Johns Hopkins Magazine -- November 1998
Johns Hopkins 
     Magazine Home


H E A L T H    &    M E D I C I N E

A genetic link to schizophrenia... chlamydia and teens... X marks the spot in prostate cancer... Reducing cancer among overweight women... HIV's toll on women... Genetics for nurses ... heart healthy signs... Take me to your kidney

Pulver: On the trail
Zeroing in on schizophrenia genes

Hopkins geneticists recently took a major step toward finding a gene linked to schizophrenia, an illness that affects 1 percent of the world's population.

The scientists tracked the gene to a stretch of chromosome 13, they report in the September Nature Genetics. The next step--pinpointing the precise location of the gene within this region of the chromosome--may take about five years, predicts lead investigator Ann Pulver, ScD '79.

The current finding, which was based on DNA analysis of more than 100 schizophrenic patients and their families, is the most statistically rigorous work to date showing a link between a region of DNA and schizophrenia, a difficult to diagnose illness whose symptoms include hallucinations and delusions. There is only a two in 100,000 chance that the link occurred by chance.

Previous studies have suggested that genes for schizophrenia susceptibility are found on chromosomes 5 and 6, and Pulver and her colleagues also found hints of schizophrenia risk associated with chromosome 8. Though the statistical significance of those studies has not been confirmed, Pulver says that multiple genes "are definitely involved" in the illness.

Pulver, a genetic epidemiologist at the School of Medicine who has spent all her career studying schizophrenia, began collecting epidemiological data on schizophrenics and their families in the early 1980s. In her doctoral dissertation, she noted a higher incidence of schizophrenia among people who were born in late winter and early spring. Researchers have also found that perinatal complications such as influenza appear to increase a woman's chances of having a child who is schizophrenic.

But researchers also know that the offspring of schizophrenics have a 10 percent chance of developing the illness (compared to a 1 percent rate in the general population). So both genes and the environment are clearly involved.

The researchers are continuing to track schizophrenia susceptibility genes on chromosomes 13, 8, and 22. They are now limiting their study population to volunteers who are Ashkenazi Jews. Ashkenazim are more genetically homogeneous than a random sample of the population, which simplifies the genetics. There is no evidence that schizophrenia occurs more frequently among Ashkenazi Jews, notes Pulver.

The researchers hope that when they find their genetic quarry, it will help other scientists improve the treatment of this devastating illness. "Right now we really don't know the causes of schizophrenia, and medications are less than perfect," says Pulver. "One way to develop new medications is to understand genetic defects and target medications to these genetic defects."

There is one other reason Pulver would like to understand the roots of schizophrenia: to dispel the stigma associated with this mental illness. "This is a medical condition," she says, "just like diabetes or cancer." --Melissa Hendricks

Chlamydia (bottom) is the most common communicable disease in the U.S.
Screening urged for chlamydia

Chlamydia is so prevalent among sexually active young women that they should be tested for the illness twice a year, report Hopkins researchers. Current guidelines, which recommend yearly testing, are not sufficient, they say, because many young women are developing new chlamydia infections well before they are due for an annual screening test.

Chlamydia, which is caused by the bacterium Chlamydia trachomatis, is the most common communicable disease in the United States, with 4.5 million new cases occurring each year, says Thomas Quinn, professor of medicine and molecular microbiology and immunology. It is also a major source of infertility. If left untreated, it can infect and scar the fallopian tubes and lead to pelvic inflammatory disease or ectopic pregnancy.

Fortunately, chlamydia is easily cured, sometimes with a single dose of an antibiotic. The catch is that women who are infected usually have no symptoms. Years can go by before a woman learns she has been infected. She may find out only when she starts having problems with infertility.

Quinn and his colleagues screened 3,202 sexually active adolescents for chlamydia at Baltimore school-based clinics over a two-year period. Twenty-four percent of the girls tested positive for chlamydia infection during an initial visit. These girls promptly received antibiotics for their infections. Fourteen percent of the girls tested positive on repeat visits. The median time for infections to develop in between visits was six months, they report. The longer an infection is left untreated, the more opportunity there is for the infected person to spread the disease to other sex partners. "That is why we recommend screening twice a year," says Quinn.

"Teenagers are highly susceptible to chlamydia," says Quinn. This appears to be because their anatomy allows more cells to be exposed to the bacterium, and also because sexually active teenagers have more sex partners. The highest rate of chlamydia occurred among 14-year-old girls. The researchers reported their findings in the August 12 Journal of the American Medical Association.

In a separate study, reported in the September 9 New England Journal of Medicine, Quinn and epidemiologist Charlotte Gaydos conclude that almost one in 10 female Army recruits is infected with chlamydia.

The researchers used a relatively new urine test that eliminates the need to do a pelvic exam to collect a cervical sample. The same simple test could be used on men and boys, who can also be silent carriers of chlamydia. Screening men and teenage boys will be essential for reducing the spread of chlamydia. --MH

X marks the spot

The X chromosome, which children inherit only from their mothers, is the site of a gene for prostate cancer, according to a study by Hopkins urology researchers and their colleagues at the National Institutes of Health and other research centers. The Hopkins team, which includes geneticist William Isaacs and urologist-in-chief Patrick Walsh, published its results in the October Nature Genetics.

The discovery is the first time a gene for a major cancer has been tracked to the X chromosome, which was already known to be the home of genetic traits for hemophilia and muscular dystrophy.

Mapping the gene, which is called HPCX, is only a first step. Next the researchers will try to isolate the gene and then possibly use that information to see who is a carrier.

In 1996, the same team of researchers found the location of the first gene associated with the risk of prostate cancer. That gene, HPCI, is located on chromosome 1. --MH

HIV takes twice the toll on women

Women and men are not equal when it comes to HIV infection. It takes only half the amount of human immunodeficiency virus to cause the equivalent AIDS symptoms in women as it does in men, according to a study of injection drug users conducted by epidemiologists at the School of Public Health. The findings mean that a woman who has the equivalent severity of AIDS as a man probably has half the viral load, or amount of virus circulating in her bloodstream.

The differences remained even when the scientists controlled for weight of the volunteers, frequency of drug use, and level of CD4, a marker of immune suppression, says Homayoon Farzadegan, the principal investigator. The study is due out in an upcoming issue of the Lancet and was presented in June at the International AIDS Conference in Geneva.

The results suggest that the criteria for AIDS treatment might now warrant revision, says Farzadegan. For example, the federal Centers for Disease Control recommends that patients begin receiving anti-retroviral treatment when they have at least 10,000 copies of HIV RNA per milliliter of blood. "But women with 10,000 copies have more advanced progression to disease," says Farzadegan. Authorities might want to revise that benchmark for women to 5,000 copies of HIV per milliliter, he suggests.

The results do not mean that women who are infected with AIDS die sooner than men, says Farzadegan. The time it takes for an HIV-infected patient to develop full-blown AIDS is probably also the same for women as it is for men. The researchers do not know what accounts for the difference in viral load. One possibility is that women clear HIV from their bodies faster than men do. Another is that they produce the immune cells that HIV targets at a faster rate. --MH

Reducing cancer among overweight women

Obese women have higher rates of breast, endometrial, cervical, and ovarian cancers than do women who are not obese. But they are also less likely to have Pap smears, gynecological exams, and clinical breast exams, which can detect these illnesses at their earliest, most treatable stages, reports Kevin Fontaine, a research psychologist at the Johns Hopkins Weight Management Center.

"Some data suggest that obese women are less likely to have these exams because they are embarrassed about their bodies," says Fontaine. But doctors may also be to blame, Fontaine reports in the summer issue of the Archives of Family Medicine. Gynecological exams are more difficult to perform on obese women, and physicians may be sending "covert or overt signals" that discourage their obese patients from having the screening tests, he says.

"Physicians need to be more sensitive to the fact that [obese] women may be embarrassed to have the tests," concludes Fontaine. The studies also speak to the fact that women need to be assertive in seeking regular exams, he says.

The results were based on a national health survey of 6,981 women. Obese women were defined as those having a body mass index of 35 or more (equivalent to being about 50 pounds overweight or more).

Gynecological and breast exams are essential components of preventive health, sa, the researchers. Consider: regular Pap smears followed by prompt treatment when cancer is discovered can prevent virtually all deaths from cervical cancer. --MH

Genetics for nurses

"Every professional nurse needs some knowledge of genetics," says Sue Donaldson, dean of the Johns Hopkins School of Nursing.

To accomplish that goal, Donaldson has vowed by the end of the academic year to increase the number of genetics courses in the school's curriculum and to integrate more aspects of genetics training into existing courses. The school also recently began holding workshops on genetics for its faculty, taught by genetics experts at the schools of Medicine and Public Health and other institutions. And in September, the school's Institute for Johns Hopkins Nursing hosted a two-day conference on genetic nursing, which was sponsored by a grant from the National Human Genome Research Institute of the National Institutes of Health. The conference was attended by faculty from Hopkins and other universities, nursing journal editors, and representatives of nursing organizations.

Since nurses spend more time with patients than do other healthcare professionals, they need to be able to explain to patients what having a particular gene does and does not mean, according to nursing administrators. For example, a woman who tests positive for a gene associated with an increased risk of breast cancer has not necessarily been handed a death sentence. As educators, nurses can also help patients use genetic test results to change their lifestyles to reduce their risk of disease. --MH

Healthy steps

Would a sign like this persuade you to take the stairs instead of the escalator? In a study at a Baltimore area shopping mall, Hopkins researchers found that the number of shoppers opting for the stairs increased from about 5 to about 7 percent following the posting of signs that promote stair use. The results are based on observations of 18,000 shoppers.

Signs in malls could be an inexpensive tool for boosting exercise levels, says lead investigator Ross Andersen. In the September Annals of Internal Medicine, he and his colleagues calculate that for only $111,000, signs encouraging stair use could be placed in each major mall in America.

Though the increase in stair use may seem slight, it is "extremely statistically significant," says Andersen, a physiologist at the Johns Hopkins Weight Management Center. Over the course of a year, a 4 percent boost in stair use (which was seen in the most overweight patients) would translate into 320,000 additional shoppers at the Baltimore mall and 1.6 million more shoppers nationwide taking the stairs.

While climbing a 20-step staircase is not the 30-minute workout three times a week that exercise physiologists recommend, it is more daily exercise than many Americans get, say the researchers, considering that one in four adults is completely sedentary. Climbing stairs, choosing the parking space farthest from the grocery store and walking the rest of the way, and other forms of moderate exercise do benefit cardiovascular health, says Andersen.

The signs may take some fine-tuning, however. Curiously, stair use did not increase, and actually decreased slightly, among African Americans following posting of the signs. "I really don't have an explanation for that," says Andersen, who is seeking funding to investigate what types of signs would be more effective. Colleagues have suggested that signs featuring an African-American celebrity such as Oprah Winfrey might be more effective. --MH

Take me to your kidney

A few years ago, a small group of surgeons and engineers at Hopkins began developing robots and computers they hoped would improve surgery. They even tried out some of their inventions in the operating room. They were convinced that they were on the cusp of the next great technological revolution in medicine. The National Science Foundation is now bolstering their efforts with $12.9 million to establish the nation's first research center for integrating computers and robotics into surgery and medicine.

Hopkins computer scientist Russell Taylor will direct the Engineering Research Center in Computer-Integrated Surgical Systems and Technology, which will be based at Hopkins and also include investigators at MIT and Carnegie Mellon University.

Surgical robotics already in use include a robot arm that holds a special camera used in laparoscopic procedures and a robotic device that is used to drill holes in bone very precisely for orthopedic procedures, explains radiologist James Anderson, who is deputy director of the center. Hopkins robotics researchers would now like to take those capabilities a step further, and build robots that can hold a retractor as well as an endoscope, for example, or remove tissue from the spine or brain during surgery. Another device that holds promise could be used to inject and deliver needles containing chemotherapy directly to the site of a tumor, thereby avoiding the need for surgery.

"Hopefully, such tools will reduce the trauma and reduce the cost to the patient," says Anderson.

A second component of the new research center involves developing computerized methods for crafting three-dimensional models of a patient from CT scans, MRI images, or other techniques. Surgeons could use such models to practice surgical procedures. Hopkins neurosurgeon Ben Carson used such a tool last year to rehearse a challenging separation of a pair of conjoined twins. -- MH