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Henri Plauchu - One of the best experts on this subject based on the ideXlab platform.
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Hereditary Hemorrhagic Telangiectasia from molecular biology to patient care
Journal of Thrombosis and Haemostasis, 2010Co-Authors: Sophie Dupuisgirod, Sabine Bailly, Henri PlauchuAbstract:Summary. Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by severe and recurrent nosebleeds, mucocutaneous telangiectases, and, in some cases, life-threatening visceral arteriovenous malformations of various types, including pulmonary, hepatic, cerebral, and spinal. Gastrointestinal telangiectases are frequent and may cause severe bleeding. HHT type 1 results from mutations in ENG on chromosome 9 (coding for endoglin), and HHT type 2 results from mutations in ACVRL1 on chromosome 12 (coding for activin receptorlike kinase 1). Mutations of either of these two genes account for most clinical cases. In addition, mutations in MADH4 (encoding SMAD4), which cause a juvenile polyposis/HHT overlap syndrome, have been described, and recently, an HHT3 locus on chromosome 5 (5q31.3–5q32) has been reported. The mutated genes in HHT encode proteins that modulate transforming growth factor-b superfamily signaling in vascular endothelial cells. Management of patients has changed considerably in the last 20 years, in terms of both treatment and the prevention of complications. The goal of this review was to describe the underlying molecular and cellular physiopathology, explore clinical and genetic diagnostic strategies for HHT, and present clinical management recommendations in order to treat symptomatic disease and to screen for vascular malformations.
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Liver involvement in Hereditary Hemorrhagic Telangiectasia: Consensus recommendations
Liver International, 2006Co-Authors: Elisabetta Buscarini, Jean Cristophe Saurin, Guadalupe Garcia-tsao, Robert I. White, Franklin Miller, Jean-pierre Pelage, Gaetan Lesca, Henri Plauchu, Carlo Sabba, Marie Jeanne MarionAbstract:STUDY PURPOSE: To formulate recommendations about clinical management of liver involvement in Hereditary Hemorrhagic Telangiectasia (HHT), using a formal consensus development process. CONSENSUS PROCESS: A nominal group technique was used. A list of main clinical, diagnostic and therapeutic issues about liver involvement in HHT was generated by the organizing committee. Panel members then scored their agreement with each statement; the median score, and standard deviation for each statement were determined for each of the three successive panel rounds. These consensus statements formed the basis for recommendations graded with the strength and quality of supporting evidence. RECOMMENDATION STATEMENTS: Doppler US is sufficiently accurate and suitable for first-line imaging of the liver in the general HHT population. Liver biopsy in any patient with proven or suspected HHT should be avoided. Liver involvement in HHT is generally asymptomatic; in the minority of patients where it is symptomatic, morbidity and mortality can be substantial. The prevalence of focal nodular hyperplasia is much higher in patients with liver involvement by HHT than in the general population. Invasive therapies for liver involvement by HHT (namely liver transplantation) should be considered only in patients who have failed to respond to intensive medical therapy.
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Pulmonary arteriovenous malformations in patients with Hereditary Hemorrhagic Telangiectasia
American Journal of Respiratory and Critical Care Medicine, 2004Co-Authors: Vincent Cottin, Henri Plauchu, Jean-yves Bayle, Martine Barthelet, Didier Revel, Jeanfrancois CordierAbstract:Pulmonary arteriovenous malformations (PAVMs) associated with Hereditary Hemorrhagic Telangiectasia may cause severe cerebral complications that may be prevented by embolization therapy. We retrospectively compared the diagnostic value of noninvasive tests for the screening of treatable (amenable to embolization) PAVMs in a series of 105 patients, using chest computerized tomography (CT) and/or pulmonary angiography as a "gold standard." Patients had assessment of dyspnea, chest radiograph, alveolar-arterial PO2 gradient under 100% oxygen (AaPO(2)), contrast echocardiography, and radionuclide perfusion lung scanning. Contrast echocardiography in the supine position was the most sensitive test (93%). The sensitivity of self-reported dyspnea (59%), chest radiograph alone (70%), measurement Of AaPO(2) by the 100% oxygen method (62%), or radionuclide lung scanning (71%), was not suitable for efficient screening. A 100% sensitivity and negative predictive value could be obtained when combining anteroposterior chest radiograph and contrast echocardiography. Our data support a screening algorithm based on the combined use of contrast echocardiography and anteroposterior chest radiograph, followed by chest CT if either test is positive. An alternative is to screen directly by chest CT. However, this algorithm may obviate the need for chest CT in patients without PAVM, who represent a majority of patients with Hereditary Hemorrhagic Telangiectasia.
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Diagnostic criteria for Hereditary Hemorrhagic Telangiectasia (Rendu- Osler-Weber Syndrome)
American Journal of Medical Genetics, 2000Co-Authors: Claire L. Shovlin, Anette Drøhse Kjeldsen, Marie E. Faughnan, Robert H Hyland, Cornelis J J Westermann, Alan E Guttmacher, Elisabetta Buscarini, Henri PlauchuAbstract:Hereditary Hemorrhagic Telangiectasia (HHT) is easily recognized in individuals displaying the classical triad of epistaxis, Telangiectasia, and a suitable family history, but the disease is more difficult to diagnosis in many patients. Serious consequences may result if visceral arteriovenous malformations, particularly in the pulmonary circulation, are unrecognized and left untreated. In spite of the identification of two of the disease-causing genes (endoglin and ALK-1), only a clinical diagnosis of HHT can be provided for the majority of individuals. On behalf of the Scientific Advisory Board of the HHT Foundation International, Inc., we present consensus clinical diagnostic criteria. The four criteria (epistaxes, Telangiectasia, visceral lesions and an appropriate family history) are carefully delineated. The HHT diagnosis is definite if three criteria are present. A diagnosis of HHT cannot be established in patients with only two criteria, but should be recorded as possible or suspected to maintain a high index of clinical suspicion. If fewer than two criteria are present, HHT is unlikely, although children of affected individuals should be considered at risk in view of age-related penetration in this disorder. These criteria may be refined as molecular diagnostic tests become available in the next few years.
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liver transplantation resolves the hyperdynamic circulation in Hereditary Hemorrhagic Telangiectasia with hepatic involvement
Gastroenterology, 1999Co-Authors: Olivier Boillot, Francesco Bianco, Jeanpaul Viale, Francois Mion, Isabelle Mechet, Danielle Gille, Jacques Delaye, P Paliard, Henri PlauchuAbstract:Abstract Background & Aims: Hepatic involvement in Hereditary Hemorrhagic Telangiectasia is common but often asymptomatic. However, in some cases, the vascular lesions that involve the liver may lead to high-output cardiac failure and pulmonary hypertension that is predominant over hepatobiliary manifestations. Liver transplantation and treatment of these complications are described and discussed in this article. Methods: Three patients with Hereditary Hemorrhagic Telangiectasia and hepatic involvement received transplants. They had pulmonary hypertension and chronic right-sided heart failure caused by disseminated intrahepatic Telangiectasias with shunts between the hepatic artery and hepatic veins or portal vein. Left-to-right intrahepatic shunt output was estimated to range between 51% and 57.5% of cardiac output. Results: Hyperdynamic circulation disappeared after liver transplantation in all patients. Results of computed tomography and right-sided heart catheterization performed 6 months later were normal. Follow-up periods currently are 65, 53, and 29 months, and each patient continues to be asymptomatic. Conclusions: This report suggests that liver transplantation can be considered as an alternative and successful curative treatment that may prevent the irreversible evolution of cardiopulmonary disease. GASTROENTEROLOGY 1999;116:187-192
Robert I. White - One of the best experts on this subject based on the ideXlab platform.
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Liver involvement in Hereditary Hemorrhagic Telangiectasia: CT and clinical findings do not correlate in symptomatic patients.
AJR. American journal of roentgenology, 2006Co-Authors: Jim S Wu, Katherine J. Henderson, Sanjay Saluja, Guadalupe Garcia-tsao, Alice Chong, Robert I. WhiteAbstract:OBJECTIVE: The purpose of our study was to report the multiphasic CT findings in patients with symptomatic liver involvement by Hereditary Hemorrhagic Telangiectasia (HHT) and to correlate the CT findings with the type of clinical presentation.\n\nCONCLUSION: Patients with symptomatic HHT liver disease have diffuse hepatic telangiectases, a dilated common hepatic artery, and a high incidence of biliary abnormalities. Multiphasic CT is useful in diagnosing liver involvement due to HHT; however, no strong correlation was seen between CT findings and the clinical subtype of HHT liver disease.
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Liver involvement in Hereditary Hemorrhagic Telangiectasia: Consensus recommendations
Liver International, 2006Co-Authors: Elisabetta Buscarini, Jean Cristophe Saurin, Guadalupe Garcia-tsao, Robert I. White, Franklin Miller, Jean-pierre Pelage, Gaetan Lesca, Henri Plauchu, Carlo Sabba, Marie Jeanne MarionAbstract:STUDY PURPOSE: To formulate recommendations about clinical management of liver involvement in Hereditary Hemorrhagic Telangiectasia (HHT), using a formal consensus development process. CONSENSUS PROCESS: A nominal group technique was used. A list of main clinical, diagnostic and therapeutic issues about liver involvement in HHT was generated by the organizing committee. Panel members then scored their agreement with each statement; the median score, and standard deviation for each statement were determined for each of the three successive panel rounds. These consensus statements formed the basis for recommendations graded with the strength and quality of supporting evidence. RECOMMENDATION STATEMENTS: Doppler US is sufficiently accurate and suitable for first-line imaging of the liver in the general HHT population. Liver biopsy in any patient with proven or suspected HHT should be avoided. Liver involvement in HHT is generally asymptomatic; in the minority of patients where it is symptomatic, morbidity and mortality can be substantial. The prevalence of focal nodular hyperplasia is much higher in patients with liver involvement by HHT than in the general population. Invasive therapies for liver involvement by HHT (namely liver transplantation) should be considered only in patients who have failed to respond to intensive medical therapy.
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liver disease in patients with Hereditary Hemorrhagic Telangiectasia
The New England Journal of Medicine, 2000Co-Authors: Guadalupe Garciatsao, Joshua R Korzenik, Lawrence Young, Katharine J Henderson, Dhanpat Jain, Boyd Byrd, Jeffrey Pollak, Robert I. WhiteAbstract:Background Hereditary Hemorrhagic Telangiectasia, or Rendu–Osler–Weber disease, is an autosomal dominant disorder characterized by angiodysplastic lesions (telangiectases and arteriovenous malformations) that affect many organs. Liver involvement in patients with this disease has not been fully characterized. Methods We studied the clinical findings and results of hemodynamic, angiographic, and imaging studies in 19 patients with Hereditary Hemorrhagic Telangiectasia and symptomatic liver involvement. Results We evaluated 14 women and 5 men who ranged in age from 34 to 74 years. All but one of the patients had a hyperdynamic circulation (cardiac index, 4.2 to 7.3 liters per minute per square meter of body-surface area). In eight patients, the clinical findings were consistent with the presence of high-output heart failure. The cardiac index and pulmonary-capillary wedge pressure were elevated in the six patients in whom these measurements were performed. After a median period of 24 months, the condition o...
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Hereditary Hemorrhagic Telangiectasia
The New England Journal of Medicine, 1995Co-Authors: Alan E Guttmacher, Douglas A Marchuk, Robert I. WhiteAbstract:Identified nearly a century ago, Hereditary Hemorrhagic Telangiectasia, or Rendu–Osler–Weber syndrome, has long been viewed as a rare condition producing minor discomfort for affected persons. However, this disorder is now considered to be more common than previously thought,1–5 and the associated brain and pulmonary lesions are sources of substantial morbidity and mortality.3,6–8 Wider recognition of the condition and awareness of its sequelae can help avoid the considerable risks associated with its mismanagement. Advances in molecular genetics have demonstrated that Hereditary Hemorrhagic Telangiectasia is actually a group of autosomal dominant disorders.9–13 The recent identification of the gene . . .
Jeanfrancois Cordier - One of the best experts on this subject based on the ideXlab platform.
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pulmonary vascular manifestations of Hereditary Hemorrhagic Telangiectasia rendu osler disease
Respiration, 2007Co-Authors: Vincent Cottin, Gaetan Lesca, Sophie Dupuisgirod, Jeanfrancois CordierAbstract:Hereditary Hemorrhagic Telangiectasia (HHT) or Rendu-Osler-Weber disease is a genetic disorder with autosomal dominance and variable penetrance, characterized by epistaxis, Telangiectasia and visceral
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Pulmonary arteriovenous malformations in patients with Hereditary Hemorrhagic Telangiectasia
American Journal of Respiratory and Critical Care Medicine, 2004Co-Authors: Vincent Cottin, Henri Plauchu, Jean-yves Bayle, Martine Barthelet, Didier Revel, Jeanfrancois CordierAbstract:Pulmonary arteriovenous malformations (PAVMs) associated with Hereditary Hemorrhagic Telangiectasia may cause severe cerebral complications that may be prevented by embolization therapy. We retrospectively compared the diagnostic value of noninvasive tests for the screening of treatable (amenable to embolization) PAVMs in a series of 105 patients, using chest computerized tomography (CT) and/or pulmonary angiography as a "gold standard." Patients had assessment of dyspnea, chest radiograph, alveolar-arterial PO2 gradient under 100% oxygen (AaPO(2)), contrast echocardiography, and radionuclide perfusion lung scanning. Contrast echocardiography in the supine position was the most sensitive test (93%). The sensitivity of self-reported dyspnea (59%), chest radiograph alone (70%), measurement Of AaPO(2) by the 100% oxygen method (62%), or radionuclide lung scanning (71%), was not suitable for efficient screening. A 100% sensitivity and negative predictive value could be obtained when combining anteroposterior chest radiograph and contrast echocardiography. Our data support a screening algorithm based on the combined use of contrast echocardiography and anteroposterior chest radiograph, followed by chest CT if either test is positive. An alternative is to screen directly by chest CT. However, this algorithm may obviate the need for chest CT in patients without PAVM, who represent a majority of patients with Hereditary Hemorrhagic Telangiectasia.
Sophie Dupuis-girod - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of TIMOLOL nasal spray as a treatment for epistaxis in Hereditary Hemorrhagic Telangiectasia. A double-blind, randomized, placebo-controlled trial
Scientific Reports, 2019Co-Authors: Sophie Dupuis-girod, Vincent Pitiot, Cyrille Bergerot, Anne-emmanuelle Fargeton, Marjolaine Beaudoin, Bettina Colombet, Valentine Bréant, Pierre Philouze, Evelyne Decullier, Frederic FaureAbstract:Hereditary Hemorrhagic Telangiectasia is a rare vascular genetic disease. Epistaxis is the most frequent and disabling manifestation, and timolol appears to be a new therapeutic option as non-selective beta-blockers have in vitro and in vivo anti-angiogenic properties. Our main objective was to evaluate the efficacy of TIMOLOL nasal spray as a treatment for epistaxis in Hereditary Hemorrhagic Telangiectasia. This study is a single-center, randomized, phase 2, double-blind placebo-controlled study with an allocation ratio of 1:1. It was proposed to patients with Hereditary Hemorrhagic Telangiectasia monitored at the French Reference Center, and we included patients aged over 18 years, diagnosed with Hereditary Hemorrhagic Telangiectasia and epistaxis. The treatment was self-administered by the patient with a posology of one spray (50 µL) of timolol 0.5% or placebo in each nostril twice a day for 28 consecutive days. The primary efficacy endpoint was mean monthly epistaxis duration, assessed by monitoring epistaxis grids. A total of 58 patients were randomized and treated. The baseline characteristics were similar in the 2 groups. Mean monthly epistaxis duration measured at 3 months was not significantly different in the 26 patients receiving the drug in comparison with the placebo group (p = 0.54). Toxicity was low and no severe adverse events were reported. One limitation is that we included all HHT patients with nosebleeds and did not take into account history of nasal surgery or nasal crusts. Timolol, administered by nasal spray at a dose of 0.25 mg in each nostril twice a day for 28 consecutive days, did not improve epistaxis in patients with Hereditary Hemorrhagic Telangiectasia at 4 months after the beginning of the treatment.
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The Lung in Hereditary Hemorrhagic Telangiectasia.
Respiration; international review of thoracic diseases, 2017Co-Authors: Sophie Dupuis-girod, Vincent Cottin, Claire L. ShovlinAbstract:Hereditary Hemorrhagic Telangiectasia (HHT) is a dominantly inherited genetic vascular disorder with an estimated prevalence of 1 in 6,000, characterized by recurrent epistaxis, cutaneous Telangiectasia, and arteriovenous malformations (AVMs) that affect many organs including the lungs, gastrointestinal tract, liver, and brain. Its diagnosis is based on the Curaçao criteria, and is considered definite if at least 3 of the 4 following criteria are fulfilled: (1) spontaneous and recurrent epistaxis, (2) Telangiectasia, (3) a family history, and (4) pulmonary, liver, cerebral, spinal, or gastrointestinal AVMs. The focus of this review is on delineating how HHT affects the lung.
Frederic Faure - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of TIMOLOL nasal spray as a treatment for epistaxis in Hereditary Hemorrhagic Telangiectasia. A double-blind, randomized, placebo-controlled trial
Scientific Reports, 2019Co-Authors: Sophie Dupuis-girod, Vincent Pitiot, Cyrille Bergerot, Anne-emmanuelle Fargeton, Marjolaine Beaudoin, Bettina Colombet, Valentine Bréant, Pierre Philouze, Evelyne Decullier, Frederic FaureAbstract:Hereditary Hemorrhagic Telangiectasia is a rare vascular genetic disease. Epistaxis is the most frequent and disabling manifestation, and timolol appears to be a new therapeutic option as non-selective beta-blockers have in vitro and in vivo anti-angiogenic properties. Our main objective was to evaluate the efficacy of TIMOLOL nasal spray as a treatment for epistaxis in Hereditary Hemorrhagic Telangiectasia. This study is a single-center, randomized, phase 2, double-blind placebo-controlled study with an allocation ratio of 1:1. It was proposed to patients with Hereditary Hemorrhagic Telangiectasia monitored at the French Reference Center, and we included patients aged over 18 years, diagnosed with Hereditary Hemorrhagic Telangiectasia and epistaxis. The treatment was self-administered by the patient with a posology of one spray (50 µL) of timolol 0.5% or placebo in each nostril twice a day for 28 consecutive days. The primary efficacy endpoint was mean monthly epistaxis duration, assessed by monitoring epistaxis grids. A total of 58 patients were randomized and treated. The baseline characteristics were similar in the 2 groups. Mean monthly epistaxis duration measured at 3 months was not significantly different in the 26 patients receiving the drug in comparison with the placebo group (p = 0.54). Toxicity was low and no severe adverse events were reported. One limitation is that we included all HHT patients with nosebleeds and did not take into account history of nasal surgery or nasal crusts. Timolol, administered by nasal spray at a dose of 0.25 mg in each nostril twice a day for 28 consecutive days, did not improve epistaxis in patients with Hereditary Hemorrhagic Telangiectasia at 4 months after the beginning of the treatment.