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January 6, 2000

RESEARCH NOTES

Med school project gets research contract

The Image Engine Project, a system that combines clinical images with textual data, was recently awarded a two-year, $800,000 research contract from the National Library of Medicine (NLM) for work on the continuation, development and evaluation of this multimedia electronic medical record system. The Image Engine Project is housed at Pitt's School of Medicine.

Since 1994, the NLM has awarded nearly $3.2 million in research funding to support this medical informatics project, positioning UPMC Health System as a national leader in the area of informatics research.

"This new contract from the NLM and funding support from UPMC will allow us to scale and evaluate Image Engine as a complete multimedia patient record system at the University of Pittsburgh Cancer Institute," said Henry Lowe, director of Image Engine, associate professor of medicine and director of the University's Clinical Multimedia Laboratory in the Center for Biomedical Informatics. "This new system, called Chart Engine, extends the current Image Engine architecture by using secure Internet technologies and supporting access to an integrated multimedia view of the patient record on certain types of computer programs."

According to Lowe, most, if not all, existing computer medical records systems store only text. But increasingly, medicine has become very image-intensive, and clinical images have become an important part of a patient's medical records.

"This is a problem," Lowe said. "In the great majority of computer-based medical records systems, this increasingly important resource simply can't be stored in the system — maintaining the need for 'hard copy' files that undermine the speed and ease of a computerized system."

The Image Engine system, however, may ameliorate this problem. This type of computer system can store and retrieve visual images much the same way that traditional systems store text. Ideally, an image engine would be able not only to pull up a clinical image by patient name and type of image, but also by type of disease, stage of disease and even specified visual elements present in the image.

The system allows clinicians to download a series of thumbnail images on the screen that are used to help the physician select which full-size images to retrieve for viewing. Currently, the system can acquire, compress, store, retrieve, display and manipulate many kinds of clinical images, including radiographs, CT scans, MRI scans, nuclear medicine studies, gastrointestinal endoscopy images, EKGs and microscopic pathology.

Additionally, the system could aid in research. A researcher could scan a hospital's records for patients with a medical condition under study and correlate that condition with any number of diagnostic or treatment results.

Lowe explained that the system is secure, as it requires log-ons and passwords at every session and is firewalled and isolated from the Internet, ensuring confidentiality. "We're designing the system to provide access only to authorized users from anywhere in the world."

In effect, clinicians would be able to consult through use of Image Engine by simply taking a particular image and sending it through e-mail. This could be useful, according to Lowe, in situations where patients are seen by physicians in emergency situations while traveling out of state. Internet access could also facilitate collaborative research projects or telemedicine initiatives.

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Pitt develops virus for first intranasal equine influenza vaccine

Julius Youngner, distinguished service professor, and Patricia Whitaker-Dowling, associate professor, both in the department of molecular genetics and biochemistry at Pitt's School of Medicine, developed the live, attenuated virus used in the first equine intranasal influenza vaccine.

Scientific literature reports tests of a human vaccine based on the same technology. These human studies have been underway for approximately 10 years at institutions outside the University, and a human intranasal flu vaccine may be available in the near future.

The Pittsburgh researchers also worked in collaboration with investigators from the Heska Corporation of Fort Collins, CO, which will be manufacturing and marketing this new product, Flu Avert I.N. vaccine, to equine veterinarians.

"The majority of upper viral infections in horses can be attributed to equine influenza," Youngner said. "Previous vaccines were killed-virus injectable vaccines, which have been shown to leave horses vulnerable to equine influenza, even when horses are vaccinated up to six times a year."

Equine influenza is a serious disease in horses. Although infections are not usually life threatening, the disease is evidenced by coughing, fever, lack of appetite and tracheobronchitis, which can often lead to secondary bacterial pneumonia.

The studies involved more than 600 horses at locations throughout North America to verify both the safety and efficacy of Flu Avert I.N. vaccine. Previously, vaccines were licensed based on their ability to stimulate an antibody titer. These titers have been shown to decrease quickly and do not necessarily correlate with protection in the face of an outbreak. Flu Avert I.N. vaccine was tested in a challenge model in which both vaccinated horses and controls were heavily exposed to wild-type equine influenza virus. While the non-vaccinated horses showed the typical clinical signs of cough, fever, nasal discharge, poor appetites and depression, vaccinated horses were completely protected from clinical signs at three months and still demonstrated significant protection at six months and one year after vaccination.

"The cold-adapted virus used in the vaccine has a big advantage of replicating only at the temperature found in the upper respiratory tract," Whitaker-Dowling explained. "It produces the kind of immunity that a natural infection would, but doesn't make the animal sick."

Vaccination requires a 1 ml dose that is administered into one nostril. Administration of the vaccine is safe and painless, allowing horses to avoid the risk of injection site reactions and muscle soreness associated with vaccines that are administered with a needle.

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Geographic variation in heart attack deaths among men explained

Differences in smoking patterns and education levels among men in various states may account for wide fluctuations in the cardiovascular disease rates, according to a study at the Graduate School of Public Health.

In examining numbers of recorded deaths from coronary heart disease (CHD) in men aged 35-44 in different states and different countries, researchers found a surprisingly wide range of death rates across the United States.

Akira Sekikawa, principal investigator of the study, said: "Surprisingly, we found that the numbers of these younger men who die from CHD differ among regions of the United States as much as they differ among countries of the world."

Southern states have the highest rates of CHD deaths, and western states have the lowest. The study also revealed startling differences between CHD mortality in blacks and whites in the United States (44/100,000 men for blacks; 28/100,000 men for whites).

To account for the wide degree of variation among rates of CHD mortality, Sekikawa and Lewis H. Kuller, chair of epidemiology, pointed to variations in smoking and education levels, as indicated by records of deaths from cancers of the lung and bronchus and corresponding degree of cigarette smoking, and percentage of high-school graduates.

"The relatively strong correlation between mortality rates from CHD and cancer of lung and bronchus suggests that cigarette smoking is one of the potential candidates in the differences among CHD mortality rates," said Sekikawa.

Similarly, the researchers noticed a moderate correlation between the rates of CHD mortality among men aged 35-44 and rates of high school graduation.

Quality of emergency medical care was not considered in assessing the numbers of deaths because most of the victims die before help arrives.

To demonstrate the differences among states, as well as between blacks and whites, Sekikawa pointed to statistics showing that CHD mortality rates for southern black men are higher than for men in Poland, a country with one of the top CHD mortality rates (89/100,000 men in Mississippi, 67/100,000 men in Missouri, 63/100,000 men in South Carolina and 54/100,000 men in Poland). Conversely, rates for white men in western states such as Colorado, Utah and Washington rank alongside France (10-20/100,000), that has a relatively low rate as compared with other countries.

Less of a difference is noted in CHD mortality rates between blacks and whites in the east, with states such as New York, New Jersey and Pennsylvania having rates ranging between 25/ and 35/100,000 for men of both races.

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Pitt to study new drug for Lou Gehrig's Disease

University researchers are hoping to learn if a new investigational drug may offer a safe and effective treatment for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease. ALS is a fatal neurological disorder in which patients progressively lose the ability to use muscles that control the limbs and trunk as well as vital functions like speech, swallowing and breathing. ALS does not affect intellectual functioning. Approximately 200-300 people in western Pennsylvania have ALS.

Scientists do not know what causes ALS or how to cure it.

"ALS is one of the most devastating of the disorders that affect the functioning of nerves and muscles," said Michael J. Giuliani, professor of neurology at the School of Medicine and the study's principal investigator.

Most people who develop ALS are ages 40-70. The illness strikes males at a rate 1.4 to 2.5 times more than women. The life expectancy of an ALS patient averages 2-5 years from the time of diagnosis, but some may live more than 10 years.

ALS affects individuals at different rates and in different ways. Symptoms include twitching and cramping of muscles; impairment of the use of the arms and legs; "thick speech" and difficulty in projecting the voice; and in more advanced stages, shortness of breath, difficulty in breathing and swallowing.

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Researchers find genetic clues to preeclampsia

Women with changes in a gene that breaks down fatty particles are at four times the risk of developing the life-threatening condition preeclampsia, according to research published in Clinical Genetics by a team of investigators at Magee-Womens Research Institute and the University.

"This is one of the few findings to date linking specific genetic alterations with susceptibility to preeclampsia," stated Carl Hubel, principal investigator of the study at Magee-Womens Research Institute and assistant professor of obstetrics and gynecology and reproductive services at Pitt.

Preeclampsia, which develops in up to 7 percent of pregnant women, is the leading cause of maternal, fetal and neonatal disability and death. Preeclampsia often strikes suddenly, causing high blood pressure and metabolic problems that are relieved only after a baby is delivered. Untreated, preeclampsia may lead to eclampsia, an end-stage condition involving seizures. Female relatives of women who have had preeclampsia are as much as three times more likely to develop the condition themselves during pregnancy.

"For some time, we've known that changes in blood vessels lead to high blood pressure characteristically seen in this condition," said James Roberts, co-author on the study, director of Magee-Womens Research Institute and professor of obstetrics and gynecology and reproductive sciences. "We've also seen metabolic changes leading to excessive amounts of certain fats called triglycerides or VLDL (very low-density lipoproteins) in the blood of women with preeclampsia. Excessively high VLDL may trigger problems with the lining of blood vessels, contributing to progression of the disease."

The Pittsburgh team looked at blood samples from 330 Caucasian women, 104 of whom had preeclampsia and 226 of whom had uncomplicated pregnancies.

The investigators found that women with preeclampsia were more likely than women without this condition to have either one of two common mutations in the gene for lipoprotein lipase. This enzyme is responsible for clearing triglycerides from the blood.

Women with either gene mutation produce poorly functioning lipoprotein lipase. As a result, their blood carries excess triglycerides. Increased triglyceride levels are associated with increased risk of coronary disease. In addition, poorly functioning lipoprotein lipase causes lower levels of so-called "good cholesterol," or high-density lipoproteins (HDL), and promotes formation of abnormally small-sized low-density lipoproteins (small LDL), both of which also are associated with heart disease.

"These gene mutations do not commonly cause problems in non-pregnant women. Only when poorly functioning lipoprotein lipase is called upon to do excessive work — as in the case of pregnancy, obesity or diabetes — do problems become apparent," Roberts said.

The genetic analysis was carried out in collaboration with Robert Ferrell, professor in the Graduate School of Public Health.


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