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https://www.readbyqxmd.com/read/29330194/telotristat-ethyl-in-carcinoid-syndrome-safety-and-efficacy-in-the-telecast-phase-3-trial
#1
Marianne E Pavel, David J Gross, Marta Benavent, Petros Perros, Raj Srirajaskanthan, Richard R P Warner, Matthew H Kulke, Lowell Anthony, Pamela Kunz, Dieter Hörsch, Martin O Weickert, Pablo Lapuerta, Wenjun Jiang, Kenneth Kassler-Taub, Suman Wason, Rosanna Fleming, Douglas Fleming, Rocio García-Carbonero
Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the Phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a Phase 3 companion study, assessed safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea, or elevated urinary 5-hydroxyindoleacetic acid [u5-HIAA]) with <4 BMs/day on SSAs (or ≥1 symptom or ≥4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE)...
January 12, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29206084/identity-crisis-in-pulmonary-arterial-hypertension
#2
G Ruffenach, S Bonnet, S Rousseaux, S Khochbin, S Provencher, F Perros
Pulmonary arterial hypertension (PAH) shares many hallmarks with cancer. Cancer cells acquire their hallmarks by a pathological Darwinian evolution process built on the so-called cancer cell "identity crisis." Here we demonstrate that PAH shares the most striking features of the cancer identity crisis: the ectopic expression of normally silent tissue-specific genes.
January 2018: Pulmonary Circulation
https://www.readbyqxmd.com/read/29108819/pulmonary-vascular-remodeling-patterns-and-expression-of-general-control-nonderepressible-2-gcn2-in-pulmonary-veno-occlusive-disease
#3
Esther J Nossent, Fabrice Antigny, David Montani, Harm Jan Bogaard, Maria Rosa Ghigna, Mélanie Lambert, Vincent Thomas de Montpréville, Barbara Girerd, Xavier Jaïs, Laurent Savale, Olaf Mercier, Elie Fadel, Florent Soubrier, Olivier Sitbon, Gérald Simonneau, Anton Vonk Noordegraaf, Marc Humbert, Frédéric Perros, Peter Dorfmüller
BACKGROUND: Heritable pulmonary veno-occlusive disease (PVOD) is linked to mutations in the eukaryotic initiation factor 2 alpha kinase 4 (EIF2AK4) gene, leading to a loss of general control nonderepressible 2 (GCN2). The role of GCN2 expression in pulmonary vascular remodeling remains obscure. We sought to identify specific histologic and biologic features in heritable PVOD. METHODS: Clinical data and lung histology of 24 PVOD patients (12 EIF2AK4 mutation carriers, 12 non-carriers) were submitted to systematic histologic analysis and semiautomated morphometry...
October 4, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28931663/targeting-fatty-acid-amide-hydrolase-as-a-therapeutic-strategy-for-antitussive-therapy
#4
Michael A Wortley, John J Adcock, Eric D Dubuis, Sarah A Maher, Sara J Bonvini, Isabelle Delescluse, Ross Kinloch, Gordon McMurray, Christelle Perros-Huguet, Marianthi Papakosta, Mark A Birrell, Maria G Belvisi
Cough is the most common reason to visit a primary care physician, yet it remains an unmet medical need. Fatty acid amide hydrolase (FAAH) is an enzyme that breaks down endocannabinoids, and inhibition of FAAH produces analgesic and anti-inflammatory effects. Cannabinoids inhibit vagal sensory nerve activation and the cough reflex, so it was hypothesised that FAAH inhibition would produce antitussive activity via elevation of endocannabinoids.Primary vagal ganglia neurons, tissue bioassay, in vivo electrophysiology and a conscious guinea pig cough model were utilised to investigate a role for fatty acid amides in modulating sensory nerve activation in vagal afferents...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28900641/core-shell-colloidal-particles-with-dynamically-tunable-scattering-properties
#5
Guangnan Meng, Vinothan N Manoharan, Adeline Perro
We design polystyrene-poly(N'-isopropylacrylamide-co-acrylic acid) core-shell particles that exhibit dynamically tunable scattering. We show that under normal solvent conditions the shell is nearly index-matched to pure water, and the particle scattering is dominated by Rayleigh scattering from the core. As the temperature or salt concentration increases, both the scattering cross-section and the forward scattering increase, characteristic of Mie scatterers. The magnitude of the change in the scattering cross-section and scattering anisotropy can be controlled through the solvent conditions and the size of the core...
September 27, 2017: Soft Matter
https://www.readbyqxmd.com/read/28881789/pulmonary-endothelial-cell-dna-methylation-signature-in-pulmonary-arterial-hypertension
#6
Aurélie Hautefort, Julie Chesné, Jens Preussner, Soni S Pullamsetti, Jorg Tost, Mario Looso, Fabrice Antigny, Barbara Girerd, Marianne Riou, Saadia Eddahibi, Jean-François Deleuze, Werner Seeger, Elie Fadel, Gerald Simonneau, David Montani, Marc Humbert, Frédéric Perros
Pulmonary arterial hypertension (PAH) is a severe and incurable pulmonary vascular disease. One of the primary origins of PAH is pulmonary endothelial dysfunction leading to vasoconstriction, aberrant angiogenesis and smooth muscle cell proliferation, endothelial-to-mesenchymal transition, thrombosis and inflammation. Our objective was to study the epigenetic variations in pulmonary endothelial cells (PEC) through a specific pattern of DNA methylation. DNA was extracted from cultured PEC from idiopathic PAH (n = 11), heritable PAH (n = 10) and controls (n = 18)...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28834559/improving-the-prehospital-safety-of-steroid-dependent-patients-in-northern-england-a-hospital-initiated-ambulance-service-registration-pathway
#7
LETTER
Anna L Mitchell, Kerri Devine, Vikram Lal, Paul Galloway, Matthew House, Katherine White, Julie Watson, Steve Parry, Margaret Miller, Margaret Morris, R Andy James, Petros Perros, Simon H S Pearce, Richard Quinton
No abstract text is available yet for this article.
August 23, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28801076/early-development-of-right-ventricular-ischemic-lesions-in-a-novel-large-animal-model-of-acute-right-heart-failure-in-chronic-thromboembolic-pulmonary-hypertension
#8
David Boulate, Jennifer Arthur Ataam, Andrew J Connolly, Genevieve Giraldeau, Myriam Amsallem, Benoit Decante, Lilia Lamrani, Elie Fadel, Peter Dorfmuller, Frederic Perros, Francois Haddad, Olaf Mercier
BACKGROUND: Our aim was to develop a model of acute right heart failure (ARHF) in the setting of pulmonary hypertension and to characterize acute right ventricular lesions that develop early after hemodynamic restoration. METHODS AND RESULTS: We used a described piglet model of chronic pulmonary hypertension (cPH) induced by pulmonary artery occlusions. We induced ARHF in animals with cPH (ARHF-cPH group, n = 9) by volume loading and iterative acute pulmonary embolism until hemodynamic compromise followed by dobutamine infusion for hemodynamic restoration before sacrifice for right ventricular tissue evaluation...
December 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28755510/raising-awareness-of-graves-orbitopathy-with-early-warning-cards
#9
Anna L Mitchell, Janis Hickey, Bijay Vaidya, Rhianne Mason, Ramzi Ajjan, Nicola Zammitt, Petros Perros, Colin Dayan
BACKGROUND: Clinically significant Graves' orbitopathy (GO) develops in about 25% of those with Graves' disease (GD); most cases of GD in the UK are managed by endocrinologists. Despite this, patients report significant delays before a diagnosis of GO is made. Measures to increase awareness of the early signs of GO and establishing a fast-track referral pathway to specialist care should overcome these delays and potentially improve outcomes. AIMS: We aimed to determine whether issuing a "GO early warning card" to all GD patients raises awareness of GO and facilitates early diagnosis, what percentage of cards result in a telephone contact, the number of "false reports" from card carriers and patient perceptions of the cards...
July 29, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28725652/rescuing-bmpr2-driven-endothelial-dysfunction-in-pah-a-novel-treatment-strategy-for-the-future
#10
EDITORIAL
Rozenn Quarck, Fréderic Perros
No abstract text is available yet for this article.
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28655554/t-type-ca-2-channels-elicit-pro-proliferative-and-anti-apoptotic-responses-through-impaired-pp2a-akt1-signaling-in-pasmcs-from-patients-with-pulmonary-arterial-hypertension
#11
Safietou Sankhe, Sevasti Manousakidi, Fabrice Antigny, Jennifer Arthur Ataam, Sana Bentebbal, Yann Ruchon, Florence Lecerf, Jessica Sabourin, Laura Price, Elie Fadel, Peter Dorfmüller, Saadia Eddahibi, Marc Humbert, Frédéric Perros, Véronique Capuano
Idiopathic pulmonary arterial hypertension (iPAH) is characterized by obstructive hyperproliferation and apoptosis resistance of distal pulmonary artery smooth muscle cells (PASMCs). T-type Ca(2+) channel blockers have been shown to reduce experimental pulmonary hypertension, although the impact of T-type channel inhibition remains unexplored in PASMCs from iPAH patients. Here we show that T-type channels Cav3.1 and Cav3.2 are present in the lung and PASMCs from iPAH patients and control subjects. The blockade of T-type channels by the specific blocker, TTA-A2, prevents cell cycle progression and PASMCs growth...
October 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28572541/pulmonary-endothelial-cell-dna-methylation-signature-in-pulmonary-arterial-hypertension
#12
Aurélie Hautefort, Julie Chesné, Jens Preussner, Soni S Pullamsetti, Jorg Tost, Mario Looso, Fabrice Antigny, Barbara Girerd, Marianne Riou, Saadia Eddahibi, Jean-François Deleuze, Werner Seeger, Elie Fadel, Gerald Simonneau, David Montani, Marc Humbert, Frédéric Perros
Pulmonary arterial hypertension (PAH) is a severe and incurable pulmonary vascular disease. One of the primary origins of PAH is pulmonary endothelial dysfunction leading to vasoconstriction, aberrant angiogenesis and smooth muscle cell proliferation, endothelial-to-mesenchymal transition, thrombosis and inflammation. Our objective was to study the epigenetic variations in pulmonary endothelial cells (PEC) through a specific pattern of DNA methylation.DNA was extracted from cultured PEC from idiopathic PAH (n = 11), heritable PAH (n = 10) and controls (n = 18)...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427469/graves-orbitopathy-as-a-rare-disease-in-europe-a-european-group-on-graves-orbitopathy-eugogo-position-statement
#13
P Perros, L Hegedüs, L Bartalena, C Marcocci, G J Kahaly, L Baldeschi, M Salvi, J H Lazarus, A Eckstein, S Pitz, K Boboridis, P Anagnostis, G Ayvaz, A Boschi, T H Brix, N Currò, O Konuk, M Marinò, A L Mitchell, B Stankovic, F B Törüner, G von Arx, M Zarković, W M Wiersinga
BACKGROUND: Graves' orbitopathy (GO) is an autoimmune condition, which is associated with poor clinical outcomes including impaired quality of life and socio-economic status. Current evidence suggests that the incidence of GO in Europe may be declining, however data on the prevalence of this disease are sparse. Several clinical variants of GO exist, including euthyroid GO, recently listed as a rare disease in Europe (ORPHA466682). The objective was to estimate the prevalence of GO and its clinical variants in Europe, based on available literature, and to consider whether they may potentially qualify as rare...
April 20, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28364092/use-of-%C3%AE-blockers-in-pulmonary-hypertension
#14
REVIEW
Frédéric Perros, Frances S de Man, Harm J Bogaard, Fabrice Antigny, Gérald Simonneau, Sébastien Bonnet, Steeve Provencher, Nazzareno Galiè, Marc Humbert
Contrasting with the major attention that left heart failure has received, right heart failure remains understudied both at the preclinical and clinical levels. However, right ventricle failure is a major predictor of outcomes in patients with precapillary pulmonary hypertension because of pulmonary arterial hypertension, and in patients with postcapillary pulmonary hypertension because of left heart disease. In pulmonary hypertension, the status of the right ventricle is one of the most important predictors of both morbidity and mortality...
April 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28296512/management-of-thyroid-eye-disease-in-the-united-kingdom-a-multi-centre-thyroid-eye-disease-audit
#15
F E Mellington, C M Dayan, A J Dickinson, J L Hickey, C J MacEwen, J McLaren, P Perros, G E Rose, J Uddin, B Vaidya, P Foley, J H Lazarus, A Mitchell, D G Ezra
This article aims to provide baseline data and highlight any major deficiencies in the current level of care provided for adult patients with thyroid eye disease (TED). We undertook a prospective, nonrandomized cross-sectional multicenter observational study. During a 3-month period June-August 2014, consecutive adult patients with TED who presented to nominated specialist eye clinics in the United Kingdom, completed a standardized questionnaire. Main outcome measures were: demographics, time from diagnosis to referral to tertiary centre, time from referral to review in specialist eye clinic, management of thyroid dysfunction, radioiodine and provision of steroid prophylaxis, smoking, and TED classification...
June 2017: Orbit
https://www.readbyqxmd.com/read/28265532/corrigendum-to-a-simple-method-to-assess-in-vivo-proliferation-in-lung-vasculature-with-edu-the-case-of-mmc-induced-pvod-in-rat
#16
Fabrice Antigny, Benoît Ranchoux, Valérie Nadeau, Edmund Lau, Sébastien Bonnet, Frédéric Perros
[This corrects the article DOI: 10.1155/2015/326385.].
2017: Analytical Cellular Pathology (Amsterdam)
https://www.readbyqxmd.com/read/28248132/gut-lung-connection-in-pulmonary-arterial-hypertension
#17
Benoît Ranchoux, Amélie Bigorgne, Aurélie Hautefort, Barbara Girerd, Olivier Sitbon, David Montani, Marc Humbert, Colas Tcherakian, Frédéric Perros
No abstract text is available yet for this article.
March 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28176220/does-early-response-to-intravenous-glucocorticoids-predict-the-final-outcome-in-patients-with-moderate-to-severe-and-active-graves-orbitopathy
#18
COMPARATIVE STUDY
L Bartalena, G Veronesi, G E Krassas, W M Wiersinga, C Marcocci, M Marinò, M Salvi, C Daumerie, C Bournaud, M Stahl, L Sassi, C Azzolini, K G Boboridis, M P Mourits, M R Soeters, L Baldeschi, M Nardi, N Currò, A Boschi, M Bernard, G von Arx, P Perros, G J Kahaly
PURPOSE: Intravenous glucocorticoids (ivGCs) given as 12-weekly infusions are the first-line treatment for moderate-to-severe and active Graves' orbitopathy (GO), but they are not always effective. In this study, we evaluated whether response at 6 weeks correlated with outcomes at 12 (end of intervention) and 24 (follow-up) weeks, particularly in patients initially unresponsive. METHODS: Our database (Bartalena et al. J Clin Endocrinol Metab 97:4454-4463, 10), comprising 159 patients given three different cumulative doses of methylprednisolone (2...
May 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28162460/-230-steps-a-novel-tool-to-phenotype-and-rate-the-severity-of-painful-polyneuropathy
#19
J Scholz, J Rathmell, W David, D Chad, A Broderick, S Perros, N Shin, J Wells, J Davis, C DiMaggio, S Wang, S Tate
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28126608/oil-in-microgel-strategy-for-enzymatic-triggered-release-of-hydrophobic-drugs
#20
C A Busatto, H Labie, V Lapeyre, R Auzely-Velty, A Perro, N Casis, J Luna, D A Estenoz, V Ravaine
Polymer microgels have received considerable attention due to their great potential in the biomedical field as drug delivery systems. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan composed of N-acetyl-d-glucosamine and d-glucuronic acid. This polymer is biodegradable, nontoxic, and can be chemically modified. In this work, a co-flow microfluidic strategy for the preparation of biodegradable HA microgels encapsulating hydrophobic drugs is presented. The approach relies on: (i) generation of a primary oil-in-water (O/W) nanoemulsion by the ultrasonication method, (ii) formation of a double oil-in-water-in-oil emulsion (O/W/O) using microfluidics, and (iii) cross-linking of microgels by photopolymerization of HA precursors modified with methacrylate groups (HA-MA) present in the aqueous phase of the droplets...
May 1, 2017: Journal of Colloid and Interface Science
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