Davis Hyperbaric Laboratory USAF HYPERBARIC NEWSLETTER January 1998 nated Coccidiodes immites infection”) with the manu- ***TABLE OF CONTENTS*** script to follow in the first quarter of 1998. Hyperbaric oxygen has long been recognized as a limb saving treatment for non-healing foot wounds in Research & Development 1 the diabetic. Why do antibiotics fail in these patients and why is HBO so effective? If the bacteria isolated Clinical Hyperbarics 3 from these wounds are sensitive to the antibiotics given then why do the wounds persist? Could it be that or- Operational Hyperbarics 10 ganisms that cannot be cultured in vitro are the cause of some of the problems? In collaboration with researchers Hyperbaric Training & Education 10 at the University of Scranton (PA) and the AF Epidemi- ology lab at Brooks, we identified bacterial species in a wound using standard clinical microbiology and mo- Parallel Universes 13 lecular biology techniques that do not require in vitro culture isolation. Both techniques found a problem Personals 16 bacteria: Bacteroides fragilis. However, the molecular biology approach also found Proteobacterium, an un- usual pathogenic organism that is difficult to grow in RESEARCH & DEVELOPMENT vitro. This finding tends to support the idea that previ- ously unidentified bacteria may play a role in diabetic wounds and that appropriate treatments (including HBO) must be used to defeat them. This ground BASIC SCIENCE RESEARCH breaking work is being submitted to the journal Diabe- tes Care (“Bacterial species identification in a non- This past year has been a busy one for cellular healing diabetic foot wound: identification by 16s ribo- hyperbaric research at Brooks AFB. In the area of in- somal DNA sequence”). We plan to use this prelimi- fectious disease we are exploring the feasibility of using nary work as a springboard to funding a more extensive hyperbaric oxygen as a means of treating problem lung study in the coming year. infections. The scientific basis for this study is the well Hyperbaric oxygen has been known to lessen known phenomenon that prolonged exposure to pure the damage produced during ischemia-reperfusion, oxygen can cause severe inflammation in the lungs and mainly through reduced sequestration of neutrophils that short exposures to hyperbaric oxygen have systemic (the cells that cause the most tissue damage during a immune effects. Taken together this suggests that hy- stroke or heart attack). Neutrophils do their damage by perbaric oxygen may increase the immune response in producing small highly reactive molecules that damage susceptible individuals giving them an edge in defeating essential components of the living cell, especially DNA difficult infections. We are studying this question in and membranes. One of the most important of these mice that are susceptible to a nasty, incurable fungal dangerous molecules, peroxynitrite, has been the subject infection caused by the organism Coccidiodes immites of our investigations. We have found that in activated which is found in soil in the southwestern US. While immune cells that have plenty of oxygen available, ex- the study is not yet complete, preliminary indications posure to HBO reduces production of peroxynitrite by are that HBO does produce changes in infected lungs about 40%. Activated immune cells maintained under that are consistent with an improved response. The hypoxic conditions produce only about 25% as much preliminary results of the study, in collaboration with peroxynitrite as cells grown under normal oxygen con- scientists at the Texas Center for Infectious Disease, are ditions. HBO exposure does not have any effect on per- to be reported at the AsMA annual meeting in Seattle oxynitrite production in hypoxic cells. Taken together (“Hyperbaric oxygen treatment of mice with dissemi- these observations suggest that HBO serves to attenuate an active immune response in normal tissues thereby preventing unwanted damage, while having little effect locations, and modular steel section (panels) chambers in hypoxic tissues. that can be transported for far forward deployment or This investigation along with another related contingency hospital placement. For monoplace paper are being submitted to the Journal of Cellular emergency transport/evacuation use we entered into a Physiology for publication. In collaboration with Dr. collaborative evaluation of existing technologies with Bowden at the Brooke Army Medical Center, Clinical the US Navy. We are convinced these technologies Investigations Branch, we are developing some new will bring clinical hyperbaric treatment to the combat- studies to examine the role of hyperbarics in limiting ant in-theater, meeting CONOPS requirements for cellular adhesion. Much needed in vitro dose response low-cost, cube, modularity and flexibility for deploy- studies (i.e., pressure-time relationships) of HBO’s ef- ment of far forward support of the warfighter. fect on adhesion are planned, as well as, a clinical trial Pursuant to that goal of developing an alternate to examine in detail the effects of HBO on various adhe- material multiplace chamber, the USAF constructed a sion molecules. prototype concrete contingency hospital room (CCHR) What effect does hyperbaric oxygen have on using post-tensioned concrete construction materials. tumor growth? Based on current epidemiology the an- The project demonstrated several advantages includ- swer is none at all. Could hyperbarics be used as an ing: 1) large, rectangular, floor-flush doors facilitating adjuvant to cancer chemotherapy or radiation treat- rapid and easy causality ingress/egress, 2) significant ment? We have examined this issue in one of the most cost reduction over steel vessels -- approximately 30%, problematic of all human cancers: advanced prostate 3) variable room size and configurations (square, rec- cancer. In a manuscript accepted for publication in the tangular or irregular) offering flexibility to accommo- journal Anticancer Research (“The effect of hyperbaric date existing building designs, 4) sliding doors that do oxygen on growth and chemosensitivity of metastatic not encroach floor space, and with vertical walls sig- prostate cancer”) we showed that there was a slight nificantly improving space efficiency, and 5) modular benefit when hyperbarics was given along with doxoru- support systems for easy transport and installation. A bicin and taxol, two front-line anticancer drugs. In a significant advantage of this technology is that the follow-up paper we examined in detail the pressure de- CCHR can be constructed by military or contractor pendent effect of HBO on tumor growth (“Exposure to civil engineers instead of mechanical engineer pres- hyperbaric oxygen induces cell cycle perturbation in sure vessel specialists. Furthermore, the CCHR can be prostrate cancer cells”, submitted to the journal Pros- rapidly constructed, in-theater, in a minimum of 36 tate and presented at 1997 UHMS annual meeting) and days (steel vessels average more than a year). The found that pressures of 3 ATA and greater can synchro- prototype chamber completed pressure cycling tests nize a tumor cell population, setting the tumor up for with over 25,000 cycles (simulating a service life of greater damage during chemotherapy and slowing more than 25 years) and peak pressure successfully growth. tested to 85 psig (> 6 ATA), far surpassing the de- John Kalns, PhD signed pressure level of 29.4 psig (3 ATA). The code Research Scientist case to certify the technology is before the American Society of Mechanical Engineers (ASME) Committee CHAMBERS: THE NEXT GENERATION! for Pressure Vessels for Human Occupancy (PVHO). Once this approval cycle is completed, the technology Most of us in Hyperbaric Medicine (HBO) are will be available for implementation. aware that up to now an operational limitation of our An alternative to the CCHR is a modular, ex- discipline has been the lack of in-theater/field support pandable hyperbaric chamber system (MEHCS). Al- for the requirement of combat casualty care and man- though this chamber is composed of traditional steel agement. The size, cost and fabrication time of steel materials, the MECHS has many advantages over pressure vessels made forward deployment prohibitive. welded steel chamber technology including: 1) modu- We acknowledge that the efficacy of hyperbaric oxy- lar design for optimizing deployability configuration-- gen is significantly enhanced if treatment is initiated meeting the requirements for reduced medical assem- quickly (within 4 - 6 hours) following injury. There- blage, 2) large doors facilitating rapid and easy cau- fore, to get HBO as close to the point of wounding as sality ingress/egress, 3) flexibility to extend treatment tactically possible, thus advancing our wartime readi- room size depending upon patient load requirements, ness mission, and addressing the Joint Health Service 4) sliding doors that do not encroach floor space, 5) Support Plan: Vision 2010, we are pursing alternate optimized interior illumination, and 6) vertical walls chamber materials technologies. These technologies maximizing interior space efficiency. This chamber is include, for multiplace chambers: concrete/resin com- designed as a 3 ATA system and has the nominal posite materials for placement at contingency hospital configuration of approximately 8 feet by almost 11 2 feet, and weighs about 14,000 pounds. This chamber Finally, I mentioned we are pursuing technol- meets all safety codes prescribed by ASME-PVHO. ogy to combine