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Hemic and Lymphatic Diseases Commons

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Correcting Glucose-6-Phosphate Dehydrogenase Deficiency With A Small-Molecule Activator, Sunhee Hwang, Karen Mruk, Simin Rahighi, Andrew G. Raub, Che-Hong Chen, Lisa E. Dorn, Naoki Horikoshi, Soichi Wakatsuki, James K. Chen, Daria Mochly-Rosen 2018 Stanford University

Correcting Glucose-6-Phosphate Dehydrogenase Deficiency With A Small-Molecule Activator, Sunhee Hwang, Karen Mruk, Simin Rahighi, Andrew G. Raub, Che-Hong Chen, Lisa E. Dorn, Naoki Horikoshi, Soichi Wakatsuki, James K. Chen, Daria Mochly-Rosen

Pharmacy Faculty Articles and Research

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human genetic enzymopathies, is caused by over 160 different point mutations and contributes to the severity of many acute and chronic diseases associated with oxidative stress, including hemolytic anemia and bilirubin-induced neurological damage particularly in newborns. As no medications are available to treat G6PD deficiency, here we seek to identify a small molecule that corrects it. Crystallographic study and mutagenesis analysis identify the structural and functional defect of one common mutant (Canton, R459L). Using high-throughput screening, we subsequently identify AG1, a small molecule that increases the activity of the wild-type, the ...


Reducing O Negative Blood Product Usage In A Tertiary Care Academic Medical Center, Wendy Weiler, Tracy Cook, MMC Blood Bank, Mark Parker, Stephen Tyzik, Suneela Nayak, Ruth Hanselman, Amy Sparks 2018 Maine Medical Center

Reducing O Negative Blood Product Usage In A Tertiary Care Academic Medical Center, Wendy Weiler, Tracy Cook, Mmc Blood Bank, Mark Parker, Stephen Tyzik, Suneela Nayak, Ruth Hanselman, Amy Sparks

Operational Excellence

MANAGEMENT OF O NEGATIVE BLOOD USE

O registered blood cells are the universal donor but it comprises only 7% of the blood supply. As a result, inappropriate use can result in shortages.

At an academic tertiary care medical center, a performance improvement goal was established that O negative blood cells would make up less than 12% of all blood type transfused by the end of their fiscal year.

A root cause analysis established reasons for the use of O negative blood cells. A number of countermeasures were initiated using the plan, do, study, act (PDSA) problem solving model. Using newly ...


Opposing Roles Of Fancj And Hltf Protect Forks And Restrain Replication During Stress, Min Peng, Ke Cong, Nicholas J. Panzarino, Sumeet Nayak, Jennifer Calvo, Bin Deng, Lihua Julie Zhu, Monika Morocz, Lili Hegedus, Lajos Haracska, Sharon B. Cantor 2018 University of Massachusetts Medical School

Opposing Roles Of Fancj And Hltf Protect Forks And Restrain Replication During Stress, Min Peng, Ke Cong, Nicholas J. Panzarino, Sumeet Nayak, Jennifer Calvo, Bin Deng, Lihua Julie Zhu, Monika Morocz, Lili Hegedus, Lajos Haracska, Sharon B. Cantor

Open Access Articles

The DNA helicase FANCJ is mutated in hereditary breast and ovarian cancer and Fanconi anemia (FA). Nevertheless, how loss of FANCJ translates to disease pathogenesis remains unclear. We addressed this question by analyzing proteins associated with replication forks in cells with or without FANCJ. We demonstrate that FANCJ-knockout (FANCJ-KO) cells have alterations in the replisome that are consistent with enhanced replication stress, including an aberrant accumulation of the fork remodeling factor helicase-like transcription factor (HLTF). Correspondingly, HLTF contributes to fork degradation in FANCJ-KO cells. Unexpectedly, the unrestrained DNA synthesis that characterizes HLTF-deficient cells is FANCJ dependent and correlates with S1 ...


Prevalence And Management Of Iron Overload In Pyruvate Kinase Deficiency: Report From The Pyruvate Kinase Deficiency Natural History Study, Eduard J. van Beers, Peter E. Newburger, Rachael F. Grace 2018 University Medical Center Utrecht

Prevalence And Management Of Iron Overload In Pyruvate Kinase Deficiency: Report From The Pyruvate Kinase Deficiency Natural History Study, Eduard J. Van Beers, Peter E. Newburger, Rachael F. Grace

Open Access Articles

Pyruvate kinase (PK) deficiency is the most common red cell glycolytic enzyme defect causing hereditary non-spherocytic hemolytic anemia. Current treatments are mainly supportive and include red cell transfusions and splenectomy.11 Regular red cell transfusions are known to result in iron overload; however, the prevalence and spectrum of transfusion-independent iron overload in the overall PK deficient population has not been well defined. This analysis describes the prevalence and clinical characteristics of iron overload in patients enrolled in the PK Deficiency Natural History Study (NHS) with a focus on those patients who are not regularly transfused.2


Primary Cardiac Lymphoma: Importance Of Tissue Diagnosis, Lauren Mendelson, Emily Hsu, Hojune Chung, Andrew Hsu 2018 University of Massachusetts Medical School

Primary Cardiac Lymphoma: Importance Of Tissue Diagnosis, Lauren Mendelson, Emily Hsu, Hojune Chung, Andrew Hsu

Open Access Articles

Primary cardiac lymphoma (PCL) is a rare disease entity that can present with severe cardiac and cardioembolic symptoms. We present a 79-year-old male with history of polymalgia rheumatica on chronic prednisone who presented with a two-week history of progressively worsening dyspnea, cough, and a 10 pound weight loss. Transthoracic echocardiogram (TTE) and computed tomography (CT) of the chest showed a large mediastinal mass with invasion of the pericardium. A biopsy of an abdominal soft-tissue mass confirmed the diagnosis of PCL. The patient was treated with two cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) which was complicated by ...


Multiple Myeloma, Anne Doup 2018 Otterbein University

Multiple Myeloma, Anne Doup

Master of Science in Nursing (MSN) Student Scholarship

No abstract provided.


Pre-Diagnosis Plasma Immune Markers And Risk Of Non-Hodgkin Lymphoma In Two Prospective Cohort Studies, Mara M. Epstein, Bernard Rosner, Elizabeth C. Breen, Julie L. Batista, Edward L. Giovannucci, Larry Magpantay, Jon C. Aster, Scott J. Rodig, Kimberly A. Bertrand, Francine Laden, Otoniel Martinez-Maza, Brenda M. Birmann 2018 University of Massachusetts

Pre-Diagnosis Plasma Immune Markers And Risk Of Non-Hodgkin Lymphoma In Two Prospective Cohort Studies, Mara M. Epstein, Bernard Rosner, Elizabeth C. Breen, Julie L. Batista, Edward L. Giovannucci, Larry Magpantay, Jon C. Aster, Scott J. Rodig, Kimberly A. Bertrand, Francine Laden, Otoniel Martinez-Maza, Brenda M. Birmann

Open Access Articles

Inflammation and B-cell hyperactivation have been associated with non-Hodgkin lymphoma development. This prospective analysis aimed to further elucidate pre-diagnosis plasma immune marker profiles associated with non-Hodgkin lymphoma risk. We identified 598 incident lymphoma cases and 601 matched controls in Nurses' Health Study and Health Professionals Follow-up Study participants with archived pre-diagnosis plasma samples and measured 13 immune marker levels with multiplexed immunoassays. Using multivariable logistic regression we calculated odds ratios and 95% confidence intervals per standard deviation unit increase in biomarker concentration for risk of non-Hodgkin lymphoma and major histologic subtype, stratifying additional models by years ( < 5, 5 to < 10, > /=10) after blood draw ...


Poorly Cytotoxic Terminally Differentiated Cd56(Neg)Cd16(Pos) Nk Cells Accumulate In Kenyan Children With Burkitt Lymphomas, Catherine Forconi, Cormac P. Cosgrove, Pryia Saikumar-Lakshmi, Christina E. Nixon, Joslyn Foley, John Michael Ong'echa, Juliana A. Otieno, Galit Alter, Christian Munz, Ann M. Moormann 2018 University of Massachusetts Medical School

Poorly Cytotoxic Terminally Differentiated Cd56(Neg)Cd16(Pos) Nk Cells Accumulate In Kenyan Children With Burkitt Lymphomas, Catherine Forconi, Cormac P. Cosgrove, Pryia Saikumar-Lakshmi, Christina E. Nixon, Joslyn Foley, John Michael Ong'echa, Juliana A. Otieno, Galit Alter, Christian Munz, Ann M. Moormann

Open Access Articles

Natural killer (NK) cells are critical for restricting viral infections and mediating tumor immunosurveillance. Epstein-Barr virus (EBV) and Plasmodium falciparum malaria are known risk factors for endemic Burkitt lymphoma (eBL), the most common childhood cancer in equatorial Africa. To date, the composition and function of NK cells have not been evaluated in eBL etiology or pathogenesis. Therefore, using multiparameter flow cytometry and in vitro killing assays, we compared NK cells from healthy children and children diagnosed with eBL in Kenya. We defined 5 subsets based on CD56 and CD16 expression, including CD56(neg)CD16(pos) We found that licensed and ...


Fatal Case Of Ttp In Patient With Underlying Pulmonary Aspergillosis, Shimool A. Rabbani DO, Ankit Shah DO, Joan Wiley DO, Jay Kirkham DO 2018 Rowan University SOM

Fatal Case Of Ttp In Patient With Underlying Pulmonary Aspergillosis, Shimool A. Rabbani Do, Ankit Shah Do, Joan Wiley Do, Jay Kirkham Do

Stratford Campus Research Day

A 70-year- old Caucasian male with history of renal transplant on tacrolimus presented with 5-days of fevers, productive cough, and confusion. Patient was initially diagnosed with pneumonia, presumed bacterial, but soon noted to have worsening neurologic status, renal failure, and respiratory failure requiring mechanical ventilation. He further developed thrombotic microangiopathy (TMA); TMA along with the other clinical findings led to diagnosis of Thrombotic Thrombocytopenic Purpura (TTP). Despite aggressive treatment of TTP with plasmapheresis, patient expired on day five of his hospitalization. Fungal cultures from a bronchoscope performed on day three of hospitalization that resulted postmortem grew many aspergillus flavus and ...


Preleukemia And Leukemia-Initiating Cell Activity In Inv(16) Acute Myeloid Leukemia, John A. Pulikkan, Lucio H. Castilla 2018 University of Massachusetts Medical School

Preleukemia And Leukemia-Initiating Cell Activity In Inv(16) Acute Myeloid Leukemia, John A. Pulikkan, Lucio H. Castilla

Open Access Articles

Acute myeloid leukemia (AML) is a collection of hematologic malignancies with specific driver mutations that direct the pathology of the disease. The understanding of the origin and function of these mutations at early stages of transformation is critical to understand the etiology of the disease and for the design of effective therapies. The chromosome inversion inv(16) is thought to arise as a founding mutation in a hematopoietic stem cell (HSC) to produce preleukemic HSCs (preL-HSCs) with myeloid bias and differentiation block, and predisposed to AML. Studies in mice and human AML cells have established that inv(16) AML follows ...


Bexarotene-Induced Hypertriglyceridemia: A Case Report, Chris Maminakis, Arin C. Whitman, Nahida Islam 2018 Western New England University

Bexarotene-Induced Hypertriglyceridemia: A Case Report, Chris Maminakis, Arin C. Whitman, Nahida Islam

Open Access Articles

We present a case of a patient with cutaneous T-cell lymphoma started on bexarotene 300 mg/m(2) due to progressing disease. The patient experienced good clinical response, but unfortunately, she developed rapid and profound hypertriglyceridemia. Although hypertriglyceridemia occurs in high incidence with bexarotene therapy, management recommendations are scarce. Due to the rise in triglycerides, atorvastatin 10 mg daily was initiated in combination with fenofibrate 120 mg daily. Triglycerides continued to increase, so the patient was instructed to take atorvastatin 40 mg, fenofibrate 120 mg, and to hold bexarotene for 2 weeks. After the 2-week break, bexarotene was restarted at ...


Designing A Social Norms-Based Intervention To Reduce Anemia In India: A Formative Research Protocol, Aika Aluc, Erica Sedlander, Rajiv N. Rimal, Sameera A. Talegawkar, Hagere Yilma, Wolfgang Munar 2018 George Washington University

Designing A Social Norms-Based Intervention To Reduce Anemia In India: A Formative Research Protocol, Aika Aluc, Erica Sedlander, Rajiv N. Rimal, Sameera A. Talegawkar, Hagere Yilma, Wolfgang Munar

GW Research Days 2016 - Present

Background: Economic and gender inequalities are important determinants of anemia in low and middle income countries. Gender dimensions of food security contribute to the undernutrition among women. More than half of women of reproductive age in India are anemic. Anemia causes increased risk of preterm delivery, higher maternal mortality and contributes to fatigue, which influences women’s work productivity. The World Health Organization (WHO) recommends daily oral iron and folic acid (IFA) supplements during pregnancy and weekly supplements for women of reproductive age. Despite the efforts of government programs and global donors to reduce anemia in India, both initial uptake ...


Evaluating The Impact Of A Standardized Education Class On A Person Diagnosed With Chronic Kidney Disease, Stage Iv, Nancy K. Uhland, DNP, MSN, RN, FNP-C 2018 George Washington University

Evaluating The Impact Of A Standardized Education Class On A Person Diagnosed With Chronic Kidney Disease, Stage Iv, Nancy K. Uhland, Dnp, Msn, Rn, Fnp-C

Doctor of Nursing Practice Projects

Background: Chronic kidney disease (CKD) is a complex, progressive, and costly disease impacting more than 26 million Americans. Providing effective education is necessary so the patient may actively participate in managing the disease process, but the effectiveness of the delivery of education to the patient with CKD is not well-known.

Objective: To evaluate the effectiveness of a standardized education class on the basic kidney knowledge of persons diagnosed with CKD, stage IV.

Method: This pilot study, using a one-group pre and post-test design, was conducted in an outpatient nephrology clinic located in Washington, D.C. The study participants, recruited using ...


Designing A Socio-Normative Intervention To Reduce Anemia In Odisha India: A Formative Research Protocol [Version 1; Referees: 2 Approved], Erica Sedlander, Rajiv N Rimal, Sameera A Talegawkar, Hagere Yilma, Wolfgang Munar 2018 George Washington University

Designing A Socio-Normative Intervention To Reduce Anemia In Odisha India: A Formative Research Protocol [Version 1; Referees: 2 Approved], Erica Sedlander, Rajiv N Rimal, Sameera A Talegawkar, Hagere Yilma, Wolfgang Munar

Prevention and Community Health Faculty Publications

Background: More than half of women of reproductive age in India are anemic. Anemia is associated with increased risk of preterm delivery, higher maternal mortality and contributes to fatigue, which affects women’s work productivity. The World Health Organization (WHO) recommends daily oral iron and folic acid (IFA) supplements during pregnancy and weekly supplements for women of reproductive age. Government programs and global donors have distributed and promoted IFA supplements in India for over four decades. However, initial intake and compliance remain inadequate.
Objectives: This protocol describes the formative research phase of a larger study, which will test, through a ...


Autologous/Allogeneic Hematopoietic Cell Transplantation Versus Tandem Autologous Transplantation For Multiple Myeloma: Comparison Of Long-Term Postrelapse Survival, Myo Htut, Muthalagu Ramanathan, Parameswaran Hari 2018 City of Hope Medical Center

Autologous/Allogeneic Hematopoietic Cell Transplantation Versus Tandem Autologous Transplantation For Multiple Myeloma: Comparison Of Long-Term Postrelapse Survival, Myo Htut, Muthalagu Ramanathan, Parameswaran Hari

Open Access Articles

We compared postrelapse overall survival (OS) after autologous/allogeneic (auto/allo) versus tandem autologous (auto/auto) hematopoietic cell transplantation (HCT) in patients with multiple myeloma (MM). Postrelapse survival of patients receiving an auto/auto or auto/allo HCT for MM and prospectively reported to the Center for International Blood and Marrow Transplant Research between 2000 and 2010 were analyzed. Relapse occurred in 404 patients (72.4%) in the auto/auto group and in 178 patients (67.4%) in the auto/allo group after a median follow-up of 8.5 years. Relapse occurred before 6 months after a second HCT in ...


Hodgkin Lymphoma: Differences In Treatment Between Europe And The United States/North America: Evolving Trends In Protocol Therapy, Thomas J. Fitzgerald, Maryann Bishop-Jodoin 2018 University of Massachusetts Medical School

Hodgkin Lymphoma: Differences In Treatment Between Europe And The United States/North America: Evolving Trends In Protocol Therapy, Thomas J. Fitzgerald, Maryann Bishop-Jodoin

Open Access Articles

With continued progress and success in clinical care, the management of patients with Hodgkin lymphoma (HL) has undergone continuous revision to improve patient care outcomes and limit acute and late treatment effects on normal tissue imposed by therapy. Hodgkin lymphoma is a disease that affects children, adolescents, and adults. Clinical management strategies are influenced by the patient's age at diagnosis, tumor burden, response to induction therapy, and potential expectation of treatment impact on normal tissue. The approach to patient management varies in many parts of the world and is influenced by treatment availability, physician training, and medical culture. Differences ...


Early Epstein-Barr Virus Genomic Diversity And Convergence Toward The B95.8 Genome In Primary Infection, Eric R. Weiss, Susanna L. Lamers, Jennifer L. Henderson, Alexandre Melnikov, Mohan Somasundaran, Manuel Garber, Liisa K. Selin, Chad Nusbaum, Katherine Luzuriaga 2018 University of Massachusetts Medical School

Early Epstein-Barr Virus Genomic Diversity And Convergence Toward The B95.8 Genome In Primary Infection, Eric R. Weiss, Susanna L. Lamers, Jennifer L. Henderson, Alexandre Melnikov, Mohan Somasundaran, Manuel Garber, Liisa K. Selin, Chad Nusbaum, Katherine Luzuriaga

Garber Lab Publications

Over 90% of the world's population is persistently infected with Epstein-Barr virus. While EBV does not cause disease in most individuals, it is the common cause of acute infectious mononucleosis (AIM) and has been associated with several cancers and autoimmune diseases, highlighting a need for a preventive vaccine. At present, very few primary, circulating EBV genomes have been sequenced directly from infected individuals. While low levels of diversity and low viral evolution rates have been predicted for double-stranded DNA (dsDNA) viruses, recent studies have demonstrated appreciable diversity in common dsDNA pathogens (e.g., cytomegalovirus). Here, we report 40 full-length ...


The Evaluation Of Mefloquine Drug Repurposing On Acute Myeloid Leukemia, Jessica L. Phan, Bhavuk Garg, Hrishikesh Mehta, Seth Corey 2018 Virginia Commonwealth University

The Evaluation Of Mefloquine Drug Repurposing On Acute Myeloid Leukemia, Jessica L. Phan, Bhavuk Garg, Hrishikesh Mehta, Seth Corey

Undergraduate Research Posters

The aim of this study is to observe cell proliferation, cell viability, apoptosis, and autophagy on acute myeloid leukemia (AML) cell lines, NB4 and U937, with the drug repurposing of mefloquine (MQ). Methods such as the 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay and trypan blue staining have shown a decrease in live cells with high concentrations of mefloquine. Using their average perspective IC50 values of MQ concentration, Western blotting was applied by means of apoptosis and autophagy markers to determine if the induction of apoptosis and inhibition of autophagy was present in MQ-treated AML cells. The experiment will ...


A Healthcare Improvement Initiative To Increase Multidisciplinary Pain Management Referrals Of Youth With Sickle Cell Disease, Rae Ann Kingsley, Gail Robertson, Lynne Covitz, Areli Ramphal 2018 Children's Mercy Hospital

A Healthcare Improvement Initiative To Increase Multidisciplinary Pain Management Referrals Of Youth With Sickle Cell Disease, Rae Ann Kingsley, Gail Robertson, Lynne Covitz, Areli Ramphal

Posters

No abstract provided.


Medication Timeliness In Emergency Department In Pediatric Sickle Cell Disease Population Presenting With Vaso-Occlusive Episode, Derrick Goubeaux, Kaitlyn Hoch, Gerald Woods, Julie Routhieaux, Maureen Guignon, Valerie McDougall Kestner 2018 Children's Mercy Hospital

Medication Timeliness In Emergency Department In Pediatric Sickle Cell Disease Population Presenting With Vaso-Occlusive Episode, Derrick Goubeaux, Kaitlyn Hoch, Gerald Woods, Julie Routhieaux, Maureen Guignon, Valerie Mcdougall Kestner

Posters

No abstract provided.


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