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March 22, 2001

RESEARCH NOTES

UPMC offers bloodless cardiac surgery

UPMC Health System is offering patients who have religious or personal objections to receiving blood products the option of undergoing bloodless cardiac surgery.

The recently established Bloodless Cardiac Surgery Program draws on UPMC's years of experience performing heart valve replacement and coronary artery bypass procedures, as well as organ transplants, without the use of donated blood.

Jehovah's Witnesses constitute one population of patients who refuse transfusion for religious reasons. However, there may be a significant number of patients who delay or even decline surgery because of concerns about the blood supply. Bloodless surgery provides an alternative for those who feel strongly about avoiding transfusion.

"During a normal procedure patients lose anywhere from 100 cc to several units of blood, although it varies from patient to patient," said Brack Hattler, professor of surgery in the Pitt medical school's Division of Cardiothoracic Surgery. Hattler has performed more than 100 bloodless surgeries in 10 years.

Blood loss is reduced both during and after surgery using various techniques that allow patients to retain their own blood. Several weeks before surgery, patients are injected three times a week with epogen, a genetically engineered drug that stimulates production of red blood cells in bone marrow.

"The patient builds up to a supernormal level and can then stand to lose a small amount during surgery," Hattler explained. "Any amount of blood lost during surgery is captured and returned to the patient using a sophisticated operating room device called the Cellsaver, which is typically used during transplant operations to minimize donor blood requirements."

Surgeons also use laser coagulators to halt capillary bleeding.

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Researchers present research on preventing heart disease in older adults

New findings related to the development of heart disease in older adults were presented by Pitt researchers Feb. 28-March 3 at the American Heart Association's 41st Annual Conference on Cardiovascular Disease — Epidemiology and Prevention in San Antonio.

Coronary artery calcification related more to age than baseline risks Coronary artery calcification continues to increase in people into advanced old age and is more strongly related to age than to baseline risk factors, according to a Pitt study.

Anne B. Newman, associate professor of geriatric medicine and principal investigator, measured coronary artery calcification in 614 men and women with a mean age of 80 using electron beam tomography. The prevalence of clinical coronary vascular disease (CVD) was 33 percent, and another 33 percent had at least one marker of subclinical CVD.

Median CVD increased with age and was usually higher in men than in women, regardless of the presence or absence of clinical or subclinical CVD. No detectable coronary artery calcification was found in 6 percent of men and 11 percent of women, but the proportion with a zero score decreased with age from 15 percent under age 80 to 5 percent of those over 80 years.

Elevated homocysteine levels can lead to hypertension in healthy older adults Healthy older adults can develop hypertension if they have high blood levels of homocysteine, a metabolite of the essential amino acid methionine, and the risk increases if they are overweight and smoke, according to an eight-year study conducted at Pitt's Graduate School of Public Health.

"Elevated plasma homocysteine has been linked to arterial stiffness and the development of hypertension, but most of the previous research has been conducted using patients with renal disease and has been retrospective," said researcher Rachel Wildman. "This study is the first to assess homocysteine's effect on hypertension in healthy older adults with normal baseline blood pressure, and to follow them prospectively. Our results show that 35 percent of healthy adults could develop hypertension within eight years, and high homocysteine levels may increase the risk."

Wildman and her colleagues evaluated 187 men and women from the Carotid Assessment Program in the Elderly, a control population from the multi-center Systolic Hypertension in the Elderly Program. Median age was 71.

Over an eight-year period of observation, 35 percent of the participants developed hypertension. Higher homocysteine levels, higher body mass index, current smoking and higher systolic blood pressure levels were factors independently associated with the development of hypertension.

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Smaller cholesterol particles pose greater risk than larger ones in development of atherosclerosis

Small-sized low density lipoproteins (LDLs, or "bad" cholesterol) and high numbers of these particles pose a greater risk for coronary calcification among post-menopausal women than do medium- or large-sized LDLs, according to a study conducted at Pitt's Graduate School of Public Health.

"In post-menopausal women, the size and the concentrations of various-sized LDL particles may be a better predictor of atherosclerosis than the currently used standard cholesterol test, which measures the total amount of cholesterol carried by all the LDL particles, regardless of size," said researcher Rachel Mackey. "Some explanations of why the smaller LDL particles may be more atherogenic are that they might pass more easily into the arterial wall or that they may be more susceptible to oxidation."

Calcification of the coronary arteries occurs only where atherosclerosis or hardening of the arteries also is present. Thus, according to Mackey, calcification can signal the presence of atherosclerosis, which increases the risk of heart disease — the leading killer of women in the United States.

Findings presented by Mackey were based on 287 healthy, post-menopausal women aged 57-65 from Pitt's Healthy Women's Study, which looked at cardiovascular risk factor changes over the course of menopause.

In measuring LDL particle size, Mackey and her colleagues used a new laboratory test called the NMR LipoProfile (Lipo-Med, Inc.), which rapidly measures the size and concentrations of lipoproteins.

NMR (nuclear magnetic resonance) technology works by measuring and recording radio signals emitted by lipoproteins and other blood fats transported in the blood. The signals vary according to the size of the particles. A computer reads the signals and determines the concentration of each lipoprotein subclass by the strength of its signal.

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Cardiovascular Institute gets funds from golf tournament

Bill Hillgrove, sportscaster and play-by-play announcer for the Pitt Panthers and Pittsburgh Steelers, and Ron Simmons, president of Simmons Business Systems, recently presented a check for $151,001.17 to Arthur M. Feldman, director of UPMC Health System's Cardiovascular Institute.

The funds were raised during the Bill Hillgrove Invitational Golf Tournament held last summer at Alcoma Golf Club. This is the seventh year that the tournament has benefited the institute. Sponsors participating in the tournament have raised more than $450,000 for cardiovascular research.

UPMC Cardiovascular Institute provides treatments for every type of heart and vascular disease, including diagnostic and surgical procedures, heart disease and prevention programs, research projects and coronary rehabilitation programs.

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NASA-funded study at Pitt to simulate space mission sleep schedules

A new NASA-funded research study at Pitt's School of Medicine will help the space agency determine the safest method for rearranging astronauts' sleep schedules to meet time-critical mission demands.

"In space, night and day, as we know them, cease to exist," said Timothy H. Monk, Pitt professor of psychiatry. "In an orbiting spacecraft the sun rises and sets every 90 minutes, while the body clock is still running on a 24-hour cycle. It can wreak havoc on alertness and performance."

According to Monk, certain missions require astronauts to shift their sleep schedules several hours in order to be awake and alert for, say, a rendezvous with a satellite. If they made the time shift all at once, they would get crippling jet lag and might not be alert enough to carry out the mission safely. Imagine moving instantly from Sydney, Australia, to Pittsburgh and then being expected to work an eight-hour day.

In order to avoid these problems as much as possible, NASA developed "Appendix K," a set of rules that governs how and when astronauts can safely rearrange their sleep schedules.

For example, suppose repairs had to be made to a satellite that could only be reached by the space shuttle crew at 3 a.m. Performance would need to be optimal, so how could the crew best change their routine to be both awake and alert for the 3 a.m. rendezvous?

The solution, according to Appendix K, is to shift the sleep pattern gradually over several days, either by having the astronaut wake up later each day or earlier each day. The gradual shift allows the body clock to adjust more safely. The Pitt study will help NASA determine which direction of sleep shift works best.

In the research study, volunteers aged 30 to 59 will spend 16 days in the Biological Rhythms Laboratory (BRL) located in Western Psychiatric Institute and Clinic. The BRL is able to closely approximate the unusual time conditions that exist in space. It is a completely enclosed living space, similar to an apartment, in which there are no clues as to the true time of day — even light coming in through the "windows" is artificial and is controlled by technicians. During their stay in the BRL, study participants will be given performance tests so researchers can keep track of their alertness and ability to perform the types of tasks real astronauts need to do and will have their sleep and circadian rhythms measured.

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Nursing study aims to delay sexual behavior in adolescents

A Pitt nursing professor has received a $1.7 million grant from the National Institute of Child Health and Development for a five-year study seeking ways to delay early sexual behavior of 11- to 13-year-old African-American girls.

"The best time to intervene is early in adolescence, before girls become involved in high-risk sexual behaviors, inappropriate decision making, and adverse peer relationships," said Willa Doswell, principal investigator of this study and assistant professor at the School of Nursing.

During previous pilot studies examining the causes of teen pregnancy, Doswell discovered that preteen girls are more strongly influenced by their mothers than peers or siblings. Doswell's current four-part interventional study will give African-American mothers strategies for helping their daughters delay premature sexual behavior.

One component of the study will require girls to work with their mothers on special homework assignments dealing with sex. In another component, daughters and mothers will attend a sexual responsibility workshop together. Vignettes will be staged, giving girls an opportunity to act out hypothetical encounters with boys who want to be sexually active with them. In addition, each girl will be given a computerized, life-like baby to "care for" during a weekend. These dolls are the same size and weight as newborns and cry when they need to eat or have their diapers changed.

"We want to show pre-teen girls that caring for a baby is a big responsibility," Doswell explained.

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Neurosurgeon studies substitute brain covering

A Pitt neurosurgeon has begun a study to evaluate the use of a medical material created from pig intestines to substitute as a covering for the brain or spinal cord following trauma or surgery. The medical device is called Durasis Dural Substitute and is being studied to determine if it can be a good substitute for dura mater, which is the toughest and most fibrous layer of tissue covering the brain and spinal cord.

"Following most craniotomy procedures, the dura mater requires repair or augmentation in order to stop leakage of cerebral spinal fluid and prevent infection," said Ghassan Bejjani, assistant professor in the Department of Neurological Surgery and principal investigator in the study. "The ideal substitute for dura mater has not been found despite over 100 years of experimentation using many types of biologic and non-living tissues."

The ideal dura mater substitute, according to Bejjani, must be non-toxic, easily suturable, non-permeable, have minimal elasticity and be readily available and inexpensive.

In laboratory studies, Durasis (made from the pig small intestinal submucosa) has been found to have many of the ideal material properties required for repairing and replacing dura mater.

"Over time, Durasis is expected to take on the cellular characteristics of surrounding dural tissue," Bejjani said. "In addition to forming a nonpermeable barrier, Durasis acts as a scaffold on which human tissue grows. As it becomes overgrown with cells, it is absorbed by the body."

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Drug for COPD being studied

Pulmonologists from Pitt's Department of Pulmonary, Allergy and Critical Care Medicine are studying an experimental drug that could make breathing easier for people with chronic obstructive pulmonary disease (COPD).

COPD is a progressive illness that leads to the obstruction of air into and out of the lungs and shortness of breath. It includes chronic bronchitis, emphysema and asthmatic bronchitis; 90 percent of COPD is due to smoking. It is the fourth leading causes of death in the United States.

The international study will evaluate whether Spiriva (Tiotropium), a bronchodilator that opens the airway passages to make it easier for air to get in and out of the lungs, taken by inhalation once per day, can decrease the sensation of shortness of breath during exercise resulting in improvement in the length of time that a person can exercise.

"A study presented last year by researchers at the World Congress on Lung Health and the 10th European Respiratory Society Annual Congress showed that Spiriva was effective in improving key clinical and health outcomes in COPD patients," said Frank Sciurba, associate professor of medicine at Pitt and principal investigator in the study. "The drug is similar to Atrovent, which is a widely used bronchodilator. One of the main differences between the two drugs is that Spiriva can open up the airways for a longer period than Atrovent, which may allow patients to take fewer doses per day."

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Pitt to begin second phase of cell implant study for stroke patients

UPMC physicians have begun the second phase of an investigational clinical research study to evaluate the safety and efficacy of implanting nerve cells to reverse the neurologic deficits of stroke patients.

Layton BioScience Inc. of Sunnyvale, Ca., is sponsoring the study and manufactures the cells, called LBS-Neurons. Stanford University Medical Center also is participating in the study.

An earlier study by Pitt researchers found that the procedure was safe and feasible and that one year after implant half of the 12 stroke patients who underwent neuronal transplantation showed improvement in motor function. PET scan images, a measurement of metabolic activity in the area of the stroke, improved in six patients.

"We are encouraged by our initial studies," said Douglas Kondziolka, professor of neurological surgery and radiation oncology at Pitt and principal investigator on the study. "If therapy with LBS-Neurons proves effective in improving the neurologic deficits of stroke, it would have important health, quality of life and economic benefits for thousands of people."

"The University of Pittsburgh was the first in the world to undertake this pioneering research, which has the potential to make a significant impact on the way stroke is treated in the future," said L. Dade Lunsford, Lars Leksell professor and chairperson of the Department of Neurological Surgery and co-director of the Center for Image-Guided Neurosurgery at the School of Medicine. "It represents a major change in stroke medicine by addressing the issue of reversing neurological deficits from stroke."

"Participants in the study will be closely monitored," said Lawrence Wechsler, Pitt professor of neurology and neurosurgery, director of the UPMC Health System Stroke Institute and a co-investigator on the study. "Their neurologic status will be assessed before surgery and at numerous follow-up visits using various stroke measures. "

Stroke is the third leading cause of death and the most common cause of adult disability in the United States, according to the National Institutes of Health. Each year, 700,000 Americans suffer a stroke. Thirty percent die, and 20 to 30 percent become severely and permanently disabled. The total cost for caring for all aspects of stroke is estimated at $42 billion annually in the United States. Currently, rehabilitation through physical and occupational therapy is the only treatment available for patients with established stroke.

The procedure to implant LBS-Neurons 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 CT or MRI scan of the brain and the neurosurgical team makes its final decision for location of cell implantation.

Concurrently, the Pitt immunologic monitoring and diagnostic laboratory team thaws the human neuronal cells that were frozen by and transported from Layton BioScience Inc. to Pittsburgh. In the operating room, the cells are transferred to a long-needled syringe, and using the CT scan as a guide, neurological surgeons inject the cells through a small opening in the skull to the site of the damaged brain tissue. Patients are discharged from the hospital within 24 to 48 hours.

With the start of the second phase of the study, neurological surgeons and physicians in the UPMC Health System Stroke Institute are now reviewing the many hundreds of stroke patients who are on a waiting list of potential study participants.


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