Apixaban proves superior to warfarin for preventing stroke, reducing bleeding and saving lives
August 28, 2011
A large-scale trial finds that apixaban, a new anticoagulant drug, is superior to the standard drug warfarin for preventing stroke and systemic embolism in patients with atrial fibrillation. Moreover, apixaban results in substantially less bleeding and also results in lower mortality.
The results were presented by Duke University Medical Center researchers at the European Society of Cardiology in Paris, France, today, and published simultaneously online in the New England Journal of Medicine.
“These are important findings because they show that, when compared to warfarin, a very effective treatment to prevent stroke, apixaban resulted in an additional 21 percent relative reduction in stroke or systemic embolism,” says Christopher B. Granger, M.D., the study’s lead author and professor of medicine at Duke. “It also resulted in a 31 percent relative reduction in major bleeding, as well as an 11 percent relative reduction in overall mortality.”
The improvement in stroke prevention was statistically significant with P=0.011, the lower rate of major bleeding at P<0.001, and the lower mortality at P=0.047. Hemorrhagic stroke was reduced by about 50%.
The randomized, double-blind clinical trial known as ARISTOTLE randomized 18,201 patients at 1034 clinical sites in 39 countries, giving them either 5 mg twice daily of apixaban or warfarin for an average of 1.8 years.
Apixaban has several major practical advantages over warfarin in addition to the therapeutic benefits, says John Alexander, M.D., a study co-author and Duke cardiologist. “It does not require monitoring and has few interactions with other medications or food. Apixaban was better tolerated than warfarin, with fewer discontinuations.”
The benefits of reducing stroke and lower rates of bleeding were consistent across all major subgroups, and despite the heterogeneity that exists in the quality of warfarin use across the world, says Alexander.
The number of events prevented per 1,000 people, which indicate absolute risk reduction, was also impressive, says Alexander. Apixaban prevented 6 patients from having a stroke, 15 patients from having major bleeding, and 8 patients from dying. The major effect on stroke prevention was on hemorrhagic stroke. Apixaban prevented 4 patients from having hemorrhagic stroke and 2 patients from having an ischemic or uncertain type of stroke.
Atrial fibrillation is a common abnormal heart rhythm that affects more than 2.6 million Americans. It occurs when the heart’s electrical activity becomes disorganized, resulting in an irregular heartbeat with ineffective contraction of the upper chambers of the heart. The potential for blood clots to form, and one’s risk for stroke, increases as a result.
Warfarin is a vitamin K antagonist that is well documented for its ability to prevent blood clots. Previous studies indicate that long-term use of warfarin in patients with atrial fibrillation and other stroke risk factors can reduce stroke by up to 70 percent. But only about half of patients who could benefit from warfarin actually do. Patients on warfarin must have regular blood tests to monitor and adjust the dose and avoid certain foods and medications that interfere with warfarin’s effect. Warfarin also increases bleeding rusj including including intracranial hemorrhage.
“There is an enormous unmet need for treatment of patients at risk for stroke associated with atrial fibrillation,” says Granger. “Only about half of patients who should be treated are being treated. The disparity exists because warfarin treatment has several limitations.”
Doctors and patients have been eagerly awaiting alternative therapies to warfarin, one of which is currently available. Several others are currently under investigation in large clinical trials.
Apixaban is an oral direct factor Xa inhibitor that showed promise last year when trial findings presented at the European Society of Cardiology showed apixaban patients were 54 percent less likely to have a stroke or blood clot than those who took aspirin. Apixaban and aspirin showed similar risks of major bleeding.
“Our study indicates treatment with apixaban is more effective than warfarin in preventing stroke without the need for anticoagulation monitoring,” says Lars Wallentin, M.D., the study committee’s co-chair, professor of cardiology, and director of the Uppsala Clinical Research Center University Hospital in Sweden.
The study also shows apixaban is safer than warfarin, according to Wallentin. “Our findings show a single dose of apixaban accomplishes the same stroke prevention goal as adjusted-dose warfarin with a substantially lower risk of all types of bleeding across different ages, and with lower rates of discontinuation.”
The study was coordinated by Uppsala Clinical Research Institute, Sweden and the Duke Clinical Research Institute.
It was funded by Bristol-Myers Squibb, Co and Pfizer Inc.
Additional study authors include: John J. V. McMurray, M.D., Cardiovascular Research Centre, University of Glasgow; Renato Lopes, DCRI; Elaine Hylek, Boston University; Michael Hanna, BMS; Hussein Al-Khalidi, DCRI; Jack Ansell, Lenox Hill Hospital; Dan Atar, Oslo University Hospital; Alvaro Avezum, Dante Pazzanese Institute of Cardiology; M. Bahit, ECLA Estudios Cardiologicos Latinoamerica; Rafael Diaz, ECLA Estudios Cardiologicos Latinoamerica; J. Donald Easton, Brown University; Justin Ezekowitz, University of Alberta; Greg Flaker, University of Missouri Health Care; David Garcia, University of New Mexico; Margarida Geraldes, BMS; Bernard Gersh, Mayo Clinic; Sergey Golitsyn, Russian Cardiology Research Center; Shinya Goto, Tokai University School of Medicine; J. Antonio Gonzalez-Hermosillo; Instituo N de Cardiologia Ignacio Chavez; Stefan Hohnloser, J.W. Goethe University; John Horowitz, University of Adelaide; Puneet Mohan, BMS; Petr Jansky, Motol University Hospital; Basil Lewis, Lady Davis Carmel Medical Center; Jose Lopez-Sendon, La Paz University Hospital; Prem Pais, St. John’s Medical College; Alexander Parkhomenko, Institute of Cardiology; Freek Verheugt, Radboud University Nijmegen Medical Centre; Jun Zhu, Fuwai Hospital
Contact: Debbe Geiger
Debbe.Geiger@duke.edu
919-660-9461
Duke University Medical Center
New study finds no nutritional difference between free-range and cage-produced eggs
August 27, 2011
Eggs produced by free-range hens are often perceived by the public to be nutritionally superior to eggs obtained from layers kept in traditional battery cages. However, a recent scientific study has called this popular perception into question by finding essentially no differences in the nutritional quality of eggs produced by hens from both management systems, said the Poultry Science Association (PSA).The findings also showed that cholesterol levels in all eggs were lower than U.S. Department of Agriculture guidelines, prompting the USDA to review and revise downward its estimates for average cholesterol levels in eggs.
The study, “Comparison of Fatty Acid, Cholesterol, and Vitamin A and E Composition in Eggs from Hens Housed in Conventional Cage and Range Production Facilities,” appeared in the July issue of Poultry Science, a journal published by PSA. Its author, Dr. Kenneth E. Anderson, a Professor in the Department of Poultry Science at North Carolina State University, collected data for the study in 2008 and 2009. The study was conducted concurrently with the North Carolina Layer Performance and Management Test (NCLP&MT), which evaluates the major commercial layer lines used in the United States.
“The key take away from this research is that an egg, no matter where it’s produced, is a very nutritious product. Eggs from a range production environment did have higher levels of total fat than eggs produced by caged hens, but they did not have higher levels of cholesterol. Perhaps the most striking finding was that both cage- and range-produced eggs actually have lower cholesterol levels than previously believed, which has led the USDA to lower the cholesterol guidelines for eggs in the USDA Nutrient Database for shell eggs to 185 mg per egg, down from 213 mg,” said Dr. Anderson.
Research Framework
Dr. Anderson conducted his study in North Carolina using more than 400 Hy-Line Brown pullets. The pullets were raised in accordance with the laying environment (range or cage) in the 37th NCLP&MT. All of the pullets in the study were hatch mates. Identical rearing dietary programs were used for both the range and cage pullets, with the only difference being the access the latter group had to the range paddock, a common hay mixture for North Carolina comprising both warm- and cool-season forages.
Pullets designated for the range facilities were brooded on litter until 12 weeks of age and then moved to a range environment. At 17 weeks, they were then moved to one of three production range paddocks. A parallel pattern was followed for the cage hens, which were reared in a cage rearing facility, and then at 17 weeks assigned to one of three groups of laying cages. All other rearing parameters were maintained as similar as possible.
Research Findings
Egg samples were collected at 50, 62, and 74 weeks of age during the productive life of the flock and sent to four different laboratories commonly used for egg nutrient analysis. The results showed no influence of housing environment (range or cage) on egg levels of vitamin A or vitamin E. However, β-carotene levels were higher in the range eggs, which, according to Dr. Anderson, may have contributed to the darker colored yolks observed in these eggs during the study. The study also found no difference in cholesterol content between range- and cage-produced eggs. Based on these results, Dr. Anderson concluded that “a significant nutritional advantage of eggs produced by chickens housed on range versus in cages could not be established.”
About PSA
The Poultry Science Association (PSA) is a global scientific society dedicated to the discovery and dissemination of knowledge generated by poultry research – knowledge that enhances human and animal health and well-being and provides for the ethical, sustainable, and economical production of food. Founded in 1908, PSA has a global membership of about 2,000. For more information, go to www.poultryscience.org.
About the American Egg Board (AEB)
AEB is the U.S. egg producer’s link to the consumer in communicating the value of The incredible edible egg and is funded from a national legislative checkoff on all egg production from companies with greater than 75,000 layers, in the continental United States. The board consists of 18 members and 18 alternates from all regions of the country who are appointed by the Secretary of Agriculture. The AEB staff carries out the programs under the board direction. AEB is located in Park Ridge, Ill. Visit www.IncredibleEgg.org for more information.
About the Egg Nutrition Center (ENC) The Egg Nutrition Center (ENC) is the health education and research center of the American Egg Board. Established in 1979, ENC provides science-based information to health promotion agencies, physicians, dietitians, nutritional scientists, media and consumers on issues related to egg nutrition and the role of eggs in the American diet. ENC is located in Park Ridge, IL. Visit www.eggnutritioncenter.org or www.nutritionunscrambled.com for more information.
Contact:
Egg Nutrition Center
Egg Nutrition News Bureau
312-233-1211
info@incredible-egg.org
Results of medication studies in top medical journals may be misleading to readers
August 26, 2011
Studies about medications published in the most influential medical journals are frequently designed in a way that yields misleading or confusing results, new research suggests.
Investigators from the medical schools at UCLA and Harvard analyzed all the randomized medication trials published in the six highest-impact general medicine journals between June 1, 2008, and Sept. 30, 2010, to determine the prevalence of three types of outcome measures that make data interpretation difficult.
In addition, they reviewed each study’s abstract to determine the percentage that reported results using relative rather than absolute numbers, which can also be a misleading.
The findings are published online in the Journal of General Internal Medicine.
The six journals examined by the investigators the New England Journal of Medicine, the Journal of the American Medical Association, The Lancet, the Annals of Internal Medicine, the British Medical Journal and the Archives of Internal Medicine included studies that used the following types of outcome measures, which have received increasing criticism from scientific experts:
Surrogate outcomes (37 percent of studies), which refer to intermediate markers, such as a heart medication’s ability to lower blood pressure, but which may not be a good indicator of the medication’s impact on more important clinical outcomes, like heart attacks.
Composite outcomes (34 percent), which consist of multiple individual outcomes of unequal importance lumped together such as hospitalizations and mortality making it difficult to understand the effects on each outcome individually.
Disease-specific mortality (27 percent), which measures deaths from a specific cause rather than from any cause; this may be a misleading measure because, even if a given treatment reduces one type of death, it could increase the risk of dying from another cause, to an equal or greater extent.
“Patients and doctors care less about whether a medication lowers blood pressure than they do about whether it prevents heart attacks and strokes or decreases the risk of premature death,” said the study’s lead author, Dr. Michael Hochman, a fellow in the Robert Wood Johnson Foundation Clinical Scholars Program at the David Geffen School of Medicine at UCLA’s division of general internal medicine and health services research, and at the U.S. Department of Veterans Affairs’ Los Angeles Medical Center.
“Knowing the effects of a medication on blood pressure does not always tell you what the effect will be on the things that are really important, like heart attacks or strokes,” Hochman said. “Similarly, patients don’t care if a medication prevents deaths from heart disease if it leads to an equivalent increase in deaths from cancer.”
Dr. Danny McCormick, the study’s senior author and a physician at the Cambridge Health Alliance and Harvard Medical School, added: “Patients also want to know, in as much detail as possible, what the effects of a treatment are, and this can be difficult when multiple outcomes of unequal importance are lumped together.”
The authors also found that trials that used surrogate outcomes and disease-specific mortality were more likely to be exclusively commercially funded for instance, by a pharmaceutical company.
While 45 percent of exclusively commercially funded trials used surrogate endpoints, only 29 percent of trials receiving non-commercial funding did. And while 39 percent of exclusively commercially funded trials used disease-specific mortality, only 16 percent of trials receiving non-commercial funding did.
The researchers suggest that commercial sponsors of research may promote the use of outcomes that are most likely to indicate favorable results for their products, Hochman said.
“For example, it may be easier to show that a commercial product has a beneficial effect on a surrogate marker like blood pressure than on a hard outcome like heart attacks,” he said. “In fact, studies in our analysis using surrogate outcomes were more likely to report positive results than those using hard outcomes like heart attacks.”
The new study also shows that 44 percent of study abstracts reported study results exclusively in relative rather than absolute numbers, which can be misleading.
“The way in which study results are presented is critical,” McCormick said. “It’s one thing to say a medication lowers your risk of heart attacks from two-in-a-million to one-in-a-million, and something completely different to say a medication lowers your risk of heart attacks by 50 percent. Both ways of presenting the data are technically correct, but the second way, using relative numbers, could be misleading.”
Still, the authors acknowledge that the use of surrogate and composite outcomes and disease-specific mortality is appropriate in some cases. For example, these outcomes may be preferable in early-phase studies in which researchers hope to quickly determine whether a new treatment has the potential to help patients.
To remedy the problems identified by their analysis, Hochman and McCormick believe that studies should report results in absolute numbers, either instead of or in addition to relative numbers, and that committees overseeing research studies should closely scrutinize study outcomes to ensure that lower-quality outcomes, like surrogate makers, are only used in appropriate circumstances.
“Finally, medical journals should ensure that authors clearly indicate the limitations of lower-quality endpoints when they are used something that does not always occur,” McCormick said.
The authors did not receive any internal or external funding for this research.
The Robert Wood Johnson Foundation focuses on the pressing health and health care issues facing our country. As the nation’s largest philanthropy devoted exclusively to improving the health and health care of all Americans, the Foundation works with a diverse group of organizations and individuals to identify solutions and achieve comprehensive, meaningful and timely change. For more than 35 years, the Foundation has brought experience, commitment, and a rigorous, balanced approach to the problems that affect the health and health care of those it serves. When it comes to helping Americans lead healthier lives and get the care they need, the Foundation expects to make a difference in your lifetime.
General Internal Medicine and Health Services Research is a division within the Department of Medicine at the David Geffen School of Medicine at UCLA. It provides a unique interactive environment for collaborative efforts between health services researchers and clinical experts with experience in evidence-based work. The division’s 100-plus clinicians and researchers are engaged in a wide variety of projects that examine issues related to access to care, quality of care, health measurement, physician education, clinical ethics and doctor/patient communication. The division’s researchers have close working relationships with economists, statisticians, social scientists and other specialists throughout UCLA and frequently collaborate with their counterparts at the RAND Corp and Charles Drew University.
Cambridge Health Alliance is an innovative, award-winning health system that provides high quality care in Cambridge, Somerville, and Boston’s metro-north communities. It includes three hospital campuses, a network of primary care and specialty practices, the Cambridge Public Health Dept., and the Network Health plan. CHA is a Harvard Medical School teaching affiliate and is also affiliated with Harvard School of Public Health, Harvard School of Dental Medicine, and Tufts University School of Medicine.
For more news, visit UCLA Newsroom and UCLA News|Week and follow us on Twitter.
Contact: Enrique Rivero
erivero@mednet.ucla.edu
310-794-2273
University of California – Los Angeles Health Sciences
HIV infection rates are on the rise
August 25, 2011
Since HIV infection rates began to rise again around 2000, researchers have been grasping for answers on what could be causing this change, especially in the homosexual community. The rising numbers are a stark contrast to the 1990′s, when infection rates dropped due to increased awareness of the virus. A new study in Israel reveals that the number of new HIV cases diagnosed each year in the last decade saw a startling increase of almost 500% compared to the previous decade, and similar trends have been reported in a number of other developed nations, including the U.S.
According to Prof. Zehava Grossman of Tel Aviv University’s School of Public Health at the Sackler Faculty of Medicine and the Central Virology Laboratory of the Ministry of Health, a new approach to studying HIV transmission within a community has yielded a disturbing result. By cross-referencing several databases and performing a molecular analysis of the virus found in patients, an astonishingly high number of newly-diagnosed men with male sexual partners were found to have contracted the virus from infected, medicated partners who are already aware of their HIV-positive status.
Reported in the journal Clinical Infectious Diseases, these findings indicate that the public health approach towards HIV counselling and education needs to be reconsidered, Prof. Grossman says.
Bypassing the questionnaires
Researchers had begun to suspect that the rise in infection rates was due to a change in social behavior, but hard evidence was lacking. The answers, Prof. Grossman says, were not easy to find by asking the patients themselves. Questionnaires and similar methods to gather information are hard to interpret because, in addition to the difficulty of recruiting an accurate cross-section of the population, people are often unwilling to be frank about risky sexual behavior.
To unravel the mystery, Prof. Grossman and her colleagues at the Central Virology Laboratory directed by Prof. Ella Mendelson and Israel’s leading AIDS clinicians turned to the virus itself. Working with senior epidemiologists of the Public Health Services of Israel’s Ministry of Health, they conducted a comprehensive analysis of laboratory, clinical, and epidemiological data, including information about patients’ diagnosis and treatment, sexually transmitted diseases contracted along with HIV, and the molecular characteristics of the virus in different patients.
Prof. Grossman and her colleagues found that an overwhelming number of new cases were infected with HIV strains that had already developed resistance to existing HIV drug therapies. Because the virus can only become resistant if previously exposed to medication, this result indicates that new patients are often infected by an HIV-positive partner already receiving the therapies. More often than in the past, HIV found in different patients could be traced back to a common source.
Changing the educational approach
While people are now more knowledgeable about the virus and aware of the risks of unprotected sex, it appears that an increasing number of homosexual men, including those who are infected and treated for HIV, are likely to engage in risky sexual behaviour. Public health authorities, educators, and activists should be encouraged to find new ways of changing this attitude and of better imprinting the message about the risk and consequences of HIV transmission, particularly within the gay community.
Clearly, Prof. Grossman warns, the need to establish the values of safe sex within at-risk populations is as imperative as it has ever been.
American Friends of Tel Aviv University (www.aftau.org) supports Israel’s leading, most comprehensive and most sought-after center of higher learning. Independently ranked 94th among the world’s top universities for the impact of its research, TAU’s innovations and discoveries are cited more often by the global scientific community than all but 10 other universities.
Internationally recognized for the scope and groundbreaking nature of its research and scholarship, Tel Aviv University consistently produces work with profound implications for the future.
Contact: George Hunka
ghunka@aftau.org
212-742-9070
American Friends of Tel Aviv University
Is marriage good for the heart?
August 22, 2011
Giving your heart to a supportive spouse turns out to be an excellent way to stay alive, according to new research from the University of Rochester. Happily wedded people who undergo coronary bypass surgery are more than three times as likely to be alive 15 years later as their unmarried counterparts, reports a study published online August 22 in Health Psychology, a publication of the American Psychological Association.
“There is something in a good relationship that helps people stay on track” says Kathleen King, professor emerita from the School of Nursing at the University of Rochester and lead author on the paper.
In fact, the effect of marital satisfaction is “every bit as important to survival after bypass surgery as more traditional risk factors like tobacco use, obesity, and high blood pressure,” says coauthor Harry Reis, professor of psychology at the University of Rochester.
But the marriage advantage plays out differently for men and women. For men, marriage in general is linked to higher survival rates and the more satisfying the marriage, the higher the rate of survival. For women, the quality of the relationship is even more important. While unhappy marriages provide virtually no survival bonus for women, satisfying unions increase a wife’s survival rate almost fourfold, the study found.
“Wives need to feel satisfied in their relationships to reap a health dividend,” explains Reis. “But the payoff for marital bliss is even greater for women than for men.” Some studies have suggested that marriage is not beneficial for women, Reis explains. But by factoring in the level of satisfaction, this research provides a more nuanced picture. “A good marriage gets under your skin whether you are male or female,” he says.
The researchers tracked 225 people who had bypass surgery between 1987 and 1990. They asked married participants to rate their relationship satisfaction one year after surgery. The study adjusted for age, sex, education, depressed mood, tobacco use, and other factors known to affect survival rates for cardiovascular disease.
Fifteen years after surgery, 83 percent of happily wedded wives were still alive, versus 28 percent of women in unhappy marriages and 27 percent of unmarried women. The survival rate for contented husbands was also 83 percent, but even the not-so-happily married fared well. Men in less-than-satisfying unions enjoyed a survival rate of 60 percent, significantly better than the 36 percent rate for unmarried men.
“Other research has shown that women are more physiologically sensitive to relationship distress than men, so an unhappy marriage can take a greater toll on their health,” explains Reis.
“Coronary bypass surgery was once seen as a miracle cure for heart disease,” says King. “But now we know that for most patients, graphs are a temporary patch, even more susceptible to clogging and disease than native arteries. So, it’s important to look at the conditions that allow some patients to beat the odds.”
King is skeptical of the widespread belief that a major health scare like going through bypass surgery leads to life-changing behavior. “The data show that many people go back to the lifestyle that they had before,” she says.
King says that this study points to the importance of ongoing relationships for both men and women. Supportive spouses most likely help by encouraging healthy behavior, like increased exercise or smoking cessation, which are critical to long-term survival from heart disease. She also suggests that a nurturing marriage provides patients with sustained motivation to care for oneself and a powerful reason to “stick around so they can stay in the relationship that they like.” These are qualities of the relationship that likely existed before bypass surgery, and continued afterward, says King.
The study cites earlier research showing that people with lower hostility in their marriages have less of the kind of inflammation that is linked to heart disease, which may help explain why people in this study benefited from satisfying marriages.
About the University of Rochester
The University of Rochester (www.rochester.edu) is one of the nation’s leading private universities. Located in Rochester, N.Y., the University gives students exceptional opportunities for interdisciplinary study and close collaboration with faculty through its unique cluster-based curriculum. Its College, School of Arts and Sciences, and Hajim School of Engineering and Applied Sciences are complemented by its Eastman School of Music, Simon School of Business, Warner School of Education, Laboratory for Laser Energetics, School of Medicine and Dentistry, School of Nursing, Eastman Institute for Oral Health, and the Memorial Art Gallery.
Contact: Melissa Greco Lopes
mgrecolo@admin.rochester.edu
585-276-3693
University of Rochester
Mayo Clinic receives FDA approval for ovarian and breast cancer vaccines
August 17, 2011
ROCHESTER, Minn. Mayo Clinic has received investigational new drug approval (http://www.fda.gov/BiologicsBloodVaccines/DevelopmentApprovalProcess/InvestigationalNewDrugINDorDeviceExemptionIDEProcess/default.htm) from the Food and Drug Administration (http://www.fda.gov/) for two new cancer vaccines that mobilize the body’s defense mechanisms to destroy malignant cells. The vaccines are among the first aimed at preventing cancer recurrence. The approval clears the way for Phase I clinical trials with women treated for ovarian or breast cancer.
VIDEO ALERT: Additional audio and video resources, including comments by Dr. Keith Knutson are available at the Mayo Clinic News Blog (http://dev.newsblog.mayoclinic.org/2011/08/17/mayo-clinic-studies-cancer-vaccines/).
“People who’ve had cancer are at high risk for relapse, and later rounds of treatment can become more difficult,” says Mayo Clinic immunologist Keith Knutson, Ph.D., (http://mayoresearch.mayo.edu/mayo/research/staff/Knutson_KL.cfm) who developed the vaccines with colleagues at Mayo Clinic. While most cancer vaccines to date have been developed to fight patients’ tumors, Knutson’s group is interested in immunizing patients immediately after therapy, when they’re healthy, to protect against relapse.
One new vaccine targets a protein that exists in abundance in breast and ovarian cancer cells. Containing fragments of the folate receptor alpha protein, the vaccine teaches the body’s immune system to detect and eliminate diseased cells. Because the protein is typical of nearly all breast and ovarian tumors, the vaccine is the first that may be applicable to the majority of patients, instead of sub-populations with distinct types of cancer.
“I’m quite optimistic that if we can combine early detection, effective conventional therapies and vaccination, we can reduce recurrence and long-term morbidity associated with breast and ovarian cancer,” Knutson says. Ultimately, the vaccine may be useful as a preventive strategy for all women.
The second vaccine to receive FDA approval is designed to be administered after breast cancer patients receive conventional chemotherapy. It targets the highly aggressive Her2/neu molecule, a protein that promotes the growth of cancer cells.
“One of the greatest fears for women who’ve been treated for breast cancer is that the cancer will return,” Knutson says. “Our hope is that the vaccine will boost the cancer-fighting capabilities of the immune system and will be a leg up on this aggressive cancer after conventional treatment is complete.”
About Mayo Clinic
Mayo Clinic is a nonprofit worldwide leader in medical care, research and education for people from all walks of life. For more information, visit www.mayoclinic.com and www.mayoclinic.org/news.
Contact:
Joe Dangor
507-284-5005 (days)
507-284-2511 (evenings)
Contact: Joe Dangor
newsbureau@mayo.edu
507-284-5005
Mayo Clinic
Want to keep your exercise resolutions? New research offers pointers
August 16, 2011
Sticking with an exercise routine means being able to overcome the obstacles that invariably arise. A key to success is having the confidence that you can do it, researchers report. A new study explores how some cognitive strategies and abilities increase this “situation-specific self-confidence,” a quality the researchers call “self-efficacy.”
“You can apply the concept of self-efficacy to every single health behavior you can think of because in many ways that really is what gets us through the day, gets us through the tough times,” said University of Illinois kinesiology and community health professor Edward McAuley, who led the research. “People who are more efficacious tend to approach more challenging tasks, work harder and stick with it even in the face of early failures.”
Those lacking self-efficacy often won’t even try to start a new routine, or will quit at the earliest sign of difficulty, McAuley said. “Almost 50 percent of people who begin an exercise program drop out in the first six months,” he said.
All is not lost, however, for those with low self-efficacy, McAuley said. Research has shown that there are ways to increase your confidence in relation to specific goals. Remembering previous successes, observing others doing something you find daunting and enlisting others’ support can increase your self-efficacy enough to get you started. Every step toward your goal will further increase your confidence, he said.
In the new study, published in the American Journal of Preventive Medicine, McAuley and his colleagues were interested in whether specific cognitive abilities and strategies enhanced older adults’ ability to stay with an exercise program by boosting their self-efficacy.
The researchers conducted a battery of cognitive tests on 177 men and women in their 60s and early 70s and also asked them whether and how often they set goals for themselves, monitored their progress, managed their time and engaged in other “self-regulatory” behaviors.
“These self-regulatory processes are really concerned with our ability to plan, to schedule physical activity into our daily life, to inhibit undesirable responses, such as sitting in front of the TV when you could be out working in your yard or walking around the block,” McAuley said. “These processes can be measured in a very objective way.”
The cognitive tests were “measures such as spatial memory, being able to multitask and being able to inhibit undesirable responses,” he said. Collectively, these tests assess what is known as “executive function.”
Participants were then randomly assigned either to a stretching, toning and balance program or a walking program that met three times a week for a year. Their self-efficacy was assessed after three weeks in the program.
The researchers found that some abilities and strategies did increase participants’ adherence to the exercise programs. Two executive function skills – the ability to multitask and to inhibit undesirable responses – significantly contributed to adherence by increasing self-efficacy, the researchers found. And more frequent use of self-regulatory strategies such as goal-setting, time management, self-monitoring and recruiting others for support increased study subjects’ participation in the program – again, by boosting their self-efficacy, McAuley said.
“We can potentially use this information to identify who might be poor adherers to an exercise program,” McAuley said. “And then offer those people an array of different coping skills and strategies to inhibit or overcome bad behaviors.”
Because executive function declines with age, McAuley said, previously sedentary older adults hoping to exercise more will likely benefit most if they adopt strategies that help them manage obstacles and build their self-efficacy.
Other studies have shown that aerobic exercise such as walking improves brain function in older adults. Thus, participation in an exercise program is likely to enhance cognitive functions that raise self-efficacy, positively reinforcing a person’s ability to pursue his or her exercise goals, McAuley said.
Edward McAuley is also a part-time faculty member of the Beckman Institute for Advanced Science and Technology. Collaborators on this study from the Illinois department of kinesiology and community health include postdoctoral researcher Sean Mullen and students Amanda Szabo, Siobhan White, Thomas Wójcicki, Emily Mailey, Neha Gothe and Erin Olson. Collaborators from the Beckman Institute include graduate research assistant Michelle Voss, postdoctoral researcher Kirk Erickson (now at the University of Pittsburgh), former doctoral student Ruchika Prakash (now at Ohio State University) and Beckman Institute director Art Kramer, who is a professor of psychology.
The National Institute on Aging funded this research.
Editor’s notes: To reach Edward McAuley, call 217-333-6487; email emcauley@illinois.edu.
The paper, “Self-Regulatory Processes and Exercise Adherence in Older Adults,” is available from the U. of I. News Bureau.
Contact: Diana Yates
diya@illinois.edu
217-333-5802
University of Illinois at Urbana-Champaign
Study reveals green tea is effective in treating genetic disorder and types of tumors
August 15, 2011
A compound found in green tea shows great promise for the development of drugs to treat two types of tumors and a deadly congenital disease. The discovery is the result of research led by Principal Investigator, Dr. Thomas Smith at The Donald Danforth Plant Science Center and his colleagues at The Children’s Hospital of Philadelphia. Their findings are published in the recent article, “Green Tea Polyphenols Control Dysregulated Glutamate Dehydrogenase In Transgenic Mice By Hijacking The ADP Activation Site” in The Journal of Biological Chemistry.
Glutamate dehydrogenase (GDH) is found in all living organisms and is responsible for the digestion of amino acids. In animals, GDH is controlled by a complex network of metabolites. For decades it was not clear why animals required such regulation but other kingdoms did not. This was partially answered by the Stanley group’s finding that a deadly congenital disease, hyperinsulinism/hyperammonemia (HHS), is caused by the loss of some of this regulation. In this disorder, patients (typically children) respond to the consumption of protein by over secreting insulin, becoming severely hypoglycemic, often leading to death.
Using atomic structures to understand the differences between animals and plants, Dr. Smith and his colleagues discovered that two compounds found naturally in green tea are able to compensate for this genetic disorder by turning off GDH in isolated and when the green tea compounds were administered orally. The Smith lab also used X-ray crystallography to determine the atomic structure of these green tea compounds bound to the enzyme. With this atomic information, they hope to be able to modify these natural compounds to design and develop better drugs.
Interestingly, two other research groups have validated and extended these findings to demonstrate that blocking GDH with green tea is very effective at killing two different kinds of tumors; glioblastomas, an aggressive type of brain tumor, and tuberous sclerosis complex disorder, a genetic disease that causes non-malignant tumors to grow on a number of organs.
“While these compounds from green tea are extremely safe and consumed by millions every day, they have a number of properties that make them difficult to use as actual drugs. Nevertheless, our ongoing collaboration with the Stanley lab shows that there are natural compounds from plants that can control this deadly disorder and, with the atomic structure in hand, can be used as a starting point for further drug design.”
About The Donald Danforth Plant Science Center
Founded in 1998, the Donald Danforth Plant Science Center is a not-for-profit research institute with a mission to improve the human condition through plant science. Research at the Danforth Center will feed the hungry and improve human health, preserve and renew the environment, and enhance the St. Louis region and Missouri as a world center for plant science. The Center’s work is funded through competitive grants and contract revenue from many sources, including the National Institutes of Health, U.S. Department of Energy, National Science Foundation, U.S. Department of Agriculture, U.S. Agency for International Development, the Bill & Melinda Gates and Howard G. Buffett Foundations.
The Donald Danforth Plant Science Center invites you to visit its new website, www.danforthcenter.org, featuring interactive information on the Center’s scientists, news, public education outreach, RSS feeds and the brand-new “Roots & Shoots” blog help keep visitors up to date with Center’s current operations and areas of research.
Contact: Melanie Bernds
mbernds@danforthcenter.org
314-587-1647
Donald Danforth Plant Science Center
Fat and healthy? Study finds thin isn’t always superior
August 15, 2011
A study out of York University has some refreshing news: Being fat can actually be good for you.
Published today in the journal Applied Physiology, Nutrition and Metabolism, the study finds that obese people who are otherwise healthy live just as long as their slim counterparts, and are less likely to die of cardiovascular causes.
“Our findings challenge the idea that all obese individuals need to lose weight,” says lead author Jennifer Kuk, assistant professor in York’s School of Kinesiology & Health Science, Faculty of Health. “Moreover, it’s possible that trying – and failing – to lose weight may be more detrimental than simply staying at an elevated body weight and engaging in a healthy lifestyle that includes physical activity and a balanced diet with plenty of fruits and vegetables,” she says.
Kuk’s team looked at 6,000 obese Americans over a 16-year span, comparing their mortality risk with that of lean individuals.
They found that obese individuals who had no (or only mild) physical, psychological or physiological impairments had a higher body weight in early adulthood, were happier with this higher body weight, and had attempted to lose weight less frequently during their lives. However, these individuals were also more likely to be physically active and consume a healthy diet.
Researchers used a newly-developed grading tool, the Edmonton Obesity Staging System (EOSS), which has been found to be more accurate than body mass index (BMI) for identifying who should attempt to lose weight. Developed by University of Alberta researchers, it is modelled on staging systems that classify the extent and severity of other diseases such as cancer, mental illness and heart disease. It offers five stages of obesity based on both traditional physical measurements such as BMI and waist-to-hip ratio, plus clinical measurements that reflect medical conditions often caused or aggravated by obesity (such as diabetes, hypertension and heart disease).
Kuk stresses that in order to determine whether or not they should lose weight, individuals should see a physician to be evaluated using the EOSS criteria.
The study, “Edmonton Obesity Staging System: Association with Weight History and Mortality Risk,” is co-authored by Chris Ardern, Assistant Professor, York University; Timothy S. Church, Director of the Laboratory of Preventive Medicine, Pennington Biomedical Research Center; Arya M. Sharma, Professor of Medicine & Chair in Obesity Research and Management at the University of Alberta, and Scientific Director of the Canadian Obesity Network; Raj Padwal, Associate Professor, University of Alberta; Xuemei Sui, Assistant Professor, University of South Carolina; and Steven N. Blair, Professor, University of South Carolina.
York University is the leading interdisciplinary research and teaching university in Canada. York offers a modern, academic experience at the undergraduate and graduate level in Toronto, Canada’s most international city. The third largest university in the country, York is host to a dynamic academic community of 50,000 students and 7,000 faculty and staff, as well as 200,000 alumni worldwide. York’s 10 Faculties and 28 research centres conduct ambitious, groundbreaking research that is interdisciplinary, cutting across traditional academic boundaries. This distinctive and collaborative approach is preparing students for the future and bringing fresh insights and solutions to real-world challenges. York University is an autonomous, not-for-profit corporation.
Contact: Melissa Hughes
mehughes@yorku.ca
416-736-2100 x22097
York University
How fatty diets cause diabetes
August 14, 2011
Newly diagnosed type 2 diabetics tend to have one thing in common: obesity. Exactly how diet and obesity trigger diabetes has long been the subject of intense scientific research. A new study led by Jamey D. Marth, Ph.D., director of the Center for Nanomedicine, a collaboration between the University of California, Santa Barbara and Sanford-Burnham Medical Research Institute (Sanford-Burnham), has revealed a pathway that links high-fat diets to a sequence of molecular events responsible for the onset and severity of diabetes. These findings were published online August 14 in Nature Medicine.
In studies spanning mice and humans, Dr. Marth’s team discovered a pathway to disease that is activated in pancreatic beta cells, and then leads to metabolic defects in other organs and tissues, including the liver, muscle and adipose (fat). Together, this adds up to diabetes.
“We were initially surprised to learn how much the pancreatic beta cell contributes to the onset and severity of diabetes,” said Dr. Marth.”The observation that beta cell malfunction significantly contributes to multiple disease signs, including insulin resistance, was unexpected. We noted, however, that studies from other laboratories published over the past few decades had alluded to this possibility.”
In healthy people, pancreatic beta cells monitor the bloodstream for glucose using glucose transporters anchored in their cellular membranes. When blood glucose is high, such as after a meal, beta cells take in this additional glucose and respond by secreting insulin in a timed and measured response. In turn, insulin stimulates other cells in the body to take up glucose, a nutrient they need to produce energy.
In this newly discovered pathway, high levels of fat were found to interfere with two key transcription factors – proteins that switch genes on and off. These transcription factors, FOXA2 and HNF1A, are normally required for the production of an enzyme called GnT-4a glycosyltransferase that modifies proteins with a particular glycan (polysaccharide or sugar) structure. Proper retention of glucose transporters in the cell membrane depends on this modification, but when FOXA2 and HNF1A aren’t working properly, GnT-4a’s function is greatly diminished. So when the researchers fed otherwise normal mice a high-fat diet, they found that the animals’ beta cells could not sense and respond to blood glucose. Preservation of GnT-4a function was able to block the onset of diabetes, even in obese animals. Diminished glucose sensing by beta cells was shown to be an important determinant of disease onset and severity.
“Now that we know more fully how states of over-nutrition can lead to type 2 diabetes, we can see more clearly how to intervene,” Dr. Marth said. He and his colleagues are now considering various methods to augment beta cell GnT-4a enzyme activity in humans, as a means to prevent and possibly cure type 2 diabetes.
“The identification of the molecular players in this pathway to diabetes suggests new therapeutic targets and approaches towards developing an effective preventative or perhaps curative treatment,” Dr. Marth continued. “This may be accomplished by beta cell gene therapy or by drugs that interfere with this pathway in order to maintain normal beta cell function.”
In the United States, more than 24 million children and adults – nearly eight percent of the population – have diabetes. In adults, type 2 diabetes accounts for about 90 to 95 percent of all diagnosed cases of diabetes. This study was primarily funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health (NIH). Co-authors of this study include Kazuaki Ohtsubo at Sanford-Burnham and Mark Z. Chen and Jerrold M. Olefsky from the University of California, San Diego.
For more information about Sanford-Burnham research, visit our blog (http://beaker.sanfordburnham.org) or follow us on Twitter (http://twitter.com/SanfordBurnham).
About Sanford-Burnham Medical Research Institute
Sanford-Burnham Medical Research Institute is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Sanford-Burnham, with operations in California and Florida, is one of the fastest-growing research institutes in the country. The Institute ranks among the top independent research institutions nationally for NIH grant funding and among the top organizations worldwide for its research impact. From 1999 – 2009, Sanford-Burnham ranked #1 worldwide among all types of organizations in the fields of biology and biochemistry for the impact of its research publications, defined by citations per publication, according to the Institute for Scientific Information. According to government statistics, Sanford-Burnham ranks #2 nationally among all organizations in capital efficiency of generating patents, defined by the number of patents issued per grant dollars awarded.
Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a nonprofit public benefit corporation. For more information, please visit www.sanfordburnham.org.
About Center for Nanomedicine
The Center for Nanomedicine (CNM) is a collaborative partnership that leverages and synergizes the expertise of two world-renowned institutions, Sanford-Burnham Medical Research Institute (Sanford-Burnham) and the University of California, Santa Barbara (UCSB). This model of collaboration brings together Sanford-Burnham’s biomedical research capabilities and UCSB’s biomedical engineering. The partnership creates fertile ground for developing the next generation of effective disease diagnostics and therapeutics.
Contact: Heather Buschman, Ph.D.
hbuschman@sanfordburnham.org
858-795-5343
Sanford-Burnham Medical Research Institute