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Hydroxyurea

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https://www.readbyqxmd.com/read/29337597/hydroxyurea-for-lifelong-transfusion-dependent-%C3%AE-thalassemia-a-meta-analysis
#1
Ali H Algiraigri, Nicola A M Wright, Elizabeth Oddone Paolucci, Aliya Kassam
OBJECTIVE: Chronic blood transfusion remains the most feasible therapeutic option for lifelong transfusion-dependent β-thalassemia (lifelong TDβT). However, it is associated with serious risks and complications. Hydroxyurea (HU), an oral chemotherapeutic drug, is expected to increase hemoglobin levels, thereby minimizing the burden of blood transfusion and its complications. Growing literature over the last twenty years suggests promising results of the use HU in lifelong TDβT; however, its role and safety remain unanswered questions...
January 16, 2018: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29324574/sleep-problem-risk-for-adolescents-with-sickle-cell-disease-sociodemographic-physical-and-disease-related-correlates
#2
Cecelia R Valrie, Krystal L Trout, Kayzandra E Bond, Rebecca J Ladd, Nichelle L Huber, Kristen J Alston, Alicia M Sufrinko, Erik Everhart, Beng R Fuh
The aims of the current study were to investigate whether SCD incurs an additional risk for poor sleep over and above the influence of sociodemographic factors (ie, race and sex) during adolescence, and to explore the relationships between sociodemographic, physical (ie, age and pubertal status), and disease-related factors (ie, SCD genotype and hydroxyurea use) on sleep problem risk during adolescence. Black adolescents (age, 12 to 17 y) with SCD (n=53) were recruited from regional pediatric SCD clinics in the southeast and a sample of healthy black adolescents (n=160) were recruited from middle and high schools...
January 10, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29321547/polycythemia-vera-treatment-algorithm-2018
#3
REVIEW
Ayalew Tefferi, Alessandro M Vannucchi, Tiziano Barbui
Recently reported mature survival data have confirmed the favorable prognosis in polycythemia vera (PV), with an estimated median survival of 24 years, in patients younger than age 60 years old. Currently available drugs for PV have not been shown to prolong survival or alter the natural history of the disease and are instead indicated primarily for prevention of thrombosis. Unfortunately, study endpoints that are being utilized in currently ongoing clinical trials in PV do not necessarily target clinically or biologically relevant outcomes, such as thrombosis, survival, or morphologic remission, and are instead focused on components of disease palliation...
January 10, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29321520/essential-thrombocythemia-treatment-algorithm-2018
#4
REVIEW
Ayalew Tefferi, Alessandro M Vannucchi, Tiziano Barbui
Current drug therapy for myeloproliferative neoplasms, including essential thrombocythemia (ET) and polycythemia vera (PV), is neither curative nor has it been shown to prolong survival. Fortunately, prognosis in ET and PV is relatively good, with median survivals in younger patients estimated at 33 and 24 years, respectively. Therefore, when it comes to treatment in ET or PV, less is more and one should avoid exposing patients to new drugs that have not been shown to be disease-modifying, and whose long-term consequences are suspect (e...
January 10, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29318647/realizing-effectiveness-across-continents-with-hydroxyurea-enrollment-and-baseline-characteristics-of-the-multicenter-reach-study-in-sub-saharan-africa
#5
Patrick T McGann, Thomas N Williams, Peter Olupot-Olupot, George A Tomlinson, Adam Lane, José Luís Reis da Fonseca, Robert Kitenge, George Mochamah, Ham Wabwire, Susan Stuber, Thad A Howard, Kathryn McElhinney, Banu Aygun, Teresa Latham, Brígida Santos, Léon Tshilolo, Russell E Ware
Despite its well-described safety and efficacy in the treatment of sickle cell anemia (SCA) in high-income settings, hydroxyurea remains largely unavailable in sub-Saharan Africa, where more than 75% of annual SCA births occur and many comorbidities exist. Realizing Effectiveness Across Continents with Hydroxyurea (REACH, ClinicalTrials.gov NCT01966731) is a prospective, Phase I/II open-label trial of hydroxyurea designed to evaluate the feasibility, safety, and benefits of hydroxyurea treatment for children with SCA in four sub-Saharan African countries...
January 10, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29299197/inhibition-of-5-lipoxygenase-inhibitor-zileuton-in-high-fat-diet-induced-nonalcoholic-fatty-liver-disease-progression-model
#6
Kuifen Ma, Yihe Chen, Xingguang Liang, Jing Miao, Qingwei Zhao
Objectives: Arachidonic Acid/5-lipoxygenase (AA/5-LOX) pathway connects lipid metabolism and proinflammatory cytokine, which are both related to the development and progression of nonalcoholic fatty liver disease (NAFLD). Therefore, the present study was designed to investigate the role of AA/5-LOX pathway in progression of NAFLD, and the effect of zileuton, an inhibitor of 5-LOX, in this model. Materials and Methods: Animal model for progression of NAFLD was established via feeding high saturated fat diet (HFD)...
November 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29298824/mof-suppresses-replication-stress-and-contribute-to-resolution-of-stalled-replication-forks
#7
Dharmendra Kumar Singh, Raj K Pandita, Mayank Singh, Sharmistha Chakraborty, Shashank Hambarde, Deepti Ramnarain, Vijaya Charaka, Kazi Mokim Ahmed, Clayton R Hunt, Tej K Pandita
The hMOF protein belongs to the MYST family of histone acetyltransferases and plays a critical role in transcription and the DNA damage response. MOF is essential for cell proliferation, however its role during replication and replicative stress is unknown. Here we demonstrate that cells depleted for MOF and under replicative stress induced by cisplatin, hydroxyurea or camptothecin have reduced survival, a higher frequency of S-phase specific chromosome damage and increased R-loop formation. MOF depletion decreased replication fork speed and, when combined with replicative stress, also increased stalled replication forks as well as new origin firing...
January 3, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29296825/disease-severity-and-slower-psychomotor-speed-in-adults-with-sickle-cell-disease
#8
Dana R Jorgensen, Andrea Metti, Meryl A Butters, Joseph M Mettenburg, Caterina Rosano, Enrico M Novelli
Psychomotor slowing is common in children with sickle cell disease (SCD), but little is known about its severity in adults. We conducted a cross-sectional study to quantify psychomotor speed, measured with the digit symbol substitution test (DSST), in relationship with disease severity in adults with SCD attending an outpatient clinic (n = 88, age 36.3 years). Genotype was used to group patients in "severe" (homozygous for hemoglobin S or compound heterozygous with β0 thalassemia) or "moderate" groups (compound heterozygous for HbS, with either HbC or β+ thalassemia)...
September 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296801/pharmacotherapeutical-strategies-in-the-prevention-of-acute-vaso-occlusive-pain-in-sickle-cell-disease-a-systematic-review
#9
REVIEW
Joep W R Sins, David J Mager, Shyrin C A T Davis, Bart J Biemond, Karin Fijnvandraat
Sickle-cell disease (SCD) is characterized by frequent and painful vaso-occlusive crises (VOCs). Various treatments have been evaluated over the years. However, a clear overview is lacking. The objective of this study was to systematically review all pharmacotherapeutical strategies in the prevention of VOCs beyond hydroxyurea. We performed a systematic literature search (MEDLINE, Embase, CENTRAL). Eligible studies were controlled clinical trials evaluating pharmacotherapeutical interventions targeting the reduction of VOCs in patients with SCD...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290171/health-care-costs-and-thromboembolic-events-in-hydroxyurea-treated-patients-with-polycythemia-vera
#10
Shreekant V Parasuraman, Nianwen Shi, Dilan C Paranagama, Machaon Bonafede
BACKGROUND: Patients with polycythemia vera (PV) are at increased risk of thromboembolic events (TEs), which are key contributors to reduced overall survival compared with the age- and sex-matched general population. In addition to aspirin and phlebotomy to maintain hematocrit level < 45%, many patients receive cytoreduction with hydroxyurea (HU), which is associated with improved survival and may reduce the risk of cardiovascular events and TEs. However, 1 in 4 patients become resistant to or intolerant of HU...
January 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/29285836/disease-and-treatment-characteristics-of-polycythaemia-vera-patients-in-belgium-results-from-a-scientific-survey
#11
Timothy Devos, Yves Beguin, Lucien Noens, Koen Van Eygen, Pierre Zachée, Philippe Mineur, Laurent Knoops, Chantal Doyen, Koen Theunissen, Fleur Samantha Benghiat, Michael Reusens, Wim Pluymers
OBJECTIVE: The current survey aimed to gather pre-defined disease parameters and treatment strategies to characterize the polycythaemia vera (PV) patient population in Belgium METHODS: Cross-sectional data from PV patients, seen at least once between May 2014 and May 2015 at 10 sites in Belgium, were collected in aggregated form and analysed descriptively and quantitatively RESULTS: Data from 343 PV patients were collected. Of these, 174 (50.7%) were male and 256 (74.6%) were ≥60 years of age...
December 29, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29279787/acute-chest-syndrome-in-children-with-sickle-cell-disease
#12
REVIEW
Shilpa Jain, Nitya Bakshi, Lakshmanan Krishnamurti
Acute chest syndrome (ACS) is a frequent cause of acute lung disease in children with sickle cell disease (SCD). Patients may present with ACS or may develop this complication during the course of a hospitalization for acute vaso-occlusive crises (VOC). ACS is associated with prolonged hospitalization, increased risk of respiratory failure, and the potential for developing chronic lung disease. ACS in SCD is defined as the presence of fever and/or new respiratory symptoms accompanied by the presence of a new pulmonary infiltrate on chest X-ray...
December 1, 2017: Pediatric Allergy, Immunology, and Pulmonology
https://www.readbyqxmd.com/read/29279479/fatal-disseminated-tuberculosis-during-treatment-with-ruxolitinib-plus-prednisolone-in-a-patient-with-primary-myelofibrosis-a-case-report-and-review-of-the-literature
#13
Yasuhiro Tsukamoto, Junichi Kiyasu, Mariko Tsuda, Motohiko Ikeda, Motoaki Shiratsuchi, Yoshihiro Ogawa, Yuji Yufu
A 73-year-old man with primary myelofibrosis (PMF) was being treated with hydroxyurea, which was changed to ruxolitinib treatment because of worsening constitutional symptoms. Although ruxolitinib rapidly induced relief, he developed a high-grade fever. A comprehensive fever work-up found no apparent cause of the fever, except for PMF. Therefore, we increased the dose of ruxolitinib and added prednisolone, which was gradually withdrawn with resolution of the fever. However, the patient subsequently developed disseminated tuberculosis and died eight months after initiation of ruxolitinib...
December 27, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29279302/genetic-evidence-for-roles-of-yeast-mitotic-cyclins-at-single-stranded-gaps-created-by-dna-replication
#14
Laurence Signon
Paused/stalled replication forks are major threats to genome integrity; unraveling the complex pathways that contribute to fork stability/restart is crucial. Experimentally, fork stalling is induced by growth in presence of hydroxyurea (HU), which depletes the pool of deoxynucleoside triphosphates (dNTPs) and slows down replication progression in yeast. Here, I report an epistasis analysis, based on sensitivity to HU, between CLB2, the principal mitotic cyclin gene in S. cerevisiae, and genes involved in fork stability and recombination...
December 26, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29251012/enhancing-effect-of-hydroxyurea-on-hb-f-in-sickle-cell-disease-ten-year-egyptian-experience
#15
Ilham Youssry, Amina Abdel-Salam, Rania Ismail, Rayan Bou-Fakhredin, Rania Mohamed Samy, Fatma Ezz El-Deen, Ali T Taher
Patients with sickle cell disease experience hemolytic anemia and vaso-occlusions that result in pain, organ injury, and premature mortality. Several prospective studies have verified the efficacy and tolerability of hydroxyurea (HU), and demonstrated its efficacy in reducing painful vaso-occlusive crises (VOCs) in addition to its ability to increase Hb F levels. We aimed to evaluate the long-term effects of HU therapy on Hb F and assess its long term efficacy and safety in sickle cell disease patients. A retrospective study on 60 sickle cell disease patients was conducted...
December 18, 2017: Hemoglobin
https://www.readbyqxmd.com/read/29242203/hydroxyurea-for-sca-in-africa-no-malaria-harm
#16
Isaac Odame
No abstract text is available yet for this article.
December 14, 2017: Blood
https://www.readbyqxmd.com/read/29228353/the-roles-of-p53-and-its-family-proteins-p63-and-p73-in-the-dna-damage-stress-response-in-organogenesis-stage-mouse-embryos
#17
Nazem El Husseini, Barbara F Hales
Members of the P53 transcription factor family, P53, P63 and P73, play important roles in normal development and in regulating the expression of genes that control apoptosis and cell cycle progression in response to genotoxic stress. P53 is involved in the DNA damage response pathway that is activated by hydroxyurea in organogenesis-stage murine embryos. The extent to which P63 and P73 contribute to this stress response is not known. To address this question, we examined the roles of P53, P63 and P73 in mediating the response of Trp53-positive and Trp53-deficient murine embryos to a single dose of hydroxyurea (400 mg/kg) on gestational day 9...
December 7, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29227281/targeting-mcl-1-enhances-dna-replication-stress-sensitivity-to-cancer-therapy
#18
Guo Chen, Andrew T Magis, Ke Xu, Dongkyoo Park, David S Yu, Taofeek K Owonikoko, Gabriel L Sica, Sarah W Satola, Suresh S Ramalingam, Walter J Curran, Paul W Doetsch, Xingming Deng
DNA double-strand breaks (DSBs) are mainly repaired either by homologous recombination (HR) or by nonhomologous end-joining (NHEJ) pathways. Here, we showed that myeloid cell leukemia sequence 1 (Mcl-1) acts as a functional switch in selecting between HR and NHEJ pathways. Mcl-1 was cell cycle-regulated during HR, with its expression peaking in S/G2 phase. While endogenous Mcl-1 depletion reduced HR and enhanced NHEJ, Mcl-1 overexpression resulted in a net increase in HR over NHEJ. Mcl-1 directly interacted with the dimeric Ku protein complex via its Bcl-2 homology 1 and 3 (BH1 and BH3) domains, which are required for Mcl-1 to inhibit Ku-mediated NHEJ...
December 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29226507/age-is-the-only-predictor-of-small-decrease-in-lung-function-in-children-with-sickle-cell-anemia
#19
Shaina M Willen, Robyn Cohen, Mark Rodeghier, Fenella Kirkham, Susan S Redline, Carol Rosen, Jane Kirkby, Michael R DeBaun
The longitudinal pattern of lung function in children with sickle cell anemia (SCA) has shown a decrease in FEV1 % predicted, a risk factor for death in adults with SCA, but predictors for this decline are poorly characterized. In a prospective longitudinal multi-center cohort of children with SCA, we tested the hypotheses that: 1) FEV1 % predicted declines over time; and 2) SCA-specific characteristics and therapy predict this decline. At three clinical centers, children with SCA (HbSS or HbSβ0 thalassemia), unselected for respiratory disease, were enrolled in the Sleep and Asthma Cohort (SAC) study...
December 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29222303/responsiveness-of-patient-reported-outcome-measurement-information-system-promis-pain-domains-and-disease-specific-patient-reported-outcome-measures-in-children-and-adults-with-sickle-cell-disease
#20
REVIEW
Susanna Curtis, Amanda M Brandow
Case 1: A 33-year-old man with hemoglobin SS (homozygous hemoglobin S) disease presents for his regular clinic visit. He had 6 hospital admissions for pain over the past year. He also has avascular necrosis of the right hip. He takes daily hydroxyurea with hematologic changes indicative of compliance. He also takes morphine sustained release twice daily and morphine immediate release every 6 hours as needed for pain. He feels that more optimal pain control at home would help him reduce his number of hospital admissions in the upcoming year and improve his daily functioning at home...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
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