University Times

Study looks at walking as exercise for pregnant women at risk of developing preeclampsia

A study focusing on whether daily walking can reduce the risk of developing a possibly life-threatening complication of pregnancy called preeclampsia is taking place at the Magee-Womens Research Institute (MWRI).

Women who have previously experienced the condition, also known as toxemia and characterized by high blood pressure, swollen ankles and the presence of protein in the urine, have an even greater chance of developing the disorder in subsequent pregnancies.

"This is a complication that can have potentially devastating consequences," said Thelma E. Patrick, a research assistant professor in the department of obstetrics, gynecology and reproductive sciences at Pitt's School of Medicine and the study's principal investigator. "In fact, it's one of the leading causes of maternal, fetal and neonatal disability and death."

Affecting about 7 percent of pregnancies, preeclampsia is more common in the second half of pregnancy. It also can develop during labor and after delivery. Other risk factors include maternal age of less than 25 or more than 35 years and preexisting high blood pressure, diabetes or kidney disease. Untreated, it can develop into the far more serious eclampsia, which can lead to seizures, coma and death.

"Preeclampsia often strikes suddenly," said James M. Roberts, MWRI director and a professor and vice chair of research in Pitt's department of obstetrics, gynecology and reproductive sciences. "Female relatives of women who have had preeclampsia are as much as three times more likely to develop the condition themselves during pregnancy." Up to 20 percent of cases are among women of color.

"The risk factors for preeclampsia are looking more and more like those for cardiovascular disease," said Patrick, who is also a registered nurse. For this reason, she and her MWRI colleagues think exercise is likely to help reduce the chances that preeclampsia will strike. "Exercise is obviously an important factor in helping to reduce cardiovascular disease."

Roberts also noted that preeclampsia has been associated with insulin resistance, a metabolic disorder related to Type 2 diabetes. Recent studies have shown that mild exercise can reduce insulin resistance in people with Type 2 diabetes, he said.

The goal of the study is to enroll 320 volunteers over the next five years.

For more information on the study, call Beth Elinoff, research coordinator, at (412) 641-3306.

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Lower dose of mifepristone effective when used with misoprostol in early pregnancy termination

A 100-milligram dose of mifepristone may be an effective alternative to larger doses of the drug when used with misoprostol for early pregnancy termination, according to the results of a study published in the September issue of Obstetrics and Gynecology.

Previously, dosages of mifepristone given to women have ranged from 200 to 600 milligrams.

Sold under the name Mifeprex(r), mifepristone was approved by the U.S. Food and Drug Administration in September for use in the United States. The drug is commonly known in Europe as RU-486, or the abortion pill. It is part of a regimen prescribed by doctors in many countries that includes misoprostol, an ulcer drug.

"The long-term benefit of the study shows that a lower effective dose of mifepristone could lower overall cost of treatment," said Mitchell Creinin, lead study author and director of family planning in the Pitt medical school's Department of Obstetrics, Gynecology and Reproductive Sciences. "Most importantly, this information provides more knowledge for future developments of antiprogestins."

Mifepristone blocks the hormone progesterone, which is necessary for a pregnancy to continue. Misoprostol causes the uterus to contract and expel the fetus. The drug combination was approved in 1988 for use in France as an abortifacient. It has been used in Britain since 1991, and Sweden since 1992. It is only effective early in pregnancy, usually within the first 49 days.

In the study, 80 women were given 100-milligram doses of mifepristone, followed 48 hours later by the administration of misoprostol in either a dose of 400 micrograms orally or 800 micrograms vaginally. Participants returned for evaluation approximately 24 hours following use of misoprostol, and then again two to three weeks later.

In the 24 hours following administration of misoprostol, a majority of women — 72 out of 80 — had experienced complete abortions. Four women who had received a 400-microgram dose of misoprostol orally required a surgical abortion after two weeks. None of those who received an 800-microgram dose of misoprostol vaginally required further intervention.

Side effects, mainly nausea, vomiting, cramping and diarrhea, were comparable for both groups. Creinin noted that women who suffer spontaneous abortion, or miscarriage, early in pregnancy suffer similar symptoms. Many participants reported that pain was manageable by using nonprescription painkillers such as ibuprofen or acetaminophen.

"This study suggests that both regimens tested in this trial, using a mifepristone dose of 100 milligrams, provides clinical efficacy in the same range as regimens using higher doses," wrote Creinin. "Prospective trials are needed to find the mifepristone and misoprostol regimen with the most acceptable side-effect profile."

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Recurrent, early-onset depression common within some families

While researchers have known for some time that depression tends to run in families, a landmark study from Pitt's School of Medicine examined the genetic and environmental impact of recurrent, early-onset major depression on affected individuals and their family members.

Among the results, researchers found that nearly half of close relatives of individuals who developed recurrent depression before the age of 25 also suffered from one or more mood disorders themselves.

The study, published in the Sept. 5 American Journal of Medical Genetics, is one of the largest to characterize the mental and other health related problems of individuals with this subtype of clinical depression and their family members.

Researchers evaluated more than 1,300 members of 81 families identified by a relative with recurrent, early-onset major depression (RE-MDD). They found that the rate of mood disorders among these family members far exceeded that of the general population. In fact, close relatives (parents, siblings, children) of the individuals with RE-MDD developed major depression at eight times the rate of the general population, while extended relatives had a rate four times higher than normal.

"The news is not good for families of individuals with RE-MDD," said George S. Zubenko, Pitt professor of psychiatry and adjunct professor of biological sciences at Carnegie-Mellon University. "This form of clinical depression runs strongly in families, is often associated with other mental disorders that include prominent disturbances of mood, and has a significant negative impact on the health and longevity of patients and their family members."

Among the other mental disorders that commonly accompany major depression are alcohol and drug use disorders, anxiety disorders, and certain personality disorders. "Because RE-MDD and these other mental disorders occur at elevated rates in the same families, share clinical features, and often respond to the same treatments, we suspect that there may also be similarities in their root causes," Zubenko said. "Current evidence suggests that these disorders arise in part from the effects of overlapping groups of susceptibility genes. Nongenetic influences also play a role. For example, having a close relative with a disabling psychiatric condition often leads to increased stress and caregiving burden that may precipitate clinical depression and other health problems among the remaining family members."

Other alarming data from the study show an extraordinary effect of RE-MDD on the longevity of family members that the researchers say may begin before birth. The mean and median ages of death for relatives of people with RE-MDD were shifted toward younger ages across the entire lifespan, including a five-fold increase in the infant mortality rate. In the study, family members lived an average of eight fewer years; more than 40 percent died before reaching age 65. Older family members were also at greater than average risk for developing neurodegen-erative diseases such as Alzheimer's.

"From the time of conception until death, a dynamic balance involving the birth of neurons, their migration and formation of interconnections, and programmed cell death play a critical role in determining normal brain activity," said Zubenko. "Inborn or prenatal errors that alter this process may contribute to the later development of psychiatric disorders as well as hastening or exacerbating the development of neurodegenerative events."

Zubenko cautioned that further research needs to be done to clarify his findings.

"Our findings have clear and current significance for physicians and other health care providers," he said. "Clinical depression and related disorders constitute major public health problems that warrant early detection and appropriate treatment. These considerations are of special concern for patients who suffer from recurrent depressive episodes that first emerge early in life. Futhermore, a high index of suspicion for mood and related disorders appears warranted during evaluations of family members who may under-report signs or symptoms of these conditions during routine examinations or during evaluations of other maladies.

"Screening for alcohol and substance abuse, as well as suicide risk, in this high risk group also seems prudent," Zubenko said. "In the foreseeable future, results from our ongoing genetic studies that rely on a unique library of transformed cell lines representing these families may also provide new opportunities for treating or even preventing these disorders."

Other study authors were: Pitt faculty members Wendy N. Zubenko, Duane G. Spiker and Donna E. Giles, and Barry B. Kaplan, of the National Institute of Mental Health.

The study was supported by the National Institute of Mental Health.

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More black men sought for Pitt Men's Study

Pitt's Graduate School of Public Health (GSPH) has launched a campaign to recruit additional African-American men into the Pitt Men's Study, the local arm of a national, four-site study that since 1984 has been investigating the natural history of the human immunodeficiency virus (HIV), which causes AIDS.

"The National Institutes of Health has recognized that the scientific community does not know enough about how the human immunodeficiency virus affects African Americans, who constitute one of the fastest growing groups of HIV-infected individuals," said Anthony Silvestre, associate professor of infectious diseases and microbiology at GSPH and recruitment coordinator for the Pitt Men's Study.

To bolster research of HIV in African Americans, the NIH is funding recruitment efforts at Pitt and the additional three sites in the Multicenter AIDS Cohort Study (MACS). Pitt researchers hope that within a year they can double the current local study population from 400 to 800 men who have sex with men.

For nearly two decades, the Pitt Men's Study and its sister MACS sites in Baltimore, Chicago and Los Angeles have been focused on understanding how HIV works. Together, these four study sites have uncovered important information about HIV and AIDS, such as the identification of viral load as a predictor of HIV progression, the effectiveness of triple-drug therapy, and the link between human herpesvirus 8 and Kaposi's sarcoma, a type of cancer that often strikes AIDS patients.

Traditionally, African-Americans have been underrepresented in the Pitt Men's Study and at the other MACS sites. "Until recently, AIDS was considered a white man's disease, so there was little interest on the part of African Americans in participating in a research study devoted to it," said Silvestre.

While Census Bureau statistics show that only 12.4 percent of men in the United States are black, a full 50 percent of newly HIV-infected men in the country are black, according to the Centers for Disease Control and Prevention (CDC), indicating that the virus is disproportionately affecting African-American men. The CDC also reports that the majority of newly infected men acquire the virus by engaging in unprotected sex with other men.

"The concern is that just as African Americans tend to get sickle cell anemia, hypertension and cardiovascular disease more often than whites, for reasons that can be genetic or environmental, blacks may react differently than whites to HIV and to the medications used to treat HIV," said Charles Rinaldo, professor and chair of the department of infectious diseases at GSPH and principal investigator of the Pitt Men's Study.

Participation in the Pitt Men's Study requires semi-annual visits to the study clinic in Oakland for a physical exam and interview, and to give blood samples. Participants receive $1,500-$2,000-worth of medical services per year, including free screening for hepatitis A, B and C, anemia, sexually transmitted diseases, prostate and colorectal cancers and diabetes, as well as assessments of liver function, blood pressure and cholesterol levels.

Researchers will use the collected data and blood samples to study HIV and other related diseases in infected and non-infected men, gaining information on how HIV causes disease, the benefits and side effects of drug treatment, and ways that the immune system can be modified to help control infection.

Participants receive all of their test results, as well as information on disease prevention. They have the option of having test results released to their primary care physicians. Otherwise, participation and all related information are kept confidential.

Participation in the study is open to those who are infected or not infected with HIV, who are or are not on AIDS medications, and who are of any age and any race. A small stipend is offered to cover transportation costs. For more information or to participate, call 4-2008 or 1-800/987-1963.