Skip to Navigation
University of Pittsburgh
Print This Page Print this pages

February 6, 2003


Grants awarded to researchers

Shi-Yuan Cheng of the University of Pittsburgh Cancer Institute has received a $435,376 grant from the U.S. Army Medical Research and Development Command for a study, “The Role of VEGF (vascular endothelial growth factor) in Estrogen Dependent and Independent Breast Cancer Growth.”

Cheng’s research is aimed at advancing knowledge of the molecular mechanisms behind tumor growth and providing the scientific basis for developing novel combination human breast cancer therapies.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases has granted $282,550 to Anthony Delitto of the School of Health and Rehabilitation Sciences for a randomized clinical trial of treatment for lumbar spinal stenosis.

Alcon Laboratories has granted $284,594 to the medical school’s Thomas Friberg for a study, “Protocol C 0100 Study Agreement.”

Robert Hayden of Pitt’s University Center for International Studies has been awarded a $480,236 grant from the U.S. Department of State for a Balkans educational partnerships program.

Pitt’s Center for Russian and East European Studies and its subcontractors will administer six exchange programs with Balkan universities to support faculty and curriculum development in political science, civic education, law, business administration, economics and public administration.

The U.S. Department of State has granted $699,905 to David Miller of Pitt’s Graduate School of Public and International Affairs to fund the school’s Center for Public Policy and Management.


USAID grants $631,000 for Bolivia research

Pitt’s longstanding tradition of research on Bolivia will get a boost from a $631,000 grant by the United States Agency for International Development to Mitchell Seligson, Daniel Wallace Professor of Political Science.

The grant will support a series of surveys of the national population of Bolivia. The University of Pittsburgh Latin American Public Opinion Project, which Seligson directs, has been carrying out national survey samples of Bolivian democratic attitudes and behaviors since 1998.

The USAID grant also will support a survey of public officials in key institutions in the country. The survey will be carried out in collaboration with Mellon Professor Barry Ames and assistant professor Aníbal Pérez-Liñán, both of the Department of Political Science.

In addition, the grant will support graduate research assistantships for Bolivian students to study for their Ph.D.s at Pitt in Latin American politics with an emphasis on mass politics. This is part of a larger effort to understand the evolution of democracy in Latin America and the factors that might stimulate its consolidation.


Advanced testing not necessary for all cases of repeated pregnancy loss

Current standard practice in cases of repeated pregnancy loss frequently involves a lengthy series of diagnostic tests that often do not pinpoint a cause yet amass thousands of dollars in unnecessary costs, according to a Pitt geneticist.

With a minor adjustment concerning those patients who are recommended for an advanced work-up, patients, health care facilities and insurers could save millions of dollars each year, while still giving many couples an answer for their losses, said W. Allen Hogge, professor of obstetrics, gynecology and reproductive sciences and associate professor of human genetics at Pitt’s School of Medicine.

Hogge, who also is a clinical investigator at Magee-Womens Research Institute and medical director of genetics at Magee-Womens Hospital, presented his findings Jan. 27 at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists. Results of the study also will be published in an upcoming issue of the American Journal of Obstetrics and Gynecology.

“Recurrent miscarriage is defined clinically as three consecutive pregnancy losses,” said Hogge. “But even an extensive work-up will fail to find a recognizable cause in up to half of these cases.”

Hogge and his colleagues analyzed the results of karyotyping tests to determine the chromosomal characteristics of cells on 517 tissue samples from miscarriages gathered over nearly five years at Magee-Womens Hospital. Overall, nearly 56 percent were found to have chromosomal abnormalities, with even higher rates of abnormalities when adjusted for maternal age. More than 82 percent of miscarriages were found to be chromosomally abnormal in women age 35 or over.

“Because 50 percent to 70 percent of miscarriages can be attributed to chromosomal abnormalities, and one in five pregnancies ends in miscarriage, many second and third miscarriages are likely to be simply by chance alone. In addition, other studies have shown that these couples have a 70 percent chance of having a successful subsequent pregnancy,” Hogge said. “If there is a chromosomal abnormality, there’s no reason to do more extensive — and expensive — testing.”

Hogge and his colleagues recommend that karyotyping tests be pursued regularly after the second loss, with more advanced diagnostic tests ordered for both parents only when no genetic abnormality is found. “Having an explanation for the loss often removes significant guilt regarding whether the couple ‘did something wrong to cause the miscarriage,’” he said. 


UPMC studies recovery of high school athletes from mild cases of concussion

High school athletes who sustained even mild concussions showed significant decline in memory processing and other symptoms within one week post-injury, in a study conducted by researchers at the UPMC Sports Medicine Concussion Program.

The study, published in the February Journal of Neurosurgery, is the first to evaluate recovery from mild concussion in high school athletes and the first to show that even mild concussions can have significant effects, suggesting the need for more cautious return-to-play guidelines.

“Our findings underscore the need for more careful on-the-field evaluation of even seemingly mild concussions,” said principal investigator Mark Lovell, who is a neuropsychologist and director of the UPMC Sports Medicine Concussion Program. “Furthermore, our study results may lead to a suggestion that any high school athlete with a suspected concussion of any severity be kept out of that particular game and not return to play until further neurocognitive testing can be done,” he said.

Current return-to-play guidelines commonly used nationwide stipulate that a mildly concussed athlete whose on-the-field symptoms disappear within 15 minutes may be allowed to return to play in that particular game.

“We also believe that our study results suggest an urgency for more research into the effects of concussion in high school athletes, as well as the access to formal neurocognitive testing at the high school level,” Lovell added.

“There are 1.25 million high school athletes playing contact sports, which represents the population with the highest participation in contact sports and the highest risk for sports-related concussion. An estimated 63,000 concussions occur in this group each year,” he said.

“Mild concussion is the most frequently occurring type of concussion. Because on-the-field symptoms disappear within a few minutes and the athlete reports he or she is fine and appears to the sports medicine team to be fine, mild concussions often are unrecognized, overlooked or considered a trivial injury, and often the athlete is allowed to return to play,” said Michael Collins, study investigator and neuropsychologist who is assistant director of the UPMC program.

“We are concerned about returning a concussed athlete to play too soon before the brain has had time to heal because previous research has shown that once an athlete sustains an initial concussion, he is more susceptible to further, more serious damage,” said Collins, who also was principal investigator for a recent UPMC study proving that the effects of multiple concussions in high school athletes can be cumulative.

Concussion occurs when the brain is violently rocked back and forth inside of the skull due to a blow to the head or upper body.

“Most athletes who sustain an initial concussion can recover completely as long as they are not returned to contact sports too soon,” said study investigator Joseph Maroon, professor of neurological surgery at UPMC. “However, the concern is that concussion symptoms are not always straightforward and not always reported by the athlete. On-the-field evaluation of the injury’s effects and knowing when it is safe to return the athlete to play can be difficult to objectively measure.”

The UPMC team studied the recovery of 64 male and female high school athletes throughout the country who sustained concussions during the 2000-2001 school year. The athletes who sustained mild concussions were those whose symptoms disappeared within 15 minutes of injury. They were evaluated on the field by a certified athletic trainer or team physician, who documented the injury details. The athletes were then evaluated at 36 hours post-injury, four days post-injury and seven days post-injury.

Athletes with mild concussions demonstrated significant declines in memory processes that were still evident at four and seven days post-injury. Other self-reported symptoms — including headaches, dizziness and nausea — resolved by day four.

The mild concussion group was further divided into two sub-groups according to the duration of their on-the-field symptoms. One sub-group represented athletes whose on-the-field symptoms disappeared within five minutes and were considered less severely injured. The other sub-group included athletes whose symptoms lasted between 5 minutes and 15 minutes, and were considered more severely injured. The study found that the duration of on-the-field symptoms served as a prognostic indicator of post-injury symptom duration. The group whose on-the-field symptoms lasted longer than 5 minutes had longer lasting post-injury symptoms and was five times more likely to demonstrate a major drop in memory performance at 36 hours post-injury.


Hormone leads to increase in bone mineral density

Large doses of a bone anabolic hormone called parathyroid hormone-related protein, PTHrP, increases spine bone mineral density in post-menopausal women by almost 5 percent in only three months, according to a Pitt study published in the February issue of the Journal of Clinical Endocrinology and Metabolism.

“Our study results were remarkable since PTHrP was found to produce significant results in only three months when it would normally take as much as one to three years for this much of an increase to occur using most currently available treatments,” said Mara Horwitz, assistant professor of clinical medicine in the Division of Endocrinology and Metabolism and lead investigator in the study. “Even though this was a small study, this research takes us one step further in identifying an anabolic agent that can be effective even in the short term.”

The double blind, placebo controlled randomized clinical study enrolled 16 postmenopausal women with osteoporosis between the ages of 50 and 75. All had been on hormone replacement therapy for an average of eight years and still had osteoporosis. Women who had been taking any other type of osteoporosis medication were excluded from the study. Half of the participants received a self-administered injection of PTHrP and the other half received a placebo. The patients were followed for three months. Despite the large dose of PTHrP as compared to other osteoporosis medications, participants tolerated the treatment without developing hypercalcemia, hypotension, nausea, flushing or other adverse effects.

“The rate of bone mineral density increase of 4.7 percent in such a short time period is larger than the rate observed using most of the currently available anti-resorptive osteoporosis medications,” said Andrew Stewart, chief of the Division of Endocrinology and Metabolism at Pitt and senior author of the study. “Increases of this magnitude have not been reported using calcitonin or raloxifene even when they are used for as long as three years. They compare very favorably to the recently approved parathyroid hormone (PTH), a very exciting newly FDA-approved bone anabolic agent for osteoporosis.”

Even though the study was designed as a pilot, the results were surprisingly more favorable than expected, according to Stewart. Because of the small number of participants, a larger study will be needed to confirm the results. Also, he added, no data are available on the PTHrP’s ability to prevent fractures.

PTHrP is one of several normal hormones that regulate calcium metabolism. It was discovered by several investigators including Stewart in 1987 and is responsible for hypercalcemia in cancer patients. Since that time, Stewart’s research has led to the purification, sequencing and synthesis of PTHrP. Based on the results of this study, Stewart has formed a company, Ostotrophin, L.L.C., to enable large-scale studies of PTHrP for commercialization.


Study finds cost-effective treatment for severe sepsis

The only FDA-approved drug for the treatment of severe sepsis, drotrecogin alfa (activated) (Xigris), is a cost-effective treatment and has a cost-benefit ratio superior or similar to that of many widely used medical treatments, according to a Pitt-led study published in the January issue of the journal Critical Care Medicine.

In “Cost-effectiveness of Drotrecogin Alfa (Activated) in the Treatment of Severe Sepsis,” researchers led by Derek Angus, a Pitt associate professor of critical care medicine, also report that the drug is significantly more cost-effective when used in severe sepsis patients at highest risk of death, and that the drug saves lives without significantly increasing short-term costs or use of medical resources.

“Our study shows that the cost-effectiveness of drotrecogin alfa (activated) is in line with many other life-saving medical interventions,” Angus said. “Cost-effectiveness, rather than price alone, is the true measure of a drug’s value, and ought to be our bottom line when making critical treatment decisions in severe sepsis and other serious conditions.”

Importantly, the study also looked at the effect of drotrecogin alfa (activated) on the costs of other aspects of care.

The authors found that there was no significant change in other hospital or short-term costs of care: the sole economic impact on hospitals was the acquisition cost for the drug, and there was no effect on other hospital costs, such as duration of ICU care. Previous studies have shown that drotrecogin alfa (activated) improved patients’ short- and long-term survival, and that the majority of survivors are discharged directly to home rather than requiring care at another institution.

“Hospitals and pharmacies are certainly faced with painful choices in today’s cost-containment environment and, from a practical standpoint, need to find ways to cover the acquisition costs for this therapy,” said Angus. “The recent commitment from Medicare to offset costs should be seen as a great help in this regard.”

The Medicare, Medicaid SCHIP Benefits Improvement and Protection Act of 2000 is designed to address the increased cost to hospitals of new treatments by providing additional payments to hospitals that provide new technologies or services that substantially improve patient outcomes.

The Centers of Medicare and Medicaid Services determined that drotrecogin alfa (activated) meets the required criteria and, since Oct. 1, 2002, hospitals have been eligible for additional compensation when using the drug for Medicare patients.


Computer modeling can evaluate rupture potential of abdominal aortic aneurysms

Scientists at Pitt’s McGowan Institute for Regenerative Medicine have developed a computational tool to predict the rupture potential for individual abdominal aortic aneurysms (AAA), an advance that could positively impact the lives of thousands of patients a year.

Aneurysms result when the wall of a blood vessel becomes weak or damaged. Over time, the constant pressure of blood flowing through the weakened vessel can cause a section of it to slowly enlarge, creating a bulge. The majority of aneurysms are called AAAs because they are located in the abdominal aorta, a large blood vessel leading from the heart through the abdomen. Others can occur in the brain. These are called cerebral aneurysms.

The popular view is that aneurysms strike rarely, suddenly and unpredictably. In fact, most lethal AAAs are easy to diagnose with an inexpensive ultrasound test, and can usually be treated. The question is when.

“Until now, all abdominal aortic aneurysms have been treated more or less the same way in that they are surgically repaired when the maximum diameter reaches a certain size — usually five centimeters,” said David Vorp, assistant professor of surgery and bioengineering at Pitt’s School of Medicine and director of the Vascular Biomechanics and Vascular Tissue Engineering Research laboratories at the McGowan Institute.

“We are looking at AAA in a more biomechanical way; that is to say that material failure, or a rupture, will occur when the stress at any point exceeds the strength of the material.”

Vorp presented these findings last week at “Bringing Basic Science Into Clinical Practice,” the 2003 Congress on Abdominal Aortic Aneurysms, an international symposium sponsored by the vascular surgery department at the Karolinska Institute and Hospital. The symposium is designed for vascular surgeons, radiologists, researchers and other professionals interested in AAA treatment.

U.S. surgeons repair about 50,000 AAAs yearly, typically replacing the bulging area with a plastic or fabric tube. Some now use a less-invasive procedure that threads a tubular device called a stent-graft into the weakened area.

“But because surgical repair carries its own risks, being able to pinpoint when an AAA is likely to rupture gives surgeons a valuable tool,” said Elena DiMartino, a research associate in Pitt’s Department of Surgery who is a member of Vorp’s team and worked on the study.

“We know at a certain point that the aneurysm will rupture,” she said. “We are trying to predict when.”

Only follow-up clinical studies can help to validate this new technology, Vorp and DiMartino said. While additional studies are planned soon, a clinical trial in patients is a more long-term project. 

Over the last 20 years, the number of intact AAAs diagnosed in the United States has tripled to about 200,000 a year, partly because of the increased use of computed tomography, magnetic resonance imaging and other diagnostic scans. Most, however, are never diagnosed, resulting in the deaths of about 18,000 Americans a year of rupture — more than AIDS or brain cancer, and four times as many as cervical cancer.

Leave a Reply