University Times

UPMC Presby using new generation gamma knife

UPMC Presbyterian is the first hospital in the United States to house a new generation gamma knife surgical unit, which performs non-invasive, computer-driven, bloodless brain surgery to destroy tumors and vascular malformations, once considered inoperable. The treatment requires no surgical incision.

"This newly refined instrument uses robotic engineering to enable us to deliver optimal treatment for deadly brain tumors and abnormal brain arteries and veins that can cause disastrous or even fatal bleeding in the brain," said L. Dade Lunsford, professor and chief of neurological surgery and co-director of the Center for Image-Guided Neurosurgery at Pitt's School of Medicine.

The gamma knife was introduced in this country at UPMC Presbyterian in 1987. In 1996, UPMC Presbyterian became the first hospital to house two gamma knife units.

The gamma knife delivers a single high dose of irradiation at targets of just several millimeters up to three centimeters in diameter. Because the beam focuses precisely on the offending tissues, effects on surrounding brain tissue are minimized.

Surgery using the gamma knife is safer than many existing procedures because patients need not undergo risky open-skull procedures and adult patients do not require general anesthesia. It causes few side effects, and patients usually leave the hospital within 24 hours.

The new generation gamma knife provides rapid creation of dose-optimized treatment plans that mean better clinical outcomes for patients. A robotic automatic patient-positioning system allows for even greater accuracy of treatment.

"The automatic positioning system will make the procedure time shorter and therefore easier for appropriate patients," Lunsford said.

The unit is housed in the Center for Image Guided Neurosurgery at UPMC Presbyterian and contains 201 sources of cobalt 60 in a heavily shielded room.

Each patient's procedure, which lasts from 10 to 40 minutes, is custom designed in consultation with a radiation physicist and radiation oncologist. The patient is monitored throughout the session using a video camera and television monitor.

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Improvement reported in some who underwent neuronal transplantation after stroke

Some patients who underwent neuronal transplantation following stroke showed improvement in motor function, a Pitt professor has found.

Douglas Kondziolka, professor of neurological surgery and radiation oncology in the Department of Neurological Surgery, reported on the six-month neurologic outcome and 12-18 month safety data of patients in the first research study of a treatment aimed at reversing neurological deficits from stroke.

Kondziolka's study, presented at the annual meeting of the American Association of Neurological Surgeons, involved 12 patients in a phase I trial that evaluated the safety and feasibility of implanting human neuronal cells for treatment of chronic stroke in the basal ganglia region of the brain.

The nine men and three women in the study varied in age from 44 to 75 years. In eight patients, the stroke involved only the basal ganglia region of the brain and in four patients, both the basal ganglia and regional cortex were involved. All patients had stable neurologic deficits at least two months prior to implantation.

The first four patients were treated with two million neurons implanted at three sites along a single needle pass within the basal ganglia. The remaining eight patients were randomized to receive either two million neurons along one needle pass or a total of six million neurons implanted along three trajectories.

Following implantation, subjective improvement, which included increased strength, sensation and coordination, was reported in eight patients.

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New system predicts impending arrhythmia, sudden death

A team of Pitt computer software engineers, led by Vladimir Shusterman of UPMC Health System's Cardiovascular Institute, has developed and patented a computerized system that can predict a cardiac arrhythmia or sudden death up to eight hours prior to the onset of symptoms.

The system is based on the team's research into the general biological mechanisms underlying cardiac arrhythmias and sudden death.

When incorporated into a heart monitor or internal defibrillator, the system can provide ample warning to patients at risk for sudden death that an arrhythmia is imminent and allow time for them to take appropriate action.

In the future, the system may be used as an external cardiac monitoring device in hospital intensive care units and has the potential for development as a continuous home-based monitor, according to the researchers.

It also may help to prevent unnecessary defibrillator shocks.

"Shocks can be a psychological burden for a person implanted with a defibrillator," said Kelley Anderson, Pitt associate professor of medicine, director of Cardiac Electrophysiology Research at UPMC Presbyterian Hospital and a principal investigator for the clinical part of the study.

"If we can predict when an arrhythmia is about to occur, then we can take steps to intervene," Anderson added.

An arrhythmia is an abnormal rhythm of the heart that can be fatal. An internal defibrillator is a battery-powered electronic device implanted near the collarbone of people who are at risk for sudden death. It monitors the heart rhythm continuously and restores normal rhythm by delivering an electrical shock when it detects an arrhythmia. Over 40,000 defibrillators are implanted yearly in the United States.

Some 300,000 people in the United States die suddenly each year from arrhythmia — about one person every one to two minutes.

"Heart rate dynamics are complex and differ from patient to patient. In our research we found that each individual's heart rate has its own traits, like fingerprints," said Shusterman, an expert in computer technologies and cardiovascular physiology. "The computer system we developed captures these subtle changes in the heart rate pattern."

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No apparent increase in cancer deaths among Three Mile Island residents, GSPH research indicates

Radioactivity released during the Three Mile Island (TMI) accident in 1979 does not appear to have caused an increase in cancer deaths among people living within a five-mile radius of the nuclear accident, according to researchers at Pitt's Graduate School of Public Health (GSPH).

The findings were published April 28 on the web site of Environmental Health Perspectives, a journal of the National Institutes of Health's National Institute of Environmental Health Sciences. The paper also will be published in the June issue of the journal.

While several previous follow-up studies on the TMI population have been conducted, this one is the most extensive due to its longer, 13-year time frame and the use of information about residents' lifestyles (such as smoking habits and education levels) and everyday background radiation exposure beyond what was caused by the TMI incident.

"This study helps put to rest the lingering question of whether the residents of Three Mile Island are experiencing an increase in cancer deaths as a result of the nuclear accident," said Evelyn Talbott, associate professor in the Department of Epidemiology and principal investigator on the study.

The TMI incident occurred at a nuclear power plant near Harrisburg on March 29, 1979, when a reactor leaked small amounts of radioactive gases. It often is referred to as the worst nuclear accident in American history.

Scientists have calculated that the average person in the area during the 10 days after the incident was exposed to considerably less radiation than the annual dose an individual receives from the everyday environment in the United States.

The GSPH study covered the years 1979-1992. For demographic and lifestyle data on the individuals living in the TMI area, researchers used information collected by the Pennsylvania Department of Health in interviews conducted with TMI residents within two months of the accident.

Information collected on these 32,135 individuals included education, occupation, smoking status, residential history, medical history, previous radiation exposure and daily travel in and out of the area during the 10 days following the accident at Three Mile Island.

While researchers found no consistent evidence suggesting that the low-dose radiation released during the TMI accident had a measurable impact on the mortality of those living in the area for 13 years after the event, they acknowledge that further study is warranted.

"Because the latency period for many cancers is 20 years or more, continued follow-up on the TMI residents will provide a more comprehensive look at their mortality, as well as morbidity, from various cancers," Talbott said.

The Pitt research team is currently analyzing data collected through 1999 on the same population.

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Anti-cancer compound may damage liver

An anti-cancer compound initially set to enter clinical trials within months could harm a patient, according to a Pitt report in the May issue of Nature Medicine.

The Pittsburgh scientists found that the compound TNF-related apoptosis-inducing ligand (TRAIL) causes catastrophic damage to human liver cells while proving harmless to liver cells from mice and nonhuman primates used in preclinical testing.

Previous studies of TRAIL showed that this compound only triggered cancer cell death, and the drug was slated for use in early treatment studies for many types of cancer, including those of the central nervous system. This is the first study indicating that TRAIL also may kill normal, healthy cells.

"Our findings with TRAIL indicate that results of standard preclinical tests may mislead investigators into believing that an agent is safe for use in humans," said Stephen Strom, associate professor of pathology at Pitt's School of Medicine and senior author of the report. "We've shown that differences in the sensitivity of various species to the same compound can prove critical. Significant toxicity could result if TRAIL were used in human cancer therapy."

TRAIL kills a cell by interrupting its normal life cycle, thereby causing it to commit suicide (also called programmed cell death). Subtle molecular differences among species may regulate the sensitivity of cells to TRAIL, according to Strom. Human hepatocytes carry specific cell receptors known to initiate TRAIL's killing effects. Dubbed "death receptors", these markers are found on most or all cells. Investigations with TRAIL are relatively recent, and it is not clear when and why TRAIL binding leads to cell death and when there is no biological effect. The reasons for these differences are under study in the laboratory.

UPCI receives $1 million grant for oncology informatics The Claude Worthington Benedum Foundation has granted the University of Pittsburgh Cancer Institute (UPCI) $1 million to expand its current oncology informatics program by establishing the new Benedum Oncology Informatics Center.

This center, the first of its kind, will be located at the Hillman Cancer Center, UPMC Shadyside. The Hillman Cancer Center is slated to open in early 2002.

"To establish a highly efficient informatics program for a major cancer center such as UPCI is of great importance, especially because informatics is key to providing quality patient care and performing leading edge biomedical research," said Ronald B. Herberman, director of UPCI, Hillman Professor of Oncology and Pitt associate vice chancellor for research, Health Sciences.

Because cancer centers have become increasingly dependent on information technology, UPCI established an Oncology Informatics Program in 1998 under the direction of Henry Lowe, director of Oncology Informatics at UPCI, director of the new Benedum Oncology Informatics Center, and a nationally recognized informatics expert.

The oncology informatics program was developed in an attempt to combine information technology and the Internet to improve the care of cancer patients across the region and integrate clinical, research and genomics data, making it available in a meaningful way to cancer patients.

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Researcher awarded grant to study those who are mechanically ventilated

Leslie Hoffman, professor of nursing and chairperson of the Department of Acute/Tertiary Care in Pitt's School of Nursing, and her team of researchers have received a $1.1 million National Institute of Nursing Research grant for their studies on improving outcomes in mechanically ventilated patients.

"Each year, there is a substantial number of chronically ill patients who recover from illness but have difficulty regaining the ability to breathe on their own," Hoffman said. "This results in longer hospital stays, which can be quite costly, diminish the quality of life and increase the risk of medical complications."

Hoffman's research will assess whether nurse practitioners who are specially trained in caring for critically ill patients can improve outcomes of these patients and wean them off ventilators more quickly and efficiently when compared to the standard care provided in a university setting.

According to Hoffman, the goal of the four-year study is to determine if patients can be weaned more efficiently from ventilators and if they will benefit from more constant attention given by the nurse practitioner compared to the rotational schedule used for physicians-in-training.

Hoffman's study also will examine what type of information is communicated to the patient and the patient's family, and whether the information shared by the nurse practitioner with the patients and their family members plays a role in the outcome of the patients.