- Noninvasive Sensor System to Determine Tissue Perfusion and Guide Resuscitation
- Use of PC-NSAIDs in Chronic Pain
- A Bioengineered Gene Therapy System with Potential to Heal War Wounds
Trauma and hemorrhage are a leading cause of death in the United States and a major concern of the military. Significant loss of blood leads to shock: inadequate organ perfusion and tissue oxygenation. The goal of resuscitation from shock is to correct the mismatch between available oxygen and the demands of critical organs. Under-resuscitation from shock may lead to Systemic Inflammatory Response Syndrome (SIRS), irreversible body-wide ischemia, Multiple Organ Dysfunction Syndrome (MODS) and death. Mortality from MODS is estimated to be 40% to 60%. Additionally, medics carry a minimal amount of resuscitation fluids, and judicious use of this resource is important in treating the largest number of casualties. Accurate endpoints of resuscitation are needed to guide therapeutic treatment, in the most efficient manner, with the goal of restoring critical tissue perfusion and oxygenation early in shock to prevent irreversible cell injury and MODS. Dr. Babs Soller and colleagues, in collaboration with Luxtex Corporation and Nimbis Medical, are developing and conducting human testing of a prototype of a portable sensor system based on near infrared spectroscopy to noninvasively measure tissue perfusion. This system quickly and accurately measures muscle pH, muscle oxygen, and hematocrit from light reflected from the forearm and will guide military medical personnel in resuscitation care and evacuation.
Soyemi O, Landry M, Yang Y, Soller B. 2005. Standardization method for correcting spectral differences across multiple units of a portable near infrared-based medical monitor. Proceedings of SPIE Vol 5702:135-142.
Patients with spinal cord injury (SCI) suffer from numerous (neurological, renal, and gastrointestinal) complications, and a majority experience chronic pain. Accordingly, many of these patients are on anti-inflammatory, analgesic, and narcotic drugs, each with its own deleterious side effects. The use of nonsteroidal anti-inflammatory drugs (NSAIDs), which have potent anti-inflammatory and analgesic activity in patients with SCI, has been limited because of the drugs' gastrointestinal (GI) side effects that result in peptic ulceration, hemorrhage, and anemia, which can be particular devastating in a debilitated patient. Dr. Lichtenberger is investigating the utility of a new class of NSAIDs, which are coupled with phosphatidylcholine (PC), in the treatment and/or prevention of chronic neuropathic pain associated with SCI. Preliminary results in rodent model systems show that PC?NSAIDs have lower GI toxicity and more enhanced therapeutic effectiveness than the parent NSAID to inhibit fever, inflammation, and pain. Positive results in these preclinical studies should hasten the development of PC?NSAID formulations for parenteral and enteral use for improved treatment of patients suffering from Chronic Pain Syndrome. The research performed during this project is expected to result in better treatment for military personnel immediately following battle and/or accidents to help prevent early inflammatory processes that lead to painful central nervous system injury.
Impaired healing of war wounds is a serious military medical problem. Wound healing could be improved by exogenous application of growth factors, but the short half-life of the growth factors requires repeated applications, limiting its clinical usefulness. Gene therapy can continuously deliver growth factors deep within the tissue to maximally enhance healing. However, the potential of gene therapy has not been exploited because the technology to deliver the genes has not been successful. Dr. John Harmon and colleagues at Johns Hopkins University are using electroporation, a technique in which an electric field passed through tissue opens small pores in cell membranes, to successfully deliver DNA molecules into cells. The Johns Hopkins team used mouse models to study the effect of delivering the gene for keratinocyte growth factor (KGF) by electroporation. The technique improved the speed of closure in slow-healing wounds produced experimentally in mice. An additional benefit of this technique may be the treatment of slow wound healing in diabetics as observed in diabetic mice having KGF delivered into wounds by electroporation.