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Evaluating A Preoperative Protocol That Includes Magnetic Resonance Imaging For Lymph Node Metastasis In The Cholangiocarcinoma Screening And Care Program (Cascap) In Thailand., Metha Songthamwat, Nittaya Chamadol, Narong Khuntikeo, Jadsada Thinkhamrop, Supinda Koonmee, Nathaphop Chaichaya, Jeffrey Bethony, Bandit Thinkhamrop 2017 George Washington University

Evaluating A Preoperative Protocol That Includes Magnetic Resonance Imaging For Lymph Node Metastasis In The Cholangiocarcinoma Screening And Care Program (Cascap) In Thailand., Metha Songthamwat, Nittaya Chamadol, Narong Khuntikeo, Jadsada Thinkhamrop, Supinda Koonmee, Nathaphop Chaichaya, Jeffrey Bethony, Bandit Thinkhamrop

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Treatment planning especially liver resection in cholangiocarcinoma (CCA) depends on the extension of tumor and lymph node metastasis which is included as a key criterion for operability. Magnetic resonance imaging (MRI) offers a rapid and powerful tool for the detection of lymph node metastasis (LNM) and in the current manuscript is assessed as a critical tool in the preoperative protocol for liver resection for treatment of CCA. However, the accuracy of MRI to detect LNM from CCA had yet to be comprehensively evaluated.

METHODS: The accuracy of MRI to detect LNM was assessed in a cohort of individuals with ...


Flow Cytometric And Demographic Analysis Of T Cell Acute Lymphoblastic Leukemia In Pakistani Population., M R. Khawaja, S S. Allana, N N. Akbaral, S N. Adil, M. Khurshid, Shahid Pervez 2017 Aga Khan University

Flow Cytometric And Demographic Analysis Of T Cell Acute Lymphoblastic Leukemia In Pakistani Population., M R. Khawaja, S S. Allana, N N. Akbaral, S N. Adil, M. Khurshid, Shahid Pervez

Mohammad Khurshid

Background: This study was carried out to analyze the proportion of T cell acute lymphoblastic leukemia (TALL) among all acute lymphoblastic leukemia (ALL) in Pakistani population and its correlation with the demographic features. Accuracy of cell surface markers used in flow cytometric analysis of the leukemic cells was also determined. Methods: Data of 209 consecutive cases of acute lymphoblastic leukemia (ALL) presenting between July 1995 and July 2003 was analyzed. Flow cytometry was performed on all ALL cases using the standard protocols. TALL markers included CD3, CD5 and CD7. Results: Proportion of TALL among known ALL Pakistani patients was 17 ...


Determining The Longitudinal Validity And Meaningful Differences In Hrql Of The Pedsql™ Sickle Cell Disease Module., Julie A Panepinto, J Paul Scott, Oluwakemi Badaki-Makun, Deepika S Darbari, Corrie E Chumpitazi, Gladstone E Airewele, +several additional authors 2017 George Washington University

Determining The Longitudinal Validity And Meaningful Differences In Hrql Of The Pedsql™ Sickle Cell Disease Module., Julie A Panepinto, J Paul Scott, Oluwakemi Badaki-Makun, Deepika S Darbari, Corrie E Chumpitazi, Gladstone E Airewele, +Several Additional Authors

Pediatrics Faculty Publications

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.

METHODS: An ancillary study was conducted utilizing a multi-center prospective trial design. Children ages 4-21 years with sickle cell disease admitted to the hospital for an acute painful ...


Pediatric Critical Care Transfusion And Anemia Expertise Initiative, Stacey L. Valentine, Scot T. Bateman, Mela Bembea, Phillip Spinella, Allan Doctor, Nabil Hassan, Robert Parker, Marie Steiner, Marisa Tucci, Jacques Lacroix 2017 University of Massachusetts Medical School

Pediatric Critical Care Transfusion And Anemia Expertise Initiative, Stacey L. Valentine, Scot T. Bateman, Mela Bembea, Phillip Spinella, Allan Doctor, Nabil Hassan, Robert Parker, Marie Steiner, Marisa Tucci, Jacques Lacroix

UMass Center for Clinical and Translational Science Research Retreat

Introduction/Hypothesis: Despite evidence that a lower hemoglobin threshold is safe in hemodynamically stable children, studies have shown that transfusion thresholds in practice are higher, exposing these children to the morbidity and mortality associated with RBC transfusion. Therefore, there is increased need for evidence-based blood management strategies for clinicians caring for critically ill children.

Methods: The Pediatric Critical Care Transfusion and Anemia Expertise Initiative has brought together a group of 49 international experts in pediatric transfusion/critical care in collaboration with the Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI), to ...


Rosai-Dorfman Disease Of The Breast, Eileen E. Delaney, Anne C. Larkin, Sue MacMaster, Ali Sakhdari, Carolynn M. Debenedictis 2017 University of Massachusetts Medical School

Rosai-Dorfman Disease Of The Breast, Eileen E. Delaney, Anne C. Larkin, Sue Macmaster, Ali Sakhdari, Carolynn M. Debenedictis

Radiology Publications and Presentations

Rosai-Dorfman disease (also known as sinus histiocytosis with massive lymphadenopathy) is a rare benign proliferative disorder of histiocytes that typically involves the lymph nodes and can also involve extranodal sites. Rosai-Dorfman disease confined to the breast is extremely rare, but important to recognize as it can mimic malignancy. We present the case of a 63-year-old woman who presented with a palpable breast lump that was highly suspicious for malignancy based on mammogram and ultrasound appearance. Biopsy revealed inflammatory tissue with lymphoplasmacytic and histiocytic predominance. The diagnosis of Rosai-Dorfman was made based on characteristic staining of histiocytes with S-100 and the ...


Human And Epstein-Barr Virus Mirna Profiling As Predictive Biomarkers For Endemic Burkitt Lymphoma, Cliff I. Oduor, Mercedeh Movassagh, Yasin Kaymaz, Kiprotich Chelimo, Juliana A. Otieno, John M. Ong'echa, Ann M. Moormann, Jeffrey A. Bailey 2017 Maseno University

Human And Epstein-Barr Virus Mirna Profiling As Predictive Biomarkers For Endemic Burkitt Lymphoma, Cliff I. Oduor, Mercedeh Movassagh, Yasin Kaymaz, Kiprotich Chelimo, Juliana A. Otieno, John M. Ong'echa, Ann M. Moormann, Jeffrey A. Bailey

University of Massachusetts Medical School Faculty Publications

Endemic Burkitt lymphoma (eBL) is an aggressive B cell lymphoma and is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum malaria co-infections. Central to BL oncogenesis is the over-expression of the MYC proto-oncogene which is caused by a translocation of an Ig enhancer in approximation to the myc gene. While whole genome/transcriptome sequencing methods have been used to define driver mutations and transcriptional dysregulation, microRNA (miRNA) dysregulation and differential expression has yet to be fully characterized. We hypothesized that both human and EBV miRNAs contribute to eBL clinical presentation, disease progression, and poor outcomes. Using sensitive and precise deep ...


Aapt Diagnostic Criteria For Chronic Sickle Cell Disease Pain., Carlton Dampier, Tonya M Palermo, Deepika S Darbari, Kathryn Hassell, Wally Smith, William Zempsky 2017 George Washington University

Aapt Diagnostic Criteria For Chronic Sickle Cell Disease Pain., Carlton Dampier, Tonya M Palermo, Deepika S Darbari, Kathryn Hassell, Wally Smith, William Zempsky

Pediatrics Faculty Publications

Pain in sickle cell disease (SCD) is associated with increased morbidity, mortality, and high health care costs. Although episodic acute pain is the hallmark of this disorder, there is an increasing awareness that chronic pain is part of the pain experience of many older adolescents and adults. A common set of criteria for classifying chronic pain associated with SCD would enhance SCD pain research efforts in epidemiology, pain mechanisms, and clinical trials of pain management interventions, and ultimately improve clinical assessment and management. As part of the collaborative effort between the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities ...


Post-Transfusion Purpura: A Case Report Of An Underdiagnosed Phenomenon, Hind Rafei, Raza Yunus, Samah Nassereddine 2017 George Washington University

Post-Transfusion Purpura: A Case Report Of An Underdiagnosed Phenomenon, Hind Rafei, Raza Yunus, Samah Nassereddine

Medicine Faculty Publications

Post-transfusion purpura is a rare transfusion-related complication that often goes undiagnosed. It is due to alloimmunization against platelet antigens which leads to acute profound thrombocytopenia following the transfusion of any platelet-containing product (red blood cells or platelets). It is commonly seen in multiparous women. Here, we report a case of post-transfusion purpura in a 56-year-old multiparous woman who developed acute thrombocytopenia seven days following a packed red blood cell transfusion. We will discuss the clinical presentation, diagnosis, workup and treatment of this rare disease. It is important to recognize this entity separately and to include it in the differential diagnosis ...


Pseudomembranous Tracheitis Caused By Aspergillus Fumigatus In The Setting Of High Grade T-Cell Lymphoma, Prashant Malhotra, Karan Singh, Paul Gill, Sonu Sahni, Mina Makaryus, Arunabh Talwar 2017 Touro College of Osteopathic Medicine (New York)

Pseudomembranous Tracheitis Caused By Aspergillus Fumigatus In The Setting Of High Grade T-Cell Lymphoma, Prashant Malhotra, Karan Singh, Paul Gill, Sonu Sahni, Mina Makaryus, Arunabh Talwar

Touro College of Osteopathic Medicine (New York) Publications and Research

Pseudomembranous tracheitis (PMT) is a rare condition most commonly caused by fungal or bacterial infection that is characterized by a pseudomembrane that partially or completely covers the tracheobronchial tree. PMT is most commonly found in immunocompromised patient populations, such as post-chemotherapy, AIDS, post-transplant and hematological malignancies. Due to its rarity, PMT is often not included in the differential diagnosis. This case describes a 65 year old male with persistent fever and refractory cough despite high dose empiric antibiotics. Subsequent bronchoscopy with biopsy revealed pseudomembranous tracheitis due to Aspergillus fumigatus in the setting of T-cell lymphoma. PMT should be considered in ...


A Rare Breed: Wild-Type Braf And Ighv Expression In A 29 Year Old Lady With Classical Hairy Cell Leukemia, A. Hossain, Hind Rafei, Amar Jariwala, Khaled El-Shami 2017 George Washington University

A Rare Breed: Wild-Type Braf And Ighv Expression In A 29 Year Old Lady With Classical Hairy Cell Leukemia, A. Hossain, Hind Rafei, Amar Jariwala, Khaled El-Shami

Medicine Faculty Publications

The V600 BRAF mutation has been described as a key mutation in the pathogenesis of classical hairy cell leukemia (c-HCL) cases without expression of a mutant immunoglobulin heavy chain (IgHV). Here we present a rare case of c-HCL with neither V600 BRAF mutation nor the aforementioned IgHV variant successfully treated with cladribine and review the current literature on its use in women of childbearing age/pregnancy.


Regulatory T Cells In Endemic Burkitt Lymphoma Patients Are Associated With Poor Outcomes: A Prospective, Longitudinal Study, Emily Parsons, Juliana A. Otieno, John Michael Ong'echa, Christina E. Nixon, John Vulule, Christian Munz, V. Ann Stewart, Ann M. Moormann 2016 Uniformed Services University of the Health Sciences

Regulatory T Cells In Endemic Burkitt Lymphoma Patients Are Associated With Poor Outcomes: A Prospective, Longitudinal Study, Emily Parsons, Juliana A. Otieno, John Michael Ong'echa, Christina E. Nixon, John Vulule, Christian Munz, V. Ann Stewart, Ann M. Moormann

Open Access Articles

Deficiencies in Epstein-Barr virus (EBV)-specific T cell immunosurveillance appear to precede the development of endemic Burkitt lymphoma (eBL), a malaria-associated pediatric cancer common in sub-Saharan Africa. However, T cell contributions to eBL disease progression and survival have not been characterized. Our objective was to investigate regulatory and inflammatory T cell responses in eBL patients associated with clinical outcomes. By multi-parameter flow cytometry, we examined peripheral blood mononuclear cells from 38 eBL patients enrolled in a prospective cohort study in Kisumu, Kenya from 2008-2010, and 14 healthy age-matched Kenyan controls. Children diagnosed with eBL were prospectively followed and outcomes categorized ...


Properdin Levels In Individuals With Chemotherapy-Induced Neutropenia, Artsiom Tsyrkunou, Sarika Agarwal, Bibek Koirala, Robert W. Finberg, Rajneesh Nath, Bruce A. Barton, Stuart M. Levitz, Jennifer P. Wang, Sanjay Ram 2016 University of Massachusetts Medical School

Properdin Levels In Individuals With Chemotherapy-Induced Neutropenia, Artsiom Tsyrkunou, Sarika Agarwal, Bibek Koirala, Robert W. Finberg, Rajneesh Nath, Bruce A. Barton, Stuart M. Levitz, Jennifer P. Wang, Sanjay Ram

Open Access Articles

BACKGROUND: Neutrophils produce and carry key components of the alternative pathway (AP) of complement, including properdin (P). The effect of chemotherapy-induced absolute neutropenia on circulating P levels and AP function has not been previously established.

METHODS: We prospectively measured free P levels in serum from 27 individuals expected to develop neutropenia after administration of chemotherapy for hematological malignancies in preparation for hematopoietic stem cell transplantation and here describe the relationship between serum P levels and the neutrophil count over time.

RESULTS: When the absolute neutrophil count (ANC) was > 500 cells/mm3 pre-chemotherapy, P levels were significantly higher than P levels ...


In Vivo Correction Of Anaemia In Beta-Thalassemic Mice By Gammapna-Mediated Gene Editing With Nanoparticle Delivery, Raman Bahal, Dale L. Greiner, Michael A. Brehm, Peter M. Glazer 2016 Yale University

In Vivo Correction Of Anaemia In Beta-Thalassemic Mice By Gammapna-Mediated Gene Editing With Nanoparticle Delivery, Raman Bahal, Dale L. Greiner, Michael A. Brehm, Peter M. Glazer

Open Access Articles

The blood disorder, beta-thalassaemia, is considered an attractive target for gene correction. Site-specific triplex formation has been shown to induce DNA repair and thereby catalyse genome editing. Here we report that triplex-forming peptide nucleic acids (PNAs) substituted at the gamma position plus stimulation of the stem cell factor (SCF)/c-Kit pathway yielded high levels of gene editing in haematopoietic stem cells (HSCs) in a mouse model of human beta-thalassaemia. Injection of thalassemic mice with SCF plus nanoparticles containing gammaPNAs and donor DNAs ameliorated the disease phenotype, with sustained elevation of blood haemoglobin levels into the normal range, reduced reticulocytosis, reversal ...


P27kip1 And P130 Cooperate To Regulate Hematopoietic Cell Proliferation In Vivo, Inês Soeiro, Azim Mohamedali, Hanna M. Romanska, Nicholas C. Lea, Emma S. Child, Janet Glassford, Stephen J. Orr, Claudia Roberts, Kikkeri N. Naresh, El-Nasir Lalani, David J. Mann, Roger J. Watson, N. Shaun B. Thomas, Eric W. -F. Lam 2016 Hammersmith Hospital

P27kip1 And P130 Cooperate To Regulate Hematopoietic Cell Proliferation In Vivo, Inês Soeiro, Azim Mohamedali, Hanna M. Romanska, Nicholas C. Lea, Emma S. Child, Janet Glassford, Stephen J. Orr, Claudia Roberts, Kikkeri N. Naresh, El-Nasir Lalani, David J. Mann, Roger J. Watson, N. Shaun B. Thomas, Eric W. -F. Lam

El Nasir Lalani

To investigate the potential functional cooperation between p27Kip1 and p130 in vivo, we generated mice deficient for both p27Kip1 and p130. In p27Kip1−/−;p130−/− mice, the cellularity of the spleens but not the thymi is significantly increased compared with that of their p27Kip1−/− counterparts, affecting the lymphoid, erythroid, and myeloid compartments. In vivo cell proliferation is significantly augmented in the B and T cells, monocytes, macrophages, and erythroid progenitors in the spleens of p27Kip1−/−; p130−/− animals. Immunoprecipitation and immunodepletion studies indicate that p130 can compensate for the absence of p27Kip1 in binding to and ...


Efficient Immortalization Of Luminal Epithelial Cells From Human Mammary Gland By Introduction Of Simian Virus 40 Large Tumor Antigen With A Recombinant Retrovirus, Bartek J, Bartkova J, Kyprianou N, El-Nasir Lalani, Staskova Z, Shearer M, Chang S, Taylor Papadimitriou J 2016 Imperial Cancer Research Fund

Efficient Immortalization Of Luminal Epithelial Cells From Human Mammary Gland By Introduction Of Simian Virus 40 Large Tumor Antigen With A Recombinant Retrovirus, Bartek J, Bartkova J, Kyprianou N, El-Nasir Lalani, Staskova Z, Shearer M, Chang S, Taylor Papadimitriou J

El Nasir Lalani

When defined in terms of markers for normal cell lineages, most invasive breast cancer cells correspond to the phenotype of the common luminal epithelial cell found in the terminal ductal lobular units. Luminal epithelial cells cultured from milk, which have limited proliferative potential, have now been immortalized by introducing the gene encoding simian virus 40 large tumor (T) antigen. Infection with a recombinant retrovirus proved to be 50-100 times more efficient than calcium phosphate transfection, and of the 17 cell lines isolated, only 5 passed through a crisis period as characterized by cessation of growth. When characterized by immunohistochemical staining ...


Discovery And Development Of Human Monoclonal Antibodies To Block Rhd Alloimmunization During Pregnancy, Tushar Gupta, Melissa Gawron, Colby A. Souders, Michael A. Brehm, Dale Greiner, Leonard D. Shultz, Smita Jaiswal, Sean McCauley, Ann Dauphin, Jeremy Luban, Lisa Cavacini 2016 University of Massachusetts Medical School

Discovery And Development Of Human Monoclonal Antibodies To Block Rhd Alloimmunization During Pregnancy, Tushar Gupta, Melissa Gawron, Colby A. Souders, Michael A. Brehm, Dale Greiner, Leonard D. Shultz, Smita Jaiswal, Sean Mccauley, Ann Dauphin, Jeremy Luban, Lisa Cavacini

UMass Center for Clinical and Translational Science Research Retreat

Exposure of an Rh negative mother to red blood cells (RBCs) of an Rh positive fetus results in alloimmunization and development of anti-RhD antibodies. The anti-RhD antibodies cause hemolytic disease of the new born babies during subsequent pregnancies. Current prophylactic treatment involves polyclonal anti-RhD IgG purified from plasma of humans and is administered in approximately 20% of pregnancies. While the current prophylaxis is effective, it involves the use of human plasma and non-RhD specific antibodies, thus posing a risk of transmitting infections and undesired antibody reactions. Moreover, there is a serious scarcity of plasma donors to meet the requirement of ...


Conditional Screening For Ultra-High Dimensional Covariates With Survival Outcomes, Hyokyoung Grace Hong, Jian Kang, Yi Li 2016 Michigan State University

Conditional Screening For Ultra-High Dimensional Covariates With Survival Outcomes, Hyokyoung Grace Hong, Jian Kang, Yi Li

The University of Michigan Department of Biostatistics Working Paper Series

Identifying important biomarkers that are predictive for cancer patients' prognosis is key in gaining better insights into the biological influences on the disease and has become a critical component of precision medicine. The emergence of large-scale biomedical survival studies, which typically involve excessive number of biomarkers, has brought high demand in designing efficient screening tools for selecting predictive biomarkers. The vast amount of biomarkers defies any existing variable selection methods via regularization. The recently developed variable screening methods, though powerful in many practical setting, fail to incorporate prior information on the importance of each biomarker and are less powerful in ...


Novel Oral Transforming Growth Factor-Beta Signaling Inhibitor Ew-7197 Eradicates Cml-Initiating Cells, Kazuhito Naka, Shaoguang Li, Dae-Kee Kim 2016 Kanazawa University

Novel Oral Transforming Growth Factor-Beta Signaling Inhibitor Ew-7197 Eradicates Cml-Initiating Cells, Kazuhito Naka, Shaoguang Li, Dae-Kee Kim

Open Access Articles

Recent strategies for treating CML patients have focused on investigating new combinations of tyrosine kinase inhibitors (TKIs) as well as identifying novel translational research agents that can eradicate CML leukemia-initiating cells (CML-LICs). However, little is known about the therapeutic benefits such CML-LIC targeting therapies might bring to CML patients. In this study, we investigated the therapeutic potential of EW-7197, an orally bioavailable transforming growth factor-beta signaling inhibitor which has recently been approved as an Investigational New Drug (NIH, USA), to suppress CML-LICs in vivo. Compared to TKI treatment alone, administration of TKI plus EW-7197 to CML-affected mice significantly delayed disease ...


Examination Of Reticulocytosis Among Chronically Transfused Children With Sickle Cell Anemia., Megha Kaushal, Colleen Byrnes, Zarir Khademian, Natalie Duncan, Naomi L. Luban, Jeffery L Miller, Ross Fasano, Emily R. Meier 2016 George Washington University

Examination Of Reticulocytosis Among Chronically Transfused Children With Sickle Cell Anemia., Megha Kaushal, Colleen Byrnes, Zarir Khademian, Natalie Duncan, Naomi L. Luban, Jeffery L Miller, Ross Fasano, Emily R. Meier

Pediatrics Faculty Publications

Sickle cell anemia (SCA) is an inherited hemolytic anemia with compensatory reticulocytosis. Recent studies have shown that increased levels of reticulocytosis during infancy are associated with increased hospitalizations for SCA sequelae as well as cerebrovascular pathologies. In this study, absolute reticulocyte counts (ARC) measured prior to transfusion were analysed among a cohort of 29 pediatric SCA patients receiving chronic transfusion therapy (CTT) for primary and secondary stroke prevention. A cross-sectional flow cytometric analysis of the reticulocyte phenotype was also performed. Mean duration of CTT was 3.1 ± 2.6 years. Fifteen subjects with magnetic resonance angiography (MRA) -vasculopathy had significantly ...


Interview With Scott Hamilton Goodnight, Jr., M.D., Scott Hamilton Goodnight Jr., M.D. (interviewee), Grover C. Bagby M.D. (interviewer) 2015 Oregon Health & Science University

Interview With Scott Hamilton Goodnight, Jr., M.D., Scott Hamilton Goodnight Jr., M.D. (Interviewee), Grover C. Bagby M.D. (Interviewer)

Oral History Collection

Scott Goodnight, Jr., M.D., reflects on his life and career in medicine. He begins the interview by discussing his father’s medical school career and practice in downtown Portland and Goodnight’s childhood growing up in Northwest Portland. He goes on to describe his undergraduate and graduate education in medicine at the University of Oregon, meeting his wife Cecelia, and his early involvement in biomedical research. Drafted by the Army, Goodnight also discusses his time spent at the Fitzsimmons General Hospital and General Medicine Clinic as well as the 85th Evacuation Hospital in Vietnam. He goes on to describe ...


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