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Association Between Corticosteroids And Infection, Sepsis, And Infectious Death In Pediatric Acute Myeloid Leukemia (Aml): Results From The Canadian Infections In Aml Research Group, David Dix, Sonia Cellot, Victoria Price, Biljana Gillmeister, Marie Chantal Ethier, Donna L. Johnston, Victor Lewis, Bruno Michon, David Mitchell, Kent Stobart, Rochelle Yanofsky, Carol Portwine, Mariana Silva, Lynette Bowes, Shayna Zelcer, Josée Brossard, Jeffrey Traubici, Upton Allen, Joseph Beyene, Lillian Sung

Paediatrics Publications

Background. Infection continues to be a major problem for children with acute myeloid leukemia (AML). Objectives were to identify factors associated with infection, sepsis, and infectious deaths in children with newly diagnosed AML.Methods. We conducted a retrospective, population-based cohort study that included children ≤18 years of age with de novo, non-M3 AML diagnosed between January 1995 and December 2004, treated at 15 Canadian centers. Patients were monitored for infection from initiation of AML treatment until recovery from the last cycle of chemotherapy, conditioning for hematopoietic stem cell transplantation, relapse, persistent disease, or death (whichever occurred first). Consistent trained research associates …

Secondary Structure, A Missing Component Of Sequence-Based Minimotif Definitions, David P. Sargeant, Michael R. Gryk, Mark W. Maciejewski, Vishal Thapar, Vamsi Kundeti, Sanguthevar Rajasekaran, Pedro Romero, Keith Dunker, Shun Cheng Macdonald, J. Rogers, L. Bucci, P. Mousmanis, E. Lang, S. A. Halperin, S. Bowles, C. Halpert, M. Ipp, G. J.G. Asmundson, M. Rieder, K. Robson, E. Uleryk, M. M. Antony, V. Dubey, A. Hanrahan, D. Lockett, J. Scott

Paediatrics Publications

Minimotifs are short contiguous segments of proteins that have a known biological function. The hundreds of thousands of minimotifs discovered thus far are an important part of the theoretical understanding of the specificity of protein-protein interactions, posttranslational modifications, and signal transduction that occur in cells. However, a longstanding problem is that the different abstractions of the sequence definitions do not accurately capture the specificity, despite decades of effort by many labs. We present evidence that structure is an essential component of minimotif specificity, yet is not used in minimotif definitions. Our analysis of several known minimotifs as case studies, analysis …

A Prospective Study Of Physician-Observed Concussion During A Varsity University Hockey Season: White Matter Integrity In Ice Hockey Players. Part 3 Of 4, Inga K. Koerte, David Kaufmann, Elisabeth Hartl, Sylvain Bouix, Ofer Pasternak, Marek Kubicki, Alexander Rauscher, David K.B. Li

Paediatrics Publications

Object: The aim of this study was to investigate the effect of repetitive head impacts on white matter integrity that were sustained during 1 Canadian Interuniversity Sports (CIS) ice hockey season, using advanced diffusion tensor imaging (DTI). Methods: Twenty-five male ice hockey players between 20 and 26 years of age (mean age 22.24 ± 1.59 years) participated in this study. Participants underwent pre- and postseason 3-T MRI, including DTI. Group analyses were performed using paired-group tract-based spatial statistics to test for differences between preseason and postseason changes. Results: Tract-based spatial statistics revealed an increase in trace, radial diffusivity (RD), and …

In Utero Programming Of Later Adiposity: The Role Of Fetal Growth Restriction, Ousseynou Sarr, Kaiping Yang, Timothy R.H. Regnault

Paediatrics Publications

Intrauterine growth restriction (IUGR) is strongly associated with obesity in adult life. The mechanisms contributing to the onset of IUGR-associated adult obesity have been studied in animal models and humans, where changes in fetal adipose tissue development, hormone levels and epigenome have been identified as principal areas of alteration leading to later life obesity. Following an adverse in utero development, IUGR fetuses display increased lipogenic and adipogenic capacity in adipocytes, hypoleptinemia, altered glucocorticoid signalling, and chromatin remodelling, which subsequently all contribute to an increased later life obesity risk. Data suggest that many of these changes result from an enhanced activity …

Conserved Region 3 Of Human Papillomavirus 16 E7 Contributes To Deregulation Of The Retinoblastoma Tumor Suppressor, Biljana Todorovic, Katherine Hung, Paola Massimi, Nikita Avvakumov, Frederick A. Dick, Gary S. Shaw, Lawrence Banks, Joe S. Mymryk

Paediatrics Publications

The human papillomavirus (HPV) E7 oncoprotein binds cellular factors, preventing or retargeting their function and thereby making the infected cell conducive for viral replication. A key target of E7 is the product of the retinoblastoma susceptibility locus (pRb). This interaction results in the release of E2F transcription factors and drives the host cell into the S phase of the cell cycle. E7 binds pRb via a high-affinity binding site in conserved region 2 (CR2) and also targets a portion of cellular pRb for degradation via the proteasome. Evidence suggests that a secondary binding site exists in CR3, and that this …

Pandemic (H1n1) 2009 Influenza In Canadian Pediatric Cancer And Hematopoietic Stem Cell Transplant Patients, Dat Tran, Michelle Science, David Dix, Carol Portwine, Shayna Zelcer, Donna L. Johnston, Rochelle Yanofsky, Adam Gassas, Marie Chantal Ethier, Lillian Sung

Paediatrics Publications

Background The impact of pandemic H1N1 influenza (pH1N1) virus in pediatric cancer is uncertain. The objectives of this study were to characterize the clinical course of pH1N1 and identify factors associated with severe outcomes. Methods We conducted a Canadian multicenter retrospective review of children with cancer and stem cell transplant (SCT) recipients who were diagnosed with laboratory-confirmed pH1N1 infection between May 1, 2009 and January 31, 2010. Results We identified 100 (19 in wave 1 and 81 in wave 2) cases of pH1N1 infection. Median age was 8·7years. 71% had a hematologic malignancy, and 20% received SCT. Median duration of …

Male Gender Promotes An Increased Inflammatory Response To Lipopolysaccharide In Umbilical Vein Blood., Shunaha Kim-Fine, Timothy Regnault, James S Lee, Sarah A Gimbel, Jill A Greenspoon, Jonathan Fairbairn, Kelly Summers, Barbra De Vrijer

Paediatrics Publications

OBJECTIVES: To establish gender-specific differences in maternal and fetal immune response in healthy human fetuses at term.

METHODS: Forty-five women with elective caesarean sections for uncomplicated singleton pregnancies were recruited for two studies. Using a multiplex biomarker immunoassay system, unstimulated maternal and fetal plasma concentrations of interleukin (IL)-1β, IL-1ra, IL-6, IL-8, macrophage inflammatory protein (MIP)-1α, and tumor necrosis factor (TNF)-α were measured from one study population. Lipopolysaccharide (LPS)-stimulated cytokine response was measured in a second study.

RESULTS: There were no significant gender differences in either maternal or fetal unstimulated plasma cytokine concentrations, but concentrations of the proinflammatory cytokines IL-1β and …

The Long And Short Of It: The Role Of Telomeres In Fetal Origins Of Adult Disease, Stephanie E. Hallows, Timothy R.H. Regnault, Dean H. Betts

Paediatrics Publications

Placental insufficiency, maternal malnutrition, and other causes of intrauterine growth restriction (IUGR) can significantly affect short-term growth and long-term health. Following IUGR, there is an increased risk for cardiovascular disease and Type 2 Diabetes. The etiology of these diseases is beginning to be elucidated, and premature aging or cellular senescence through increased oxidative stress and DNA damage to telomeric ends may be initiators of these disease processes. This paper will explore the areas where telomere and telomerase biology can have significant effects on various tissues in the body in IUGR outcomes. © 2012 Stephanie E. Hallows et al.

Overexpression Of Pyruvate Dehydrogenase Kinase 1 And Lactate Dehydrogenase A In Nerve Cells Confers Resistance To Amyloid Β And Other Toxins By Decreasing Mitochondrial Respiration And Reactive Oxygen Species Production, Jordan T. Newington, Tim Rappon, Shawn Albers, Daisy Y. Wong, R. Jane Rylett, Robert C. Cumming

Paediatrics Publications

Background: Aerobic glycolysis promotes resistance against Aβ toxicity. Results: Increased LDHA and PDK1 expression attenuates mitochondrial activity and confers resistance to Aβ. These proteins are down-regulated in a transgenic Alzheimer disease (AD) mouse model, and PDK1 is decreased in AD brain. Conclusion: PDK and LDHA are central mediators of Aβ resistance. Significance: Drugs that augment aerobic glycolysis may enhance brain cell survival in AD patients. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

The Fetal Origins Of The Metabolic Syndrome: Can We Intervene?, Noelle Ma, Daniel B. Hardy

Paediatrics Publications

Epidemiological studies have suggested that metabolic programming begins during fetal life and adverse events in utero are a critical factor in the etiology of chronic diseases and overall health. While the underlying molecular mechanisms linking impaired fetal development to these adult diseases are being elucidated, little is known about how we can intervene early in life to diminish the incidence and severity of these long-term diseases. This paper highlights the latest clinical and pharmaceutical studies addressing how dietary intervention in fetal and neonatal life may be able to prevent aspects of the metabolic syndrome associated with IUGR pregnancies. © 2012 …

Genetic And Environmental Vulnerabilities In Children With Neurodevelopmental Disorders, Annette Karmiloff-Smith, Dean D'Souza, Tessa M. Dekker, Jo Van Herwegen, Fei Xu, Maja Rodic, Daniel Ansari

Paediatrics Publications

One might expect that children with varying genetic mutations or children raised in low socioeconomic status environments would display different deficits. Although this expectation may hold for phenotypic outcomes in older children and adults, cross-syndrome comparisons in infancy reveal many common neural and sociocognitive deficits. The challenge is to track dynamic trajectories over developmental time rather than focus on end states like in adult neuropsychological studies. We contrast the developmental and adult approaches with examples from the cognitive and social domains, and we conclude that static models of adult brain lesions cannot be used to account for the dynamics of …

Effect Of Fresh Red Blood Cell Transfusions On Clinical Outcomes In Premature, Very Low-Birth-Weight Infants: The Aripi Randomized Trial, Dean A. Fergusson, Paul Hébert, Debora L. Hogan, Louise Lebel, Nicole Rouvinez-Bouali, John A. Smyth, Koravangattu Sankaran, Alan Tinmouth, Morris A. Blajchman, Lajos Kovacs, Christian Lachance, Shoo Lee, C. Robin Walker, Brian Hutton, Robin Ducharme, Katelyn Balchin, Tim Ramsay, Jason C. Ford, Ashok Kakadekar, Kuppuchipalayam Ramesh, Stan Shapiro

Paediatrics Publications

Context: Even though red blood cells (RBCs) are lifesaving in neonatal intensive care, transfusing older RBCs may result in higher rates of organ dysfunction, nosocomial infection, and length of hospital stay. Objective: To determine if RBCs stored for 7 days or less compared with usual standards decreased rates of major nosocomial infection and organ dysfunction in neonatal intensive care unit patients requiring at least 1 RBC transfusion. Design, Setting, and Participants: Double-blind, randomized controlled trial in 377 premature infants with birth weights less than 1250 g admitted to 6 Canadian tertiary neonatal intensive care units between May 2006 and June …

Sequencing The Cortical Processing Of Pitch-Evoking Stimuli Using Eeg Analysis And Source Estimation, Blake E. Butler, Laurel J. Trainor

Paediatrics Publications

Cues to pitch include spectral cues that arise from tonotopic organization and temporal cues that arise from firing patterns of auditory neurons. fMRI studies suggest a common pitch center is located just beyond primary auditory cortex along the lateral aspect of Heschl's gyrus, but little work has examined the stages of processing for the integration of pitch cues. Using electroencephalography, we recorded cortical responses to high-pass filtered iterated rippled noise (IRN) and high-pass filtered complex harmonic stimuli, which differ in temporal and spectral content. The two stimulus types were matched for pitch saliency, and a mismatch negativity (MMN) response was …

School Nutrition Policy: An Evaluation Of The Rhode Island Healthier Beverages Policy In Schools, Chad D. Jensen, Amy F. Sato, C. Meghan Mcmurtry, Chantelle N. Hart, Elissa Jelalian

Paediatrics Publications

Background. School policies limiting the availability of sweetened beverages are often considered to be effective interventions for improving children's diet and weight-related health. This study was designed to examine the effectiveness of the Rhode Island Healthier Beverage Policy in reducing consumption of unhealthy beverages and in producing changes in children's weight status. Method. Students in 2 public middle schools in Rhode Island completed self-reported measures of dietary intake and were measured for height and weight prior to and 1 year following the implementation of a state-mandated healthier beverage policy. An inventory of beverages available in vending machines after the beverage …

Umbilical Cord Blood-Derived Aldehyde Dehydrogenase-Expressing Progenitor Cells Promote Recovery From Acute Ischemic Injury, David M. Putman, Kevin Y. Liu, Heather C. Broughton, Gillian I. Bell, David A. Hess

Paediatrics Publications

Umbilical cord blood (UCB) represents a readily available source of hematopoietic and endothelial precursors at early ontogeny. Understanding the proangiogenic functions of these somatic progenitor subtypes after transplantation is integral to the development of improved cell-based therapies to treat ischemic diseases. We used fluorescence-activated cell sorting to purify a rare (<0.5%) population of UCB cells with high aldehyde dehydrogenase (ALDHhi) activity, a conserved stem/progenitor cell function. ALDHhicells were depleted of mature monocytes and T- and B-lymphocytes and were enriched for early myeloid (CD33) and stem cell-associated (CD34, CD133, and CD117) phenotypes. Although these cells were primarily hematopoietic in origin, UCB ALDHhi cells demonstrated a proangiogenic transcription profile and were highly enriched for both multipotent myeloid and endothelial colony-forming cells in vitro. Coculture of ALDHhi cells in hanging transwells promoted the survival of human umbilical vein endothelial cells (HUVEC) under growth factor-free and serum-free conditions. On growth factor depleted matrigel, ALDHhicells significantly increased tube-like cord formation by HUVEC. After induction of acute unilateral hind limb ischemia by femoral artery ligation, transplantation of ALDHhi cells significantly enhanced the recovery of perfusion in ischemic limbs. Despite transient engraftment in the ischemic hind limb, early recruitment of ALDHhi cells into ischemic muscle tissue correlated with increased murine von Willebrand factor blood vessel and CD31+ capillary densities. Thus, UCB ALDHhi cells represent a readily available population of proangiogenic progenitors that promote vascular regeneration. This work provides preclinical justification for the development of therapeutic strategies to treat ischemic diseases using UCB-derived ALDH hi mixed progenitor cells. © AlphaMed Press.

Bridging Prevention And Health: Exploring Community Perceptions Of Intimate Partner Violence In Rural Honduras, Javeed Sukhera, Catherine Cerulli, Barbara A. Gawinski, Diane Morse

Paediatrics Publications

This qualitative study rooted in community-based participatory research principles utilized semi-structured interviews with 2 focus groups (n = 9) with female healthcare volunteers (FCVs) and 3 male key informants who were community leaders (MCLs). The study aimed to examine how a rural Honduran community defines and responds to intimate partner violence (IPV) in order to lay the foundation for future interventions. Based on grounded theory, the authors assessed for common themes across transcripts. Authors found that a number of participants denied the existence of IPV. Perspectives on the causes and definitions of IPV varied between FCVs and MCLs. All participants …

Regulation Of B Cell Linker Protein Transcription By Pu.1 And Spi-B In Murine B Cell Acute Lymphoblastic Leukemia, Li S. Xu, Kristen M. Sokalski, Kathryn Hotke, Darah A. Christie, Oren Zarnett, Jan Piskorz, Gobi Thillainadesan, Joseph Torchia, Rodney P. Dekoter

Paediatrics Publications

B cell acute lymphoblastic leukemia (B-ALL) is frequently associated with mutations or chromosomal translocations of genes encoding transcription factors. Conditional deletion of genes encoding the E26-transformation-specific transcription factors, PU.1 and Spi-B, in B cells (ΔPB mice) leads to B-ALL in mice at 100% incidence rate and with a median survival of 21 wk. We hypothesized that PU.1 and Spi-B may redundantly activate transcription of genes encoding tumor suppressors in the B cell lineage. Characterization of aging ΔPB mice showed that leukemia cells expressing IL-7R were found in enlarged thymuses. IL-7R-expressing B-ALL cells grew in culture in response to IL-7 and …

Why Multidisciplinary Clinics Should Be The Standard For Treating Chronic Kidney Disease, Guido Filler, Steven E. Lipshultz

Paediatrics Publications

In adults, strong evidence indicates that slowing progression of chronic kidney disease (CKD) requires an integrated, multidisciplinary approach. In children, however, this approach has not been studied. This editorial commentary to the study by Ajarmeh et al in this volume of Pediatric Nephrology highlights how a dedicated, multidisciplinary team of physicians, nurses, pharmacists, dieticians, social workders and clinic data managers slowed the progression of CKD in children to a remarkable degree. We discuss the strengths and limitations of the study and its cost implications, as well as the issue of determining the optional complement of physicians and allied health care …

A Cd11d Monoclonal Antibody Treatment Reduces Tissue Injury And Improves Neurological Outcome After Fluid Percussion Brain Injury In Rats, Feng Bao, Sandy R. Shultz, Jeff D. Hepburn, Vanessa Omana, Lynne C. Weaver, Donald P. Cain, Arthur Brown

Paediatrics Publications

Traumatic brain injury (TBI) is an international health concern often resulting in chronic neurological abnormalities, including cognitive deficits, emotional disturbances, and motor impairments. An anti-CD11d monoclonal antibody that blocks the CD11d/CD18 integrin and vascular cell adhesion molecule (VCAM)-1 interaction following experimental spinal cord injury improves functional recovery, while reducing the intraspinal number of neutrophils and macrophages, oxidative activity, and tissue damage. Since the mechanisms of secondary injury in the brain and spinal cord are similar, we designed a study to evaluate fully the effects of anti-CD11d treatment after a moderate lateral fluid percussion TBI in the rat. Rats were treated …

Acetaminophen Overdose In Children, Jacqueline D. Ogilvie, Michael J. Rieder, Rodrick Lim

Paediatrics Publications

No abstract provided.

Introduction To The Special Section On "Numerical And Mathematical Processing", Daniel Ansari, Bert De Smedt, Roland H. Grabner

Paediatrics Publications

No abstract provided.

Cystatin C For The Assessment Of Gfr In Neonates With Congenital Renal Anomalies, Guido Filler, Joanne Grimmer, Shih Han Susan Huang, Erika Bariciak

Paediatrics Publications

No abstract provided.

Peyer's Patch M Cells Derived From Lgr5+ Stem Cells Require Spib And Are Induced By Rankl In Cultured Miniguts, Wim De Lau, Pekka Kujala, Kerstin Schneeberger, Sabine Middendorp, Vivian S.W. Li, Nick Barker, Anton Martens, Frans Hofhuis, Rodney P. Dekoter, Peter J. Peters, Edward Nieuwenhuis, Hans Clevers

Paediatrics Publications

Peyer's patches consist of domains of specialized intestinal epithelium overlying gut-associated lymphoid tissue (GALT). Luminal antigens reach the GALT by translocation through epithelial gatekeeper cells, the so-calledMcells. We recently demonstrated that all epithelial cells required for the digestive functions of the intestine are generated from Lgr5-expressing stem cells. Here, we show thatMcells also derive from these crypt-based Lgr5 stem cells. The Ets family transcription factor SpiB, known to control effector functions of bone marrow-derived immune cells, is specifically expressed inMcells. In SpiB-/-mice, Mcells are entirely absent, which occurs in a cell-autonomous fashion. It has been shown that Tnfsf11 (RankL) can …

Regulation Of Transcription And Chromatin Structure By Prb: Here, There And Everywhere, Srikanth Talluri, Frederick A. Dick

Paediatrics Publications

Commitment to divide is one of the most crucial steps in the mammalian cell division cycle. It is critical for tissue and organismal homeostasis, and consequently is highly regulated. The vast majority of cancers evade proliferative control, further emphasizing the importance of the commitment step in cell cycle regulation. The Retinoblastoma (RB) tumor suppressor pathway regulates this decision-making step. Since being the subject of Knudson's 'two hit hypothesis', there has been considerable interest in understanding pRB's role in cancer. It is best known for repressing E2F dependent transcription of cell cycle genes. However, pRB's role in controlling chromatin structure is …

Molecular Mechanisms Underlying The Fetal Programming Of Adult Disease, Thin Vo, Daniel B. Hardy

Paediatrics Publications

Adverse events in utero can be critical in determining quality of life and overall health. It is estimated that up to 50 % of metabolic syndrome diseases can be linked to an adverse fetal environment. However, the mechanisms linking impaired fetal development to these adult diseases remain elusive. This review uncovers some of the molecular mechanisms underlying how normal physiology may be impaired in fetal and postnatal life due to maternal insults in pregnancy. By understanding the mechanisms, which include epigenetic, transcriptional, endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS), we also highlight how intervention in fetal and neonatal …

Survivin Is Required For Beta-Cell Mass Expansion In The Pancreatic Duct-Ligated Mouse Model, Xiaohong Wu, Qinfeng Zhang, Xiaojing Wang, Jiayu Zhu, Kuangfeng Xu, Hitoshi Okada, Rennian Wang, Minna Woo

Paediatrics Publications

Aims/Hypothesis: Pancreatic beta-cell mass expands through adulthood under certain conditions. The related molecular mechanisms are elusive. This study was designed to determine whether surviving (also known as Birc5), which is transiently expressed perinatally in islets, was required for beta-cell mass expansion in the pancreatic duct-ligated mouse model. Methods: Mice with beta cell-specific deletion of survivin (RIPCre+survivinfl/fl) and their control littermates (RIPCre+survivin+/+) were examined to determine the essential role of survivin in partial pancreatic duct ligation (PDL)-induced beta-cell proliferation, function and survival. Results: Resurgence of survivin expression occurred as early as day 3 post-PDL. By day 7 post-PDL, control mice showed …

Targeting Cox-2 And Ep4 To Control Tumor Growth, Angiogenesis, Lymphangiogenesis And Metastasis To The Lungs And Lymph Nodes In A Breast Cancer Model, Xiping Xin, Mousumi Majumder, Gannareddy V. Girish, Vik Mohindra, Takayuki Maruyama, Peeyush K. Lala

Paediatrics Publications

We reported that cyclo-oxygenase (COX)-2 expression in human breast cancer stimulated cancer cell migration and invasiveness, production of vascular endothelial growth factor (VEGF)-C and lymphangiogenesis in situ, largely from endogenous PGE2-mediated stimulation of prostaglandin E (EP)1 and EP4 receptors, presenting them as candidate therapeutic targets against lymphatic metastasis. As human breast cancer xenografts in immuno-compromised mice have limitations for preclinical testing, we developed a syngeneic murine breast cancer model of spontaneous lymphatic metastasis mimicking human and applied it for mechanistic and therapeutic studies. We tested the roles of COX-2 and EP receptors in VEGF-C and-D production by a highly metastatic …

Additive Effects Of The Dopamine D2 Receptor And Dopamine Transporter Genes On The Error-Related Negativity In Young Children, A. Meyer, D. N. Klein, D. C. Torpey, A. J. Kujawa, E. P. Hayden, H. I. Sheikh, S. M. Singh, G. Hajcak

Paediatrics Publications

The error-related negativity (ERN) is a negative deflection in the event-related potential that occurs approximately 50ms following the commission of an error at fronto-central electrode sites. Previous models suggest dopamine plays a role in the generation of the ERN. We recorded event-related potentials (ERPs) while 279 children aged 5-7 years completed a simple Go/No-Go task; the ERN was examined in relation to the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes. Results suggest an additive effect of the DRD2 and DAT1 genotype on ERN magnitude such that children with at least one DRD2 A1 allele and children with at …

High Incidence Of Vertebral Fractures In Children With Acute Lymphoblastic Leukemia 12 Months After The Initiation Of Therapy, Nathalie Alos, Ronald M. Grant, Timothy Ramsay, Jacqueline Halton, Elizabeth A. Cummings, Paivi M. Miettunen, Sharon Abish, Stephanie Atkinson, Ronald Barr, David A. Cabral, Elizabeth Cairney, Robert Couch, David B. Dix, Conrad V. Fernandez, John Hay, Sara Israels, Caroline Laverdier̀E, Brian Lentle, Victor Lewis, Mary Ann Matzinger, Celia Rodd, Nazih Shenouda, Robert Stein, David Stephure, Shayne Taback, Beverly Wilson, Kathryn Williams, Frank Rauch, Kerry Siminoski

Paediatrics Publications

Purpose: Vertebral fractures due to osteoporosis are a potential complication of childhood acute lymphoblastic leukemia (ALL). To date, the incidence of vertebral fractures during ALL treatment has not been reported. Patient and Methods: We prospectively evaluated 155 children with ALL during the first 12 months of leukemia therapy. Lateral thoracolumbar spine radiographs were obtained at baseline and 12 months. Vertebral bodies were assessed for incident vertebral fractures using the Genant semiquantitative method, and relevant clinical indices such as spine bone mineral density (BMD), back pain, and the presence of vertebral fractures at baseline were analyzed for association with incident vertebral …

Vascular Stem Cells In Diabetic Complications: Evidence For A Role In The Pathogenesis And The Therapeutic Promise, Emily C. Keats, Zia A. Khan

Paediatrics Publications

Long standing diabetes leads to structural and functional alterations in both the micro- and the macro-vasculature. Vascular endothelial cells (ECs) are the primary target of the hyperglycemia-induced adverse effects. Vascular stem cells that give rise to endothelial progenitor cells (EPCs) and mesenchymal progenitor cells (MPCs) represent an attractive target for cell therapy for diabetic patients. A number of studies have reported EPC dysfunction as a novel participant in the culmination of the diabetic complications. The controversy behind the identity of EPCs and the similarity between these progenitor cells to hematopoietic cells has led to conflicting results. MPCs, on the other …