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 ]



Study Finds ‘Firm Evidence’ Acupuncture Relieves Chronic Pain

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*



Source: The Augusta (Ga.) Chronicle

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
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.”

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 


Program: GWIRP 

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

Partnering Awards:
Award Amount: $859,673.00


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.


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.

Wednesday, October 17, 2012

Sleep Issues -- Common in Gulf War Veterans -- Linked to Disease in Health People

Veterans suffering from Gulf War Illness have long complained about sleep problems, including feeling unrefreshed even after long periods of sleep, fragmented sleep, chronic fatigue, and even sleep apneas and narcolepsy.

In September 2010, I wrote a short series of blog posts about Gulf War veterans' symptoms, including some of my personal experiences as an ill Gulf War veteran.  One focused on sleep issues, and another on neurological symptoms and consequences and Gulf War neurotoxic exposures.   And, an August 2010 study found that use of CPAP machine helped not only Gulf War veterans' sleep issues, but other GWI symptoms as well.  

Now, a new study published this week, below, provides new evidence that insufficient sleep can result in even more serious health consequences even in otherwise healthy people.  

A number of medical treatment and treatment target development studies funded by the treatment-focused Gulf War Illness Congressionally Directed Medical Research Program (CDMRP) have had GWI sleep issues as their focus.  Two are currently seeking study participants, including one at the University of Wisconsin-Madison and another at the University of Utah in Salt Lake City.

The UW-Madison study, "Homeostatic and Circadian Abnormalities in Sleep and Arousal in Gulf War Syndrome," is led by Dr. Timothy Juergens, who specializes in sleep medicine for veterans.  (GW093035)  Information about how to participate will be forthcoming here on 91outcomes.

The Utah study, led by Dr. Yoshio Nakamura, is entitled, "Investigating Clinical Benefits of a Novel Sleep-Focused, Mind-Body Program on Gulf War Illness Symptoms: An Exploratory Randomized Controlled Trial." (GW100068)  This study is actively seeking ill Gulf War veteran participants.  

Another pending CDMRP study is focused on metabolic syndrome.  Metabolic syndrome, a group of risk factors that can lead to diabetes and other serious health outcomes, and which has now been linked in the newly published sleep study (below) to inadequate sleep.  It's not yet recruiting.  

More information about many ongoing medical studies specifically focused on Gulf War Illness can be found at  


Source:  CNN's

Sleep deprivation increases risk of serious health problems

By Amanda Gardner,
updated 6:10 AM EDT, Tue October 16, 2012

( -- People who consistently get too little sleep face bigger concerns than daytime fatigue and crankiness. Over the long term, sleep deprivation also increases the risk of serious health problems including obesity and type II diabetes.
Scientists have come up with a number of plausible explanations for this increased risk. Various studies have shown, for instance, that how much we sleep can affect blood sugar levels, hormones that control appetite, and even the brain's perception of high-calorie foods.
A small new study, published Monday in the Annals of Internal Medicine, adds a key piece to the puzzle by drilling down to the cellular level: Sleep deprivation, the study found, impairs the ability of fat cells to respond to insulin, a hormone that regulates metabolism and is involved in diabetes.
In the study, seven healthy young men and women spent a total of eight days and nights in a sleep lab. They were allowed to sleep normally on four of the nights, and on the other nights they were limited to just 4.5 hours. In order to neutralize the effects of appetite or overeating, the researchers strictly controlled the participants' meals and calorie intake.

After the four nights of sleep deprivation, blood tests revealed that the participants' overall insulin sensitivity was 16% lower, on average, than after the nights of normal sleep. Moreover, their fat cells' sensitivity to insulin dropped by 30%, to levels typically seen in people who are obese or who have diabetes.
"This is the equivalent of metabolically aging someone 10 to 20 years just from four nights of partial sleep restriction," says Matthew Brady, the senior author of the study and an associate professor of medicine at the University of Chicago. "Fat cells need sleep, and when they don't get enough sleep, they become metabolically groggy."
Specifically, the participants' fat cells -- which were collected via biopsy and analyzed -- required nearly three times as much insulin to activate an enzyme known as Akt, which plays a crucial role in regulating blood sugar. If insulin resistance of this sort becomes persistent, excess sugar and cholesterol can accumulate in the blood, increasing the risk of diabetes and heart disease.
Previous sleep-lab studies have found that insufficient sleep can affect overall insulin sensitivity, but this is the first to identify a concrete cellular mechanism that might underlie the well-established links between sleep, diabetes and obesity.
"This takes the research on the effect of sleep deprivation on metabolism one step further, by revealing a molecular mechanism involved in the reduction of total body insulin sensitivity," says Dr. Nathaniel F. Watson, co-director of the University of Washington Medicine Sleep Center, in Seattle, who was not involved in the study.
"If you want to make a causal argument that short sleep is causing diabetes," Watson adds, "one of the key elements is coming up with a physiological mechanism by which this would happen."
Brady and his coauthors aren't yet sure how exactly fat cells recognize and register sleep deprivation. One possibility, they say, is that lack of sleep triggers the body's stress response, leading to the release of the stress hormones cortisol and norepinephrine, which are associated with insulin resistance.
The new findings will need to be confirmed in different populations and settings. The study included only seven people (and just one woman), and they were all young, healthy, and lean, so the results can't necessarily be extrapolated to people who are older or overweight.
Likewise, the sleep deprivation in the study was relatively drastic and short-lived. It's unclear whether less severe sleep deprivation over longer periods of time -- a more common real-world scenario -- would have the same effect on fat cells.
If the results are borne out in the future, the good news is that the treatment for the type of insulin resistance seen in the study is straightforward: sleep more.
Sleep is "as important to your health as a healthy diet and exercise," Watson says. "Until somebody invents a procedure or a pill that's going to approximate all aspects of sleep, really what you're left with is what is a pretty simple treatment... Just turn off the computer and go to bed earlier."