Johns Hopkins Magazine - November 1996 Issue

Health & Medicine: In Short

A viral link to fatty arteries?... cancer pain relief that's under the skin... more natural results in hair restoration... new Heart head

Virus suspected in atherosclerosis

A common virus that usually causes only asymptomatic infections could be a risk factor for atherosclerosis, according to a report by Hopkins School of Public Health epidemiologists in the September 1 Circulation. In a study of 300 Maryland residents, researchers led by F. Javier Nieto, assistant professor of epidemiology, found that elevated levels of antibodies to cytomegalovirus (CMV) correlated to thickening of the carotid artery walls.

If the study is confirmed, it would add a new type of villain to the list of factors implicated in the thickening of the arterial walls, or atherosclerosis, which is a salient feature in heart disease and stroke. The list includes lifestyle factors such as a high-fat or high-cholesterol diet and a lack of exercise.

Between 60 and 70 percent of adults in the United States are infected with CMV, says Nieto. Many do not even know it. CMV belongs to the herpes family of viruses, but unlike its cousins, herpes virus 1 and 2, CMV generally does not cause symptoms except in newborns and people whose immune systems are suppressed, such as AIDS patients. In those cases, it can cause a blinding eye infection.

The subjects of the Hopkins study were recruited from a group of 4,000 healthy volunteers from Washington County, Maryland, who are participating in the national Atherosclerosis Risk in Communities (ARIC) study, which is funded by the National Institutes of Health. Many of the ARIC volunteers had also participated in a public health survey conducted by professor of epidemiology George Comstock at the Hopkins Training Center for Public Health Research, in Washington County. In 1974, blood samples of those volunteers were collected and frozen.

Using ultrasound, Nieto's team measured the thickness of the carotid artery in the necks of the ARIC volunteers. They then selected 150 participants with especially thick arterial walls and another 150 with especially thin walls. Next, the investigators retrieved the frozen blood samples of those volunteers, thawed them, and tested them for CMV antibodies. They then compared the ultrasound results of volunteers who tested positive for CMV to those who tested negative.

Volunteers who had CMV infection in 1974 were more likely to have atherosclerosis than volunteers who had not been infected. The investigators also say that the risk appears to increase with the level of CMV antibodies. "People with very high CMV levels in 1974 are about five times more likely to have thickening of the arteries than those who did not have CMV antibodies," says Nieto.

A note of caution: after the researchers accounted for confounding variables, the results were only statistically significant for volunteers with the highest level of antibodies. Nieto also stresses that because the study group was small, the results must be confirmed before they are called statistically significant.

However, several other lines of evidence are pointing to the CMV-atherosclerosis connection, including a study published just a week before the Hopkins team's. In the New England Journal of Medicine, researchers from the National Heart, Lung and Blood Institute and the Washington Hospital Center described evidence that patients undergoing angioplasty for blocked arteries have a greater risk of recurrence if they are infected with CMV. "If you put everything together, you have something, though we can't yet say it is causal," says Nieto. "Atherosclerosis looks very much like an inflammatory reaction," he adds. "It makes sense that viruses could trigger it." If anything, says Nieto, CMV may work synergistically with other risk factors. "There is some data suggesting that infected cells are more susceptible to accumulating fat and cholesterol," notes Nieto. Perhaps neither a high-fat, high-cholesterol diet nor CMV alone would be a significant risk, but together--pow!

Scalp Stretcher

Plastic surgery techniques originally used in breast reconstruction are now being tapped for a new mission: hair restoration, says James Vogel, instructor of plastic surgery at Hopkins.One such technique, pictured below, involves surgically implanting a balloon-type stretching device beneath the hair-bearing region of the scalp, then, over the course of three months, slowly expanding this region. Once the device is removed, Vogel manipulates the now-baggy flap of hair-rich scalp into the balding area. "The results are permanent, effective, and dramatic, for suitable candidates," says Vogel, who teaches this and other techniques to Hopkins residents.

Hair restoration has come a long way since the unnatural looking hair grafts, or "plugs," of the 1980s, says Vogel, who is president of the International Society for Hair Restoration Surgery. Today he and other plastic surgeons use a variety of techniques, including micrografts as small as a single hair, and scalp reduction (to bring hair-bearing scalp areas closer together), to create more natural-looking and less painful results.

Says the plastic surgeon, "Just like painting on a canvas, no two hair transplants are going to be alike."

New promise for cancer pain relief

Each year, millions of cancer patients in developing nations experience pain that could be alleviated if they had access to medications such as morphine.

The reasons they don't have access are complicated, says Stuart Grossman, associate professor of oncology and director of the Johns Hopkins Oncology Center's cancer pain program. Governments are more concerned about supplying vaccines and antibiotics. Physicians worry that villagers will not comply with medication schedules, or that painkillers will end up on the illicit drug market. Thus, in India, for example, cancer patients are rarely prescribed morphine, although India produces 80 percent of the world's medicinal opium (the source of morphine)

Grossman is hoping that a plastic device the size of a shirt button will help reduce suffering among cancer patients in developing nations. The device, which contains the morphine derivative hydromorphone (Dilaudid), is designed to be implanted under the skin in any part of the body, and to slowly release a constant dose of the drug over a one-month period. It works similarly to the way continuous-release birth control implants do, and is the first under-the-skin implant for delivering narcotics to cancer patients.

With the implant, cancer patients will not have to travel to the doctor or pharmacy several times a month to have a prescription refilled, nor worry about skipping a dose, says Grossman. The polymer from which it is made is "extraordinarily inexpensive," he adds. "It is the same plastic used in ski boots, the soles of shoes, and hundreds of other applications."

While the need for such a device may be greatest in developing nations, Grossman says it will also fit a niche in the U.S., particularly as a less costly alternative to subcutaneous pumps for delivering pain medication. Many cancer patients are put on the pumps because they cannot take medication by mouth or cannot tolerate the peaks and troughs of pain relief that can accompany oral painkillers. The costs of nursing agencies and renting and maintaining a pump can run from $4,000 to $6,000 per month, says Grossman.

In the July issue of the journal Pain, Grossman and his colleagues report that tests in rabbits show that the implant is safe and that it releases the drug accurately. They plan to conduct clinical trials in the near future, probably at the Hopkins Oncology Center. They will then make the implant available for further testing at cancer centers in developing nations. A patent is pending. Grossman and associate professor of biomedical engineering Kam Leong are listed as the principal inventors. Other researchers include Glenn Lesser, Hungnan Lo, and Susan Eller.

The implant consists of hydromorphone sandwiched between two disks made of the polymer ethylene vinyl acetate. A hole (the central channel) is drilled through the center of the disks, and all of the device except the hole is coated with bone cement. Once the device is implanted, the drug slowly seeps out the channel.

The researchers found that the thickness and diameter of the implant and the polymer from which it is made dictate the release rate of the drug. It is possible to make an implant that releases a drug over a longer period, say, three months, says Grossman.

As an added benefit, says Grossman, the implant also has potential as an alternative to oral methadone. Since hydro-

morphone and methadone are both opiates that work on the same brain receptors, one drug can be substituted for another. He says the cost of an implant (though not finalized) will be a fraction of the cost of methadone management. Each of the 117,000 people enrolled in federally funded methadone management programs costs taxpayers $4,500 per year.

Hill to lead Heart Association

Hopkins's Martha Hill, a nursing practitioner who is a nationally known expert on hypertension, has become the first non-physician ever to be elected president of the American Heart Association (AHA). She will assume the post next June.

Her appointment represents a new direction for the 72-year-old organization, she says. "The AHA was founded by cardiologists who were concerned about cardiac disease, the what and how, and why, and the what to do," says Hill, who earned her doctorate in behavioral science at Hopkins ('87), and is director of Hopkins's Center for Nursing Research. "The area of primary care and public health has only recently begun to receive major attention."

Hill has conducted several studies of hypertension among African-Americans, a group particularly hard-hit by the condition. Left untreated, it can trigger heart attacks, strokes, and kidney disease. In one such study, outreach workers counseled hypertensive patients in their homes, and even drove them to clinic appointments, while nurses handed them medication rather than relying on them to get prescriptions filled. This hands-on approach worked: participants were more likely to control their high blood pressure than when their only contact had been with a physician.

Despite her leadership in this area, Hill says she doesn't plan to put it at the top of the organization's agenda. "It used to be that the president of the Heart Association was asked, What is your agenda? And the topic of greatest interest to that person would become the theme for the year," she says. "I see myself trying to help integrate a menu of priorities that have already been established." Those priorities include government funding for research, secondary prevention efforts among people who have already had heart attacks, and heart-healthy programs for children and youth.

Hill is the fifth person with Hopkins ties to be named the top leader of the AHA, which today includes 30,000 doctors, nurses, and other healthcare professionals, as well as 4.2 million volunteers. Past presidents from Hopkins have included former medical dean Richard Ross and "blue-baby" operation pioneer Helen Taussig.

Written by Sue De Pasquale and Melissa Hendricks.

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