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Michael Huntgeburth, Johannes Kießling, Gerrit Weimann, Verena Wilberg, Soundos Saleh, Nicolas Hunzelmann, Stephan Rosenkranz
BACKGROUND AND OBJECTIVE: Raynaud's phenomenon (RP) is characterized by transient digital ischemia and is commonly associated with connective tissue disease. Treatment remains unsatisfactory. Here we evaluate the efficacy, safety, and pharmacokinetics of a single dose of the soluble guanylate cyclase stimulator riociguat in RP. METHODS: DIGIT was a double-blind, randomized, placebo-controlled pilot study. Patients with primary or secondary RP were randomized to a single oral dose of riociguat 2 mg or placebo in a cross-over design (7 ± 3 days)...
September 20, 2018: Clinical Drug Investigation
Joshua M Cohen, Rachel A Sibley, Ernest S Chiu, Sheel Sharma
GENERAL PURPOSE: To provide information about the pathophysiology, diagnosis, and treatment options for systemic sclerosis. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant should be better able to:1. Describe the pathophysiology, signs, symptoms, and diagnosis of systemic sclerosis...
October 2018: Advances in Skin & Wound Care
Giuseppina Abignano, Gianna A Mennillo, Giovanni Lettieri, Angela Padula, Dennis McGonagle, Salvatore D'Angelo
A 40-year-old gentleman was diagnosed with anti-topoisomerase-I antibody positive diffuse cutaneous systemic sclerosis (SSc). Raynaud's phenomenon, diffuse skin sclerosis and severe interstitial lung disease (ILD) were the onset features causing digital ischemia, disability and dyspnea. He subsequently developed inflammatory polyarthritis (IA) with hands and wrists involvement. His brother had psoriasis. Physical examination showed fingertip pitting scars, subcutaneous calcinosis, skin sclerosis with hyper- and hypopigmentation, flexion and extension contractures and shortened fingers (Figure 1...
September 17, 2018: Arthritis & Rheumatology
Tido von Schoen-Angerer, Bernhard Deckers, Jörg Henes, Eduard Helmert, Jan Vagedes
INTRODUCTION: Raynaud's phenomenon is the earliest manifestation of systemic sclerosis. Nitroglycerin gel is the only proven topical therapy. METHODS: A 53-year-old woman with systemic sclerosis had topical Rosamarinus officinalis (rosemary) oil, often used in anthroposophic medicine, applied to her hands over 3days and then, separately, olive oil. RESULTS: Thermography images showed significant warming of fingers after rosemary oil, but not after olive oil, coinciding with the patient's subjective experience...
October 2018: Complementary Therapies in Medicine
Franck Raynaud, Marco Mina, Daniele Tavernari, Giovanni Ciriello
Genomic instability is a major driver of intra-tumor heterogeneity. However, unstable genomes often exhibit different molecular and clinical phenotypes, which are associated with distinct mutational processes. Here, we algorithmically inferred the clonal phylogenies of 6,000 human tumors from 32 tumor types to explore how intra-tumor heterogeneity depends on different implementations of genomic instability. We found that extremely unstable tumors associated with DNA repair deficiencies or high chromosomal instability are not the most intrinsically heterogeneous...
September 13, 2018: PLoS Genetics
Fiorella Villano, Adriana Peixoto, Eloísa Riva, Carina Di Matteo, Lilián Díaz
Digital ischemia is associated with atherosclerotic, thromboembolic, or connective tissue diseases. Less often, it can be related to malignancy. Paraneoplastic vascular acrosyndromes (Raynaud's syndrome, acrocianosis, and acronecrosis) are associated with adenocarcinoma and less frequently with hematological malignancies. We report the case of a 45-year-old male, smoker, with a 10-day history of pain, cyanosis, and progressive digital necrosis in both hands. In the previous four months, he noticed painless mass in the right axillary gap, drenching night sweats, and weight loss...
2018: Case Reports in Hematology
John R Eisenbrey, Maria Stanczak, Flemming Forsberg, Fabian A Mendoza-Ballesteros, Andrej Lyshchik
The purpose of this study was to investigate the use of photoacoustic imaging for quantifying fingertip oxygenation as an approach to diagnosing and monitoring Raynaud's phenomenon. After 30 min of acclimation to room temperature, 22 patients (7 patients with secondary Raynaud's associated to Scleroderma and 15 healthy controls) provided informed consent to undergo fingertip Doppler imaging and high-frequency photoacoustic imaging before and 5, 15 and 30 min after cold stimulus (submerged hand in a 15 °C water bath for 1 min)...
October 2018: Ultrasound in Medicine & Biology
Thapat Wannarong, Chayawee Muangchan
The objective of this study is to investigate the impact of skin sclerosis burden on an internal organ involvement over a 1-year period, as measured by time-adjusted accrual-modified Rodnan skin score (TA-mRSS), and to evaluate association between TA-mRSS patterns and laboratory tests in patients with systemic sclerosis (SSc). This prospective study was conducted at Siriraj Hospital (Bangkok, Thailand) during the November 2013-November 2016. SSc patients by ACR/EULAR 2013 or ACR 1980 criteria were eligible...
September 11, 2018: Rheumatology International
Ngoc-Phuong-Thao Nguyen, Céline Raynaud, Isabelle Meynial-Salles, Philippe Soucaille
Developing a commercial process for the biological production of n-butanol is challenging as it needs to combine high titer, yield, and productivities. Here we engineer Clostridium acetobutylicum to stably and continuously produce n-butanol on a mineral media with glucose as sole carbon source. We further design a continuous process for fermentation of high concentration glucose syrup using in situ extraction of alcohols by distillation under low pressure and high cell density cultures to increase the titer, yield, and productivity of n-butanol production to the level of 550 g/L, 0...
September 11, 2018: Nature Communications
Hannah L Woodward, Paolo Innocenti, Kwai-Ming J Cheung, Angela Hayes, Jennie Roberts, Alan T Henley, Amir Faisal, Grace Wing-Yan Mak, Gary Box, Isaac M Westwood, Nora Cronin, Michael Carter, Melanie Valenti, Alexis De Haven Brandon, Lisa O'Fee, Harry Saville, Jessica Schmitt, Rosemary Burke, Fabio Broccatelli, Rob L M van Montfort, Florence I Raynaud, Suzanne A Eccles, Spiros Linardopoulos, Julian Blagg, Swen Hoelder
Monopolar spindle 1 (MPS1) occupies a central role in mitosis and is one of the main components of the spindle assembly checkpoint. The MPS1 kinase is an attractive cancer target, and herein, we report the discovery of the clinical candidate BOS172722. The starting point for our work was a series of pyrido[3,4- d]pyrimidine inhibitors that demonstrated excellent potency and kinase selectivity but suffered from rapid turnover in human liver microsomes (HLM). Optimizing HLM stability proved challenging since it was not possible to identify a consistent site of metabolism and lowering lipophilicity proved unsuccessful...
September 10, 2018: Journal of Medicinal Chemistry
Amaal E Abdulle, Gilles F H Diercks, Martin Feelisch, Douwe J Mulder, Harry van Goor
Systemic sclerosis (SSc) is a rare connective tissue disease characterized by autoimmunity, vasculopathy, and progressive fibrosis typically affecting multiple organs including the skin. SSc often is a lethal disorder, because effective disease-modifying treatment still remains unavailable. Vasculopathy with endothelial dysfunction, perivascular infiltration of mononuclear cells, vascular wall remodeling and rarefaction of capillaries is the hallmark of the disease. Most patients present with vasospastic attacks of the digital arteries referred to as 'Raynaud's phenomenon,' which is often an indication of an underlying widespread vasculopathy...
2018: Frontiers in Physiology
Reza Alizadeh, Laura Vickers, Pradtana Hirunpatravong, Pablo Romero, Mark C Lin, Farideh Sharifipour, Joseph Caprioli
PURPOSE: Primary open angle glaucoma (POAG) patients constitute a heterogeneous group. Identification of phenotypic subtypes among these patients may provide a deeper understanding of the disease and aid associations with genotypes. We describe a phenotype of POAG patients associated with a constellation of systemic disorders; patients with this phenotype appear to be vulnerable to optic nerve damage at low intraocular pressures. MATERIALS AND METHODS: In this retrospective study, we evaluated the medical records of active Jules Stein Eye Institute glaucoma patients from January 1996 to January 2017 and included subjects with POAG, acquired pits of the optic nerve (APON) and at least one of the following: systolic blood pressure persistently ≤100▒mmHg, history of migraine headaches or migraine variant, and Raynaud's syndrome...
September 4, 2018: Journal of Glaucoma
Ruma G Singh, Ngoc N Nguyen, Steve V DeSouza, Sayali A Pendharkar, Maxim S Petrov
Current knowledge on biomarkers of intra-pancreatic fat deposition (IFD) is limited. We aimed to analyse comprehensively body composition and insulin traits as biomarkers of IFD in healthy normoglycaemic individuals as well as individuals with new-onset prediabetes and diabetes after acute pancreatitis (NODAP). A total of 29 healthy and 34 NODAP individuals took part in this cross-sectional study. The studied biomarkers belonged to the following domains: body composition (anthropometry and magnetic resonance imaging (MRI)-derived variables), indices of insulin secretion, indices of insulin sensitivity, incretins and related peptides, as well as pancreatitis-related factors...
September 5, 2018: Diabetes, Obesity & Metabolism
Jenny M Held, Jason Daily, Terrence Kilfoil, Michael Johnston
No abstract text is available yet for this article.
August 1, 2018: American Surgeon
Sven Weum, Louis de Weerd
Vasospastic disorders in the hand have been treated with surgical sympathectomy and recently with botulinum toxin A (BTX) injections in the palm. The purpose of this study was to evaluate if it is possible to obtain precise administration of BTX around the radial artery using a single ultrasound-guided injection. We present a novel technique using 1 single ultrasound-guided BTX injection around the radial artery to treat vasospastic symptoms. Ten patients were included in a pilot study. All patients were referred by a rheumatologist after been diagnosed with primary or secondary Raynaud...
July 2018: Plastic and Reconstructive Surgery. Global Open
Udai Banerji, Nivedita Sain, Swee Y Sharp, Melanie Valenti, Yasmin Asad, Ruth Ruddle, Florence Raynaud, Michael Walton, Suzanne A Eccles, Ian Judson, Ann L Jackman, Paul Workman
The corresponding author of this article has informed us of concerns about the immunoblots in Fig. 2 which were carried out in the collaborating laboratory of Professor Ann Jackman.
September 1, 2018: Cancer Chemotherapy and Pharmacology
Olivia Qiu, Theresa Chan, Matthew Luen, Joseph E Cruz, Evelyn R Hermes-DeSantis
Raynaud's phenomenon (RP) is a microvascular condition in which reversible ischemic attacks occur in the extremities. Due to the unpredictable nature of these attacks, pharmacologic agents that can be administered on as-needed basis are currently being sought after. Topical nitrates are well suited for as-needed use, and several different formulations have been studied for the treatment of RP, including ointments, gels, patches, and tapes. However, these different dosage forms are not all equal in terms of safety and efficacy, and not every one is commercially available for use in clinical practice...
August 22, 2018: Rheumatology International
Evangelia Zampeli, Aliki Venetsanopoulou, Ourania D Argyropoulou, Clio P Mavragani, Maria G Tektonidou, Panayiotis G Vlachoyiannopoulos, Athanasios G Tzioufas, Fotini N Skopouli, Haralampos M Moutsopoulos
Myositis-specific (MSAs) or-associated autoantibodies (MAAs) have been linked to particular clinical phenotypes of idiopathic inflammatory myopathies (IIM) and appear to aid diagnosis. The objective of this study was to analyze the prevalence of MSAs and MAAs and their possible clinical associations in Greek IIM patients. This study comprised 95 IIM patients classified based on the 2017 EULAR/ACR classification criteria. All patients had MSAs and MAAs measured in their sera by line immunoblot assay. Dermatomyositis was the most prevalent IIM clinical subtype...
August 25, 2018: Clinical Rheumatology
Javier A Cavallasca, Julia L Riera, Jorge L Musuruana
No abstract text is available yet for this article.
August 20, 2018: Medicina Clínica
Lucas Raynaud, Diane Mege, Magaly Zappa, Nathalie Guedj, Valérie Vilgrain, Yves Panis
PURPOSE: Very few data are available about the clinical relevance of magnetic resonance (MR) imaging in preoperative evaluation of rectal villous adenoma. The aim is to evaluate the impact of MR imaging for the surgical management of rectal villous adenoma treated by transanal endoscopic microsurgery (TEM). METHODS: All patients with histologically proven rectal villous tumours operated by TEM who had a preoperative MR imaging between 2009 and 2017 were retrospectively reviewed...
August 22, 2018: International Journal of Colorectal Disease
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