Johns Hopkins Magazine -- February 2000
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Vital Signs

Capturing the heart in motion
HIV test avoids the needle stick
A new recipe for preventing malaria
Study questions merits of tube feeding

Capturing the heart in motion

Hopkins researchers are developing a faster, more efficient way to test how well a patient's heart works. The technique, which they've named HARP MRI (harmonic phase magnetic resonance imaging), could lead to safer cardiac stress tests and more informed decisions regarding heart surgery or other cardiac treatments.

Currently, doctors use ultrasound during cardiac stress tests; it provides immediate feedback but doesn't give detailed images of the heart. MRI technology allows doctors to view the anatomy of the heart, thus enabling them to locate more accurately blocked arteries and dysfunctional muscles. But an MRI scanner is too impractical and costly to use during a stress test.

"If a doctor suspects heart disease, it is helpful to analyze the motion of the heart, but you don't want to give the patient myocardial infarction. If the stress test goes on a few minutes too long, you have the potential of heart damage being done," says Jerry L. Prince, professor of engineering in the Whiting School's Department of Electrical and Computer Engineering. "We hope to improve this [system] by providing more quantitative information faster. It would enable sicker people to take this test."

Prince (l) and Osman are developing a technique that could lead to safer cardiac stress tests.
Photo by Keith Weller
What's more, by more accurately diagnosing problems earlier, doctors and patients could better choose between changes in diet, medicine, or surgery--or see how well any of these methods is working. And the researchers could more easily test the efficiency of drugs meant to revive a stunned heart muscle.

To develop the HARP MRI, Prince and Nael Osman, a PhD student in the department, have refined MRI scanning by adapting a technique known as MRI "tagging."

Currently in use only in research arenas, tagging "marks" planes within the heart muscle so that movement can be tracked. If the left ventricle is being deprived of oxygen, for example, portions of the heart muscle won't contract properly. Until now, the time needed to process and interpret such images has been too costly and unwieldy: "Tagging can be computed in several hours," says Osman. "That's great. But if you are a doctor, you don't have that kind of time."

To speed up the imaging and analysis, Prince and Osman are applying communications theory--the mathematics behind FM and AM radio--and utilizing computer software they've engineered. The $2 million-plus HARP-MRI project is being funded by the National Heart, Lung and Blood Institute, and the two researchers recently applied for a U.S. patent to cover the technique.

Prince and Osman have done preliminary tests using MRI scanning data from various sources, including cardiac patients at the Johns Hopkins Medical Institutions. "It's very straightforward, very fast, and we can get results in three to five minutes," says Jerome Garot, a Hopkins research fellow in cardiology. "The quality of the image is very good." Soon, it could be even faster. Says Osman: "We hope we can do this in real-time."

The HARP MRI system is still under development, but Prince and Osman have already seen doctors' jaws drop at what they've done so far. The current system can provide two-dimensional color computer images, mostly of the left ventricle, and they are working on creating 3-D views of the entire heart.

And, as images of the heart in motion become more detailed, analysis could become even more accurate. "Instead of just eyeballing the change, a doctor can detect a 10 to 12 percent difference in how the muscle stretches," Prince says. "The more reliable and fast [scanning] is, the more people you can test to save lives." --Joanne Cavanaugh Simpson

HIV test avoids the needle stick

A urine test for HIV is virtually as accurate as the conventional HIV blood test, report Hopkins researchers.

The study, which involved 222 volunteers in rural southwestern Uganda, is the first community-based evaluation of the relatively new urine test. The results validate earlier limited studies, says Ronald Gray, a professor of population and family health sciences at the School of Public Health.

"The urine test has enormous advantages in terms of its simplicity and safety and acceptability," says Gray. Many people are reluctant to have their blood drawn but are willing to submit to a urine test, he says. Urine testing is also safer for the health workers, who run the risk of pricking themselves with an HIV-contaminated needle while drawing blood from an infected patient. Urine contains antibodies to HIV, but not the infectious virus itself.

Gray and colleagues published their results in the October 19 Sexually Transmitted Diseases. --Melissa Hendricks

A new drug combination may be useful in protecting travelers in malaria-prone regions.
Photo by Nirbhay Kumar
©Molecular Cell, June 1999
A new recipe for preventing malaria

Malaria drug researchers face a never-ending challenge. Each time they develop a new drug, a drug-resistant strain of Plasmodium falciparum, the malaria parasite, emerges.

A new Hopkins study offers some hope. Johns Hopkins clinical pharmacologist Theresa Shapiro recently demonstrated that the drug atovaquone protected volunteers from malaria. Other studies indicate that atovaquone paired with another drug called proguanil confers protection against malaria with an extremely low risk of resistance.

In the near term, the drug combination may be used to protect travelers to malaria-prone regions.

In the Hopkins study, 12 volunteers received atovaquone and four received a placebo drug. Each volunteer was then bitten by five mosquitoes infected with Plasmodium. All of the volunteers taking the placebo contracted malaria while the ones on atovaquone remained healthy. Shapiro, Nirbhay Kumar, and their colleagues reported the results in the September American Journal of Tropical Medicine and Hygiene. (The study was rigorously designed to minimize the health risks to volunteers, notes Shapiro. Volunteers were required to report to a clinic daily throughout the study. Those who contracted malaria were diagnosed and treated immediately, which significantly reduces the severity of the illness.)

Other studies, however, suggest that administering atovaquone alone to patients with malaria will lead to resistance. In one study, a significant fraction of malaria patients taking the drug developed atovaquone-resistant Plasmodium parasites.

A better bet, says Shapiro, would be combining atovaquone and another drug called proguanil.

"It seems the drugs hit different molecular reactions and something about the combination is greater than the sum of the parts," says Shapiro. Because the two drugs inflict a "double whammy" on the parasite, they might reduce the risk of resistance, she suggests. Another advantage is that travelers will only have to take the drugs while they are in a malaria region. Anti-malarials currently prescribed must be taken during and for several weeks after a journey to such a region.

Glaxo Wellcome Inc. has applied to the FDA to market the atovaquone/proguanil package as a malaria prophylactic for travelers and as treatment for patients with malaria infections. --MH

Illustration by James Yang
Study questions merits of tube feeding

Nursing home patients with advanced dementia often have problems eating, and tube feeding is used in about 10 percent of such cases nationwide as a way of ensuring proper nutrition.

But according to a recent review study by Hopkins geriatrics specialists, there is no evidence that tube feeding benefits these patients--and may even do more harm than good.

In tube feeding, patients receive a liquid diet through a tube inserted either through the nose or directly into the stomach. The rationale usually given to explain the practice is that it reduces the risk of pneumonia (caused by inhaled food), and prevents suffering and early death caused by malnutrition, says Hopkins geriatrician Thomas Finucane.

But in a review of all 72 papers in the literature on tube feeding in dementia patients, published over the past 33 years, Finucane found no evidence that the practice reduces these risks. Several studies even indicated that tube feeding increases the risk of pneumonia and infections. Exactly why is not clear, but one theory is that insertion of a naso-gastric tube loosens the sphincter muscle that prevents reflux, explains Finucane. Neither did patients who were tube-fed live longer, or have fewer bedsores or infections, which would have indicated they were receiving better nutrition. In some cases, patients became so agitated by the discomfort of the tubes that they required restraint.

Finucane reported the results in the October 13 Journal of the American Medical Association.

Many patients could do just as well, if not better, if nursing home staff fed them by hand and used other simple techniques such as frequently reminding patients to swallow, concludes Finucane. Of course, that would require more staffing. "It's an open question," he adds, "if we'll fund nursing homes adequately" to achieve that end. --MH