PULMONOLOGY

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

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

Two cases of children with asthma will be presented. The group will work through these cases formulating a plan for diagnosis and management. Objectives Include: Recognize warning signs of asthma, determination of asthma, class severity; identification of asthma triggers; familiarity with concepts of pulmonary function testing and peak flow monitoring; understanding of the role of inflammation and anti-inflammatory therapy; recognition and comprehension of potential side effects of medications and the disease patterns, development of asthma action plans using peak flow measurements and formulation of environmental control measures based on history and allergy testing.

Diane Schuller, Penn State College of Medicine, Jay Selcow, AAP Section on Allergy and Immunology

Quality improvement activities are intended to close the gap between desired evidence-based structures and processes of health care and what is actually delivered. The Federal Agency for Healthcare Research and Quality (AHRQ, formerly the Agency for Health Care Policy and Research) continues to encourage and support rigorous research so that quality improvement efforts can themselves be evidence-based. In this workshop, AHRQ awardees will explain how they successfully applied for grants for quality improvement research, and how they are conducting quality improvement research in real world settings. The grantees will discuss the theoretical and conceptual QI frameworks that informed their approaches, the interventions they designed and implemented, the tools they used and developed, the importance of collaborations with health systems, the real world barriers and opportunities they encountered, and how they handled IRB requirements. Panelists' projects concern jaundice (Palmer, funded in 1998): timely delivery of surfactant to high-risk neonates (Horbar, funded in 1999); and pediatric asthma (project(s) to be funded in 2000). The workshop will include substantial opportunities to address participants' questions about individual research projects and the overall QI theme.

D. M. Dougherty and M. Miller (co-chairs), Agency for Healthcare Research and Quality, Rockville, MD; R. Heather Palmer, Harvard University; Jeffrey D. Horbar, M.D., University of Vermont College of Medicine; other awardees of AHRQ quality improvement grants.

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

Advances in molecular genetics and high through-put analytical chemistry like tandem mass spectrometry (MS/MS) are enabling technologies that permit expanded newborn screening for presymptomic diagnosis of disorders not previously feasible. The prototype genetic disease for which newborn screening is now available is cystic fibrosis. The group of metabolic diseases that can now be diagnosed by MS/MS includes medium chain acyl-CoA dehydrogenase (MCAD) deficiency and related disorders of fatty acid oxidation. This symposium will address the issue of whether these diseases should be added to expanded newborn screening profiles. If so, what is the sensitivity and specificity of the currently available tests? If included in expanded screening programs, who should do the testing and how? What are the implications for genetic counseling? Should any of the new approaches be adapted to preconceptual testing? What important policy issues are created by this new capacity? There is substantial variation among states currently on screening programs. Should there be national guidelines? Who should decide about expanded screening? How will these new tests be paid and by whom?

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

Newborn Screening for Cystic Fibrosis: An Opportunity To Give Every CF Patient a Healthy Start
Philip M. Farrell, Dean and Alfred Dorrance Daniels Professor on Diseases of Children, University of Wisconsin Medical School, Madison, WI

Tandem Mass Spectrometry and Expanded Newborn Screening
Charles R. Roe, Medical Director, Institute of Metabolic Diseases, Baylor University Medical Center, Dallas, TX

Public Policy Issues in Expanded Newborn Screening
Bradford L. Therrell, Director and Professor, National Newborn Screening and Genetics Resource Center, University of Texas Health Science Center, San Antonio, TX

Part One of this session will address emerging data concerning nitric oxide use in the NICU. Controversies, uses, abuses and treatment of the LBW infant and the child with acutely decompensated CLD will be discussed.

Part Two of this session will cover the expanding understanding of hyperinsulinemic neonatal hypoglycemia. Presentation, diagnosis, identification of focal versus diffuse hypersecretion and the results of tailored interventions will be discussed.

Expanded Uses of Nitric Oxide in the Neonate
John P. Kinsella, University of Colorado, Children's Hospital, Denver, CO

Roberta A. Ballard, University of Pennsylvania and Children's Hospital, Philadelphia, PA

Krisa P. Van Meurs, Stanford University School of Medicine, Stanford, CA