U.S. research links Gulf War nerve agent with long-term heart damage

 

LOS ANGELES, Oct. 13 (Xinhua) -- The American Heart Association (AHA) announced on Wednesday that a research in mice has shown that Gulf War nerve agent may be tied to long-term heart damage.

An analysis of data on mice found that mice developed heart damage 10 weeks after low-dose exposure to sarin, but not earlier, the AHA said in a news release.

The heart damage included enlargement of the left ventricle, an electrical conduction problem that could lead to heart rhythm abnormalities, and reduced ability of the ventricles to contract and pump blood, according to the AHA.

Sarin is known to affect the nervous system and can cause convulsions, breathing difficulties and death.

In this study, researchers examined how sarin affected the hearts of mice. The chemical was injected into the animals at doses too low to produce visible symptoms and the mice were checked 10 weeks after exposure.

"These results have implications for the military in terms of conflict and for civilian populations in cases of environmental or occupational exposure," Mariana Morris, of the Boonshoft School of Medicine at Wright State University in Dayton, Ohio, said in the news release.

"The two-month period was used to simulate the late-onset effect of sarin/nerve agents in Gulf War veterans. There are suggestions that Gulf War illness, in which symptoms are long-lasting, may be related to exposure to low-dose chemical warfare agents," said Morris.

Editor: Mo Hong'e

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Gulf War Nerve Agent Tied to Late-Onset Heart Damage in mice

By Robert Preidt

WEDNESDAY, Oct. 13 (HealthDay News) -- Low-dose exposure to the chemical warfare agent sarin may lead to long-term heart damage, a new study suggests.

Sarin is known to affect the nervous system and can cause convulsions, breathing difficulties and death. In this study, researchers examined how sarin affected the hearts of mice. The chemical was injected into the animals at doses too low to produce visible symptoms and the mice were checked 10 weeks after exposure.

"The two-month period was used to simulate the late-onset effect of sarin/nerve agents in Gulf War veterans. There are suggestions that Gulf War illness, in which symptoms are long-lasting, may be related to exposure to low-dose chemical warfare agents," Mariana Morris, of the Boonshoft School of Medicine at Wright State University in Dayton, Ohio, said in a news release from the American Heart Association.

Heart damage that was noted in the mice 10 weeks after exposure to sarin, but not earlier, included: enlargement of the left ventricle; an electrical conduction problem that could lead to heart rhythm abnormalities; and reduced ability of the ventricles to contract and pump blood, the researchers found.

"These results have implications for the military in terms of conflict and for civilian populations in cases of environmental or occupational exposure," Morris said in the news release.

The study results are scheduled for presentation Wednesday at the American Heart Association's High Blood Pressure Research 2010 Scientific Sessions, held in Washington, D.C.

SOURCE: American Heart Association, news release, Oct. 13, 2010

HealthDay:  URL of this page: http://www.nlm.nih.gov/medlineplus/news/fullstory_104351.html (*this news item will not be available after 01/11/2011)

Low Level Sarin can have negative effects on Brain Structure, Function Long After Exposure

 

Effects of low-level exposure to sarin and cyclosarin during the 1991 Gulf War on brain function and brain structure in US veterans

Linda L. Chao^{a, b, c,} Johannes C. Rothlind^b, Valerie A. Cardenas^{a, c}, Dieter J. Meyerhoff^{a, c} and Michael W. Weiner^{a, b, c}

^a Center for Imaging of Neurodegenerative Diseases, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, 114 M, San Francisco, CA, 94121, United States

^b Department of Psychiatry, University of California, San Francisco, San Francisco, CA, United States

^c Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States

Received 10 December 2009;  accepted 16 May 2010.   Available online 24 May 2010.

Abstract

Background

Potentially more than 100,000 US troops may have been exposed to the organophosphate chemical warfare agents sarin (GB) and cyclosarin (GF) when a munitions dump at Khamisiyah, Iraq was destroyed during the Gulf War (GW) in 1991. Although little is known about the long-term neurobehavioral or neurophysiological effects of low-dose exposure to GB/GF in humans, recent studies of GW veterans from the Devens Cohort suggest decrements in certain cognitive domains and atrophy in brain white matter occur individuals with higher estimated levels of presumed GB/GF exposure. The goal of the current study is to determine the generalizability of these findings in another cohort of GW veterans with suspected GB/GF exposure.

Methods

Neurobehavioral and imaging data collected in a study on Gulf War Illness between 2002 and 2007 were used in this study. We focused on the data of 40 GW-deployed veterans categorized as having been exposed to GB/GF at Khamisiyah, Iraq and 40 matched controls. Magnetic resonance images (MRI) of the brain were analyzed using automated and semi-automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM), cerebrospinal fluid (CSF) and hippocampus.

Results

GW veterans with suspected GB/GF exposure had reduced total GM and hippocampal volumes compared to their unexposed peers (p ≤ 0.01). Although there were no group differences in measures of cognitive function or total WM volume, there were significant, positive correlations between total WM volume and measures of executive function and visuospatial abilities in veterans with suspected GB/GF exposure.

Conclusions

These findings suggest that low-level exposure to GB/GF can have deleterious effects on brain structure and brain function more than decade later.

Sarin, Pesticides Lead to Memory Loss

Written by Anthony Hardie, 91outcomes

(91outcomes.blogspot.com) - Families of victims of the 1994 sarin nerve agent subway attack by the Aum terrorist group held a memorial today in recognition of the anniversary of the attack, which took place 15 years ago today, on June 27, 1994.

Even while there was major news coverage of the anniversary events reflecting on the lives that were lost due to the attacks, the lasting effects of sarin exposures continue to affect the survivors.

In a 2001 study involving the survivors of the Aum subway attack, it was clear that even low-dose exposures to sarin led to signficantly declining, long-term memory loss -- one of the most commonly (and repeatedly) reported symptoms among ill Gulf War veterans.

However, despite confirmed exposures of at least 100,000 Gulf War ground troops to low-dose sarin following the Khamisiyah detonation, the federal VA has yet to provide presumptive service-connection for memory loss to the thousands of Gulf War veterans whose disabling memory conditions began in 1991.


Pesticides

Another source of cognitive disability in Gulf War veterans may be linked to the industrial-strength pesticides used by Gulf War troops on their uniforms, skin, and sprayed in work, sleeping, and eating areas.

A 2001 French study found that workers regularly exposed to low-level pesticides experienced decreases in memory, selective attention, verbal fluency, and abstraction.

Again, these are common symptoms among Gulf War veterans with Gulf War illness. And again, despite the recognized high-level pesticide exposures of virtually all Gulf War ground troops, Gulf War veterans suffering from cognitive impairments do not have the benefit of VA presumptive service-connection as should have been enacted nearly two decades ago.

Change is needed -- Soon.


A pair of 2001 articles, summarizing the Japanese subway attack survivors study, and providing an overview of the French pesticide study, follow.

The Tokyo Attacks in Retrospect

Sarin Leads to Memory Loss

Written by Ernie Hood, Environmental Health Perspectives, November 2001.

In the wake of the 11 September 2001 terrorist attacks on New York City and Washington, D.C., the threat posed by chemical and biological weapons has instantaneously evolved from hypothetical nightmare to clear and present danger. Under this new set of circumstances, any addition to the body of scientific knowledge about the health effects of chemical or biological agents is particularly timely. In this month's issue, a group of Japanese researchers led by Yuji Nishiwaki report the results of their investigation into the long-term physical and psychiatric effects of acute poisoning by sarin, a deadly military nerve gas [EHP 109:1169-1173].

Flashback to Tokyo. The 1995 sarin attack on the Tokyo subway killed 12, but exposure to the nerve gas may cause many more to suffer long-term memory effects.

Photo credit: Kyodo News International, Inc.

On 20 March 1995, members of the Aum Shinrikyo religious cult released sarin in the Tokyo subway, using umbrellas to puncture newspaper-wrapped bags of the gas as they left the trains. Twelve people were killed in the incident, and more than 5,500 required emergency medical treatment. Although several studies have looked at the acute clinical manifestations of sarin poisoning, the authors felt there was an urgent need to perform an epidemiologic study of the chronic effects of sublethal exposures to sarin.
The team examined rescue workers and police officers who had been dispatched to the scene and were exposed to sarin in the course of performing their duties--a group of subjects with similar occupational, socioeconomic, and educational backgrounds. The study included 56 exposed subjects from the Tokyo fire and police departments, who were subdivided into high- and low-exposure groups, and 52 nonexposed subjects of similar backgrounds from the same departments. The research was conducted three years after the exposure.
To assess neurobehavioral effects, the investigators administered five tests designed to measure psychomotor function and memory function. A significant causal relationship was discovered between exposure to sarin and memory disturbance. The exposed group performed less well, in a dose-effect manner, than the control group in the digit span memory test. In this test, the subject is asked to memorize a series of digits displayed on a computer screen at 1-second intervals and then enter the digits into the computer in the correct order within 10 seconds. Later, the subject is asked to enter the digits in reverse order. It was this backward digit portion of the test that uncovered significant memory loss in the exposed subjects. Other tests suggested other exposure-related memory effects, but the results were not statistically significant.
Subjects were also given psychometric tests to assess traumatic stress symptoms, in order to examine whether there was any correlation between psychologic stress and chronic physiologic effects. No such correlation was discovered.
The authors conclude that their findings suggest causality between the sarin attack and memory disturbance, although the mechanism behind that disturbance is unclear. They recommend further study of the link between sarin exposure and memory loss.

==============================

Pondering on Pesticides

Long-Term Low Levels Impair Thinking

Written by Tina Adler, Environmental Health Perspectives, August 2001.
As Homer wrote, "Wine can of their wits the wise beguile," but what of the grapes that make the wine--or rather, the pesticides with which they are treated? Isabelle Baldi of the Institut de Santé Publique d'Epidémiologie et de Développement in Bordeaux, France and colleagues went to their local vineyards to measure workers' cognitive well-being and see how it related to the amount of pesticides they had encountered over the years [EHP 109:839-844]. Previous studies had shown that high-dose pesticide poisoning can cause acute human health effects such as motor skill damage, impaired intellectual functioning, and memory loss. In this study, the first to assess long-term neuropsychologic effects of chronic, low-level pesticide exposures in a large sample of workers, Baldi and colleagues found many examples of impaired cognitive functioning among exposed workers.
The team interviewed 917 men and women, aged 43-58, between February 1997 and August 1998. Of the study participants, 528 had been directly exposed to pesticides through mixing or spraying over a mean of 22 years, another 173 had been indirectly exposed by contact with treated plants, and 216 had never been exposed. The pesticides used were primarily fungicides.

Lost in thought among the vines. A study conducted on vineyard workers showed for the first time that long-term low-level exposures to pesticides have measurable effects on cognition.

Photo credit: PhotoDisc

The team administered nine neuropsychologic tests to the workers, including the Mini-Mental Status Examination (which measures different cognitive components), the Wechsler Paired Associates Test of memory, the Benton Visual Retention Test, the Isaacs Set Test (which measures the ability to quickly generate lists of words in different semantic categories), and the Finger Tapping Test (which assesses motor speed). The team controlled for factors that could alter test scores, including educational level, age, sex, alcohol consumption, smoking, environmental exposures, and depressive symptoms.
Workers who were either directly or indirectly exposed performed worse on tests of memory, selective attention, verbal fluency, and abstraction compared with nonexposed workers. On a test of both selective attention and working memory, directly exposed workers were 3.5 times more likely to score low compared with nonexposed subjects. On a similar test of selective attention and mental flexibility, the exposed individuals were 3.1 times more likely to score low. The exposed men and women processed information less quickly than nonexposed colleagues, although performances of exposed workers were similar to those of the nonexposed if the tasks were slowed.
The study participants' symptoms were subclinical and didn't appear to interfere with their work, the team writes, and the participants didn't complain about their cognitive deficits. But they might run into cognitive problems as they age, Baldi notes. "This is why we planned a four-year follow-up of the population [starting in 2001] to assess evolution of performances," she says.
One surprising finding: although large amounts of alcohol are neurotoxic, the workers who drank moderately had better test scores than nondrinkers. Other studies have shown a protective effect of moderate wine consumption on cognitive performance. Baldi can't explain the finding, but notes that among these workers alcohol is considered "a noble product."

BLAST FROM THE PAST: The history of Iraq's chemical weapons

Written by John Kemp - John Kemp is a Reuters columnist. The opinions expressed are his own -- (Part one of two)

LONDON, June 25 (Reuters) - Perhaps the most frustrating aspect of much western comment on the unfolding crisis in Iran has been its over-simplification and lack of historical awareness. Perspectives are shaped by a single issue (western concerns about whether Iran is pursuing a nuclear weapons programme) and the desire to draw a simple Manichean distinction between good guys (liberal-democrats) and bad ones (clerical-authoritarians).

The reality is far more complicated.

Part of the problem is a truncated sense of history. For most western commentators, the history of Iran's troubled relations with the west starts in 1979 with the triumphant return of the glowering Ayatollah Ruhollah Khomeini at the head of the revolution which swept away Shah Reza Pahlavi's western-backed regime and replaced it with a new Islamic Republic.

Western anxiety was compounded by the 444-day American hostage crisis that helped destroy the presidency of Jimmy Carter, and humiliated a United States still reeling from defeat in Vietnam and the Watergate crisis. Iran and the United States soon became embroiled in a series of proxy conflicts fought in Iraq, Lebanon, and via terrorist attacks on U.S. targets.

But for many Iranians the country's troubled relations with the west can be dated further back -- to at least the CIA-backed coup against Prime Minister Mohammed Mossadegh in 1953.

It marked a crucial turning point in Iranian history, something a bit like the Prague Spring, in which a popular, reforming and democratising but also nationalist prime minister, who believed Iran should control the exploitation of its own petroleum resources, was removed by western intelligence agencies anxious to protect their countries' interest in the oilfields.

The Pahlavist regime which replaced Mossadegh may have been modernising and reforming, but it was also absolutist, dissolute and corrupt, and the Shah's secret police, the SAVAK, ruthlessly hunted down and murdered opponents at home and abroad. While Pahlavist exiles abroad promote the memory of a modernising golden age, there is no enthusiasm for monarchist restoration at home, and the Shah went into exile largely unmourned.

Criticism of the Shah's regime was never confined just to religious conservatives. Even liberals were critical of the excesses of the Peacock Throne.

Iran therefore has no reason to love the western powers. Subsequent events have deepened the mutual suspicion. When Iraqi President Saddam Hussein launched an unprovoked aerial attack on Tehran in 1980 and sent the Iraqi army across the Shatt al-Arab in a brutal war of aggression designed to exploit the turmoil and internal weakness of the fledgling Islamic Republic, the western powers stood aside.

Iraqi forces occupied the oil-rich and strategically vital province of Khuzestan, Iran's cultural cradle, and captured the half-million strong city of Khorramshahr -- and the
west did nothing.

When Iran's regular army and the volunteer forces of the Revolutionary Guard and the basij (the same groups now being used to suppress the protests) drove Iraqi forces back across the border and then moved into the al-Faw peninsula and began to threaten Iraq's second city of Basra, Iraq resorted to chemical weapons -- first the nerve gas sarin and then, when Iranian soldiers were given atropine-filled syringes as an antidote, switching to mustard gas.

Still the west did nothing. In fact, western companies were busy supplying the precursors Iraq needed to make its chemical arsenal and breach the Geneva Protocol. Meanwhile, western intelligence agencies were supplying Iraq with satellite reconnaissance photographs to aid the war effort. Funding was catalysed from friendly regional regimes to support Iraq's faltering war effort and avert the risk of an outright Iranian victory.

To counter Iran's successes on the ground, Iraq's air force began strategic bombing of Iran's cities, then switched to missile attacks on Tehran using Scuds, as Iran suffered its own version of the blitz.

None of this is to suggest Iran did not commit atrocities of its own, or to take Iran's side over Iraq. But when western leaders condemn Iran's alleged quest for "weapons of mass destruction" and fulminate against Iran's missile programme, they betray a startling lack of perspective. Some estimates put the number of Iranian soldiers who fell victim to chemical weapons as high as 100,000. Total casualties (killed or wounded) are put as high 1 million.

When Iran accepted a UN-mediated ceasefire proposal in 1988, Khomeini not unreasonably likened it to drinking a cup of poison.

Given this history, western leaders are in no position to deliver credible moral lectures, and it is hardly surprising that Iran's leaders and media mutter darkly about western interference. Nor is it surprising that the Obama administration, seeking to improve relations, has been anxious to avoid the impression of meddling.

Mustard Gas and Lewisite - Symptoms of WWII "Volunteers" Used in Experiments Similar to Many Gulf War Veterans'

Written by Anthony Hardie, 91outcomes

(91outcomes.blogspot.com) -- The Institute of Medicine (IOM), part of the National Academies of Science, published an extensive series of medical reviews on deployment health of our veterans of the U.S. Armed Forces.

Among those is one from IOM's series on WWII veterans, published shortly after the 1991 Gulf War, entitled, "The Health Effects of Mustard Gas and Lewisite: Veterans at Risk," (1993).

For many Americans, this would seem like the stuff of science fiction.

However, it's not necessarily so for veterans of the 1991 Gulf War and other veterans affected by chemical warfare agent exposures followed by decades of official denial.

For the 60,000 "human subjects in this chemical defense research program," (IOM, 1993) one can only imagine how it must have felt for these once-young veterans to have suffered a lifetime of serious health effects, including those from the following list demonstrated as being caused by Lewisite and Lewisite-Mustard exposures -- and probably many more:

• Respiratory cancers (nasopharyngeal, laryngeal, lung)
• Skin cancer
• Pigmentation abnormalities of the skin
• Chronic skin ulceration and scar formation
• Leukemia (typically acute nonlymphocytic type, nitrogen mustard)
• Chronic respiratory diseases (also Lewisite) (asthma, chronic bronchitis, emphysema, chronic obstructive pulmonary disease COPD), chronic laryngitis)
• Recurrent corneal ulcerative disease
• Delayed recurrent keratitis of the eye
• Chronic conjunctivitis
• Bone marrow depression and (resulting) immunosuppression
• Psychological disorders (mood disorders, anxiety disorders (including traumatic stress disorder), other traumatic stress disorder responses (These may result from traumatic or stressful features of the exposure experience, not a toxic effect of the agents)
• Sexual dysfunction (scrotal or penile scarring may prevent or inhibit normal sexual activity)

According to the IOM summary:


World War II (WWII) has been called “the unfought chemical war.” Both sides had produced millions of tons of chemical weapons and had made massive preparations for their use, yet the weapons were never used. These preparations included the establishment of secret research programs to develop better weapons and better methods of protecting against those weapons.

In the United States, some of this research was focused on the development of protective clothing and skin ointments, which could prevent or lesson the
severe blistering effects of mustard agents (sulfur and nitrogen mustard) and
Lewisite (an arsenic-containing agent).

By the time the war ended, over 60,0000 U.S. servicemen had been used as human subjects in this chemical defense research program, in a wide range of exposures from mild to quite severe.

All those undergoing the latter exposure. and some undergoing the former were told at the time that they should never reveal the nature of the experiments. Almost to a man, they kept this secret for the next 40 years.

Public attention was drawn to these experiments when some of the WWII human subjects began to seek compensation from the Department of Veterans Affairs (VA) for health problems that they believed were caused by their exposures to mustard agents or Lewisite.

Resolution of these cases was complicated by a lack of records documenting individual participation in the experiments, and uncertainty as to which health problems were in fact the result of these exposures.

In June 1991 [just over three months after the end of the 1991 Persian Gulf War] the VA announced guidelines for the handling of these cases, including the loosening of normal requirements for documenting individual participation in the experiments, and the identification of seven diseases to be considered as caused by mustard agents or Lewisite.

In addition, the VA requested that the Institute of Medicine (IOM) convene a committee to assess the strength of association between exposure to these agents and the development of specific diseases. The committee was also charged with identifying the gaps in the literature, and making recommendations as to closing them.

IOM made the following general conclusions:

• The lack of follow-up health assessments of the human subjects in the WWII gas chamber and field tests severely diminished the amount and quality of information that could be applied in the assessment of long-term health consequences of exposure to mustard agents and Lewisite.
• The levels of exposure to mustard agents and Lewisite may have been much higher than inferred in the summaries of the gas chamber and field tests.
• There were no epidemiologic studies done of mustard-agent exposed U.S. chemical weapons productions workers, war gas handlers and trainers, or combat casualties from WWII.

The lack of follow-up of exposed WWII veteran "volunteers," the identified possibility that levels of exposure may have been higher, and the lack of epidemiological studies on those exposed are troubling. Yet, decades later, responsible federal officials at DOD and VA failed in these same areas with veterans of the 1991 Gulf War.

The timing of the 1993 publication of this material is of note -- nearly 50 years after the fact, but just two years after the Gulf War, the veterans of which had already begun to complain of mysterious symptoms.

Mass exposures of Gulf War troops to sarin and cyclosarin have already been proven with the Khamisiyah incident in which a bunker complex filled with chemical munitions was detonated, resulting in a chemical plume that drifted over a wide swath of troop areas for at least three days. Lesser known is the fact that mustard blister agent was also present at Khamisiyah, the Iraqi munitions storage facility where U.S. Gulf War troops' demolitions at the end of the war included munitions containing sarin nerve agent.

Given that the Iraqi military had forward deployed mustard to Khamisiyah, and given the history of Iraq's offensive use of mustard, lewisite, and mustard-lewisite mixtures during the Iran-Iraq war, it should be assumed that Gulf War troops were exposed to mustard and/or lewisite vapors -- which would certainly explain many Gulf War veterans' commonly reported symptoms.

In fact, DOD admitted to "one" mustard gas exposures in a 1997 press release, entitled, "Mustard Gas Exposure Likely, report finds." And IOM noted that Gulf War veterans who were Khamisiyah "witnesses" were highly likely to report that they recalled several symptoms of mustard agent exposure, including coarse voice, rash, and blisters.

Meanwhile, IOM noted the Presidential Advisory Commission's 1996 finding that:

Two other storage sites in central Iraq, Muhammadiyat and Al Muthanna, sustained damage from air attacks during the Gulf War. Munitions containing 2.9 metric tons of sarin–cyclosarin and 1.5 metric tons of mustard gas were damaged at Muhammadiyat, and munitions containing 16.8 metric tons of sarin–cyclosarin were damaged at Al Muthanna (PAC 1996a).

It is time for Congress to conclude that Gulf War troops were exposed to not only sarin and cyclosarin, DU, and the full range of pesticides and PB pills, but also mustard and lewisite blister agents -- and to provide presumptive service-connection to ensure VA healthcare for the range of known health outcomes from these exposures.