University Times

PCOS may lead to early onset atherosclerosis even among thin women

Young women with polycystic ovary syndrome (PCOS) have metabolic abnormalities, including higher levels of lipids and insulin, that may result in premature atherosclerosis by middle age, according to a Pitt study published in the November issue of Arteriosclerosis, Thrombosis and Vascular Biology.

PCOS is one of the most common reproductive disorders, affecting approximately 5 percent of women in the United States. It is characterized by menstrual irregularities, excessive body hair, infertility, high insulin levels and, often, obesity.

Pitt researchers have found that women with PCOS are also at high risk of developing early-onset atherosclerosis, even if they are thin. This connection is due to their lifetime of exposure to higher levels of cardiovascular disease risk factors, such as insulin and LDL, or "bad," cholesterol.

Despite these dangers, PCOS often goes undiagnosed.

"Women with PCOS are usually seen by their doctors for symptoms such as menstrual irregularities or infertility," said Evelyn Talbott, associate professor of epidemiology at Pitt's Graduate School of Public Health (GSPH) and principal investigator on the study. "Because it appears that PCOS may cause early onset of atherosclerosis, these women may represent the largest female group at high risk for the development of early onset coronary heart disease. Therefore it is important that physicians recognize these reproductive symptoms as signs of a broader, chronic disorder and treat it accordingly with early lifestyle interventions and/or medications that will reduce cardiovascular disease risks."

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Pitt developing tests to predict tolerance for transplants

Researchers at Pitt's Thomas E. Starzl Transplantation Institute have been awarded $728,000 through the Immune Tolerance Network to study a group of transplant patients who are completely off immunosuppressive drugs to see if clues can yield simple laboratory tests predictive of transplant tolerance, the most elusive goal in the field of transplantation.

Transplant tolerance, which refers to the state by which a patient's immune system has fully accepted a transplanted organ, is one of the key areas of study of the network, an ambitious $144 million undertaking supported by the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases and Juvenile Diabetes Foundation International.

The Pitt team was selected because of its ongoing contributions in transplant immunology and its body of research that has resulted in about 40 liver transplant recipients in a physician-controlled trial being able to be completely weaned off anti-rejection drugs. The patients have been drug-free for a mean of 6.6 years.

Typically, a life-long regimen of anti-rejection drugs, or immunosuppressive drugs, is required to prevent the transplanted organ from being attacked by the patient's immune system. Such drugs can cause serious complications, such as tumor growth, and make patients more susceptible to infections.

"We hope to yield a better understanding of the specific immunological process that occurs in these liver transplant patients who are off all immunosuppression. This will provide a 'roadmap' for clinicians, to help identify those for whom immunosuppression can be safely withdrawn," said Angus Thomson, Pitt professor of surgery and molecular genetics and biochemistry, and co-principal investigator.

The Immune Tolerance Network envisions findings of this study to have application to other areas of clinical research, from pancreatic islet transplantation to the treatment of multiple sclerosis.

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Women need healthy lifestyles prior to menopause to avoid heart disease

Women must exercise and watch their diets before menopause to prevent life-threatening coronary calcium deposits from developing later in life, according to research presented recently by Pitt researcher Lewis H. Kuller at the 73rd Scientific Sessions of the American Heart Association in New Orleans.

The findings grew out of the Women's Healthy Lifestyle Project, a five-year, randomized clinical trial testing the efficacy of a behavioral lifestyle intervention program of exercise and low-fat diet in preventing increases in low-density lipoprotein (LDL) cholesterol (the so-called "bad" cholesterol) and weight gain during the peri- to post-menopausal period.

"Women cannot afford to wait until middle age to begin a healthy lifestyle. They need to control poor diet, lack of exercise, obesity and high blood pressure while they are still young," said principal investigator Kuller, chairman of the epidemiology department at the Graduate School of Public Health. "By middle age, the damage from an unhealthy lifestyle could already be done."

The study included 535 pre-menopausal women who were randomly assigned to a behavioral lifestyle intervention group, which included a low-fat, reduced-calorie diet and physical activity component, or to an assessment-only control group. At the start of the study their average age was 47. After 54 months 176 of the participants were considered to be post-menopausal, with 59 percent of them on hormone replacement therapy.

At the conclusion of the study, significant differences in coronary calcium were discovered between those women who showed high levels of risk factors at baseline, and those whose risk factors were low. The study found that women who were much heavier, with higher body mass index and larger waists, had developed coronary calcium. Their total cholesterol was 203 mg, compared with a level of 189 mg for women without coronary calcium.

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Pitt-Bradford professor awarded grant to study nerve cells in fruit flies

The National Institute of Neurological Disorders and Stroke has awarded Lauren Yaich, assistant professor of biology at the Bradford campus, a $137,046, three-year grant to study nerve cells in fruit flies in the hope of ultimately learning more about humans.

Yaich said she will use the money to purchase new laboratory equipment and supplies and to provide stipends for students to conduct research over the summer.

The grant is specifically geared toward training students in predominantly undergraduate colleges in modern biomedical research methods.

The best part about getting the grant, Yaich said, is that it will enable her students to participate in advanced research techniques. Students can then take part in and get a feel for research, which can help them decide if they want to pursue biomedical research for a living.

Yaich said she has been conducting research on the fruit flies, because humans and flies have many similar genes. Therefore, information that she and her students learn from the fruit fly research may prove to be relevant to humans or other mammals.

As part of her research, Yaich and her students are looking at abnormal flies and normal flies side by side to see if the abnormal flies' nerves have been altered in any way because of their genetic abnormality.

Yaich said there are usually three different ways the nerve cells of the genetically abnormal flies are affected. First, there can be fewer, more or no nerves at all in the altered fly. Second, a nerve cell that controls one particular neural function, such as the sense of touch, can change and will control a different sense. Or, the neural connections, much like an electrical system in a house, can become miswired.

She and her students are also injecting abnormal genetic material into normal fly eggs and normal genetic material into abnormal fly eggs to see what results.

Yaich said there are some advantages to researching flies, even though they are so small. By conducting experiments on flies, researchers can examine many generations quickly; they can identify a gene and how it may be interacting in flies faster than in any vertebrate animal; and it's easier to see how the genes interact in the flies, particularly since similar experiments couldn't be conducted on humans.

Shortly before joining the Bradford faculty in fall 1998, Yaich found an interaction between two genes in the fruit flies that led to a change in the shape of their heads, from smooth to bumpy. Now, she said, she has to find out how genes were involved in the development of the misshapen heads.

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Balloon treatment yields results similar to surgery for repair of mitral valve stenosis

For patients with rheumatic mitral stenosis, balloon mitral valvotomy yields similar long-term results compared to a surgical procedure called commissurotomy, according to a Pitt study presented Nov. 15 at the American Heart Association annual meeting in New Orleans.

Mitral stenosis is caused by childhood rheumatic fever, which damages the heart valve. The valve slowly wears out and becomes more scarred over time. The scarring prevents the valve from opening and closing properly.

"Open surgery is the traditional method of treatment of mitral stenosis," said Galal Ziady, Pitt professor of medicine, director of clinical cardiology at the UPMC Health System Cardiovascular Institute, and principal investigator of the study. "In this study, we wanted to determine if outcomes for the balloon procedure would be comparable and sustained over the long term."

In the procedure, a surgeon uses a scalpel to remove scar tissue from the mitral valves. In the balloon procedure, a deflated balloon is inserted through an artery to the heart and into the area between the mitral valves. When it is inflated, it breaks the scar tissue and frees up the two valves to work properly.

The study followed a group of 40 rheumatic mitral stenosis patients since 1988.

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Nursing faculty receive grants

Nursing school professor Jacqueline Dunbar-Jacob has been awarded a $2,577,891 grant from the National Institute of Diabetes and Digestive and Kidney Diseases to find ways to improve medication adherence in comorbid conditions.

Dunbar-Jacob also received a $69,172 grant from the National Institute of Nursing Research to examine ethnic differences in adherence to pharmacological therapy.

Assistant professor Lorah Dorn received a $906,707 grant from the National Institute of Nursing Research to study endocrine changes and the treatment of conduct problems.

Pitt nursing professor Judith Erlen and Geraldine Brown of Howard University were awarded a $188,982 grant from the National Institute of Nursing Research to study adherence to protease inhibitors.

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Research finds legal myths undermine end-of-life care

Legal myths about end-of-life care can undermine good care and ethical medical practice, say researchers in an article published in the Nov. 15 Journal of the American Medical Association (JAMA) special issue.

"Seven Legal Barriers to End-of-Life Care: Myths, Realities, and Grains of Truth," was written by Alan Meisel, Pitt law professor and director of the University's Center for Bioethics and Health Law; Lois Snyder, director of the Center for Ethics and Professionalism at the American College of Physicians-American Society of Internal Medicine (ACP-ASIM), and Timothy Quill, a University of Rochester internist.

A significant barrier to good end-of-life medical care is that some doctors believe various myths about the law, specifically that the law requires them in some situations to practice bad medicine. The authors argue that this is not the case. Most significantly in light of the current debate about the legalization of physician-assisted suicide, it is essential that doctors understand that prescribing high doses of medication to relieve pain or other discomfort in a terminally ill patient is legal even if it results in the patient's death as long as the doctor's intent was to relieve the patient's pain. Similarly, when a terminally ill patient's suffering is overwhelming despite palliative care, it is not illegal for doctors to withhold artificial fluids and nutrition and sedate the patient.

The authors conclude that while many legal barriers to end-of-life care are more mythical than real, sometimes a grain of truth does exist. Ultimately, it is necessary for physicians to know state law where they practice medicine.

The paper resulted from the 1997 ACP-ASIM End-of-Life Care Consensus Panel convened to identify clinical, ethical and policy problems in end-of-life care; to analyze critically the available evidence and guidelines; and to offer recommendations on how to improve care of the dying.