PHILADELPHIA INTERNATIONAL MEDICINE NEWS BUREAU
Contact: Leonard N. Karp
lkarp@philadelphiamedicine.com
215-735-3989
June 24, 2002

For Immediate Release:

1. Penn Researchers Determine Urine Test Can Predict Diagnosis of Alzheimer's Disease

2. Temple Interventional Cardiologists Implanting Stent That May Dramatically Lower Risk of Subacute Stent Thrombosis

3. Jefferson Trial Looks to Improve Diagnosis of Prostate Canceron

4. Children's Hospital Hematologist Recognized For Patient-Oriented Research

Philadelphia -- Philadelphia International Medicine (PIM) hospitals are making the news with new research, new services and great outcomes. Below are three examples of how the hospitals of PIM are working hard to maintain their status as among the best health care organizations in the world. For more information, contact PIM at 215-735-3575.

Penn Researchers Determine Urine Test Can Predict Diagnosis of Alzheimer's Disease

A urine sample taken at the doctor's office can be the step in determining your chances of developing Alzheimer's disease (AD), according to researchers at the University of Pennsylvania Medical Center, part of Philadelphia International Medicine (PIM). They have determined that a urine test can reliably detect free radical damage associated with people with Mild Cognitive Impairment (MCI) - a recognized precursor to AD. The test detects isoprostanes, fatty acids that are formed as the result of free radical damage in the brain - damage that correlates with clinical diagnosis of AD.

"This is the first noninvasive test that can predict a clinical diagnosis of Alzheimer's disease," said Domenico Praticò, MD, assistant professor in Penn's department of pharmacology. "Since there is no cure for Alzheimer's disease, physicians could slow the course of the disease if it is caught early enough."

Within four years of initial diagnosis, up to 50 percent of people with MCI develop Alzheimer's disease. As AD progresses, it attacks the brain and causes severe damage in the areas important for memory, judgment and language.

This destruction leads to other clinical complications and, eventually, death. In the study, published in the June edition of Archives of Neurology, Praticò and his colleagues measured isoprostane in blood and urine samples obtained from 50 patients with a clinical diagnosis of AD, 33 patients with MCI, and 40 healthy volunteers. Two weeks later, a CSF sample and a second urine sample were taken from 28 of the AD patients, 17 of the MCI patients, and 18 of the control subjects. The researchers found significantly higher levels of isoprostane in CSF, blood and urine of MCI and AD subjects than in the volunteers. Remarkably, the samples taken from the MCI subjects and the volunteers differed only in respect to their isoprostane levels.

"We found that patients with MCI have increased brain oxidative damage before the onset of AD - damage that can be detected in the form of isoprostanes in urine, as this study shows," said Praticò. "In fact, five MCI subjects, all with high isoprostane levels, converted to AD during follow-up."

Patients that are diagnosed with Mild Cognitive Impairment typically present their physicians with persistent memory loss that is not normal for someone of their age and education. Although their memory is impaired, MCI patients are capable of living largely independent lives. At this stage, it is difficult to determine whether a person with MCI will eventually have Alzheimer's or whether they will progress to a form of unrelated dementia.

A urine sample taken in the doctor's office may be a first point of decision in gauging the risk of developing AD. Further tests could then determine the severity of a patient's condition and course of treatment. For example, studies have shown that the transition from MCI to AD occurs fastest in people who have a gene called apoE4 and whose brain's hippocampus region is shown to be smaller as measured in an MRI scan.

"One hypothesis is that, in AD, healthy brain tissue is damaged by the local formation of large amounts of free radicals," said Praticò. "Isoprostanes are the byproducts of fats in the human body that were warped by free radical attack. They then accumulate in CSF, blood, and urine as the body works to get rid of them."

While at the moment this test is not yet clinically available, the team is working on the development of a version of it that could be broadly and easily performed. Unlike a spinal tap, a urine test is simple to do and provides a painless and noninvasive way of assessing the situation. "The advantages are clear: with an easier test, doctors can diagnose the disease sooner and respond better to the patient's needs," said Praticò.

Temple Interventional Cardiologists Implanting Stent That May Dramatically Lower Risk of Subacute Stent Thrombosis

Interventional cardiologists at Temple University Hospital, a member of PIM, are the first in the region to have implanted a new type of coronary stent that has the potential to dramatically lower the risk of subacute stent thrombosis. The new line of stents, marketed under the name BiodivYsio, has a unique biocompatible monomer coating of phosphorylcholine (PC-coated) that mimics the surface of a red blood cell and has been shown in studies to reduce platelet and protein adhesion.

While risk of subacute stent thrombosis is typically about 1 percent, for patients who have suffered an MI the risk can be as high as 5 percent. "This new stent has the potential to lower the risk for subacute stent thrombosis, especially in the case of acute MIs and small vessels," says Timothy Jayasundera, MD, an interventional cardiologist and assistant professor of medicine at Temple.

The biocompatibility of the PC-containing polymer has been confirmed by several studies to reduce the thrombogenicity of PC-coated surfaces. "Because of the novel coating, the new stent has the potential to lower patients' risk of clot formation and prevents reocculation of the revascularized vessel," says Dr. Jayasundera.

A study specifically looking at "Six-month Results of Small Vessel Stenting" found that restenosis rates for the new stent were 10.6 percent versus 16.6 percent in the total group (J Invasive Cardiology 2001;13:628-631).

The BiodivYsio stent is available in several sizes including 2.0mm, making it the smallest size stent available on the market. Having the smallest crossing diameter gives it greater accessibility to lesion sites. "The small size and design allow us to revascularize the smaller vessels with greater confidence," says Jayasundera, who has used the new stent in several of his patients with great success.

Ideal candidates for the new PC-coated stents include patients with smaller vessels; patients who are undergoing percutaneous intervention (PCI) for acute MI; those with bifurcation lesions; and those with conditions that would prevent optimal anti-platelet therapy, such as a previous history of stroke or bleeding conditions.

"For our patients, this new stent is one of the stents of choice at this time," says Jayasundera. "The company that produces the PC-coated stent will be introducing a drug-eluting stent based upon this platform, which has exciting potential in the future."

Stent technology is an area where great advances are being made. "At Temple, we are committed to offering the latest technologies available for our patients. Being the first in the region to use the new PC-coated stent is a perfect illustration of that commitment," says Jayasundera.

Jefferson Trial Looks to Improve Diagnosis of Prostate Cancer

Radiologists and urologists at Thomas Jefferson University Hospital and Jefferson 's Kimmel Cancer Center, members of Philadelphia International Medicine, are hoping a new type of imaging can improve the diagnosis of prostate cancer. They are conducting the first large-scale clinical trial in the United States to find out whether a form of ultrasound that uses a contrast agent can improve detection and cut the cost of diagnosis.

Diagnosing prostate cancer can be frustrating. Standard methods, such as the prostate specific antigen (PSA) test and the digital rectal examination, often turn up false positives. The digital rectal exam, in particular, is simple and inexpensive - and subjective and inexact. And screening studies can't pinpoint a cancer's exact location. As a result, biopsies of the prostate are performed on areas that are only best guesses where cancer may lie.

Some 200,000 cases of prostate cancer are diagnosed annually in the United States, yet only one in three persons receiving a biopsy is found to have cancer. Physicians and patients would like a better way. The key to the trial's success, says Ethan Halpern, MD, professor of radiology and urology at Jefferson Medical College of Thomas Jefferson University, who is leading the study, lies in the nature of the cancerous tumor itself.

Cancerous tissue in the prostate may have up to twice as many blood vessels as does healthy tissue. Many researchers believe that without this additional blood supply, cancerous tumors cannot grow and spread.

But Halpern, who is co-director of the Jefferson Prostate Diagnostic Center, says that conventional Doppler ultrasound may not be good enough to find those tumors that contain more blood vessels than usual. In addition, it can only detect vessels larger than 1 to 2 mm in size. Contrast-enhanced ultrasound, he says, can detect vessels smaller than 1 mm.

Halpern believes that by using contrast-enhanced ultrasound "we can find areas in the prostate that have more blood vessels," enabling physicians to direct biopsies there. At the same time, he says, "We hope to show that those areas in the prostate that don't have more vessels don't require biopsy."

Once cancer is suspected, say by a high or rising PSA, says Halpern, the standard procedure is the sextant biopsy - six biopsies distributed on the prostate gland. But since no one knows where the cancer is, a negative result doesn't rule out cancer. If the PSA continues to go up, another sextant biopsy is performed three to six months later. Halpern and his team hope to be able to improve cancer detection with fewer biopsies.

"We'd like to find the clinically significant cancers that will impact a person," he says. "By looking for cancers located in vessel-rich tissue, we're hoping that not only will we improve the detection of cancer, we'll improve the detection of clinically significant cancers that will more likely be dangerous to the patient. It may not be important if we miss tumors with fewer vessels because we think they will be less dangerous." Cancers that are vascular-rich, he notes, are more likely to spread.

While prostate cancer is the most common male cancer in the Western world and the second leading cause of cancer death in men, it is a disease men often die with, not of. It can be extremely slow growing; half of all men who die at age 80 have prostate cancer, though they may not necessarily have any symptoms or even know it.

In the study, every patient is evaluated first with both standard "gray scale" and Doppler ultrasound. The exam is repeated twice, once before infusion of the contrast agent and again during the infusion. A biopsy of suspicious areas in each part of the prostate is performed during infusion of the contrast agent.

The contrast agent being studied, Imavist (AF0150), is awaiting final approval from the U.S. Food and Drug Administration (FDA). Halpern is evaluating the enhancement provided by Imavist with conventional Doppler imaging as well as a newer harmonic gray scale inversion technique. "The phase inversion technique provides better spatial and temporal resolution," he notes. He adds that these techniques may enable them to identify slight irregularities in the normal prostate blood flow pattern that are not seen with conventional Doppler.

The researchers plan to follow the patients with positive biopsies for three years to see if contrast-enhanced imaging can also predict which cancers are more aggressive and more likely to return after treatment.

"If this new method is shown to be sensitive for detection of moderate- to-high-grade cancers of the prostate, many future patients could avoid biopsy," he says.

The Jefferson Prostate Diagnostic Center aims to improve the detection of cancer within the prostate, providing state-of-the-art prostate imaging and biopsies.

Children's Hospital Hematologist Recognized For Patient-Oriented Research

Katherine A. High, MD, director of hematology research at The Children's Hospital of Philadelphia, a member of PIM, has been named a Howard Hughes Medical Institute (HHMI) investigator. High is one of 12 physician-scientists recently selected by the prestigious research organization for major accomplishments in patient-oriented research.

"We are extremely pleased and proud of the fact that one of our physicians was honored by one of the world's leading biomedical research institutions," said Steven M. Altschuler, MD, president and chief executive officer of The Children's Hospital of Philadelphia. "This appointment recognizes High's pioneering achievements in advancing gene therapy, a novel field of medicine."

High is internationally prominent for her studies of the molecular biology of the inherited bleeding disorder hemophilia. Over the past decade, she has investigated a gene transfer approach to treating hemophilia B, the form of hemophilia caused by a deficiency of blood clotting factor IX. That approach holds the potential of treating human disease at a fundamental level, by delivering therapeutic genes directly into a patient's cells.

In 1999, High's research team showed that gene therapy could achieve long-term improvement in dogs having naturally occurring hemophilia. Based on these studies, she and her collaborators have undertaken human gene therapy trials seeking to improve blood clotting in patients with severe hemophilia B. Even small increases in clotting factor in a patient's blood can improve hemophilia from a severe form to a much milder form, and result in great improvements in quality of life.

She leads an NIH-funded laboratory and is active in many scientific societies, particularly the American Society of Hematology, the American Society for Gene Therapy and the International Society on Thrombosis and Hemostasis.

Established in 1953, the Howard Hughes Medical Institute is a nonprofit medical research organization that currently supports approximately 325 investigators throughout the United States. Based in Maryland, the Institute conducts medical research and supports science education in the United States and biomedical scientists in other countries. The most recent group of 12 investigators was chosen because their combination of scientific expertise and medical training holds great potential for translating basic science discoveries into useful medical treatments.

Philadelphia International Medicine is an organization that provides medical and patient support services to international patients. It also provides continuing medical education and health care training and education to international physicians, administrators and other practitioners. As the international department of several Philadelphia-area hospitals, international patients gain access to physicians and hospitals rated among the best in the world through one telephone call to PIM. You can reach PIM by calling 1-215-735-3575; fax, 1-215-790-1267; or e-mail, physicians@philadelphiamedicine.com. You can find out more about PIM through its Website at www.philadelphiamedicine.com.

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