The question as to whether or not Iraq actually used chemical weapon-loaded Scud missiles during the 1991 Gulf War is still an open one. Further to this, there still remain outstanding questions about the claims that Iraq possessed illegally-retained Scud Missiles in the period prior to the 2003 Invasion of Iraq. There is no complete record to draw upon and no one organisation has ever been seen to have compiled an exhaustive and comprehensive analysis.

- A review by a former member of the Dhahran Scud Watchers Club


Autonomic Dysfunction May Play a Role in Gulf War Syndrome

Laurie Barclay, MD

Sept. 30, 2004 - Some symptoms of Gulf War syndrome may be related to subtle autonomic dysfunction, according to the results of a matched cohort study published in the Oct. 1 issue of the American Journal of Medicine.

"While the cause of the illness remains controversial, evidence of chronic central nervous system damage from exposure to low-level sarin nerve gas has emerged," write Robert W. Haley, MD, from the University of Texas Southwestern Medical Center in Dallas, and colleagues. "The symptoms of autonomic dysfunction without orthostatic hypotension or other signs of sympathetic neural failure led us to hypothesize a subtle abnormality of the autonomic nervous system similar to that found in very early diabetic neuropathy."

Investigators blinded to group status compared 22 ill Gulf War veterans and 19 control veterans matched for age, sex, and education. Measurements included circadian rhythm of heart rate variability on 24-hour electrocardiography, ambulatory blood pressure recording, Valsalva ratio testing, sympathetic skin response evaluation, sweat imprint testing, and polysomnography.

Control subjects had a normal increase in high-frequency spectral power of heart rate variability by 2.2-fold during sleep, whereas this increase was only 1.2-fold in ill veterans (P < .0001). Compared with control subjects, ill veterans had lower heart rate variability at night (P = .0006), higher during the morning (P = .007), and no different during the rest of the day (P = .80).

In the Gulf War group, mean heart rate decreased less at night (P = .0002), and corrected QT intervals tended to be longer over the full 24 hours (P = .07), especially at night (P = .03). Polysomnography (P = .03) and 24-hour automatic ambulatory blood pressure monitoring (P = .05) confirmed the blunting of nocturnal heart rate dip in ill veterans. These differences remained significant after adjustment for potential confounding factors. Both groups were similar in measures of sympathetic adrenergic and sudomotor function, sleep architecture, respiratory function, and circadian variation in blood pressure and body temperature.

"Our findings document an abnormality of the neuroregulation of high-frequency heart rate variability, most likely indicative of parasympathetic nervous system activity, in members of a Naval Reserve construction battalion who became chronically ill during or shortly after service in the 1991 Gulf War," the authors write. "Our findings, although unable to attribute specific symptoms of Gulf War veterans directly to early autonomic dysfunction, suggest possible links to be explored in future research."

The U.S. Army Medical Research and Materiel Command cooperative agreement, the U.S. Public Health Service, and the Perot Foundation supported this study.

Am J Med. 2004;117:469-478

Reviewed by Gary D. Vogin, MD

http://www.medscape.com/viewarticle/490366





Brain shrink linked to Gulf War syndrome

12:00 01 May 2007

NewScientist.com news service

Roxanne Khamsi


People suffering "Gulf War syndrome" have a 5% reduction in brain size, a small study suggests.

The anatomical differences between veterans of the first Gulf War in 1991 who report multiple health problems - such as fatigue, skin rash and nausea - and other healthier colleagues, were revealed during brain scans.

Those with symptoms of the controversially named Gulf War syndrome (GWS) have 5% less cortical brain matter than healthier counterparts. The researchers say that the finding provides hard biological evidence to support claims that some veterans of the war suffered real neurological damage, perhaps as a result of nerve gas or other toxins.

Roberta White of the Boston University School of Public Health in Massachusetts, US, and colleagues studied 18 Gulf War veterans who reported more than five health problems such as joint pain, fatigue, skin rash, headaches and nausea.

The researchers conducted brain scans on these subjects - using magnetic resonance imaging technology - as well as 18 control counterparts, who served in the same war but reported only a few of the symptoms.

Memory loss

The scans revealed that the overall brain cortex of the veterans with GWS was about 5% smaller on average than that of the healthier veterans. The cortex includes the outermost and top layer of the brain, including the grey matter, and controls complex functions such as language.

It also includes a specific part of the brain thought to be involved in memory processing and learning, known as the rostral anterior cingulate gyrus, which was about 6% smaller in the ill veterans, on average.

Subjects were also asked to complete a cognitive test that involved memorising a list of 16 words and recalling those words 20 minutes later. Veterans with GWS performed about 15% worse in the test than the healthier control group.

"I think these findings are really important," says White, who presented the results at the American Academy of Neurology annual meeting in Boston this week.

She says that when you combine these findings with others, such as the greater incidence of brain tumours and movement disorders such as ALS (amyotrophic lateral sclerosis) among those deployed in the war, "it's pretty clear that something has happened to central nervous system function and structure of Gulf War veterans and that we're just getting to the point where were finally seeing what these effects were."

Pointing the finger

White's team hopes to review information from the study participants and the government to estimate the level of exposure the subjects might have had to the nerve gas sarin and other toxins. A cocktail of toxins could perhaps have produced GWS, though some experts still debate whether this is a unique illness.

Epidemiologist Robert Haley at the University of Texas Southwestern Medical Center in Dallas, US, says that the brain differences highlighted by the new study do not explain what could have caused GWS.

"It doesn't point to one cause, but it is compatible with what we know about sarin exposure," says Haley, who was not involved in the study. He notes that researchers saw similar reductions in brain volume in Tokyo commuters exposed to sarin gas released in the subway system in 1995.

Haley, who spearheaded early efforts to understand GWS, notes that previous studies have found other biological differences in the brains of veterans of the 1991 war.

Damaged nerves

Specifically, a technique called magnetic resonance spectroscopy found lower levels of a molecule called N-acetylaspartate (NAA), which indicates healthy nerve function, in the brains of symptomatic Gulf War veterans. All this, he says, adds further weight to the argument that GWS is a real illness.

White acknowledges that her new study does not prove that the reduced brain volume was caused by exposure to chemicals in the war. "This could be a pre-existing vulnerability or an exposure-outcome relationship," she says.

But Haley notes that the veterans did not show cognitive abnormalities before entering the war. "They weren't a bunch of people with faulty memory," he explains, since they had to pass certain standard military tests.

http://www.newscientist.com/article/dn11760-brain-shrink-linked-to-gulf-war-syndrome.html





Gas May Have Harmed Troops, Scientists Say

By IAN URBINA

Published: May 17, 2007


WASHINGTON, May 16 - Scientists working with the Defense Department have found evidence that a low-level exposure to sarin nerve gas - the kind experienced by more than 100,000 American troops in the Persian Gulf war of 1991 - could have caused lasting brain deficits in former service members.

Though the results are preliminary, the study is notable for being financed by the federal government and for being the first to make use of a detailed analysis of sarin exposure performed by the Pentagon, based on wind patterns and plume size.

The report, to be published in the June issue of the journal NeuroToxicology, found apparent changes in the brain's connective tissue - its so-called white matter - in soldiers exposed to the gas. The extent of the brain changes - less white matter and slightly larger brain cavities - corresponded to the extent of exposure, the study found.

Previous studies had suggested that exposure affected the brain in some neural regions, but the evidence was not convincing to many scientists. The new report is likely to revive the long-debated question of why so many troops returned from that war with unexplained physical problems. Many in the scientific community have questioned whether the so-called gulf war illnesses have a physiological basis, and far more research will have to be done before it is known whether those illnesses can be traced to exposure to sarin. The long-term effects of sarin on the brain are still not well understood.

But several lawmakers who were briefed on the study say the Department of Veterans Affairs is now obligated to provide increased neurological care to veterans who may have been exposed.

In March 1991, a few days after the end of the gulf war, American soldiers exploded two large caches of ammunition and missiles in Khamisiyah, Iraq. Some of the missiles contained the dangerous nerve gases sarin and cyclosarin. Based on wind patterns and the size of the plume, the Department of Defense has estimated that more than 100,000 American troops may have been exposed to at least small amounts of the gases.

When the roughly 700,000 deployed troops returned home, about one in seven began experiencing a mysterious set of ailments, often called gulf war illnesses, with problems including persistent fatigue, chronic headaches, joint pain and nausea. Those symptoms persist today for more than 150,000 of them, according to the Department of Veterans Affairs, more than the number of troops exposed to the gases.

Advocates for veterans have argued for more than a decade and a half that a link exists between many of these symptoms and the exposure that occurred in Khamisiyah, but evidence has been limited.

The study, financed by the Department of Veterans Affairs and the federal Centers for Disease Control and Prevention, is the first to use Pentagon data on potential exposure levels faced by the troops and magnetic resonance imaging to scan the brains of military personnel in the exposure zone. It found signs of brain changes that could be due to exposure, showing that troops who had been exposed at higher levels had about 5 percent less white matter than those who had little exposure.

White matter volume varies by individual, but studies have shown that significant shrinkage in adulthood can be a sign of damage.

The study was led by Roberta F. White, chairman of the department of environmental health at the Boston University School of Public Health. Dr. White and other researchers studied 26 gulf war veterans, half of whom were exposed to the gases, according to a Defense Department modeling of the likely chemical makeup and location of the plume. The researchers found that troops with greater potential exposure had less white matter.

In a companion study, the researchers also tested 140 troops believed to have experienced differing degrees of exposure to the chemical agents to check their fine motor coordination and found a direct relation between performance level and the level of potential exposure. Individuals who were potentially more exposed to the gases had a deterioration in fine motor skills, performing such tests at a level similar to people 20 years older.

Dr. White says this study and the results of research from other studies provide "converging evidence that some gulf war veterans experienced nervous system damage as a result of service, and this is an important development in explaining gulf war illnesses."

Phil Budahn, a spokesman for the Department of Veterans Affairs, said the research required further examination.

"It's important to note that its authors describe the study as inconclusive," Mr. Budahn said, adding, "It was based upon a small number of participants, who were not randomly chosen."

Dr. White said she did not describe her study as inconclusive, though she said it would be accurate to call it preliminary.

(Page 2 of 2)

Lea Steele, a Kansas State University epidemiologist and the scientific director of the veterans department's advisory committee on gulf war illnesses, said she thought the study was extremely important. Dr. Steele said that gulf war illnesses had been described by their symptoms, but that until now scientists had struggled to find physiological conditions that corresponded with those symptoms

But the new research, Dr. Steele said, used previously nonexistent brain scanning technology to, essentially, "look into the brain to evaluate the difficult-to-characterize problems affecting gulf war veterans."

Thus, she said, it is "the first to demonstrate objective indicators of pathology in association with possible low-level sarin-cyclosarin exposures."

Dr. Daniel J. Clauw, professor of medicine and director of the Chronic Pain and Fatigue Research Center at the University of Michigan, said that while the study indicated that the veterans had not imagined their illnesses, more research was needed.

"Future studies need to compare the results of brain scans of gulf war veterans with individuals with chronic pain and other symptoms who were not deployed to the gulf war before concluding that any changes are due to wartime exposures," Dr. Clauw said.

For more than five years after the explosions at Khamisiyah, the Pentagon denied that any American military personnel had been exposed to nerve gas. Confronted by new evidence in 1996 and 1997, it acknowledged that up to 100,000 troops might have been in the path of the plume and exposed to low-level doses that produced no immediate effect. In 2002, it released a report saying the exposures had been too low to have caused a long-term adverse effect on health.

Now, the government is straining to handle the health and rehabilitation needs of soldiers returning from the current wars in Iraq and Afghanistan, and lawmakers say they are concerned that veterans facilities will soon need to provide brain scans and treatment to soldiers from the 1991 war who learn of the new research.

On May 2, after learning about the research, Senators Patty Murray, Democrat of Washington, and Christopher S. Bond, Republican of Missouri, wrote the Defense and Veterans Affairs Departments, asking about their plans for outreach and expanded benefits for exposed troops.

The new research, the senators wrote, finally provides "comfort to the thousands of gulf war veterans who have fought for answers and now know that there is a 'significant association' between gulf war illnesses and nerve agent exposure in Khamisiyah, Iraq, in 1991."

The Pentagon has not decided whether to inform veterans about the possibility of a link between exposure and brain damage.

Dr. Michael E. Kilpatrick, deputy director of the Force Health Protection and Readiness Initiative at the Defense Department, said that while Dr. White's study represented an important finding, he did not believe that his department would send letters to potentially exposed veterans alerting them of it.

The impact of the study was limited, Dr. Kilpatrick said, because it did not establish a direct causal connection between sarin exposure and gulf war illnesses, and it depended on Defense Department data that was at best an estimate and at worst a guesstimate of exposure levels by troops.

"But I'm sure we will be talking with members of Congress about it in deciding how to go forward," said Dr. Kilpatrick, who has handled much of the department's work on Khamisiyah and troop health issues.

In 2005, the Pentagon notified about 100,000 gulf war veterans who had been exposed that a study showed a link between brain cancer and gas exposure. Ms. Murray said the Pentagon needed to send similar letters about the new research, expressing concern that many veterans might not know that something might be wrong with them.

http://www.nytimes.com/2007/05/17/us/17sarin.html?_r=1&hp&oref=slogin





Study: Sarin at root of Gulf War syndrome

By Kelly Kennedy - Staff writer

Posted : Wednesday May 30, 2007 12:08:25 EDT


As benefits administrators, officials and politicians argue the worthiness of studies on Gulf War syndrome, researchers say they have no doubts that they've found the root of the problem.

Sarin gas.

And they have advice for as many as 300,000 troops exposed to small doses of sarin in 1991: Don't use bug spray, don't smoke and don't drink alcohol.

"Don't do anything that would aggravate a normal, healthy body," said Mohamed Abou-Donia, a neurobiology scientist at Duke University who conducted two studies for the Army.

Research released in early May showed that 13 soldiers exposed to small amounts of sarin gas in the 1991 Gulf War had 5 percent less white brain matter - connective tissue - than soldiers who had not been exposed. A complementary report showed that 140 soldiers who were exposed had the fine motor skills of someone 20 years older - what researchers called a "direct correlation" to exposure.

The data was the work of Roberta White, chairwoman of the Department of Environmental Health at Boston University School of Public Health.

Her study was noteworthy because it was funded by the Veterans Affairs and Defense departments, and used Pentagon data to triangulate the locations of troops who were in the path of a huge sarin plume unleashed when U.S. forces destroyed an Iraqi chemical weapons dump in Khamisiyah in March 1991. The study also used new technology to look at troops' brains.

Of the 700,000 service members who served in Desert Storm, 100,000 have reported mysterious symptoms. Until recently, each study commissioned by the VA and Pentagon concluded the problems were caused by stress and had no physical cause.

"We've been asking for this for so long," said Denise Nichols, a Gulf War veteran who spends much of her time fighting for more information. "It's not surprising to me. It's what I would expect."

Nichols, like the other veterans, has heart palpitations, a cough, nose bleeds, joint aches, spine pain, twitching in her legs and leg pain. She also reacts to strong chemical smells with coughing so heavy she can't breathe, she said.

The issue surged to the fore in a Senate hearing Wednesday as Sen. Patty Murray, D-Wash., asked if the VA would send out letters to veterans who may have been affected, as they did to 100,000 troops at higher risk of brain cancer because of sarin exposure.

Murray called the study a "great example" of how recent research can provide guidelines for care. It seems easy enough: If a soldier complains of Gulf War syndrome, why not check him out with an MRI?

She called the study's findings "overwhelming," but noted that the VA's response, once again, was merely: "We're going to study this."

"They were told, 'It's all in your head, you're making it up.' Now there is a study that provides a direct link. They deserve to know the answer," Murray said.

Sen. Bernie Sanders, I-Vt., called the research "profound."

"We started out by denying there was any problem," he said. "It shows that many soldiers may have suffered brain damage."

Dr. Gerald Cross, acting principal deputy undersecretary for health at the Veterans Health Administration, agreed with Murray that troops deserve answers.

But Cross said Sanders' description of the findings "is different from how I read it." Cross called the findings of White's research a "slight anatomical variation."

The debate over this issue goes back 16 years to when U.S. forces blew up the chemical munitions dump in Khamsiyah and released a plume of sarin gas to which thousands of U.S. troops were exposed - something the Pentagon denied until 1997.

As more research was done, and as veterans systematically sought details through the Freedom of Information Act, scientists showed Desert Storm vets exposed to sarin were at higher risk for brain cancer. And the veterans eventually showed the Pentagon knew that as many as 300,000 service members had breathed in small doses of the toxic fumes.

Paul Sullivan, of Veterans for Common Sense, said he filed FOIA requests in 1994, and then helped ensure research was made public that showed veterans were not making up their illnesses.

Eventually, 10 years after the Gulf War, the Research Advisory Committee on Gulf War Veterans' Illnesses was created by Congress. It held meetings to determine what needed to be done, to review research, and to fund further research outside the VA and Defense Department, Sullivan said.

"That's why, in the last few years, you've seen all the sarin, depleted uranium and pyridostigmine bromide research," Sullivan said. "It's a bittersweet victory because people waited so long."

To date, he said, no one has contradicted that research. As such, Sullivan said he thinks every Gulf War veteran should automatically be presumed to have been exposed to sarin.

In 1999, working on behalf of the Rand Corp., Beatrice Golomb, professor of internal medicine at the University of California, San Diego School of Medicine, reviewed every study she could find on the issue. She said it was the first time anyone had pulled all that research together.

Golomb said she found a link between symptoms of Gulf War veterans and their exposure to sarin, pyridostigmine bromide (PB) and bug repellent, all of which overstimulate muscles by inhibiting acetylcholinesterase, a chemical that signals muscles to stop moving. The tongue, being a big muscle, eventually cuts off a person's ability to breathe if it is overstimulated.

In the case of the bug repellent, the ill effects are aimed at the bug, not the person wearing the repellent.

In large enough amounts, PB is harmful, but in small doses it acts to prevent nerve agents from overstimulating muscles, and the effects of PB itself are temporary and reversible.

Exposure to sarin alone would be problematic enough. But for Gulf War veterans, exposure to sarin as well as PB and/or bug repellent may have been what ushered in Gulf War syndrome.

Abou-Donia's research showed the combination of nerve agents, PB, bug spray and stress could cause any of those chemicals - as well as any lurking viruses - to cross the blood-brain barrier, causing other problems. He said he has no doubt there are other long-term effects of low doses of sarin on other body systems, citing chronic fatigue, muscle weakness and fibromyalgia as symptoms.

White's work came in the wake of animal research that showed persistent central nervous system effects and acetylcholinesterase inhibition following exposure to sarin at levels too low to produce clinically observable symptoms.

The use of PB among troops, and PB's potential role in Gulf War syndrome in combination with other substances, also has been scrutinized.

PB slows the effects of nerve agents, giving troops more time to self-administer antidotes. Research has shown PB offers troops a better chance of survival against the nerve agent soman, rather than sarin, because soman works much quicker than sarin.

Golomb's research showed that just before the Gulf War, the U.S. government knew Iraqi leader Saddam Hussein had sarin in his arsenal, but had no evidence he possessed soman.

As such, she said "there was no benefit" to giving troops PB to increase their survival odds in the event of a sarin attack as long as they had access to the antidote, she said.

Yet according to the Pentagon, about 250,000 troops were given PB during the Gulf War.

Golomb said the U.S. military changed its PB policy because of the report she did for Rand and is not dispensing it to troops in the current war in Iraq.

John Rash, who did research on PB for the Pentagon in the late 1970s and early 1980s, was charged with ensuring people could react with their antidotes quickly enough to prevent nerve gas poisoning.

Rash's research looked at the long-term effects of PB in combination with sarin and soman on rats. At first, he said, the filaments separating muscle cells "turned to soup." But within days, the membranes reappeared and the rats seemed to have recovered.

"That's what made the Army particularly like our study," he said.

But he said he didn't look at how the drug would affect any other body system. And, he said, he knew the combination of stress and drugs could cause the agents to cross the blood-brain barrier.

Rash said his study was never published because the U.S. military didn't necessarily want to publicize the results during the Cold War era. But he said it will come out within the next two years.

A human study in 1997 showed subtle deficits in short-term memory and attention, a slight elevation of hospitalization for circulatory diseases, and a twofold increase in brain cancer deaths more than four years after exposure.

To Abou-Donia, the connection became clear after terrorists hit a Tokyo subway with sarin in 1995. Hospital workers who were never in the subway but who worked with sickened passengers came down with the same symptoms reported by Gulf War vets.

"At last they can have peace of mind because they know what it was, most likely," he said.

But, he said, there isn't much that can be done now - although he cautioned Gulf War vets not to use insecticide.

"It's kind of too late to do much of anything," he said. "But the body has many redundant systems. Usually, if the damage is small, other neurons will take over. As time goes by, people will adapt."

http://www.armytimes.com/news/2007/05/military_sarin_gulfwar_070525w/





Health Problems In Persian Gulf War Veterans Higher Due To Chemical Exposure, Study Shows

ScienceDaily (Mar. 13, 2008) - A study by researchers at the University of California, San Diego School of Medicine shows there is increasing evidence that high rates of illness in Persian Gulf War Veterans can be explained, in part, by exposure to certain chemicals, including pesticides and nerve agents. Veterans from the 1990-91 conflict have a higher rate of chronic, multi-symptom health problems than either non-deployed personnel or those deployed elsewhere. Symptoms routinely reported by these veterans include fatigue, muscle or joint pain, memory problems, trouble sleeping, rash and breathing problems.

"This evidence suggests that exposure to this certain class of chemical may be linked to elevated risk of health problems," said Beatrice Golomb, M.D., Ph.D., associate professor of medicine at the UC San Diego School of Medicine, whose study will be published in the early online edition of the Proceedings of the National Academy of Sciences (PNAS) the week of March 10.

"Health issues among Gulf War veterans have been a concern for nearly two decades. Now, enough studies have been conducted, and results shared, to be able to say with considerable confidence that there is a link between chemical exposure and chronic, multi-symptom health problems," said Golomb. "Furthermore, the same chemicals affecting Gulf War veterans may be involved in similar cases of unexplained, multi-symptom health problems in the general population."

The study synthesized evidence regarding a class of chemicals known as acetylcholinesterase inhibitors (AChEis) and organophosphates (OP), which includes nerve gas chemicals. Some military personnel were exposed to nerve gas (sarin) when demolishing Iraqi munitions. Also, the pesticides used aggressively in Gulf regions to control sand flies and other insects fall in the same category of chemicals. This includes the carbamate pyridostigmine bromide (PB) pills originally given to service members to protect against potential nerve-agent exposure. (Note: As a result of an earlier RAND corporation report by Golomb outlining the risks of using such pills, military policy has been changed.)

The study linked exposure to each of these chemicals with the chronic, multi-symptom health problems in 25 to 33 percent of returning Gulf War veterans.

"There is evidence that genetics have something to do with how a body handles exposure to these chemicals," said Golomb. "Some people are genetically less able to withstand these toxins and evidence shows that these individuals have higher chance of suffering the effects of exposure." Specifically, illness is linked to lower activity of enzymes that detoxify AChEis, due to genetic variants The enzymes known to be involved are paraoxonase (PON) for OPs, including sarin, and butyrylcholinesterase (BChE) for PB.

Among those service members given PB pills as a preventive measure, those with the mutations that reduced their ability to detoxify the pills were at significantly higher risk of illness, according to Golomb.

Previous studies have shown genetic variants of these enzymes are also associated with increased rates of some neurological diseases, such as amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease. Golomb says this may explain the elevated levels of ALS seen in Gulf War veterans.

Some of the chemicals linked to these multi-symptom illnesses continue to be used in agriculture, and at homes and offices for pest control in the United States and around the globe. Studies not related to the Gulf War showed that agricultural workers exposed to organophosphate pesticides had 10 times the number of health symptoms as those not exposed.

"Again, genetic variants that hamper defense against these chemicals were linked to higher risk of health problems. These findings carry important implications for current members of the armed forces as well as the general public, suggesting that exposure to these pesticides in any setting may increase risk for impaired neuropsychological function and poor health" said Golomb.

http://www.sciencedaily.com/releases/2008/03/080310181550.htm





Published online on March 10, 2008, 10.1073/pnas.0711986105 PNAS | March 18, 2008 | vol. 105 | no. 11 | 4295-4300

BIOLOGICAL SCIENCES / MEDICAL SCIENCES

Acetylcholinesterase inhibitors and Gulf War illnesses

Beatrice Alexandra Golomb*

Department of Medicine, University of California, San Diego, CA 92093-0995

Communicated by Stephen F. Heinemann, Salk Institute for Biological Studies, San Diego, CA, January 15, 2008 (received for review December 5, 2006)

(Abstract)

Increasing evidence suggests excess illness in Persian Gulf War veterans (GWV) can be explained in part by exposure of GWV to organophosphate and carbamate acetylcholinesterase inhibitors (AChEis), including pyridostigmine bromide (PB), pesticides, and nerve agents. Evidence germane to the relation of AChEis to illness in GWV was assessed. Many epidemiological studies reported a link between AChEi exposure and chronic symptoms in GWV. The link is buttressed by a dose–response relation of PB pill number to chronic symptoms in GWV and by a relation between avidity of AChEi clearance and illness, based on genotypes, concentrations, and activity levels of enzymes that detoxify AChEis. Triangulating evidence derives from studies linking occupational exposure to AChEis to chronic health symptoms that mirror those of ill GWV. Illness is again linked to lower activity of AChEi detoxifying enzymes and genotypes conferring less-avid AChEi detoxification. AChEi exposure satisfies Hill's presumptive criteria for causality, suggesting this exposure may be causally linked to excess health problems in GWV.

Gulf War veteran | pyridostigmine | pesticide | sarin | organophosphate

http://www.pnas.org/cgi/content/abstract/105/11/4295?maxtoshow= &HITS=10&hits=10&RESULTFORMAT=&fulltext=gulf+war+syndrome&searchid= 1&FIRSTINDEX=0&resourcetype=HWCIT