By Douglas J. Gillert American Forces Press Service WASHINGTON -- The decision to give battlefield troops the anti- nerve agent drug pyridostigmine bromide won't be as easy in the future as it was during the 1991 Gulf War, DoD officials said Oct. 19 at the Pentagon. An estimated 250,000 U.S. service members, as well as troops from other nations participating in the Gulf War, were given the drug to protect them against soman, a deadly nerve agent. At the time, intelligence reports couldn't confirm the presence of soman in Iraqi arsenals. Instead, the decision to issue PB tablets was based partially on prior Soviet possession of the agent and concerns it might have been passed on to Iraq. Also, Iraq was known to have used nerve agents against Iran and the Kurds. "Given the deadliness of soman and the lack of other treatments available, we certainly cannot rule out using PB to protect our forces in the future," said Dr. Sue Bailey, assistant secretary of defense for health affairs. "However, our leadership would be very judicious in deciding to use PB in the future. The decision would involve weighing concerns about possible long-term health effects with a threat-risk assessment of how likely it is that soman would be used against our troops." During the Gulf War, service members were issued PB tablets and told to take them during high-threat periods. The medication would bind and block an enzyme that, when attacked by soman, breaks down excessive amounts of a nerve-signaling chemical, acetylcholine, and leads to muscle twitching, glandular secretions, abnormal moods and thinking and, at higher dose levels, paralysis and respiratory failure. PB produces temporary effects similar to low-level dosages of soman but it also blocks the nerve agent from causing permanent damage. However, results of studies commissioned by DoD suggest PB may cause lasting effects in some humans, with symptoms of the type reported by tens of thousands of Gulf War veterans. Thousands of veterans have reported difficulty with sleeping, pain, mood swings, muscle fatigue and memory loss. These are precisely the symptoms medical research shows could be caused by PB. The revelations are contained in a lengthy review of scientific literature produced by the RAND Corp. and made public Oct. 19. The research, however, is inconclusive, and DoD has commissioned RAND and others to continue studying PB for a more complete picture. The Defense Department has directed 23 of the 26 federally funded PB studies currently under way. The DoD- commissioned studies specifically address the health consequences of PB as a nerve agent pre-treatment and include evaluations of the interaction of PB with other chemicals and low-level exposure to nerve agents. "Most of the ongoing studies to date reveal no definitive results to link PB to illnesses seen in our Persian Gulf veterans," Bailey said, "but we must continue this very important research to really determine any causal relationship." Dr. Beatrice Golomb, who authored the RAND review of scientific literature pertaining to Gulf War illnesses, said future studies will address three plausible theories on how PB may cause long- term or permanent health problems. One hypothesis is that people may process PB differently, making some more susceptible than others to long-lasting effects. "Our literature review found that the same dose administered of PB would lead to sevenfold differences in blood levels of PB from one individual to another," Golomb said. "Moreover, the same blood level of PB may lead to widely different percentages of inhibition of the enzyme." A second theory suggests that certain conditions could cause the brain to absorb PB. "PB is largely barred from accessing the brain by something termed 'blood-brain carrier,'" Golomb said. But laboratory animal research suggests conditions such as heat, stress and chemical exposures could cause more PB to pass to the brain, she said. "One study suggests that PB itself may enable access to the brain of substances that are normally excluded, such as infectious viruses," she said. Under conditions where PB may access the brain, there may be increased susceptibility to the toxic effects of PB, she said. Finally, RAND will look at how and if PB is linked to chronic illness in those who may have these conditions of heightened susceptibility, that PB may in fact lead to permanent changes in regulation of the nerve-signaling chemical acetylcholine. "The question," Golomb said, "is, could these long-lasting or permanent changes in regulation of this key nerve-signaling chemical be linked to illness in Gulf War veterans? And the answer right now is that we simply don't know." Bernard Rostker, DoD special assistant for Gulf War illnesses, said he's frustrated no definitive cause for the illnesses has been found. But even as the research continues, he said the role of his office is coming to an end. "We're trying to bring to closure the various pieces of research that we have outstanding," Rostker said. "We will be republishing much of what we've done before to bring it up to date. And then, I think, the issue becomes, where do we go in the future with the whole question of deployment and the outstanding work that's been done on medical force protection over the last decade." All published information on the Pentagon's Gulf War illness investigation is available at the GulfLINK Web site.