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NASA LED Irradiation and Wound Healing 313 U.S. Naval Station–San Diego on a 6-month mission is equipped with a LED snap-light array on board. In addition, we have recently begun using NASA LEDs to promote healing of acute oral lesions in pediatric leukemia pa- tients. As a final life-saving effort, leukemia patients are given healthy bone marrow from an HLA-matched donor. Prior to the transplant, the patient is given a lethal dose of chemotherapy in order to destroy his or her own cancerous bone marrow. Be- cause many chemotherapeutic drugs, as well as radiation ther- apy, kill all rapidly dividing cells indiscriminately, the mucosal linings of the gastrointestinaltract are often damaged during the treatment. As a result of these gastrointestinal effects, greater than one-third of patients treated with cytotoxic drugs develop ulcers in their mouths (oral mucositis) and/or suffer from nau- sea and diarrhea. Oral mucositis, which causes severe pain, bleeding, an increased risk for infection, and compromised abil- ity to chew and swallow, is a significant risk for this population. Current treatment for mucositis addresses pain management and infection prevention. The use of oral agents to promote cleansing, debridement, and comfort are recommended, and prophylactic oral antiviral and antifungal agents have been used to minimize infections. Because lasers have been shown to speed healing of oral mucositis,25,26 we have recently expanded the wound-healing abilities of LED light therapy to include these oral lesions. A 4 J/cm2, 50 mW/cm2 dose of 670-nm light from LEDs was applied daily to the outside of each patient’s left cheek begin- ning on the day of bone marrow transplantation. The status of their oral mucosa, mouth, and throat pain was assessed three times a week by two calibrated dental clinicians. Each side of the mouth was scored using the Schubert Oral Mucositis Index (OMI), the mucosa were photographed, and mouth and throat pain were assessed using a 1–10 Visual Analog scale.27 We have now completed treatment to half of our intended patient population and have noticed some very encouraging trends, but statistical significance will require more patients, as intended in our current study design. We have assessed left cheek, right cheek, and throat pain in each patient, and have noted that there is no statistical difference in perceived pain on either side of the mouth, consistent with the expected tissue penetration (23 cm) of LED light. Throat pain, however, was consistently higher than mouth pain, and because our light does not extend into this region, we have used this pain as our control. Although mouth and throat pain were initially similar, mouth pain peaked at 86% of throat pain on day 5 after transplant and subsequently fell to only 53% of reported throat pain by day 7 (Table 1, Fig- ures 12 and 13). The greatest difference between throat and mouth pain was reported on day 7, when, surprisingly, oral mu- cosal ulceration is believed to be worst in untreated patients. Additionally, we are determining extent of ulceration, heal- ing rate in mm2/day, and healing time in days for these patients, and we will compare these values with epidemiological control data. A chart review is also in progress to assess morphine pump use and requirements for intravenous feedings in LED- treated patients compared to controls. Contact with the FDA’s Richard Felten of the General Surgery Devices Branch has pro- duced an avenue for guidance to final data collection and FDA approval of this technology as the standard of therapy for treat- ment of mucositis. FDA review of our current data and protocol design is ongoing, and has already led to an FDA recommenda- tion for expanding our study to include at least three more aca- demic medical centers, in addition to our own, to be supplied with NASA LED arrays by Quantum Devices, Inc. A multisite trial is being planned through the International Bone Marrow Transplant Registry. RESEARCH COLLABORATION We are now investigating new collaborations with the De- fense Advanced Research Projects Agency (DARPA) for fur- ther military applications of NASA LED wound healing tech- nology in military medicine. Several uniquely military situations and indications could be addressed in the new collab- oration. These include burns, injuries from chemical agents, ra- diation, highly infected wounds (which are typical for the hy- gienic conditions occurring in battlefields), infectious diseases, and external wounds occurring in environments with no solar irradiation, low oxygen, and high carbon dioxide (submarines and space environments).The dramatic results with use of near- infrared NASA LED light to prevent digestive mucosal lesions (mucositis) and pain in cancer patients, after high-dose chemotherapy and radiation, suggest the potential for military use of near-infrared light to treat U.S. troops exposed to chemi- cal and radioactive warfare agents in the field28 These life-sav- ing applications require especially accelerated wound healing, rapid reduction of infections, and pain modulation. ACKNOWLEDGMENTS We wish to thank Karen Zeqiri for assistance in manuscript preparation.The LED arrays were provided by Quantum Devices, Inc.(Barneveld,WI).WealsogratefullyacknowledgetheDepart- ment of Defense, Air Force Material Command, Armstrong Lab- oratories, Davis Hyperbaric Laboratory, Brooks Air Force Base, Texas, for providing the hyperbaric chamber used in this research. The hyperbaric oxygen treatments of our human subjects were performed by Estelle Woodard, C.R.T., C.H.T. This work was supported by the Defense Advanced Research Projects Agency grant N66001-01-1-8969and the National Aeronautics and Space Administration, Marshall Space Flight Center SBIR grants NAS8-99015 and NAS8-97277, Children’s Hospital Foundation, the MACC Fund, and Quantum Devices, Inc. REFERENCES 1. Conlan, MJ., Rapley, J.W., and Cobb, C.M. (1996). Biostimulation of wound healing by low-energy laser irradiation. J. Clin. Peri- odont. 23, 492–496. 2. Beauvoit,B.,Kitai,T.,andChance,B.(1994).Correlationbetween the light scattering and the mitochondrial content of normal tissues and transplantable rodent tumors. Biophys. 67, 2501–2510. 3. Beauvoit,B.,Evans,S.M.,Jenkins,T.W.,Miller,E.E.,andChance B. (1995). Contribution of the mitochondrial compartment to the optical properties of the rat liver: a theoretical and practical ap- proach. Anal. Biochem. 226, 167–174. 4. Abergel, R.P., Lyons, R.F., Castel, J.C., Dwyer, R.M., and Uitto, J. (1987) Biostimulation of wound healing by lasers: experimentalPDF Image | Effect of NASA Light-Emitting Diode Irradiation on Wound Healing
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