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May 29, 2003


Grants awarded to researchers

Anthony Grace of the neuroscience department has received a grant of $330,162 from the National Institute on Drug Abuse for a study, “Stress Induced Alterations in Amygdala LC Interactions.” Stress is known to be a factor in the etiology or exacerbation of psychiatric disorders, and plays an important role in reinstatement of drug-taking behavior. Grace’s study will use primarily electrophysiological recordings in anesthetized rats to examine the effects of acute and chronic stress on the regulation of the locus coeruleus (LC) by the amygdalar complex.

The National Institute of Nursing Research has granted $332,495 to the nursing school’s Leslie Hoffman for a study, “Improving Outcomes in Mechanically Ventilated Patients.” The primary aim is to test the effectiveness of an intervention (acute care nurse practitioner-managed care versus care managed by physicians-in-training) to improve outcomes in patients who require extended mechanical ventilatory support during admission to a step-down intensive care unit and in the post-discharge period.

Ada Mezzich of the pharmacy school has received a $382,039 grant from the National Institute of Dental Research for research seeking to determine the impact of parents’ substance abuse on medical/dental, psychological and educational neglect of their children.

The medical school’s Thomas Smithgall has been awarded a $397,436 National Cancer Institute grant for a project, “Regulation of P93 C FES Tytosine Kinase Activity.”

Mary Kay Stein of the Learning Research and Development Center has received a $919,589 National Science Foundation grant for a project bringing together expertise from various theoretical perspectives to conceptualize and test a model for “scaling up” mathematics curricula.

The U.S. Department of Energy has awarded $260,000 to Judith Yang of the engineering school for a project, “Theoretical Development to Directly Correlate the Nanoscale Oxygen Metal Surface Interactions Visualized by in Situ UHV TEM.”

The education school’s Naomi Zigmond has received a $4 million grant from the state’s Department of Education for continued funding of the Pennsylvania Alternate System of Assessment Project. PASAP is developing alternate assessments to allow students with severe disabilities to demonstrate mastery of skill and attainment of knowledge.


Two genes associated with anorexia

An international team of researchers has identified two genes associated with anorexia in families and patients with the eating disorder. The study, in the May 19 issue of Molecular Psychiatry, provides a direct genetic connection between anorexia and the brain mechanisms controlling appetite and anxiety, two hallmarks of eating disorders.

Anorexia nervosa is a serious, potentially lethal illness. It is characterized by the relentless pursuit of thinness and emaciation, and the obsessive fear of gaining weight. It commonly begins during adolescence in girls and it runs in families. A number of traits, such as perfectionism and anxiety, contribute to the risk of developing anorexia.

“We used a process called candidate gene association analysis to identify two genes from a region on the short arm of chromosome 1, previously identified as likely to contain genes contributing to anorexia nervosa, that may contribute to the risk of developing anorexia nervosa,” said author Andrew W. Bergen, a staff scientist at the National Cancer Institute’s Core Genotyping Facility in Gaithersburg, Md. “When we compared anorexia patients to control individuals, we found statistically significant association of sequence polymorphisms at these two genes to anorexia nervosa, with increasing risk to individuals carrying specific alleles for developing anorexia nervosa.”

To perform the gene association analysis, the researchers focused on a region of the short arm of chromosome 1 that earlier studies by the same researchers found was likely to contain genes contributing to anorexia nervosa in families. The researchers used a process known as candidate gene analysis to investigate several genes in the chromosome 1 region, using both positional information and biological information about genes in this region to nominate three genes for detailed analysis. In the candidate gene association analysis, the researchers analyzed sequence polymorphisms in DNA samples from families with anorexia and other eating disorders and from individuals not affected with anorexia nervosa. Two genes in the chromosome 1 region, HTR1D, the gene that codes for the serotonin 1D receptor, and OPRD1, the gene that codes for the delta opioid receptor, demonstrated statistically significant association to anorexia nervosa.

“This study is evidence that we’re on the right track in our search for genes that contribute to eating disorders,” said Walter H. Kaye, a Pitt professor of psychiatry and principal investigator for the study. “These efforts could eventually lead to more effective treatments or preventive measures.”

Funding for the study was provided by the Price Foundation, which has provided financial support for the research team for more than a decade.

For more information, call 1-888/895-3886 or visit


Combination therapy safe, effective in treating osteoporosis

Elderly women with osteoporosis can significantly and safely improve their bone mass with a combination therapy of hormone replacement and the bisphosphonate alendronate (Foxamax). The findings are published in the May 21 issue of the Journal of the American Medical Association by Pitt researchers.

“Our study found that a combination therapy of hormone replacement and alendronate was well tolerated by elderly women with low bone mass. After three years of treatment, these women showed significantly greater increases in bone mass than we saw in similar women taking only one of the therapies,” said lead author Susan Greenspan, professor of medicine at Pitt’s School of Medicine and director of the Osteoporosis Prevention and Treatment Center at the University of Pittsburgh Medical Center. “Combination therapy is a safe, viable option for postmenopausal women who have been unable to improve their bone density with an individual therapy, or in women with osteoporosis severe enough to require a greater increase in bone density.”

Earlier research has suggested similar results with younger women, but up to now little data were available on the effectiveness and safety of combination therapy in older, post-menopausal women.

The study was conducted with 373 women aged 65 to 90 years. At baseline, participants as a group had bone mass thin enough to be classified as osteopenia, a precursor of osteoporosis. Thirty-four percent of the women had osteoporosis.

Participants were evenly randomized to receive hormone replacement therapy (HRT) (conjugated estrogen with or without medozyprogesterone) plus alendronate, HRT alone, alendronate alone, or placebo. All received calcium and vitamin D supplements.

After three years, dual-energy X-ray absorptiometry (DXA) scans showed that participants taking combination therapy had greater improvements in bone mineral density (BMD) at the hip and spine than did those participants taking HRT or alendronate alone, or placebo.

For instance, the mean increase in BMD at the hip was 5.9 percent with combination therapy, 4.2 percent with alendronate, 3.0 percent with HRT and 0.0 percent with placebo. At the lumbar spine the mean increases in BMD were 10.4 percent with combination therapy, 7.7 percent with alendronate, 7.1 percent with HRT and 1.1 with placebo.

Also, in comparing HRT with alendronate, researchers found that participants taking alendronate alone had greater improvements in BMD at the hip.

While the study was not designed to examine fractures as an outcome, a higher bone density is usually associated with fewer fractures.

“We applied a logistic model to our data and determined that combination therapy would provide an additional 10 percent reduction in fracture over HRT alone and an additional 8 percent over alendronate alone,” said Greenspan.


Gamma knife provides long-term control of benign brain tumors

Treating benign brain tumors with gamma knife radiosurgery resulted in long-term tumor control in 95 percent of patients, according to a study by Pitt researchers presented May 21 at the quadrennial meeting of the American Society for Stereotactic and Functional Neurosurgery.

“Stereotactic radiosurgery using the gamma knife provided high rates of tumor growth control, often with tumor regression, and low morbidity rates for patients with benign intracranial tumors when evaluated over the long term,” said Douglas Kond-ziolka, principal investigator in the study and professor of neurological surgery and radiation oncology, vice chairman of education in the Department of Neurological Surgery and co-director of the Center for Image-Guided Neurosurgery at the University of Pittsburgh Medical Center (UPMC).

The study evaluated 285 consecutive patients who underwent radiosurgery for benign brain tumors between 1987 and 1992 at UPMC. In the study, 157 patients had acoustic neuromas, 85 had meningiomas, 28 had pituitary adenomas, five had craniopharyngiomas and 10 had other cranial nerve schwannomas. Prior surgical resection had been performed in 44 percent of these patients and prior radiation therapy administered to 5 percent. Median follow-up of patients was 10 years. Mean patient age was 60 years.

The study found that tumor volume reductions usually occurred slowly, beginning as early as six months following the gamma knife procedure, but continuing even years later. The majority of tumors (63 percent) eventually reduced in size. Some tumors that had regressed by five years after radiosurgery were even smaller seven and 10 years later. Delayed tumor growth was identified in 5 percent of patients. Surgical resection after radiosurgery was performed in 13 patients (5 percent). No patient developed a radiation-induced tumor. After 10 years, 81 percent of patients were still alive. Normal facial function was maintained in 95 percent of patients who underwent gamma knife treatment for acoustic neuroma.

“Gamma knife radiosurgery appears curative for many patients with small or medium sized benign brain tumors,” said Kondziolka. “Our study found that it was rare for a tumor to enlarge once four years of follow-up had passed. Similarly, radiation-related morbidity usually occurred early, within three years. Radiosurgery is best chosen for patients with tumors that do not cause significant symptoms from brain compression. For that reason, we recommend it for patients who have residual or recurrent tumors after resection, but also as an important choice for patients with newly diagnosed tumors.”

Benign tumors of the brain and its coverings can lead to functional deficits that may persist for many years.

The gamma knife contains 201 cobalt-60 sources of approximately 30 curies each, placed in a circular array in a heavily shielded unit. The unit directs gamma radiation to a target point. Such target points selected in the brain can be placed at the center of the radiation focus, allowing a radiation dosage to be delivered in one treatment session.

Also involved in the study were L. Dade Lunsford, professor and chairman of the neurological surgery department and co-director of the Center for Image-Guided Neurosurgery at the Pitt School of Medicine; John C. Flickinger, professor of radiation oncology and neurological surgery; Ajay Niranjan, research assistant professor of neurological surgery; Ann Maitz, assistant professor of neurological surgery and radiation oncology, and Narenda Nathoo, clinical fellow.


Diabetic medication adherence studied

A team of Pitt researchers are engaged in a study to learn more about managing multiple medications for type 2 diabetes, high blood pressure and high cholesterol.

Approximately 50 percent of patients taking medications have trouble adhering to their regimen, research studies have shown. Those at particular risk are people contending with more than one illness.

The Pitt study, funded by a $1.57 million grant from the National Institutes of Health, focuses on researching the difference telephone intervention makes to provide significant increases in the regularity of medication use among half of the 396 study participants. The study will not change any of the participants’ medications. Instead, the examiners will make bi-weekly telephone calls to provide counseling for participants with poor stability taking medications.

During the first stage of the study, participants are asked to complete a series of questionnaires. Also, for a 30-day period, participants will be asked to keep three of their regular medications in special pill bottles that contain a counter. Then participants will be classified into either good adherers or poor adherers.

For the second phase, the researchers ask participants to continue keeping medications in the special pill bottles over the course of one year. Also, participants are asked to attend three office visits for blood tests and memory tests and fill out two more sets of questionnaires. Participants will be reimbursed for travel to and from the hospital and parking. The 198 poor adherers will then receive bi-weekly phone calls from a nurse to discuss their treatment plans.

The goal of this survey is to learn more about the influences on how people with type 2 diabetes, high blood pressure and high cholesterol carry out their treatment programs and to learn how to better help people manage a complex treatment program.

The team includes principal investigator Jacqueline Dunbar-Jacob, dean of Pitt’s School of Nursing; nursing faculty members Judith A. Erlen, Joan Rogers, Christopher Ryan, Elizabeth Schlenk, Susan Sereika, Carol Stilley, Lisa Tamres (project director) and Maura McCall (project nurse); Pamela Peele of the Graduate School of Public Health, and Eric Rodriguez of the School of Medicine.


Cardiologists using new drug-eluting stent

Physicians at the University of Pittsburgh Medical Center’s (UPMC) Cardiovascular Institute have begun using a new drug-eluting stent to prevent reblockage of arteries following angioplasty.

Called the CYPHER Sirolimus-eluting Stent, it is the first drug-eluting stent to receive marketing approval from the Food and Drug Administration for the treatment of blocked coronary arteries.

The new stent, which is approved for the treatment of previously untreated coronary artery lesions, was developed to address the problem of in-stent reblockage, or restenosis, which occurs in as many as 15-30 percent of patients who receive a bare metal stent. The stent is coated with the drug sirolimus, which is slowly released into the intima, or vessel lining, to prevent scar tissue growth through the openings in the stent mesh, which frequently leads to restenosis.

“The stent provides new hope for patients with challenging case histories,” said Conrad Smith, interim chief of the Division of Cardiology at UPMC.

Results of large-scale studies involving nearly 1,400 patients worldwide show that the stent, manufactured by Cordis Corporation, a Johnson & Johnson company, reduces the incidence of restenosis by more than 90 percent over a bare metal stent.

For more information, call 412/647-6136.


UPB unveils results of home health care study

The University of Pittsburgh Center for Rural Health Practice, housed at Pitt’s Bradford campus, recently released a report highlighting results of a year-long study of home health agencies’ financial vulnerability.

The research was directed by Michael Meit, director of the Center for Rural Health Practice, and was conducted by Chyongchiou Jeng Lin, a health economist from Pitt’s Graduate School of Public Health. The study provides recommendations to improve the financial status of rural home health agencies.

“Rural agencies experience greater financial strains than their urban counterparts,” Meit explained. “Payments to these agencies need to account for the higher cost of providing services in rural areas. Further, we believe that rural agencies would benefit from training and technical assistance that would help them to reduce their administrative costs, which significantly impact their financial well-being.”

Funding for the study was secured by U.S. Congressman John Peterson, R-Pa., who co-chairs the Rural Health Care Coalition’s Home Health Working Group and the Congressional Rural Caucus.

Study results were combined with those of a complementary study conducted by the Pennsylvania Office of Rural Health through a grant from the Center for Rural Pennsylvania, a legislative agency of the Pennsylvania General Assembly.

“Home health agencies provide critical health care services to some of our most frail and vulnerable citizens,” Peterson said, “especially in rural areas where hospital services may not be as readily available as in larger cities. Home care agencies not only provide health care services in a comfortable setting, but they often save families and taxpayers money by keeping patients out of more costly environments like inpatient hospital settings and nursing homes.”


Is age factor in sports-related concussion recovery?

Does age play a role in how long it takes for an athlete to recover from concussion? In the first published study to examine age as a factor, University of Pittsburgh Medical Center (UPMC) sports concussion researchers found that high school athletes demonstrated prolonged memory dysfunction requiring longer recovery compared to college athletes.

The study’s results, published in the Journal of Pediatrics, supports more conservative management and comprehensive assessment of the concussed high school athlete and may have serious implications for return-to-play guidelines.

In the study, post-concussion neuropsychological recovery of high school athletes was compared to that of college athletes at 24 hours, 3 days, 5 days and 7 days post-injury. In tests of neurocognitive function and self-reported symptoms, high school athletes performed significantly worse than age-matched control subjects at 7 days post-injury. Concussed college athletes, despite sustaining more severe injuries, displayed commensurate performance with age-matched control subjects by day 3 post-injury. Specifically, following mild concussion, high school athletes showed significant memory impairment at day 7; conversely, college athletes revealed significant memory deficits only within the first 24 hours post-injury.

“Our finding that high school athletes did not recover from concussion as quickly as college athletes is a cause for concern because the largest majority of at-risk athletes are at the high school level or below,” said principal investigator Melvin Field, chief resident in UPMC’s Department of Neurological Surgery. “Furthermore, existing return-to-play guidelines assume a standard use for all age groups and levels of play, from school-age to professional.”

Recent studies show that more than 62,000 concussions occur each year in high school sports, with football accounting for about 63 percent of them. At the college level, 34 percent of football players have had at least one concussion and 20 percent have had more than one.

Concussion is a trauma-induced alteration of mental status, which may or may not result in unconsciousness. Other symptoms may include dizziness, disorientation, headache, nausea, amnesia and poor hand-eye coordination. Concussion occurs when the brain is violently rocked back-and-forth inside the skull due to a blow to the head, neck or upper body.

“The problem with concussion in sports is that symptoms are not always straightforward, not always reported by the athlete and usually difficult to objectively measure,” said study co-investigator Joseph Maroon, professor and vice chairman of Pitt’s Department of Neurological Surgery. “Meanwhile, the typically competitive high school athlete is usually quite anxious to return to the game despite any minor symptoms. The concern is that previous studies have proven that before an athlete is fully recovered from an initial concussion, he or she is more susceptible to a second concussion and is at higher risk for further, more serious damage. Thus, keeping an athlete out of contact play until he or she is fully recovered from initial concussion is absolutely crucial to preventing further injury,” said Maroon. “No concussed athlete should ever return to contact sports before it is determined that their recovery is complete.”  

“This study suggests that further studies are needed in children of all ages before current adult-based return-to-play management guidelines are maintained or implemented in high schools and other adolescent-related sports,” said Mark Lovell, study co-investigator and director of the UPMC Sports Medicine Concussion Program. Michael Collins, assistant director of the program, was also a study co-investigator.

The study, conducted by sports concussion researchers in the neurological surgery and the Sports Medicine Concussion Program, evaluated 39 high school athletes and 53 college athletes.


National emphysema treatment trial results reported

Lung volume reduction surgery as a treatment for emphysema increases the chances of improvement in exercise capacity, lung function and quality of life without increasing mortality, according to a study presented May 20 at the American Thoracic Society (ATS) International conference.

A subgroup of patients with upper lobe emphysema and a low baseline exercise capacity prior to surgery also were found to have a significant survival benefit in addition to the functional improvement. The two-year survival rate in this subgroup was greater than twice that of patients in a non-surgical control group.

Physicians from the University of Pittsburgh Medical Center (UPMC), who participated in the 18-center National Emphysema Treatment Trial (NETT), presented a portion of the findings at the ATS conference.

“This study proves that, in a properly selected patient, lung volume reduction surgery has become the only available treatment other than supplemental oxygen to increase the survival rate for these patients,” said Frank Sciurba, associate professor of medicine, Division of Pulmonary and Critical Care Medicine at UPMC and principal investigator for the Pittsburgh arm of the study. “However, it is important to note that this surgery is not for everyone and, in fact, there are subgroups of patients where surgery may be harmful.”

In lung volume reduction surgery, surgeons remove about 20 to 35 percent of the diseased portion of the lungs. The procedure is not a cure and does not stop the disease, but it offers patients an alternative to lung transplantation.

The study enrolled 1,218 patients with severe emphysema between January 1999 and July 2002. All participants in the study first underwent six to 10 weeks of pulmonary rehabilitation and then were randomized to either lung reduction surgery (608) or continued medical treatment (610).  

Among the 290 patients with upper lobe predominant emphysema and low post-rehabilitation baseline exercise capacity, surgery patients had both a lower mortality rate and a greater likelihood of improvement in exercise capacity after 24 months. However, among the 220 patients with non-upper lobe predominant emphysema and high post-rehabilitation baseline exercise capacity, surgery patients had a greater mortality rate with little chance of exercise improvement.

“While those patients with upper lobe emphysema clearly gained from lung volume reduction surgery, non-upper lobe patients with higher baseline exercise capacity were found to be poor candidates for this procedure,” Sciurba said.

Emphysema, the destruction and enlargement of the lungs’ peripheral air sacs, affects an estimated 2 million people in the United States. Smoking causes the majority of cases. Because of emphysema, the lungs are over-expanded at all times and the movement of air from the chest cavity is greatly reduced.

The study was funded by the National Heart, Lung and Blood Institute and the Health Care Financing Administration.

UPMC is one of the most experienced centers performing lung surgery in the country and a major contributor to the medical literature in lung reduction surgery. Sciurba authored one of the first papers detailing how lung volume reduction surgery works in a 1996 publication.

For patient information, call 412/648-6388.

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