Johns Hopkins Magazine -- June 2000
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JUNE 2000

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Vital Signs

Earlier, easier cancer detection
Ooo-la-la! Pain relief that's a fantasy
The more the deadlier, for teen drivers
Gynecology: Not just for gals anymore
Why schizophrenia hits men harder
Doctors in the movies
A new doctoral program for Nursing

Sidransky: honing in on mutations in the DNA of mitochondria
Earlier, easier cancer detection A new noninvasive method for detecting mutations in DNA might one day be used to detect cancer years before disease symptoms arise, according to Hopkins oncology researchers who are developing the technique.

Their method identifies mutations in the DNA of mitochondria, the bean-shaped, energy-producing organelles found in the cytoplasm of cells.

The researchers demonstrated that these mutations are associated with tumors and can even be detected in bodily fluids of cancer patients, for example in the urine of a patient with the very earliest stages of bladder cancer.

"This test is very, very sensitive," says Makiko Fliss, a postdoctoral fellow and first author of the paper that appeared in the March 17 Science. "If you have only five to six tumor cells in the bladder, it could probably detect it." Identifying cancer at such an early stage, of course, has enormous advantages for treatment.

Fliss and her colleagues tested mitochondrial DNA from bladder, head and neck, and lung tumors from 20 patients, finding mitochondrial DNA mutations in all of the bladder and lung cancer patients and most of those with head and neck cancer. The scientists also applied the test to samples of bodily fluids (urine, saliva, or bronchial fluids) from several of the same patients, and found the same mitochondrial DNA mutations. Since their report in Science they have confirmed their results on many more patients.

When tumor cells die, they are sloughed off into the blood and other bodily fluids, explains Fliss. Making use of such bodily fluids to screen for cancer would allow patients to avoid the pain and discomfort of invasive tests, such as a test for bladder cancer that involves threading through the urethra a tiny camera on the end of a catheter. It would also be less expensive and allow for earlier detection.

Whether or not mutations in mitochondrial DNA contribute to cancer is not clear, says David Sidransky, professor of otolaryngology and oncology and senior author on the paper. But regardless of whether mitochondrial DNA mutations help cause or simply accompany cancer, they might still be useful signatures of the disease.

In previous research conducted over the past several years, Sidransky and his colleagues developed cancer diagnostic tests that screen for mutations in nuclear DNA (of which chromosomes are made). The tests, which are now in clinical trials, are showing promise of being highly accurate.

However, his new method, screening for mutations in mitochondrial DNA, offers an advantage. That's because each cell contains only two copies of each chromosome, and thus only two copies of any particular mutation that occurs in chromosomal DNA. But several hundred to thousands of mitochondria reside in the cytoplasm of each cell, each one bearing a clone of any mutation. As a result, the signal from mitochondrial mutations is 20 to 200 times stronger than the signal from nuclear DNA mutations, according to the researchers. Thus, even if only a few cells bear mutations in mitochondrial DNA, the new technique could probably detect them.
--Melissa Hendricks

Illustration by James Yang
Ooo-la-la! Pain relief that's a fantasy

Research projects are often crafted as scientists huddle over graphs and charts in the laboratory or debate the significance of new findings in a conference auditorium.

But sometimes ideas spring from more pedestrian sources--like a supermarket tabloid. Such was the case for Hopkins anesthesiologist Peter Staats, director of the Division of Pain Medicine.

Staats and his colleagues had developed a broad theory of pain. It encompassed aspects of biology, behavior, and emotion, and said that the perception of pain was closely tied to emotions. In 1995, the researchers tested this theory on volunteers who were asked to plunge a hand in a tank of ice-cold water and keep it there as long as possible. Staats then discovered that various messages could increase or diminish their tolerance to pain. For example, volunteers who were told positive things during the experiment, such as, "Ice water has the ability to heal," reported less pain than a control group of volunteers.

Researchers in the pain field gave the study and underlying theory high marks. However, it garnered little media attention.

A few years later, Staats' secretary, Linda Stevens, was thumbing through an issue of the National Enquirer. There she found a story about the pain study. Or, at least, it was an Enquirer version of the study. A reporter had inventively penned: "Sexy thoughts banish pain."

"It was quite humorous," says Staats. "But it had nothing to do with my study. I'd never been interviewed by the National Enquirer."

But, Staats got to thinking, maybe there is something to the notion that sexual fantasies reduce pain.

So he and his colleagues repeated their experiment, this time asking college student volunteers to think of a sexual fantasy while they kept a hand in the ice water. Other students were given more mundane topics, such as walking to class, or were not told to think about anything in particular. During the experiment, the students were asked questions about their mood, worries, and degree of pain.

Indeed, the researchers found, volunteers who lost themselves in sexual fantasies reported less pain, just as the Enquirer had foretold. Staats reported the results this past October at the annual meeting of the American Pain Society, in Fort Lauderdale.

Unlike the earlier study, this report has received widespread media attention, including coverage in USA Today, Penthouse, and The New York Times. It has even become fodder for comedian Jay Leno.

But seriously, folks...the study also supports the theory that pain and emotion are linked. Notes Staats, "Emotions are likely processed in the thalamus, a region of the brain also closely involved in processing pain responses." Further, the study suggests that patients might be able to effect some of their own pain management, using their minds.

The more the deadlier, for teen drivers

The risk that a teenage driver will be killed in a car crash increases with every passenger in the vehicle, according to a recent School of Public Health study.

Sixteen- and 17-year-old drivers who carry three or more passengers have triple the risk of dying in a car crash, compared to solo drivers in that age group.

"It's possible that when teenagers drive with peers they may be more likely to speed or run red lights. They may be encouraged by their peers [to drive hazardously] or try to impress them," suggests lead author Li-Hui Chen, a research associate in Health Policy and Management, who published her results in the March 22 Journal of the American Medical Association.

Chen and her colleagues also found that the risk was highest for male teenage drivers carrying three or more passengers. And driving at night greatly increased teen driver fatality rates.

In contrast to the teen statistics, the risk of dying in a car crash for drivers in their 30s through 50s declined with passenger number.

Gynecology: Not just for gals anymore

"Let's face it, guys. Most of you wouldn't know a Pap smear from a reindeer. You probably think that a vulva is a Swedish sports sedan. You know your girlfriend's got PMS, but you'd rather join the Witness Relocation Program than learn anything about it. The long and short of it is, when she comes home from the gynecologist, trying to discuss the exam with you is like trying to get the pope to do a condom commercial."

So write Udo Wahn, MD '75, and Bruce Bekkar, in Your Guy's Guide to Gynecology: A Resource for Men and Women (Ant Hill Press, 2000). Both are OB/GYNs at the University of California at San Diego; they argue that despite men's ignorance or reluctance to know about their partners' reproductive health, men ought to learn more; a woman's reproductive health affects her partner's. In their book, Wahn and Bekkar provide information on birth control, endometriosis, hysterectomy, uterine fibroids, and other "female-only" topics, interspersed with quizzes and answers to many commonly asked questions.

Why schizophrenia hits men harder

One of the many puzzling characteristics of schizophrenia is that men generally suffer from the mental illness more severely than do women. Symptoms appear in males years before they do in women, and men overall are less responsive to medication. Now, recent imaging studies in a Johns Hopkins lab suggest that the way schizophrenia shapes the brains of men and women may underlie these gender differences.

In a healthy male, the left IPL is larger than the right.

Researchers led by psychiatrist Godfrey Pearlson focused on a part of the cerebral cortex called the inferior parietal lobule (IPL)--a sort of neural crossroads where pathways from many different brain structures converge. Each hemisphere of the brain contains an IPL. On the left side, the IPL is involved in visual perception and spatial relationships, such as gauging how fast a ball is moving. On the right side, the IPL governs a person's understanding of where each body part is in relation to another, a skill that is used in rock climbing or ballet, for example. The right IPL also comes into play in judging how another person feels by reading his or her facial expression or body posture.

In a previous study involving healthy volunteers, Pearlson and his colleagues found that men have a larger IPL than women (even after the volumes were adjusted for the relatively larger size of men) and that their left IPL is larger than their right. In contrast, healthy women had a reverse asymmetry: their right IPL was slightly larger than their left.

In the recent study, the researchers compared MRI brain scans of 30 schizophrenic men and women with scans from 30 healthy closely matched volunteers. They used a software program created by Hopkins psychiatrist and biomedical engineer Patrick Barta that uses MRI data to calculate IPL volume.

The results showed that schizophrenic men have a reversed asymmetry in the IPL, compared to healthy men. Their right IPL is larger than their left. Further, the overall size of the IPL of schizophrenic men is 16 percent smaller than it is in healthy men. Women with schizophrenia did not show significant differences in IPL size or asymmetry compared to healthy women.

The gender differences in IPL size and asymmetry could underlie clinical differences seen in men and women with schizophrenia, say the researchers, who reported their recent findings in the March issue of the American Journal of Psychiatry. Men who have schizophrenia generally begin showing signs of the illness between ages 15 and 20, compared to ages 20 to 25 for women. Likewise, "men have more subtle neurological abnormalities," says Pearlson. "They have more deficit symptoms such as a lack of will and directed energy. They [have difficulty] planning, completing things, or making decisions."

Although schizophrenia is best known for its hallucinations and delusions, those symptoms are often easier to treat than the broader, subtler deficits. As a result, women schizophrenics are more likely to marry, hold a job, and live relatively normal lives. But schizophrenic men often have symptoms that persist, and they tend to have more personal troubles such as being unemployed or homeless, Pearlson says.

"There is probably something in the whole circuit of which the IPL is part that gets miswired in schizophrenia," says Pearlson, who with his colleagues has identified other anatomical differences in the brains of schizophrenics. Understanding such differences, says Pearlson, could lead to interventions for delaying the onset or diminishing the severity of schizophrenia in people who are at risk, he says.

The IPL develops relatively late in adolescence or in early adulthood, notes Pearlson. "Because the brain is so plastic, if we could identify people at risk for schizophrenia, and give them some cognitive training, perhaps we could strengthen other areas, which could compensate for deficits in the IPL." Currently, however, he adds, "that is a highly hypothetical possibility."

Doctors in the movies

Peter Dans became a movie buff while growing up on New York's Lower East Side in the 1940s; he frequently escaped his family's cold-water flat to spend long afternoons at the Tribune Theater.

Dans, an associate professor of medicine at Hopkins, was able to indulge in his passion once again while researching and writing Doctors in the Movies: Boil the Water and Just Say, "Aah" (Medi-Ed Press, 2000). The book, the product of thousands of hours of movie watching, examines how movies reflect changes in medicine and the way society perceives doctors and other healthcare professionals.

Photo courtesy Photofest
Dans describes two characterizations of doctors and medical institutions: the noble and godlike, such as the compassionate and heroic neurologist Malcolm Sayer (Robin Williams) in Awakenings; and the evil and conspiring. Perhaps the most memorable portrayal of an evil health professional is the notorious Nurse Ratched (Louise Fletcher), who tries to break the belligerent Randle McMurphy (Jack Nicholson, at left) in One Flew Over the Cuckoo's Nest.

A new doctoral program for Nursing

The current trend toward cost-cutting in the nation's health-care system has prompted the School of Nursing to launch a new doctoral program--the Doctor of Nursing Science (DNSc).

The 50-credit program will focus on health outcomes measurement, healthcare economics, statistical analysis, and informatics. The goal: to prepare nursing leaders for top spots in health care systems administration, academia, professional organizations, and government agencies. Coursework, which will be offered during the summer and take four to five years to complete, will focus on analyzing healthcare data in ways that will allow policy-makers to better evaluate patient care, program quality, and economic outcomes.

The new DNSc program complements the school's existing PhD program, which focuses on basic discovery and clinical intervention studies.