Johns Hopkins Magazine -- September 1997
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SEPTEMBER 1997
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H E A L T H    &    M E D I C I N E

A killing agent that could help in cystic fibrosis... the fallout from childhood abuse... an alternative to methadone... number one for the seventh year running... new hope for a sinister eye disease... something else to lose sleep over... nurse practioners fill need



CF patients lack a toxic peptide that may prevent lung infections.
A new line of defense
Scientists have found them in frog skin, cow throats, and human skin. Now Hopkins biologists demonstrate their presence in human lung cells. What are "they"? Natural killer peptides called defensins that appear to help protect the body from infection.

Antibodies and T cells are no longer the body's only defense mechanisms, says Pete Pedersen, a professor of biological chemistry at the School of Medicine. With research associate Young Hee Ko, Pedersen shows that healthy lung cells appear to secrete one or more of the toxic peptides (a peptide is something like a miniature protein).

The peptides appear to kill the bacterium Pseudomonas aeruginosa. In contrast, lung cells from cystic fibrosis patients, who are particularly prone to Pseudomonas infection, appear to lack the peptide.

In cystic fibrosis, which occurs in one in 2,000 people, the bacterium Pseudomonas aeruginosa infects most patients, says professor of physiology Bill Guggino, who conducts research on CF. Many patients are infected early in life and never manage to shake the bug, which inflames the lungs and can make it difficult to breathe.

The Hopkins team's experiments show that normal lung cells clear a thick infection of Pseudomonas in a matter of hours. Lung cells from cystic fibrosis patients, in contrast, are overrun by bacteria, which bind to every nook and cranny and eventually even penetrate the cells.

Pedersen theorizes that defensins "punch holes in the bacterial cell wall and membrane" before Pseudomonas even has a chance to latch onto lung tissue. But so far they have only indirect evidence. Their next task is to bag an actual defensin. They are now inspecting the secretory fluid from healthy and CF lungs to see if they can isolate the killer peptides.

"When we know what the killing agent is," says Pedersen, "it can potentially be used to treat CF patients." --MH


The lingering effects of abuse
Women who were physically or sexually abused as children are more likely to suffer health problems later--including headaches, frequent stomach pain, and depression, a Hopkins
School of Medicine study indicates.

A survey of about 1,900 women treated at four primary care practices showed that one in five women reported being abused as children and that those women were more likely to have chronic health troubles than women who weren't abused. These problems included chest pains, back pain, and drug or alcohol problems.

Published in the May 7 Journal of the American Medical Association, the study also showed that suicide attempts were nearly four times more common among women who were abused when they were young.

Lead author Jeanne McCauley of the Division of General Internal Medicine at Hopkins's Bayview Medical Center found that many patients are afraid to tell doctors of past abuse, often out of embarrassment. "Our study suggests that the wounds of childhood abuse may go unhealed," McCauley says.

The link between abuse and symptoms remains unclear, though experts theorize that psychological repercussions, such as low self-esteem and stress, may compound health problems. Study authors urged that physicians be trained to look for signs of abuse and to ask questions about past abuse. Patients can be directed to support groups or treated for post-traumatic stress disorder. --JC


An alternative to methadone
Heroin users given a drug called LAAM reduced their heroin use by as much as 90 percent, report researchers at the Johns Hopkins
Bayview Medical Center, in the June 25 Journal of the American Medical Association. LAAM, or levomethadyl acetate, works as well as methadone, says Hopkins psychologist George Bigelow, but only needs to be given three times a week while methadone requires daily doses. "Methadone is a wonderfully effective treatment, but inconvenient," says Bigelow. A thrice weekly drug regimen would interfere less with work schedules and other daily activities.

Although LAAM was approved by the U.S. Food and Drug Administration as a therapy for opioid dependence in 1993, states must individually okay its use in licensed clinics. It is slowly gaining approval, says Bigelow.

Another drug called buprenorphine now under investigation at Bayview may be even more promising than LAAM, say Hopkins researchers. Buprenorphine appears to be abuse-proof and incapable of causing an overdose. The researchers will complete a comparative clinical study of buprenorphine, methadone, and LAAM sometime next year. --MH


#1
For the seventh year running, Johns Hopkins Hospital has been ranked tops in the country in U.S. News & World Report's annual "Honor Roll" of hospitals. Hopkins ranked in the top 10 in 16 of the 17 specialties listed by U.S. News. Three Hopkins specialties ranked first: gynecology, ophthalmology, and urology.



A healthy retina imaged by the new camera.
Nabbing retinopathy before it's too late
Diabetic retinopathy can be sinister. A person can have the potentially blinding eye disease but not even know it, while blood vessels encroach on the retina like vines in a jungle. If left unchecked, such overgrowth can permanently blind.

If diabetic retinopathy is caught in time, laser therapy can dramatically reduce its progression and prevent vision loss, says Ran Zeimer, professor of ophthalmology at the School of Medicine. The problem is that only about half of the 16 million diabetics in the United States visit an ophthalmologist annually.

Most diabetics, however, visit their primary care physician several times a year, says Zeimer. So Zeimer and a team of engineers and ophthalmologists developed a camera for spotting diabetic retinopathy that can be used by general practitioners. It will enable diabetic retinopathy to be diagnosed in its earlier, more treatable stages, says Zeimer.

The leading cause of vision loss in working-age Americans, diabetic retinopathy is typically diagnosed by an ophthalmologist through a routine test called the dilated eye exam. With ordinary ophthalmic tools, the ophthalmologist examines the retina, or image-forming lining of the eye, for the telltale pathology: the growth of new vessels or swelling. In later stages, vessels can bleed into the eye, and patients notice floaters or cloudy regions.

With Zeimer's apparatus, a diabetic patient views a series of images through an eyepiece in a box, similar to the vision-testing apparatus at the Motor Vehicle Administration. A camera collects digital images of the patient's retina.

Eventually, says Zeimer, physicians will be able to transfer images electronically from the camera to a reading center, where an ophthalmologist or trained specialist will examine them for signs of retinopathy.

The Hopkins team, which includes biomedical engineers Shazhou Zou and Xinrong Guo, and ophthalmologists Morton Goldberg and Daniel Finkelstein, along with EyeTel Imaging Corporation, developed the camera, which is now being tested on patients. Hopkins shares royalties with EyeTel. The company plans to make the camera available free-of-charge to physicians, and to charge for its reading services.

"We've proven feasibility so far," says Zeimer. "We've shown that images taken with the camera are as good as the gold standard." The team will have to prove that the new technique is less expensive than the cost of an ophthalmic exam, he notes. In the future, the new test could also be used to diagnose glaucoma and age-related macular degeneration. --MH



Something else to lose sleep over
Insomnia could help predict a young adult's risk of developing clinical depression in midlife. A long-term study of 1,000 male physicians reveals that volunteers who had insomia during medical school had twice the rate of clinical depression in subsequent years, even 20 years after med school, Hopkins researchers report in the July 15 American Journal of Epidemiology. -- MH


Nurse practitioners fill acute need
In the Cardiology Division of Johns Hopkins Hospital, two nurse practitioners now perform tasks that interns and residents once did, including prescribing medications. The NPs are part of a pilot program created to plug a hole left as interns and residents move from hospital wards to outpatient centers and doctors' offices, in search of primary care experience.


Moving nurse practitioners into acute care roles may well become a national trend, says Karen Haller, nursing director for the Department of Medicine, who notes that the demand for NPs trained in acute care is growing exponentially.

This fall, the Johns Hopkins School of Nursing will launch its first master's degree program in acute care for nurse practitioners. A dozen students have already enrolled. The program is aimed at preparing NPs to treat patients in emergency departments, trauma settings, and critical and intensive care units. --MH

Written by Joanne P. Cavanaugh (MA'97) and Melissa Hendricks.


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