University Times

Professor gets contract for research on management-labor relations

Katz Graduate School of Business professor Marick Masters has been awarded a $235,000 contract from President Clinton's National Partnership Council and the U.S. Office of Personnel Management for research on labor-management partnerships in the federal sector.

Masters' research in labor-management relations has been widely cited across the country. He has published more than 60 articles on industrial relations topics, and is working on a book about labor relations, partnerships and reinvention in the federal sector.

His contract-winning proposal suggested that not enough systematic research has been conducted on the operations and accomplishments of labor-management partnerships, or their effect on federal agency performance.

In 1993, the National Performance Review recommended creating labor-management partnerships as part of a broader effort to "reinvent" the federal government. Clinton created the National Partnership Council to promote that goal.

Masters' major research mission is to understand the nature of partnership activities, and to guide policy that improves the quality of government service cost effectively.

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Raloxifene cuts risk of invasive breast cancer

The drug raloxifene dramatically reduces the risk of invasive breast cancer in post-menopausal women, according to a large-scale study involving Pitt's Graduate School of Public Health (GSPH).

Results of the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, which measured the effect of raloxifene on breast cancer rates after three years of follow-up, were published in a June issue of the Journal of the American Medical Association.

"This study showed that raloxifene reduces the risk of invasive breast cancer by 76 percent in women who took this drug daily for three years," said Jane Cauley, study co-author and associate professor of epidemiology at GSPH. "Specifically, raloxifene reduced the risk of estrogen-receptor positive invasive breast cancer by 90 percent. This finding indicates that raloxifene is very effective at curbing the development of estrogen-fed breast tumors."

The multicenter MORE trial involved 7,705 post-menopausal women at the average age of 66.5 years. These women had a history of osteoporosis but no history of breast cancer or estrogen use.

Participants were randomly assigned to receive 60 mg or 120 mg of raloxifene per day or a placebo. Thirteen cases of breast cancer were confirmed among the 5,129 women assigned to either dose of raloxifene versus 27 among the 2,576 women assigned to the placebo.

The hormone estrogen declines as women pass through menopause, causing hot flashes, bone loss and changes in cholesterol that could predispose the women to heart disease. At the same time, however, estrogen is known to fuel the growth of certain breast and endometrial cancers. 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.

Raloxifene and another SERM, tamoxifen, have been studied intensely for possible benefits and side effects. The large-scale Breast Cancer Prevention Trial (BCPT) found that tamoxifen 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.

"What we found in MORE is actually a larger reduction in risk of invasive breast cancer using raloxifene in an older population of women with an average breast cancer risk," Cauley said. "However, because the MORE and BCPT populations are substantially different in their makeup, a direct comparison of raloxifene and tamoxifen for the reduction of breast cancer risk is difficult. It's possible that young, high-risk women in the BCPT are less likely than older, average-risk women to benefit from SERMs because they may have genetic risk factors that don't involve estrogen."

The Study of Tamoxifen and Raloxifene, a recently initiated five-year breast cancer prevention trial involving 22,000 high-risk participants, will offer a head-to-head comparison of the two drugs. This trial is expected to show whether the two agents are equivalent in reducing breast cancer risk in women at high risk for this disease and whether one agent produces fewer undesirable side effects.

One such side effect, an increase in cases of endometrial cancer, was seen in women taking tamoxifen during the BCPT. Thus far in the MORE study, raloxifene has not increased the risk of this cancer. Unlike tamoxifen or estrogen, raloxifene does not stimulate the growth of the endometrium.

"If additional follow-up confirms that raloxifene continues to decrease the risk of breast cancer and does not increase the risk of endometrial cancer, then raloxifene might be preferred over tamoxifen for reduction in the risk of breast cancer and fractures in women who have a uterus," remarked the study investigators in the journal report.

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.

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Interpersonal, social rhythm therapy may improve health of patients with bipolar disorder

Doctors at Pitt's School of Medicine have found that interpersonal and social rhythm therapy (IPSRT) may have an important role in improving the quality of long-term remission in patients with bipolar disorder.

In a study comparing two maintenance treatments for the illness, Pitt researchers found that drug therapy combined with IPSRT did a better job of keeping patients free from depressive symptoms. Researchers learned both approaches were able to keep the majority of patients free of manic symptoms.

According to principal investigator Ellen Frank, professor of psychiatry and psychology, patients participating in IPSRT plus drug therapy were more likely to maintain a normal state over time, while those involved in drug therapy in combination with intensive clinical management were more likely to be depressed.

"We are now beginning to break down some of the barriers that have made the treatment of bipolar disorder so challenging," Frank said. "One of the main obstacles facing doctors and their patients is the presence of chronic, low-level depression. This study shows that there are ways to alter that picture considerably."

Bipolar disorder is also known as manic depressive illness and affects 2-3 million Americans. The illness is characterized by mood swings from deep depression to mania.

While traditional treatments for the disorder, including lithium and other mood stabilizers, work well in the short term, doctors have found they meet with limited long-term success.

Because of its strong biological basis, for decades since the discovery of lithium, bipolar disorder was not thought of as a condition in which psychotherapy had a role. A series of landmark studies presented during the Second International Conference on Bipolar Disorder in 1997 introduced a way to improve the relatively poor long-term prognosis for many with the disease.

Frank and others reported that people with bipolar disorder were vulnerable to new episodes of the disease when they experienced disruptions to their daily routines or social rhythms, in everything from sleeping to working to eating meals. Conversely, they found patients with the illness who did not experience such disruptions tended to fare much better.

The latest research builds on Frank's 1997 work, using techniques focused on regularizing daily routines and improving interpersonal relations to dampen depressive symptoms, thereby improving the quality of long-term remission they experience.

The findings were reported June 17 at the Third International Conference on Bipolar Disorder, in Pittsburgh.

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Medical school prof receives Independent Scientist Award

Clifton Callaway, assistant professor of emergency medicine, has received an Independent Scientist Award from the National Institute of Neurological Disorders and Stroke.

He is the first faculty member in his department, and one of a handful in the country, to have received this award. Callaway is investigating neuronal damage, death and protection in ischemic states in collaboration with James J. Menegazzi, research associate professor of emergency medicine, and Donald B. DeFranco, professor of biological sciences.

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Pitt team finds gene that hikes osteoporotic fracture risk

Women over age 65 who inherit a specific form of the gene for apolipoprotein E, called APOE*4, are at substantially increased risk of hip and wrist fractures, according to a Pitt-led study published in the July issue of the Journal of Bone and Mineral Research.

Impressively, APOE*4 acts independently of two important common risk factors — bone mineral density and falling.

"Our findings suggest that osteoporotic fractures may result from genes that do not influence bone mineral density directly. Identifying this new marker could improve our ability to understand how these fractures occur and allow us to identify women at increased risk," said Jane Cauley, associate professor of epidemiology at the Graduate School of Public Health and lead author on the study, which also involved investigators from the University of California at San Francisco.

Applying this new genetic marker to a larger population could eventually benefit the 250,000 women who suffer life-threatening hip fractures each year in the United States, according to Cauley. One in six older white women will suffer a hip fracture sometime during her lifetime.

The APOE gene produces a combination protein-lipid that carries cholesterol to cells. This gene comes in three common forms, or alleles, called APOE*2, APOE*3 and APOE*4. Each person carries two copies of the APOE gene, and the two copies may be the same allele or two different alleles. People with one or more copies of the APOE*4 allele are known to be at increased risk of developing Alzheimer's disease.

In the "Study of Osteoporotic Fractures," the researchers followed a group of 1,750 Caucasian women age 65 and older for seven years.