Stroke Study Reveals a Key Target For Improving Treatment

For over a decade, the drug called tPA has proven its worth as the most effective emergency
treatment for the most common kind of stroke. But its promise is blemished by two facts: tPA can cause dangerous bleeding in the brain, and its brain-saving power fades fast after the third hour of a stroke.

Now, a new paper published online in Nature Medicine reveals why tPA has these limitations. It also gives tantalizing evidence about how those problems might be overcome, if a stroke victim first takes a drug currently used to treat leukemia.

The researchers, from the University of Michigan and the Ludwig Institute for Cancer Research (LICR) Stockholm Branch at Karolinska Institutet in Stockholm, Sweden, emphasize that it's still too early to apply their findings -- made in mice -- to the treatment of stroke victims
everywhere.

But the LICR-Karolinska Institutet team will soon begin a clinical trial to test the theory in humans, using the leukemia drug known as imatinib (Gleevec). In mice, that drug greatly reduced bleeding, even if tPA wasn't given until five hours after a stroke began.

The new paper details a series of molecular and cellular experiments conducted by the two teams, which began collaborating after hearing of each other's work.

They report that tPA apparently causes its risk of bleeding, and leakage of fluid within the brain, by accident. The culprit: tPA's tendency to act upon a protein called PDGF-CC, and the PDGF-alpha receptor that it binds to. This interaction causes the usually impervious "blood-brain barrier" to become porous, leading to leakage. Gleevec inhibits the PDGF-alpha receptor, apparently counteracting tPA's effect.

This unwanted effect on the blood-brain barrier appears to be unrelated to tPA's main job, which is to break down clots that have lodged in the brain's blood vessels, cutting off blood supply to the area and starving brain tissue until it begins to die.

Such clots cause 80 percent of the 15 million strokes that occur each year worldwide. Five million people die, and 5 million more are permanently disabled, by strokes each year, according to the World Health Organization.

"Our findings may have immediate clinical relevance, and could be applied to find new treatments that will benefit stroke patients," says senior author Daniel Lawrence, professor of cardiovascular medicine in the U-M Medical School and member of the U-M Cardiovascular Center. "By better understanding how the brain regulates the permeability of the blood-brain barrier, and how tPA acts upon that system, we hope to reduce the risks and increase the time window for stroke treatment."

Ulf Eriksson, the leader of the team at the Ludwig Institute for Cancer Research Stockholm Branch at Karolinska Institutet, comments, "Our research group identified the growth factor PDGF-CC 10 years ago and we are now very excited having unraveled a mechanism in the brain involving this factor, which potentially will be a revolution in the treatment of stroke. Together with our clinical colleagues at the Karolinska University Hospital in Stockholm we are now rapidly continuing to explore this exciting possibility in clinical trials involving stroke patients."

If the clinical trial in human patients in Sweden bears out the findings seen in mice, perhaps Gleevec could be given immediately upon suspicion of stroke-like symptoms, before diagnostic scans and other tests can be made to determine if a patient could benefit from tPA.

Watch more breaking news now on our video feed:



Bookmark http://universeeverything.blogspot.com/ and drop back in sometime.

Foundation Announces $500 Million Commitment to Reverse Childhood Obesity in U.S.

The Robert Wood Johnson Foundation (RWJF) today announced it will commit at least $500 million over the next five years to tackle one of the most urgent public health threats facing the United States: childhood obesity. This is the largest commitment by any foundation to this issue, RWJF says. The foundation's goal is to reverse the epidemic of childhood obesity in the United States by 2015.

During the past four decades, obesity rates have soared among all age groups, more than quadrupling among children ages 6 to 11. Today, more than 33 percent of children and adolescents -- approximately 25 million kids -- are overweight or obese.

Preventing obesity during childhood is critical, because habits that last into adulthood frequently are formed during youth. Research shows that overweight adolescents have up to an 80 percent chance of becoming overweight or obese adults. Earlier onset of obesity leads to the earlier onset of related illnesses, such as type 2 diabetes, heart disease, stroke, and certain types of cancer.

In addition to the toll on U.S. health, obesity also poses a tremendous financial threat to the U.S. economy and health care system. It's estimated that the obesity epidemic costs the United States $117 billion per year in direct health care costs and lost productivity. Childhood obesity alone carries a huge price tag -- up to $14 billion per year in direct healthcare costs to treat kids.

"This is an all-American crisis," says Dr. Risa Lavizzo-Mourey, M.D., M.B.A., president and CEO of RWJF. "It affects all Americans, and it will require all of America working together to turn it around. Our commitment is a call to action for families, schools, government, industry, healthcare and philanthropy. To reverse the obesity epidemic and create a culture of health, we must provide families with better access to healthy choices."

The foundation says it will focus on improving access to affordable healthy foods and opportunities for safe physical activity in schools and communities. It will place special emphasis on reaching children at greatest risk for obesity and related health problems: African-American, Latino, Native American, Asian American and Pacific Islander children living in low-income communities.

Bookmark http://universeeverything.blogspot.com/ and drop back in sometime.

Study: MRI and Echocardiography Together Can ID More Causes of Stroke Before They Strike

Based on a new study released today, researchers urge more comprehensive imaging for patients presenting to hospitals with stroke symptoms. Using both MRI and echocardiography to image the heart greatly enhances the detection of thecause and selection of the best treatment of cardioembolic strokes, the"meanest" type of stroke.

A cardioembolic stroke occurs when a thrombus (clot) dislodges from the heart, travels through the cardiovascular system and lodges in the brain, first cutting off the blood supply and then often causing a hemorrhagic bleed -- a double whammy of both types of stroke, ischemic first and then hemorrhagic. The study found that MRI detected nearly twice as many sources of stroke in the heart than echocardiogram alone. It also showed theability of MRI to reveal more heart disease conditions that contribute to clot formation in the first place. Echocardiography, however, was strong inthe detection of heart valve lesions. Combined, these imaging systems can more clearly identify underlying causes of future stroke, helping doctors decide the best initial therapy and the best treatment to prevent asecondary stroke.

The research was presented today at the Society of Interventional Radiology's 32nd Annual Scientific Meeting.

"This can revolutionize patient care because we can detect the underlying cause of the stroke and prevent it from occurring again," says lead author John Sheehan, M.D., an interventional radiologist at Northwestern University and Northwestern Memorial Hospital. "A potential cardiac source should be considered in all patients presenting with ischemic strokes. All stroke patients should routinely have an MRI and ultrasound of their heart, in addition to having their brain and carotids imaged with CT and MRI. It's nice to be on the front end of a stroke --able to stop it, than on the back end, figuring out how to deal with its damage."

Stroke teams generally consist of emergency room physicians, neurologists and interventional radiologists. Interventional radiologistsare a critical part of the stroke team because they can diagnose and treatischemic stroke with clot-busting drugs, or open a blocked carotid artery nonsurgically. They are also actively involved in creating more stroke teams across the country.

Cardioembolic strokes, which account for 20 percent of embolic strokes,have a worse prognosis, producing larger, more disabling strokes that aremore likely to recur compared to other types of stroke. Blood clots can betreated with drugs before they can leave the heart, in conjunction with treating identified heart conditions, to prevent another life-threatening stroke. In the United States stroke is the leading cause of adult disability and the third leading cause of death; only heart disease and cancer cause more deaths annually.

In the study, of the 93 patients who had an MRI and echocardiogram oftheir heart after a stroke, MRI detected nearly twice as many potential causes of stroke originating from the heart compared to echocardiography. MRI also detected significant heart conditions that predispose a patient tostroke in 30 percent of patients compared to echocardiography. These additional findings included acute myocardial infarction, myocardial scarring and left ventricular aneurysms. Echocardiography was, however,more sensitive to detecting potential embolic lesions on prosthetic cardiacvalves and strokes related to a hole in the heart.

Bookmark http://universeeverything.blogspot.com/ and drop back in sometime.