Volume 19 Number 1 Winter 2002

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‘scope

A QUICK LOOK AT THE LATEST DEVELOPMENTS FROM STANFORD UNIVERSITY MEDICAL CENTER

• Leadership Changes
• Stanford’s bioterrorism plan provides model for nation
• Camera in a capsule
• Learning to Serve
• Asthma gene family uncovered
• Bio-X project on track despite funding setback
• Targeted brain tumor treatment

Leadership Changes

Recent months have brought major changes in the leadership of Stanford University Medical Center.

In January, Martha Marsh, a veteran leader in the health care field, was named president and CEO of Stanford Hospital & Clinics. Marsh’s appointment will become effective in April. She replaces Malinda Mitchell, who retired in May 2001.

"Martha Marsh is a very experienced and dedicated individual who can ensure that Stanford Hospital & Clinics continues to lead the way in quality patient care while supporting medical education and biomedical research," said Denise O’Leary, chair of the hospital’s board of directors.

Marsh has more than 23 years of experience as a leader in health care, devoting much of that time to work at university-affiliated centers. For the past three years, she has directed the University of California-Davis Health Care System. Prior to that, from 1994 to 1998, she served the University of Pennsylvania Health System as senior vice president for professional services and managed care and vice president for managed care.

From 1986 to 1994, Marsh was president and CEO of the Matthew Thornton Health Plan, an HMO affiliated with the Dartmouth-Hitchcock Medical Center. Her other related experiences include seven years serving in various managerial positions at Elliot Hospital in New Hampshire.

Marsh is a graduate of the University of Rochester and received MPH and MBA degrees from Columbia University. Another big leadership change took place in December when Eugene Bauer, MD, stepped down from his position as vice president for medical affairs to resume teaching and research upon return from a one-year sabbatical.

"Dr. Bauer has made an enormous contribution to Stanford since he arrived in 1988," said University President John Hennessy when Bauer announced his decision in October. No replacement for Bauer has been named. Instead, an executive committee, chaired by Philip Pizzo, MD, dean of the School of Medicine, is governing the medical center.

The committee consists of Pizzo; Christopher Dawes, president and CEO of Lucile Packard Children’s Hospital; and Michael Peterson, interim president and CEO of Stanford Hospital & Clinics. Marsh will replace Peterson when she steps into her new position in April

Stanford's bioterrorism plan provides model for nation

Health care organizations racing to develop a plan for treating patients exposed to bioterrorist agents now have a useful tool at their disposal: a comprehensive preparedness plan developed by Stanford University Medical Center. A team of Stanford physicians, scientists and medical staff members have developed a plan outlining ways to assess and treat victims of bioterrorism while limiting the potential

spread of contamination. Stanford is now sharing the plan with hospitals, physicians and public health agencies nationwide. It is available online at www.bioterrorism.stanford-hospital.com. "We initially focused our efforts on the local community but then realized our work could benefit the greater medical community," says Philip Pizzo, MD, dean of Stanford University School of Medicine.

Stanford’s plan is drawing high marks from organizations that have studied it. "We reviewed the plan and thought it was a good product," says Eric Koscove, chief of the emergency department at Kaiser Permanente Santa Clara Medical Center in Northern California. The Stanford plan has two purposes – to ensure the health and proper treatment of the patient and to limit the potential exposure of medical staff and facilities.

"If a patient’s exposure to a biological agent results in contamination of the emergency department and its personnel, a hospital would potentially have to close down its emergency department and thus be unable to help other patients," says Eric A. Weiss, MD, co-chair of the task force. The task force that created the plan is continually updating it to accord with frequent changes from the national Centers for Disease Control and public health organizations, Weiss says. "The information about anthrax is changing rapidly," Weiss says. "The cases being treated on the East Coast vary from what has been reported in the medical literature, and we have to adapt our understanding in light of these differences. "

Camera in a capsule

A new pill-sized camera is giving Stanford doctors an unprecedented glimpse at the bumps, bulges and possible blemishes that make up the small intestine – all while the patient goes about his or her normal day.

"The great thing about this is that previously there was no non-invasive way to view the small bowel," says Michelle Nguyen, MD, a gastroenterology fellow at Stanford University Medical Center. Nguyen

is testing the "camera in a capsule" as part of a multiclinic trial for patients who require transfusions because of blood loss.

Doctors suspect internal bleeding in patients with consistently low levels of hemoglobin (the bloodborne protein that carries oxygen). Nguyen says the bleeding is usually in the colon or stomach, but sometimes doctors can’t find the source. Often these patients must get regular transfusions to make up for the lost blood. To detect bleeding in the throat, stomach or colon, doctors use an endoscope – a camera on the end of a long, flexible tube. If repeat endoscopies turn up no bleeding, the small intestine becomes the natural suspect. With no reliable device for viewing inside the deepest portions of the small intestine, however, exploratory surgery with endoscopy is the only way to know for sure – no small feat, given the organ’s 20-foot length. The new capsule is set to change all that. Patients fast in prepa-ration for the procedure, then swallow the camera. The device, developed by Israel-based Given Imaging Ltd., snaps two images per second for the eight hours it takes to traverse the small intestine. During this time, the camera sends images to a recorder the patient wears on a belt. When the procedure is over, the patient can forget about the camera, which eventually passes with the stool. The next day, the patient returns the recorder to the doctor, who then examines the images for signs of bleeding. Depending on the findings, the doctor might remove the damaged portion of the intestine or begin treatment for other ailments such as Crohn’s disease. Stopping the bleeding is a big improvement in the lives of transfusion-dependent people, Nguyen says. "They are limited in their activities, they have difficulty traveling long distances or out of the country. They have difficulties working and maintaining normal lives," she says.

Learning to Serve

A few years ago several public service-minded Stanford medical students were struck by what seemed to them a gap in their otherwise first-rate medical education. In their eyes, the school’s curriculum left them unprepared for the challenges they expected to face as physicians dedicated to public service.

The students spurred the school’s leaders to fill that gap. The resulting fellowship, the Public Service Medical Scholars Program, enters its third year this winter.

A Zimbabwean sculptor and his art -
which will be sold through House of Stone
charitable organization.

Asthma gene family uncovered

Researchers have identified a gene family that appears critical to the development of asthma in mice. The finding may revolutionize treatment and diagnosis of the roughly 17 million people in the United States who suffer from asthma.

The finding may also explain why incidence rates have climbed rapidly in industrialized countries over the past 20 years, say the researchers – a team based at Lucile Packard Children’s Hospital at Stanford.

Asthma researchers have known for years that the disease has a genetic component, but efforts to pinpoint specific genes have been stymied by the complexity of the disease, which involves more than a dozen independently acting genes. However, when the Stanford researchers used DNA from specially bred mice to look at the effects of only small stretches of DNA at a time, they identified a previously unknown group of nearby genes, called the Tim family, as primary culprits.

"It was especially interesting when we found that the gene we homed in on encoded the hepatitis A receptor gene," says Rosemarie DeKruyff, PhD, senior author of the study, published in the December 2001 Nature Immunology.

Infection with hepatitis A protects against asthma for reasons that have not been well understood. The newly discovered link between family member TIM-1 and the hepatitis A virus may help explain the association between the two diseases. Researchers speculate that binding of the virus to the hepatitis A receptor gene TIM-1, somehow interferes with disease development in these infected individuals.

If so, their finding may provide a clue as to why asthma rates have increased where hepatitis A infection rates have dropped over the past two decades.

"It may be that when hepatitis A binds to this receptor it somehow brings about a deletion of those cells that bias the immune response toward asthma," says DeKruyff, a professor of pediatrics. "But there are also other possible scenarios."

The finding has diagnosis and treatment implications as well.

Identifying which variant of a gene increases susceptibility to asthma could help in diagnosing the disease, says DeKruyff.

That information could also make possible treatments that work by blocking the activation of receptors that leads to asthma or by altering the immune response, she adds.

Bio-X project on track despite funding setback

Stanford University’s broad-based biomedical initiative, known as Bio-X, is moving ahead despite this summer’s news that its leading financial backer will withhold $60 million of the funds he had pledged.

The multidisciplinary collaboration, which has been in the works for the past four years, still has the momentum to fundamentally change the nature of research and education at Stanford, says the project’s original director, biochemistry professor James Spudich, PhD.

In January, Spudich turned over the reins to develop-mental biology and genetics professor Matthew Scott, PhD.

The program’s goal, says Spudich, is to boost research and teaching in bioengineering, biomedicine and biosciences by breaking down long-standing barriers to collaboration between researchers and clinicians across three of Stanford’s schools – humanities and sciences, engineering and medicine.

After months of discussion, the Bio-X concept became a reality in October 1999 when former Stanford electrical engineering professor Jim Clark, the founder of Netscape and Silicon Graphics, announced his $150-million donation to the project. An anonymous donor pledged an additional $60 million, raising the Bio-X commitment to $210 million.

But in August 2001 Clark announced he would hold back $60 million. Clark said this act was to protest President Bush’s decision to limit human embryonic stem cell research and to contest a bill passed by the U.S. House of Representatives banning therapeutic cloning of human embryos.

Clark’s decision has not altered Stanford’s plans to build the 225,000-sq.-ft. research center that will form the core of the Bio-X initiative, says Spudich. The $150-million James H. Clark Center for Biomedical Engineering and Sciences is on track to open in the summer of 2003. Centrally located between the three schools and designed to offer researchers an open atmosphere, the building is intended to foster sharing of ideas, technologies and research methods to advance research and discovery.

Ultimately 50 faculty members will be situated at the Clark Center. Proposed initiatives include single molecule analysis, regenerative medicine and the creation of a "digital man" using biocomputation and magnetic resonance imaging technology.

In addition to developing the Clark Center, the Bio-X team has granted $7 million to build or upgrade 17 shared research facilities around campus. Facilities include a supercomputer and immersive visualization center, as well as an electron microscopy center.

In October, the team announced the recipients of $3 million granted as seed money for supporting research that pushes the frontiers of interdisciplinary research. Of 84 proposals received, Bio-X funded 19 projects.

"Bio-X will result in new technologies that allow us to do things that we can’t even think of today. In the long run, the Bio-X program will facilitate all interdisciplinary sciences on campus," says Spudich. "It should become a way of life here."

Targeted brain tumor treatment

A Stanford University Medical Center neurosurgeon is one of the first in the country to treat brain tumors with a new radiation device that works within the cavity left when a tumor is removed.

In October, neurosurgery professor Griff Harsh, MD, began treating patients with this highly effective method of delivering intratumoral radiation – making Stanford the first hospital on the West Coast to perform surgeries using the device, the GliaSite radiation delivery system.

"This technique is an important new treatment option for patients with malignant brain tumors," says Harsh, who directs the Stanford Brain Tumor Center. "Radiation combined with surgery is the single most effective way to treat brain tumors, and intratumoral radiation is a highly advantageous way of delivering additional radiation to the site of the cancer."

According to the American Cancer Society, more than 16,000 Americans are diagnosed with malignant primary brain tumors each year, and Harsh says the majority of patients are treated with a combination of surgery and external beam radiation therapy. With typical treatment, external beams of X-rays are sent from outside the body to the tumor cavity – passing through healthy brain tissue.

Traditional radiation therapy suppresses tumor regrowth at least temporarily – but almost all patients experience recurrences.

The new method uses an implanted balloon to deliver a controlled dose of radiation to the targeted area while minimizing the exposure of nearby healthy brain tissue.

The balloon is connected by a catheter to a reservoir placed just beneath the patient’s scalp. Several weeks later, the balloon is filled with a liquid source of radiation. Over a course of three to seven days, high doses of radiation are delivered through the balloon directly to the tissue surrounding the cavity, where recurring tumors are most likely to appear. The balloon, catheter, reservoir and liquid radiation are then removed.

Harsh says a short recovery time and the low incidence of side effects are benefits of the technique.

In the past, patients with recurring brain tumors have had few treatment options. A second course of traditional radiation typically isn’t advised for a recurring tumor because of the high risk of damage to healthy surrounding brain tissue.

The reliability of the new device was demonstrated in a recent National Cancer Institute-sponsored study of patients with recurring primary brain tumors, all of whom had undergone previous surgery and radiation therapy and half of whom had received chemotherapy. It found a high rate of patient survival and no evidence of radiation necrosis after a year.