University Times

GSPIA to study reform of local government in Russia

Pitt's Graduate School of Public and International Affairs (GSPIA) has received a $132,210 grant from the Eurasia Foundation to study local government reform and training in Russia.

The project team will conduct field research in three Russian cities to assess implementation of reforms and training efforts for administrators at the local government level, and to make recommendations regarding training needs.

GSPIA will work with a Russian partner, the Institute for Urban Economics in Moscow.

Principal investigator is GSPIA Associate Professor Janine Wedel. Other faculty participating include GSPIA Dean Carolyn Ban and Jonathan Harris, a professor in the political science department. Among the Pitt graduate students involved will be Ioulia Bolotskikh, a Ph.D. student at GSPIA from St. Petersburg, Russia.

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Prourokinase is effective for all stroke patients, study finds

The clot-busting drug Prourokinase was effective for all patients in a multi-center trial, regardless of their risk level, according to study results presented by Pitt researchers at the American Heart Association's 26th International Stroke Conference in Fort Lauderdale Feb. 14.

The study evaluated the effectiveness of intra-arterial Prourokinase in patients with ischemic stroke.

"Our objective in this arm of the study was to identify predictive factors for outcome in this patient population and to assess whether patients with different risk profiles responded differently to Prourokinase," said Lawrence Wechsler, professor of neurology and neurosurgery at Pitt's School of Medicine, director of the UPMC Health System Stroke Institute and principal investigator of this arm of the study.

In the study — called PROACT II — a total of 35 variables were evaluated, including CT findings, severity of stroke deficits and age of the patient at the time of the stroke.

"Despite the stratification of patients based on these and other variables, there was no evidence of a difference in treatment effect across risk categories," Wechsler said. "All PROACT-eligible patients stand to benefit from early intra-arterial Prourokinase treatment."

An ischemic stroke is caused by an artery blockage in the brain. If Prourokinase can be administered by a catheter directly to the site of the clot in the brain within six hours from the onset of symptoms, it may dissolve the clot and restore blood flow to the brain.

The PROACT II study was a multi-center randomized controlled trial that included 180 patients at 54 medical centers in the United States and Canada. In the study's primary findings, published in the Journal of the American Medical Association in 1999, 40 percent of patients treated with Prourokinase and 25 percent of control patients had a good neurological recovery 90 days after the stroke.

Stroke is the third most common cause of death and the leading cause of adult disability in the United States. Some 700,000 Americans suffer a stroke each year; 70 percent of these are ischemic strokes in which a clot blocks oxygen delivery to a portion of the brain. Annually, 160,000 Americans die from stroke.

Symptoms include weakness or paralysis on one side of the body, numbness or loss of sensation on one side of the body, difficulty with speech or inability to speak, sudden onset of loss of balance or dizziness and sudden loss of vision in one eye.

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Study begins to extend limits of tPA use following stroke

Physicians at UPMC Health System Stroke Institute are beginning a National Institutes of Health study using MRI scans to determine whether selected stroke patients may benefit from tissue plasminogen activator (tPA) therapy administered between three and six hours after the onset of a stroke.

The current time window of up to three hours after a stroke significantly limits the number of patients that can receive this important treatment since only a small fraction of stroke patients currently reach the hospital in this time frame. This study hopes to extend the benefits of tPA to many more patients with stroke by selecting those patients beyond three hours who are likely to benefit from this treatment.

tPA is a clot busting drug that is an approved and effective treatment when given intravenously to patients who have strokes due to an artery blockage in the brain (called an ischemic stroke), if the drug can be given within three hours from the onset of symptoms. It dissolves the clot and allows blood flow to the brain to be restored.

"Although tPA is beneficial when administered within three hours of stroke onset, clinical trials have failed to document significant benefits when given beyond that time frame," said Lawrence Wechsler, professor of neurology and neurosurgery at Pitt's School of Medicine, director of the UPMC Health System Stroke Institute and principal investigator in the study.

"MRI imaging may allow us to identify those patients who are likely to benefit from tPA therapy beyond the three-hour limit."

The study is called the Diffusion-weighted imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study. If they agree to participate in this research study, patients who are brought to UPMC Presbyterian emergency department and diagnosed as having an ischemic stroke (caused by a blockage), will undergo MRI scanning. The scans will include diffusion-weighted imaging, perfusion-weighted imaging and MRI angiography.

"These are new MRI imaging techniques that show us very early changes in the brain with stroke," Wechsler said. "Diffusion tells us which part of the brain is already damaged and perfusion tells us which areas of the brain do not have sufficient blood flow. We may be able to save the part of the brain that has abnormal perfusion but not abnormal diffusion."

All eligible patients will receive intravenous tPA therapy immediately following their initial MRI scan, but no later than six hours from the onset of stroke symptoms. A total of 80 patients will be enrolled over three years at five centers nationwide.

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Study confirms raloxifene protects those past menopause from invasive breast cancer

The drug raloxifene significantly reduces the risk of invasive breast cancer in post-menopausal women, according to results of a large-scale study involving Pitt's Graduate School of Public Health (GSPH) and published in the January issue of Breast Cancer Research and Treatment.

The Multiple Outcomes of Raloxifene Evaluation (MORE) trial measured the effects of raloxifene, which has been approved by the U.S. Food and Drug Administration for prevention and treatment of osteoporosis, on breast cancer rates after four years of follow-up. The results confirm the study's preliminary findings, which were published in the June 1999 issue of the Journal of the American Medical Association.

"The MORE trial showed that raloxifene reduces the risk of invasive breast cancer by 72 percent in women who took this drug daily for four years," said Jane Cauley, lead author on the study and associate professor of epidemiology at GSPH. "Specifically, raloxifene reduced the risk of estrogen-receptor positive invasive breast cancer by 84 percent. This finding indicates that raloxifene is very effective at curbing the development of estrogen-fed breast tumors among older women with an average breast cancer risk."

MORE, a multi-center osteoporosis trial, involved 7,705 post-menopausal women, average age of 66.5 years, with a history of osteoporosis. About 12 percent reported a family history of breast cancer. Participants were randomly assigned to receive 60 mg or 120 mg of raloxifene per day or a placebo. Neither investigator nor participant knew who received placebos and who received raloxifene.

After four years, 39 cases of breast cancer were confirmed among the 5,129 women assigned to either dose of raloxifene, versus 28 cases among the 2,576 women assigned to the placebo. There were no significant differences in outcome between the group taking 60 mg of the drug and those taking 120 mg. Overall, raloxifene was well-tolerated by participants.

The hormone estrogen declines as women pass through menopause. Without it, women suffer problems including hot flashes, bone loss and changes in cholesterol that could predispose them to heart disease. At the same time, however, estrogen is known to fuel the growth of certain breast and endometrial cancers whose cells have estrogen receptors. For these reasons, investigators have been searching for estrogen alternatives, or selective estrogen-receptor modifiers (SERMs), that interact with the cell receptor for estrogen and confer estrogen's beneficial properties, yet curtail its tumor-promoting role. The MORE trial showed that raloxifene blocks the estrogen receptors in estrogen-receptor-positive breast cancers, or those that are fueled by estrogen. The drug showed no effect on estrogen-receptor-negative breast cancers, or those that do not depend on estrogen for growth.

In a separate study, the large-scale Breast Cancer Prevention Trial (BCPT), researchers found that tamoxifen, another SERM, reduced the incidence of invasive breast cancer in women at significantly increased risk of this disease. As in the case of raloxifene, tamoxifen produced its greatest risk reduction in women with estrogen-receptor positive breast cancers.

The Study of Tamoxifen and Raloxifene (STAR), a five-year breast cancer prevention trial that will enroll up to 22,000 high-risk participants, will offer a head-to-head comparison of the two drugs. Completing this trial is very important, according to Cauley, because it is expected to show whether the two agents are equivalent in reducing breast cancer in women at high risk for this disease and whether one agent produces fewer undesirable side effects.

In the MORE study, raloxifene also was shown to increase bone density and reduce vertebral fractures. Previous studies of tamoxifen also have shown its ability to increase bone density and reduce fractures, but this effect was not statistically significant in the BCPT. Both agents also reduce levels of so-called bad cholesterol, which could reduce heart disease; however, the effects of tamoxifen on reducing heart disease were not statistically significant in the BCPT. The effect of raloxifene on reducing heart disease and breast cancer is currently under study in the Raloxifene Use for the Heart (RUTH) study, which recently completed enrolling more than 10,000 older women at risk of heart disease. Longer-term effects of raloxifene on reducing the incidence of breast cancer in post-menopausal women will be evaluated in the Continuing Outcomes Relevant to Evista (CORE) trial.

Venous thromboembolism, or obstruction of a blood vessel, is a serious, although infrequently reported side effect of raloxifene. Other side effects associated with raloxifene include flu symptoms, hot flashes, leg cramps, endometrial cavity fluid and peripheral edema.