Johns Hopkins Magazine -- April 1999
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APRIL 1999

H E A L T H    &    M E D I C I N E

Sleuthing to save endangered elephants... a simple remedy for fatigue... the wonders of American rat chow... the hazards of youthful drivers... risky roads for minority children... is there a doctor on line?... an alternative to the pap smear?

Endangered: Asian elephants
Photo courtesy
National Zoo
The case of the dying pachyderms

In 1995, a 16-month-old Asian elephant at the National Zoo in Washington, D.C., suddenly became ill. "She had lethargy, a lack of appetite. She stopped nursing and playing. Her tongue turned purple and swelled," recalls Laura Richman, who was then a veterinary pathologist at the zoo. Within five days, the elephant, Kumari, was dead. "It was a mystery," says Richman. "We did a full necropsy, and it was still a mystery."

Kumari's death troubled zookeepers and wildlife conservationists. The population of Asian elephants has plummeted, and they are an endangered species. Every calf born in captivity is important for perpetuating the species. Kumari was the first Asian elephant born at the National Zoo.

Richman, now a doctoral student at the School of Medicine, concludes that a herpes virus killed Kumari, and was responsible for several earlier unexplained elephant deaths in the United States and Canada. She and her colleagues have also determined that herpes was transmitted across species, from African to Asian elephants. Richman and Hopkins molecular virologist Gary Hayward report their findings in the February 19 Science.

"The work they've done is a supreme piece of molecular biology," notes Murray Fowler, a world authority on wildlife medicine and professor emeritus at the University of California at Davis. "It is going to have far-reaching implications for the protection of these animals."

"Viral factories"
After Kumari's death, Richman and National Zoo veterinarian Richard Montali examined tissue samples from the elephant. In cells lining its blood vessels, they discovered dark, purple "viral factories" called inclusion bodies. Closer inspection through the electron microscope revealed the telltale rounded structures of a herpes virus. The virus damages these cells and others in the heart and liver, causing internal bleeding and heart failure.

By then Richman had begun doing a fellowship with Hayward, who is one of the leading herpes virologists in the nation. They and other scientists analyzed the viral DNA and confirmed that it indeed was a form of herpes, perhaps representing an altogether new subfamily of the virus, says Richman.

Richman and her colleagues then examined zoo records of elephants throughout North America. Several of the animals had died after experiencing symptoms similar to Kumari's. All told, seven of 34 Asian elephants born in zoos in North America between 1983 and 1996 had died from herpes virus and two more with incomplete records appear to have died from it.

In the course of her research, says Richman, veterinarians diagnosed herpes in an Asian elephant at a Missouri zoo and one at a conservation facility in Florida. After treatment with the antiviral-drug famciclovir, the same medicine used to treat people infected with herpes, elephants Chandra and Doc are now healthy.

But how did Asian elephants suddenly fall victim to this fatal disease? Through further sleuthing, Richman and her colleagues found a report describing herpes-like skin lesions in a few African elephants that were imported to Florida in the early 1980s. The scientists obtained specimens preserved from those elephants and, through collaborating scientists in South Africa and Zimbabwe, from wild African elephants. In both sets of samples, the researchers discovered viral DNA with a sequence nearly identical to the one found in the infected Asian elephants.

For an as-yet-unknown reason, the herpes virus is not lethal to African elephants. The scientists propose that elephant herpes was first brought to North America by African elephants bearing either a mild or latent form of the disease. Apparently, the virus then jumped to Asian elephants, most likely in zoos and safaris, through contact with bodily secretions such as saliva or urine.
--Melissa Hendricks

Victoria Mock, director of oncology nursing research
Brisk steps to overcoming fatigue

When oncology nurse Victoria Mock began working with breast cancer patients 10 years ago, she observed that many women dropped out before completing their prescribed course of radiation and/or chemotherapy. While the patients experienced many ill effects as a result of treatment, their number one complaint was fatigue.

Mock, now the director of oncology nursing research at Johns Hopkins Hospital, proposes a very simple remedy for fatigue: walking.

Though it sounds anything but restful, walking 15 to 30 minutes per day and other moderate forms of exercise appear to decrease fatigue by half in breast cancer patients undergoing treatment, says Mock, who has conducted several small studies on exercise and cancer-related fatigue. She is continuing to investigate the theory in a larger, more rigorous study involving 150 breast cancer patients at Hopkins and three other hospitals.

Compared to other cancer patients, those with breast cancer experience some of the highest levels of fatigue, reports Mock. Part of the reason probably has to do with the especially lengthy treatment--typically six weeks for radiation and four to six months for chemotherapy.

Radiation and chemotherapy destroy many cancerous cells, along with healthy ones. The body then works overtime to clear away the breakdown products that remain, a process that requires extra energy. A commonly prescribed chemotherapeutic drug called adriamycin may also sap patients' energy. Adriamycin damages mitochondria, the cell's energyproducing organelles.

"Exercise probably helps circulation to all body systems," says Mock. "Better circulation clears waste products better. It strengthens muscles. It helps injured cells heal better because they get more oxygen. The better circulation you have, the better you clear any wound."

In their present study, Mock and her colleagues will also assess whether exercise helps to reduce other potential causes for fatigue, including depression, anxiety, and insomnia.

Next, she plans to expand her study to include patients with prostate and colorectal cancer. --MH

It's all in the rat chow

Changing brands of rat chow may have been one of the smartest things Yoram Shir ever did.

Although the switch was unintentional, it has revealed a potential new remedy for a peculiar type of pain whose cause has eluded scientists for decades.

The serendipitous route of discovery began several years ago when Shir, an anesthesiologist and neuroscientist at Hadassah University Hospital in Jerusalem, began working as a visiting scientist in the laboratory of Hopkins pain authority James Campbell. Shir had developed a rat model of a form of pain called SMP, or sympathetically maintained pain, which occurs after a nerve is injured. He planned to build upon the model with the Hopkins neurosurgeon.

In SMP, pain spreads from the nerve to the nearby skin, which becomes extremely sensitive to touch and cold temperatures. "A mere breeze can trigger severe burning pain, as does going outside on a hot summer day," says Campbell. Curiously, the pain often remains even after the nerve itself has healed.

"You can often tell the SMP patients in the waiting room," says Campbell. "They're the ones who quickly recoil an arm or a leg when you approach them."

Doctors believe that the initial injury prompts adjacent nerves that are involved in the sympathetic nervous system to fire and keep firing, says Campbell. Although certain high blood pressure medications and surgery help some patients, says Campbell, "We struggle to get some of these patients better." Pain can linger for five or 10 years.

Shir created the rat model in Israel. After partially suturing the sciatic nerve leading to a back paw, he then measured each animal's response to various stimuli. Some of the rats exhibited a heightened sensitivity to pain comparable to SMP.

When Shir arrived at Campbell's lab, he first set about duplicating the model. But to his surprise, the rats did not show the same heightened sensitivity.

Shir ordered new strains of rat and tried the experiment again but still could not replicate his earlier results. He changed other variables--the suture material, time of day the experiment was performed, lab temperature, type of cage, age and size of the rats. Nothing worked.

Finally, Campbell suggested that they alter the rats' diet. "We imported Israeli chow," says Campbell, "and bang! We started seeing the model."

The neuroscientists did some digging and discovered that the American chow contained more soy than the Israeli chow. Their conclusion: Soy appeared to protect rats from SMP.

Vendors aren't precise about the amount of soy in their formulas, so it is difficult to tell how much soy is necessary. "But our recent preliminary data suggest it doesn't take a huge amount to prevent pain," says Campbell.

In subsequent experiments, Shir and Campbell compared rats that ate dairy products to rats that ate soy as the sole protein source. The soy-fed rats were strikingly less prone to SMP. Shir, Campbell, and colleagues from Hebrew University reported their findings in a recent issue of Neuroscience Letters.

"Two hundred questions are now unanswered," says Campbell. Namely, what in soy prevents or reduces this type of pain? One possibility is phytoestrogens, proteins with weak estrogen-like activity. Does it matter whether the rat eats soy before or after the ligation procedure? Preliminary studies suggest that soy consumed immediately prior to the surgery confers the maximum protection, says Campbell.

Of course, the biggest question is whether humans will respond to soy as rats do. "We're not close to doing [research] in patients," notes Campbell, "though we will." --MH

Illustration by
Kevin O'Malley
The hazards of youthful drivers

Teenage drivers who have completed driver's education courses don't have safer driving records than those who haven't taken such courses, according to a review of driving safety literature by Jon Vernick, an assistant professor of health policy and management at Hopkins's School of Public Health. In fact, driver's ed graduates may be at greater risk for crashes and violations.

That may be because many states allow teens who've completed driver's ed to get their licenses at a younger age, thereby increasing the number of younger drivers on the road. And young drivers have a much higher rate of accidents. Sixty-five of every 100,000 licensed drivers less than age 21 were involved in a fatal crash in 1996. That is twice the overall crash fatality rate for drivers of all ages.

To reduce the number of teen driving accidents, Vernick suggests rethinking early licensing policies. A safer bet: graduated licensing policies (now used by some states), which afford privileges to new drivers gradually. The results of Vernick's study appear in the January issue of The American Journal of Preventive Medicine. --MH

Risky roads for minority children

Black and Hispanic children ages 5 through 19 are more likely to die in a motor vehicle accident than are white youngsters, according to a study led by Susan Baker, a professor of health policy and management at Hopkins's School of Public Health.

The study, published in the December 1998 Archives of Pediatrics and Adolescent Medicine, was based on motor vehicle death rates collected from 1989 to 1993 by the National Center for Health Statistics and U.S. Department of Transportation data.

Per billion miles of vehicle travel, black children ages 5 to 12 were almost three times as likely to die as were white children, Baker found. Hispanic children were almost twice as likely to die. The greatest disparity occurred among male teenagers: 66 for blacks and 61 for Hispanics, compared to 37 for whites.

Several studies have shown that black and Hispanic children are placed in safety belts or child restraints less often than white children. Research, including a national breath alcohol survey, also suggests that alcohol use is involved in more accidents involving Hispanics and blacks. Further research is needed to confirm and expand on such studies, say the authors. --MH

Illustration by
Kevin O'Malley
Is there a doctor on line?

Passengers on Renaissance Cruise Lines will soon be only a computer link away from physicians at the Johns Hopkins Emergency Department.

Two 700-passenger ships that tour the South Pacific and Mediterranean are introducing technology that will allow X-rays, EKGs, and other clinical data to be beamed via satellite to Hopkins. Within minutes, an emergency physician will review the images and then discuss the case over the phone with the ship's doctor and nurse.

"The physicians will put their heads together and decide whether the patient needs to be evacuated by helicopter, taken to the nearest port, or is safe to stay on board ship," says James Scheulen, administrator for the department of emergency medicine. "Typically, the [system] will be used to provide a second set of eyes, a second opinion, someone whom the ship's doctor can ask, `This is my plan. Do you agree?'"

Renaissance is actively marketing cruises to the 55 and older age group, notes Scheulen; 24-hour access to Hopkins physicians is a big selling point. He anticipates that the telemedicine link will be used most often for heart attacks, stroke, respiratory problems, or injuries.

Engineers at Hopkins's Applied Physics Laboratory are performing the technical wizardry behind the connection. They have engineered similar telemedicine links between Hopkins and a dozen Navy ships. --MH

An alternative to the pap smear?

Cultural barriers, embarrassment, or lack of access to a health clinic prevent many women from having a pap smear. Developing countries have particularly low rates of compliance. The test, however, can help save lives, by detecting changes in the cells of the cervix that indicate cancer or its early warning signs.

Now School of Public Health researcher Keerti Shah is testing a method that would allow women to collect a specimen for cervical cancer screening themselves.

Shah, a professor of molecular microbiology and immunology, and collaborators in Mexico are recruiting 7,500 volunteers from health clinics in Morelos, Mexico.

Each volunteer will collect a specimen of her vaginal secretions using a special Q-tip. Using a new test developed by the Digene Corporation, technicians will then screen each specimen for the presence of the human papilloma virus. HPV is associated with more than 95 percent of cervical cancers.

Clinic health workers will also collect specimens for HPV screening and will conduct a pap smear on each volunteer. In a pap smear, a health worker scrapes cells from the cervix, places them on a slide, and examines them under the microscope.

Women who have a positive result on either the pap smear or HPV tests will be referred for a follow-up examination in which their cervix is inspected with a special microscope.

"A number of studies have shown that the HPV assay on a sample the physician collects works as well as the pap smear," says Shah. If tests on self-collected samples prove as reliable, then this method could be used in place of or to supplement pap smear testing. --MH