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Jing Huang, Leyan Wang, Chen Lu, Qun He, Yajing Xu, Fangping Chen, Xielan Zhao
OBJECTIVE: Previous studies compared the predictive ability of European Treatment Outcome Study (EUTOS), Sokal, and Hasford scoring systems and demonstrated inconsistent findings with unknown reason. This study is to determine a useful scoring system to predict the prognosis of patients with chronic myeloid leukemia (CML) and identify the probable factors that affect the scoring. MATERIALS AND METHODS: This is a retrospective cohort study. The predictive ability of EUTOS and the factors that affect scoring were analyzed in 234 Chinese CML-CP patients treated with front-line imatinib, including few patients temporarily administered hydroxyurea for cytoreduction before imatinib...
October 18, 2016: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Julia H Indik, Vineet Nair, Ruslan Rafikov, Iwan S Nyotowidjojo, Jaskanwal Bisla, Mayank Kansal, Devang S Parikh, Melissa Robinson, Anand Desai, Megha Oberoi, Akash Gupta, Taimur Abbasi, Zain Khalpey, Amit R Patel, Roberto M Lang, Samuel C Dudley, Bum-Rak Choi, Joe G N Garcia, Roberto F Machado, Ankit A Desai
Sudden death is a leading cause of mortality in sickle cell disease, implicating ventricular tachyarrhythmias. Prolonged QTc on an electrocardiogram (ECG), commonly seen with myocardial ischemia, is a known risk for polymorphic ventricular tachycardia (VT). We hypothesized that prolonged QTc is associated with mortality in sickle cell disease. ECG were analyzed from a cohort of 224 sickle patients (University of Illinois at Chicago, UIC) along with available laboratory, and echocardiographic findings, and from another cohort of 38 patients (University of Chicago, UC) for which cardiac MRI and free heme values were also measured...
2016: PloS One
Byung Kwon Chong, Dana Mun, Chae Hoon Kang, Chong-Bin Park, Won Chul Cho
Essential thrombocytosis (ET) is a myeloproliferative disorder characterized by an anomalous increase in platelet production. Many patients with ET are asymptomatic. Few studies have reported ET-associated thromboembolism in large vessels such as the aorta. We report a patient with ET who presented with peripheral embolism from an abdominal aortic thrombus and developed acute limb ischemia. The patient underwent aortic replacement successfully. The patient's platelet count was controlled with hydroxyurea, and no recurrence was noted over 2 years of follow-up...
October 2016: Korean Journal of Thoracic and Cardiovascular Surgery
Beverly A Schaefer, Jonathan M Flanagan, Ofelia A Alvarez, Stephen C Nelson, Banu Aygun, Kerri A Nottage, Alex George, Carla W Roberts, Connie M Piccone, Thad A Howard, Barry R Davis, Russell E Ware
Discovery and validation of genetic variants that influence disease severity in children with sickle cell anemia (SCA) could lead to early identification of high-risk patients, better screening strategies, and intervention with targeted and preventive therapy. We hypothesized that newly identified genetic risk factors for the general African American population could also impact laboratory biomarkers known to contribute to the clinical disease expression of SCA, including variants influencing the white blood cell count and the development of albuminuria and abnormal glomerular filtration rate...
2016: PloS One
Emily Riehm Meier, Angeli Rampersad
Once a fatal disease of childhood, more than 95% of patients born today with sickle cell disease (SCD) in developed countries are expected to survive into adulthood, largely because of improvements in supportive and preventive care (newborn screening, penicillin prophylaxis, transcranial Doppler (TCD) screening). Hydroxyurea (HU) therapy, the only oral medication currently available to prevent SCD complications, has become more widespread over the past 20 years. The NHLBI recommends that HU be offered to all patients with HbSS beginning at nine months of age, and the recently published Abnormal TCD with Transfusions Changing to HU (TWiTCH) trial has shown HU as an acceptable alternative to transfusion therapy for patients at high risk of stroke...
October 5, 2016: Pediatric Research
Susan Creary, Deena J Chisolm, Sarah H O'Brien
BACKGROUND: Hydroxyurea (HU) is the only disease-modifying medication for patients with sickle cell disease (SCD). HU can reduce SCD-related complications but only 35% to 50% of pediatric patients adhere to HU at the rates achieved in clinical trials and this limits its clinical effectiveness. Mobile Directly Observed Therapy (Mobile DOT) is a pilot-tested, electronic, multidimensional, HU adherence intervention that targets many components of the Health Behavior Model. OBJECTIVE: The aim of this study is to evaluate the impact of Mobile DOT on HU adherence in children with SCD...
October 3, 2016: JMIR Research Protocols
Anu Marahatta, Vandana Megaraj, Patrick T McGann, Russell E Ware, Kenneth D R Setchell
BACKGROUND: Sickle cell anemia (SCA) is a life-threatening blood disorder characterized by the presence of sickle-shaped erythrocytes. Hydroxyurea is currently the only US Food and Drug Administration-approved treatment and there is a need for a convenient method to monitor compliance and hydroxyurea concentrations, especially in pediatric SCA patients. METHODS: We describe a novel approach to the determination of hydroxyurea concentrations in dried whole blood collected on DMPK-C cards or volumetric absorptive microsampling (VAMS) devices...
September 30, 2016: Clinical Chemistry
Daniel J Zinn, Amanda B Grimes, Howard Lin, Olive Eckstein, Carl E Allen, Kenneth L McClain
No abstract text is available yet for this article.
September 29, 2016: Blood
Harriët M Loovers, Nienke Tamminga, André B Mulder, Rienk Y J Tamminga
Case reports on the effect of hydroxyurea (HU) therapy for unstable hemoglobins (Hbs) are sparse; only three adult cases have been reported. We report for the first time on the effect of HU therapy in children carrying unstable Hbs. The first case concerns a female child with a familial history of chronic hemolytic anemia. She was diagnosed with Hb Volga (HBB: c.83C>A) at the age of 7 months. At age 6, treatment options were reconsidered due to increasing fatigue and decreasing Hb concentration. The second case also concerns a female child with chronic hemolytic anemia and icterus since the age of 5...
September 30, 2016: Hemoglobin
Esprit Ma, Vijayveer Bonthapally, Anita Chawla, Patrick Lefebvre, Ronan Swords, Marie-Hélène Lafeuille, Jonathan Fortier, Bruno Emond, Mei Sheng Duh, Bruce J Dezube
BACKGROUND: Many elderly patients with acute myeloid leukemia (AML) are considered ineligible for standard intensive induction therapy due to performance status and comorbidities. We analyzed treatment patterns and outcomes among elderly patients newly diagnosed with AML in the US community oncology setting. METHODS: A retrospective observational study was conducted using patient-level data from a network of US community oncology practices provided by Altos Solutions...
August 10, 2016: Clinical Lymphoma, Myeloma & Leukemia
Alberto Alvarez-Larrán, Manuel Pérez-Encinas, Francisca Ferrer-Marin, Juan-Carlos Hernández-Boluda, María José Ramírez, Joaquín Martínez-López, Elena Magro, Yasmina Cruz, María Isabel Mata, Pilar Aragües, María Laura Fox, Beatriz Cuevas, Sara Montesdeoca, José Angel Hernández-Rivas, Valentin García-Gutiérrez, María Teresa Gómez-Casares, Juan Luis Steegmann, María Antonia Durán, Montse Gómez, Ana Kerguelen, Abelardo Bárez, Mari Carmen García, Concepción Boqué, José María Raya, Clara Martinez, Manuel Albors, Francesc Garcia, Carmen Burgaleta, Carlos Besses
Hematocrit control below 45% is associated with a lower rate of thrombosis in polycythemia vera. In patients receiving hydroxyurea, this target can be achieved with hydroxyurea alone or with the combination of hydroxyurea plus phlebotomies. However, the clinical implications of phlebotomy requirement under hydroxyurea therapy are unknown. For such purpose, need of additional phlebotomies during the first 5 years of hydroxyurea therapy was evaluated in 533 patients with polycythemia vera. Patients requiring 3 or more phlebotomies per year (n=85, 16%) showed a worse hematocrit control than those requiring 2 or less phlebotomies per year (n=448, 84%)...
September 29, 2016: Haematologica
Halima Bello-Manga, Michael R DeBaun, Adetola A Kassim
Sickle cell disease (SCD) is the most common inherited hemoglobinopathy in the world, with the majority of cases in sub-Saharan Africa. Concomitant nutritional deficiencies, infections or exposure to environmental toxins exacerbate chronic anemia in children with SCD. The resulting relative anemia is associated with increased risk of strokes, poor cognitive function and impaired growth. It may also attenuate optimal response to hydroxyurea therapy, the only effective and practical treatment option for SCD in sub-Saharan Africa...
October 17, 2016: Expert Review of Hematology
Keffy Kehrli, Michael Phelps, Pavlo Lazarchuk, Eleanor Chen, Raymond Monnat, Julia M Sidorova
The WRN helicase/exonuclease is mutated in Werner syndrome of genomic instability and premature aging. WRN-depleted fibroblasts, while remaining largely viable, have a reduced capacity to maintain replication forks active during a transient hydroxyurea-induced arrest. A strand exchange protein RAD51 is also required for replication fork maintenance, and here we show that recruitment of RAD51 to stalled forks is reduced in the absence of WRN. We performed a siRNA screen for genes that are required for viability of WRN-depleted cells after hydroxyurea treatment, and identified HDAC1, a member of the class I histone deacetylase family...
September 26, 2016: Journal of Biological Chemistry
Michael Leung, Kaitlin Highsmith, Amber Rexwinkle
Myelofibrosis is a BCR-ABL-negative myeloproliferative neoplasm characterized by abnormal hematopoiesis. Alterations to the Janus kinase-signal transducer and activator of transcription pathway result in dysregulation of gene transcription and cell proliferation. Patients with symptomatic myelofibrosis present with a variety of signs and symptoms including, but not limited to myelosuppression, marked splenomegaly, abdominal discomfort, fatigue, and blood transfusion-dependence. Traditional myelosuppressive therapies including hydroxyurea, azacitidine, and cladribine aim to reduce constitutional symptoms and control the burden of disease...
September 26, 2016: Journal of Oncology Pharmacy Practice
Minxing Li, Francesca Cole, Dharm S Patel, Sarah M Misenko, Joonyoung Her, Amy Malhowski, Ali Alhamza, Haiyan Zheng, Richard Baer, Thomas Ludwig, Maria Jasin, André Nussenzweig, Lourdes Serrano, Samuel F Bunting
BRCA1 mutations strongly predispose affected individuals to breast and ovarian cancer, but the mechanism by which BRCA1 acts as a tumor suppressor is not fully understood. Homozygous deletion of exon 2 of the mouse Brca1 gene normally causes embryonic lethality, but we show that exon 2-deleted alleles of Brca1 are expressed as a mutant isoform that lacks the N-terminal RING domain. This "RING-less" BRCA1 protein is stable and efficiently recruited to the sites of DNA damage. Surprisingly, robust RAD51 foci form in cells expressing RING-less BRCA1 in response to DNA damage, but the cells nonetheless display the substantial genomic instability...
September 26, 2016: EMBO Reports
Maryam Iman, Zeynab Khansepid, Asghar Davood
BACKGROUND: Ribonucleotide Reductase (RNR) is an important anticancer chemotherapy target. It has main key role in DNA synthesis and cell growth. Therefore several RNR inhibitors, such as Hydroxyurea, have entered the clinical trials. Based on our proposed mechanism, radical site of RNR protein reacts with Hydroxyurea in which hydroxyurea is converted into its oxidized form compound III, and whereby the tyrosyl radical is converted into a normal tyrosine residue. OBJECTIVE: In this study, docking and molecular dynamics simulations were used for proposed molecular mechanism of Hydroxyurea in RNR inhibition as anticancer agent...
September 26, 2016: Recent Patents on Anti-cancer Drug Discovery
Harikanth Venkannagari, Patricia Verheugd, Jarkko Koivunen, Teemu Haikarainen, Ezeogo Obaji, Yashwanth Ashok, Mohit Narwal, Taina Pihlajaniemi, Bernhard Lüscher, Lari Lehtiö
Members of the human diphtheria toxin-like ADP-ribosyltransferase (ARTD or PARP) family play important roles in regulating biological activities by mediating either a mono-ADP-ribosylation (MARylation) of a substrate or a poly-ADP-ribosylation (PARylation). ARTD10/PARP10 belongs to the MARylating ARTDs (mARTDs) subfamily, and plays important roles in biological processes that range from cellular signaling, DNA repair, and cell proliferation to immune response. Despite their biological and disease relevance, no selective inhibitors for mARTDs are available...
September 22, 2016: Cell Chemical Biology
Frank A Ferrone
Sickle cell disease is probably the first known assembly disease, and its mechanism has been extensively studied. It arises because of the expression of a mutant hemoglobin that can polymerize, and which does so by a double nucleation mechanism that is now seen to operate in other diseases. The polymers so formed lead to circulatory obstruction in the microcirculation. The accuracy of the description that has been developed is sufficient to describe precisely the impact of molecules that cannot join polymers but that still crowd the solution, including fetal hemoglobin...
September 22, 2016: International Journal of Biological Macromolecules
Shardul Soman, G D Tharadara, Naitik Chhatrala, Shubham Jain
INTRODUCTION: Extramedullary hematopoeisis (EMH) is defined as formation of blood cells outside the bone marrow. It occurs most commonly in the liver and spleen in patients having disorders that lead to chronic anaemia. EMH in spinal canal is a very rare site and cauda equina syndrome due to EMH has very few cases presented in literature. CASE PRESENTATION: A 28 year old male patient presented with complain of incontinenance of bladder and bowel along with saddle anaesthesia from 10 days...
2016: International Journal of Spine Surgery
Huimin Ma, Teng Song, Tianhua Wang, Shui Wang
Mammalian p53 is a super tumor suppressor and plays a key role in guarding genome from DNA damage. However, p53 has not been found in plants which do not bear cancer although they constantly expose to ionizing radiation of ultraviolet light. Here we introduced p53 into the model plant Arabidopsis and examined p53-conferred phenotype in plant. Most strikingly, p53 caused early senescence and fasciation. In plants, fasciation has been shown as a result of the elevated homologous DNA recombination. Consistently, a reporter with overlapping segments of the GUS gene (1445) showed that the frequency of homologous recombination was highly induced in p53-transgenic plants...
2016: PloS One
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