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Thierry Chinet

Publications and source records attributed to Thierry Chinet.

11 recordsLinked to original sources
PubMed2007

Pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: a series of 126 patients.

Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder characterized by epistaxis, telangiectasia, and visceral vascular manifestations. Infectious and ischemic central nervous system (CNS) manifestations due to embolism through pulmonary arteriovenous malformations (PAVMs) represent the main causes of morbidity. To improve the phenotypic characterization of HHT with PAVM, we conducted a retrospective multicenter study of patients with HHT and at least 1 PAVM detected by chest computed tomography (CT) and/or pulmonary angiography, with particular attention to CNS and infectious manifestations. The study included 126 patients (47 men, 79 women), with a mean age of 43.1 +/- 17.4 years; 45 patients had a mutation of the ENG gene and 16 had a mutation of ACVRL1. PAVMs were diagnosed as a result of systematic screening procedures (29%), incidental imaging findings (15%), dyspnea (22%), or CNS symptoms (13%). The PAVMs were diagnosed at a mean age of 43 +/- 17 years, with a linear distribution of diagnosis between 20 and 75 years. Dyspnea on exertion was present in 56% of patients. Four patients had a hemothorax, including 1 during pregnancy. Fifty-three CNS events directly related to HHT (excluding migraine) were observed in 35% of patients: cerebral abscess (19.0%), ischemic cerebral stroke (9.5%), transient cerebral ischemic attack (6.3%), and cerebral hemorrhage (2.4%). The median age of onset was 33 years for cerebral abscesses (range, 11-66 yr), and 53.5 years for ischemic cerebral events (range, 2-72 yr). Migraine was reported in 16% of patients. The diagnoses of PAVM and HHT were made at the time of the cerebral abscess in 13 cases (54%). Forty-three percent of patients were hypoxemic at rest. Contrast echocardiography showed intrapulmonary right-to-left shunting in 87% of tested patients. PAVMs were seen on chest radiograph in 54% of patients, and on the CT scan in all patients. One hundred five patients (83%) underwent treatment of the PAVM, by percutaneous embolization (71%) and/or by surgical resection (23%). A high frequency of CNS and infectious complications was observed in this large series of patients with HHT-related PAVM. Physicians may not be sufficiently aware of the clinical manifestations of this orphan disorder. Patients diagnosed with HHT should be informed by physicians and patient associations of the risk of PAVM-related complications, and systematic screening for PAVM should be proposed, regardless of a patient's symptoms, familial history, or genetic considerations.

Abscess↗
PubMed2006

Ion and fluid transport properties of small airways in cystic fibrosis.

RATIONALE: Small airways constitute a major site of pathology in cystic fibrosis (CF) and provide most of the surface area of the conducting airways of the lung. Little is known, however, about the impact of CF on ion and fluid transport in small (bronchiolar) airways. OBJECTIVES: To describe the ion and fluid transport properties of CF bronchiolar epithelium. METHODS: Primary cultures of human bronchial and bronchiolar (non-CF and CF) epithelial cells were obtained. The bioelectric properties were studied in Ussing chambers and the airway surface liquid (ASL) height was measured with confocal microscopy. MAIN RESULTS: Primary cultures of DeltaF508 CF bronchiolar epithelial cells displayed higher transepithelial resistance than non-CF cultures, whereas baseline short circuit current and amiloride-inhibitable short circuit current were similar in both preparations. The ASL height was significantly smaller in CF compared with non-CF preparations. In the presence of amiloride, addition of forskolin increased short circuit current in non-CF but not in CF bronchiolar cultures, and the ATP-induced increase in short circuit current was lower in CF than in non-CF cultures. Non-CF bronchiolar preparations displayed larger short circuit current and fluid secretion in responses to forskolin than non-CF bronchial preparations, suggesting that CFTR-dependent Cl(-) transport may play a more important role in the regulation of fluid transport in small airways than in large airways. CONCLUSION: In CF small airways, defective Cl(-) secretion combined with unregulated (persistent) Na(+) absorption results in ASLdepletion.

Body Water↗
PubMed2004

Nociceptin inhibits vanilloid TRPV-1-mediated neurosensitization induced by fenoterol in human isolated bronchi.

Chronic exposure to beta(2)-adrenoceptor agonists, especially fenoterol, has been shown to increase smooth muscle contraction to endothelin-1 in human bronchi partly through tachykinin-mediated pathways. The purpose of this work was to further investigate the role of sensory nerves in fenoterol-induced sensitization of human airways and the effect of nociceptin, a nociceptin/orphanin FQ (NOP) receptor agonist, on the increase in contraction after fenoterol exposure. Human bronchi from 62 patients were sensitized to endothelin-1 by prolonged incubation with fenoterol (0.1 microM, 15 h). The sensitizing effect of fenoterol was inhibited by high concentration of capsaicin (10 microM, 30 min before fenoterol sensitization), which induces depletion of mediators from sensory nerves, or co-incubation of fenoterol and capsazepine (1 microM), a vanilloid TRPV-1 receptor antagonist. Moreover, short pretreatment of bronchi with capsaicin (10 microM) or capsazepine (1 microM) after sensitization by fenoterol decreased the rise in smooth muscle contraction to endothelin-1. Nociceptin (1 microM) also inhibited the increased contraction in fenoterol-sensitized bronchi. Tertiapin (10 microM), an inhibitor of the inward-rectifier K(+) channels, but not naloxone (0.1 microM), a DOP/KOP/MOP receptor antagonist, prevented the inhibitory effect of nociceptin. In conclusion, fenoterol induces sensitization of human isolated bronchi to endothelin-1 in part through the stimulation of the vanilloid TRPV-1 receptor on tachykininergic sensory nerves. Nociceptin inhibits airway hyperresponsiveness via NOP receptor activation. This effect involves inward-rectifier K(+) channels.

Adrenergic beta-Agonists↗
PubMed2004

Isolation and air-liquid interface culture of human large airway and bronchiolar epithelial cells.

This article describes the techniques of isolation and culture of human airway epithelial cells from large airways and from distal airways. Both cell types are obtained from lung pieces collected during surgery. The protocols start with an initial step of washing and dissection of the lung pieces to separate large airways or distal airways from the surrounding parenchyma. The second step is enzymatic isolation of epithelial cells from the dissected large or distal airways. Cells are then collected by centrifugation and then seeded onto collagen surfaces. Epithelial cells can be grown at an air-liquid interface and usually form a confluent and functional epithelial layer within days.

Cell Culture Techniques↗
PubMed2003

Effects of endothelin-1 on epithelial ion transport in human airways.

Endothelin-1 (ET-1) exerts many biological effects in airways, including bronchoconstriction, airway mucus secretion, cell proliferation, and inflammation. We investigated the effect of ET-1 on Na absorption and Cl secretion in human bronchial epithelial cells. Addition of 10(-7) M ET-1 had no effect on the inhibition of the short circuit current (Isc) induced by amiloride, a Na channel blocker. Addition of 10(-7) M ET-1 to the apical bath in the presence of amiloride increased Isc in cultured human bronchial epithelial cells studied in Ussing chambers. No effect was observed when ET-1 was added to basolateral bath, indicating that the involved ET-1 receptors are likely present only in the apical membrane of the cells. Use of Cl-free solutions and bumetanide reduced the ET-1-induced increases in Isc, indicating that ET-1 stimulates Cl secretion. The ET-1-induced increase in Isc was prevented by exposure to the ETB receptor antagonist BQ-788 but not to the ETA receptor antagonist BQ-123. ET-1 did not raise intracellular Ca levels, but increased the intracellular concentration of cAMP. These findings indicate that ET-1 is a Cl secretagogue in human airways and acts presumably through apically located ETB receptors and activation of the cAMP pathway.

Amiloride↗
PubMed2003

[Genetics and cellular biology of cystic fibrosis].

Cystic fibrosis (CF) is the most frequent lethal genetic disease in caucasians. It behaves as an autosomal recessive disease. The CF gene encodes a protein named CFTR (for "Cystic Fibrosis Transmembrane conductance Regulator") which exerts multiple functions. One of the most important function is the regulation of sodium and chlorine transport in epithelia. Defects in this control induce dehydration of airway surface liquid, which results in recurring bronchopulmonary infections, and increases in Na and Cl concentrations in sweat, which constitutes the rationale for the sweat test. CFTR also participates in the regulation of inflammation. Over one thousand mutations in the CFTR gene have been reported, the most frequent of which is the absence of the phenylalanine residue at amino acid position 508 (delta F508).

Blood Proteins↗
PubMed2002

In vitro sensitization of human bronchus by beta2-adrenergic agonists.

Incubation of human distal bronchi from 48 patients for 15 h with 10(-7) M fenoterol induced sensitization characterized by an increase in maximal contraction to endothelin-1 (ET-1) and acetylcholine (ACh). Incubation of human bronchi with 10(-6), 3 x 10(-6), and 10(-5) M forskolin (an adenyl cyclase activator) reproduced sensitization to ET-1 and ACh. The sensitizing effect of fenoterol was inhibited by coincubation with gliotoxine (a nuclear factor-kappaB inhibitor), dexamethasone, indomethacin (a cyclooxygenase inhibitor), GR-32191 (a TP prostanoid receptor antagonist), MK-476 (a cysteinyl leukotriene type 1 receptor antagonist), SR-140333 + SR-48968 + SR-142801 (neurokinin types 1, 2, and 3 tachykinin receptor antagonists) with or without HOE-140 (a bradykinin B(2) receptor antagonist), SB-203580 (an inhibitor of the 38-kDa mitogen-activated protein kinase, p38(MAPK)), or calphostin C (a protein kinase C blocker). Our results suggest that chronic exposure to fenoterol induces proinflammatory effects mediated by nuclear factor-kappaB and pathways involving leukotrienes, prostanoids, bradykinin, tachykinins, protein kinase C, and p38(MAPK), leading to the regulation of smooth muscle contraction to ET-1 and ACh.

Acetylcholine↗
PubMed2002

Characterization of ion and fluid transport in human bronchioles.

The regulation of the volume and composition of airway surface liquid is achieved through epithelial ion transport processes. In humans, these processes have been characterized in proximal but not distal airways. Segments of human bronchioles were dissected from surgically removed lung pieces. The transmural potential difference of microperfused bronchioles was inhibited by luminal exposure to amiloride and increased when exposed to the Cl secretagogues forskolin and ATP in the presence of amiloride. Human bronchiolar epithelial cells were cultured on permeable supports and studied in Ussing chambers. They generated a short circuit current (Isc) that decreased in response to amiloride and increased in response to forskolin and to ATP in the presence of amiloride. In low-Cl Kreb's Ringer bicarbonate, the baseline Isc and amiloride-induced decrease in Isc were not different, whereas the forskolin- and ATP-induced increases in Isc were smaller. Fluid transport measurement in excised bronchioles revealed a basal absorptive flow that was reduced by amiloride, whereas forskolin and ATP combined induced a secretory flow in the presence of amiloride. We conclude that human bronchioles actively absorb Na and fluid in unstimulated conditions and are capable of active Cl and fluid secretion when exposed to forskolin and to ATP.

Adenosine Triphosphate↗
PubMedDate not supplied

Reperfusion of complex pulmonary arteriovenous malformations after embolization: report of three cases.

The purpose of this report is to discuss the different mechanisms of reperfusion of pulmonary arteriovenous malformations (PAVMs) after embolization. Transcatheter embolotherapy is currently the first-line treatment of PAVMs to prevent neurologic complications or pulmonary hemorrhage. Initial good results can be expected but we report three cases of reperfusion of complex large PAVMs after coil embolization. After adequate embolization, reperfusion of PAVMs may occur by several mechanisms including recanalization of embolized arteries, recruitment of normal arterial branches, growth or enlargement and development of a systemic arterial supply.

Adolescent↗
PubMedDate not supplied

Pulmonary artery interventions: an overview.

Interventional radiologists should be familiar with minimally invasive procedures used to treat various abnormalities of the pulmonary arteries. These well-established techniques, which obviate open surgery, are safe and effective when performed by an experienced interventionalist. Catheter-based thrombolysis with intrapulmonary arterial infusion of thrombolytic drugs, percutaneous thrombectomy, or embolus fragmentation can be performed in patients with life-threatening pulmonary embolism. Pulmonary artery stenoses, mainly encountered in patients with pulmonary vasculitis (as in Behçet disease or Takayasu arteritis), may be treated with balloon angioplasty and stent placement. Transcatheter embolization of pulmonary arteriovenous malformation is the standard treatment for hereditary hemorrhagic telangiectasia and is a very effective alternative to surgery to correct an aneurysm or pseudoaneurysm. In cases of hemoptysis that originates in the pulmonary artery, early diagnosis is mandatory for treatment with embolization. Percutaneous retrieval of foreign bodies from the heart or the pulmonary arteries and endovascular biopsy should also be part of the armamentarium of interventional radiologists.

Adult↗