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April 27, 2000


Grants awarded to researchers

Lani Hummel, of the Mid-Atlantic Technology Applications Center, was awarded a $500,000 grant from the National Aeronautics and Space Administration to promote NASA technologies, expertise and facilities to minority- and women-owned business in Pennsylvania, Maryland, Virginia, West Virginia and Delaware during the last three months of 1999.

The National Center for Research Resources has awarded an $851,625, one-year grant to medical school Dean Arthur Levine to fund the General Clinical Research Center.

The center consists of three clinical research facilities, available for use by Pitt faculty, at Montefiore University Hospital, Western Psychiatric Institute and Clinic, and Magee Womens Hospital.

Scott Nelson, of the Faculty of Arts and Sciences chemistry department, has received $375,000 from the American Cancer Society to develop strategies, modeling and evaluation of microtubule stabilizing agents.

The National Institutes of Mental Health awarded Todd Reinhart, of the Graduate School of Public Health, a $445,849, nine-month grant through May to investigate "Local Changes in Gene Expression During SIV Encephalitis."

Yan Xu, of the medical school's anesthesiology department, has received a $335,083, one-year grant by the National Institute of General Medical Sciences for "NMR Studies of Mechanisms of General Anesthesia."

Orthopaedic researchers report findings Orthopaedic researchers from Pitt reported on the following study results at the recent 67th annual meeting of the American Academy of Orthopaedic Surgeons in Orlando, Fla.


Airbags, seat belts prevent spinal injuries

Airbags along with seat belt use decrease spinal injuries in automobile crashes, reported William F. DonaldsonIII and his orthopaedic research team from UPMC Health System.

Researchers analyzed medical records of 7,170 patients who suffered spinal injuries in automobile crash injuries. Patients were divided into four groups based upon protection devices used — no protective devices (4,636 patients); seat belts only (2,268 patients); air bags only (110 patients); and seat belts and air bags (138 patients).

When compared to individuals using air bags and seat belts who were involved in crashes, the researchers found patients using no protective devices were 37 percent more likely to suffer a spinal injury; those using seat belts only were 42 percent more likely; and those protected by an airbag only were 35 percent more likely to suffer spinal injury.

"Not wearing a seat belt or getting into a car without air bags greatly increases the chance of having a spinal injury," said Donaldson, who is associate professor and chief of orthopaedic spinal surgery in UPMC's department of orthopaedic surgery. He noted that older persons were more likely to wear a seat belt and drive an automobile with airbags.


Wrist fracture risk in women identified

Researchers identified the major predictors of distal radius (wrist) fractures in older women. This 10-year, multi-center study, funded by the National Institutes of Health (NIH), was presented by Molly Vogt, associate professor of orthopaedic surgery and epidemiology.

Wrist fractures often are indicators of osteoporotic bone, according to Vogt.

A total of 9,704 women aged 65 years and older were enrolled in the study. They completed questionnaires about their age; weight; height at 25 years old; smoking history; exercise activities; functional impairments; history of selected medical conditions such as diabetes, arthritis and fractures; and family history of fractures.

Of the 9,704 women, 527 had sustained a wrist fracture during the 10-year period. The women's average age at the time of the fracture was 76 years.

Researchers reported that key indicators for wrist fractures in women include low bone mineral density, recurrent falling, prior fractures and no current use of estrogen. "We now can identify those individuals at increased risk and be able to instruct them about preventive measures early in life," Vogt said.


Simple insulin resistance test predicts heart disease in type 1 diabetics

A simple series of questions and measurements to determine insulin sensitivity could help save the lives of many people with type 1 diabetes by identifying those who are at an increased risk of heart disease.

The new test is described by researchers from Pitt's Graduate School of Public Health and School of Medicine in a paper published in the April issue of Diabetes, a journal of the American Diabetes Association.

Dubbed the Insulin Resistance Syndrome (IRS) score, the test is a clinical means of measuring insulin resistance, a condition that researchers believe may be common, but often overlooked, in patients with type 1 diabetes. In the past, insulin resistance has been associated only with type 2 diabetes.

In type 1 diabetes, which affects 10 to 15 percent of all diabetics, the pancreas cannot make insulin to regulate blood glucose. The condition often develops in patients before the age of 30 and requires insulin therapy.

Insulin resistance occurs when the body does not properly use insulin to metabolize blood sugar. To compensate, the body produces more insulin, resulting in an oversupply.

Insulin resistance is associated with an increased risk of coronary artery disease, a leading cause of death in people with type 1 diabetes. With the new IRS score, physicians can identify insulin resistant patients and begin heart-saving treatment including exercise, weight loss and medication.

"Insulin resistance has long been recognized in type 1 diabetes, but few studies have examined the association between clinical IRS risk factors and insulin resistance in this population," said Trevor J. Orchard, professor of epidemiology at GSPH and senior author of the article.

This study is the first to develop a method of estimating a patient's insulin sensitivity and validating it with the use of the insulin clamp, a three-hour test during which glucose and insulin are administered intravenously and adjusted to achieve stable blood glucose levels. The clamp measures an individual's glucose disposal rate (GDR). A low GDR shows that the body is not using insulin effectively to process glucose, indicating insulin resistance.

"Up until now, the clamp has been the most accurate means of determining insulin resistance, but it is used only in research because it is expensive and time consuming," said study clinical investigator Katherine V. Williams, of Pitt's division of endocrinology and metabolism. "But our research study has shown that the IRS score is a good proxy measure, and the beauty is that it is not costly, intimidating, invasive or time consuming."

The IRS score is based on clinical risk factors in adults with type 1 diabetes, including hypertension, high waist-to-hip ratio, family history of type 2 diabetes and glycemic control.

The study was funded by the National Institutes of Health and UPMC Health System's General Clinical Research Center.


Researchers develop new model to study transmission of HIV in women

A new understanding about HIV transmission in women — information that could lead to preventative strategies for this population — will likely come from an organ culture model recently developed by researchers at Pitt's Graduate School of Public Health .

The new model, described in the April issue of the journal Nature Medicine, may result in breakthroughs such as barrier medications that prevent HIV from crossing through tissue linings of the female genital tract.

"The main route of HIV transmission has always been sexual, and heterosexuals are quickly becoming the largest HIV-positive population, particularly in Third World countries," said researcher Phalguni Gupta, professor of infectious diseases and microbiology. "A model such as this is long overdue in understanding the virologic and host factors involved in HIV transmission in women."

According to Gupta, the new model will help researchers develop and test creams, suppositories or other medications to block the transmission of HIV.

Models to date have demonstrated HIV transmission across a single layer of human cells grown specifically for that purpose. The new Pittsburgh model uses actual human tissue and thus closely mimics the stratified cell layers that are present at the sites of sexual transmission in women.


Estrogen may fuel lung cancer growth

Estrogen, long known for its role in fueling the growth of breast cancer, may spur the same process in lung cancer, according to Pitt research findings presented this month at the annual meeting of the American Association for Cancer Research.

The results are the first to directly demonstrate increased growth of non-small cell lung cancer in the presence of estrogen.

"In our studies, we found greater numbers of estrogen receptors on lung cancer cells than on normal lung cells, strongly suggesting a role for this hormone in enhancing tumor growth," said Jill Siegfried, principal investigator of the study and vice chairperson of Pitt's pharmacology department.

Annually, lung cancer kills about 60,000 women in the United States, making it the leading cancer killer of women. Non-small cell lung cancer comprises 80 percent of lung cancer cases.

Some population studies have suggested that women develop the disease at an earlier age and with less reported tobacco exposure than men, prompting scientists to search for biological reasons that could account for these discrepancies. Investigations by Siegfried and others have indicated that lung cancer is different in women than in men, both with regard to the type of tumors that develop and the molecular mechanisms underlying the disease.

"Women have a naturally higher circulating estrogen level than men, and this difference may contribute to their increased susceptibility to lung cancer," Siegfried said. "As in breast cancer, blocking the effects of estrogen could prove an important therapeutic strategy to halt disease progression or prevent recurrence. In addition, blocking estrogen receptors could prove beneficial in preventing lung cancer in women at high risk, much like blocking estrogen's effect has been shown to prevent breast cancer in women at increased risk for that disease."

Siegfried's research on estrogen is supported by the University of Pittsburgh Cancer Institute's Lung Cancer Program and the National Cancer Institute.


Bypass more effective than angioplasty in protecting diabetics from heart attack, study finds

Diabetic patients on medication who have had coronary bypass surgery are more likely to survive a heart attack than are diabetics who have had angioplasty, announced researchers from Pitt's Graduate School of Public Health (GSPH) in the April 6 issue of The New England Journal of Medicine.

"Bypass surgery provides a protective effect that accounts for the dramatic difference we found in the overall death rates of diabetic patients who underwent one of these two revascularization procedures," said Katherine Detre, director of the Epidemiology Data Center at GSPH and a principal investigator of the study.

This finding is a result of the Bypass Angioplasty Revascu-larization Investigation (BARI), an international, multi-center randomized study coordinated by GSPH and funded by the National Heart, Lung and Blood Institute. The study compared coronary artery bypass graft surgery with percutaneous transluminal coronary angio-plasty in patients with multivessel coronary artery disease who had not previously received either procedure but who were medically qualified for both.

BARI researchers found that mortality at five years was 8 percent for the 2,962 patients without diabetes and 20 percent for the 641 patients with diabetes. Mortality rates were 7 percent for non-diabetics and 18 percent for diabetics among those patients who underwent bypass surgery, and 8 percent and 25 percent, respectively, for those who had angioplasty.

However, among diabetic patients who had heart attacks subsequent to the start of the study, mortality at five years after the heart attack was 17 percent for those who had undergone bypass surgery (similar to the rate for non-diabetics), as compared with 80 percent among those who had undergone angioplasty.

Both types of coronary revascularization resulted in an immediate increase in the amount of heart muscle receiving blood flow. But investigators noted that after one year, the vessels of patients who had undergone bypass surgery remained open to a greater degree, thus protecting them from the potentially fatal damage brought on by a heart attack.

An estimated 14 million people in the United States have diabetes. Diabetics are two to four times more likely to have heart disease than are non-diabetics, researchers say.


Menstrual cycle may affect success of women who are trying to quit smoking

Research shows that timing is everything for women trying to quit smoking.

In research published in a recent issue of the Journal of Consulting and Clinical Psychology, psychiatry professor Kenneth A. Perkins found that women who quit smoking during the follicular phase of the menstrual cycle (1-14 days following menstruation) experienced less severe symptoms of tobacco withdrawal and depression than women who quit during the luteal phase (day 15 or longer post-menstrual).

According to Perkins, the differences in symptoms could be due to the menstrual cycle's hormonal changes and their influence on mood. Negative mood due to cycle phase combined with tobacco withdrawal could make sustained quitting very difficult.

"One implication of these results is that younger women preparing to quit smoking should select a quit day early in their menstrual cycle to minimize withdrawal symptoms and depression," Perkins said. "This simple behavioral strategy for timing the quit day may decrease negative mood effects of cessation."

Further study of hormonal influences and sex differences in factors affecting smoking behavior may lead to improved treatment of smoking cessation in women, Perkins said.

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