopulmonary syndrome.

Animals↗