SPRING 2010 i

VA RESEARCH

Newtechnologyforspinalcordinjury,limbloss

TBI-PTSD:Helpingclinicianstowardbetterdiagnosis

andtreatment

Lookingback—andahead—atVAcomparativeeffectiveness

research

Polytrauma:Focusonfamilycare

Personalizedmedicine:Whatthefutureholds

To day

Building on 85 Years of Discovery, Innovation, and Advancement 

SPRING 2010 Published in commemoration of the 85th anniversary of VA Research
m E SSAGE

A dIffERENt woRld, yEt AN ENduRING 

CommItmENt to VEtERANS

Eighty-five years ago, the first generation of VA researchers began publishing the 

U.S. Veterans’ Bureau Medical Bulletin to “promote research along practical lines.” 

Today, we live in a different world. Medical research, in particular, has advanced beyond 

anything those early Va researchers could have imagined. yet one thing has not changed: 

The research conducted by the department of Veterans affairs is designed to be practical, 

and it is wholly focused on Veterans’ needs. It is designed to directly address the health issues 

affecting Veterans and improve their lives in tangible, significant ways. 

This publication, which we’ve called VA Research Today, helps tell our story. The magazine 

was produced to help commemorate the 85th anniversary of Va Research, which is the 

theme of National Va Research Week 2010. 

The articles in this magazine speak to the tremendous spirit of discovery, innovation, and 

advancement that has characterized Va research for so many decades. Some of the stories 

showcase state-of-the-art technology we are developing—such as advanced prosthetic 

devices, or new electrodes for implantation in the brain. other articles tell of innovative 

studies that have already made a difference in the lives of Veterans—for example, those with 

chronic obstructive pulmonary disease, or serious mental illness. other features explain 

work in progress that aims to revolutionize cancer treatment, for instance, or greatly improve 

the diagnosis and treatment of traumatic brain injury or posttraumatic stress disorder. 

you’ll also find inspiring stories of Veterans who have returned from combat in Iraq and 

afghanistan with polytrauma injuries and read how Va researchers are learning the best 

ways to involve family members in their care. 

The common theme throughout these pages is the focus on Veterans. as it was in 1925, 

so it is in 2010. 

We hope you enjoy this magazine and gain a new understanding of the scope and impact 

of the work being done by talented, dedicated investigators at Va medical centers 

nationwide. Thanks to their brilliant efforts, and the many Veterans who volunteer to 

take part in Va research, we proudly carry forth our longstanding tradition of discovery, 

innovation, and advancement. 

Sincerely, 

Joel Kupersmith, Md 

Chief Research and Development Officer 

Veterans Health Administration 
C o N t E N t S

85 yEARS of dISCoVERy, INNoVAtIoN, ANd AdVANCEmENt

2 aPT Center is home to emerging technology for Veterans with disabilities 

From ‘smart’ electrodes to electric bandages, APT researchers are creating a new generation 

of adaptive and therapeutic devices

6 From cancer to cardiology, Nobel-winning scientist is closing in on cures 

Dr. Andrew Schally is still going strong in VA after nearly five decades of groundbreaking research 

9 Facing down CoPd: Learning to live with chronic lung ailments 

A trial at the Phoenix VA and 21 other sites is teaching Veterans better ways of coping 

with chronic obstructive pulmonary disease

13 Genomics research: Paving the way to personalized care

VA researchers are helping to unlock genetic keys to health risks and treatment responses

18 Lifelong disability can’t keep her down 

Determination and a soaring spirit underpin Dr. Lisa Hannold’s work on behalf of injured Veterans

21 Research targets wars’ signature injuries 

Researchers are probing new types of brain scans and other tools to boost diagnosis and treatment 

for traumatic brain injury and posttraumatic stress disorder

34 Va’s Cooperative Studies Program: Large-scale trials to inform 

evidence-based medicine 

From heart disease to mental health, CSP comparative effectiveness trials and other studies 

yield valuable data to help guide health care for VA and the nation 

38 Major meeting marks milestone for Va research on women’s health 

Top experts are gathering to help plan the next steps for VA women’s care 

41 a biohybrid approach to rebuilding the body 

At VA’s Center for Restorative and Regenerative Medicine, leading-edge scientists are working 

on innovative ways to help injured Veterans regain their independence

46 Brain banks—providing precious clues about why a brain breaks down 

A collection of specimens at the Bedford VA is providing insights on Alzheimer’s disease and traumatic 

brain injury 

50 Exploring the family’s role in helping severely wounded Veterans 

Caregivers and family members are at the heart of new polytrauma research 

54 Managing medications made easier 

Patients with serious mental illness may benefit from a new pharmacy approach, says a study 

at the Ann Arbor VA

27 Historical milestones

30 Program overview

32 Resources

58 National Va Research Week awardees

62 Recent advances

FeATureSTorIeS ABouTVAreSeArcH

21 27

Forquestionsoradditionalcopiescontact:

r&Dcommunications(12)

103SouthGayStreet,Ste.517

Baltimore,MD21202

(410)962-1800x223

research.publications@va.gov

Cover: Navy Veteran and VA employee David 

Haldane (left) and research assistant Doug 

Benedicto test the Lokomat—a robotic treadmill 

that supports the patient's weight and helps 

restore walking ability after certain types of 

injury—at VA's Center for Restorative and 

Regenerative Medicine. See feature on page 41. 
2 VA R E S E A R C H T O D AY

t E CHN o l o G y

APt CENtER IS HomE to EmERGING tECHNoloGy 

foR VEtERANS wItH dISAbIlItIES

From ‘smart’ electrodes to electric bandages, APT researchers are creating a new generation 

of adaptive and therapeutic devices

What goes on at the advanced Platform Technology 

(aPT) Center might sound more like something 

out of a novel by asimov or Heinlein. at this research 

center of excellence, based at the Louis Stokes Va in 

Cleveland, some scientists and engineers are developing 

a material that can mimic brain tissue. others are 

refining a muscle-powered brace that could allow 

paraplegics to walk easily and climb stairs. Still others 

are creating disposable electric bandages for wounds 

that won’t heal, and artificial limbs that sync up with 

the nervous system.

“We try to capitalize on advances in materials science 

and microelectronics, and focus them on the needs of 

Veterans with disabilities,” says aPT Center executive 

director Ronald Triolo, Phd. 

a case in point is a new type of electrode for use in 

brain-computer systems. Groups within Va and 

elsewhere are testing technology wherein electrodes 

are implanted in the brain to pick up signals that can 

be changed into commands for computers or robotic 

limbs. Electrodes like this already exist, but they have 

limitations: Because they are made of stiff silicon, they 

don’t fit well in the watery environment of the brain. 

an aPT Center team has created a material that 

softens once inside the brain, rendering it mechanically 

invisible. Results were published in Science in 2007. 

Now aPT director of research and scientific affairs 

Christian Zorman, Phd, and others are working out 

how to incorporate the new material into a device 

that can record neural activity or stimulate nerves. 

The device must be extremely small: 1 mm long and 

0.05 mm wide (by contrast, a sheet of paper is about 

0.1 mm thick). 

“If we can perfect the design, we hope to mass produce 

it, and at low cost,” says Zorman. “But the main 

attribute is the miniaturization, so a surgeon could 

implant many of these, and not just a few.” a prototype 

electrode is in preclinical testing. 

another early-stage project is the design of a wireless 

system for recording brain waves. In some people with 

epilepsy, brain tumors or brain injuries, neurologists 

pinpoint the damage by placing a grid of electrodes on 

the brain and reading the resulting waves. Currently, 

the electrode contacts are embedded in a silicone rubber 

sheet that is placed directly on the brain, with wires 

running from the sheet to the recording device. any 

tests using this grid require surgery, a hospital stay and 

precautionary antibiotics. aPT Center researchers 

want to make it possible to record brainwave 

information wirelessly, without needing to expose the 

brain or run wires. 
SPRING 2010 3

APT engineers are working on 

new devices to stimulate nerves 

and record brain-cell activity. 

Dr. Christian Zorman’s team is developing an 

electronics interface board, seen here, along with 

implantable brain electrodes that will be only 1 mm 

long and .05 mm wide. The board, external to the 

body, would allow brain signals from the implants 

to be decoded and used to control devices such as 

prosthetic limbs. 
4 VA R E S E A R C H T O D AY

Says Triolo, “If we could get this device to last for years, 

we could have something like a Holter monitor for brain 

disease.” (Holter monitors are used to track the heart’s 

electrical activity. Worn for days at a time, they have 

several electrodes that are taped to the patient’s chest.) 

This would revolutionize the field of neurology, asserts 

Triolo, providing continuous, long-term data on what’s 

going on in the brain. It also could improve patient 

selection for surgery and surgical accuracy. 

Like the grid of brain electrodes, other medical 

equipment doesn’t translate well to the battlefield, or 

the living room. Heart-lung machines can save lives, 

but only in the hospital. Center engineers are 

researching ways to create a portable heart-lung machine 

that could provide life-sustaining oxygen just about 

anywhere, at least until the patient could be transported 

to a medical center. 

Electrodes also are helpful—but unwieldy—when it 

comes to wound healing. For slow-healing wounds, the 

standard of care involves applying low-intensity current 

to the area. “It’s commonly accepted but not commonly 

used, and we think that’s because it’s so inconvenient,” 

Triolo says. Patients must receive treatment in a 

hospital, and placing the electrodes on fragile skin can 

be tricky. 

To solve the problem, aPT engineers are at work on an 

electronic bandage. “If we can combine the electrical 

current with a bandage and make it disposable, we’d 

have a sterile, occlusive dressing,” says lead investigator 

Kath Bogie, d.Phil. “The bandage would apply current 

through the wound until the battery wore down. It 

could then be thrown out and replaced.” 

Veteran Don Crago (center) has been helping APT engineers test a 

dynamic brace that uses electrical stimulation to excite paralyzed 

muscles and controllers that lock and unlock leg joints, allowing patients 

to walk after full or partial paralysis. With Crago are Dr. Musa Audu, 

Curtis To, Rudi Kobetic and Thomas Bulea. The inset shows the brace 

with the knee joint in the unlocked (sitting ) position. 
once made, the bandage might be easily tweaked 

into a wireless patch for pain control. Transcutaneous 

electrical nerve stimulation (TENS) is used to treat 

chronic pain, but portable units have electrodes 

and wires that keep the system—and the patient—

homebound. “We might be able to make a disposable 

TENS patch that would relieve pain for a week,” 

notes Bogie. “and thanks to wireless technology, a 

physician could change the type and pattern of electrical 

stimulation as easily as he or she makes a phone call.” 

Given the number of Veterans affected by partial or 

total limb loss, a main focus of the aPT Center is 

prosthetics and orthotics. Several ongoing projects 

aim to find ways to restore some sense of feeling to 

the residual limb. By activating nerves in the residual 

limb, says lead researcher dustin Tyler, Phd, “We 

hope to provide some sense of how hard the prosthesis 

is squeezing something, for example, and where the 

prosthesis is in relation to the rest of the body.” 

By combining multiple disciplines and technologies, an 

orthotics project led by Triolo hopes to build a better 

brace, one that would allow a paralyzed Veteran to walk 

at variable speed and climb stairs. 

Today’s full-leg braces—called reciprocating gait 

orthotics—are designed to help paraplegics to stand and 

walk in a straight line over a level surface. The braces 

are constructed such that when one leg extends, the 

other flexes. “Walking is slow and awkward, and not 

cosmetic or functional,” says Triolo. “you can’t 

go up a curb, or up or down steps.”

The center’s biomedical engineers, working 

with a robotics lab at Case Western Reserve 

University, are developing a more dynamic 

brace. The ankle, knee and hip joints can be 

locked and unlocked using a small, wearable 

computer. The group also is working on 

hydraulics that slowly release the knee joints. 

Lock one hip, unlock the other and flex the 

knee slowly, and stairs become possible.

The brace also uses electrical stimulation to excite 

paralyzed muscles, inciting movement and avoiding the 

need for a bulky battery.

Veteran don Crago, 48, is one of two people testing 

the brace at the center. Crago was paralyzed from the 

chest down in an automobile accident in 1983. He’s 

adept with a wheelchair, but limitations abound. This 

past winter, Crago was able to go down the slopes at a 

Maryland resort on a monoski, but had to be carried up 

a set of stairs to a restaurant that night.

Crago has been testing the brace technology with aPT 

researchers for three years. “The first time [the brace] 

worked for me, it felt great,” he remembers. “It was like 

my steps were effortless. It’s still a prototype, but when it 

works, it feels really stable.”

The brace is still too heavy and continues to be refined, 

says co-investigator Rudi Kobetic, MS. one day, aPT 

researchers hope it will be ready for technology transfer 

and eventual U.S. Food and drug administration 

approval, making it an option for the hundreds of 

thousands of americans who are paralyzed due to spinal 

cord injury or disease. 

Another APT device in the works: a micromachined 

artificial lung with air inlet and outlet ports and tiny 

channels for blood and air flow. 
6 VA R E S E A R C H T O D AY

d I S C o V E R y

fRom CANCER to CARdIoloGy, NobEl-wINNING 

SCIENtISt IS CloSING IN oN CuRES 

Dr. Andrew Schally is still going strong in VA after nearly five decades 

of groundbreaking research 

Va distinguished Medical Research Scientist and 

University of Miami researcher dr. andrew Schally 

may not yet have found the fabled “cure for cancer,” 

but he’s come about as close as any medical researcher. 

Nowadays, at age 80-plus, this winner of the 1977 

Nobel Prize in Physiology or Medicine is hot on the 

trail of compounds he believes will revolutionize 

cancer treatment. But over his decades-long career, 

Schally has been credited with weighty advances in 

a wide range of additional specialties—among them, 

gynecology, gastroenterology and endocrinology. and 

now, cardiology can be added to the list (see sidebar 

on page 8). all told, the European-born scientist and 

proud naturalized american for 48 years has published 

more than 2,200 papers, more than 1,200 of them after 

winning the Nobel Prize.

Schally is a “national asset,” says Norman Block, Md, 

a 30-year professional colleague of Schally’s who gave 

up his surgical career in urology about five years ago to 

support the Nobel laureate’s research full-time. “It was 

an easy choice,” says Block of his professional transition. 

“doing surgery, I was helping one person a day to stay 

alive. Working with dr. Schally, I may be helping a 

couple of hundred a day to stay alive.” 

Joining Va in 1962, Schally set up a lab devoted 

to research on the hypothalamus. His early work 

established the fact that the pituitary gland and certain 

other glands of the endocrine system are regulated by 

the region in the brain called the hypothalamus. This 

work, which has been called the foundation of modern 

endocrinology, earned him his Nobel in 1977. The 

prize was shared with Rosalyn yalow, a friend and Va 

colleague who pioneered the field of radioimmunoassay, 

and hormone researcher Roger Guillemin. 

In those early years, Schally’s focus was in the field of 

human reproduction, leading to the development of 

both fertility and contraceptive compounds. His work 

since then has pyramided on these initial scientific 

breakthroughs. It’s his scientific curiosity, Schally says, 

that has fueled his long line of achievements in medical 

science. “This is a trait I still have,” says the scientist. “I 

want to know how nature controls these mechanisms.” 

It was this curiosity—along with a strong sense of 

ethical responsibility as a scientist—that in the 1970s 

caused Schally to shift the focus of his earliest hormone 

research from reproductive health to oncology. “I began 

to see the role of hormones in breast and prostate cancer 

was much greater than originally demonstrated,” he 
SPRING 2010 7

“I want to know how nature 

controls these mechanisms.”

remembers. “We had patients with various tumors. 

We could inject our hormones and show inhibition 

of the tumor. So I realized I would be a fool—even 

scientifically criminal—to not use in oncology some 

 of the hormones which I discovered in the brain.” 

Harnessing anti-cancer hormones

one example of Schally’s revolutionary discoveries 

in the fight against cancer: The current treatment 

for testosterone-dependent prostate cancer—used 

successfully in hundreds of thousands of men around 

the world—is derived from a brain chemical called 

luteinizing hormone-releasing hormone (LHRH), 

which he discovered. Schally calls LHRH the “biggest 

prize” of his long career. “after I gave my lecture on the 

discovery of LHRH to 2,000 people in San Francisco in 

June of 1971,” Schally recalls, “the audience disappeared 

suddenly to phone the structure all over the world, in 

view of its expected medical importance.” 

More recently, a Schally-led research team found that a 

synthetic compound called JMR-132 stops the spread 

of human prostate cancer cells and also acts as a strong 

antioxidant. Like some other compounds that Schally 

has explored, the compound works as an antagonist to a 

tumor-nourishing natural body chemical called growth 

hormone-releasing hormone.

Schally has studied thousands of potential therapies, 

including analogs—modified compounds that can 

pack 100 times the punch of natural hormones—and 

out of this far-reaching investigation has created 

several auspicious cancer therapies. Schally is now 

exploring hormone-based treatments for breast, 

ovarian, pancreatic, lung and other tumors, and his 

team is involved in several clinical trials of hormonebased therapies. “I believe we are very, very close to 

new methods for cancer treatment,” says Schally, who 

recently received a Meritorious Service award from Va 

for his work on innovative cancer therapies. 

Dr. Andrew Schally, with VA Research since 1962, has won a Nobel Prize and numerous other awards for his biomedical discoveries. 
8 VA R E S E A R C H T O D AY

Schally is now set on developing “smart” chemotherapies 

to zap cancer cells while leaving surrounding tissue 

unscathed. While Schally is careful to distinguish 

between effective treatments and “cures,” he brims 

with excitement when describing this latest work. “The 

beauty of these methods is that they are targeted to 

tumors,” says Schally of his approach, which combines 

cancer drugs with synthetic versions of hormones 

and then hunts down tumors that have receptors for 

those hormones. “They go to the tumor and they can 

destroy malignant cells. If you repeat it two, three times, 

you can perhaps totally destroy the tumor. In such a 

case, you have a treatment that comes very close to 

being a cure.” 

A half-century of uninterrupted research

In all, Schally is approaching 50 years in his Va research 

career, without any interruption worth mentioning. 

When Hurricane Katrina threatened to disturb his work, 

then based at the New orleans Va Medical Center, 

Schally moved to the Miami Va to avoid disruption, 

telling a reporter from the Sun Sentinel in Fort 

Lauderdale, “What worried me most was my research 

would come to a standstill for two or three months. It’s a 

tremendous relief to be among friends and be able to do 

something practical to continue my research.” 

one of the friends welcoming Schally to Miami was 

urologist Block, who calls Schally a “genius,” but stresses 

his kindness above all. “It’s unbelievable that the same 

person can have his credentials and accomplishments 

and be so caring.” The Nobel laureate’s self-described 

“hardest blow and the biggest tragedy in my life” came 

with the death in 2004 of the person he cared most 

about—his wife of 28 years, ana Maria ComaruSchally, Md, an endocrinologist and his research 

partner for many years. Schally’s solace after her 

death, he has written, came from his ongoing medical 

investigation: “I am seeking consolation and comfort by 

continuing my work in cancer research.” 

While he continues to work as hard as ever, Schally 

also finds time to relax—watching soccer, and carving 

out time in his pressing schedule to swim a mile several 

days each week. He shows no sign of slowing down. 

“I am in good health,” says Schally, “and Nobelists 

never retire.” 

Heart-protective 

compound identified 

In a potentially important advance in the study of congestive 

heart failure—a leading cause of disability—Dr. Andrew 

Schally and his University of Miami colleagues have found 

a compound that sparked major recovery in rats after heart 

attack, which often leads to heart failure. The compound is a 

derivative of growth hormone-releasing hormone (GHRH), and 

the research team’s findings were published earlier this year in 

the Proceedings of the National Academy of Sciences.

Schally has studied GHRH extensively for its cancer-fighting 

potential, and his laboratory synthesized the compound used 

in this study. He and his colleagues plan to study the 

mechanisms further so they can move the compound into 

human testing, and Schally predicts that GHRH will prove able 

to repair the heart in humans, too. “This should be possible 

in human beings because the hormone works well in all 

species,” Schally says. In a University of Miami press release, 

the study’s principal investigator, Joshua Hare, MD, said, 

“This discovery is a major step forward in harnessing a new 

therapeutic opportunity for heart disease that avoids unwanted 

side effects.” 
SPRING 2010 9

E d u C A t I o N

fACING dowN CoPd: lEARNING to lIVE wItH CHRoNIC 

luNG AIlmENtS

A trial at the Phoenix VA and 21 other sites is teaching Veterans better ways of coping 

with chronic obstructive pulmonary disease

ron Greenberg is a Korean War Veteran and a retired 

newspaper pressman. He’s sung in musicals and 

coached baseball, and he loves to golf. Greenberg, 76, 

is a “wherever you are, that’s where you’re supposed 

to be” kind of person. But when chronic obstructive 

pulmonary disease (CoPd) took hold, Greenberg 

found himself intimately acquainted with a place that 

no one really wants to be: a hospital emergency room. 

He visited the Phoenix Va Medical Center ER four 

days in a row. on the fourth day, he met Pat Jacobs.

Jacobs is the Phoenix coordinator of a five-year Va study 

on the effects of patient education and case management 

on hospitalizations for CoPd. The Phoenix center, one 

of 22 Va study sites, enrolled 59 Veterans. 

after joining the study in November 2007, Greenberg 

spent a couple of hours each week reviewing patient 

education information with Jacobs. He learned what 

CoPd was, how his medicines worked, and how to 

handle flare-ups. He also received case management that 

included 24/7 support. Jacobs gave out her cell-phone 

number and email address to the Veterans. “If they got 

in trouble or had a question, they called me,” she says. 

When John Snyder joined the study in august 2008, 

he’d had five years of treatment for his CoPd. Snyder 

got around via scooter. “I couldn’t really walk. I was 

always out of breath,” he recalls. 

John Snyder has been able to stay more active since taking part in a VA 

study aimed at improving care and self-management for COPD. 
10 V A R E S E A R C H T O D AY

The study helped him in two ways: It taught him about 

his condition and what he could do to control it, and 

helped him get his medications in order. 

“I was on the wrong medications, and wasn’t taking them 

properly,” he said. Snyder was taking inhaled steroids up 

to six times a day before he entered the study. Now he 

takes them once a day, always at the same time. “I have 

specific times to take everything, and I’m consistent with 

that, which has helped enormously,” he says.

Jacobs, the study coordinator, explains that fine-tuning 

medication regimens for CoPd can often be tricky 

and involves a learning curve for patients. In the study, 

she spent up to two hours a week one-on-one with 

patients. “I think it’s the individual attention as much as 

anything that helped,” she says. 

another stumbling block for Snyder—and for many 

with CoPd—was anxiety. Not surprisingly, he became 

anxious when it became difficult to breathe. He learned 

that giving in to the fear only made things worse, and 

practiced techniques to calm himself.

“I tell myself, ‘all right Snyder, take over, don’t let it 

rule you. Stay calm and use some common sense’,” he 

says. “and that pulls me out of it. you don’t learn that 

one overnight, that’s for sure. But taking control has 

changed my life.”

The education materials helped immensely, says study 

participant david Richards, 74. “you read them, practice 

what is said, and there’s no reason you won’t get better.” 

Richards had been relying on a scooter to get around 

since 1999. When he entered the study in January 2007, 

he had been in and out of the hospital several times each 

year with bronchitis.

He also wasn’t taking his medications properly, and 

he didn’t know when to rest. “The study helped me 

understand what CoPd was and how it worked,” 

says Richards. “I learned to know my limitations and 

control the CoPd without it controlling me.”

after seven months in the study, Richards was walking 

again. He sold the scooter in 2008. “I’m 100 percent 

better. I can do housework and laundry and shopping. 

I walk on a treadmill. Before, I couldn’t take a shower 

without resting.”

another study volunteer, Paul Glessing, says the study 

taught him how to be kinder to himself. “you have to be 

your own best friend,” he reflects. “There are bumps in 

the road, and you have to resolve them.”

“You have to be your own best friend,” says Paul Glessing, 82, about looking after his health and coping with COPD. 
SPRING 2010 11

Top: Ron Greenberg, 76, is back on the golf 

course, able to play nine holes, since learning 

how to better manage his COPD. 

Left: Dave Richards, 74, says the VA study 

has helped him regain the ability to exercise, 

do household chores and get around without 

a scooter. 

The Veterans learned what 

COPD was, how their 

medicines worked, and how 

to handle flare-ups.
12 V A R E S E A R C H T O D AY

COPD at a glance

Try breathing through a drinking straw, and you’ll have some 

idea what it’s like to have chronic obstructive pulmonary 

disease (COPD). COPD is an umbrella term for a group of 

lung diseases that complicate breathing. The most common 

types are emphysema and chronic bronchitis. (Asthma is not 

included in the definition of COPD, however.) People with COPD 

usually have several of these symptoms:

Shortness of breath

Tiredness

Wheezing

Coughing

Coughing up mucus (phlegm)

Frequent lung infections

Between 80 and 90 percent of COPD cases are caused by 

smoking. Air pollution, frequent childhood lung infections, 

secondhand smoke, and rare genetic diseases also can 

cause COPD. 

According to the National Heart, Lung, and Blood Institute, 

COPD affects about 24 million people, but only half have been 

diagnosed. About 13 percent of adults in nursing homes, and 6 

percent of adults outside nursing homes, have the disease.

COPD has been linked with lung infections, high blood 

pressure, heart problems, lung cancer and depression. It is 

the fourth-leading cause of death in the U.S. (behind heart 

disease, cancer and stroke), causing more than 120,000 

deaths each year and about 670,000 hospitalizations.

Glessing, 82, found himself in critical care at least 

once a year due to his CoPd. after entering the study 

in august 2007, he attended his first support-group 

meeting, The study requires that Veterans attend at 

least one such meeting, but Glessing kept coming back. 

“you never leave without picking up at least one thing 

that might help,” he says. 

The other patients agree. “In the group, I learned what 

worked for other guys, and you’re grateful for that,” says 

Snyder. “you bring your own experience to bear too, in 

case it can help someone else.” 

The four found the group meetings so useful that 

they chose to meet monthly long after their study 

requirements had been met. Now they are working with 

Jacobs on establishing an ongoing group for Veterans 

with CoPd at the Phoenix Va. The group would 

include an educational component. “They’re going to be 

doing some of the teaching,” says Jacobs. “They know 

they can be of help to other people with CoPd.”

Richard Robbins, Md, the site principal investigator 

for the study, adds that “programs stressing patient 

education are of great benefit to our Veterans and have 

been shown to improve their quality of life.” 

He notes that the Phoenix Va has one of the highest 

admission rates in the country for CoPd. Part of it 

is demographics—many older retirees live in the area. 

also, arizona’s dry air has made the area a target locale 

for those with lung and sinus problems. 

Even with decades of experience as a respiratory 

therapist, Jacobs was surprised at the positive changes 

seen in the study. She believes that if the education and 

case management strategies could be applied around the 

country, they could bring measurable improvements for 

people with CoPd. 

“Case management is done all the time in diabetes and 

I think it’s feasible to do on a large-scale basis [with 

CoPd patients]. It’s the idea that you have someone you 

can call whenever you need it.” 

also, she notes: “We started this study with people who 

were very sick. These Veterans could not walk. If we 

could provide education and support when people are 

first diagnosed, I think we’d see an extension of life and 

an improvement in quality of life.” 

The study outcome won’t be known for at least a year, 

but the program already has changed at least four lives. 

“I’m proud to be a Veteran and to know these people,” 

says Glessing. “I didn’t think I’d live this long.”
SPRING 2010 13

GEN o m I C S

GENomICS RESEARCH: PAVING tHE wAy 

to PERSoNAlIzEd CARE

VA researchers are helping to unlock genetic keys to health risks and treatment responses

Finding out in her early 20s about a gene that puts her 

at extremely high risk for some types of cancer was 

more of a blessing than a blow to Lisa Collins, says the 

now-25-year-old air Force Veteran whose mother was 

diagnosed with breast cancer in her 30s and experienced 

a recurrence several years later. 

Collins discovered, through testing at the Tampa 

Va Medical Center, that she has a variant of the 

gene BRCa1 that compounds her risk for breast and 

ovarian cancer. Normally, the gene suppresses tumors; 

a change in it can have the opposite effect. “[The BRCa 

mutation] isn’t a good thing, but being enlightened 

about it is,” says Collins, who is now using strategies 

recommended by her Va health care providers to try to 

preserve her health. 

Va scientists specializing in the field of genomics 

are hunting down disease-associated genes and gene 

mutations, such as the one affecting Collins, to improve 

Veterans’ health. New discoveries in this area can enhance 

screening and diagnosis and point toward more effective 

therapies. Some cancers, for instance, may be shut down 

by subduing a damaging gene or activating a beneficial 

one. advances in genomics could also help predict a 

person’s response to a medication or other treatment.

Joel Kupersmith, Md, Va’s chief research and 

development officer, says the role of genomics in 

medical research during the coming years can’t be overemphasized. “The future of medicine is determined by 

research, and genomics is the direction for research in 

the 21st century.” 

The more researchers learn about the effects of different 

genetic variations, the better doctors will be able 

to individualize care—in terms of both treatment 

and prevention. For her part, Collins gets an annual 

mammogram to screen for breast cancer. That’s more 

frequent and earlier in life than what is recommended 

for average-risk women. Moreover, Collins says she is 

leaning toward a double mastectomy within the next 

year. To thwart ovarian cancer, she gets a twice-a-year 

Weleetka Carter works with DNA samples at the Pharmacogenomics 

Analysis Lab at the Little Rock VA Medical Center. 
14 V A R E S E A R C H T O D AY

screening ultrasound and may choose to have her ovaries 

removed by the time she’s 35. “True, this is a huge ordeal 

for any woman to have to go through, especially at 

my age,” she reflects. “But so many people are walking 

around with no clue about their risk and their cancer is 

detected too late.” 

Today’s medical literature is replete with new discoveries 

relating to genes and disease, particularly with regard 

to cancer. For example, one team of Va researchers 

recently found that genetic variations associated with 

a protein called macrophage migration inhibitory 

factor may signal an increased risk for prostate cancer 

recurrence. another Va team found that while one 

variant of the BC12 gene is generally associated with 

longer survival in patients with kidney cancer, another 

variant of the gene may actually predict worse outcomes.

But experts say research has just skimmed the surface 

of the potential of genomics in disease prevention and 

treatment. Va’s ongoing research in this area includes 

studies of: 

 Schizophrenia and bipolar disorder. In what is 

expected to be one of the largest studies of its kind 

to date, a Va-funded research team will probe the 

genetic basis of schizophrenia and bipolar disorder, 

which together affect some 170,000 patients in Va’s 

health system. Researchers will scan dNa from up 

to 38,000 Veterans at some 25 Va sites, looking for 

gene variants found in those with mental illness but 

not in others. 

Lou Gehrig’s disease. Va researchers are seeking 

to identify genes that contribute to the risk of 

amyotrophic lateral sclerosis (aLS), commonly 

known as Lou Gehrig’s disease. The study is also 

evaluating possible environmental triggers by looking 

at participants’ family and medical histories, diets, 

medications, and exposures to toxins. 

Posttraumatic stress disorder. Va researchers are 

working to identify genes that may affect how service 

members cope with deployment and combat. By 

conducting clinical assessments in those affected by 

combat-related PTSd and analyzing their genetic 

samples, researchers hope to pinpoint genetic variants 

that contribute to PTSd and other post-deployment 

adjustment disorders, such as depression. 

New technology speeds quest for disease-linked genes

There’s only a small portion of our dNa—less than one 

percent—that’s of special interest to researchers. That’s 

where individual variations called SNPs (pronounced 

“snips”) occur. SNPs—short for single nucleotide 

At VA’s Pharmacogenomics Analysis Lab, this carrier contains slides loaded with common gene variants and DNA from research volunteers. A laser 

scanner will detect matches and help researchers learn which variants are linked to which health conditions. The slides are bar-coded for privacy. 
SPRING 2010 15

polymorphisms—are changes in one of the chemical 

bases that make up the dNa sequence, such as guanine 

or cytosine. Some of these changes might be of little 

consequence. others might raise our risk for a serious 

disease. There are millions of these SNPs—among 

the three billion chemical base pairs that make up our 

dNa—so finding the critical ones is like finding the 

proverbial needle in the haystack. But thanks to recent 

advances in technology, researchers are able to make far 

quicker progress than they could even just a few years ago. 

“We can do in a few weeks what we couldn’t do in 

years,” says Steven Schichman, Md, Phd, director of 

the Pharmacogenomics analysis Lab at the Little Rock 

Va Medical Center. “We’re using technology 

that enables you to simultaneously detect a million 

SNPs at a time in the genome [the entire genetic 

material] of a person.” 

detecting SNPs in an individual patient is one thing. 

Solving the mystery of which SNPs have crucial health 

effects is another. 

anjanette Stone, a biomedical technician who helps 

run Schichman’s lab, explains: “you have to study 

hundreds of patients to see if there’s a ‘phenotypic’ effect 

to a particular SNP. That polymorphism may not do 

As many as a million Veterans expected to take part in ‘MVP’ 

A major initiative called the Million Veteran Program (MVP) is 

being launched this year in VA to gain new knowledge about 

the role of genes in health. The study is expected to involve as 

many as a million Veterans over the next five to seven years. 

According to VA deputy chief research and development 

officer Timothy J. O’Leary, MD, PhD, the effort will be among 

the largest of its kind to date, worldwide. “We have a unique 

opportunity in VA to make discoveries in this area that will 

impact not only the care we provide to Veterans, but medical 

care in general,” he says. “This opportunity stems, in large 

part, from the altruistic volunteering of so many VA patients 

who become involved in research because they want to 

help make a difference for others. The generosity of today’s 

Veterans who become part of this effort will improve the 

health care of tomorrow’s Veterans.” 

Volunteers in the study will donate a blood sample from which 

their DNA will be extracted. They’ll also fill out a survey about 

their health and health-related behaviors, and allow access 

to their VA medical records. The records will be added to the 

secure VA Central Research Database. By comparing the 

genetic profiles of large numbers of people and studying their 

health information—for example, which medical conditions 

they have, or how they respond to certain drugs—the 

researchers hope to pinpoint the genetic factors involved. This 

could lead to new treatments or preventive measures. 

More information about MVP will be available on the VA 

Research website (www.research.va.gov) later this year. 

Dr. Donald Humphries processes blood samples at VA’s Massachusetts 

Veterans Epidemiology Research and Information Center. The center 

will securely house DNA and data for the Million Veteran Program. 
16 V A R E S E A R C H T O D AY

To accommodate large-scale 

genomics studies, VA has 

created significant 

infrastructure at its 

Massachusetts Veterans 

Epidemiology Research 

and Information Center.
SPRING 2010 17

anything. It may not change a thing in your body. or 

it could: What if it changes an amino acid sequence in 

a protein, and it totally changes the function of that 

protein? once again, that may not do anything, or it 

may change how you metabolize a drug, for example. 

There could be many effects of a polymorphism, and the 

only way to understand them is to do these studies with 

huge numbers of patients.” 

The studies Stone refers to are called genome-wide 

association studies, in which dNa samples are obtained 

from large numbers of people with and without a 

particular disease. SNPs that show up more commonly 

in the affected population become prime suspects in 

the hunt for disease-related genes. The schizophrenia 

study mentioned above is one example. another is the 

Million Veteran Program, being launched by Va this 

year (see sidebar on page 15).

To accommodate these large-scale genomics studies, 

Va has created significant infrastructure at the 

Massachusetts Veterans Epidemiology Research and 

Information Center (MaVERIC), housed at the 

Boston Va. Several years ago, the facility began housing 

dNa samples from Veterans taking part in clinical 

trials through Va’s Cooperative Studies Program. More 

recently, the facility has been expanding into a stateof-the-art central biorepository for Va, adding robotic 

processing equipment and storage capacity as the agency 

ramps up its genomics program. MaVERIC is also 

developing a powerful data warehouse that will enable 

Va researchers to securely access and analyze genomic 

and other health data on millions of Veterans. 

Veterans express support for genomics research 

Large-scale Va genomics studies are possible only with 

the cooperation of many Veterans. In fact, a majority 

of Veterans who have received health care through Va 

would participate in genomics research, according to 

a recent Va-initiated study conducted by a group at 

Johns Hopkins University. Survey participants’ greatest 

concern was privacy. That issue is addressed through 

strict safeguards put in place by Va. For example, 

specimens from those participating in genomics studies 

are coded and “de-identified” so researchers don’t know 

who the specimen came from. The key that links the 

code to the identity is kept in a secure location and only 

a few authorized Va personnel have access to it. 

addressing concerns about privacy is just one of the 

challenges facing Va as its genomics program evolves. 

For example, Va has a state-of-the art computerized 

system of health records for its patients, but researchers 

still have to determine the best ways to incorporate 

genetic information into those records. a Genomic 

Medicine advisory Committee, made up of genetics 

experts and representatives from Veterans’ groups, helps 

guide Va on various issues related to the development of 

its Genomic Medicine Program, including privacy. 

While the use of genomic medicine is still limited in 

scope—within Va and in the U.S. generally—research 

in the field is growing, and genomics-based medical 

knowledge is increasingly playing a role in the lives 

of patients. 

Lisa Collins finds peace of mind in knowing she can 

take steps to minimize her risk of the disease for which 

her mother—cancer-free since 2004 and turning 50 in 

July—underwent arduous treatment. 

“With my risk being as high as it is, I can go through 

preventive treatment now, while I’m healthy and have 

the best support,” says the Veteran. “Being aware of a 

high risk for cancer makes it a fair fight.” She adds that 

she is passing along what’s she’s learned to her three 

sisters so they, too, can opt to take a preemptive stand 

against cancer. 

Christine Govans prepares to remove frozen biospecimens from a liquidnitrogen tank at VA’s Massachusetts Veterans Epidemiology Research 

and Information Center, housed at the Boston VA.
18 V A R E S E A R C H T O D AY

INdEPENdENCE

lIfEloNG dISAbIlIty CAN’t kEEP HER dowN

Determination and a soaring spirit underpin Dr. Lisa Hannold’s work on behalf 

of injured Veterans

When severely injured Veterans talk with Elizabeth 

(Lisa) Hannold, Phd, about “freedom,” she 

understands they are not talking about the same 

freedom they fought for on the battlefield. When they 

share their struggles, she empathizes, and they know 

they have found a friend.

an investigator at Va’s Rehabilitation outcomes 

Research Center (RoRC) in Gainesville, Fla., Hannold 

was born with a rare disease called spinal muscular 

atrophy. She has never walked, and as a result of severe 

curvature of the spine, she is only 4 feet 10 inches tall. 

Poor range of motion in her arms and overall weakness 

keep her from reaching and lifting everyday objects. She 

is prone to respiratory infections and fatigue. despite 

its physical impact, however, the disease does not affect 

the mind: People with the condition tend to be bright, 

sociable and highly verbal, and Hannold is no exception. 

Home-tutored from elementary through high school, 

Hannold attended Gannon University in her hometown 

of Erie, Pa., where she loved chemistry and biology. 

“Science was my thing,” she says. In her sophomore 

year, when a department chair refused to allow special 

accommodations for her to complete lab experiments—

he felt it gave her an unfair edge—Hannold gained a 

lesson that would steer her future career: “at the time, 

I was devastated, but it was one of those life-defining 

moments that really caused me to re-focus and find 

another way to accomplish my goals. It also showed me 

the importance of vocational evaluations and in-depth 

job exploration to enable people with disabilities to 

establish realistic work goals.” 

She switched her major to avoid having to meet lab 

requirements, earned her bachelor’s degree in 1986 and 

began looking into Phd programs in neuroscience and 

psychopharmacology. at the time, though, relatively 

few people with disabilities were in the sciences, and the 

issue of lab accommodations came up again. 

Rethinking her options, she enrolled in a residential 

independent living skills training program. She also 

began volunteering at a nearby center that provided 

similar services. after a week, she was offered a job 

there. Within two years, she became director of the 

independent living skills program at a complex of 

affordable, wheelchair-accessible apartments for people 

with disabilities. Hannold cites this as an example of 

how fate “always intervenes just as it is supposed to. My 

work experience provided a phenomenal foundation for 

my current research.”

While working full-time, she returned to Gannon 

to earn a master’s in counseling. She and her parents 

moved to Gainesville in 1999 so she could pursue a Phd 
SPRING 2010 19

“ Thinking outside the box is really important. 

When you have a disability, you are forced to 

think of different ways of doing things.” 

Dr. Lisa Hannold is an investigator at VA’s Rehabilitation Outcomes Research Center in Gainesville, Fla.

in rehabilitation science from the University of Florida. 

It was here she was introduced to Va: She was awarded a 

fellowship at the RoRC in 2002 and became a research 

health scientist at the center in 2004, after she earned 

her doctorate. 

In the years since, she has co-authored several publications and presentations about topics such as the effects 

of locomotor training. The therapy is used for patients 

with incomplete spinal cord injury: They walk on a 

treadmill, their body weight supported in a harness, and 

gradually improve their walking ability. Hannold has 

also studied how to redesign outcome measures so they 

incorporate the perspectives of disabled Veterans and 

address the issues they consider important. 

Last year, she received Va funding to study the 

challenges faced by Iraq and afghanistan Veterans with 

polytrauma as they reintegrate into the work force. She 

relies not only on her research expertise but also her 

unique personal perspective. “Historically, there has 

been a tendency in vocational rehab to get people with 

disabilities back to work immediately, but the necessary 

foundation of independent living skills is not always in 

place,” she reflects. “From my personal experience, it is 

imperative that individuals can meet their daily needs 
20 V A R E S E A R C H T O D AY

in the home and community first—independently or 

with support. If not, life falls apart and stacks the deck 

against success in the workplace.” 

The research is now in the pilot phase. Hannold and 

colleagues are interviewing small groups of Veterans, 

caregivers and service providers. The results will guide a 

larger proposal. “The goal of this work is to help answer 

several questions about the daily living skills of this 

unique Veteran population,” notes Hannold. “What’s 

easy? What’s difficult? What’s going well? What’s not? 

How will this translate to a work setting and successful 

employment?”

as Hannold’s research career moves forward, she is 

determined to help her colleagues with disabilities 

succeed as well. She organized a symposium at the 2009 

joint educational meeting of the american Congress of 

Rehabilitation Medicine and the american Society of 

Neurorehabilitation. Her event was titled “Rehabilitation 

Researchers with disabilities: Empowering Full 

Participation.” appropriately, it was simulated—in real 

time, to sync with the live meeting—in the Web-based 

virtual world known as Second Life so that researchers 

who couldn’t physically attend could still take part. 

Navy Veteran dan Parks, founder of the company 

Virtualis, had his team create a computer-generated 

conference space identical to the actual meeting 

setting. They custom-designed avatars—3d graphical 

representations of people—to resemble the panel 

members. Some panelists preferred to be designed 

without their assistive device, while others—

Hannold among them—wanted it included. “I love 

my wheelchair,” she says. “It’s an extension of me. It 

symbolizes my freedom.”

Hannold hopes the approach will be used for other 

conferences. “It was a remarkable opportunity for 

collaboration. Without this technology, none of us 

would have been able to participate.” She adds that 

“thinking outside of the box is really important. When 

you have a disability you are forced to think about 

different ways of doing things.” 

Hannold’s Va office is fairly typical, except for features 

such as a document turntable and voice-recognition 

equipment that helps her enter text into her computer. 

one item she is rarely without is her “elevator stick.” She 

jokes about it being “high-tech. It cost all of $1.50 for a 

wooden dowel with an eraser on the end. Without it, I 

can’t push elevator buttons or door-opener push pads!”

Now that her parents are aging—she calls them the 

“best caregivers anyone could ask for”—Hannold relies 

on a team of attendants to help with day-to-day activities 

such as showering and dressing. Hannold enjoys hiring 

and mentoring rehabilitation students as attendants.

Thinking about the future, she hopes to enjoy a long 

career with Va. “My dad is a Veteran, all of his brothers 

were Veterans, and so is my mom’s brother. I have 

always been interested in empowering Veterans, so 

I’d love to still be doing research at the Va many years 

from now.”

Left: When a company designed Hannold’s avatar for a virtual conference, she asked that her wheelchair be included: “It’s an extension of me. It 

symbolizes my freedom.” Right: In her office at the Gainesville VA, Hannold uses voice-recognition software that helps her enter text into her computer.
SPRING 2010 21

To help troops returning home from Iraq and Afghanistan with brain injuries, Drs. Mingxiong Huang (standing ) and Roland Lee at the VA San Diego 

Healthcare System are exploring new combinations of brain-imaging techniques. 

t b I & P t S d

RESEARCH tARGEtS wARS’ SIGNAtuRE INjuRIES

Researchers are probing new types of brain scans and other tools to boost diagnosis and 

treatment for traumatic brain injury and posttraumatic stress disorder

Since 2001, more than 1.6 million U.S. troops 

have been deployed to Iraq and afghanistan. The 

“signature injuries” of these wars—posttraumatic stress 

disorder (PTSd) and traumatic brain injury (TBI)—

can’t easily be diagnosed with a blood test, brain scan or 

other lab test. 

What’s more, they often co-occur: Nearly half of 

military personnel with TBI also report symptoms of 

PTSd. The association seems natural; the traumatic 

event of being injured in combat may induce PTSd 

in some cases. Though early reports showed that TBI 

protected against PTSd, perhaps due to the loss of 

consciousness and amnesia surrounding the trauma 

itself, newer research shows that two in five returning 

troops with mild TBI also have PTSd. Current 

thinking is that TBI might make someone more 

vulnerable to PTSd, or the two conditions might 

simply result from the same traumatic event. 

Currently, Va has a comprehensive screening process 

that aims to identify depression, substance abuse, TBI 

and PTSd. The screening is designed to cast a wide net.

“We don’t want to take the chance that we’re missing 

someone who needs attention,” says physician-researcher 

david Cifu, Md. Cifu is chief of physical medicine and 
22 V A R E S E A R C H T O D AY

rehabilitation at the Richmond Va Medical Center 

and chair and professor of the department of physical 

medicine and rehabilitation at Virginia Commonwealth 

University. “about 20 percent of those screened have 

a positive screen, but only about 5 to 7 percent are 

confirmed as having TBI,” he says. 

Many mild TBIs don’t require treatment, and 85 to 

95 percent of patients with mild TBI recover in 3 to 

12 months. However, Cifu advocates for an aggressive 

approach to treating TBI symptoms, especially if PTSd 

might be complicating the picture.

“Watching and waiting is not the best approach,” says 

Cifu. “While it’s always optimal to have a definitive 

diagnosis before starting treatment, many times there 

are multiple co-occurring conditions, and identifying a 

specific cause of all the symptoms isn’t feasible. you may 

never get a confirmed diagnosis, so instead you treat 

the symptoms and monitor closely to see what happens. 

Very often you can get a clearer picture of the diagnosis 

based on the response to treatment. 

“If the Veteran appears to have both TBI and PTSd, 

for example, then treat elements of both conditions—

because if you don’t, the small percentage of people who 

won’t get better on their own will get worse.”

In Iraq and afghanistan, TBI most often results from 

blasts, usually from improvised explosive devices (IEds). 

Mild TBI may go undiagnosed: Troops may stay in 

combat and not report symptoms, such as headache or 

ringing in the ears. Cifu points out that this may lead 

to exacerbations, even without further combat injuries. 

“When you get a brain injury in a setting where you 

don’t eat or sleep well, where you’re under stress, it’s 

going to look worse. When the brain tries to heal in 

that sort of environment, it may not recover well. That’s 

why we can see slow recovery rates and a higher rate of 

persistent symptoms.”

Newer imaging methods may help

In december 2009, a panel of experts, including Cifu, 

developed clinical practice guidelines for diagnosing 

and treating mild TBI. Though created by Va and 

the military, the guidelines apply to anyone affected 

by concussion. The panel included sports medicine 

specialists, psychiatrists, neurologists, and experts from 

other disciplines.

While the guidelines take advantage of the best existing 

technology, Va researchers are eager to put new tools in 

clinicians’ hands. 

For example, in a small pilot study, a team with Va 

and the University of California, San diego, found 

that a combination of two imaging technologies—

magnetoencephalography (MEG) and diffusion tensor 

imaging (dTI)—can show subtle brain injuries that go 

undetected in conventional CT and MRI scans. The 

first type of scan picks up the signals that neurons give 

off when they fire. The second picks up abnormalities 

in the brain’s nerve fibers. according to lead researcher 

Mingxiong Huang, Phd, injured brains generate 

pathological low-frequency brain waves—like those seen 

in normal patients during deep, dreamless sleep. and he 

believes that damaged neurons may become like frayed 

wires, unable to conduct impulses efficiently. 

Researchers agree that the damage from TBI can take 

various forms. In addition to head wounds from IEd 

shrapnel, troops are exposed to tremendous, nearinstantaneous changes in air pressure that can rupture 

eardrums. The effects of these pressure changes on the 

brain aren’t clear, but Va researchers are working to 

understand them.

Va investigator Pamela VandeVord, Phd, an associate 

professor in the department of biomedical engineering 

at Wayne State University in detroit, is studying the 

effects of IEd pressure waves at the cellular level. 

Dr. Apostolos Georgopoulos, with the Brain Sciences Center at the 

Minneapolis VA, has used a technology called magnetoencephalography 

to try to identify brain-wave patterns unique to PTSD. 
SPRING 2010 23

“ When you get a brain injury in a 

setting where you don’t eat or sleep 

well, where you’re under stress, it’s 

going to look worse.”

Members of Bravo Section, 2nd Brigade 

Recon Troop, in action in Iraq in 2004.
24 V A R E S E A R C H T O D AY

Blast waves cause different injuries than blunt trauma, 

VandeVord says. “With trauma from impact, you get 

a pressure wave that can last up to 100 milliseconds. 

The pressure wave from a blast causes a less than 

5-millisecond change in pressure.”

The pressure wave from an IEd is so fast, in fact, that 

it’s difficult to measure. only about a dozen places 

in the United States have the technology to replicate 

such pressure waves. Wayne State is one of them, and 

VandeVord has tested two types of brain cells—neurons 

and glial cells—by exposing them to the same type of 

compression wave that affects troops.

Neurons are hardy, surviving at even extremely high 

pressures. But at relatively low pressures, glial cells 

produce chemicals that might damage neurons. 

VandeVord is now conducting studies using mixtures 

of both cell types, to see if such damage occurs.

“If it does, we could look for drugs that block the 

synthesis of those chemicals,” she says. “We could find 

pharmacologic agents for blast-related brain injury.”

Non-human studies by her group have shown that 

certain pressures result in behavioral and microscopic 

anatomical changes, as well as decreases in blood flow to 

the brain, hallmark signs of brain injury. one surprising 

finding was that the pressures that caused these effects 

were not the highest pressures. “Now we’re looking at the 

biomechanics in this specific pressure range,” VandeVord 

says. “The shock wave appears to have a unique 

interaction with the skull, so we’re trying to figure that 

out.” The studies might result in the development of 

new types of helmets or other protection to block the 

transmission of specific pressure waves to the brain and 

reduce the risk for injury.

Seeking signature brain changes

other Va research is looking for signature brain 

changes associated with PTSd, TBI or both. Michael 

Weiner, Md, is director of the Center for Imaging of 

Neurodegenerative diseases at the San Francisco Va 

Medical Center, as well as a professor of radiology, 

medicine, psychiatry, and neurology at the University 

of California, San Francisco. He emphasizes that 

PTSd involves physiological and anatomical changes 

24 V A R E S E A R C H T O D AY

Facts on PTSD and TBI

According to a 2009 report in the American Journal of Public 

Health by VA researchers, about one in five returning Veterans 

who enrolled in VA health care between 2002 and 2008 

received a diagnosis of posttraumatic stress disorder, a form 

of anxiety. 

Anyone, military or civilian, can develop PTSD after a traumatic 

event. Such events include combat, automobile accidents, 

assault, abuse and natural disasters. 

Most people have short-term psychological reactions to these 

events, but in people with PTSD, symptoms last for at least a 

month and interfere with everyday life. Symptoms appear in 

four key areas:

 Reliving the event—Nightmares are common. Many 

people have flashbacks that can be triggered by sounds, 

news reports or other experiences.

 Avoiding situations that trigger thoughts of the event—

People may refuse to discuss the event, or keep busy so 

they won’t think about it.

 Feeling numb—People may find it hard to express 

feelings, positive or negative. They can lose interest in 

activities and in being with people.

 Feeling keyed up—People are hyperalert for danger. 

They can be easily angered, have trouble sleeping, 

have concentration problems and be overly worried 

about safety.

Estimates vary on how many returning Veterans have 

traumatic brain injury, but VA statistics show that mild TBI 

is diagnosed in about six to seven percent of all Iraq and 

Afghanistan Veterans who are screened. 

TBI can be caused by a direct blow to the head—from a bullet 

or shell fragment or in a motor vehicle accident—or from 

changes in air pressure caused by a nearby explosion.

TBI’s immediate effects run the gamut from a temporary 

woozy, “off” feeling to concussion to coma. About 15 percent 

of all TBIs are moderate or severe; they involve a loss of 

consciousness, hospitalization and usually other injuries. 

Only about half of military personnel with mild TBI seek care, 

although DoD and VA have significantly boosted screening 

efforts in this area. Currently, more than 22,000 Veterans 

are being compensated for TBI, including more than 5,800 

Veterans of the current wars.

24 V A R E S E A R C H T O D AY
SPRING 2010 25

in the brain, even though—unlike TBI—it may not be 

brought on by external forces to the head. 

“Generally, you can say that there are structural and 

functional biological changes that can be detected in 

people with PTSd, and that these changes affect areas 

that make sense: They are areas involved in our fear 

response,” Weiner says. 

Weiner and colleagues have studied subjects with PTSd 

only, TBI only, and both PTSd and TBI. He says early 

results suggest that the changes in the brain are different 

in the two conditions, but he emphasizes that “much 

more work needs to be done.” 

“Research like this will give us a better understanding of 

what’s going on—why people have symptoms, who’s at 

risk,” Weiner says. Ultimately, “We could use it for better 

diagnosis, to tailor treatments, or in treatment trials.”

In the past couple of years, Va funded several new 

centers to advance TBI-PTSd research and bolster 

efforts under way at other sites. a new program in 

Houston, led by Harvey Levin, Phd, is using MRI as 

a study tool, along with tests that resemble computer 

games to measure problem-solving ability, short-term 

memory, and other brain functions. In Boston, a group 

led by Henry Lew, Md, Phd, is exploring a range of 

new approaches to the diagnosis and treatment of TBI 

and PTSd. another key site is the Center of Excellence 

for Research on Returning War Veterans in central 

Texas, where a mobile functional MRI unit travels 

between the Waco Va and Fort Hood, the largest 

army base in the United States. In still other work, San 

diego Va psychiatry researcher Murray Stein, Md, 

MPH, is leading a $60-million, five-year, 10-site clinical 

consortium focused on preventing and treating PTSd 

and TBI. The effort is funded by the department of 

defense (dod). 

Much of this work is still in the early stages. But results 

such as those reported earlier this year by a Minneapolis 

Alessandra Leonardi Dal Cengio checks the settings on the “shock tube” that a VA and Wayne State University team is using to 

simulate the effects of bomb blasts. 
26 V A R E S E A R C H T O D AY

Va team may be a harbinger of things to come. The 

researchers published findings of distinctive MEG scans 

in Veterans with PTSd. They were able to differentiate 

between those with PTSd and healthy controls with 

better than 90 percent accuracy.

“These findings document robust differences in brain 

function between the PTSd and control groups that 

can be used for differential diagnosis,” says neuroscientist 

apostolos Georgopoulos, Md, Phd, who led the study 

along with psychologist Brian Engdahl, Phd. Both 

are with the Brain Sciences Center at the Minneapolis 

Va Medical Center and University of Minnesota. 

Georgopoulos says MEG technology could also be used 

to track disease progression and the effects of therapy. He 

noted that if the PTSd biomarker holds up in further 

study, Va and dod could use it to help determine the 

medical status of service members and Veterans.

Removing the stigma from PTSD

Beyond being able to more easily identify TBI and 

PTSd, clinicians and the military also want to find 

ways to prevent the conditions. PTSd, in particular, is 

the focus of a large collaborative effort toward that end. 

The San diego-based Marine Resilience Study involves 

Va and dod researchers and more than 2,000 Marines. 

The troops are evaluated one month before deployment 

and then at three time points after they return. 

The researchers are looking at many factors that might 

be associated with resistance to, and risk for, PTSd, 

ranging from biological to psychological, social and 

environmental factors. 

Some of what’s learned may help guide dod efforts 

to better prepare and support troops before and after 

combat deployments. also, to the extent the study helps 

pinpoint the physical changes linked to PTSd, it may 

help change the way some people think about the illness. 

Study co-leader William Nash, Md, a former Navy 

psychiatrist who deployed to Iraq with the 1st Marine 

division in 2004, says:“The Marine Corps would love 

for us to find objective, physical markers for PTSd 

in our study because that would go a long way toward 

reducing the stigma that surrounds PTSd. There are 

still too many military service members, including 

health care professionals, who don’t believe PTSd is 

a real illness resulting from real injuries to the mind 

and brain, but instead think it is caused by a personal 

weakness. If we can show them biological markers for 

PTSd, Marines will better accept that PTSd is no 

more their own fault than any other wound of war.”

In the future, a clearer picture is likely to emerge of who 

is at risk for PTSd, how to differentiate between PTSd 

and TBI, and how imaging and other technologies can 

inform diagnosis and treatment of both conditions. 

Until then, Cifu says, diligence and vigilance are the 

best strategies. “you do your best to clarify the problem, 

treat the symptoms aggressively, and then monitor the 

patient long term,” he says. “doctors love one-time fixes, 

but that’s not life.”

Subtle visual impairment is common in mild traumatic brain injury, and VA 

researchers are testing new methods to detect and treat the problem. Here, therapist 

Paul Koons of the VA Palo Alto Healthcare System uses a Neuro Vision Technology 

scanner with Veteran Angie Stoltz to help improve her visual function. 
SPRING 2010 27

Dr. Rosalyn Yalow was one of two VA 

researchers to win the Nobel Prize in 1977. 

HIS t o R y

HIStoRICAl mIlEStoNES

On the following pages, a snapshot of milestones in VA’s rich 

85-year history of research on behalf of Veterans
1925: Conducted the first hospital-based medical studies to be formally 

considered part of Va’s newly established research program. 

Began publishing the U.S. Veterans’ Bureau Medical Bulletin,

designed, in part, to “promote research along practical lines.”

1928: Reported findings from early Va studies looking at treatments 

for malaria, the long-term health effects of chemical warfare, and 

hospitalization and mortality among Veterans with mental illness. 

1932: Published data comparing outcomes at Va clinics with those 

at other hospitals. The Va facilities compared favorably. also, 

established the Tumor Research Laboratory at the Hines (Ill.) 

Va—the first research lab to receive funds from Va Central 

office specifically for research. 

1935: Published a series of articles in the New England Journal of 

Medicine about heart disease among Veterans.

1941: Established a research lab at the Northport (N.y.) Va 

medical center to conduct clinical and biomedical research 

in neuropsychiatric disorders; contribute to the nationwide 

standardization of diagnostic and treatment methods; 

and teach the latest concepts and methods in neurology, 

psychiatry, and neuropathology to Va doctors.

1946: developed and tested effective therapies for tuberculosis 

following World War II. These tuberculosis studies were among 

the first-ever large-scale clinical trials and led to development 

of the Cooperative Studies Program, which has since produced 

effective treatments for diseases and conditions including 

schizophrenia, diabetes, depression, heart disease, and stroke.

1958: Contributed to the development and early use of the implantable 

cardiac pacemaker, helping many patients prevent potentially 

life-threatening complications from irregular heartbeats. 

1960: Pioneered concepts leading to development of computerized 

axial tomography (CaT scan). 

1968: Performed the first successful liver transplants and developed 

techniques for suppressing the body’s natural attempt to reject 

transplanted tissue.

1970: Published the results of a landmark Va cooperative study 

on hypertension, showing that drug treatment was effective 

in controlling blood pressure and reducing the incidence of 

major cardiovascular events. 

1977: Nobel Prize awarded to Va researchers dr. andrew Schally, for 

his research on peptide hormone production in the brain; and 

dr. Rosalyn yalow, for her development of radioimmunoassay 

to detect and measure various substances in the blood. 

1984: developed the nicotine patch and other therapies to help 

smokers give up the habit.

1989: Invented a computer system that provides patients on 

ventilators with more accurate respirator settings, fewer 

medical complications and better outcomes. 

28 V A R E S E A R C H T O D AY
1991: developed Functional Electrical Stimulation (FES) systems 

that allow patients to move paralyzed limbs.

1994: demonstrated that one aspirin tablet a day reduced by half 

the rate of death and nonfatal heart attacks in patients with 

unstable angina. also, identified a gene associated with a major 

risk for schizophrenia.

1999: Established, through a large clinical trial using the drug 

gemfibrozil, that raising HdL (“good”) cholesterol and 

lowering triglycerides could prevent heart attacks and 

coronary deaths.

2000: Conducted the first large clinical trials of hearing aids, 

documenting that the devices can help the hearing-impaired 

in both quiet and noisy environments.

2001: Initiated a landmark clinical trial to assess the effectiveness 

of deep brain stimulators for Parkinson’s disease.

2002: Published, together with National Institutes of Health 

colleagues, the main results from the landmark aLLHaT 

study, the largest hypertension study ever, which found that 

conventional diuretics were better than newer medicines for 

treating high blood pressure.

2003: Launched the largest-ever clinical trial of psychotherapy to 

treat posttraumatic stress disorder (PTSd).

2004: Took on leadership of a five-year, $60 million nationwide 

study—funded by the National Institute on aging and other 

partners—to identify brain changes linked to alzheimer’s disease.

2005: Showed the effectiveness of a new vaccine for shingles, a 

painful skin and nerve infection that affects older adults.

2006: Launched a Genomic Medicine initiative to advance 

knowledge of how genes affect health and to promote 

personalized medicine for Veterans.

2007: Unveiled the first powered ankle-foot prosthesis, developed in 

collaboration with researchers at MIT and Brown University.

2008: Sponsored an international conference on traumatic brain injury 

and expanded Va research in this area, including studies looking 

at TBI in association with posttraumatic stress disorder, hearing 

and vision loss, chronic pain, and other conditions.

2009: Began first-of-its kind study at Va medical centers to optimize 

the design of an advanced prosthetic arm, made by dEKa 

Research and development through funding from the 

defense advanced Research Projects agency. also, initiated 

the largest health study ever of Vietnam-era women Veterans, 

with up to 10,000 women expected to take part. 

2010: as part of the Va Genomic Medicine Program, announced 

a groundbreaking genetics study—the Million Veteran 

Program—to study the effects genes have on health, with as 

many as a million Veterans expected to take part over the next 

five to seven years.

SPRING 2010 29
30 V A R E S E A R C H T O D AY

For more than 85 years, the Veterans affairs (Va) Research and 

development program has been improving the lives of Veterans and all 

americans through health care discovery and innovation. n The Va 

Research program is unique because of its focus on medical issues that affect 

Veterans. It is part of an integrated health care system with a state-of-the-art 

electronic health record and has come to be viewed as a model for superior benchto-bedside research. n The groundbreaking achievements of Va investigators—70 

percent of whom also provide direct patient care—have resulted in three 

Nobel prizes, six Lasker awards, and numerous other distinctions. n While 

realizing the advantages of an intramural program and embracing its close ties to 

academic affiliates, the Va Research and development program fosters dynamic 

collaborations with other federal 

agencies, nonprofit organizations, 

and private industry—thus furthering 

the program’s impact on the health 

of Veterans and the nation.

“ by spearheading research that directly 

advances the medical care of Veterans, the 

VA Research and development program has 

become an acclaimed model for conducting 

superior bench-to-bedside research.”

— Joel Kupersmith, MD, Chief Research and Development Officer 

Veterans Health Administration

o V ERVIE w

tHE VA RESEARCH ANd dEVEloPmENt PRoGRAm:

ImPRoVING VEtERANS’ lIVES tHRouGH HEAltH CARE RESEARCH

VA Research — Discovery, Innovation, Advancement
SPRING 2010 31

biomedical laboratory

Research and Development 

This division conducts preclinical research to 

understand life processes from the molecular, genomic, 

and physiological level in regard to diseases affecting 

Veterans. It includes research on animal models and 

investigations of tissues, blood, or other biologic 

specimens from humans, but does not include studies 

with people. 

clinical science

Research and Development

This division focuses on clinical trials and other 

research involving human volunteers to study new 

treatments, compare existing therapies, and improve 

clinical practice and care. 

The Cooperative Studies Program within this division 

is responsible for planning and conducting Va’s large 

multicenter clinical trials and epidemiological studies 

on health issues vital to our nation’s Veterans. 

health services

Research and Development

This division supports research to improve the delivery 

of health care to Veterans. among the areas studied 

are quality and organization of care; patient access and 

outcomes; and cost-effectiveness. 

The division’s Quality Enhancement Research Initiative

(QUERI) is designed to translate research findings into 

advancements in Veterans’ care.

rehabilitation

Research and Development

This division conducts research to discover knowledge 

and create innovations that restore Veterans who 

have become disabled due to injury or disease to their 

greatest possible functional capacity in their families, 

communities, and workplaces. 

cross-cutting components

other programs are cross-cutting. The Program 

for Research Integrity Development and Education

(PRIdE), for example, is responsible for policy 

development, guidance, training, and education 

in relation to the protection of human research 

participants throughout Va. and the Technology 

Transfer Program is dedicated to translating discoveries 

and inventions by Va researchers into practice.

productive partnerships

While embracing its status as an intramural program 

with close ties to its academic affiliates, the Va 

Research program also fosters and develops dynamic 

collaborations with other federal agencies, nonprofit 

organizations, and private industry. Such teamwork 

promotes the leveraging of resources, speeds the 

translation of study results into clinical practice, and 

maximizes the overall impact of Va Research. 

INtRAmuRAl PRoGRAm, CollAboRAtIVE SPIRIt

The VA Research program consists of four main research services working together to address 

the full spectrum of Veterans’ health needs 

As we mark the 85th year of VA’s research program, we 

celebrate our innovative researchers who helped turn so 

many hopes into realities. VA’s forward-looking contributions 

to medical research continue to bring life-improving 

treatments and pharmaceuticals to our Veterans and the 

Nation. we will maintain our steadfast commitment to lead 

the way as we transform VA into a 21st century organization. 

 — Eric K. Shinseki, Secretary, Department of Veterans Affairs
32 V A R E S E A R C H T O D AY

RES o u R CES

RESEARCH fuNdING: VA R&d by tHE NumbERS

An overview of the resources that fuel VA’s innovative medical and rehabilitation studies

I

n fiscal year 2009, Va Research and development 

supported more than 2,000 research projects at 

Va medical centers nationwide, ranging from 

preclinical studies to health services research to 

multisite clinical trials. The types of research that 

Va Research sponsors are: 

Investigator-initiated research (Merit Review) 

Mentored research (Career development) 

 Large-scale, multisite clinical trials (Cooperative 

Studies Program) 

Centers of Excellence 

 Service-directed research (sponsored by one of the four 

services that make up VA Research; see page 31)

Va Research is an intramural program, meaning that 

only Va employees can conduct research under Va’s 

auspices. Typically, though, Va researchers collaborate 

with academic colleagues and others outside Va. 

Investigators must compete for funding. They submit 

proposals, which are then peer-reviewed. only the most 

meritorious projects are funded. To meet the needs of 

the entire Veteran population, Va Research invests in a 

balanced portfolio of studies. 

The congressional allocation for Va Research for fiscal 

year 2010 is $580 million. Va studies are also supported 

in part by Va medical care dollars, as well as funding 

from non-Va sources, such as other federal agencies, 

nonprofit associations and industry partners. In fact, 

Va researchers are expected to leverage their Va 

funding whenever possible—that is, seek additional 

support from non-Va sources—to maximize the scope, 

quality and impact of their research and the resulting 

gains for Veterans. The National Institutes of Health 

is the most prominent source of such funding for Va 

investigators. another benefit of NIH funding is that 

it assures the public that Va and NIH research projects 

are of equal quality. 

Funding from industry comes mainly from drug 

companies and is typically administered through 

nonprofit corporations. In 1988, Congress passed 

legislation that empowered Va medical centers to 

establish Va-affiliated nonprofit research corporations. 

These entities provide flexible funding mechanisms 

for the administration of non-Va funds for the conduct 

of Va-approved research. 
SPRING 2010 33

Congressional allocation for VA Research (in millions)

VA research funds spent in fiscal year 2009

2005

$390

$412

$447

$480

$510

$580

$0

$100

$200

$300

$400

$500

$600

2006 2007 2008 2009 2010

Investigator Initiated 70% Career Development 9%

Centers of Excellence 11%

Service Directed 2%

Research Compliance 1%

Other 7%
34 V A R E S E A R C H T O D AY

CSP t R I A l S

VA’S CooPERAtIVE StudIES PRoGRAm: lARGE-SCAlE 

tRIAlS to INfoRm EVIdENCE-bASEd mEdICINE

From heart disease to mental health, CSP comparative effectiveness trials and other studies 

yield valuable data to help guide health care for VA and the nation 

During the Vietnam War, allen Wright served 

aboard the USS Oriskany. He helped fix and 

maintain the Skyhawk fighter jets and other aircraft 

that would fly from the ship. 

Today, the Baltimore resident has trouble using his 

right hand—one of the effects of a stroke he suffered in 

2000. “I use dumbbells and do stretching exercises at 

home,” says Wright. “My hand still feels weak and slow 

sometimes, but it’s better than it would be if I weren’t 

doing anything.” 

Wright recently got some help moving his hand 

from a robot called the MIT-Manus. He was one of 

127 Veterans who took part in a VA study that used 

robots to deliver high-intensity therapy. Other study 

volunteers received high-intensity therapy without 

the robot. Both methods proved effective. The results, 

presented at the 2010 International Stroke Conference, 

provide compelling new evidence that people can gain 

back function even years after a stroke. 

The study is one of many examples of the impact of 

VA’s Cooperative Studies Program. By conducting 

innovative trials across multiple VA sites—often 

including thousands of Veterans—CSP is able to 

generate strong evidence to help guide clinical practice. 

Findings from CSP studies not only inform VA care 

but also contribute significantly to medical care 

throughout the United States and the world. 

CSP’s innovative clinical trials and epidemiological 

studies (research looking at causes and risk factors 

for disease) cover a wide range of health topics, such 

as heart disease, diabetes, cancer, infectious diseases, 

mental health and prosthetics. Always, the first focus is 

on health problems affecting Veterans. 

Roots in tuberculosis care 

While CSP was established in its present form in 

1972, the program’s roots date back to just after 

World War II. The program conducted the first-ever 

large-scale clinical trials, looking at the effectiveness 

of tuberculosis treatments. In the decades since, CSP 

has conducted numerous landmark studies—many of 

which have appeared in prominent medical journals 

such as the New England Journal of Medicine and the 

Journal of the American Medical Association.

CSP typically has more than 30 clinical trials in 

progress at a given time—most of them “comparative 

effectiveness” studies that compare treatment options 

head to head. By seeing how therapies stack up against 

each other in defined groups of people, CSP studies 
SPRING 2010 35

A recent CSP study provided compelling 

new evidence that people can gain back 

function even years after a stroke. 

help fill critical gaps in medical knowledge. Some prime 

examples from recent years: 

“On-pump” method of heart bypass surgery. The 

traditional “on-pump” method—which uses a heartlung pump to stop the heart while doctors conduct 

the bypass—achieved better outcomes after a year 

than a newer “off-pump” technique. 

Angioplasty in stable coronary artery disease. Va 

researchers, working with Canadian colleagues, found 

that patients with stable coronary artery disease—

in which plaque buildup narrows the arteries and 

restricts the heart’s blood supply—often fare well with 

medication and lifestyle changes alone. a commonly 

used treatment called percutaneous coronary 

intervention (PCI, commonly called angioplasty) 

might best be reserved for patients with more severe 

forms of heart disease. 

Prolonged-exposure therapy for posttraumatic stress 

disorder. Va researchers showed that prolongedexposure therapy—in which therapists help patients 

recall their trauma memories under controlled 

conditions—helped women reduce their PTSd 

symptoms more than emotional support and 

counseling that focused on current problems.

Intensive therapy to support kidney function. 

Va investigators, in collaboration with NIH 

investigators, showed that delivering more intensive 

therapy—for example, dialysis six times a week 

instead of three—did not benefit patients with kidney 

failure, compared with conventional treatment. 

Genetics studies, which look at how patients’ genes 

influence their susceptibility to certain diseases and 

their responses to drugs or other treatments, account 

for an increasingly significant portion of CSP’s 

portfolio. As part of its role in VA’s Genomic Medicine 

Benson Belo uses a robotic system to strengthen his stroke-weakened right arm at the Baltimore VA Medical Center.
36 V A R E S E A R C H T O D AY

Half-decade snapshot of CSP studies

VA’s Cooperative Studies Program dates back, 

in its earliest form, to the 1940s, when it ran 

tuberculosis clinical trials. Since then, it has 

conducted numerous landmark trials, such as 

a 1970 study showing that drugs for lowering 

blood pressure can help prevent or delay 

serious cardiovascular events. Fast-forward 

more than 30 years, and here’s a glimpse at 

just the last half-decade of CSP history: 

2009

Launched a study of up to 10,000 Vietnam-era 

women Veterans to better understand their 

long-term health status and risks. 

2008

Published the results of the seven-year VA 

Diabetes Trial, which found that intensive 

control of blood glucose in type 2 diabetes 

does little to cut the risk of heart disease, 

compared with standard treatment.

2007

Began a study of prazosin, an inexpensive 

generic drug used for high blood pressure and 

prostate problems that was shown in a pilot 

study to improve sleep and lessen trauma 

nightmares in Veterans with PTSD.

2006

Published, with colleagues from the National 

Institutes of Health, the results of a major 

study of the dietary supplements glucosamine 

and chondroitin sulfate for arthritis.

2005

Also in collaboration with NIH, showed the 

effectiveness of a new vaccine for shingles, a 

painful skin and nerve infection in older adults.
SPRING 2010 37

Program, CSP established a repository to securely store 

biological specimens donated for genomics research. 

CSP plans to expand its genomic medicine capacity, 

keeping up with rapidly evolving technology for DNA 

analysis and expanding the numbers of Veterans 

involved in such studies. 

Studies include up to thousands of Veterans 

The CSP studies mentioned above—and hundreds 

more in the program’s long history—are conducted 

by research teams that include clinicians as well 

as statisticians, epidemiologists, pharmacists, and 

regulatory experts. CSP investigators also team up with 

experts outside VA, including federal, university and 

private industry partners. 

The most important partners in the studies, though, 

are the Veterans who get their health care from VA 

and who choose to participate in research. Crucial 

to VA research overall, the efforts of these volunteers 

are especially important in CSP’s multisite trials. 

The largest health study ever of Vietnam-era women 

Veterans, for example, is expected to include up to 

10,000 women. Another CSP study, on the genetics 

of schizophrenia and bipolar disorder, is expected to 

enroll some 38,000 Veterans. Study co-chair Larry 

J. Siever, MD, of the Bronx VA and Mount Sinai 

School of Medicine, says, “We’ve been hunting for 

genes of susceptibility for these two diseases, and 

you need a very large sample to establish genomicwide association.” 

For more information about the VA Cooperative 

Studies Program, go to www.csp.research.va.gov.

A CSP-NIH study published in 2006 found little benefit overall 

for two supplements used widely by patients with osteoarthritis. 

Here, Dr. Said Ibrahim examines a Veteran who has arthritis of 

the knee at the Pittsburgh VA. 

SPRING 2010 37

Spotlight on a CSP trial: Brain 

stimulation for Parkinson’s

George Schmid, a 63-year-old Army 

Veteran living in southern New 

Jersey, decided three years ago with 

his VA doctor that it was time to try 

a new treatment for his Parkinson’s 

disease. His left side would often 

stiffen up, and the drugs he took to 

tame the symptoms were wearing 

off faster and faster. 

Schmid participated in a six-year study sponsored by VA’s 

Cooperative Studies Program and the National Institutes 

of Health, in which some patients received “best medical 

therapy” (carefully managed medication plus speech, physical, 

or occupational therapy as needed), while another group 

of patients, including Schmid, received a procedure called 

deep brain stimulation. In DBS, electrodes are implanted 

into the brain, with thin wires running under the skin to a 

small pacemaker-like device placed under the skin near the 

collarbone. Electrical stimulation from the battery-operated 

device aims to jam the brain signals causing the symptoms.

The study involved 255 patients, ages 38 to 83—all of 

whom were no longer helped adequately by drugs. VA’s 

Cooperative Studies Program coordinated the trial, which 

took place at VA’s national network of Parkinson’s centers 

(www.parkinson’s.va.gov) and six university hospitals.

Researchers found that DBS, while riskier than drug therapy, 

may hold significant benefits for those with Parkinson’s 

disease who, like Schmid, no longer respond well to 

medication alone. The results, published last year in the 

Journal of the American Medical Association, would come as 

no surprise to Schmid, who says he’s felt “very, very good” 

after DBS—“at least 30 to 50 percent better” than before 

the procedure.

Overall, after six months, patients who received DBS gained 

more than four hours per day, on average, of “on time” periods 

with good motor control and few or no involuntary movements 

of the face or limbs. Also, DBS patients showed significant 

improvements in several quality-of-life measures, compared 

with little change for the other patients. On the down side, 

there was a higher likelihood of serious side effects with 

DBS compared with drug therapy. Also, while DBS generally 

improves movement, the procedure does little to help other 

Parkinson’s symptoms such as depression, declines in mental 

ability, and gait and balance problems. 
38 V A R E S E A R C H T O D AY

wom E N

mAjoR mEEtING mARkS mIlEStoNE foR VA RESEARCH 

oN womEN’S HEAltH

Top experts are gathering to help plan the next steps for VA women’s care 

When retired army Staff Sgt. June Moss came home 

from her 2003 deployment to Iraq, she found 

herself crying unexpectedly. and not sleeping. and 

“checking the perimeter” around her home to make 

sure she and her two children were safe. 

Moss eventually got divorced—her husband, also an 

Iraq Veteran struggling to readjust, was resistant to 

seeking help. She and her children became homeless at 

one point, relying on cheap motels to have a roof over 

their heads. 

The single mom would eventually receive a diagnosis 

of posttraumatic stress disorder and get help through 

Va treatment. She found the strength to be open about 

her illness partly through her children. “They helped me 

realize it’s not bad to tell other people that I was getting 

help, that I was taking medication.” 

Moss’ story is not uncommon among the hundreds 

of thousands of women Veterans who turn to Va for 

health care. To make their care the best it can be, Va 

relies on research: studying how and where care is 

delivered, and how well it meets women’s needs. 

In summer 2010, a major conference is being held 

to promote and expand research on issues affecting 

women Veterans. 

The National Meeting on Building the Evidence Base 

to Improve Health Care and outcomes for Women 

Veterans, July 15 – 16 in Washington, dC, is the first 

event of its type since 2004, when Va first set out to 

develop a comprehensive research agenda focused on 

women. Women now account for 14 percent of active 

duty military and nearly 6 percent of Va health care 

users, and Va has continued to build a diverse research 

portfolio targeted to their needs. 

“This year’s meeting is an opportunity to gauge how far 

we have come since the establishment of the research 

agenda and to accelerate our growth towards research 

that will directly impact the care that women receive 

in Va,” says Elizabeth yano, Phd, MSPH. yano is 

co-director of Va’s Center for the Study of Healthcare 

Provider Behavior and an adjunct professor of health 

services at the University of California, Los angeles, 

School of Public Health. 

Known nationally as a leading investigator in the area of 

health care for women Veterans, yano was lead author on 

a paper published in the January 2010 Journal of General 

Internal Medicine that gave an overview of Va health 

care for women, outlined Va’s research focused on their 

needs, and proposed ways to increase their representation 

in Va studies aimed at quality improvement. 
SPRING 2010 39

yano said the July conference will “partner senior Va

leaders with researchers in the field” to explore how to 

best use research to guide care and services for women. 

as of the printing of this magazine, leaders from several 

Va offices, such as the Center for Women Veterans, 

are expected to attend, as are researchers and women’s 

health experts from the military, other federal agencies, 

and the nonprofit and private sectors. 

dozens of Va researchers will present their study results 

in areas such as: 

access to and quality of care for women Veterans; 

interventions to improve care and outcomes; 

post-deployment mental health care for women;

 the overall effects of military service on women’s 

health; and 

transforming Va care for women. 

In the past few years, Va has been funding an active 

and varied portfolio of research for women Veterans 

that has resulted in upwards of 75 scientific publications 

each year. Here are examples of key findings from 

recent studies: 

Homelessness and women Veterans—

Unemployment, disability and unmarried status 

are among the strongest predictors of homelessness 

for women Veterans, according to a Va study of 

nearly 200 women in Los angeles. Homeless women 

were also more than four times as likely to have 

experienced military sexual trauma, and five times 

as likely to screen positive for posttraumatic stress 

disorder. Notably, the homeless women in the study 

were just as likely as housed women to have a regular 

health care provider, and were twice as likely to 

have used any Va health care in the past year. The 

researchers said this may both illustrate the impact of 

Va’s homeless outreach and represent an opportunity 

for further interventions to help this population. 

(Journal of Health Care for the Poor and Underserved,

February 2010) 

Emerging issues among women OEF/OIF 

Veterans—Following the Gulf War, policy changes 

and new legislation eased rules excluding women from 

combat-related positions. as a result, women deployed 

to Iraq and afghanistan serve in support positions 

that involve leaving military bases, working sideby-side with combat troops, and coming under fire. 

In this review study, a Va team found that combat 

exposure in particular is not associated with a higher 

risk of mental health problems for women compared 

with men. However, women are more likely than 

men to develop PTSd following a range of traumatic 

experiences. The authors also found evidence that 

women who suffered abuse prior to their military 

Veteran Gladys Colón receives care at the Providence (R.I.) VA Medical Center. 

Women now account for 14 

percent of active duty military 

and nearly 6 percent of VA 

health care users. 
40 V A R E S E A R C H T O D AY

service may be more likely to develop PTSd after 

combat exposure. another finding: among women, 

concerns about family or relationships play a stronger 

role in the development of PTSd. (Clinical Psychology 

Review, october 2009) 

Men and women receive equal heart attack care 

in VA—Women, in general, are less likely than men 

to undergo cardiac catheterization and receive other 

evidence-based therapies for heart attack, but no prior 

studies had examined how Va patients fare in this 

regard. This Va study, which included 236 women 

and 13,259 men, found similar care and survival rates 

between the two groups. For example, catheterization 

was provided for about 35 percent of men and 37 

percent of women. More men were prescribed aspirin 

and angiotensin-converting enzyme inhibitors, 

but there were no differences with regard to other 

platelet inhibitors, beta-blockers, or lipid-lowering 

medications. (Journal of Women’s Health, May 2009) 

 ongoing Va research on women’s health is exploring 

issues such as barriers to Va care for women; military 

sexual trauma; mental health issues such as PTSd, 

anxiety, depression and suicide; and the development 

of new models of health care and psychosocial 

reintegration for women Veterans, including those 

who are raising children. among current studies being 

conducted: 

Vietnam women Veterans—Va has launched the 

largest and most comprehensive study to date of 

Vietnam-era women Veterans. The $5.6 million 

study, aimed at understanding the long-term effects 

of military service on women’s mental and physical 

health, will enroll as many as 10,000 women who 

served during the war in Vietnam, elsewhere in asia, 

or in the U.S.

Studying access to care—Va recently undertook 

the first national survey of women Veterans since 

1985. This survey of 3,611 women has amassed 

comprehensive data on health care needs and Va 

experiences, differences among cohorts of women 

Veterans by military era, and their preferences and 

perceptions about access to Va care and its quality. 

The data will guide future efforts to improve outreach, 

access and care. 

Synthesizing research results—a synthesis of 

published research on women Veterans from the past 

five years will be completed by summer 2010—in 

time for the July conference—and will help guide 

further efforts to improve Va care for this fastgrowing segment of Va’s patient population. 

For Veterans like June Moss, Va health care is integral 

to recovery. ongoing weekly therapy has helped Moss 

restore her life. Today, she is a valued program assistant 

for the chaplaincy program at the Palo alto Va. She 

also takes part in research on PTSd—another way to 

help her fellow Veterans in need. 

“If it hadn’t been for my faith and my family and the 

Va and my medical attention,” she says, “I could not be 

here today.” 

For more information on the National Meeting on 

Building the Evidence Base to Improve Health Care 

and Outcomes for Women Veterans, sponsored by VA’s 

Health Services Research and Development Service, 

visit www.research.va.gov. 

Left: Air Force medical technician Kahliha Love works at an U.S. expeditionary hospital in Chile after being deployed there in March to help earthquake 

victims. Right: Veteran June Moss, seen here with children Briona and Jacob, struggled with PTSD and homelessness after returning from Iraq in 2003.
SPRING 2010 41

R E b u I l d I N G

A bIoHybRId APPRoACH to REbuIldING tHE body

At VA’s Center for Restorative and Regenerative Medicine, leading-edge scientists are 

working on innovative ways to help injured Veterans regain their independence

researchers with the Center for Restorative and 

Regenerative Medicine (CRRM) are content to 

leave Superman’s bounds over tall buildings and the 

Six Million dollar Man’s bulldozer-strength bionic 

arm in the realm of implausible fiction. It’s the natural 

body’s real-life feats of movement and function that 

CRRM researchers are bent on mimicking. The 

center’s investigators, representing the Providence 

(R.I.) Va Medical Center, Brown University and the 

Massachusetts Institute of Technology, are studying 

new-millennium methods for restoring quality of life 

to those hurt by disease or injury. a primary focus is 

the marrying of human tissue and mechanical elements 

into lifelike “biohybrid” limbs that handily outperform 

currently available prostheses. 

The center—which was founded in 2004 and will be 

rededicated this year with a new 24,000-square-foot, 

state-of-the-art research space—specifically targets 

problems experienced by Veterans, notes the director 

of CRRM, Brown University professor of orthopedic 

surgery Roy aaron, Md. “People in civilian life are 

affected by the conditions we study,” he says, “but 

mostly we’re focused on conditions such as devastating 

limb injury, burns, traumatic brain injury, and 

posttraumatic stress disorder, which are much more 

prevalent in Veterans.” 

The CRRM collaboration addresses these needs 

through a team approach. Its researchers boast expertise 

in tissue engineering, orthopedics, neurotechnology, 

prosthetic design and rehabilitation. “at the end of 

the day, the science and medicine of limb restoration 

and advanced rehabilitation are creative processes 

that benefit from all sorts of disciplines,” says al Lo, 

Md, Phd, a neurorehabilitation expert and CRRM’s 

associate director. 

Bionic ankle embodies ‘biohybrid’ concept

Today’s hip and knee replacements are examples 

of the use of biohybrids that blend 

natural and manmade parts to restore 

the deteriorated originals. “It’s not a 

fanciful concept,” aaron says. What’s 

novel now, he explains, is the increased 

sophistication of materials and 

design that can be matched 

up with a type of injury 

for improved 

motion and 

PowerFoot, a bionic ankle developed by Dr. Hugh Herr of the 

Massachusetts Institute of Technology and VA’s Center for 

Restorative and Regenerative Medicine. 
42 V A R E S E A R C H T O D AY

function. Every battlefield injury is different, for 

example—sometimes it’s better to rely on biological 

reconstruction to salvage a limb, and in other cases it’s 

preferable to do an amputation and prosthetic fitting. 

“The biohybrid concept allows the unification of metals 

and other disparate materials that influence biological 

tissue differently depending on their shape, texture and 

other characteristics,” aaron explains.

The first powered ankle-foot prosthesis, constructed 

by MIT prosthetics engineer Hugh Herr, Phd, is 

an example of a biology-mimicking (“biomimetic”) 

component developed through the center. The 

computerized below-the-knee prosthesis, called 

PowerFoot, propels a user forward with tendon-like 

springs and an electric motor. “This design releases 

three times the power of a conventional prosthesis to 

propel you forward, and for the first time, provides 

amputees with a truly humanlike gait,” says Herr, 

who many years ago lost both of his own legs below 

the knee from frostbite suffered during a mountainclimbing expedition. 

Garth Stewart, a 24-year-old army Veteran who lost 

his left leg below the knee from an injury in Iraq, 

demonstrated the new prosthesis at its unveiling at 

the Providence Va Medical Center. “one of the first 

things I noticed was a huge relief in back pressure,” said 

Stewart of the prosthetic, which was designed to reduce 

fatigue and improve balance better than previously 

available alternatives. 

Joel Kupersmith, Md, Va’s chief research and 

development officer, points out that “up to now, 

prosthetic devices have not been able to duplicate the 

complex functions of our feet and ankles as we walk 

and run. The ingenious computerized design of this new 

prosthesis changes all of this. It constantly ‘thinks’ and 

responds, allowing the person to walk or run in a more 

natural and comfortable way.” 

Optimizing a space-age artificial arm

For those who have lost an arm from a battlefield injury 

or other cause, a CRRM-led Va study will help put the 

polish on the design of a sophisticated prosthetic arm 

that supports tasks as intricate and diverse as picking 

up a key, holding a pencil, and using a power drill. The 

artificial arm, developed by the dEKa Research and 

development Corporation through funding from the 

defense advanced Research Projects agency, is being 

tested at four Va sites before being commercialized. 

Frederick downs Jr., director of Va’s Prosthetic and 

Sensory aids Service, who lost his left arm during 

combat in Vietnam, says he was “brought to tears” 

recently when the device allowed him to smoothly bring 

a water bottle to his mouth and drink—a task that may 

sound simple but that requires fine control to accurately 

maneuver the bottle without crushing it. 

“The device has six different grips, including a fine 

pinch for picking up paper clips, a spherical grip to pick 

up a round ball, and a lateral pinch to cut with scissors,” 

explains study leader Linda Resnik, Phd, a Va research 

scientist and Brown University associate professor. 

The other extraordinary feature of the arm under 

Iraq Veteran Garth Stewart helped Dr. Hugh Herr’s lab test PowerFoot, 

which propels users forward with tendon-like springs and an electric motor. 
SPRING 2010 43

“ Our studies will help amputee patients by 

improving their function and ability to navigate 

through different terrains and obstacles.”

Dr. Susan D'Andrea directs the Gait and Motion Analysis Lab, part of the 

Center for Restorative and Regenerative Medicine at the Providence VA. 
44 V A R E S E A R C H T O D AY

study, according to Resnik, is a fully powered shoulder, 

which allows people who have lost an arm at that high 

a level to function far better than they could with any 

previously available artificial arm. “Many people who 

have lost their arm including their shoulder don’t even 

use a prosthetic limb,” Resnik points out, “because they 

can get so little function out of it.” 

Turning brain waves into action

CRRM researchers are working on additional 

prostheses to respond more accurately to the user’s 

intent. “you can have the most beautiful prostheses, but 

if people can’t power them to perform as they intend,” 

they’re hardly useful, says CRRM director aaron. 

a system called BrainGate, developed by Brown-Va 

researcher John donoghue, Phd, allows signals from 

the brain to be picked up by a sensor implanted in a 

part of the brain that controls voluntary movement. 

The signals are then decoded into commands that drive 

prosthetic or other robotic and electronic devices. In a 

pilot study, the BrainGate system enabled a 25-year-old 

man with quadriplegia to operate a computer cursor and 

perform other tasks solely through his thoughts. When 

the BrainGate study team, led by Leigh Hochberg, 

Md, Phd, published the results, the research earned 

headlines worldwide: a London newspaper, for 

example, referred to the trial participant as “the first 

bionic man” and a Canadian newspaper proclaimed, 

“Movement by Thought: Science Fiction to Fact.” 

The BrainGate research team is now focused on 

extracting the neural signals related to the intention 

to move one’s limb, and in turn a computer cursor, to 

use applications such as e-mail and word processing. 

The researchers are also working on allowing people 

to use the system to control prosthetic limbs or even 

their own limbs that have lost function. The device 

has the potential to restore the fundamental ability 

to communicate and to increase independence for 

those with spinal cord injury, stroke, aLS (also known 

as Lou Gehrig’s disease) and other disorders of the 

nervous system. 

High-tech approaches to PTSD

Many other sophisticated tools are in early testing at 

CRRM to improve Veterans’ physical, as well as mental, 

functioning. For example, a recently launched study 

A study volunteer runs on a treadmill in the Gait and Motion Analysis Lab at the Center for Restorative and Regenerative Medicine, his legs taped 

with reflective markers that are tracked by motion-capture cameras. Meanwhile, researchers check the results from software that creates a 3D 

representation of the volunteer’s leg movements.
SPRING 2010 45

is evaluating whether a “Virtual Iraq” virtual reality 

program, used for years in exposure-based therapy to 

recreate distressing situations in controlled clinical 

settings, can identify someone at increased risk for 

posttraumatic stress disorder before major symptoms 

appear. “Experts believe that early intervention will 

make a difference,” says William Unger, Phd, chief 

of the PTSd program at the Providence Va Medical 

Center and a Brown University assistant clinical 

professor. “What we’re working on now is an objective 

way to identify those at higher risk who might benefit 

from such early treatment.” 

In another example of forward-looking research, aaron 

and a team of CRRM researchers are developing a 

method to measure blood flow in bones noninvasively, 

just by an MRI, to distinguish live from dead tissue. 

“Surgeons have a tough time telling live from dead 

tissue in a fresh wound,” aaron explains. “This 

distinction is extremely important for wound 

management because we want to save all live tissue, 

but dead tissue can become dangerously infected.” 

Because Veterans wounded in the conflicts in Iraq and 

afghanistan are returning with devastating injuries that 

would have been fatal in past wars, there is a heightened 

need for these types of progressive healing approaches. 

It’s a prime example of scientific inquiry driven by realworld needs. Sums up aaron, “We’re cranking up our 

research base to catch up with the clinical need.” 

Terms in restorative and regenerative medicine

biohybrid limbs. Artificial arms and legs that incorporate human 

tissue with manmade elements to perform like natural limbs. 

tissue Engineering. Replacement, repair, or regrowth of tissues 

using synthetic materials and human cells.

biomimetics. Creation of materials that imitate natural biology. 

Neurotechnology. Application of science to elucidate and 

harness the brain’s power to improve the body’s ability to function. 

Dr. Roy Aaron is director of VA’s Center for Restorative and Regenerative 

Medicine and a professor of orthopedic surgery at Brown University. 
46 V A R E S E A R C H T O D AY

t H E b R AIN

bRAIN bANkS—PRoVIdING PRECIouS CluES About 

wHy A bRAIN bREAkS dowN 

A collection of specimens at the Bedford VA is providing insights on Alzheimer’s disease and 

traumatic brain injury

The brain, running right, is a staggeringly capable 

instrument—commander of thought and behavior. 

But degraded by disease or injury, this three-pound 

organ is associated with some 600 neurological 

disorders, according to the National Institute of 

Neurological disorders and Stroke. 

The brain has long kept scientists baffled: What 

biological changes are to blame in medical conditions 

such as traumatic brain injury and alzheimer’s disease? 

Its elaborate structure makes the brain uniquely 

difficult to study. also, brain biopsies are too risky, as 

a rule, and diagnostic images generally fall short of the 

desired detail. So neurology researchers rely heavily on 

brain banks, including some housed at the Bedford Va 

Medical Center in Massachusetts, for collecting clues 

about the biological nature of brain-related medical 

conditions. People with these types of diseases—and 

others without—arrange to donate their brains after 

death to advance scientists’ understanding of the ravages 

wreaked by various ailments. 

“We can’t treat what we don’t understand,” says ann 

McKee, Md, head of the neuropathology service for 

the Va New England Healthcare System and director 

of the Bedford Va-based brain banks. “The idea with 

these banks is to learn as much as possible about brain 

diseases, including their origins and any environmental 

or genetic triggers.” 

Concussions: The sports-military link

at the Boston University Brain Bank at the Bedford 

Va Hospital, McKee studies the enduring effects of 

repeated head injury from contact sports and military 

combat. In the last couple of years, she has focused 

her investigation on the brains of deceased athletes 

who received many concussions during their careers—

commonly boxers, football players and hockey players. 

In many of these athletes, researchers have identified 

a degenerative neurological condition called chronic 

traumatic encephalopathy, which during life can cause 

memory loss and erratic behavior. 

“We’re starting to understand so much about the parts 

of the brain involved in traumatic injury, and about 

links between brain structures and clinical symptoms,” 

explains McKee, who is now also studying whether 

military troops with traumatic brain injury from 

blasts or other exposures on the battlefield experience 

the same types of effects. “There are clear parallels 

with Veterans,” notes McKee—chronic traumatic 

encephalopathy is associated with brain trauma, and 

exactly how the trauma occurs may not be critical in 

some of the scientific questions being studied. 
SPRING 2010 47

Medical students visit one of the brain banks 

housed at the Bedford VA Medical Center. 

“ We’re starting to understand so much about 

the parts of the brain involved in traumatic 

injury, and about links between brain 

structures and clinical symptoms.”
48 V A R E S E A R C H T O D AY

McKee believes researchers “are on the brink of a 

huge breakthrough” in understanding what people 

go through after a traumatic injury, and that brain 

banks hold promise, too, for studying mental health 

conditions such as posttraumatic stress disorder. “We 

really need to do exactly what we’re doing with other 

conditions—establish a special brain bank to allow 

us to fully analyze the brains of those who are diagnosed 

with PTSd,” says McKee, who surmises that many 

people with this “very heterogeneous condition” may 

have structural brain lesions leading to their symptoms. 

To help researchers resolve remaining questions, 

29-year-old Iraq Veteran Will Reynolds III has already 

decided to donate his brain for study after his death. 

He plans to make the donation through the Sports 

Legacy Institute, which studies the effects of concussion 

and often partners in its research with McKee and the 

Boston University Brain Bank. Reynolds, a West Point 

alum, was exposed to multiple blasts while serving in 

Iraq, including an IEd explosion that left his left leg 

and arm severely injured. “Being in my unique scenario, 

exposed to so many blasts, my brain and other organs 

may be useful to help Veterans down the line with the 

same kinds of trauma,” he says. 

This type of altruistic donation, to spare others 

suffering, is common, says McKee. “With Veterans, 

as with athletes, donations are driven by an esprit de 

corps—‘I hope by donating my brain I will help my 

fellow soldiers in the future.’” In other situations, people 

want to understand what their family member went 

through, or if a disease such as alzheimer’s may run 

in their family.

How Alzheimer’s unfolds 

alzheimer’s disease—which affects some 4.5 million 

americans, including many aging Veterans, with the 

figure expected to triple by 2050—is a primary focus 

of brain bank research along with traumatic brain 

injury. Va researchers approach the study of alzheimer’s 

from many perspectives, but the far-reaching role of 

brain banks in such investigation is hard to overstate, 

according to Neil Kowall, Md, director of the Va New 

England Geriatric Research, Education and Clinical 

Center and the NIH-funded Boston University 

alzheimer’s disease Center. 

Currently, brain autopsy is the only way to definitively 

diagnose alzheimer’s disease, Kowall points out. 

Looking at the brain under a microscope after death is 

far superior to diagnostic imaging for scrutinizing the 

telltale brain changes in alzheimer’s: protein clumps 

called amyloid beta “plaques” and twisted protein fibers 

called neurofibrillary “tangles.” 

animal models have helped scientists understand 

certain molecular events that the disease involves, 

but these models’ usefulness is extremely limited, says 

Kowall: “Even between the brain of a monkey and that 

of a person, there’s a massive difference in complexity. 

They say ‘you can’t teach an old dog new tricks,’ but 

there’s no animal analog to a person not being able to do 

something that once was easy—balancing a checkbook, 

or taking apart an engine.” 

Ruth Henry says difficulty balancing a checkbook 

was one of the first signs of alzheimer’s disease for 

her husband, John, who was diagnosed with the 

condition at age 62 and donated his brain to the 

Bedford Va, where he received care for several years 

before his 2004 death. “Math had been a game to 

John,” she says of the post-World War II army Veteran, 

who, perhaps ironically, fully embraced the standard 

recommendations for reducing alzheimer’s risk. He 

stayed mentally and physically active and ate a healthful 
SPRING 2010 49

diet. “He just wanted to do whatever he could to help 

other people avoid what he was going through,” Henry 

says about her husband’s reasons for donating his brain 

for scientific study. John’s gift to medical science may be 

especially valuable to researchers because his identical 

twin brother, Charles, also contributed his brain after 

death from a cause unrelated to alzheimer’s disease. 

By studying donated brains from those with and 

without alzheimer’s, says Kowall, Va and other 

researchers are already homing in on some of the early 

brain changes in the disease, and how alzheimer’s 

differs from typical memory loss. “Many people have 

memory trouble. We are uncovering clues to tell us 

when mild cognitive impairment is an opening shot 

of alzheimer’s.”

Identifying early changes, Kowall says, could steer 

scientists toward interventions to halt the progression 

of alzheimer’s disease before it becomes disabling. 

“This is a disease without a cure right now. Blocking 

the early biological processes in alzheimer’s disease 

requires an understanding of how the dominos fall 

as the disease unfolds.” For understanding how 

alzheimer’s and other neurological diseases evolve—

and in turn, how they might be effectively treated—

brain donation is, in Kowall’s words, a “unique gift 

with no adequate substitute.” 

Research based at the Bedford (Mass.) VA Medical Center is examining the underlying biological damage that may be common to combat troops who 

survive blasts and football players, boxers and other athletes who sustain head injuries. 

Bedford VA houses several brain banks

Dr. Ann McKee of VA and Boston University oversees several brain banks, all housed 

at the Bedford VA Medical Center. They include those of: 

 The Boston University Alzheimer’s Disease Center and the school’s New 

England Centenarian Study, the largest and most comprehensive study of 

centenarians and their families in the world

 The Center for the Study of Traumatic Encephalopathy, a major collaboration 

with the Sports Legacy Institute that is partly funded by the VA New England 

Geriatric Research and Clinical Center and several other agencies, including 

the National Institute on Aging

 The Framingham Heart Study, a project of Boston University and the National 

Heart, Lung and Blood Institute
50 V A R E S E A R C H T O D AY

f A m I l y

ExPloRING tHE fAmIly’S RolE IN HElPING SEVEREly 

wouNdEd VEtERANS

Caregivers and family members are at the heart of new polytrauma research 

I

t was shortly after Christmas 2006 when an insurgentmade missile tore through Juan Roldan’s Humvee 

and changed his life forever. The young army staff 

sergeant suffered major injuries to his spinal cord, brain 

and other organs and would eventually need both legs 

amputated. The gunner on the vehicle was also severely 

wounded, and the driver—a private who Roldan says 

was “one of the best soldiers you could ever ask for”—

was killed instantly. Today, Roldan wears a memorial 

bracelet engraved with his name. 

Roldan, now 25, bears painful memories of the incident 

and struggles to keep a positive attitude. He relies on 

his devoted mother, Carmen, for day-to-day help in 

the Silver Spring, Md., apartment provided to him by 

operation Homefront. He goes to the Washington, 

dC, Va Medical Center or Walter Reed army Medical 

Center for care at least weekly. Now divorced, he proudly 

shows visitors a picture of his little daughter, Bryana, and 

says she’s a big part of his motivation to keep going. 

Families such as the Roldans are the focus of research 

based at the Minneapolis Va Medical Center, home to 

one of Va’s four main polytrauma centers, where the 

nation’s most severely wounded Veterans receive care. 

one study under way is called Family and Caregiver 

Experiences with Polytrauma, or FaCES. Lead 

investigator Joan Griffin, Phd, says the study should 

provide much-needed information about the current 

and long-term needs of families—people who, in many 

cases, will continue to be involved in their loved ones’ 

care for years or even decades to come. 

“That’s the big question for us—the long-term needs,” 

says Griffin, who is with Va’s Center for Chronic 

disease outcomes Research and the polytrauma 

and brain-injury wing of Va’s Quality Enhancement 

Research Initiative (QUERI). “These Veterans, for the 

most part, are a young population. So you’ve got parents 

who are in the prime of their working years and looking 

forward to retirement, who are all of a sudden thrown 

into a whole new experience they weren’t expecting. 

or you’ve got a 21-year-old wife who may not have the 

coping skills to deal with a husband who has a brain 

injury and who now may not be employable. What are 

these families going to do over the long term?” 

The FaCES study team is analyzing survey responses 

from 565 families and conducting in-depth interviews 

with some of the respondents. Most of the respondents 

are the parents, spouses or significant others of Veterans 

with polytrauma injuries. In some cases, the caregiver 

may be a friend or other relative. The situations are 

diverse: In some cases, the Veteran has improved and no 
SPRING 2010 51

One study under way is called 

Family and Caregiver Experiences 

with Polytrauma, or FACES. 

Carmen Roldan is helping to care for her son, Army Veteran 

Juan Roldan, as he continues to struggle to regain his 

independence. He was severely wounded in Iraq in late 2006. 
52 V A R E S E A R C H T O D AY

longer needs substantial help. In others, intensive family 

caregiving is still required. In these families, the burden 

on caregivers can be grueling: 

 Many caregivers are spending more than eight hours a 

day helping their loved one. 

 They are often struggling to hold down a job and care 

for other family members. 

 Many have had to stop working and drain their 

savings or retirement accounts to help pay for care. 

Besides focusing on long-term needs, the study is 

also yielding insights on what families go through 

immediately after their loved ones are injured. 

“Both the literature and the first glimpses of our data 

are showing that it’s those first few months that are very 

difficult for families,” says Griffin. “They’re difficult 

emotionally and financially. They are often taking off 

a lot of work, and possibly paying for travel and hotels 

on top of everything. Financially it’s a burden, and 

emotionally they’re still in a state of shock.” 

For perhaps the first time in U.S. history, says Griffin, 

many military families are involved in the care of their 

seriously injured loved one from a very early stage. That’s 

partly because in the past, far fewer military personnel 

survived grievous wounds. It’s also because jet travel is 

now easier and more common, and people know about 

the injuries a lot faster. 

“you might find out 24 hours afterward, get on a plane 

and be there [in Germany] within three days, whereas 

before it might have taken weeks,” says Griffin. 

Severely wounded troops are typically evacuated from 

the war zone to the main U.S. military hospital in 

Germany. The next stop is generally a stateside military 

hospital such as Walter Reed, which specializes in 

acute and rehab care for polytrauma, followed by a Va 

polytrauma center, where rehab care continues with a 

multidisciplinary team of experts. 

Those first few weeks and months may be just the 

beginning of a very long haul for polytrauma Veterans 

and their loved ones, says Griffin, but this period is what 

breaks some families—especially if there was underlying 

economic or emotional stress or poor relationships to 

begin with. other families seem able to withstand the 

strain. Griffin hopes her research will reveal factors that 

help families rebound from adversity. 

“We’ve heard countless stories that are inspiring, to 

the point where they bring us to tears,” she says. “Some 

families have been through this horrible thing but 

found purpose in it and become stronger through it. 

The human spirit is resilient. It’s a powerful thing.” 

other studies by the Minneapolis group aim to make 

Va polytrauma care more family-centered. That means 

involving families in the care plan, giving them the right 

resources, and seeing to their needs. 

“If we keep families informed and involved in a way 

that they want to be involved, and in which the patient

wants them to be involved, adherence to treatment, 

and outcomes, are likely to be better,” says Nina Sayer, 

Marine Cpl. Jason Poole, seen here with his mother, Trudie, suffered 

a brain injury and other severe wounds in Iraq in 2004. 
SPRING 2010 53

Phd, research chairperson for the polytrauma-brain 

injury QUERI. 

The researchers have looked to other areas of 

medicine—such as pediatrics—for guidance on how 

to best involve family members in a patient’s care. The 

polytrauma population, though, is obviously different in 

many ways. and finding the right balance—how much 

to involve the family—can be tricky, says Carmen Hall, 

RN, Phd, also with the QUERI. 

“We’re learning how to do that,” she says. “We don’t 

have a lot of guidance on this issue from the previous 

work in pediatrics. For an autonomous adult, family 

involvement and support looks different. It’s a little 

more challenging, because of privacy rules and our wish 

to optimize the autonomy of the Veteran. With younger 

Veterans whose parents may become very involved in 

their lives, a tension can develop between the Veteran’s 

need for independence and the parents’ instinct to take 

care of their son or daughter.” 

one tool developed by the researchers is called the 

Family Care Map. It’s a Web-based guide that lays out 

each stage of Va rehab care in a user-friendly way. Care 

teams use it as a reference with families during the 

Veteran’s inpatient stay. In addition to it being available 

on the Web, families receive it in notebook form, with 

worksheets and references. For one thing, it allows for 

consistent terminology—otherwise, different clinicians 

may talk about the same thing using different jargon, 

and families may get confused. 

“We wanted to provide a tool for both families and 

clinicians so they had the same ‘playbook,’” says Hall. 

“The Family Care Map creates a common framework 

from which to talk about the polytrauma rehab plan 

and how the family can participate.” 

The Family Care Map has been tested and continues 

to evolve as researchers and clinicians learn more about 

families’ needs. “It’s a dynamic document,” notes Sayer. 

She points out that the map is just one tool; more 

broadly, a family-centered culture is developing at the 

polytrauma centers. Some of the changes being guided 

and tracked by research: 

 Training for registered nurses at the sites now includes 

more family-centered skills.

 Treatment goals are posted in patients’ rooms, along 

with white boards for family and staff to exchange 

information. 

Family peer support groups are being expanded.

above all, says Hall, family-centered care is about 

“recognizing the uniqueness of each family and trying 

to explore with them and with the Veteran the ways in 

which the family will be involved in care.” 

Today, Juan Roldan is looking forward to moving to 

Florida, where the organization Homes for our Troops 

is building him a house. His mother, Carmen, is 

prepared to continue caring for her son—but only in 

a way that works for him. 

“I do whatever I have to do for my son. When he 

says ‘I don’t need you anymore,’ I will go out of the 

picture. But until that time, I’ll be here for whatever 

he needs.” 

Juan Roldan displays a photo of himself with his three-year-old 

daughter, Bryana. 
54 V A R E S E A R C H T O D AY

“ It simplifies my taking [my 

medications] and lets me know 

if I have or haven’t taken them.” 
SPRING 2010 55

P H A R m A C y

mANAGING mEdICAtIoNS mAdE EASIER

Patients with serious mental illness may benefit from a new pharmacy approach, says a 

study at the Ann Arbor VA

call it pill bottle sprawl. For millions of americans— 

especially the elderly and those with chronic 

illnesses—kitchen cabinets and counters are 

increasingly taken up by white and amber plastic 

bottles containing their myriad medications. It’s not 

uncommon for people to be on as many as 15 or so 

prescription drugs, not to mention vitamins and overthe-counter remedies. 

Managing it all can be a burden. Those for whom 

adherence is most critical—such as patients with serious 

mental illness—often have the hardest time keeping 

track of what drug to take when. Store-bought pill 

organizers can help, but filling them each day or week 

is a challenge in itself. Staying on top of refills adds 

another layer of confusion. 

There’s a better way, according to a recent study at the 

Va ann arbor Healthcare System. Researchers there 

worked with clinicians and pharmacy staff to develop 

and test a system they call MedsHelp. It involves 

innovative packaging, personalized refill service, and 

close cooperation among pharmacy staff, social workers, 

nurses and doctors. 

“What’s unique about MedsHelp is that Va is trying 

to meet the needs of patients with daunting medical 

conditions and medication regimens with very 

personalized care,” says agnes Jensen, a health services 

research associate and pharmacy technician who was part 

of the randomized clinical trial that led to the program.

Central to the new approach is “unit of use” packaging. 

Patients receive custom-made blister packs straight from 

the pharmacy, with their medications for each time of 

day—breakfast, lunch, dinner and bedtime—packed 

into separate plastic bubbles. There’s a row for each day 

of the week, a column for each time of day. Colorful 

graphic icons and clear instructions are printed right on 

the packs. 

The concept isn’t totally new. The packaging 

components of MedsHelp have been applied in other 

settings and have proved effective for patients, especially 

older ones, with conditions such as diabetes and heart 

disease. But the Va ann arbor team expanded on the 

idea in several ways—for example, by packaging all the 

meds for a whole week into one visually friendly sheet 

format, with complete labeling for all the drugs. 

Air Force Veteran Jeanette Eastham took part in a research project at the 

Ann Arbor VA that helped her manage her medications. 
56 V A R E S E A R C H T O D AY

The packaging is only part of MedsHelp, but it’s the 

feature that seems to elicit the most effusive feedback 

from patients who no longer have to cope with 

assembling—and remembering to take—their daily 

meds. This is critical for those with serious mental 

illness, as they often have impaired thinking skills. 

“They have a system by which I can’t make a mistake,” 

says Paul Getzen, 67, a Vietnam Veteran who developed 

bipolar disorder later in life. “It’s all organized for you.” 

He adds that if he goes to a non-Va hospital, it’s easier 

for him to give all his information. “on the back, it 

describes in great detail each pill—the size, shape, color, 

dose. So if I have to go to a civilian hospital, I just take 

that with me and everything is there. I don’t have to 

explain to the doctor what I’m on, or how often I take it, 

or the dose.” 

Veteran Jeanette Eastham, 56, who has mood and 

personality disorders and lost her voice from cancer, says, 

“It simplifies my taking them and lets me know if I have 

or haven’t taken them.” She points out that the social 

worker who visits her home can also tell easily whether 

she has missed any doses. “The pills are loaded right in 

the containers and she can see if I’ve taken them.” 

adds ann Whaley, 48, “I don’t have to think about 

getting [my medications] ready.” She has struggled with 

bipolar disorder since her 20s. 

Whaley’s doctor is Marcia Valenstein, Md, MS, a 

physician and health services researcher at the ann 

arbor Va. She led the randomized clinical trial of 

MedsHelp that led to its being implemented at her 

Va hospital and four others in the region. The study 

team, which included researchers from the ann arbor 

Va and University of Michigan as well as other Va 

and academic sites, reported their results recently in 

Schizophrenia Bulletin. They found that patients using 

MedsHelp were significantly more likely to be taking 

their antipsychotic medication at 6 and 12 months. The 

study, which involved 118 Veterans with schizophrenia, 

schizoaffective disorder or bipolar disorder, did not 

show any easing of symptoms—even with the increases 

in adherence. But the study may not have been long 

enough to capture that, suggests Valenstein. also, 

those in the study had to be able to understand key 

elements of the program, so they were “not at the higher 

end of the severity range,” says Valenstein, noting that 

symptom improvement may have been easier to see in 

patients with more severe illness. 
SPRING 2010 57

The study didn’t track drug adherence for other medical 

conditions, even though MedsHelp includes all of a 

patient’s various drugs. 

“I will have their antipsychotic, multivitamin, calcium, 

water pill, cholesterol medication, diabetes and 

hypertension drugs, all in one packet. That helps them be 

more compliant,” says pharmacist Mary Moy-Sandusky, 

citing a typical regimen for patients in MedsHelp. 

Moy-Sandusky, who now manages the program, 

says another important feature of MedsHelp is the 

personalized service. 

“Patients have a social worker through the program, and 

they can also call us in the pharmacy with any problem. 

We have a really good rapport with them.” 

adds Jensen: “Even in a large setting like a Va medical 

center, patients and pharmacy staff develop familiar, 

trusting relationships. MedsHelp patients know their 

pharmacist and pharmacy technician by name.” 

The extra care coordination and pharmacy services 

involved in MedsHelp cost Va about $125 per patient 

per month. Valenstein says that “this cost should be 

placed in the context of the high costs of the many 

medications that these patients are prescribed and the 

waste that occurs when meds are not taken regularly.” 

also, the program handles refills on a custom basis so 

that “if a doctor is going to be changing a medication, 

I can send the patient only a one- or two-week supply,” 

says Moy-Sandusky. She notes that the newergeneration antipsychotics commonly prescribed 

for those with serious mental illness can cost up to 

$400 per month.

For now, the program is limited to five Va hospitals 

in one Midwest region. as the benefits of MedsHelp 

are confirmed in larger trials, Valenstein believes it 

will be practical for Va to implement the system at 

more facilities. 

Meanwhile, most MedsHelp patients are clamoring to 

stay on the program—which now services more than 

215 Veterans—because they like it so much. 

Says Navy Veteran Getzen, “I feel great, and my kids 

say I’m on-target 110 percent.” 

From left: Pharmacist Mary Moy-Sandusky meets with MedsHelp participant Ann Whaley; a close-up of the “unit of use” packaging used in the 

program; MedsHelp participant Paul Getzen displays the medication pack that is regularly mailed to his home through the program. 
58 V A R E S E A R C H T O D AY

A w A R d E E S

Barnwell Award

The Barnwell Award was established by VA in 2007 to 

honor John Blair Barnwell, MD, director of research and 

education for VA in the 1940s. He formed the Veterans 

Administration-Army-Navy Cooperative Studies in the 

Chemotherapy of Tuberculosis Program, which pioneered 

the model of the multi-site clinical trial. The award 

recognizes senior VA investigators who have achieved 

international acclaim for clinical research in areas of 

prime importance to VA’s research mission. 

William C. Duckworth, MD

dr. William C. duckworth is 

director of diabetes research 

at the Phoenix Va Medical 

Center and a professor 

of clinical medicine and 

biochemistry at the University 

of arizona Medical School. 

His lab focuses on insulin 

degradation and the role of insulin metabolism in 

insulin action. duckworth’s primary clinical interest is 

type 2 diabetes and its complications, and he serves as 

co-chair of both the Va diabetes Trial and a separate 

Va study on diabetic nephropathy. He has also studied 

the delivery of diabetes care to Veterans. duckworth is a 

renowned author and lecturer, as well as a distinguished 

member of the Journal of Cardiometabolic Syndrome’s 

editorial board. He is a diplomate of the american Board 

of Internal Medicine and is certified by the american 

Board of Endocrinology and Metabolism. He has 

received numerous honors and awards beyond his many 

research grants and contracts, and has participated in 

various National Institutes of Health research reviews. 

William C. Cushman, MD

dr. William C. Cushman 

is chief of the preventive 

medicine section at the 

Memphis Va Medical 

Center; lead hypertension 

consultant for Va at the 

national level; and professor 

of preventive medicine, 

medicine and physiology at the University of Tennessee 

College of Medicine. Cushman served on the executive 

committee that wrote the 2003 Seventh Report of the 

Joint National Committee on Prevention, detection, 

Evaluation, and Treatment of High Blood Pressure 

(JNC 7) and is currently on the JNC 8 panel. a fellow 

of the american College of Physicians and american 

Heart association, Cushman has been an investigator on 

RECoGNIzING ExCEllENCE 

An overview of major awards presented to outstanding VA investigators during National 

VA Research Week 2010

degradation and the role of insulin metabolism in 
SPRING 2010 59

many clinical studies relating to hypertension, lipids and 

type 2 diabetes. He served as Va chair for the National 

Heart, Lung, and Blood Institute (NHLBI)-sponsored 

antihypertensive and Lipid Lowering Treatment to 

Prevent Heart attack Trial (aLLHaT)—the largest 

hypertension trial ever—and is currently principal 

investigator for the Va Clinical Center Network and 

chair of the Blood Pressure Working Group of the 

NHLBI-sponsored action to Control Cardiovascular 

Risk in diabetes (aCCoRd) trial. Cushman’s research 

has led to a Va-wide performance measure that promotes 

the evidence-based use of drugs known as thiazide 

diuretics to manage hypertension. 

Paul B. Magnuson Award

This award, established in 1998, honors Paul B. 

Magnuson, MD, who, as a bone and joint surgeon in 

VA, continuously sought new treatments and devices 

to help Veterans. The award is given annually to a 

VA rehabilitation investigator who exemplifies the 

entrepreneurship, humanitarianism and dedication to 

Veterans shown by Dr. Magnuson during his career. 

Robert L. Ruff, MD, PhD

dr. Robert L. Ruff is 

the Veterans Health 

administration’s national 

director for neurology. His 

research interests include 

stroke rehabilitation and 

combat-related traumatic 

brain injury. Ruff, who 

received his Md and Phd degrees from the University 

of Washington, has been chief of the neurology, 

rehabilitation and spinal cord injury services at the Louis 

Stokes Va Medical Center, and is medical director 

of the FES Center in Cleveland, a Va Rehabilitation 

Research Center of Excellence. a professor of neurology 

and neurosciences at Case Western Reserve University, 

Ruff has been on the editorial board of the Journal of 

Rehabilitation Research and Development since 1999, 

serving as the journal’s deputy editor since 2004 and 

as editor-in-chief from 2005 to 2007. He was associate 

editor of the journal Neurology from 1994 through 1996 

and a member of the editorial board of Muscle & Nerve

from 2004 to 2007.

PECASE winner Dr. Melina Kibbe is a vascular surgeon and biomedical researcher at the Jesse Brown VA Medical Center in Chicago. 
60 V A R E S E A R C H T O D AY

Middleton Award

VA established the Middleton Award in 1960 to honor 

William S. Middleton, MD, an educator and physicianscientist who served as VA’s chief medical director from 

1955 to 1963. The award is given each year to one or two 

senior VA investigators for major achievements in areas 

of prime importance to VA’s research mission.

Michael D. Norenberg, MD

dr. Michael d. Norenberg, 

a Va clinician-researcher 

for more than 36 years, is 

currently on staff at the Va 

Miami Healthcare System. He 

is also a professor of pathology 

and director of neuropathology 

at the University of Miami, 

Miller School of Medicine, where he holds appointments 

in the departments of biochemistry/molecular 

biology, neurology and neurosurgery. In addition, he 

is an affiliate faculty member with the Miami Project 

to Cure Paralysis. Norenberg has made essential 

contributions in a range of research areas. among other 

accomplishments, he has played a key role in elucidating 

the biology of astrocytes, the main supporting cells of 

the central nervous system; characterized pathological 

changes and identified potential targets for therapeutic 

intervention in spinal cord injury; and contributed to 

a better understanding of brain edema (swelling from 

excess fluid) as a consequence of brain trauma. also, 

his research laid the groundwork for a new treatment 

approach for hyponatremia—a sodium imbalance—

that has dramatically reduced the incidence of a related 

complication called central pontine myelinosis, which 

affects the brainstem. all told, dr. Norenberg has some 

240 scientific publications to his name. He has served on 

the editorial boards of his field’s leading journals and has 

won numerous awards for research and teaching.

Edward J. Weinman, MD

dr. Edward J. Weinman, 

with the Va Maryland 

Healthcare System, has been 

a Va clinician-investigator 

for 27 years and has made 

seminal contributions to the 

understanding of kidney 

function. His pioneering 

achievements have included mapping out the molecular 

processes involved in kidney function and isolating, 

cloning and demonstrating the function of two 

proteins, NHERF-1 and NHERF-2, that regulate 

kidney function. dr. Weinman’s discoveries have proved 

clinically relevant not only in nephrology but also in 

gastroenterology and neurology. In addition to 173 peerreviewed publications, dr. Weinman has authored or 

co-authored 27 invited reviews and several editorials and 

letters to the editor in leading medical journals. He has 

also contributed various chapters to medical textbooks, 

including Cecil Essentials of Internal Medicine. His 

research is currently funded by both Va and the 

National Institutes of Health.

Presidentialearlycareer Award for Scientists

andengineers (PecASe)

The PECASE program was established by the White 

House in 1996 to recognize and nurture outstanding 

scientists and engineers who are in the early stages of their 

careers and “who show exceptional potential for leadership 

at the frontiers of scientific knowledge during the twentyfirst century.” 

Melina R. Kibbe, MD

dr. Melina R. Kibbe, of the 

Jesse Brown Va Medical 

Center in Chicago, studies 

the effects of nitric oxide 

on vascular smooth muscle 

cell proliferation, with a 

focus on minimizing blood 

vessel damage associated 
SPRING 2010 61

with vascular bypass grafting and arterial injury. a 

Va Career development awardee, she has established 

a vibrant and robust vascular research laboratory 

located within Northwestern University’s Institute for 

BioNanotechnology in Medicine. Kibbe has received 

the university’s drew Senyei, Md, Translational 

Research award to develop a nitric oxide-releasing 

graft for better recovery following vascular surgery. Her 

research has been recognized and supported by diverse 

public and private grants, and she has also exhibited an 

award-winning dedication to teaching and a sustained 

commitment to charitable causes. Kibbe has published 

more than 50 peer-reviewed manuscripts and 10 book 

chapters, and her work has been presented at numerous 

national and international meetings.

Alexander Sox-Harris, PhD

dr. alex Sox-Harris earned 

graduate degrees in counseling 

psychology and statistics at 

Stanford University. Based 

at the Va Palo alto Health 

Care System, Sox-Harris plays 

key roles in three Va research 

centers: He is a health services 

researcher at the Center for Health Care Evaluation; 

a statistician and methodologist at the Bone and Joint 

Rehabilitation Center; and associate director of the 

Program Evaluation and Resource Center. a main 

focus for Sox-Harris has been improving the quality 

of addiction treatment. He has led efforts to examine 

and refine process-quality measures widely used to 

predict outcomes for patients treated for drug or alcohol 

addiction. Sox-Harris also examines system-wide 

variability in the use of Food and drug administrationapproved medications in the treatment of alcohol 

dependence, and studies the relationship between alcohol 

misuse screening data and subsequent medical outcomes. 

He has more than 50 scientific articles and nine book 

chapters to his credit. 

under Secretary’s Award foroutstanding

Achievement in Health Servicesresearch

This award is presented annually by VA to an investigator 

whose health services research has added significantly 

to the understanding of factors that affect the health of 

America’s Veterans or has led to a major improvement in 

the quality of their health care, and who has demonstrated 

leadership in the research community and excellence in the 

training and mentorship of young investigators.

Mary K. Goldstein, MD, MS

a health services researcher 

at the Va Palo alto Health 

Care System for more than 18 

years, dr. Mary K. Goldstein 

has focused on studying 

functional status in geriatrics, 

hypertension management, 

clinical guideline compliance, 

and automated clinical decision support systems. Her 

work in health informatics is known nationally and 

internationally. Within the Consortium for Healthcare 

Informatics Research, funded by Va Health Services 

Research and development, Goldstein is principal 

investigator for the project on translational use cases. 

as a Va Career development awardee, Goldstein led 

a team that developed an automated clinical decision 

support system for hypertension management known 

as aTHENa-CdS. The system combines patient 

information from Va’s electronic medical records system 

with an automated knowledge base of hypertension to 

generate patient-specific recommendations for managing 

hypertension. The recommendations are displayed on 

clinicians’ computer screens when they see patients. 

Goldstein serves as director of the Geriatric Research, 

Education and Clinical Center at the Palo alto Va and 

shares her expertise and experience by actively mentoring 

Va researchers and clinicians. 
62 V A R E S E A R C H T O D AY

A d V ANCES

RECENt AdVANCES by VA RESEARCHERS 

A sampling of important new scientific findings reported by VA investigators during the 

past few months

ACCORD trial reports blood pressure, lipid results

I

n a surprising result, intensive treatment of high blood 

pressure to reach normal levels—below currently 

recommended levels—did not further reduce the risk 

of stroke and heart attack in people with type 2 diabetes 

who were at very high risk for cardiovascular disease, 

according to the action to Control Cardiovascular 

Risk in diabetes (aCCoRd) clinical trial, one of the 

largest studies ever conducted in this population. The 

study also found that treating multiple blood lipids 

with a fibrate and a statin did not reduce risk more than 

treatment with a statin alone. 

The study was sponsored by the National Institutes 

of Health and included more than 10,000 patients 

with diabetes, including Veterans at 10 Va sites. The 

study tested three strategies to lower the risk of major 

cardiovascular events: intensive control of blood sugar, 

intensive control of blood pressure, and treatment of 

cholesterol and triglycerides. 

Va’s involvement in aCCoRd was led by William 

Cushman, Md, of the Memphis Va Medical Center. 

“our results provide no conclusive evidence that 

targeting a normal systolic blood pressure—less than 

120 mmHg—compared with targeting a systolic blood 

pressure of less than 140 mmHg lowers the overall risk 

of major cardiovascular events in high risk adults with 

type 2 diabetes,” said Cushman. 

He pointed out, however, that the “study suggests that 

lower blood pressure levels in patients like those in 

aCCoRd may reduce the risk of stroke. This finding 

is consistent with other blood pressure trials.” He 

also noted that more intensive blood pressure control 

resulted in a higher risk of adverse events, and that 

people with diabetes should carefully weigh the risks 

and benefits of treatment with their physicians. 

(New England Journal of Medicine, online March 14, 2010) 

Dewey Ratcliff has his blood pressure taken by nurse Margaret Penry 

at the Central Arkansas Veterans Healthcare System. 
SPRING 2010 63

Food industry effort to cut sodium would save lives, 

study suggests 

Avoluntary effort by the U.S. food service industry to 

cut salt in processed foods could have far-reaching 

implications for the health of the U.S. population, 

preventing strokes and heart attacks in nearly a million 

americans and saving $32.1 billion in medical costs, 

according to a study by researchers with Stanford 

University and the Va Palo alto Health Care System.

In the study, the researchers developed a computerized 

model that simulates the effects of reduced sodium 

intake on a large population of people between the 

ages of 40 and 85. Based on a similar salt-reduction 

campaign in the United Kingdom, the researchers 

estimated that a collaborative industry effort could lead 

to a 9.5 percent decline in americans’ salt intake. That, 

in turn, would lead to a very modest decline in blood 

pressure among american consumers, minimizing a 

major risk factor for cardiovascular problems.

“In our analysis, we found these small decreases in blood 

pressure would be effective in reducing deaths due to 

cardiovascular disease,” said Crystal Smith-Spangler, 

Md, a postdoctoral scholar with Va and first author 

of the study. “The numbers of affected people are huge, 

so even a small decrease is significant if you have large 

numbers of people involved.”

By the researchers’ calculations, some 513,885 

americans would be spared from potentially fatal 

strokes in their lifetimes, and another 480,358 would 

not suffer heart attacks as a result of the reduced 

salt campaign. 

(Annals of Internal Medicine, March 2, 2010) 

Stress-affected brain region is smaller in Veterans 

with PTSD 

Aspecific region of the hippocampus, a brain 

structure essential to memory, is significantly 

smaller in Veterans with posttraumatic stress disorder 

than in those without the condition, according to 

a study by a team with Va and the University of 

California, San Francisco. 

The researchers used MRI to scan the brains of 40 

Veterans—20 with combat-related PTSd and 20 

without—and found that the 

region known as the Ca3/

dentate gyrus was at least 

11 percent smaller, on 

average, in those with 

PTSd.

also, the Ca1 region of 

the hippocampus, which 

Researchers at the VA Palo Alto Healthcare System used a mathematical model to project the effects on Americans’ health of proposed reductions in the 

amount of sodium in processed foods. 
64 V A R E S E A R C H T O D AY

shrinks as a part of normal aging, was not significantly 

affected in the Veterans with PTSd, according to lead 

investigator Norbert Schuff, Phd. “This is the first time 

in human subjects that PTSd has been shown to be 

associated with changes in certain specific hippocampal 

regions and not in others,” said Schuff. 

The hippocampus, a small structure found on both 

sides of the brain, helps establish and retrieve memories, 

said co-author Thomas C. Neylan, Md. He noted 

that recurring or intrusive memory of traumatic 

events is a common symptom of PTSd, “and thus the 

hippocampus is of great interest in PTSd research.” 

Neylan said the results raise the possibility that since 

the dentate gyrus has the ability to create new neurons, 

“These changes might actually be reversible through 

treatment.”

The authors cautioned that the findings need to be 

replicated in larger studies. “This is an incremental step 

toward establishing a physical biomarker for PTSd,” 

said Neylan. “a biomarker is our ultimate goal, since 

currently PTSd is diagnosed based on a subjective 

neuropsychiatric examination rather than on physical 

symptoms. He added that a biomarker would provide 

clinicians and researchers with an objective way to 

measure the progress of PTSd treatment, and “would 

also allow us to no longer think of PTSd as a mental 

health diagnosis, with all of its associated stigma for our 

Veteran and military patients, but to view it as a physical 

wound instead.” 

(Archives of General Psychiatry, March 2010)

Study finds potential Alzheimer’s use for immune drug 

rapamycin, a drug that keeps the immune system 

from attacking transplanted organs, may have 

another use: fighting alzheimer’s disease. The drug—a 

bacterial product first isolated in soil from Easter Island 

in the Pacific—reversed learning and memory deficits in 

a mouse model of the disease, reported a team with Va 

and the University of Texas Health Science Center in 

San antonio. 

Rapamycin also reduced lesions in the brains of the 

mice, the team found. The lesions are similar to those 

seen in the brains of people who died with alzheimer’s. 

Last year, researchers at three institutions—including 

the Texas group—announced that rapamycin extended 

the lifespan of aged mice. It was the first pharmacologic 

intervention shown to extend life in an animal model 

of aging.

“While it remains to be determined whether our 

results obtained in mice could be translated in people, 

we are very excited as these findings may lead to a new 

therapeutic intervention to treat alzheimer’s,” said lead 

researcher Salvatore oddo, Phd. 

(Journal of Biological Chemistry, Feb. 23, 2010) 

Antibody boosts therapy for multiple sclerosis

An international team co-led by a researcher with 

Va and the University of Utah found that adding 

a treatment called daclizumab, a type of antibody, 

to standard drug therapy cuts the number of new 

or enlarged brain lesions in patients with relapsing 

multiple sclerosis. 

about 85 percent of MS patients are initially diagnosed 

with a relapsing form of the disease, in which clearlydefined attacks are followed by partial or complete 

recovery periods. 

John Rose, Md, of the Va Salt Lake City Health 

Care System and the University of Utah, said previous 

clinical trials that were not randomized suggested 

benefits from the antibody. The new findings, he said, 

confirm that “daclizumab significantly reduces MS 

lesion formation in people with active relapsing disease.” 

The study included 230 patients at 51 sites in the U.S., 

Canada and Europe. In addition to taking a standard 

MS drug called interferon beta, the volunteers were 

randomly assigned to add-on treatment with highdose daclizumab, low-dose daclizumab or placebo. 

In addition to finding that add-on treatment with 

high-dose daclizumab resulted in a significantly lower 

number of new or enlarged MS lesions, the researchers 
SPRING 2010 65

found that patients treated with either high- or lowdose daclizumab had far more natural killer cells, 

which the researchers believe may account for the 

treatment’s benefits. 

(Lancet Neurology, online Feb. 15, 2010) 

Orthopedic surgery outcomes better at specialized 

hospitals

The more specialized a hospital is in orthopedic 

surgical care, the better the outcomes appear to 

be for patients undergoing hip and knee replacement 

surgery, according to a study of Medicare data by a team 

with Va and the University of Iowa. 

among more specialized hospitals, there were fewer 

serious post-surgical complications such as blood clots, 

infections and heart problems, as well as fewer deaths.

The findings were based on data for nearly 1.3 million 

older patients who received hip or knee replacement 

surgeries between 2001 and 2005 at 3,818 U.S. hospitals. 

The study adjusted for differences in the types of patient 

seen at each hospital, as well as the number of surgeries 

that each hospital performed. Compared with the least 

specialized hospitals, the more specialized hospitals 

treated a lower proportion of women and african 

americans. These hospitals also treated patients who had 

better health overall.

In addition, the rate of post-surgery infection for 

patients who got hip and knee replacements decreased 

from 2.6 percent at the least specialized hospitals to 1.6 

at the most specialized hospitals.

“Learning more about orthopedic specialization could 

help us to better understand how to organize care 

and take ideas from more specialized hospitals to less 

specialized hospitals and result in better outcomes all 

around,” said senior author Peter Cram, Md, with the 

Center for Research in the Implementation of Innovative 

Strategies at the Iowa City Va Medical Center. 

(British Medical Journal, online Feb. 11, 2010) 

Surgeons in action at the VA Palo Alto Healthcare System. 
66 V A R E S E A R C H T O D AY

New genetic-engineering technique could speed 

drug discovery 

Drug discovery in biomedical labs worldwide may 

benefit from a new gene-insertion method being 

developed by a group with Va and Baylor College of 

Medicine in Houston. Until now, researchers have 

generally been able to insert only one gene at a time into 

cells or lab mice to study its effects. The new method 

will enable them to insert several genes at once. Lead 

researcher Matthew H. Wilson, Md, Phd, said the new 

gene-transfer technique “allows you to ask a whole new 

level of questions that you couldn’t ask before.” 

The new method uses carrier genes called transposons. 

discovered in the 1950s, transposons are also known 

as “jumping genes” because they spontaneously hop 

around to different spots on the dNa strands that 

make up an organism’s genome. Several different 

transposons have been studied in recent years because 

they offer an efficient way to ferry new genes into the 

dNa of cells or lab animals. Wilson’s lab has focused 

on one transposon in particular, known as piggyBac. In 

their experiments, the team used the gene and its related 

enzyme to efficiently transfer up to eight genes at once 

into human kidney cells. 

Besides drug discovery, transposons hold promise for 

gene therapy. They are seen as potentially safer, faster 

and more cost-effective than current methods that use 

viruses to transfer beneficial genes into patients’ dNa. 

The recipient of Career development funding from Va, 

Wilson specializes in nephrology research. He hopes to 

eventually develop a treatment for an inherited kidney 

disease called alport Syndrome, which affects 1 in 

5,000 people. His group’s breakthrough in transposonbased gene transfer came as they sought the best ways to 

deliver genes to the kidneys of mice. 

(Proceedings of the National Academy of Sciences, Jan. 26, 2010) 

Dr. Matthew Wilson of the Houston VA Medical Center and Baylor College of Medicine says a gene-transfer method his lab is developing could come 

to play a key role in drug discovery and gene therapy. 
SPRING 2010 67

Blood pressure benefits seen from low-carb diet 

I

n a head-to-head comparison, two popular weightloss methods proved equally effective at helping 

overweight and obese Veterans shed pounds. But, in a 

surprising twist, a low-carbohydrate diet proved better 

at lowering blood pressure than the weight-loss drug 

orlistat, according to researchers with Va and duke 

University Medical Center in durham. 

The findings send an important message to those with 

hypertension who are trying to lose weight, said lead 

author William S. yancy Jr., Md. “If people have 

high blood pressure and a weight problem, a lowcarbohydrate diet might be a better option than a 

weight-loss medication. It’s important to know you 

can try a diet instead of medication and get the same 

weight-loss results with fewer costs and potentially 

fewer side effects.” 

The 146 people in the year-long study had a range of 

health problems typically associated with obesity—

diabetes, high blood pressure, high cholesterol, arthritis. 

Nonetheless, they saw impressive results from the study 

treatments: The average weight loss for both groups was 

nearly 10 percent of body weight. yancy attributes the 

success in large part to the group counseling that was 

offered for 48 weeks. “People tolerated orlistat better 

than I expected,” says yancy, noting that use of the drug 

is often limited by gastrointestinal side effects, but that 

“these can be avoided, or at least lessened, by following 

a low-fat diet closely. We counseled people on orlistat in 

our study fairly extensively about the low-fat diet.” 

The two methods proved equal not only for weight loss, 

but also for reducing levels of cholesterol and blood 

sugar. With regard to blood pressure, though, there 

was a distinct edge to the low-carb approach. Some 47 

percent of patients in the low-carbohydrate group were 

able to decrease or discontinue their blood pressure 

medication, while only 21 percent of the orlistat group 

were able to do so. 

(Archives of Internal Medicine, Jan. 25, 2010)

Hypertension drugs may thwart dementia 

Drugs known as angiotensin receptor blockers 

(aRBs)—brand names such as atacand or 

avapro—are used mainly to treat high blood pressure 

and heart failure because they block a hormone that 

narrows blood vessels. a team at the Bedford (Mass.) 

and Boston Va medical centers found that the drugs 

may also help prevent dementia, adding to similar 

results from some previous studies. 

The study, based at Va’s Center for Health Quality 

outcomes and Economic Research, analyzed the 

records of more than 800,000 older Veterans who had 

been treated for hypertension or heart disease. They 

found that those taking aRBs were up to 24 percent 

less likely to develop dementia than those taking other 

drugs. Moreover, of patients who had alzheimer’s 

disease at the study’s outset, those on aRBs were half 

as likely to enter a nursing home, compared with those 

taking aCE inhibitors or other heart drugs. 

In an interview with Business Week, senior author 

Benjamin Wolozin, Md, Phd, with Va and Boston 

University, said improved blood flow to the brain is the 

likely mechanism behind the drugs’ apparent cognitive 

benefits. “If you get no blood to the brain, you’re not 

going to think well,” he said. 

Wolozin pointed out that randomized clinical trials will 

be needed to test whether aRBs are truly responsible 

for the alzheimer’s-thwarting effect seen in his group’s 

large database study. Meanwhile, he cautioned that the 

new evidence is not enough to warrant routine clinical 

use of aRBs to halt dementia, adding that the drugs 

could pose significant side effects for some patients, such 

as drops in blood pressure that lead to falls. 

(British Medical Journal, Jan. 12, 2010) 
68 V A R E S E A R C H T O D AY

OEF/OIF Veterans with mental health conditions use 

more VA medical services 

I

n a study of nearly 250,000 Veterans of the wars 

in Iraq and afghanistan, those with mental health 

diagnoses used non-mental health medical services 

in Va at higher rates than those without mental 

health disorders. 

The most striking finding was that Veterans whose 

mental health diagnosis was PTSd used Va medical 

services at almost twice the rate of those whose mental 

health diagnosis was another disorder, such as depression. 

The overall results are consistent with studies of 

Veterans from earlier wars, says lead author Beth Cohen, 

Md, MaS, a staff physician at the San Francisco Va. 

“What we don’t know from this data,” she says, “is 

whether these Veterans are using medical care more 

often because they simply have more medical diseases, 

or because they need help with mental health concerns 

but seek care in other medical settings” because of the 

stigma associated with mental health treatment.

The authors found that Veterans with PTSd used nonmental health medical services, including primary care, 

emergency care, and visits to other medical specialists, 

at a 91-percent higher rate overall than those without 

mental health diagnoses. Veterans with a mental health 

diagnosis other than PTSd had a 55-percent higher use 

rate than those without mental health diagnoses.

To explore the factors driving the Veterans’ use of 

non-mental health medical care, Cohen and colleagues 

plan to evaluate the effects of different models of care 

delivery on utilization. one such model, says Cohen, 

is the oEF/oIF Integrated Care Clinic at the San 

Francisco Va, where all patients, whether or not they 

screen positive for mental health concerns, are seen 

by primary care, mental health, and social work 

providers, potentially reducing the stigma of seeking 

mental health care.

(Journal of General Internal Medicine, January 2010) 

Soldiers with the Second Infantry Division walk through a local market in Ebnkathwer, Iraq, in March 2010. 
VA RESEARCH todAy

VA Research Today is produced by: 

Va R&d Communications 

103 South Gay Street, Ste. 517 

Baltimore, Md 21202 

(410) 962-1800 x223 

research.publications@va.gov

Editor

Mitch Mirkin (mitch.mirkin@va.gov) 

Writing

Mitch Mirkin 

Tamar Nordenberg 

Nancy Volkers 

Kristen Wing

Design

Project design Company (Washington, dC) 

Photography

Front cover: Frank Curran

Pages 3-5: Jason Miller (Pixelate Photography and Design) 

Page 7: Larry Gilstad (Miami VA Medical Center) 

Pages 9-11: Laura Segall Photography

Pages 13-14: Jeffery Bowen (Central Arkansas Veterans Healthcare System) 

Pages 15-16: Frank Curran

Page 19: Greg Westlye (Gainesville VA Medical Center) 

Page 20 (left): Virtualis

Page 20 (right): Greg Westlye (Gainesville VA Medical Center) 

Page 21 (left): Sgt. Matthew Moeller, 5th Mobile Public affairs 

detachment (U.S. Army) 

Page 21 (right): Kevin Walsh Photography

Page 22: Brain Sciences Center, Minneapolis Va Medical Center

Page 23: Tech. Sgt. Scott Reed (U.S. Air Force) 

Page 25: Lawrence Marchionda (Detroit VA Medical Center) 

Page 26: Curt Campbell (VA Palo Alto Healthcare System) 

Page 27: Bronx Va Medical Center

Page 35: Mitch Mirkin (VA R&D Communications) 

Page 36: Warren Park (Pittsburgh VA Medical Center) 

Page 39: Frank Curran

Page 40 (left): Senior airman Tiffany Trojca (U.S. Air Force)

Page 40 (right): Curt Campbell (VA Palo Alto Healthcare System)

Page 41: Massachusetts Institute of Technology

Pages 43-45 (top): Frank Curran

Page 45 (illustration): Courtesy of Center for Restorative and 

Regenerative Medicine

Page 47: Frank Curran

Page 48: Sgt. 1st Class Johancharles Van Boers (U.S. Army)

Page 49 (top left): Paul Jasienski (Getty Images)

Page 49 (top right): doug Benc (Getty Images)

Page 49 (bottom): Frank Curran

Page 51: Robert Turtil (VA Central Office)

Page 52: Curt Campbell (VA Palo Alto Healthcare System)

Page 53: Robert Turtil (VA Central Office)

Pages 54-57: Scott R. Galvin (University of Michigan) 

Page 59 (top): Jerry daliege

Page 62: Jeffery Bowen (Central Arkansas Veterans Healthcare System) 

Page 63 (top): Jon Riley (Getty Images)

Page 65: Curt Campbell (VA Palo Alto Healthcare System)

Page 66: agapito Sanchez (Baylor College of Medicine)

Page 68: Spc. advin Illa-Medina (U.S. Army) 

Back cover: Laura Segall Photography

creDITS
Korean War Veteran Ron Greenberg, 76, is back on the golf 

course after learning how to better manage his chronic lung 

ailment through a VA study. See the story inside.