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August 30, 2001


Ovarian cancer subject of Magee study

Magee-Womens Hospital is enrolling newly diagnosed ovarian cancer patients in a clinical study to evaluate the safety and efficacy of a treatment combining traditional chemotherapy with a peptide that has shown cancer-fighting properties. A peptide is a combination of amino acids.

The peptide, called IM862, appears to interfere with tumor blood vessel development, said Robert P. Edwards, medical director of gynecological oncology at Magee-Womens Hospital and director of the gynecologic oncology center at the University of Pittsburgh Cancer Institute.

"The treatment is given in nose drops that patients can administer themselves," noted Edwards, who also is an associate professor and medical director in the division of gynecologic oncology at Pitt's School of Medicine.

Developed by suburban Seattle, Washington-based Cytran Inc., IM862 also is being tested as a possible immune system booster. Magee-Womens Hospital is among 18 centers nationwide now taking part in clinical trials using IM862, which also is being evaluated for its effectiveness in treating patients with prostate, breast and colorectal cancers. Cytran is funding the Magee study.

Approximately 24,000 new cases of ovarian cancer are diagnosed each year in the United States. About 14,000 women die yearly from the disease.

Nearly half of patients who receive treatment for ovarian cancer will have a recurrence, experts say. Aggressive surgery followed by chemotherapy is the current "standard of care" for ovarian cancer treatment. Women 18 years of age or older who are newly diagnosed and have had surgery but not chemotherapy are being targeted to take part in the study. Patients who have had previous chemotherapy treatment are ineligible.


Adolescents, young adults at high risk for meningitis

Adolescents and young adults have an unusually high risk of severe and sometimes fatal bacterial meningitis, according to a study led by the Graduate School of Public Health (GSPH) and published in the Aug. 8 issue of the Journal of the American Medical Association.

In an effort to characterize, for the first time, the features of meningococcal infection in 15- to 24-year-olds during the 1990s, researchers conducted laboratory-based surveillance and reviewed 1990-1999 health department and medical records from the state of Maryland.

"We found that adolescents and young adults accounted for a relatively high proportion of all cases of meningococcal meningitis, and that infection in this age group led to death more often than expected," said study author Lee H. Harrison, associate professor of epidemiology at the GSPH and adjunct associate professor of international health at the Johns Hopkins Bloomberg School of Public Health.

"Traditionally, infants have been at the highest risk for meningococcal infection in developed countries, but during the 1990s there was an increase in the number of cases among adolescents and young adults," said Harrison, who also is head of the Infectious Diseases Epidemiology Research Unit at GSPH and Pitt's School of Medicine.

The investigators found 295 cases of meningococcal infection in Maryland from 1990 through 1999. Of those 295 cases, 71 (24.1 percent) occurred among people ages 15 to 24, and an unusually high number of these cases (16 cases, or 22.5 percent) were fatal.

The incidence of meningococcal infection in the 15- to 24-year-old age group in the study population more than doubled between 1990 and 1997. About 83 percent of the cases in this age group, and a majority of cases in other age groups, were vaccine-preventable.

Meningitis is an inflammation of the membranes that cover the spinal cord and the brain. Bacterial meningitis, which is much more severe than viral meningitis, is caused by a variety of bacteria, one of which is Neisseria meningitidis, also known as the meningococcus.

The study was funded by the Centers for Disease Control and Prevention, Aventis Pasteur and the State of Maryland.


Study using brain imaging to locate mechanisms responsible for problem drinking

Researchers at UPMC Health System are using sophisticated imaging equipment to study how brain function contributes to the difficulty many people have in stopping drinking.

The study involves imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) to locate the brain mechanisms responsible for alcohol dependency. Following the assessments, participants receive a U.S. Food and Drug Administration-approved medication and individual counseling sessions to try to help them stop drinking.

To qualify for this study, participants must be between the ages of 25 and 50 and think they drink too much. Study procedures are provided at no cost and participants are paid upon completion of the study.


Study of air pollution, hospital stays begins

Pitt's Graduate School of Public Health (GSPH) has received $132,000 from Allegheny County to conduct a one-year study of possible links between air pollution and hospitalizations for respiratory and cardiopulmonary illnesses throughout the county.

"The link between air pollution and health problems has been the topic of debate for decades, particularly in counties such as Allegheny," said Joseph Schwerha, professor of environmental and occupational health and director of the Division of Occupational and Environmental Medicine at Pitt, and principal investigator of the study. "The air quality in Allegheny county has improved over the past two decades, and we are obliged to look at whether remaining air pollution from coal-fired power plants, motor vehicles and industry affects the health of residents."

Using data from the Allegheny County Health Department air quality monitoring stations, researchers will identify any daily, monthly and quarterly trends in air pollutant releases between 1995 and 1999 and compare those findings with trends noted in hospital admissions and emergency room visits across the county during that same time period, specifically for asthma, congestive heart failure and chronic obstructive pulmonary disease. They will focus on residents ages 12 and younger, and 65 years and older — the age groups most susceptible to environmentally related health problems.

Any correlations between trends with regard to air pollution releases and hospitalizations and emergency room visits for respiratory and cardiopulmonary events will be recorded and compared with controls.

In looking for trends in air pollution, investigators will assess those pollutants that previous studies have linked with hospital admissions for respiratory illnesses, namely sulfur dioxide, hydrogen sulfide, particulate mass, sulfates, nitrous oxide and ozone.

In looking for trends in hospitalizations, researchers will review admissions and emergency room data from hospitals in Allegheny County.

Evelyn Talbott, associate professor of epidemiology, is co-principal investigator of the study.


Project studies medication to stabilize bipolar symptoms while cutting alcohol use

Researchers at the School of Medicine are studying whether the medication valproate is effective in reducing symptoms of bipolar disorder and decreasing alcohol use in those with the illness.

Currently, there are no effective treatments that can accomplish both goals, a major roadblock to recovery, according to researchers.

"We have found that many people with bipolar disorder also abuse alcohol," said Ihsan M. Salloum, associate professor of psychiatry and principal investigator of the study. "Alcohol use makes it difficult to successfully treat bipolar disorder because drinking alters a person's ability to take medication and follow treatment regimens."

During the five-year study, 94 patients who are acutely ill during a manic phase will be followed for up to 24 weeks. Researchers will observe participants for signs of alcohol withdrawal and participants will be detoxified from alcohol and other drugs and will discontinue other medications. Once participants are drug and alcohol free, they will be randomly assigned to receive either valproate plus standard treatment for bipolar disorder or placebo plus standard treatment for bipolar disorder. Once participants are stabilized and treatment starts, clinicians will assess participants' conditions weekly using standard questionnaires.

The study is funded by the National Institute on Alcohol Abuse and Alcoholism.


Effective treatments lacking for most desperate AIDS patients

New medications are urgently needed for people with drug-resistant HIV, and academia, industry and government must work together to bring them into the clinic, urged AIDS researchers John Mellors of Pitt and Julio Montaner, of the University of British Columbia, in an editorial in the Aug. 9 issue of the New England Journal of Medicine.

"Antiretroviral therapy is most effective the first time it is prescribed," wrote Mellors and Montaner. But in patients who have had previous exposure to two or all three classes of drugs used in the "cocktails," the therapy is usually unsuccessful in suppressing blood levels of HIV to undetectable amounts.

Lacking more effective therapies, some health care practitioners abandon efforts to suppress HIV levels in these treatment-exposed patients, who represent some 30 percent of treated HIV patients in the United States alone.

"The lack of viable new antiretroviral therapy options for the most desperate patients not only represents a failure on the part of the scientific, academic and governmental communities, but it also sets the stage for a dangerous epidemic of drug-resistant HIV," said Mellors, Pitt professor of medicine and chief of infectious diseases.

Without medications to suppress HIV to undetectable levels, the virus continually mutates into new forms that often do not respond to available drugs. These drug-resistant forms of the virus then are transmitted from one individual to another.

Some 5 percent to 10 percent of newly diagnosed HIV-infected patients in the U.S. are thought to have been infected with drug-resistant forms of the virus.

The three classes of drugs from which current antiretroviral cocktails are made are nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors.

A number of factors can lead to a patient's inability to get the most benefit from the drugs, including a great deficiency in the immune cell counts, high levels of virus in the blood and non-adherence to the strict and sometimes difficult treatment regimen. Without maximum exposure to the medication, viral levels are not suppressed adequately, the remaining virus mutates, drug-resistant virus is formed and the virus escapes.

Once drug-resistant virus emerges, it becomes more difficult to treat because of cross resistance between the currently available drugs, according to the authors. Specifically, a virus that has become resistant to one drug in a class of drugs often shows cross resistance to other members of the same drug class.

Obstacles need to be overcome in getting new drugs through development and into the clinic, according to the authors.

"First, there need to be stricter regulatory requirements during testing. Currently, antiretroviral drugs are gaining approval without ever having been tested on the patients who need them most — those with drug-resistant HIV," the authors contend. "Secondly, we need the simultaneous release of more than one approved drug into expanded access programs. The practice of staggering the release of new antiretroviral agents is unacceptable, as it allows clinicians to add only one new drug at a time to a failing treatment regimen. This promotes failure of the single new drug and further drug resistance. We need the ability to add several new drugs in combinations."


IV sedation safe, effective for dental outpatients

Four intravenous sedation regimens have been proven safe and effective in easing pain, fear and anxiety in dental outpatients, according to a study released in the Journal of the American Dental Association (JADA).

The study was the largest prospective clinical study to evaluate the efficacy and safety of parenteral sedation.

Fear of dentistry is a significant impediment to care for a large segment of the population, despite the decrease in dental disease and improvements in pain control. According to Paul A. Moore of Pitt's School of Dental Medicine, an author of the study, managing this fear is a primary concern of dental and medical practitioners. Intravenous conscious sedation is frequently used in medicine and dentistry to relieve patient fears during outpatient surgery.

"This study should be a reassurance to those who are scared of the dentist. Not only can we perform procedures with minimal pain, but we can also ease a patient's fear and anxiety, making the experience less traumatic for the patient," said Moore, who is a professor of pharmacology in the department of public health dentistry at Pitt's dental school.

The collaborative, multi-center study, conducted by the Collaborative Sedations Study Group, evaluated 997 outpatients who underwent removal of impacted third molars. The study was funded by the National Institute of Dental and Craniofacial Research, a division of the National Institutes of Health.

The investigation was conducted at Pitt, the University of California at Los Angeles School of Dentistry, University of Kentucky School of Dentistry, University of North Carolina School of Dentistry and University of Washington.


Neurons used in stroke damaged brain tissue show function

An imaging study of neurons implanted in damaged areas of the brains of stroke patients in the hopes of restoring function has shown the first signs of cellular growth, researchers say.

Positron Emission Tomography (PET) scans taken six months after surgery to implant LBS-neurons showed a greater than 10 percent increase in metabolic activity in the damaged parts of some patients' brains compared to scans taken just a week prior to surgery. The increased metabolism corresponds with better performance on standardized stroke tests for behavioral and motor function.

While PET scans taken at 12 months post-surgery showed that metabolism in the implanted area itself had lessened to baseline, the surrounding area in some patients showed maintained or even improved function — perhaps evidence that the LBS-neurons were becoming integrated into the brain.

Results of the study from the first human neuroimplantation trial for chronic stroke appear in the September issue of Neurosurgery.

"These changes in glucose metabolism in the stroke and surrounding brain tissue may represent cellular activity or grafting of the implanted neurons," said Carolyn Cidis Meltzer, associate professor of radiology and psychiatry, medical director of the UPMC PET facility and principal author of the study. "Although this is not direct evidence of synapse formation, it does suggest that the new neurons are being wired into the brain."

Meltzer and her colleagues performed PET imaging on 11 patients who suffered strokes resulting in persistent motor deficits at least a week before, then six months after implantation surgery. Nine of the original group went through the scans again at 12 months.

LBS-neurons originated from a human teratocarcinoma, a tumor of the reproductive organs that is composed of embryonic-like cells, which was removed from a 22-year-old cancer patient in the early 1980s. Layton BioScience Inc. has licensed a patented process that uses several chemicals to transform this cell line into fully differentiated non-dividing human neuronal cells that can be used in clinical applications. In extensive pre-clinical testing, implants of LBS-neurons reversed cognitive and motor deficits in animals in which stroke had been induced.

The implantation procedure begins with the placement of a stereotactic frame on the head of the patient. The frame is a standard tool in neurosurgery to provide a fixed way to find specific locations within the brain. The patient then receives a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain and the surgical team makes its final decision for location of cell implantation.

Concurrently, Pitt's immunologic monitoring and diagnostic laboratory team thaws the human neuronal cells that were frozen by and transported from Layton BioScience Inc.

After the cells are transferred to a long-needled syringe, the surgeon uses CT to guide their injection at multiple sites. The surgeon injects these cells through a small opening in the skull and the patient leaves the hospital the next day.

Stroke affects approximately 750,000 people in the United States each year and is the third leading cause of death and most common cause of disability. There are no known effective treatments for chronic stroke with fixed neurological deficit.

The study was funded by Layton BioScience Inc.


Cardiovascular Institute studies EECP for congestive heart failure

Physicians at UPMC Health System's Cardiovascular Institute are participating in a multi-center research study to determine if Enhanced External Counterpulsation (EECP) is an effective treatment for people with congestive heart failure.

EECP is a non-invasive, outpatient treatment currently approved by the FDA for use in patients with angina.

While undergoing treatment, the patient lies on a padded table equipped with inflation and deflation valves connected to three pairs of air-driven compressive cuffs that are wrapped around the legs and lower buttocks.

The pumping cycle of the cuffs is synchronized in time with the patient's heartbeat. When the heart is in the relaxed state, air is inflated into the cuffs to move blood back towards the heart in an attempt to increase blood flow to the heart muscle. When the heart is contracting and pumping blood, air is suddenly released from the cuffs, creating a "drained" space in the lower body, thereby lowering resistance to the heart's pumping action. As a result, the heart has to do less work to pump out the amount of blood that the body needs.

Called the Prospective Evaluation of Enhanced External Counterpulsation in Congestive Heart failure study, it will evaluate improvements in exercise capacity and the quality of life for congestive heart failure patients. The study also will evaluate the reduction in the need for certain medications that congestive heart failure patients are typically prescribed.

"Heart failure affects nearly 5 million Americans and kills 250,000 people each year," said Arthur M. Feldman, Harry S. Tack Professor of Medicine at Pitt, director of UPMC's Cardiovascular Institute, immediate past president of the Heart Failure Society of America and coordinator for the national study.

The one-year study is expected to enroll 180 patients in 18 centers, including 15 patients at UPMC Presbyterian.

Congestive heart failure occurs when the heart is unable to pump enough blood to meet the body's demands, therefore failing to empty its chambers sufficiently. Blood then accumulates in the chest and lower limbs. Once diagnosed, the average survival for patients is approximately five years.

The study is sponsored by Vasomedical, Inc., the developer of EECP.


Research to study delivery of treatment for kids with behavioral problems in primary care

Researchers from the School of Medicine, in collaboration with Children's Community Care of Children's Hospital, have begun a study that may help them design more efficient ways of delivering treatment to children with mild behavior problems in the primary care setting.

The five-year study is being funded by the National Institute of Mental Health through a special initiative designed to promote the implementation of intervention strategies for children with disruptive behaviors in diverse, community settings.

Services for Kids in Primary Care (SKIP) is designed to evaluate the outcome of a brief treatment program designed for children with behavior problems and their parents. The special intervention to be studied includes a comprehensive intake evaluation, on-site behavioral health services from a trained study nurse or enhanced services as coordinated by their pediatrician, and follow-up evaluations to document the maintenance of any gains up to one year after treatment has ended.

"Children with behavior problems may need specialized behavioral health services, but the availability of or access to such services is limited," said David J. Kolko, associate professor of child psychiatry, psychology and pediatrics. "This study will evaluate the application of a specialized psychosocial treatment protocol for children with behavior problems that may improve the mental health assessment and treatment provided to children in primary care settings."

Participants in the SKIP study will be randomly assigned to receive one of two brief services: enhanced primary care services provided or coordinated by their own pediatrician, or behavioral health services provided in the office by a nurse clinician. Participants and their parents also will be asked to complete forms and interviews with a research assistant four times during the course of the study. Two of these assessments are follow-up evaluations designed to monitor progress after treatment.

Study using laser to break up brain clots UPMC Health System's Stroke Institute soon will begin testing the use of a laser to break up clots in the brain, potentially revolutionizing the way strokes are treated.

The Endovascular Photo Acoustic Recanalization (EPAR) Laser System is being investigated in a national phase 1 research study to test its safety and effectiveness in patients who are suffering a stroke due to arterial clots in the brain.

"This is another in the arsenal of weapons being developed to help minimize the disastrous effects of strokes," said Lawrence Wechsler, professor of neurology and neurosurgery and director of UPMC Health System's Stroke Institute.

"We are interested in proving that use of this device is safe and effective," said Charles Jungreis, professor of radiology and neurological surgery at Pitt's School of Medicine.

The device is intended to break up blood clots during ischemic strokes. The earlier a clot is removed and blood flow is returned to normal, the less the damage to the brain and the quicker a person can recover.

The EPAR device is composed of a laser and a micro-catheter, which is placed in the patient's blood vessel and advanced to the clot. Pulsed laser light is used to create a "mini shock wave" that gently breaks up the clot, restoring blood flow.

Stroke is the third most common cause of death and a leading cause of chronic disability in North America.

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