This 3-hour mini-course will update primary and subspecialty care providers on the advances in our understanding of von Willebrand Disease, the most common inherited bleeding disorder. The minicourse will provide an overview of both basic and clinical aspects of this disease, including discussion of the biochemistry and genetics of von Willebrand Factor, dilemmas in the diagnosis of this highly variable disease, and advances in the management of children and adolescents with von Willebrand Disease. Congenital platelet function abnormalities, which share clinical similarities with von Willebrand Disease, will also be discussed.

Overview
Sara J. Israels, University of Manitoba, Winnipeg, Canada

The Biology and Molecular Genetics of von Willebrand Factor and von Willebrand Disease
J. Evan Sadler, Howard Hughes Medical Institute and Washington University School of Medicine, St Louis, MO

Approach to the Diagnosis of von Willebrand Disease
Robert R. Montgomery, Medical College of Wisconsin and the Blood Research Institute of the Blood Center, Milwaukee, WI

Break

Management of Children and Adolescents with von Willebrand Disease
Donna DiMichele, New York Presbyterian Hospital/Weill Medical College of Cornell University, New York, NY

This minicourse will highlight new technologies in genetics and genomics that build on the mapping and sequencing of human and model organism genomes to define the function of genes and their clinical importance in normal health and disease.

Genetic Analysis of Hematopoiesis and Cancer
Leonard I. Zon, Howard Hughes Medical Institute, Children's Hospital, Boston, MA

Genetic Polymorphisms for Linkage and Association Studies
Aravinda Chakravarti, Johns Hopkins University School of Medicine, Baltimore, MD

Gene Expression: Expression Profiling and Microarray Technology
Jeffrey M. Trent, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD

Reactive oxygen species contribute to diseases in prematurely born infants as well as aging adults. These reactive species are studied by various analytical methods based on chemical principles that are incompletely understood. The purpose of this workshop is to provide useful overviews and critical assessments of the limitations of the commonly used methods for measurement of oxidant stress responses, with particular emphasis on the application of these methods to studies in pediatric patient populations. Sample acquisition and handling, activation and effect of inflammatory responses, lipid peroxidation, thiol/disulfide redox status, protein nitration and other nitric oxide-medicated modifications, and measurement and characterization of dinitrophenylhydrazine-reactive "protein carbonyls" will be discussed. In addition to practical considerations, the utility and limitations of the data obtained with these methods will be addressed.

Introduction and Overview

Inflammation as a Cause and Effect of Oxidant Stress
Stephen E. Welty, Children's Research Institute, The Ohio State University, Columbus, OH

Sample Acquisition and Handling
Patricia L. Ramsay, Baylor College of Medicine, Houston, TX

Lipid Peroxidation: From Malonaldehyde to Isoprostanes
Jason D. Morrow, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN

Nitric Oxide and Other Reactive Nitrogen Species
Harry Ischiropoulos, Joseph Stokes, Jr., Research Institute, Philadelphia, PA

Protein and Nucleic Acid Oxidation
Charles V. Smith, Children's Research Institute, The Ohio State University, Columbus, OH

Discussion

This 3-hour minicourse will help the primary and subspecialty care providers understand better the changing field of diabetes mellitus: its pathophysiology, epidemiology, and advances in management. The availability of new treatments and devices for the care of patients with Type I diabetes has changed dramatically over the past decade. The rising prevalence of Type 2 diabetes, closely linked to the obesity epidemic, is bringing a formerly "adult" disease into the pediatricians' offices. This minicourse will provide an overview of four pertinent areas, by speakers who are leaders in the field.

Cell Biology of Human Pancreatic Islets
Alberto Hayek, University of California San Diego Medical School, La Jolla, CA

Islet Transplantation in Humans: 2001 and Beyond
R. Paul Robertson, Pacific Northwest Research Institute, Seattle, WA

BREAK

Type 2 Diabetes in Childhood and Adolescence
Francine R. Kaufman, Children's Hospital of Los Angeles, USC School of Medicine, Los Angeles, CA

As we entered the molecular genetics era, the hope had been that correlation of mutations with clinical course would permit accurate prediction of prognosis with future patients. However, as increasing information has been accumulated, what has emerged has been the recognition that clinical variability among individuals with identical mutations is the rule, not the exception. We will explore mechanisms for clinical variability, including protein activity, thresholds, modifier genes, and system complexity.

Complexity of Single Gene Disorders
Edward R. B. McCabe, University of California School of Medicine, Los Angeles, CA

Even PKU Is Not a Simple Mendelian Disorder
Charles R. Scriver, McGill University, Montreal, PQ, Canada

Genetic Heterogeneity in CF
Garry R. Cutting, Johns Hopkins University, Institute of Genetic Medicine, Baltimore, MD

Muscle Diseases as Models of Complexity
Georgirene D. Vladutiu, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Children's Hospital, Buffalo, NY

Steroid-resistant nephrotic syndrome is one of the most common forms of primary nephrotic syndrome in childhood. Recent genetic and molecular studies indicate that the podocyte plays a central role in the pathogenesis of this disorder. This symposium will address recent advances in our understanding of the development, cell biology, and pathology of the glomerular podocyte. The recent identification of NPHS2, the gene encoding the glomerular protein podocin, and its role in autosomal recessive steroid-resistant nephrotic syndrome will be discussed. Finally, new strategies for therapeutic intervention in steroid-resistant nephrotic syndrome will be described.

Development of the Glomerular Capillary Wall
Dale R. Abrahamson, University of Kansas Medical Center, Kansas City, KS

Cell Biology and Pathology of Podocytes
Peter Mundel, Albert Einstein College of Medicine, Bronx, NY

The Genetic Basis of Steroid-Resistant Nephrotic Syndrome
Corinne Antignac, INSERM, Paris, France

Advances in molecular genetics, in our understanding of the origin of metabolic diseases and in imaging techniques are all having a major impact on perinatal medicine. The role of these new insights and interventions is no greater anywhere than their impact on the care of the fetus. This symposium will review these advances from the point of "The Fetus as the Patient." We will present new data demonstrating maternal-fetal chimerism and the role of this phenomenon in various pathobiologies. Advanced fetoscopic imaging techniques and the ways they can support new fetal therapies will be presented. Molecular diagnosis of genetic metabolic disorders can now be made prenatally to allow earlier fetal treatment and improvement in outcomes.

Overview
James F. Padbury, Women & Infants Hospital of Rhode Island, Brown University, Providence, RI

Bidirectional Feto-Maternal Cell Trafficking: Relevance for Pediatric and Adult Disorders
Diana W. Bianchi, Tufts University, New England Medical Center, Boston, MA

Fetal Surgery: In Praise of Tunnel Vision
Francois Luks, Brown University School of Medicine, Rhode Island Hospital, Hasbro Children's Hospital, Providence, RI

Genetic Metabolic Disorders: Current Status of Prenatal Diagnosis and Treatment
Mark Korson, Tufts University, New England Medical Center, Boston, MA

Discussion

This session will provide important new mechanistic information about the maternal, placental and fetal influences on certain adult onset diseases. Investigators undertaking studies that are on the cutting edge will provide an overview and share some of their recent experimental results during this session. The first lecture will concentrate on maternal health and its role on adult onset diseases; the second lecture will delineate the role of placental factors; while the third session will detail fetal origins of adult hypertensive disease.

Overview
Sherin U. Devaskar, Mattel Children's Hospital, University of California, Los Angeles, CA

Maternal Health and Its Influence on Adult Onset Diseases
Judith G. Hall, University of British Columbia, Vancouver, Canada

The Placenta Dilemma
Susan Fisher, University of California, San Francisco, CA

Fetal Origins of Adult Hypertension
Susan Bagby, Oregon Health Sciences University, Portland, OR

Discussion

This session focuses on the developmental biology of hematopoiesis, utilizing the zebrafish as a genetic model. The focus of research over the next few years, described in this session, will be to understand stem cell biology, particularly focusing on the induction and self-renewal of the hematopoietic stem cell. Through the analysis of these newly derived mutant genes and cell biology, the hope is to develop a better understanding of stem cell plasticity. The fields of stem cell biology and cancer biology are likely to merge as we understand more about cell differentiation and proliferation during development.

Overview
Jeffrey M. Lipton, Schneider Children's Hospital, New Hyde Park, NY

Hematopoietic Stem Cell Development in Zebrafish
Leonard I. Zon, Howard Hughes Medical Institute, Children's Hospital, Boston, MA

Advances in Stem Cell Biology
Ron McKay, National Institutes of Health, Bethesda, MD

It has long been hypothesized that tumor expansion is dependent on the growth of new blood vessels. Recently, a new understanding of the molecular mechanisms of vascular development and growth has been achieved and has suggested new targets for cancer treatment. This program will clarify the role of novel growth factors in vascular development and tumor growth and review the novel strategies currently being developed to interfere with tumor growth.

Cellular Interactions During Vascular Development
Patricia A. D'Amore, Schepens Eye Research Institute, Harvard Medical School, Boston, MA

Angiopoietins and the Regulation of Vascular Growth
Jocelyn Holash, Regeneron Pharmaceuticals, Tarrytown, NY

Tumor Angiogenesis at the Cellular Level
Lance Munn, Massachusetts General Hospital, Boston, MA

Hormones regulate critical biological functions including neurologic growth, sexual differentiation, and organ maturation, through intricate signaling mechanisms. Pregnant women, infants, and children are increasingly exposed to chemicals in the environment that mimic or block hormones, often at very small doses. Exposure to these endocrine disruptors occurs at home, in the workplace and the community, and even as a consequence of medical care. This session will review the growing evidence of adverse health effects due to exposure to endocrine disruptors and discuss new research efforts that will help fill in the gaps in our knowledge in this area.

Overview
Philip John Landrigan, Center for Children's Health & the Environment, Mt. Sinai School of Medicine, New York, NY

Evidence of Endocrine Disruption: Lessons from Wildlife
Louis Guillette, University of Florida, Gainesville, FL, University of Florida, Gainesville, FL

NHANES: A Rich Source of National Pediatric and Adolescent Exposure Data
Elaine Gunter, NHANES Laboratory, Centers for Disease Control & Prevention, Atlanta, GA

Biomarkers in Endocrine Disruptor Research
Cynthia F. Bearer, Case Western Reserve University, Cleveland, OH

Discussion

The Human Genome Project is impacting every aspect of medicine. Dr. Craig Venter, President of Celera Genomics, one of the chief architects of this venture, will discuss the accomplishments of the human genome project and implications for future impact on health and disease in this special one-hour state of the art lecture.

Sequencing the Human Genome
J. Craig Venter, President, Celera Genomics, Rockville, MD

Supported in part by an educational grant from the Columbus Children's Hospital, Columbus, OH

Trauma is the leading cause of death in children and severe traumatic brain injury is a key contributor to this mortality and important morbidity. This session will focus on novel developments in our understanding of the mechanisms of secondary damage that evolve during the acute phase after injury and novel therapeutic approaches to this important condition-including therapies targeting brain swelling and delayed neuronal death. Finally, reorganization of the injured brain and potential therapeutic implications in the subacute/chronic phase will also be discussed.

Key Mechanisms of Secondary Damage After Traumatic Brain Injury in Infants and Children
Patrick M. Kochanek, Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine and Children's Hospital of Pittsburgh, Pittsburgh, PA

Secondary Cerebral Swelling and the Use of Hypertonic Saline
Bradley Peterson, Children's Hospital and Health Center, San Diego, CA

Understanding and Targeting Neuronal Death
Robert S.B. Clark, Children's Hospital of Pittsburgh, Pittsburgh, PA

Reorganization of the Injured Brain: Therapeutic Implications
Harvey Levin, Baylor College of Medicine, Houston, TX

Discussion