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Investigating George C. Scott's Killer
A neglected disease threatens boomers
  
By
Edward R. Winstead



Featured Article.

When a young movie star dies, people often say, "It didnít have to happen." When George C. Scott died at age 71, some doctors said the same thing.

Scott, who won an Oscar for his role as General George S. Patton Jr., died in September after a bulging blood vessel in his abdomen burst. Doctors said Scottís death was preventable because surgeons can repair a damaged blood vessel, or aneurysm. But once the main artery in the abdomen ruptures, most victims go into shock and donít make it to the hospital alive.

Scottís killer is now the subject of a major scientific investigation. No one knows what causes aneurysms in people over age 55, but the disease clearly runs in families, and researchers are hunting for the genes involved. The gene hunt is part of a broader investigation of an overlooked disease.

Many of the fieldís top researchers are collaborating to answer basic questions about aneurysms. Some researchers, for instance, will identify genes associated with changes that result in the weakening of the aorta wall. These genes could be targets for future drugs that might prevent or even repair tissue damage, making surgery unnecessary.

Too few surgeons

Select image to see a three-dimensional abdominal aortic aneurysm.
Requires Windows Media Player

More dollars and talent have been spent investigating why arteries clog than why they rupture. But ruptured aneurysms kill some 15,000 older Americans each year. Aneurysm researchers have been saying for years that new treatments are needed—and soon. By about 2015, there wonít be enough surgeons to operate on all the baby boomers who may need repairs.

In 1998, the National Heart, Lung, and Blood Institute (NHLBI) allocated funds for aneurysm research. "This is going to be a serious problem," says Momtaz Wassef, who oversaw the selection and awarding of the first grants last fall. "The population is aging—and aging fast,"

During the next four years, the NHLBI will spend $10 million—a relatively small sum—on aneurysms. "Not very much research has been done on this subject," says Wassef. "But we have an opportunity and the tools. The science is at a very high level, and itís time."

To foster collaboration among the researchers, Wassef has invited everyone to Bethesda, Maryland, for a conference next month. Investigators will have two days to compare notes, trade ideas and socialize. "Itís the first time ever in the United States that everyone involved in this effort will be together under one roof," says Wassef.

A whole-genome approach

One of the presenters at the meeting will be S. Helena Kuivaniemi of Wayne State University, who leads the search for genes linked to the inherited form of the disease. Her team collected DNA samples from 65 pairs of affected siblings, which she sent to a laboratory in Wisconsin for analysis.

The analysis may yield hotspots in the genome that contain aneurysm genes. "Weíre taking a whole-genome approach," says Kuivaniemi. "Technology has made this kind of research feasible on complex diseases that involve multiple genes."


Searching for hotspots in the genome.

Kuivaniemi plans to include 200 pairs of siblings in the study. If it turns out that one or more genes are unique to the affected siblings, the researchers may develop a diagnostic test. A gene-based test could identify individuals at risk in families with a history of the disease long before evidence of an aneurysm appears.

People who know theyíre susceptible to aneurysms could modify their lifestyle to eliminate non-genetic risk factors. Hypertension, smoking, and high cholesterol all contribute to the disease. The opposite effect of aneurysms—the hardening of the arteries, or arteriosclerosis—also may be a factor, but the relationship between arteriosclerosis and aneurysms is not clear.

The immune system theory

One of the first researchers to identify the role of genes in aneurysms was M. David Tilson, the Ailsa Mellon Bruce Professor of Surgery at Columbia University College of Physicians and Surgeons. Tilson has investigated the genetics of aneurysms since the 1970s. More recently, his research has focused on genes linked to collagen, a component of the artery wall.

"Weíre interested in cells that can destroy the collagen and in what initiates this process," he says. His theory is that aneurysms occur when the immune system goes awry and attacks the aorta wall. His laboratory is looking for genes that could make a person susceptible to such an immune response. This research also could lead to a gene test.

Some researchers want a screening program, not gene tests. The technology to detect abdominal aneurysms already exists: An ultrasound or MRI can spot aneurysms with nearly perfect accuracy.


Abdominal aortic aneurysm in a 76-year-old male.

But no one gets the scans unless they have symptoms, and most symptoms either donít appear or go unnoticed prior to a rupture.

Aneurysms probably develop slowly over many years. Sometimes one is discovered accidentally if a person has an exam for another reason, which raises the question of universal screening for aneurysms. Critics argue that most bulges arenít worthy of surgery, and thus a screening program is not worth the expense.

"At this point Iím not in favor of screening the general population," says Kuivaniemi at Wayne State, noting the potential cost. "But we should screen people at high-risk for the disease."

The size of an orange

Doctors disagree about what size aneurysm should be repaired, but a bulge the size of an orange is considered likely to rupture. In about 25 percent of cases, an aneurysm might cause mild physical pain, such as a sore back, before it ruptures. But older people usually assume they either slept wrong or overexerted themselves.

If a test uncovers the damaged artery, surgeons can repair the damage in almost every case. "Deaths from ruptured abdominal aneurysms are preventable," says Robert Thompson, a surgeon at Washington University School of Medicine in St. Louis.

"Hereís a disease," Thompson continues, "for which we have a screening test that is 100 percent accurate. And we have successful treatment. Yet people like George C. Scott die from ruptured aneurysms with frequency. Maybe we have blinders on."

After Scottís death, his publicist and friend Jim Mahoney said the actor "had never been treated properly" for an aneurysm problem in 1996, when Scott starred in a Broadway revival of "Inherit the Wind." He missed several performances after the show opened, once leaving the stage in the middle of the play. Eventually he had to be replaced by the playís producer, Tony Randall. The press learned later that Scott had an abdominal aortic aneurysm.

Asked about the fact that Scottís disease was known, Thompson responds, "Then his death is even more tragic."

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The images from the University of Iowa are part of a tutorial on imaging aortic aneurysms offered by
"Welcome to Physiologic Imaging" at: http://everest.radiology.uiowa.edu

The aneurysm imaging section can be found at:
http://everest.radiology.uiowa.edu/nlm/app/maintoc.html

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The NHLBI grantees on the pathogenesis of abdominal aortic aneurysms will meet on April 10-11, 2000. The meeting is open to the public. Location: Bethesda Marriott Suites, 6711 Democracy Boulevard, Bethesda, Maryland.
 

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