The Tulane Neonatal Outcomes Research Collaborative (TNORC)
(A Pilot Grant Application)
1/11/2011
Submitted by
Euming Chong MD, Robert Gordon MD, David Cupp MD, Jane Reynolds MD
& Phillip Gordon MD, PhD
(on behalf of the TNORC)
TNORC co-directors:
Phillip Gordon
Euming Chong - (grant to be dispensed to Dr Chong if awarded)
Members:
Jane Reynolds
Nancy Wood
Julie Elzey
Bill Gill
Kathy Smith
Angie Noya
Betty Martinez
Shelly Holcomb
Affiliates / Collaborators: (co-authors italicized and current collaborators underlined)
Robert Gordon (ophthalmology) & David Cupp (ophthalmology resident) - Tulane
Tom Yeh (pediatric cardiac surgery) - Tulane
Chi Dola (obstetrics) - Tulane
Victor Lunyong (Ochsner) - LA
Barry Bloom (Wesley Medical Center) - KS
Karen Fairchild (University of Virginia) - VA
Danny Benjamin (Duke University) - NC
Reese Clark (Pediatrix Corp.) – SC
Robert Christensen (Intermountain Health System) - UT
Joshua Benjamin (pediatric resident) - Tulane
ABSTRACT: THE TULANE NEONATAL OUTCOMES RESEARCH COLLABORATIVE
Background: The Tulane Section of Neonatology has been steadily building local, regional and national
collaborations in clinical research. This effort is now being formally designated as the Tulane Neonatal
Outcomes Research Collaborative (TNORC). In 2011, we are moving from predominantly quality
improvement-based projects, to a higher percentage of prospective trials and device-based
investigations. TNORC has a firm commitment for a ten-fold increase in federal funding of NIH funded
clinical research (including overhead) over the next year. We have ongoing projects matriculating that
should quintuple the budget again within the next 5 years (with a planned follow up RO1 submission for
the first neonatal multicenter randomized controlled trial ever based out of Tulane for $500,000 by
2012). Collaborators and parties of interest in the TNORC thus far include: neonatology (P Gordon,
Chong & Reynolds), ophthalmology (R Gordon), maternal-fetal medicine (Dola), Ochsner neonatology
(Lunyong), University of Virginia neonatology (Fairchild), The University of Kansas – Wesley Medical
Center neonatology (Bloom), Intermountain Health System (Christensen), the NICHD fast start neonatal
clinical trials program – based at Duke University (Benjamin), and pediatric cardiac surgery (Yeh).
Objectives: The TNORC has four specific aims for 2011: 1) become a major site of enrollment for the
NICHD acyclovir pharmacokinetics study in newborns (our 2nd participation in this rapid start study type).
This study should bring in approximately $100,000 in NIH clinical study revenue. 2) Initiate our first
device investigation of ophthalmic ultrasound as a means to measure opthalmic nerve sheath diameter
(an indirect measure of intracranial pressure) in premature infants with and without intraventricular
hemorrhage. This will be a real time study that documents the technology’s ability to quantify change in
intracranial pressure without the use of MRI. It has limited corporate sponsorship. 3) Analyze, present
and publish two recently completed multicenter studies that were both led by the TNORC (aminophyline
as an adjunct to cooling therapy for hypoxic ischemic encephalopathy and zosyn versus ampicillin and
gentimicin as first choice antibiotics in the NICU). The aminophylline study’s preliminary analysis looks
promising as a roadmap for an RO1 submission to fund a multicenter randomized controlled trial. The
zosyn study has not yet been analyzed but holds great promise for paradigm change. 4) Re-open our
NICU follow up clinic (which has been closed since Katrina) as a resource for neurodevelopmental follow
up in current and future studies.
Plan: What the TNORC needs to be successful in 2011: The directors of the TNORC are requesting
$35,000 during the year of 2011 to hire a mid level person as a part time study coordinator and data
manager; plus $15,000 for equipment and supplies to help support data management; software for
statistical analysis, matching and randomization; travel to meetings to present our studies (to help build
support for our RO1 application); as well as developmental assessment tools necessary for the NICU
follow up clinic (Bayley III & DPIII kits). Total request: $50,000. The current man power for the TNORC is
being supplied 100% by physicians. We cannot continue to add studies to the TNORC roster without an
expansion in dedicated personnel. We will not qualify for other studies if we do not have an active
follow up clinic. Most importantly, the TNORC will not be able to participate in the National Children’s
Study, without standardized developmental follow up. If the TNORC is to attract new (and support
existing) external funding, it must develop rudimentary infrastructure and hire essential personnel.
PROJECT DESCRIPTION: THE TULANE NEONATAL OUTCOMES RESEARCH COLLABORATIVE
Introduction: TNORC has an ambitious agenda for 2011. Each of the four specific aims
described in this proposal are designed to propel the collaborative forward as a research
enterprise; building momentum, infrastructure, revenue and stature with each step of
completion. Much like the PLAN->DO->STUDY->ACT cycles of quality improvement (PDSAs),
TNORC is also planning and executing its own continual improvement. Our ultimate vision is to
become a regional and national resource in neonatal clinical research.
Specific Aim 1: To be one of only two sites in the “Open Label Study to Describe the Pharmacokinetics
of Acyclovir in Infants” as summarized in the table below. Acyclovir is a commonly used medication in
neonatology that, like many other drugs, has no pharmacokinetic data in newborns. The approximate
reimbursement is $4000 per patient enrolled. The master grant for this study has more than 20 other
target medications in the roster for similar analyses. Dr Danny Benjamin (the study co-PI), has offered us
the opportunity to be one of these two sites. Dr Jane Reynolds would be the study coordinator. Phillip
Gordon and Euming Chong will be the site Co-PIs. TNORC approved this protocol on 1/11/2011.
Protocol Title
An Open Label Study to Describe the Pharmacokinetics of Acyclovir in
Infants IND Number: 106153
Product
Acyclovir
Objective:
This study will evaluate the safety and pharmacokinetics of intravenous acyclovir in
infants.
Study Design:
Single-center, open-label, pharmacokinetic study.
Infants < 91 days postnatal age suspected to have a systemic infection. These
participants will be divided into groups as determined by gestational and postnatal
age:
Group-1: 23-29 weeks gestational age, <14 days postnatal age
Study Population:
Group-2: ≥ 30 weeks gestational age, <14 days postnatal age
Group-3: 23-29 weeks gestational age, 14-90 days postnatal age
Group-4: ≥ 30 weeks gestational age, 14-90 days postnatal age
Number of Participants:
Approximately 24 participants with at least 3 PK samples
Number of Sites:
2 centers
Duration of
Participation:
Up to 13 days
Dose Schedule:
Estimated Start:
Estimated Finish:
3 days of intravenous acyclovir will be administered as follows: 500 mg/m2 q 8
hours for 3 days
March 2011
September 2011
Specific Aim 2: To initiate our first device study entitled, Optic Nerve Sheath Diameter Ultrasound as a
Measure of Hydrocephalus. PI = Dr Robert Gordon
Clinical background: Hydrocephalus is a condition characterized by increased intracranial pressure and
the subsequent complications that result when the brain is deformed by that pressure. Congenital
hydrocephalus occurs in 1/500 live births, making it more common than Trisomy 21 with potentially
more devastating consequences, such as generalized cerebral hypoperfusion, mental retardation and
death. The etiology of hydrocephalus can be varied, with over 180 different reasons for hydrocephalus
to develop. Intraventricular hemorrhage (IVH) is the leading cause of congenital hydrocephalus. We will
use the strong association between IVH and prematurity to screen this subgroup for development of
elevated intracranial pressure. Current methods for assessing hydrocephalus include cranial ultrasound,
CT, MRI and monitoring of head circumference. Each method has specific draw backs, including: cost,
radiation exposure, cold stress, need for specialized technicians, and varied interpretations of imaging. If
there were a simple inexpensive, noninvasive bedside tool that could assess elevated intracranial
pressure, it would greatly improve the management of premature infants at risk for hydrocephalus.
Device Background: Ultrasound (U/S) technology uses sound waves to penetrate a medium and then
record the reflective signatures of that medium to reveal an image. Its excellent safety profile and
relative ease of use has found it a role in medical diagnostics for the last 50 years. Ophthalmologists
employ U/S routinely in their offices to assess retinal and other posterior ocular structures. Recently
there has been interest in using U/S for a new role, measuring the optic nerve sheath diameter (ONSD).
Geeraerts, T. et al 1 found that OSND on T2 MRI correlates with elevated intracranial pressure. Rajajee,
V. et al 2 found that ultrasonically measured ONSD was highly sensitive and specific for identifying
intracranial pressure>20 mmHg. Gravendeel, J. et al 3 was first to publish normative values for ONSD
measured by ultrasound (values at birth, 4 and 8 months were 3.9, 5.5, and 5.8mm respectively).
Objectives: To use ONSD measured by Accutome’s B-Scan Plus U/S to establish a growth curve for
premature infants to be used for assessing likelihood of hydrocephalus development. Babies born at
less than 36 weeks gestational age will be followed weekly in the NICU for changes in head
circumference (HC), cranial ventricular width (VW), and ONSD. Upon discharge (typically at 1-3 months
of age), the infants will be monitored in the outpatient setting every 3 months until one year of age. Our
target recruitment of 60 premature babies is a starting point based on projected Tulane NICU patient
volume and the cohort size in the Gravendell, J et al report . 3 Following longitudinal collection of data
and appropriate statistical analysis, a growth curve will be plotted for the subgroup of patients who did
not develop hydrocephalus. In the hydrocephalic group we will compare ONSD, VW and HC to
determine if ONSD may be an earlier and more accurate marker for elevated intracranial pressure.
1. Geeraerts T, Newcombe VF, Coles JP, et al. Use of T2-weighted magnetic resonance imaging of the optic nerve sheath to
detect raised intracranial pressure. Critical care (London, England). 2008;12(5):R114.
2. Rajajee V, Vanaman M, Fletcher J, Jacobs T. Optic nerve ultrasonography is an accurate non-invasive bedside tool to detect
raised ICP in the neuroicu; Institutional validation of criteria may be required. Neurocritical Care. 2010;13:S161.
3.Gravendeel J, Rosendahl K. Cerebral biometry at birth and at 4 and 8 months of age. A prospective study using US. Pediatric
Radiology. 2010;40(10):1651-1656.
Specific Aim 3A: to analyze, present and publish the “Aminophylline use to prevent renal dysfunction in
patients with birth asphyxia undergoing whole body cooling” study – a large case series and matched
cohort comparison study performed by Tulane-Lakeside and Ochsner in collaboration with the
University of Virginia to investigate the safety and efficacy of aminophylline as an adjunct therapy to
cooling. Co-PIs = Dr Euming Chong and Phillip Gordon. IRB waiver granted.
Study Description: 17 infants were consecutively treated with whole body cooling for hypoxic ischemic
encephalopathy (HIE) based on predetermined, standardized criteria at the Tulane-Lakeside and
Ochsner Main Campus NICUs from 2008-2010. All but one infant received aminophylline, a therapy
known to improve renal function in HIE but not to have been paired with cooling before now. One
infant died. Another infant remains ventilator dependent at transfer. All other infants were discharged
home on full feeds by bottle. Sarnat scores of neurologic insult revealed a median score of moderate
severity in our cohort with an average initial blood gas pH of 6.96 and an average base deficit of -18.96.
Substantial improvements in renal function were noted (as shown below).
PRELIMINARY
PRIMARY OUTCOME DATA
Severe Renal
Dysfunction
< 0.5 ml/kg/h
Moderate Renal
Dysfunction
< 1 ml/kg/h
Acute Renal Failure
creatinine > 1.5 x 2 d
theophylline
(pooled data*)
21/101 (21%)
N/A
N/A
aminophylline + cooled (our study)
2/17 (12%)
6/17 (35%)
2/17 (12%)
cooled
(pooled data*)
128/257 (50%)
204/234 (87%)
N/A
cooled control
(pooled data*)
144/265 (54%)
204/226 (90%)
N/A
theophylline control
(pooled data*)
53/96 (55%)
N/A
N/A
* Pooled data derived from 8 randomized controlled trials with available data on renal function (4 from cooling
and 4 from theophylline therapy studies). References available upon request.
Data Analysis: We are collaborating with the University of Virginia (UVA), where a similar whole body
cooling guideline (sans aminophylline) is in use. We will do a 2 to 1 matched cohort comparison study of
renal function between aminophylline treated and non-treated infants, using the UVA patients as the
non treated controls. There are more than 70 cooled patients in the UVA database, allowing us to match
infants by Sarnat score and initial base deficit, thereby assuring similar severities of initial renal insult.
Plan: An abstract has been submitted to the Pediatric Academic Societies meeting in May 2011. We
intend to publish within weeks of that presentation and to use that meeting as a forum for organizing a
randomized controlled trial. The publication will be submitted by May and, as we work towards its final
publication, we will organize and write our first application for an RO1 to fund the trial, (with a
submission goal for the fall cycle of the NICHD). The NICU follow up clinic will be imperative for this
study.
Specific Aim 3B: To analyze, present and publish the “Comparison between ampicillin and gentamicin
vs. piperacillin/tazobactam use in the neonatal intensive care unit” study – a multicenter study
performed at Tulane-Lakeside and Wesley Medical Center (Wichita, KA) to investigate the safety and
efficacy of piperacillin/tazobactam as a first choice antibiotic in the NICU. Co-PIs = Dr Euming Chong and
Phillip Gordon. IRB waiver submitted.
Study Description: Tulane-Lakeside and Wesley Medical Center (KA) each entered into a PDSA cycle on
Jan 2010 in which they switched from ampicillin and gentamicin to piperacillin/tazobactam as a first
choice antibiotic for the newborn. There were a number of reasons for this quality improvement baseddecision including increased ampicillin resistance organisms, gentamicin dosing errors and associated
blood draws, gentamicin ototoxicity, gentamicin renal toxicity, and recent data demonstrating that all
members of the aminoglycoside family are potent vasodilators of the ductus arteriosus. This month (Jan
2011), an IRB waiver was submitted at Tulane (and one is pending at Wesley) to perform a review of
piperacillin/tazobactam versus ampicillin and gentamicin for the safety and efficacy of
piperacillin/tazobactam as a first choice antibiotic.
Planned Analysis and Publication: Outcomes of interest will include treatment of a patent ductus, failed
hearing screens, resistant organisms, failed antibiotic therapy events, mortality, ventilator associated
pneumonias, necrotizing enterocolitis, number of transfusions and cost. The NICHD neonatal rapid start
trial program recently performed a pharmacokinetic analysis on piperacillin/tazobactam, facilitating our
initial PDSA. The final analysis of that study is due soon. Dr Benjamin (the PI of that study) has promised
us that this data will be made available to us shortly after analysis and if that pK analysis suggests an
alteration in dosing, we will consider that as a potential future PDSA intervention. This study will be
submitted for publication in 2011.
Specific Aim 4: to re-open the Tulane-Lakeside NICU Follow Up Clinic and maintain an internal NICU
database using our existing electronic medical record system that includes neurodevelopmental
assessments.
Background: New Orleans has two other institutions that have level III regional NICUs. One does not
have a designated NICU follow up clinic (Ochsner) but has a developmental pediatrician. The other, LSU
Children’s Hospital, has never reported their outcomes nationally. It serves primarily as a means of
helping their patients get additional services from their hospital. There is currently no institution in the
Mississippi Delta region reporting neurodevelopmental outcomes on NICU graduates. This is
unfortunate for two reasons: 1) before Hurricane Katrina, Louisiana had some of the worst NICU
discharge outcomes in the country (based on Vermont Oxford data).2) post Katrina, Tulane and Ochsner
have both made significant strides in the quality of their NICU care. However, the nation currently
remembers us as the same pre-Katrina institutions. A NICU discharge clinic that includes
neurodevelopmental assessments will allow TNORC to report our current outcomes, which we believe
are exemplary. It will allow us to stand out as an institution regionally. Finally, and perhaps most
importantly for this application, it will allow TNORC to access prospective studies and trials that require
neurodevelopmental assessment as part of their study protocol (which is the most substantial limit
facing the TNORC today).
Action Plan: The TNORC directors met with HCA administrators on Jan. 6th
and brokered a plan for opening a NICU follow up clinic at Lakeside Hospital
in mid March. HCA will handle staffing needs. TNORC and Tulane pediatrics
will handle physician staffing. Approximately $5000 is needed for
developmental assessment equipment (Bayley III developmental assessment
scales, DPIII developmental survey, two large crawl-around carpets and
computerized data entry/processing of these scores).
Conclusions: This proposal demonstrates the versatility of the TNORC as a clinical research enterprise.
We started it as a quality improvement venture, focusing on PDSA cycles. Two such interventions (the
addition of aminophylline to whole body cooling and the switch from ampicillin & gentamicin to
piperacillin/tazobactam) resulted in our first two multicenter studies.
Phase I at the TNORC (2010): PDSA cycles were used to create
one year quality improvement projects. Based on available
literature, two global changes were made to current clinical
practice at the Tulane NICU: 1) Piperacillin/tazobactam was
chosen as the first choice of antibiotic instead of ampicillin &
gentamicin. 2) A single dose of aminophylline was administered
prior to the initiation of whole body cooling for asphyxiated
infants to prevent renal dysfunction. IRB waivers were applied
for prior to analysis.
From a practical point of view, neither of these studies generated immediate revenue. However, the
aminophylline study appears to be so dramatic in its preliminary results that we believe the clinical
concept is ripe for a randomized controlled trial. We will be well positioned to write that grant and lead
the study if we have sufficient infrastructure in place (namely neurodevelopmental follow up). This past
year, we also successfully completed our role as a site for the NICHD sponsored fluconazole prophylaxis
study. This was a low enrollment, low revenue study. We agreed to be a part of it primarily because we
wanted to develop expertise and infrastructure in prospective clinical trials. This led to the offer of the
Acyclovir study in 2011, (a more lucrative study). Both studies will be of lasting value to the neonatal
community and thus will improve our stature nationally.
Phase II at TNORC (2011):
a) Evolution - Dr Robert Gordon’s device study represents one new phase of our venture. Devices,
especially those which can be used in observational studies are ideal for parallel studies because they
have little likelihood of introducing extraneous bias to an existing medical study. Thus this represents an
excellent opportunity for us to learn how to coordinate device studies with an ongoing prospective
study (such as the acyclovir study). Both studies will improve our potential to generate revenue.
b) Communication / publication / advancement - The aminophylline and piperacillin/tazobactam
studies are both likely to have substantial impact upon the national neonatology community when they
are presented and published. TNORC represents an important incubation chamber for our junior faculty
and offers a clear mechanism by which they can begin to ascend the promotion ladder. These synergies
also provide the motivation and energy for future clinical studies and grant applications.
c) Remediation - The re-opening of our NICU follow up clinic is perhaps the most critical goal of all for
the coming year. We hope to have it open by March. Without this, substantial future funding will be
denied to us and we will not be on a level footing with similar neonatal research enterprises nationally.
RELEVANCE OF PROJECT TO LONG RANGE GOALS:
The budget requested in this application serves as seed / bridging money for TNORC. In our conclusions
section of the project summary, we outlined the first two years of TNORC’s existence (2010 and 2011).
We have demonstrated in these two years, a clear vision by which a new research enterprise can
transition from principally performing unfunded quality improvement research, to attracting mid level
NIH funding as a non-network clinical research site (as well as industry sponsorship), to ultimately
developing TNORC into what most investigators would consider an optimal funding opportunity (the
principal site for NIH grants).
It is perhaps worth noting that no start up money has been spent on TNORC. All the effort spent upon it
thus far is due to the vision and academic motivations of its directors and participants. Now the timing is
critical. There is only so much time that each intensivist can give to contracted studies (as we are
attracting now), because the revenue is not sufficient to create protected time. To reach the next level,
we need a mid level person to help focus and coordinate TNORC. We need dedicated equipment
(computers, software, a data backup system). These things are not expensive and our current projected
revenue should put us past the breakeven scenario by 2012 (after overhead is taken). Most importantly,
we anticipate that future funding should eventually be on par with other center-based research
enterprises at the university. This grant would be the stimulus that TNORC needs to make all of this
happen.
BUDGET FOR TNORC (2011):
Current funds: $5,000 (after overhead)
Pilot Grant Request:$50,000
$ 35,0000 TNORC employee (part time) – patient enrollment, IRB liason, data management, research
$4,500 Developmental assessment tools and equipment for the NICU follow up clinic
$3,500 Software for statistics, patient randomization, patient matching, Access (for building templates
and auto filling datasets) for data entry and management at Lakeside
$2,500 computer and miniserver for de-identified data repository at Tulane
$2,500 for miscellaneous supplies to support TNORC (including books, subscriptions, etc.)
$ 3,000 to Dr Robert Gordon for miscellaneous supplies to support his ONSD study.
$ 4,000 for travel to PAS and other meetings to present research
Total: $55,000
TIMELINE FOR COMPLETION – All 4 specific aims in this proposal will be completed by Dec 2011.
BIOGRAPHICAL SKETCH CURRENT AS OF 1/10/2010
Provide the following information for the key personnel in the order listed on Form Page 2.
Photocopy this page or follow this format for each person.
NAME
POSITION TITLE
Phillip V. Gordon MD PhD
Professor of Pediatrics
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral
training.)
INSTITUTION AND LOCATION
North Carolina State University
Florida State University
University of Florida
DEGREE
(if applicable)
YEAR(s)
B.A.
Ph.D.
M.D.
1986
1992
1995
FIELD OF STUDY
Psychology
Molecular Biology
Medicine
RESEARCH AND PROFESSIONAL EXPERIENCE: Concluding with present position, list, in chronological order, previous
employment, experience, and honors. Include present membership on any Federal Government public advisory committee. List, in
chronological order, the titles, all authors, and complete references to all publications during the past three years and to
representative earlier publications pertinent to this application. If the list of publications in the last three years exceeds two pages,
select the most pertinent publications.
Selected Professional Experience
2009-present Professor, Chief & Elsie Shaeffer Chair of Neonatology, Assistant Chair
of Pediatrics, Tulane School of Medicine, New Orleans, LA
2009-present Associate Editor, Journal of Perinatology
2007-2009
Section Head of Neonatology, Ochsner Health System, New Orleans LA
2006-2007
Associate Professor of Neonatology, University of Virginia Health
Sciences, Charlottesville VA
2004-2007
Neonatal Fellowship Director, University of Virginia Health Sciences,
Charlottesville VA
2000-2006
Assistant Professor of Neonatology, University of Virginia Health
Sciences, Charlottesville VA
2002-2007
Recipient NIDDK 1KO8DK/HD61553-0 Paracrine regulation of IGF-I in
the developing gut
2001-2003
Recipient NIH CHRCDA HD01421The role of IGF-I in developing gut
Publications by Dr Gordon in Clinical, Translation & Basic Science Research:
1. Gordon P, Rutledge J, Sawin R, Thomas S, and Woodrum D. Early postnatal
dexamethasone increases the risk of focal small bowel perforation in extremely low birth
weight infants. Journal of Perinatology 19: 573-577, 1999.
2. Gordon PV, Price WA, Stiles AD. Dexamethasone administration to newborn mice
alters mucosal and muscular morphology in the ileum and modulates IGF-I localization.
Pediatric Research 49: 93-99, 2001.
3. Gordon PV, Young ML, Marshall DD. Focal small bowel perforation: an adverse effect
of early postnatal dexamethasone therapy in extremely low birth weight infants. Journal
of Perinatology 21: 1-5, 2001.
4. Gordon PV, Marshall DD, Stiles AD, Price WA. The clinical, morphologic, and
molecular changes in the ileum associated with early postnatal dexamethasone
administration: from the baby’s bowel to the researcher’s bench. Molecular Genetics and
Metabolism 72: 91-103 (and cover photo), 2001.
5. Gordon PV, Stiles AD, Price WA, Rutledge J. Early postnatal dexamethasone
diminishes transforming growth factor alpha localization within the ileal muscularis
externa of newborn mice and extremely low birth weight infants. Pediatric and
Developmental Pathology 4: 532-537, 2001.
6. Gordon PV, Moats-Staats B, Stiles AD, Price WA. Dexamethasone changes the
composition of insulin-like growth factor-binding proteins in the newborn mouse ileum.
Journal of Pediatric Gastroenterology and Nutrition 35(4):532-8, 2002.
7. Guthrie SO, Gordon PV, Thomas V, Thorp JA, Peabody J, Clark RH. Necrotizing
Enterocolitis in a National Neonatal Data Set. Journal of Perinatology 23(4): 278-85,
2003.
8. Gordon PV, Paxton JB, Herman A, Carlisle E, Fox NS. IGF-I accelerates ileal epithelial
cell migration in culture and newborn mice and may be a mediator of steroid-induced
maturation. Pediatric Research 54(5); 2004.
9. Herman A, Carlilse E, Paxton JB, Gordon PV. Insulin-like growth factor (IGF-I)
regulates submucosal growth and thickness within the newborn mouse ileum. Pediatric
Research 55(3); 507-13, 2004.
10. Gordon PV, Paxton JB, Kuemmerle J, Fox NS. A 14 kD cathepsin L-derived-carboxylIGFBP-2 fragment is sequestered by cultured rat ileal crypt cells. American Journal of
Physiology: Gastroenterology and Liver Physiology, 2005 (Epub ahead of print).
11. Effird MM, Heerens AT, Gordon PV, Bose CL, Young D. Randomized controlled trial
of hydrocortisone for prevention of hypotension in extremely low birth weight infants.
Journal of Perinatology 25(2); 119-24, 2005.
12. Gordon PV, Paxton JB, Fox NS. A methodology for distinguishing divergent cell fates
within a common progenitor population: adenoma- and neuroendocrine-like cells are
confounders of rat ileal epithelial cell (IEC-18) culture. BMC Cell Biology 6(1):2, 2005.
13. Gordon PV, Paxton JB, Fox NS. CREG mediates glucocorticoid-induced loss of the
type-2 IGF receptor in ileal epithelial cells. Journal of Endocrinology 185(2), 2005 (Epub
ahead of print).
14. Gordon PV, Herman AC, Marcinkiewicz M, Gaston BM, Laubach VE, Aschner JL A
neonatal mouse model of intestinal perforation: Investigating the harmful synergism
between glucocorticoids and indomethacin, Journal of Pediatric Gastroenterology and
Nutrition, 2007 Nov;45(5):509-19.
15. Gordon PV, Swanson JR, Attridge JT, Clark R. Emerging trends in acquired neonatal
intestinal disease: is it time to abandon Bell's criteria? J Perinatol. 2007 Nov;27(11):66171.
16. Marcinkiewicz M, Gordon PV. A role for plasmin in platelet aggregation: differential
regulation of IGF release from IGF-IGFBP complexes? Growth Horm IGF Res. 2008
Aug;18(4):325-34.
17. Gordon PV, Marcinkiewicz M. An analysis of IGFBP evolution.Growth Horm IGF Res.
2008 Aug;18(4):284-90.
18. Stout G, Lambert DK, Baer VL, Gordon PV, Henry E, Wiedmeier SE, Stoddard RA,
Miner CA, Schmutz N, Burnett J, Christensen RD. Necrotizing enterocolitis during the
first week of life: a multicentered case-control and cohort comparison study. J Perinatol.
2008 Aug;28(8):556-60.
19. Gordon PV. Understanding intestinal vulnerability to perforation in the extremely low
birth weight infant. Pediatr Res. 2009 Feb;65(2):138-44.
BIOGRAPHICAL SKETCH CURRENT AS OF 1/10/2010
Provide the following information for the key personnel in the order listed on Form Page 2.
Photocopy this page or follow this format for each person.
NAME
POSITION TITLE
Euming Chong, MD
Assistant Professor of Pediatrics
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral
training.)
INSTITUTION AND LOCATION
University of Western Ontario, Canada
Wayne State University, Michigan
Thomas Jefferson University Hospital
DEGREE
(if applicable)
MD
YEAR(s)
2002
2002-2005
2005-2008
FIELD OF STUDY
Medicine
Pediatrics
Neonatology
RESEARCH AND PROFESSIONAL EXPERIENCE: Concluding with present position, list, in chronological order, previous
employment, experience, and honors. Include present membership on any Federal Government public advisory committee. List, in
chronological order, the titles, all authors, and complete references to all publications during the past three years and to
representative earlier publications pertinent to this application. If the list of publications in the last three years exceeds two pages,
select the most pertinent publications.
Selected Professional Experience
2008 – present
Assistant Professor of Pediatrics, Tulane University
Academic & Clinical Educator/Attending for the Pediatric Residency
Tulane University
07/2006 – 06/2008 Thomas Jefferson University Hospital, Philadelphia, PA
Neonatal-Perinatal Chief Fellow
07/2005 – 06/2008 Thomas Jefferson University Hospital, Philadelphia, PA
Neonatal-Perinatal Fellowship Program
07/2002 – 06/2005 Children’s Hospital of Michigan, Detroit, MI
Pediatric Residency Program
04/2000 – 05/2002 University of Western Ontario Faculty of Medicine, London, ON
Doctor of Medicine
04/1997 – 09/1999 International Medical University, Kuala Lumpur, Malaysia
Diploma of Advanced Medical Science
Pre-clinical years prior to transfer to University of Western Ontario
Publications by Dr. Chong in Clinical, Translation & Basic Science Research:
1. Chong E, Greenspan J, Kirkby S, Culhane J, Dysart K. Changing Use of Surfactant Over
6 Years and Its Relationship to Chronic Lung Disease. Pediatrics 2008; 122(4):e917-21
2. Chong E, Locke R, Dysart K, Chidekel A, Shaffer T, Miller T. Heat Shock Protein 70
Secretion by Tracheal Tissue during Mechanical Ventilation: Association with Indices of
Tissue Functioning and Modeling. Pediatric Research 2009; 65(4):387-91
3. Dola C, Tran T, Linhuber AM, Cierny J, Denicola N, Chong E, Bhuiyan A. Preterm
Birth After Mature Fetal Lung Indices: Is There Any Neonatal Morbidity? Journal of
Maternal –Fetal and Neonatal Medicine 2010; May Early Online e1-6 PMID: 20459338
BIOGRAPHICAL SKETCH CURRENT AS OF 1/9/2010
Provide the following information for the key personnel in the order listed on Form Page 2.
Photocopy this page or follow this format for each person.
NAME
POSITION TITLE
Jane E. Reynolds , MD
Associate Professor of Pediatrics
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral
training.)
DEGREE
INSTITUTION AND LOCATION
YEAR(s)
FIELD OF STUDY
(if applicable)
Hunter College in the Bronx, City University of NY
BA
1964-1968
Women’s Medical College of PA
MD
1968-1972
Albert Einstein Medical Center, Philadelphia, PA
1972-1973
Thomas Jefferson University Hospital, Philadelphia, PA
1973-1975
Medicine
Pediatrics
RESEARCH AND PROFESSIONAL EXPERIENCE: Concluding with present position, list, in chronological order, previous
Hospital of the Albert Einstein College of Medicine/
1975-1977
Neonatology
employment, experience, and honors. Include present membership on any Federal Government public advisory committee. List, in
chronological
order, the
titles, all NY
authors, and complete references to all publications during the past three years and to
Bronx Municipal
Hospital,
representative earlier publications pertinent to this application. If the list of publications in the last three years exceeds two pages,
select the most pertinent publications.
Selected Professional Experience
1978-1984
Assistant Professor of Pediatrics
1984-Present
Associate Professor of Pediatrics
Tulane University School of Medicine (LA)
1984-2010
Neonatal Attending
MCLNO-University Hospital (LA)
1978-1993
Neonatal Attending
Charity Hospital of Louisiana
1985-1997
Consulting Neonatologist
Slidell Memorial Hospital (LA)
1977-1978
Clinical Instructor & Neonatal Attending
Hospital of the Albert Einstein College of Medicine (NY)
1977-1978
Consulting Neonatologist
New Rochelle Hospital and Medical Center (NY)
Publications by Dr. Reynolds in Clinical Research:
1. Hot Topics 2000 In Neonatology, December 2000, “Early Postnatal Dexamethasone Therapy for
the Prevention of Chronic Lung Disease” for the Vermont Oxford Steroid Study Group, Roger F.
Soll, MD, Pediatrics, 2001 Sept;108(3):741-8.
2. Hot Topics 2000 In Neonatology, December 2000, “Neonatal Skin Care Study: The Effect of
Aquaphor Original Emollient Ointment on Nosocomial Sepsis Rates and Skin Integrity in Infants
of Birth Weight 501 to 1000 Grams” for the Vermont Oxford Group. (In Press)
3. Eidelman, AI and Reynolds, J: Gentamycin Resistant Klebsiella Infections in a Neonatal Intensive
Care Unit. Am Jour Dis Chil 4:132, April, 1978.
4. Dunn, DW and Reynolds, J: Neonatal Withdrawal Symptoms Associated with “T’s and Blues”
(Pentazocine and Triplennamine). Am Jour Dis Chil, 136:644-645, July, 1992.
5. Contributions to Practical manual of Pediatrics, 2nd edition. Waring, WW, Jeansonne, LO, et al.
CV Mosby Co., 1992.
6. Reynolds, JE, Pernoll, ML, Gill, WL, Nadell, J, Frost, A, Mabie, W: Hydrocephalus: A Case of
Ventricular-Amniotic Shunting. Southern Med J 78(2):203, Feb, 1985.
7. Reynolds, JE, Pernoll, ML, Mabie, W, Nadell, J, Gill, WL: Direct Fetal Therapy: The
Multidisciplinary Team Concept, Southern Med J 78(6):661-664, June, 1985.
8. Cryotherapy for Retinopathy of Prematurity Cooperative Group: Multicenter Trial of
Cryotherapy for Retinopathy of Prematurity. Pediatrics 81:679-706, 1988.
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Gordon, Robert Allen
Associate Professor of Clinical Ophthalmology and
Pediatrics
eRA COMMONS USER NAME (credential, e.g., agency login)
rgordon
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and
residency training if applicable.)
DEGREE
INSTITUTION AND LOCATION
MM/YY
FIELD OF STUDY
(if applicable)
Tulane University(New Orleans, La)
Tulane Medical School (New Orleans, La)
Baylor University Medical School (Houston, Tx)
Tulane University Medical Center (New Orleans,
La)
Indiana University Medical Center (Indianapolis,
Ind)
B.S.
M.D.
Internship
1965
1969
1970
Residency
1970-1973
Fellowship
1976
Chemistry
Medicine
Rotating internship
Ophthalmology
Pediatric Ophthalmology
Please refer to the application instructions in order to complete sections A, B, C, and D of the
Biographical Sketch.
A. Personal Statement
Optic nerve sheath diameter (ONSD) has been shown to directly correlate with the level of
ICP. Since there are only a few reported studies on ONSD measurements in babies, and none
on preemies, the main goal of this study is to develop a normative database of ONSD in
premature babies as measured by noninvasive ophthalmic ultrasound. A secondary goal is to
measure ONSD in preemies who develop hydrocephalus before and after ventriculoperitoneal
shunts.Since joining the faculty in 1973, my interest in ophthalmic signs and symptoms of
pediatric systemic diseases, including prematurity, has exponentially expanded during my role
as Director of the Tulane Pediatric Ophthalmology and Strabismus service. Although my
research interests have mainly focused on preventing lifetime blindness from Retinopathy of
Prematurity (25 years as principal investigator for NIH sponsored clinical trials), I have
frequently struggled to help my pediatric colleagues diagnose increased intracranial pressure
(IICP) or hydrocephalus in infants and children. In older children and adults, IICP is classically
reflected on ocular fundus examination by noting papilledema of the optic nerve head.
Unfortunately, in infants and very young children papilledema is usually not present or too
difficult to confirm as an outpatient due to poor patient cooperation. Specifically, since
premature infants, babies and children less than 2-3 years of age do not manifest papilledema
when they develop IICP, clearly new noninvasive diagnostic techniques in addition to
measuring head circumferences and performing brain ultrasound should be explored to
improve early detection of hydrocephalus in this fragile population.
B. Selected Positions and Honors
Positions and Employment
1975-present Director, Pediatric Ophthalmology and Strabismus, Tulane
University Health Sciences Center
Other Experience and Professional Memberships
1990-present Member, American Association Pediatric Ophthalmology & Strabismus,
1976-present Fellow, American Academy of Ophthalmology
Honors and Awards
2005-2010 “Best Doctors in New Orleans”-Pediatric Ophthalmology
2006 National Eye Institute-NIH, ETROP Inspiration Award
1994-1996 Pediatric Consultant, Ophthalmic Device Section, (Intraocular Lenses), Federal
Drug Administration Honor Award,American Academy of Ophthalmology
“Composite Drawing of Retinopathy of Prematurity Stages & Zones”, Published in Neonatal
Ophthalmology Slide Set, Produced & distributed by Wyeth International Laboratories,
Copyright 1992
C. Selected Peer-reviewed Publications
Publications Most Relevant to the Current Application
Additional Recent Publications of Importance to the Field
1. *The Early Treatment for Retinopathy of Prematurity Cooperative Group. Authors/Group
Information: The members of the writing Committee and the Early Treatment for Retinopathy of
Prematurity (ETROP) Study Investigators are listed on pages E7 and E8. Gordon RA (Page 7),
“Final Visual Acuity Results in the Early Treatment for Retinopathy of Prematurity Study,” Arch
Ophthalmol. 2010; 128(6) (doi:10.1001/archophthalmol.2010.72).
2. Systematic Review of Digital Imaging Screening Strategies for Retinopathy of Prematurity.
Robert A. Gordon, et al. Letter to Editor, Pediatrics 2009; 123(2) pp. e360-3361, (doi:
10.1542/peds.2008-3579).
3. VanderVeen DK, Coats
DK, Dobson V, Fredrick D, Gordon RA, et al. Prevalence and course of strabismus in the first
year of life for infants with prethreshold retinopathy of prematurity: findings from the Early
Treatment for Retinopathy of Prematurity study. Arch Ophthalmol 2006 Jun; 124(6):766-73
4. Early Treatment of ROP Cooperative Group, “Revised Indications for the Treatment of
Retinopathy of Prematurity: Results of the Early Treatment for Retinopathy of Prematurity
Randomized Trial,” Archives of Ophthalmology; 12/2003, 121 1684-1696. 5. Cryotherapy for
ROP Cooperative Group”, Multicenter Trial of Cryotherapy for ROP: Natural History ROP: Ocular
Outcome of 5 ½ years in Premature Infants with Birth Weight Less Than 1251g”, Archives of
Ophthalmology; 5/2002, 120(5)595-599. Gordon RA, Principal Investigator, Tulane CRYO-ROP
Center)
D. Selected Research Support
Recently Completed Research Support
Principal Investigator, NIH-sponsored ROP clinical trials:
2002-2009 Principal Investigator, Phase II ETROP Follow-up study, NEI
2000-2005 Principal Investigator, CRYO-ROP Follow-up study, NEI
2000-2005 Principal Investigator, "Early Treatment Study for ROP (ETROP)”, NEI Participating
Center
2000-2001 Principal Investigator, "Phase III CRYO-ROP Outcome Study Center.”
1994-1998 Principal Investigator, "Phase III CRYO-ROP Outcome Study Center”, National Eye
Institute Grant # 2U10 EY06358 08
1993-1999 Principal Investigator, "STOP-ROP" (Supplemental Oxygen for Pre-threshold ROP)
NEI/NIH Center
1989-1994 Principal Investigator, “Phase II CRYO-ROP Outcome Study Center,” National Eye
Institute Grant # 2401EY06358-05
1985-1989 “A Multicenter Trial of Cryoablation for Retinopathy of Prematurity”, Gordon RA,
Principal Investigator for Participating Center, NEI Grant # 1U01EY06358-01 ($372,000)
BIOGRAPHICAL SKETCH as of 1/12/2011
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
POSITION TITLE
NAME
David G. Cupp, MD
Ophthalmology Resident (PGY3)
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency
training if applicable.)
DEGREE
INSTITUTION AND LOCATION
YEAR(s)
FIELD OF STUDY
(if applicable)
University of California San Diego (La Jolla, CA)
Penn State College of Medicine (Hershey, PA)
Wilson Medical Center (Johnson City, NY)
Tulane University (New Orleans, LA)
B.S.
M.D.
Intern
Resident
1997-2001
2008
2008-2009
2009-present
Physics-Biophysics/PreMed
Medicine
Transitional Year
Ophthalmology
Selected Professional Experience
2001-2004
2005-2007
Biophysics Researcher. Torrey Pines Institute of Molecular Science (San Diego,
CA).
Research Assistant. Retina Research Group-Penn State College of Medicine
(Hershey, PA).
Peer Reviewed Publications and Poster
1. Cupp, DG. Kampf, PJ. Kleinfeld, AM. Fatty Acid-Albumin Complexes and the Determination of
the Transport of Long Chain Free Fatty Acids across Membranes. Biochemistry, 4473-4481,
2004.
2. Kampf, PJ. Cupp, DG. Kleinfeld, AM. Different mechanisms of free fatty acid flip-flop and
dissociation revealed by temperature and molecular species dependence of transport across
lipid vesicles. J. Biol. Chemistry, 21566-21574, 2006.
3. Alan M. Kleinfeld, David Cupp, J. Patrick Kampf. Flip-flop is Rate Limiting for Transport of Long
Chain Free Fatty Acids across Small and Large Unilamellar Lipid Vesicles. Poster presented at
48th Annual Biophysical Socitey Meeting; Baltimore, MD, 2004.