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https://www.readbyqxmd.com/read/28638723/low-dose-methotrexate-in-sickle-cell-disease-a-pilot-study-with-rationale-borrowed-from-rheumatoid-arthritis
#1
Silvia R Brandalise, Rosemary Assis, Angelo B A Laranjeira, José Andrés Yunes, Pedro O de Campos-Lima
BACKGROUND: Inflammation is a major feature of sickle cell disease (SCD). Low-dose methotrexate (MTX) has long been used in chronic inflammatory diseases. This pilot study examined the MTX effect on acute vaso-occlusive pain crises (VOC) in SCD patients. METHODS: Fourteen adults on hydroxyurea with severe and refractory VOC received one intramuscular injection of 10 mg of MTX per week for 12 weeks. A single weekly dose of 5 mg of leucovorin was administered orally 48 h after each MTX injection...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28606962/endothelin-1-promotes-vascular-smooth-muscle-cell-migration-across-the-artery-wall-a-mechanism-contributing-to-vascular-remodelling-and-intimal-hyperplasia-in-giant-cell-arteritis
#2
Ester Planas-Rigol, Nekane Terrades-Garcia, Marc Corbera-Bellalta, Ester Lozano, Marco A Alba, Marta Segarra, Georgina Espígol-Frigolé, Sergio Prieto-González, José Hernández-Rodríguez, Sara Preciado, Rodolfo Lavilla, Maria C Cid
BACKGROUND: Giant-cell arteritis (GCA) is an inflammatory disease of large/medium-sized arteries, frequently involving the temporal arteries (TA). Inflammation-induced vascular remodelling leads to vaso-occlusive events. Circulating endothelin-1 (ET-1) is increased in patients with GCA with ischaemic complications suggesting a role for ET-1 in vascular occlusion beyond its vasoactive function. OBJECTIVE: To investigate whether ET-1 induces a migratory myofibroblastic phenotype in human TA-derived vascular smooth muscle cells (VSMC) leading to intimal hyperplasia and vascular occlusion in GCA...
June 12, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28606098/determining-the-longitudinal-validity-and-meaningful-differences-in-hrql-of-the-pedsql%C3%A2-sickle-cell-disease-module
#3
Julie A Panepinto, J Paul Scott, Oluwakemi Badaki-Makun, Deepika S Darbari, Corrie E Chumpitazi, Gladstone E Airewele, Angela M Ellison, Kim Smith-Whitley, Prashant Mahajan, Sharada A Sarnaik, T Charles Casper, Larry J Cook, Julie Leonard, Monica L Hulbert, Elizabeth C Powell, Robert I Liem, Robert Hickey, Lakshmanan Krishnamurti, Cheryl A Hillery, David C Brousseau
BACKGROUND: Detecting change in health status over time and ascertaining meaningful changes are critical elements when using health-related quality of life (HRQL) instruments to measure patient-centered outcomes. The PedsQL™ Sickle Cell Disease module, a disease specific HRQL instrument, has previously been shown to be valid and reliable. Our objectives were to determine the longitudinal validity of the PedsQL™ Sickle Cell Disease module and the change in HRQL that is meaningful to patients...
June 12, 2017: Health and Quality of Life Outcomes
https://www.readbyqxmd.com/read/28596657/increased-level-of-factor-viii-and-physiological-inhibitors-of-coagulation-in-patients-with-sickle-cell-disease
#4
Mohamed Chekkal, Mohamed Chakib Arslane Rahal, Khedidja Moulasserdoun, Fatima Seghier
Sickle cell disease (SCD) is a hemoglobinopathy characterized by hemolysis, oxidative stress, and vaso-occlusive crises. Thromboembolism also remains a serious complication and probably underestimated in the SCD. Our objective was to seek the existence of hemostasis abnormalities that predispose to thrombosis such as elevation of FVIII and Physiological inhibitors of coagulation deficiency. We studied 81 patients with SCD, including 32 homozygous S/S, 20 double heterozygous S/β thalassemia and 29 heterozygous S/A...
June 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28584135/genome-wide-association-study-to-identify-variants-associated-with-vaso-occlusive-pain-in-sickle-cell-anemia
#5
Shruti Chaturvedi, Pallav Bhatnagar, Christopher J Bean, Martin H Steinberg, Jacqueline N Milton, James F Casella, Emily Barron-Casella, Dan E Arking, Michael R DeBaun
No abstract text is available yet for this article.
June 5, 2017: Blood
https://www.readbyqxmd.com/read/28579187/functional-mri-bold-response-in-sickle-mice-with-hyperalgesia
#6
Ying Wang, Xiao Wang, Wei Chen, Kalpna Gupta, Xiao-Hong Zhu
Patients with sickle cell anemia (SCA) have abnormal hemoglobin (sickle hemoglobin S) leading to the crystallization of hemoglobin chains in red blood cells (RBCs), which assume sickle shape and display reduced flexibility. Sickle RBCs (sRBCs) adhere to vessel walls and block blood flow, thus preventing oxygen delivery to the tissues leading to vaso-occlusive crises (VOC), acute pain and organ damage. SCA patients often have chronic pain that can be attributed to inflammation, vasculopathy, neuropathy, ischemia-reperfusion injury and organ damage...
June 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28578536/population-pharmacokinetic-and-exposure-response-analyses-of-prasugrel-in-pediatric-patients-with-sickle-cell-anemia
#7
Brian A Moser, Elizabeth S LaBell, Emmanuel Chigutsa, Joseph A Jakubowski, David S Small
BACKGROUND AND OBJECTIVE: Prasugrel, a P2Y12 adenosine diphosphate (ADP) receptor antagonist, inhibits ADP-mediated platelet activation and aggregation in patients with sickle cell anemia (SCA). We developed a population pharmacokinetic (popPK) model in pediatric patients from 2 to <18 years of age with SCA, and performed exposure-response evaluations to characterize the effects of prasugrel in a subset of these patients who weighed 19 kg or more and experienced at least two episodes of vaso-occlusive crises (VOC) in the past year...
June 3, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28562105/prasugrel-hydrochloride-for-the-treatment-of-sickle-cell-disease
#8
Nicola Conran, David C Rees
Therapeutic options for sickle cell disease (SCD) are limited and, currently, only one drug (hydroxyurea) has FDA approval for the treatment of adult SCD. While this genetic disease is caused by hemoglobin polymerization, subsequent downstream events trigger platelet activation, vaso-occlusion and the disease's complex pathophysiology. Areas covered: The oral thienopyridine, prasugrel hydrochloride, irreversibly inhibits the P2Y12 receptors, inhibiting ADP-dependent platelet activation. We discuss recent clinical trials evaluating the pharmokinetics of prasugrel and its potential for use in SCD...
June 12, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28554826/oxidative-pathways-in-the-sickle-cell-and-beyond
#9
REVIEW
Abdu I Alayash
Polymerization of deoxy sickle cell hemoglobin (HbS) is well recognized as the primary event that triggers the classic cycles of sickling/unsickling of patients red blood cells (RBCs). RBCs are also subjected to continuous endogenous and exogenous oxidative onslaughts resulting in hemolytic rate increases which contribute to the evolution of vasculopathies associated with this disease. Compared to steady-state conditions, the occurrences of vaso-occlusive crises increase the levels of both RBC-derived microparticles as well as extracellular Hb in circulation...
May 20, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28553571/pancreatitis-in-the-setting-of-vaso-occlusive-sickle-cell-crisis-a-rare-encounter
#10
Badar Hasan, Talal Asif, Cody Braun, Waled Bahaj, Eslam Dosokey, Rebecca R Pauly
Acute pancreatitis is a common cause of acute abdominal pain. Gallstones and alcohol abuse account for the majority of the cases. Pancreatic ischemia is an uncommon but established cause of pancreatitis associated with connective tissue diseases, vasculitis, and shock. Our case highlights a rare case of vaso-occlusive crisis (VOC) in a patient with sickle cell (SC) disease leading to pancreatitis. Treatment remains largely conservative but exchange transfusion may be the therapy of choice in severely hypoxic patients or in patients with high pre-treatment hemoglobin S levels...
April 25, 2017: Curēus
https://www.readbyqxmd.com/read/28552472/exacerbated-in-vivo-metabolic-changes-suggestive-of-a-spontaneous-muscular-vaso-occlusive-crisis-in-exercising-muscle-of-a-sickle-cell-mouse
#11
Benjamin Chatel, Laurent A Messonnier, David Bendahan
While sickle cell disease (SCD) is characterized by frequent vaso-occlusive crisis (VOC), no direct observation of such an event in skeletal muscle has been performed in vivo. The present study reported exacerbated in vivo metabolic changes suggestive of a spontaneous muscular VOC in exercising muscle of a sickle cell mouse. Using magnetic resonance spectroscopy of phosphorus 31, phosphocreatine and inorganic phosphate concentrations and intramuscular pH were measured throughout two standardized protocols of rest - exercise - recovery at two different intensities in ten SCD mice...
June 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28550627/association-between-antithrombotic-drug-use-before-chronic-subdural-haematoma-and-outcome-after-drainage-a-systematic-review-and-meta-analysis
#12
Michael T C Poon, Rustam Al-Shahi Salman
In view of their age and vascular co-morbidities, people are often taking an antithrombotic drug when diagnosed with chronic subdural haematoma (CSDH). It is unclear whether antithrombotic use at CSDH diagnosis, or resumption afterwards, is associated with recurrent CSDH or vaso-occlusive events. We systematically reviewed the literature for studies reporting CSDH recurrence or vaso-occlusive events after drainage of CSDH associated with antithrombotic drug use. We searched Medline 1946-2016 and Embase 1974-2016 inclusive for cohort studies reporting the risk of CSDH recurrence or vaso-occlusive events after CSDH associated with antithrombotic (anticoagulant or antiplatelet) drug use...
May 26, 2017: Neurosurgical Review
https://www.readbyqxmd.com/read/28548215/protein-z-and-endothelin-1-genetic-polymorphisms-in-pediatric-egyptian-sickle-cell-disease-patients
#13
Mervat M Khorshied, Nohair S Mohamed, Rania S Hamza, Rasha M Ali, Mona K El-Ghamrawy
BACKGROUND: Sickle cell disease (SCD) is a monogenic disease associated with multisystem morbidity. Vasculopathy caused by delicate imbalance between coagulation and endothelial systems plays a pivotal role in disease course. As Protein Z and Endothelin-1 genetic polymorphisms may increase the thrombotic risk, the aim of the current work was to verify the possible impact of Protein Z (PROZ G79A) and Endothelin-1 (EDN1 G5665T) polymorphisms on the clinic-laboratory features of the SCD in a cohort of Egyptian pediatric patients...
May 26, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28542469/biophysical-markers-of-the-peripheral-vasoconstriction-response-to-pain-in-sickle-cell-disease
#14
Patjanaporn Chalacheva, Maha Khaleel, John Sunwoo, Payal Shah, Jon A Detterich, Roberta M Kato, Wanwara Thuptimdang, Herbert J Meiselman, Richard Sposto, Jennie Tsao, John C Wood, Lonnie Zeltzer, Thomas D Coates, Michael C K Khoo
Painful vaso-occlusive crisis (VOC), a complication of sickle cell disease (SCD), occurs when sickled red blood cells obstruct flow in the microvasculature. We postulated that exaggerated sympathetically mediated vasoconstriction, endothelial dysfunction and the synergistic interaction between these two factors act together to reduce microvascular flow, promoting regional vaso-occlusions, setting the stage for VOC. We previously found that SCD subjects had stronger vasoconstriction response to pulses of heat-induced pain compared to controls but the relative degrees to which autonomic dysregulation, peripheral vascular dysfunction and their interaction are present in SCD remain unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28538688/in-silico-study-and-bioprospection-of-the-antibacterial-and-antioxidant-effects-of-flavone-and-its-hydroxylated-derivatives
#15
Camila de Albuquerque Montenegro, Gregório Fernandes Gonçalves, Abrahão Alves de Oliveira Filho, Andressa Brito Lira, Thays Thyara Mendes Cassiano, Natanael Teles Ramos de Lima, José Maria Barbosa-Filho, Margareth de Fátima Formiga Melo Diniz, Hilzeth Luna Freire Pessôa
Flavonoid compounds are widely used as natural protective species, which can act as anti-inflammatory, antioxidant, anticoagulant, antihypertensive and antitumor agents. This study set out to investigate the probable pharmacological activities, along with the antibacterial and antioxidant effects, of flavone and its hydroxy derivatives: 3-hydroxyflavone, 5-hydroxyflavone and 6-hydroxyflavone. To do so, we investigated their pharmacological characteristics, using in silico tests that indicate likelihood of activity or inactivity, with the PASS online software, and the antimicrobial potential against Gram positive and Gram negative bacteria was also analyzed, including bacteria of clinical importance...
May 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28527641/identifying-social-behavioral-health-needs-of-adults-with-sickle-cell-disease-in-the-emergency-department
#16
Sophia K Smith, Julia Johnston, Carlton Rutherford, Rachel Hollowell, Paula Tanabe
INTRODUCTION: Sickle cell disease (SCD) is a complex illness with many social-behavioral co-morbidities. The aim of this project was to describe unmet social-behavioral health needs for adults with SCD who presented to the emergency department for treatment of vaso-occlusive episodes (VOEs). METHODS: A descriptive study using 1:1 interviews during an ED visit for a VOE was conducted; a brief social behavioral health screening interview guide was used. A convenience sample of adults with SCD treated in the emergency department for a VOE were eligible for inclusion...
May 17, 2017: Journal of Emergency Nursing: JEN: Official Publication of the Emergency Department Nurses Association
https://www.readbyqxmd.com/read/28512557/increased-vasoocclusive-crises-in-o-blood-group-sickle-cell-disease-patients-association-with-underlying-thrombospondin-levels
#17
M Al Huneini, S Alkindi, V Panjwani, K Al Falahi, B Al Balushi, D Gravell, C H Ho, R Krishnamoorthy, A V Pathare
OBJECTIVES: To explore the incidence of vaso-occlusive crisis (VOC) in Blood Group "O" sickle cell disease (SCD) patients, and correlate it with the blood group and thrombospondin (TSP) levels. METHODS: In 89 consecutive SCD patients, blood samples were obtained for von Williebrand factor (vWF:Ag) antigen, collagen binding activity (CBA), ristocetin binding activity (RCo), blood group typing, C-reactive protein (CRP), high performance liquid chromatography (HPLC), Serum TSP 1 and TSP 2 levels, complete blood counts (CBC), lactic dehydrogenase (LDH) levels, liver function (LFT) and renal function tests (RFT) during VOC episodes and in steady state conditions...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28511389/variability-of-iron-load-in-patients-of-sickle-cell-anaemia-hbss-a-study-from-eastern-india
#18
Pranati Mohanty, Rabindra Kumar Jena, Sudha Sethy
INTRODUCTION: Sickle Cell Anaemia (SCA) is one of the commonest haemoglobinopathies due to a point mutation (A→T) of the β-globin gene. Out of five haplotypes, the Arab-Indian haplotype present in India is one of the least severe phenotype and least studied also. It is characterized by lifelong haemolytic anaemia requiring red cell transfusion leading to iron overload. In contrast, there is very high incidence of deficiency of iron, folic acid and vitamin B12. AIM: Our objective was to access the Iron status of SCA patients and to find its correlation with various parameters like red cell transfusion, haemolysis and serum hepcidin...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28510346/lack-of-effect-of-rivipansel-on-qtc-interval-in-healthy-adult-african-american-male-subjects
#19
Brinda K Tammara, Anna Plotka, Frank E Shafer, David R J Readett, Steve Riley, Joan M Korth-Bradley
Rivipansel is a pan-selectin inhibitor in phase 3 development for the treatment of vaso-occlusive crises in patients with sickle cell disease. This single-dose, randomized, 3-period, 3-treatment (400 mg moxifloxacin open-label, 4 g rivipansel-blinded, and placebo-blinded) crossover study evaluated the effect of rivipansel on the QT/QTc interval in 48 healthy male African American subjects (age, 21-53 years; weight, 60-115 kg). Time-matched, placebo-adjusted change from baseline QT interval using Fridericia's correction method (QTcF) was determined using a repeated-measures mixed-effects model...
May 16, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28509611/efficacy-of-high-resolution-cone-beam-ct-in-the-evaluation-of-perforators-in-vertebral-artery-dissection
#20
Kenji Shimada, Michihiro Tanaka, Keisuke Kadooka, Hiromu Hadeishi
Introduction A major complication of internal coil trapping for vertebral artery dissection (VAD) is medullary infarction associated with perforator occlusion. Currently, higher spatial resolution imaging can be obtained with high-resolution cone-beam computed tomography (VASO CT), and the efficacy of perforator visualization adjacent to VAD was examined. Methods Eight patients who underwent internal coil trapping or stent-supported coil embolization underwent VASO CT to evaluate perforators around VAD. Visualization of perforators was compared with conventional digital subtraction angiography (DSA) and three-dimensional rotational angiography (3D-RA)...
January 1, 2017: Interventional Neuroradiology
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