A quick look at the latest developments from Stanford University Medical Center

Illustrations by Greg Mably
Photography Amy Adams & Trujillo/Paumier

High-tech hookup for low-income kids with asthma
Oldsters can learn new tricks
No grain, no pain -- no more?
Skeff honored as consummate 'teacher's teacher'
Smallpox vaccine test
Glow to go

Telemedicine Illustration

High-tech hookup for low-income kids with asthma

Stanford researchers expect hundreds of children with asthma in a low-income San Francisco neighborhood to troop home from school this spring waving their treatment plans and telling their families about the fancy gadgets that connect them to an asthma expert at Lucile Packard Children's Hospital.

Students at three San Francisco elementary schools in the Bayview-Hunters Point community will be some of the first in the nation with asthma to benefit from telemedicine -- an emerging field that relies on interactive video and specialized medical instruments to allow physicians not only to talk to their patients from a distance but also to listen to their chests and inspect their ears.

Why Attack Asthma?

Behind the project's "cool" factor lies an alarming statistic: Up to 30 percent of the total student population in Bayview-Hunters Point are fighting asthma -- often with inadequate or outdated treatment plans.

"My guess is that at least some of these students are going to school feeling sick," says project leader David Bergman, MD. Bergman, an associate professor of pediatrics in the School of Medicine, and Paul Sharek, MD, staff physician in pediatrics, received a grant from the California Endowment for more than $600,000 to conduct a two-year pilot program to bring asthma care to the Bayview-Hunters Point students.

Asthma rates in the predominately African-American neighbor-hood are about twice the national average, most likely due to a combination of ethnic, economic and environmental factors. Bergman, Sharek and Dale Umetsu, MD, PhD, chief of Packard's allergy and immunology division, first put their heads together six years ago to design a coordinated plan of asthma treatment, education and management for low-income children.

But they found that work and school schedule conflicts caused the patients to miss about half their appointments. So the researchers joined with the San Francisco School District, the San Francisco Public Health Department, the Asthma Resource Center, community health workers and local pediatricians to take their fight into the trenches.

"We thought 'why not go to the schools, where the kids are for 160 days a year?'" says Bergman. Students at the test schools will have six visits with their school nurse and several remote "visits" with a Packard asthma specialist.

The specialist will assess the student's health through pulmonary function and medical histories during a real-time video consultation. Next comes the design of a disease-management plan for each student, including instructions on how to use medications based on daily measurements of peak airflow. Finally, the specialist will review the students' use of the peak flow meter and the medication inhaler. Community health workers will visit students' homes to assess environmental factors, such as dust or insects, and to teach parents about asthma management.

Examination results, prescriptions and the specialist's comments will be integrated into a Web-based asthma management plan that will be shared with the students' primary care providers. "The hope is that children will get more involved in the management of their disease," says Sharek.

"A well-educated child and family will be in better control. It's an empowerment issue." -- K.C

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Eric Knudsen, Brie Linkenhoker study how owls learn.

Oldsters can learn new tricks

Old owls can learn new tricks and maybe humans can too. Stanford researchers have discovered that grown-up owls adapt better when taught in small steps rather than in one big jump.

These results, published in the Sept. 19, 2002, issue of Nature, could eventually help doctors treat adults with brain injuries.

To study adult learning, graduate student Brie Linkenhoker and neurobiology professor Eric Knudsen, PhD, took advantage of a quirk in barn owl brains.

Mental maps overlap

Barn owls develop a mental map of their world that aligns the auditory world with the visual one. When the animal hears a noise at a specific location, a nerve cell in the brain's map region fires. That same nerve cell fires when the owl sees an object at that same spot. Owls use this map with deadly accuracy to pinpoint prey when hunting at night.

In young barn owls, Knudsen has been able to alter the auditory map of the world by having the owls wear lenses that shift their visual world left or right. Over time, the young owl's brain compensates so that the auditory map once again matches the visual map. But pity the poor adult owls. When they wear world-shifting lenses, their brains adjust only slightly -- about 9 percent of the shift seen in young owls. If the adult lens-wearing owl sees an object and hears a sound from that same place, two brain regions fire.

Linkenhoker wondered if shifting the adult owl's vision in small increments would overcome this learning impairment. So she fitted five owls with lenses that shifted their view in stages, going from 6 degrees, to 11 degrees and finally to 17 degrees. Adult owls that received this graded training shifted their mental maps by 53 percent of the amount of adjustment seen in juvenile owls -- the overlap between visual and hearing maps still wasn't perfect, but it was much closer than in adults that tried to learn in one fell swoop.

Knudsen says learning about how mature brains can adapt will help in treating brain injuries. "A lot of therapy is done without insight into how the brain works," he says. -- A.A.

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Celiac Sprue Illustration

No grain, no pain -- no more?

In a story that has the ring of a Hollywood drama, researchers have discovered the cause of a common immune disorder and have a lead on a potential treatment. For now, the only treatment for the disease, called celiac sprue, is to avoid eating grains such as wheat, rye and barley that contain the protein gluten -- a hardship and a huge challenge.

This fall, Chaitan Khosla, PhD, Stanford professor of chemistry and chemical engineering, reported in Science that his research team had identified the fragment of the gluten protein that causes the attack on the intestines of people with celiac sprue. He also announced that his group has found an enzyme that can attack that fragment and might someday be used to treat the condition.

When celiacs partake of gluten, their immune cells attack the lining of their intestines, thwarting digestion and increasing the risk of osteoporosis, lymphoma and cancer of the small intestine.

One of every 2,000 or 2,500 Americans has been diagnosed with celiac sprue, but the incidence is believed to be one in 200, with many people unaware that they have the condition.

In fact, Khosla's son became very sick from the disease and soon after, Khosla's wife was tested and diagnosed with it too.

A week later, Khosla learned that he had won a $500,000 grant from the National Science Foundation to support any scientific research of his choosing.

"To me the answer was simple: I'll educate myself about the cause of celiac sprue," Khosla says. This is where his collaborators, renowned Stanford expert in digestive diseases Gary Gray, MD, and Ludvig Sollid, MD, University of Oslo professor of immunology, played a pivotal role. Working with Khosla and his team, they pieced together the biomedical puzzle.

Khosla put a graduate student, Lu Shan, to work in the laboratory, exposing gluten to digestive enzymes. She identified a protein fragment of gluten, made up of 33 amino acids, that celiacs failed to break down during digestion. Further studies showed that this fragment causes the immune system's attack on the intestine.

The next step was to find an enzyme that breaks down the protein fragment. Khosla's hope is that such an enzyme will serve as a digestive aid to celiacs, allowing them to eat gluten-containing products. To Khosla's delight, the team has found an enzyme that breaks down the celiac culprit. The team hopes to start testing the enzyme in humans soon but it will be several years before a celiac pill will emerge, Khosla says. To further support celiac sprue research, Khosla has founded the Celiac Sprue Research Foundation. -- R.S.

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Kelley Skeff, MD

Kelley Skeff, 2002 Flexner award winner.

Skeff honored as consummate 'teacher's teacher'

The American Association of Medical Colleges has presented its most prestigious annual award to Kelley M. Skeff, MD, PhD, professor of medicine -- the 2002 recipient of the Abraham Flexner Award for Distinguished Service to Medical Education.

The award, which recognizes extraordinary individual contributions to the medical education community, goes to Skeff for his achievements in the field of faculty development.

Skeff became interested in faculty development during his residency and fellowship in the 1970s, when he found there were few if any methods to assist medical school teachers in improving their teaching effectiveness. So he decided to pursue a doctorate at Stanford's School of Education, where he worked with Georgette Stratos, PhD, to develop a model to improve the craft of teaching medicine.

Now Skeff and Stratos direct the Stanford Faculty Development Center and train medical school faculty from around the world. The clinical teaching program they created is considered the gold standard for faculty development in medical education. The program shows promise for training basic science teachers as well. Faculty participating this summer in a pilot seminar for basic science faculty reviewed the experience favorably. -- R.S.

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Smallpox Illustration

Smallpox vaccine test

Stanford medical center researchers are testing whether diluted doses of the smallpox vaccine will produce an adequate response in adults who have previously been vaccinated.

The results of the federally funded study will help shape U.S. policy on how the vaccine would be given in the event of a smallpox outbreak.

Routine vaccination was stopped in the United States in 1971, and smallpox was declared eradicated worldwide in 1980. But since last fall's anthrax attacks on the East Coast, smallpox has been considered another likely biowarfare agent, and there has been strong interest in determining how the United States could best protect its population in case of a smallpox attack.

Stretching the Supply

Researchers hypothesize that a diluted dose of the smallpox vaccine might be enough to protect previously vaccinated individuals -- including most Americans over age 30. If this hypothesis were confirmed, the United States' limited existing supply of the vaccine could go further.

In the Bay Area, Stanford has formed a partnership with Oakland-based Kaiser Permanente to conduct the randomized, double-blind study, funded by a grant from the National Institutes of Health. A total of 970 volunteers will participate in the study at nine sites across the nation.

To test whether diluted doses can produce an effective immune response in previously vaccinated individuals, approximately 90 healthy volunteers between the ages of 32 and 70 will be enrolled at Stanford.

Efficacy Test -- and More

In addition to determining the effectiveness of diluted doses, the study will give scientists other valuable information, says Cornelia Dekker, MD, associate professor of pediatrics and medical director of the Stanford-Lucile Packard Children's Hospital Vaccine Program.

It will help monitor the safety of the smallpox vaccine. It will help scientists understand how long the immunity from a previous vaccination lasts. And it may help advance efforts to develop a smallpox vaccine with fewer side effects.

Interested in volunteering? Call (650) 498-7423. -- S.S.

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Phototherapy Bed

Henk Vreman tests one of the phototherapy beds he built.

Glow to go

Franco Bernardo had a problem. His hockey team had made the playoffs, but the 13-year-old Canadian's participation would stop when his team hit the road. Life-threatening jaundice required Franco to sleep under fluorescent lights every night. It was out of the question to move his phototherapy bed to Montreal, the site of the competition.

That's when Franco's mom contacted Henk J. Vreman, PhD, a senior research scientist in Stanford's pediatrics department. Although Vreman is a biochemist who studies bilirubin -- the compound that gives jaundiced patients a yellowish hue -- Maria Bernardo was more interested in his other specialty: portable phototherapy beds. After hearing Franco's dilemma, Vreman made and hand-delivered a bed so Franco could play in the tournament.

"I've dedicated part of my life to helping these families with whatever it takes," says Vreman, who donates his labor to construct beds for the many families who contact him for help.

Jaundice is common in newborns. The usual treatment is temporary exposure to fluorescent light that breaks down the yellowish bilirubin pigment.

But Franco is one of about 200 people worldwide with a severe bilirubin metabolism condition called Crigler-Najjar Syndrome, or CNS. These patients lack a liver enzyme needed for bilirubin excretion. The blood bilirubin levels of infants with CNS skyrocket shortly after birth and remain high even after treatment. A liver transplant is the only cure.

Although intensive phototherapy can usually control bilirubin levels, the treatment becomes less effective over time and common childhood illnesses or injury can cause spikes.

Nightly phototherapy presents problems. Patients have trouble sleeping on the beds, which can be hot, uncomfortable and -- obviously -- brightly lit. Usually they must sleep naked without blankets to maximize their exposure to the light. Young children in particular tend to rebel and sneak out of bed.

"I asked myself 'what can I do about this?'" says Vreman. Although he knew he couldn't solve all the problems, in 1998 he designed a bed that was comfortable and portable. The bed, which folds in half for transport, looks like a camping cot with a sheer polyester fabric hammock suspended over a bank of lights.

Vreman and volunteers including his wife and young grandchildren assemble and test the comfort of the beds, which weigh about 60 pounds and cost roughly $1,000 to make. He has provided the bed to patients at cost.

"I get paid in kindness, actually," he says, adding that he has grown close to many of the families.

He has also received support from Stanford's Office of Technology Licensing.

Bright Future

Vreman continues to improve the bed. Helped by nearly $17,000 from the Dutch Crigler-Najjar Foundation, he has built a new prototype, using high-intensity blue-light-emitting diodes instead of fluorescent tubes. Since the LEDs can deliver more intense narrow wavelength light than the fluorescent bulbs, the new beds might prove more effective. -- K.C.

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