Johns Hopkins Magazine -- November 2000
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A better way to detect breast cancer
From test tube to trial
The buzz in pop
Change needed in PSA screening?
Improving the "Pill's" protection
Q&A with John D. Gearhart

A better way to detect breast cancer

A new technique developed by Hopkins surgeon William Dooley promises to improve detection of breast cancers as well as a patient's chances for breast-conserving surgery.

Dooley threads a tiny endocope--about the diameter of the lead in a mechanical pencil--in through the nipple to look inside the breast, magnifying tissue up to 60 times its normal size. In tests on 55 women, the endoscope made possible identification of minute breast lesions that would have been missed by mammography or MRI--lesions up to 1/100 the size these traditional techniques could detect. Dooley, director of the Johns Hopkins Breast Center, outlines the procedure in the September 27 issue of the Journal of the American Medical Association.

Another important benefit of the technique: "Because we can see the tumor so clearly, we can easily find the margins and thus are able to conserve more breast tissue," Dooley says. "Patients who in the past would have received mastectomies... are now candidates for lumpectomies."

Hopkins researchers caution that the new technique is best used in conjunction with standard diagnostic tests. Clinical trials currently under way involve women with symptomatic nipple discharge and those who have abnormal premalignant cells draining from the nipple. Such trials are now being expanded to include detection of precancerous breast lesions. The procedure, which can be done on an outpatient basis, requires only mild anesthesia and lasts between 20 to 30 minutes. Dooley says it is intended for the 10 to 20 percent of women ages 30 to 70 who are at high risk of developing the disease. --Sue De Pasquale

From test tube to trial

"Anything that can be done to manipulate a cell can be done in this facility," says Elizabeth Jaffee, director of the new Cell and Gene Therapy Lab that opened in late September on the second floor of Medicine's Bunting-Blaustein Building for Cancer Research in East Baltimore.

The $1.2 million ultra-modern lab will allow Hopkins researchers to come up with new drugs and therapies and move them quickly into clinical trials to treat cancer, diabetes, and other diseases. "We can alter gene expression in tumor cells as well as normal cells, insert missing enzymes, transfer genes into vaccines, or replace missing genes," says Jaffee, associate professor of oncology. Such "new and improved" cells can then be introduced to patients in the form of a vaccine, she says.

Clinical trials using drugs developed in the new lab were expected to begin as early as October. --SD

Caffeinated sodas were once depicted as energizing tonics, as this 1909 ad attests.
The buzz in pop

Soda manufacturers claim that they add caffeine to certain soft drinks to enhance flavor. But Hopkins psychopharmacologists now find that few cola drinkers can tell the difference between a cola containing caffeine and one that does not.

In taste tests involving 25 volunteers who said they preferred either caffeinated or caffeine-free cola, the researchers found that only two (8 percent) could detect caffeine in a cola containing a concentration equivalent to that found in most brands of cola (0.1 milligrams per milliliter). The researchers reported their findings in the August Archives of Family Medicine.

As drugs go, caffeine has relatively few health risks, says Roland Griffiths, who led the study. But it is mildly addictive. "A person who consumes the caffeine equivalent to that found in two to three 12-ounce cans of caffeinated soda per day and then stops will experience withdrawal symptoms-- headache, lethargy, fatigue-- which can be fairly debilitating in some people," he notes.

By its addictive nature, caffeine thus may be contributing to soda consumption, says Griffiths, who has studied the chemical's mood-altering effects for the past 15 years. Approximately 70 percent of the soda sold in the United States--including cola, birch beer, and root beer--contains caffeine. Americans consume 15 billion gallons of soda per year, a total that has increased ninefold since 1942, when the American Medical Association noted that soda is of low nutritional value. Studies suggest that drinking soda rather than other more nutritional beverages increases the risk of tooth decay, obesity, and bone fractures, especially in children and teenagers. --Melissa Hendricks

Change needed in PSA screening?

Physicians might best be advised to begin screening men earlier for prostate cancer and at less frequent intervals, according to results of a new study done by researchers at Johns Hopkins, Merck Research Labs, and the University of North Carolina.

Standard practice until now has been to start annual PSA (prostate specific antigen) blood tests at age 50. But by using a computer model to simulate prostate cancer outcomes under varied conditions, the researchers came up with a scenario they believe could save both money and lives: Test men once at 40, again at 45, and then follow up at age 50 with tests every other year.

This approach "would substantially reduce the cost we spend on prostate screening," and "also prevent more deaths from prostate cancer, compared with existing screening practices," says Hopkins urologist H. Ballentine Carter, a member of the research team, which reported its findings in the September 19 Journal of the American Medical Association.

Compared to the standard method for screening, Carter says, the model "showed you would do 3,000 fewer PSA tests and 200 fewer biopsies for every 1,000 men screened over a lifetime." Prostate cancer's slow growth and progression means annual screening is "probably not necessary," he says.

The scientists embarked on this study because of earlier work Carter did showing that cure rates for prostate cancer tend to be higher for younger men--probably because their tumors are smaller and more confined.

While Carter contends that earlier screening could save lives, he concedes that the new study is based on a computer model, and thus may not be persuasive enough to "change screening practices tomorrow." He adds, however, "because this simulation is trustworthy, it's very strong evidence indeed that what we're doing now is probably not the best way."

Improving the "Pill's" protection

If all women who took oral contraceptives strictly followed the directions, only one out of 1,000 would become pregnant in a year. But in reality, the error rate is much higher: in the U.S., 69 out of 1,000 women become pregnant during their first year of using the pill. Worldwide, the figures range from 17 women per 1,000 in Bangladesh, to 105 per 1,000 in Bolivia.

Improved education could significantly reduce the unintended pregnancy rate among pill users, according to a report in the Summer 2000 Population Reports.

Each year, 6.8 million unintended pregnancies occur in women who stop taking the pill--even briefly--and fail to replace it with another contraceptive.

Another 2 million pregnancies occur due to improper use, such as accidentally skipping a pill or taking them out of sequence. "Many women don't know that starting a new pill pack late poses the greatest risk of pregnancy," says Vera Zlidar, report author and research analyst at Hopkins's Center for Communication Programs. Better counseling, integrating messages about the pill into television and radio programs, and improved access could significantly reduce the unintended pregnancy rate, says Zlidar. --MH

Q&A with John D. Gearhart

Two years ago, Medicine's professor of physiology John D. Gearhart reported that he had isolated embryonic stem cells and developed a method for growing them in culture. The discovery suggested a vast array of therapeutic uses but also prompted ethical objections, which led to a ban on the use of federal funds for stem cell studies, forcing Gearhart to use private funds. In August, the ban was lifted, and the NIH issued guidelines for scientists receiving federal funding, including: Stem cells may only be obtained from extra embryos created for in vitro fertilization that would otherwise be discarded; they must be donated through informed consent; and donors may not be paid.

How will the new NIH guidelines affect your work?
Now we can write a grant and have it peer-reviewed for federal funding. Since we started this work, we wrote and abided by our own guidelines, which are very similar, if not identical, to the ones the NIH put through.

What injuries or illnesses will be the first candidates for clinical trials? And how soon?
I think in three to five years we'll be into clinical trials with these cells. Maybe something like a spinal cord injury will be first because it is localized. Or perhaps Parkinson's, which involves one region of the brain. I would even argue--based on clinical trials at the University of Pittsburgh on stem cells from a human tumor--that stroke would be a good target, as well. Conditions like ALS [Lou Gehrig's disease] or Alzheimer's are much too difficult because you have neurons degenerating all over the place. And we understand so little about those diseases.

Do you have any qualms about the clinical use of stem cells?
I am concerned about the hype and the hope that comes with it for patients in need. There are a lot of questions we've got to answer, such as whether we'll be able to grow pure populations of cells, or whether we'll get a mix of cells, which might not be useful clinically. On the other hand, when you talk about what is going on among scientists, it's unbelievably exciting. For the first time, we have in a laboratory a cell that's immortal--that, based on what you tinker with, can grow into any cell in the human body. --Interview by Melissa Hendricks