Saturday, November 3, 2012

Gulf War Veterans' Lung Cancer Risk and Gov't Failures




A six-month long news team investigation into lung cancer in Gulf War veterans was finally completed and aired this week in Indiana.  

The investigative team's story asks this incisive rhetorical question:


"So if doctors, the VA, and the military all know veterans from the Gulf War are at higher risk: Why isn't DOD notifying those at higher risk and why isn't the VA screening them aggressively?"

VA and DoD have known for years about higher risks of lung cancer, and other cancers, among Gulf War veterans.  Yet, that knowledge has translated into absolutely nothing in terms of DoD or VA health care screenings for affected veterans.

One of those affected veterans is Colonel Mark Smith, a Gulf War and OIF veteran with advanced lung cancer, featured in the story below.  He attributes his lung cancer to heavy exposure to the burning oil well fires lit by retreating Iraqi forces in February 1991.  

A presentation by the National Gulf War Resource Center at its annual conference in Las Vegas in 1999, attended by VA and DoD officials, presented evidence from dozens of documents received under the Freedom of Information Act showing that federal officials were aware that microfine (< 2.5u) particulates from Kuwaiti burning oil well fires exceeded safe health limits by hundreds of times, and that long term health effects included lung disease and lung cancer.  

Some 1991 Gulf War troops were also exposed to Iraqi chemical warfare agents, including following air bombing and demolitions of Iraqi chemical munitions during and following the war.  Those officially recognized include sarin, cyclosarin, and mustard gas, a known carcinogen.  

VA and Congress have received recommendations from multiple sources on the need for appropriate screening for those at greater risk for lung cancer, including detailed reports from highly reputable health and veterans advocacy organizations.   Among these is the entire section on lung cancer and veterans in the annual "Independent Budget" coauthored by a long list of veterans service organizations (VSOs).   

And, in repeated reports to the Secretary of Veterans Affairs (VA), the Congressionally chartered  Research Advisory Committee on Gulf War Veterans' Illnesses (RAC) has recommended health monitoring for cancers, including lung cancer.  In particular, the 2008 RAC report cited findings by the Institute of Medicine (IOM) that lung cancer is associated with combustion byproducts.  The report, as well as more recent reports and recommendations by the RAC, have detailed serious concerns with VA's lack of adequate medical surveillance related to cancer and other serious diseases.  

These and other reports, recommendations, and research are provided at the end of the news story, below.  More information can also be found here on 91outcomes by searching on "lung cancer," including an April 2012 post, "Higher Rates of Lung Cancer Among Gulf War, Other Veterans; Immediate Medical Research Funding Availability through CDMRP."  

Yet DoD and VA officials and bureaucrats to date have failed to act to implement lung cancer risk assessments among Gulf War veterans and screening for those deemed at risk, leading to one of many ongoing advocacy missions for the VSO's and health advocacy organizations like the Lung Cancer Alliance in Washington, DC.  

As an affected Gulf War veteran myself, one whose lung issues began in the Kuwait in 1991 and have never subsided, I can personally attest to years of battles within the VA healthcare system to get appropriate diagnostic testing and care.  Finally in 2009 -- after 15 years of fruitless battles with VA -- private healthcare paid for by expensive private health insurance included a bronchoscopy that provided obvious visible evidence of serious chronic inflammation, consistent with my two decades of lung symptoms -- and a new avenue for treatment.  For veterans like me -- with a long, well documented history of debilitating respiratory issues that began on a particular day in Kuwait in 1991 -- VA has done and continues to do nothing proactive to reach out or to provide anything other than grossly inadequate healthcare related to these Gulf War related lung issues.  

Other veterans besides Gulf War veterans with oil well fire and chemical warfare agent exposures could also be at risk for negative lung outcomes, potentially including those already suffering following exposures to hexavalent chromium exposure at Qarmat Ali and to burn pits in Iraq, Afghanistan, and elsewhere.  

It is high time that ranking officials at VA take action and implement the clearly articulated recommendations of the Lung Cancer Alliance, the Independent Budget VSO's, the RAC, and medical researchers, implement risk assessments for Gulf War (and other potentially at risk veterans), and conduct regular screening for those at higher risk for lung and other cancers.  

It is true that there are health risks associated with the screening procedures, including radiation from CT scans, that must be weighed by health care providers.  But failure to notify veterans at risk, failure to implement plans for risk assessment, and failure to do the sorts of health screening recommended for those at higher risk are all signs of unmistakable DoD and VA failure -- the kind of failure to which Gulf War veterans have grown all too accustomed over the last two decades.  

Special thanks to investigative reporter Karen Hensel for her exceptional work on this expose, and to all involved at WISH-TV8.  It was a privilege to assist you in your investigation.  

-A.H.

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SOURCE: http://www.wishtv.com/dpp/news/i_team_8/veterans-not-told-of-lung-cancer-risk






Veterans not told of lung cancer risk

Updated: Friday, 02 Nov 2012, 10:51 PM EDT
Published : Friday, 02 Nov 2012, 10:27 PM EDT


INDIANAPOLIS (WISH) - An I-Team 8 investigation is already prompting congressional action in Washington D.C. In a six-month long investigation, I-Team 8 uncovered information raising more questions than answers about government accountability to American troops.
I-Team 8’s investigation began with a U.S. Marine in Indianapolis. The investigation is now centered in Washington D.C. as we question top commanders, Veterans Affairs and congressional leaders about the deadly cancer predicted 20 years ago in what some called "The Black Lung Tour."
THE MARINE
Colonel Mark Smith is a fighter.
"I kill freakin' terrorists. That ain't hard. It's what I was born to do. These people kill cancer,” Smith said.
He is a battalion commander — a U.S. Marine.
In 2004 he led 1,200 Marines into one of the fiercest battles of Iraq, the battle of Fallujah. Looking at pictures of the Marines his battalion lost, he says, "I cried like a baby every time we lost one of our outstanding Marines in combat."
Many in central Indiana came to know Mark, also an Indiana State Trooper, his wife and daughters through letters home from Iraq that were featured on WISH-TV.
THE BATTLE
But in those letters years ago, his real battle was just beginning.
"The morning I got up, I had a bizarre pain in my calf," Smith recalled.
At a commanders conference in New Orleans, he was about to take his morning run.
"Being athletic you automatically think strain, sprain, overtraining," he said.
The pain persisted. Doctors found a blood clot in his leg, so they ordered a CT scan.
THE TURN
It was lung cancer.
"The only thing I heard in that room that night was in my own mind, planning my funeral," Smith said.
24-Hour News 8 cameras have spent months documenting how a Marine commander, always prepared, battles cancer.
"This is just something I was completely and utterly unprepared for,” Smith said. “The Marine Corps steels you."
Smith admitted it was hard to get into the car to go for his first double dose of chemotherapy and radiation.
"It's really hard because everything from the time you are diagnosed is about finding 'the new normal,’” he said.
Chemotherapy and radiation became his "new normal."
DAY ONE
Leaving his first day of treatment, Smith describes it as "awesome" then lifts his shirt to show the box outlined in marker on his chest to show the area doctors will hit with radiation. Day after day he undergoes both radiation and chemo — long, hard, grueling treatments.
He sits with an IV in his arm for chemotherapy, holding a book and saying, "This is just the Marine Corps way."
The Marine Battlebook is replaced by Mark's Cancer Battlebook. He fights fatigue and nausea as a Marine — through martial arts, the treadmill and swimming.
"THE BLACK LUNG TOUR"
Sitting on his couch at home, Smith explains where the cancer may have originated.
"My personal belief is Desert Storm," he said.
His team of doctors points to Desert Storm as a possible source for the cancer. When asked if there could be any connection between Smith's lung cancer and his time served in the Gulf War, Dr. Peter Garrett says, "He certainly had exposure."
In 1991 Smith deployed with the 3/24 Marines to Saudi Arabia — "Camp Coyote."
"Prior to the ground war — starting when the Iraqis torched some of the oil wells — we were in a significant path of the smoke from one of those oil fires for a very long time,” he said. “Four to six weeks."
His pictures tell the story.
"At high noon the sky had a blackish blue hue to it. We would routinely, constantly blow our nose and have nothing but black in the Kleenex. It wasn't uncommon to be standing there and another instructor go like this (wipes his nose) to let you know you had black gunk coming out of your nose,” Smith said.
Young and bulletproof, they joked it would kill them one day.
20 YEAR WARNING
I-Team 8 discovered experts sounding the alarm as early as 1991 that deaths "from lung cancer...are expected to rise dramatically..." (Source: John Horgan, The Danger from Kuwait's Air Pollution: Smoke from Oil Fires Threatens Healthy, Scientific American October 1991)
And I-Team 8 uncovered documentation showing Gulf War veterans with a "higher rate" and "substantially higher risk" of lung cancer. (Source: The Congressionally Directed Medical Research Program )
"We've known for years that our veterans are being diagnosed and dying of lung cancer at higher rates than civilians," Admiral T. Joseph Lopez, USN (Ret) said. He's on record saying early "screening not only saves lives but money."
NO ACCOUNTABILITY
While Veterans Affairs has been urged to offer CT screenings for veterans at high risk for lung cancer so far, the VA has not implemented it — relying solely on the less efficient X-rays. Remember, it was civilian doctors who discovered stage 3b cancer in Smith with a CT Scan. So if doctors, the VA, and the military all know veterans from the Gulf War are at higher risk: Why isn't DOD notifying those at higher risk and why isn't the VA screening them aggressively?
Should Smith have been on a priority list to be screened each year? His medical records show after returning from the Gulf War in 1991 he was diagnosed with asthma. The records show an abnormality on his right upper lobe — the same spot now riddled with cancer. I-Team 8 showed those medical records to his current doctor, asking if there is a correlation.
"Could be but I couldn't tell you for sure there was," Dr. Garrett said.
When told Smith believes the cancer originates to his time served in Desert Storm Garrett replied, "Could be."
RESEARCH BACKS WARNING
Even at the time, British scientists predicted a jump in lung cancer over the following 20 years. (Source: American University International Law Review "Environmental Terrorism: Lessons from the Oil Fires of Kuwait" 1991 Volume 10/Issue 1)
Dr. Garrett confirms it can take that long for the cancer to develop. Smith is right on target. So, if members of the military are coming back and there is a higher risk and higher rate of lung cancer that has been documented, are members of the military supposed to just wait for it to show up?
"Well, I think that is the role for the Department of Defense," Dr. Garrett said.
ALWAYS A MARINE
Smith wore his uniform for his final treatment — the same uniform that may have led to the cancer.
"One of his nurses said, ‘What is the occasion?’ He goes, 'Last treatment.' Then he said he just wanted to show respect,” Mark's daughter Nichole explained.
Respect for his Marines he still considers on his watch.
"I knew when he said that even though they are up in heaven, they were part of the team too,” Nichole said. “Part of him fought it (the cancer) because they didn't have the choice or the chance to fight something like that if it ever came up. I know a part of him did it for them and their families too."
PROGNOSIS
Smith has spent a career fighting terrorists to protect American lives. Now his fight is for his own life.
"The prognosis is good,” he said through tears. “Chances are everything will work out. But if they don't, I worry about others."
Asked if he means his daughters he breaks down with emotion and simply says, "Yeah."
And other Marines. At risk. Dying. Unaware.
I-TEAM 8 INVESTIGATION PROMPTS CONGRESSIONAL ACTION
Through months of research and digging for answers, I-Team 8 uncovered a disturbing trend. We discovered documentation that governments of Kuwait, Saudi Arabia and the United States suppressed information and a "gag order" led to a scarcity of data. (Source: John Horgan "Why are Data Being Witheld? Scientific American, July 1991) (Source: William Booth, Washington Post June 25, 1991. Also, Daphne Bramham Black Death in the Gulf: Environmentalists Accue Governments of Playing Down Potential Dangers from Blazing Oil Wells, Vancouver Sun July 27, 1991 B1, B4, B6)
Indiana Congressman Marlin Stutzman, Indiana's only member on the House Veterans Affairs committee, is launching his own investigation.
"After hearing about this case, I am very concerned,” Stutzman said. “This is an issue that needs to be brought to the immediate attention of the VA and DOD. I know one thing, being proactive in regard to early detection is the best prevention for cancer. We also need to make sure high-risk soldiers and Marines are getting the appropriate notification so they can be screened in a timely fashion. I will be following this story very closely."

Research and resources:

New CDMRP Studies to Assess Gulf War Veterans' Health Status, Develop GWI Blood Test


The studies below are funded by the Congressionally Directed Medical Research Program (CDMRP) on Gulf War  Illness (GWIRP).  

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Source: http://www.baylor.edu/mediacommunications/news.php?action=story&story=124821



Baylor University Scientist Receives Major Grants for Health Research on 1991 Gulf War Veterans


NOV. 1, 2012
Follow us on Twitter: @BaylorUMediaCom

Media contact: Frank Raczkiewicz, Assistant Vice President for Media Communications, (254) 710-1964
WACO, Texas (Nov. 1, 2012) - Baylor University has been awarded two new federal grants for research on Gulf War illness, the complex medical condition that affects veterans of the 1991 war. The grants, from the Office of Congressionally Directed Medical Research Programs of the U.S. Department of Defense, total nearly $1.6 million, and bring current federal funding for Baylor's Gulf War research program to over $2.3 million.
"These grants will support our intensive effort to find answers for the many thousands of veterans still suffering from Gulf War Illness," said Lea Steele, Ph.D., the Baylor University epidemiologist who directs the program. The funding supports projects to address multiple aspects of the problem, including studies on the biological processes causing veterans' symptoms and development of a nationwide network to advance health research, particularly studies leading to effective treatments, for Gulf War illness.
Gulf War illness is the term commonly used for the symptomatic condition that affects military personnel who served in the 1990-1991 Gulf War. Symptoms typically include some combination of chronic headache, widespread pain, memory and concentration difficulties, and digestive and other abnormalities - problems that are not explained by medical or psychiatric diagnoses or by routine laboratory tests.
Studies indicate at least one in four of the 700,000 military personnel who served in the 1990-1991 war are affected, and that few have recovered over time.
"Gulf War illness may no longer be as high profile as health issues from more recent wars in Iraq and Afghanistan, but it remains a very serious problem for many thousands of ill veterans," said Steele, who is research professor in the Baylor Institute of Biomedical Studies. "This work is especially important here in Central Texas, which is home to one of the largest concentrations of 1991 Gulf War veterans in the country."
The federal grants awarded to Baylor support three separate projects. For the first study, funded in 2011, Baylor is partnering with Scott & White Healthcare to provide clinical assessments, including an in-depth look at the brain, the immune system, and diverse other measures in Gulf War veterans. "This project should give us a clearer picture of the complex biological processes that drive veterans' symptoms," Steele said. "This is an essential step for improving the care provided for ill veterans."
The second project will focus on developing a blood test to improve the diagnosis of Gulf War illness. According to Steele, "Gulf War illness is currently defined only on the basis of veterans' symptoms. An objective test to assist in diagnosing this condition would be immensely beneficial to veterans and their healthcare providers, and can also provide an important tool to better understand and treat this condition."
The third project includes a national study to determine the current health status of veterans across the U.S. who served in the 1991 Gulf War. It will also establish an information and research network for veterans to receive periodic updates on health issues, and connect veterans with scientists who are conducting health studies of 1991 Gulf War veterans.
Steele has conducted research on the health of Gulf War veterans since 1998. Before joining the Baylor Institute of Biomedical Studies in 2010, she served as scientific director for the federal Research Advisory Committee on Gulf War Veterans' Illnesses.
"After years of false starts," she said, "research has now provided progress in our understanding of Gulf War illness." She emphasized, however, that despite this progress, many veterans remain ill, since doctors still lack effective methods for diagnosing and treating Gulf War illness. She added that "We believe these answers can be found, and are especially pleased to be partnering with Scott & White to address this problem, given its importance for veterans in Central Texas."

ABOUT BAYLOR UNIVERSITY
Baylor University is a private Christian university and a nationally ranked research institution, characterized as having "high research activity" by the Carnegie Foundation for the Advancement of Teaching. The university provides a vibrant campus community for approximately 15,000 students by blending interdisciplinary research with an international reputation for educational excellence and a faculty commitment to teaching and scholarship. Chartered in 1845 by the Republic of Texas through the efforts of Baptist pioneers, Baylor is the oldest continually operating university in Texas. Located in Waco, Baylor welcomes students from all 50 states and more than 80 countries to study a broad range of degrees among its 11 nationally recognized academic divisions. Baylor sponsors 19 varsity athletic teams and is a founding member of the Big 12 Conference.

Friday, October 26, 2012

Study Finds ‘Firm Evidence’ Acupuncture Relieves Chronic Pain


Chronic widespread pain is a common symptom among ill Gulf War veterans, and this study provides evidence of an alternative treatment that seems to help.

A Gulf War Illness focused acupuncture treatment study in Boston is currently seeking Boston-area participants.  [ More information ]

-A.H.


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Study Finds ‘Firm Evidence’ Acupuncture Relieves Chronic Pain

by RICHARD LENTI on OCTOBER 22, 2012
As many as 3 million Americans receive acupuncture treatments, most often for relief of chronic pain. While there appears to be little consensus in the scientific community to its value, a new study in the Archives of Internal Medicine suggests that relief offered by acupuncture is very real and should be considered as a viable option by the medical community .
Focusing on patients who reported chronic back and neck pain, osteoarthritis, chronic headache and shoulder pain, researchers from Memorial Sloan-Kettering Cancer Center in New York conducted a six year, meta-analysis of data from 29 prior studies involving nearly 18,000 adults.
Study participants were randomly assigned treatment with acupuncture, standard treatments such as drugs and physical therapy, or “fake” acupuncture in which needles were inserted at points other than the traditional meridians.
Using a scale from zero to 100, the average participant’s pain measured 60. Conventional methods brought the pain down to 43, fake acupuncture brought it down to 35, and the actual acupuncture dropped pain to 30.
According to Dr. Andrew J. Vickers, attending research methodologist at Memorial Sloan-Kettering Cancer Center and the lead author of the study, that means about half of the patients who got acupuncture had improvement in pain, compared with 30% who didn’t get acupuncture and 42.5% who had fake acupuncture.
“This has been a controversial subject for a long time,” Vickers told the New York Times “But when you try to answer the question the right way, as we did, you get very clear answers. We think there’s firm evidence supporting acupuncture for the treatment of chronic pain.”
One limitation of the study noted by authors was that since comparisons between acupuncture and no acupuncture could not be blinded, both performance and response bias were possible.
In an accompanying editorial,  Dr. Andrew Avins of the University of California, San Francisco pointed out that the study’s authors left themselves open to criticism by relying on fixed-effects models “that are less conservative than random-effects models and more likely to yield statistical significance.”
For him, a greater concern was the potential for skepticism generated by the study’s assertions that acupuncture works only slightly better than a placebo in treating pain.  Avins worries that colleagues who don’t seriously consider acupuncture as a treatment option will continue dismiss it as nothing more than a placebo.
“At the end of the day,” says Avins, “our patients seek our help to feel better and lead longer and more enjoyable lives, Perhaps a more productive strategy at this point would be to provide whatever benefits we can for our patients, while we continue to explore more carefully all mechanisms of healing.”
Acupuncture is the insertion and stimulation of needles at specific points on the body to facilitate recovery of health. Originally developed as part of traditional Chinese medicine, some contemporary acupuncturists approach it in modern physiologic terms, helping make it one of the most widely practiced forms of alternative medicine in the country.

Sunday, October 21, 2012

Georgia Study Connecting the Dots Between Gulf War Toxic Exposures and Veterans' Brain Damage

The article below, published earlier this year in local Augusta, Ga. media, is about a CDMRP-funded treatment target development medical study related to neurological damage in ill Gulf War veterans.  

The study is essentially a proof of concept aimed at developing treatment targets: that a class of chemicals present in the 1991 Gulf War, organophosphates, could indeed have caused the brain damage found in research on MRI scans of representative samples of the 250,000 ill veterans of the 1991 Gulf War.

According to the principal investigator of the study, Dr. Alvin Terry of the Georgia Health Sciences University, "It is expected that the results of these studies will not only contribute to a better understanding of the basis for the neurological symptoms of GWI (the first step before new therapeutic targets can be identified and new treatments can be developed), but also a better understanding of the long-term toxicity of a class of chemicals that continues to pose a significant risk for military personnel as well as millions of civilians worldwide."

This particular study looks closely at organophosphates (OP's).  Coalition troops were exposed to an array of OP's during the Gulf War, including to sarin and cyclosarin nerve agents following detonations of Iraqi chemical munitions during and after the war, including at the Khamisiyah demolitions, and to an array of Gulf War era pesticides, including DEET, chlorpyrifospermethrin (a pyrethroid), and others.  

According to a 2008 report of the Congressionally mandated Research Advisory Committee on Gulf war Veterans' Illnesses (RAC):

"The extensive body of scientific research now available consistently indicates that Gulf War illness is real, that it is a result of neurotoxic exposures during Gulf War deployment, and that few veterans have recovered or substantially improved with time."  

Nerve agent protective pills administered to about 250,000 U.S. Gulf War troops (and other Coalition troops -- pyridostigmine bromide (PB) -- have also been implicated by medical researchers in Gulf War neurotoxic exposures. PB is from a class of chemicals similar to OP's, called carbamates.


According to the 2008 RAC report:
"Many classes of chemicals are neurotoxicants, that is, exposure to these compounds can have adverse biological and physical effects on the nervous system. Three types of neurotoxicant exposures encountered by Gulf War military personnel during deployment are chemically related. They include chemical nerve agents, many of the pesticides used during the Gulf War, and pyridostigmine bromide (PB), the drug given to troops as a protective measure in the event of nerve gas attack."


Mustard gas, prominent in the Iraqi chemical munitions arsenal at the time of the 1991 Gulf War including in the Khamisiyah detonations, has also been implicated in Gulf War Illness, including in a 2012 relook at Gulf War neurotoxic exposures funded by the chemical defense arm of the U.S. Department of Defense.  Much of the what is known  about the long term health effects of exposure to mustard gas was learned following human experimentation at the end of WWII and documented in a government commissioned 1993 report by the Institute of Medicine, part of the National Academy of Sciences.

Representative OP's examined in Dr. Terry's study, below, include a surrogate for sarin nerve agent (DFP, diisopropylfluorophosphate) and chlorpyrifos, a potent pesticide used during the Gulf War.  

*Special thanks to Gulf War veteran Mark Keener for sharing this article*

-A.H.

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Source: The Augusta (Ga.) Chronicle
http://chronicle.augusta.com/news/health/2012-03-19/nerve-gas-insecticide-exposure-possible-cause-gulf-war-illness-say-ghsu#


Nerve gas, insecticide exposure possible cause of Gulf War illness, say GHSU researchers

Monday, March 19, 2012 4:50 PM
Last updated Tuesday, March 20, 2012 6:52 AM
The memory and attention problems plaguing thousands of veterans from the first Gulf War might be caused by low-level exposure to insecticides and nerve gas, said researchers at Georgia Health Sciences University.
Dr. Alvin Terry, a professor at GHSU, and his colleague, Dr. Nathan Yanasak, are conducting a three-year study on the neurological symptoms of Gulf War illness.  JACKIE RICCIARDI/STAFF
JACKIE RICCIARDI/STAFF
Dr. Alvin Terry, a professor at GHSU, and his colleague, Dr. Nathan Yanasak, are conducting a three-year study on the neurological symptoms of Gulf War illness.
Gulf War illness could be caused by a class of chemicals known as organophosphates, which can include popular pesticides and insecticides but also the nerve gases sarin and cyclosarin.
The Department of Defense and the Central Intelligence Agency estimate 100,000 people might have been exposed to low levels of those nerve gases when troops blew up a weapons depot in Khamisiyah, Iraq, on March 10, 1991. Troops were also routinely exposed to the chemical in insecticides, said Dr. Alvin Terry, the director of the Animal Behavior Center at GHSU and professor of pharmacology and toxicology.
Terry and a colleague, Dr. Nathan Yanasak, have an $860,000, three-year grant from the DOD to study whether the chemicals can cause nerve damage in the brains of animals – in this case, mice – that could lead to memory and attention problems. They will look to see whether the insecticide chlorpyrifos, which is commonly used on crops in the U.S. and around the world – when given in low doses – might hamper the ability of the nerve cells to transport food and waste up and down the nerve.
“For it to maintain its health, it has to be able to transport things” along the axon of the nerve, Terry said. The researchers are using newer technology, such as manganese-enhanced MRI, to study that because manganese is known to be taken up and transported by nerves in the brain, he said. Researchers will also check whether the protective sheath of the nerve cells, known as myelin, is depleted by the low-level exposure, which can affect nerve firing.
“It’s probably subtle if it is there,” Terry said.
In previous work, including a study published this year, Terry and colleagues showed that “subthreshold” doses of the chemical caused memory and attention problems in rats even months later.
“Long after they have been exposed, you can still pick up on these memory deficits,” he said.
What makes that intriguing is that it is similar to problems that plague veterans with Gulf War illness, Terry said. The study in animals is is being done to find out whether that is the cause of the symptoms, which could stem from a number of other causes, such as the oil well fires that raged during the conflict and had wide exposure, Terry said.
“There’s a whole multitude of things that you could say might be a possibility,” he said. The DOD has funded research over the years into what might cause Gulf War illness, “but no one has really solved it. There have been a lot of controversies.”
His work has drawn some fire from chemical companies, but Terry said he strives for balance in his view of the chemicals.
“They have without a doubt dramatically improved farming productivity, and they have helped to get rid of vector-bone illnesses,” he said. “It’s just knowing the long-term effects; we need to be more educated on that and try to be balanced.”

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MORE INFORMATION
Additional information about this study from the Gulf War Illness (GWIRP) Congressionally Directed Medical Research Program (CDMRP)

Organophosphate-Related Alterations in Myelin and Axonal Transport in the Living Mammalian Brain 



Principal Investigator: TERRY, ALVIN V 

Institution Receiving Award: GEORGIA HEALTH SCIENCES UNIVERSITY 

Program: GWIRP 

Proposal Number: GW110073
Funding Mechanism: Investigator-Initiated Research Award 

Partnering Awards:
Award Amount: $859,673.00


PUBLIC ABSTRACT

Among the variety of chronic symptoms that have been reported in those who suffer from Gulf War Illness (GWI), the neurological problems, especially the deficits in attention, concentration, and memory function, may be the most debilitating. Unfortunately, despite more than 20 years of research, the exact cause of these symptoms remains unclear. It has been hypothesized that a significant contributing factor to GWI symptoms may have been exposure to the class of chemicals known as organophosphates. These chemicals are found in many of the insecticides used in the campaign during the Gulf War, as well as nerve agents. Two nerve agents within the class of organophosphates, sarin and cyclosarin, may have been released into the environment at low levels following the destruction of an Iraqi munitions storage complex at Khamisiyah, Iraq, in March 1991. However, it has been very difficult to determine if exposure to organophosphates, specifically, underlie the cognitive deficits or the changes in brain structure (white matter volumetric changes) that have been recently detected in Gulf War Veterans by magnetic resonance imaging (MRI). The uncertainty arises because of the wide variety of other possible contributing factors (multiple vaccinations, treatments with drugs like pyridostigmine bromide, exposure to smoke from oil well fires, infectious organisms, etc.). Accordingly, one goal of the proposed studies is to determine in animals if exposures to organophosphates at levels that do not cause acute symptoms of toxicity (i.e., similar to the situation with Gulf War soldiers) indeed result in changes in the brain that have been documented by MRI studies in Gulf War Veterans. These types of prospective studies can only be conducted in animal models. We have already published several studies in animals showing that such exposures to organophosphates can result in prolonged deficits in cognitive function.

In addition, the diverse and chronic nature of the neurological symptoms of GWI suggests that some basic or fundamental neuronal process was adversely affected while these individuals were stationed in the Persian Gulf area. In previous work we have shown that one such fundamental process, axonal transport, the mechanism whereby important molecules are transported in nerve cells, is impaired in peripheral nerves of animals previously exposed to organophosphates. Our next objective is to determine if axonal transport is impaired in the brains of living animals after exposure to organophosphates, establishing a plausible explanation for the variety of neurological symptoms observed in sufferers of GWI. We have developed the capabilities to investigate each of these phenomena (white matter volumetric and structural changes as well as axonal transport) in the brains of living animals using two magnetic resonance imaging techniques, diffusion tensor imaging (DTI) and manganese-enhanced magnetic resonance imaging (MEMRI). We will study the effects of several doses of a representative organophosphate insecticide that was used during the Gulf War, chlorpyrifos, and a representative nerve agent, diisopropylfluorophosphate. It is expected that the results of these studies will not only contribute to a better understanding of the basis for the neurological symptoms of GWI (the first step before new therapeutic targets can be identified and new treatments can be developed), but also a better understanding of the long-term toxicity of a class of chemicals that continues to pose a significant risk for military personnel as well as millions of civilians worldwide.

TECHNICAL ABSTRACT

Background: It has been hypothesized that a significant contributing factor to the cognitive dysfunction and other neurological symptoms reported in those who suffer from Gulf War Illness (GWI) may have been exposures to the class of chemicals known as organophosphates (OPs). However, there are confounding factors that limit the strength of this hypothesis (e.g., other environmental exposures, vaccinations, etc.). The proposed studies will determine prospectively in living animals if OP exposure is associated with pathological features (e.g., myelin-white matter anomalies) that have been observed in Veterans suffering from GWI. The proposed studies will also prospectively examine the effects of OPs on a process (axonal transport) that is fundamental to the function of neurons (i.e., effects that could theoretically explain the diverse neurological symptoms of GWI).

Objective/Hypothesis: The objective of this application is to determine if exposure to OPs results in alterations in myelin (as observed in GWI patients) and axonal transport (as we have observed ex vivo in animals) in the living rodent brain. Our central hypothesis is that OPs compromise the integrity of myelin and impair axonal transport, effects that lead to functional impairment of neuronal pathways that support cognition and other neurological processes. We propose to study two OPs, a representative insecticide that was used in the first Gulf war, chlorpyrifos (CPF), and a representative nerve agent, diisopropylfluorophosphate (DFP).

Specific Aims: (1) Determine the consequences of repeated subthreshold exposures (defined as doses not associated with signs of acute toxicity) to representative OPs on axonal transport in the living rat brain. (2) Determine the consequences of repeated subthreshold exposures to representative organophosphates on myelin in the living rat brain.

Study Design: For Aim 1 we will determine if OP-related axonal transport deficits occur in vivo using manganese-enhanced magnetic resonance imaging (MEMRI) of the optic nerve axonal projections from the retina to the superior colliculus. To quantify Mn[2+] enhancement, manually drawn regions of interest (ROI) will be placed in 2D slices in various selected areas (eyeball, optic nerve, superior colliculus) along the Mn[2+]-enhanced and contralateral non-enhanced areas. The enhancement ratio within the ROI will be calculated by dividing the enhanced ROI intensity by the contralateral unenhanced ROI intensity.

For Aim 2 we will use image-based segmentation of brain tissue as well as diffusion tensor imaging (DTI) to characterize changes in rat white matter (WM) after OP exposure. Segmentation of WM and grey matter (GM) and subsequent volumetric quantification of total WM, GM, and ventricular volume will offer a measure of gross tissue integrity. Fractional anisotropy (FA) and diffusivity along radial and axial directions of major neural bundles will provide three metrics for quantifying changes in myelin. These bundles and tracks will include the optic nerve, corpus callosum, corticospinal tracts, and additional regions that are known to be important for cognitive function (e.g., the fornix, and stria terminalis). DTI-based metrics (which provide an indirect probe of myelin alterations in vivo) will be interpreted in conjunction with Black Gold II histology and microscopic analysis (with unbiased stereology) of tissues from additional OP-treated animals. Quality assurance of DTI performance will be ensured using phantom objects with anisotropic diffusive characteristics imaged simultaneously during the rat imaging sessions.

We will evaluate three doses of CPF (3.0, 10.0, 18.0 mg/kg) and DFP (0.125, 0.25, 0.50 mg/kg) + vehicle controls administered daily for 14 days. For MEMRI and DTI studies, six animals from each dose group will have baseline scans, will be re-scanned at the end of OP dosing, and then re-scanned again after a 4-week, OP-free washout period. Six additional animals from each dose group will be sacrificed for Black Gold histology at the end of dosing and an additional six animals will be sacrificed 4 weeks after the last OP exposure.

Impact: The proposed studies have been designed to address the question of whether exposure to OPs was likely to have been a causal factor in the pathological abnormalities observed in sufferers of GWI. It is expected that the results will not only contribute to a better understanding of the basis for the neurological symptoms of GWI (the first step before new therapeutic targets can be identified and new treatments can be developed) but, also, a better understanding of the long-term toxicity of a class of chemicals that continues to pose a significant risk for military personnel as well as millions of civilians worldwide.