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

Illustrations Jeffrey Fisher

Shingles illustration

Singling out shingles
Update: the medical school's strategic plan
Lighting up liver cancer
Flying high with a smart drug
Medical school's dean goes on rounds in peds
Summer splash
Two schools, one department

Singling out shingles

Up to 1 million people are diagnosed with shingles each year, mainly those older than 65. The itchy, burning rash can leave a legacy of shooting pain that lasts years.

"It's a very disruptive kind of pain," says Ann Arvin, MD, the Lucile Salter Packard Professor of Pediatrics and professor of microbiology and immunology. "The skin becomes so sensitive that it can be difficult to sleep and even the lightest clothing or faint breeze becomes painful."

Now researchers at Stanford University Medical Center and the Veterans Affairs Palo Alto Health Care System are examining if they can reduce the risk of contracting this disease with a vaccine for a childhood illness – chicken pox – that is caused by the same virus.

After a person recovers from chicken pox, the virus that caused it bides its time in nerve cells, waiting decades for a chance to strike again. When the immune system is weakened by age or disease, the stowaway springs to life as shingles. Researchers hope the chicken pox vaccine will bolster a person's immunity enough to keep the virus in check.

In a recent study on 111 lymphoma patients undergoing a hematopoietic cell transplant, the vaccine did just that. Because these patients' immune systems are weakened by the disease and its treatment, normally up to one-third of them would develop shingles within a year of their transplant.

So Arvin and colleagues gave half the patients four doses of a weakened form of the chicken pox vaccine, one before their transplants and three afterward. They used the weakened vaccine instead of full-strength to reduce the risk of side effects.

The study showed the vaccine helped. While 30 percent of the unvaccinated group developed shingles, only 13 percent of the vaccinated patients did so. The study was published in the July 4, 2002, New England Journal of Medicine. "We knew that these patients were at very high risk," says Arvin, who is also chief of pediatric infectious disease at Lucile Packard Children's Hospital. "We thought we could try to benefit those with impaired immune systems and also demonstrate that vaccination could help protect others who are at risk for shingles."

But will it work in the elderly, the largest at-risk population? A nationwide study of more than 38,000 people age 60 and older intends to find out.

The VA-Palo Alto is one of 21 sites for this double-blind study in which half the participants received a larger dose of the same chicken pox vaccine given to children and half received a placebo injection. Researchers are tracking participants' health; results are expected within a year. – K.C.

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Update: the medical school's strategic plan

The medical school's dean, Philip Pizzo, MD, began hosting a series of town hall meetings in late 2001 to open up a dialogue to help shape the school's long-term strategic plan. "It's important to have lots of ideas and views to invigorate the debate as much as we can," he told those in attendance at the first meeting.

With information gleaned in part from the open forums, a group of 72 faculty, staff and students traveled for a weekend retreat in Carmel, Calif., to refine a common vision for the school's future. Soon after that February retreat, work groups formed by Pizzo began acting on the plan.

Some aspects of the plan may take up to a decade before being put into place, but others are rolling along now. Following is a summary of recent initiatives related to the plan.

  • The medical school convened a Community Service Programs Committee in July. In addition, a survey was sent to faculty in August asking them to describe their community service activities.

  • The school's recently approved fiscal year budget for 2003 included seed money for developing a career center for graduate students and postdoctoral fellows.

  • A "mini-retreat" for clinical chairs took place in July to review the organization of the faculty clinical practice and discuss plans for the future.

  • The school's leadership has reviewed new guide-lines for advancement and promotion intended to help clarify the role played by medical center line, adjunct, staff physicians and voluntary faculty.

  • A new government relations position in the dean's office has been approved and posted.

  • The departments of medicine and genetics have been selected to develop new prototype departmental planning processes for the school.

  • A new associate director for graduate education has been hired to further support diversity programs at the school.

More information about the plan is available on the school's strategic plan website: – E.W.

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Cancer lights illustration

Lighting up liver cancer

By the time most liver cancer patients learn of their illness it's too late for the most effective treatment – surgical removal of the tumor. That's because there's no good way to spot liver cancer in its early days.

Fewer than 20 percent of liver cancer patients learn of their illness in time for a successful surgery.

"Most of the time, if you wait until the patient has symptoms, the diagnosis is too late," says Samuel So, MD, director of Stanford's Asian Liver Center and an associate professor of surgery at the School of Medicine, who also oversees the medical center's liver cancer program.

But liver cancer diagnosis took a big leap forward recently when Stanford University Medical Center researchers, led by So, used DNA microarrays to identify genes important in liver tumors.

"There's a real opportunity to use this information to develop better and cheaper tests for diagnosis and treatments," says So. Worldwide, about 550,000 people die each year from liver cancer. About 75 percent of those deaths are Asians and Pacific Islanders, who have roughly 10 times the risk of liver cancer as Caucasians because of high rates of chronic hepatitis B infection.

To identify the genes in this study, So and his colleagues compared the genes being used in more than 200 normal and tumor samples. First they isolated RNA from the samples. RNA is produced by active genes; the more active the gene, the more RNA it produces. Then they tacked a fluorescent molecule onto the RNA and washed it over the surface of a glass slide dotted with 17,400 human genes. Any RNA that corresponded to a gene on the array stuck, creating a fluorescent spot. A brighter spot meant more RNA and more gene activity.

By comparing the pattern of fluorescent spots created by both normal and tumor samples, the researchers determined which genes were relatively active in the tumor samples and which were relatively inactive. Now So's group has a new question: Which of the especially active liver tumor genes make proteins that wind up in liver cancer patients' bloodstreams? The answer should point the way to a better blood test to detect liver cancer, he says. —A.A.

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Smart drugs illustration

Flying high with a smart drug

Most people would like to pop a pill and become smarter. Already advertisements for a variety of herbs and drugs claim their products improve memory and learning. Although many researchers dispute these assertions, the time of "smart drugs" is approaching, says Jerome Yesavage, MD, professor of psychiatry at the medical center and director of the Mental Illness Research Educational and Clinical Center at the Veterans Affairs Palo Alto Health Care System.

Yesavage should know. He tests such drugs. In a recent study he led, healthy pilots who took donepezil, a drug prescribed to Alzheimer's patients to improve memory, performed better in a flight simulator. The finding has implications for non-pilots too, says Yesavage, who uses flight simulators to illuminate the effects of drugs and aging on memory and learning.

In the most recent study, 18 pilots with an average age of 52 took seven test runs

in a flight simulator to train them to follow complex instructions. Half then took donepezil for 30 days; the others took a placebo. At the end of the month all "flew" in the simulator two more times. Pilots who took the drug retained their flight skills better than those who did not. The largest effects were in the pilots' abilities to scan the instrument panel for signs of emergency and maintain proper speed, altitude and direction on approach to landing.

Federal law prohibits pilots from taking performance-enhancing substances, but donepezil might help the rest of us. During normal aging, the body slows down its production of acetylcholine, a molecule that transmits messages between nerve cells and is important

in memory, learning and attention. Donepezil keeps acetylcholine at near-normal levels by blocking an enzyme that would normally break it down.

Yesavage is now conducting another study in which older adults with memory loss from normal aging receive both donepezil and training in memory aids such as mnemonic devices. Yesavage hopes to show that the two techniques work together better than either one alone.

The big question, however, is whether drugs like donepezil will ever become standard for every-one from college students cramming for exams to actors struggling to remember their lines.

"I would suspect that the major market for these compounds will be professional older adults who want to continue working professionally as long as they possibly can," Yesavage says. "But the effects are indeed subtle, and whether people would be willing to pay $100 or so a month for such a treatment is questionable." – L.E.H.

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Dean Pizzo on rounds

Dean Pizzo On rounds at Lucile Packard children's hospital

Medical school's dean goes on rounds in peds

In august, Philip Pizzo, MD, took time out from his duties as dean of the School of Medicine to take the pulse of the medical center – literally. In a two-week break from his full-time desk job, Pizzo made the rounds of the pediatric wards each afternoon, tending to patients at Lucile Packard Children's Hospital, soothing nervous parents and strategizing about diagnoses and treatments with residents, students and fellows.

Though it's not required – or typical – of medical school deans to make clinical rounds, Pizzo says he sees it as an important part of his job and an opportunity to keep active his skills as a pediatric infectious disease specialist.

"In order to understand what's going on in the hospital, it's important to be a part of it," he says. "If you're removed from the environment, you're out of touch with the issues."

In addition to reviewing charts and examining patients, Pizzo found himself diverging into philosophical discussions with trainees on a wide range of issues – from limits on residents' hours to the risks of relying on anecdotal experience in making treatment decisions.

Andrea Enright, MD, a clinical fellow in pediatric infectious disease, says it's a bonus being able to consult with someone of Pizzo's experience. (He served as physician-in-chief at Boston Children's Hospital and was a leading researcher at the National Institutes of Health.)

"It's nice to have senior-level people actively involved, especially when you have patients outside the normal realm – because we often look at unusual cases," Enright says. "The more minds, the better." – R.R.

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Newsweek on sleep

The July 15 cover story featured Stanford sleep researchers Christian Guilleminault, William Dement and Emmanuel Mignot.

Summer splash

Back-to-back Newsweek cover stories this summer featured Stanford University Medical Center researchers.

The first article (July 15), "In Search of Sleep," discussed sleep disorders and advances in sleep research. It included William Dement, MD, PhD, the Lowell W. and Josephine Q. Berry Professor in the Department of Psychiatry and Behavioral Sciences, as well as professors of psychiatry and behavioral sciences Christian Guilleminault, MD, and Emmanuel Mignot, MD, PhD.

In the second article (July 22), "What's a Woman to Do?" Marcia Stefanick, PhD, associate professor of medicine, commented on the decision to terminate a nationwide study of hormone replacement therapy in post-menopausal women because of increased risks of breast cancer, heart attack and stroke. Stefanick, who chairs the steering committee for the study, was also featured in articles in the New York Times, U.S. News & World Report, the Washington Post and USA Today, as well as appearing on NPR's "All Things Considered," "NBC Nightly News" and "News Hour with Jim Lehrer." – L.E.H.

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Two schools, one department

Stanford faculty members have discussed creating a separate department of bioengineering for more than 20 years. Now it's going to happen.

In June the university's trustees approved the Department of Bioengineering, which will be jointly run by the schools of medicine and engineering. It will cater to students interested in combining life sciences research with the latest engineering technology. The department could begin accepting graduate students by October 2003 and offer a bachelor of science degree to undergraduates by autumn 2005. For now, an internal search committee is looking for a department chair to start planning educational programs and recruiting faculty.

A dozen new faculty positions in the School of Medicine and a similar number in the School of Engineering have been designated for the new department. Initially it will be housed in the Clark Center, the interdisciplinary biosciences building now under construction, although a separate bioengineering building is planned.

While Stanford faculty members have been debating the merits of a separate bioengineering department for years, other top-ranking universities – including UC-Berkeley and MIT – have forged ahead by creating degree-granting programs of their own.

"Our goal is to be ranked in the top programs nationwide within the next five years and to dominate the field within 10 years," said Philip Pizzo, MD, dean of the medical school, and Jim Plummer, PhD, dean of the engineering school, in a statement to the trustees.

"We already have tremendous strengths in the relevant disciplines. Both schools believe this new department will be a critical part of their national stature in the coming decades." – L.E.H.

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