Medical Student Research Fellowship for Summer 2009

Mentor: Jane G. Wigginton, MD
Department: Surgery; Dallas/Fort Worth Center for Resuscitation Research, Division of Resuscitative Endocrinology
Room Number: E7.202, Lab: G8.212
Mail Code: 9031
Phone Number: 8-9491
E-mail: Jane.Wigginton@UTSouthwestern.edu
Project Title: Utilization of Sex Steroids As Acute Resuscitation Drugs in Severe Traumatic Injuries
Human Subjects IRB approved project number (where applicable):
Animal Subjects IRB approved project number (where applicable):
Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects): Patient-based research, animal-based research, and bench research.
Brief Description of Projects:
Human:
1. NIFTI-TBI (Non-Interventional F-Two Isoprostane- Traumatic Brain Injury) Trial:
A significant cause of mortality and persistent morbidity in TBI is due to potentially preventable secondary injury, namely oxidant injury, inflammation, and apoptosis in the penumbra (the part of the brain that is at risk after the initial injury, but potentially salvageable), occurring in the first few hours after the severe traumatic event. This study will serially examine the levels of specific biomarkers present in both Cerebrospinal Fluid (CSF) and blood, the results of which should provide the following firsts: (1) Elucidate the peak timing of early oxidant injury, which will directly impact the timing of interventions for these patients (2) Identity the amount of oxidant injury seen in the different types of TBI, which may guide the specific therapies used for these patients (3) Identify any subsequent peaks in oxidant injury, which, if identified, will lead to further improvements in patient care (4) Identify any correlations between CSF and serum levels of F2-isoprostane, which may help guide therapy for less severely TBI patients not requiring a ventriculostomy (5) Identify correlations of marker levels with patients' progress, and need for critical interventions, which may alert physicians to problems requiring intervention before they would be otherwise clinically evident.
2. RESCUE - TBI and Shock (Resuscitative Endocrinology: Single-dose Clinical Uses for Estrogen - Traumatic Brain Injury and Hemorrhagic Shock)Trials
Epidemiologic studies have shown women often survive traumatic injury, sudden cardiac arrest, hemorrhage and sepsis better than men. Numerous recent animal studies investigating the effects of sex steroids on both sexes of injured animals have overwhelmingly found estrogen to be effective at mitigating the devastating secondary injury brought about by oxidant injury, inflammation and apoptosis with up to a 65% reduction in ultimate injury for multiple different injury types. Based on these important observations, the RESCUE - TBI & Shock Trials are the first clinical studies to ever translate these animal studies to patients, by utilizing a single dose of IV estrogen as an acute resuscitation drug. It is hoped that patients with severe TBI and Hemorrhagic Shock will have a new, safe, effective therapy in the near future, based on the results of these pilot trials.

Animal:
1. RESCUE - Rats Burns (Resuscitative Endocrinology: Single-dose Clinical Uses for Estrogen - Burns)
2. RESCUE - Rats TBI (Resuscitative Endocrinology: Single-dose Clinical Uses for Estrogen - TBI)

The goals for the student will be to:
1. Develop an improved global understanding of human and animal research
2. Learn techniques involving human specimen handling, through assistance in bedside specimen procurement in the ER and ICU, and specimen processing for future analysis
3. If desired, students will assist with all aspects of small animal injury and resuscitation models as indicated above. (Animal work is NOT required)
4. Perform basic laboratory tests, ex. ELISAs, following appropriate training
5. Experience direct patient and family member contact in a critical care setting with research team members, which will afford them the opportunity to develop important clinical skills under the research team's guidance.
6. Participate in the screening, enrolling and consenting of patients under the research team's guidance.
7. Follow patients over time, noting changes in study outcomes, alongside our staff research coordinators
8. Participate in chart review of study patients (including collection of data, verification of diagnoses, and simple entry and analysis of data)
9. Develop skills in the areas of writing abstracts and journal articles.

It is anticipated that students will achieve one or more abstracts and/or publications as a result of their work.
Sample of Previous Published Work with Students:
1) Lingo Lai - Non - Interventional F2-isoprostane Study - Traumatic Brain Injury (NIFTI - TBI) : Isofurans (IsoF) and F2-isoprostane (F2-IsoP) as Markers of Oxidant Injury. Abstract and Poster Winner Medical Student Research forum UTSWMC 2007
2) Anh Nguyen - Sex Steroid Level Alterations in the Blood and CSF Following Severe Traumatic Brain Injury Winner, Presenter at the Medical Student Research Forum 2007 UTSWMC