Living long, living well

Brandeis experts discuss their research to improve the number of good years lived

Waltham, Mass., 28 mar 2009—How does inflammation, brought on by stress, affect aging? What can we do to avert the looming public health and economic crisis of an epidemic of neurologic diseases caused by a rapidly expanding elderly population? How do older adults manage to keep a rosy outlook in the face of inevitable decline? How does exercise enhance memory function?

These and a host of other questions are the focus of the inaugural conference of the Brandeis Lifespan Initiative on Healthy Aging (LIHA) Friday, April 3, 2009, 8:30 a.m. to 12:30 p.m., at the Hassenfeld Conference Center at Brandeis University. Free and open to the public, the conference will showcase Brandeis' interdisciplinary research on healthy aging, focusing on biomedical, behavioral, and social factors that influence aging.

Anyone with a personal, professional, or scholarly interest in cutting edge research on healthy aging, from students and consumers of all ages, to elder advocates and academics, will find the half-day open forum stimulating and relevant.

Short, engaging presentations will address topics that range from the impact of hearing loss on cognitive abilities and the complex role of DNA in aging, to why nursing homes need to change the conventional model of care. There will also be time for questions after each presentation, and posters will graphically display key research findings. For a complete schedule of events, please visit http://www.brandeis.edu/lifespaninitiative/. RSVP healthyaging@brandeis.edu or call 781-736-3302.

"We take a lifespan approach that emphasizes prevention and intervention as early as possible, in contrast to the more conventional focus on treatment after problems or declines have begun," explained Professor Margie Lachman, LIHA's chair. "Although it is often "never too late" to make a difference, our research suggests that it is "never too soon" to begin thinking about successful aging."

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LIHA is a multidisciplinary, multicultural, and integrative initiative drawing scholars from biology, chemistry, medicine, neuroscience, social policy, psychology, sociology, economics, business, anthropology, history, human factors engineering, nutrition, art and literature. The initiative is establishing partnerships with other universities and institutions in Greater Boston committed to advancing healthy aging and lifelong wellbeing.

Tiny but toxic: MBL researchers discover a mechanism of neurodegeneration in Alzheimer's disease

WOODS HOLE, MA, 28 mar 2009—Tiny, toxic protein particles severely disrupt neurotransmission and inhibit delivery of key proteins in Alzheimer's disease, two separate studies by Marine Biological Laboratory (MBL) researchers have found.

The particles are minute clumps of amyloid beta, which has long been known to accumulate and form plaques in the brain of Alzheimer's patients.

"These small particles that haven't aggregated into plaques—these are increasingly being seen as the really toxic species of amyloid beta," says Scott Brady of University of Illinois College of Medicine, who has been an MBL investigator since 1982.

Brady and his colleagues found that these particles inhibit neurons from communicating with each other and with other target cells in the body.

"The disease symptoms for Alzheimer's are associated not with the death of the neurons – that is a very late event – but with the loss of functional connections. It's when the neuron is no longer talking to its targets that you start to get the memory deficits and dementia associated with the disease," Brady says.

The amyloid beta particles activate an enzyme, CK2, which in turn disrupts the "fast axonal transport" system inside the neuron, Brady found. This transport system has motor proteins that move various kinds of cargo (including neurotransmitters and the associated protein machinery for their release) from place to place in the neuron on microtubule tracks.

Brady's findings are complemented by a new study by Rudolfo Llinás of New York University School of Medicine. Brady and Llinás both conduct neuroscience research at the MBL using the giant nerve cell of the Woods Hole squid, Loligo paeleii, as a model system.

Llinás found that activation of CK2 blocks neurotransmission at the synapse – the point where the neuron connects to its target.

"Disruptions in the fast axonal transport system are probably key elements in the pathogenesis of Alzheimer's and other adult-onset neurodegenerative diseases, such as Parkinson's and ALS," says Brady. "It doesn't mean that is the only thing going on, or that it is the triggering feature of the disease. But we do know that changes in the fast axonal transport system are sufficient to cause the 'dying back' of neurons that is characteristic of these diseases."

The new findings suggest the possibility of designing a drug to inhibit CK2 activation in Alzheimer's patients. However, a prior study by Brady found that activation of another enzyme, GSK3, in Alzheimer's also disrupts the fast axonal transport system. It may therefore be necessary to inhibit both enzymes.

"There haven't yet been any therapies designed for Alzheimer's with the idea of protecting the fast axonal transport system," says Brady. "But if there were, they would have to inhibit the activation of both CK2 and GSK3. We can't think of it as a single thing going wrong. There are several things going wrong."

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Citations:

Pigino, G., et al. (2009) Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid beta. PNAS: doi 10.1073/pnas0901229106.

Moreno, H. et al. (2009) Synaptic transmission block by presynaptic injection of oligomeric amyloid beta. PNAS: doi 10.1073/pnas09000944106.

MSU researcher links cholesterol crystals to cardiovascular attacks

Findings shift how doctors approach cardiovascular care

EAST LANSING, Mich., 28 mar 2009 --- For the first time ever, a Michigan State University researcher has shown cholesterol crystals can disrupt plaque in a patient's cardiovascular system, causing a heart attack or stroke.

The findings by a team led by George Abela, chief of the cardiology division in MSU's College of Human Medicine, could dramatically shift the way doctors and researchers approach cardiovascular attacks. Abela's findings appear in the April issue of the American Journal of Cardiology.

"Any time there is something completely new or unique in medical research, it is met with healthy skepticism," said Abela, who has been working with cholesterol crystals since 2001. "But we have found something that can help dramatically change how we treat heart disease."

What Abela and his team found is that as cholesterol builds up along the wall of an artery, it crystallizes from a liquid to a solid state and then expands.

"As the cholesterol crystallizes, two things can happen," Abela said. "If it's a big pool of cholesterol, it will expand, causing the 'cap' of the deposit to tear off in the arterial wall. Or the crystals, which are sharp, needle-like structures, poke their way through the cap covering the cholesterol deposit, like nails through wood."

The crystals then work their way into the bloodstream. It is the presence of this material, as well as damage to an artery, that disrupts plaque and puts the body's natural defense mechanism -- clotting -- into action, which can lead to dangerous, if not fatal, clots.

Abela and his team studied coronary arteries and carotid plaques from patients who died of cardiovascular attacks. When comparing their findings against a control group, they found evidence of cholesterol crystals disrupting plaque.

The breakthrough in discovering the crystals' impact came after Abela and colleagues found a new way to preserve tissue after an autopsy, using a vacuum dry method instead of an alcohol solution. The previous method would dissolve the crystals and prevent researchers and doctors from seeing the impact.

Abela also has found that cholesterol crystals released in the bloodstream during a cardiac attack or stroke can damage artery linings much further away from the site of the attack, leaving survivors at even greater risk. The research means health care providers now have another weapon in their arsenal against cardiovascular diseases.

"So far, treatments have not been focused on this process," Abela said. "Now we have a target to attack with the various novel approaches. In the past, we've treated the various stages that lead to this final stage, rather than preventing or treating this final stage of the condition."

In separate research published in the March edition of medical journal Atherosclerosis, Abela and colleagues looked at the physical triggers that can cause cholesterol crystallization. They found that physical conditions such as temperature can play a role in how quickly cholesterol crystallizes and potentially causes a rupture.

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Michigan State University has been advancing knowledge and transforming lives through innovative teaching, research and outreach for more than 150 years. MSU is known internationally as a major public university with global reach and extraordinary impact. Its 17 degree-granting colleges attract scholars worldwide who are interested in combining education with practical problem solving.

External focus improves postural stability in patients with Parkinson's disease

ALEXANDRIA, VA, 28 mar 2009 – Patients with Parkinson disease may be able to improve their postural stability by directing their attention to the external effects of their movements rather than to the movements of their own body, according to a study published in the February 2009 issue of Physical Therapy, the scientific journal of the American Physical Therapy Association (APTA).

Adults with Parkinson disease are at greater risk for posture and balance impairments. These conditions may lead to falls, resulting in head injuries and fractures, which can end with hospitalization and further mobility limitations. Approximately 90 percent of people with Parkinson disease will fall at some point during their lives.₁ In the past 12 months, two-thirds of patients with Parkinson disease reported a fall.₂

According to physical therapist researcher and APTA spokesperson Merrill Landers, PT, DPT, OCS, "of the major motor signs of Parkinson disease, postural instability is the least responsive to medication. It is crucial that physical therapists continue to develop effective rehabilitation strategies to address this issue."

Lead researcher Gabriele Wulf, PhD, and her team observed 14 adults with idiopathic Parkinson disease as they balanced on an unstable surface (an inflated rubber disk) under three attentional focus conditions -- external focus, internal focus, and a control condition.

Patients were instructed to either focus on reducing movements of the rubber disk (external focus) or movements of their feet (internal focus), or they were not given attentional focus instructions (control condition). The results were consistent with previous findings on attentional focus, which showed that directing attention to the effects of an individual's movement on the environment (external focus) improved postural stability, compared with internal focus and control conditions, during standing for individuals with Parkinson disease.

"In the past 12 years or so, numerous studies have been done – many of them involving healthy adults learning sport skills – and it has consistently been found that individuals perform and learn motor skills more effectively when they are instructed to adopt an external focus. Other studies have shown that those advantages generalize to people after stroke as well as to the rehabilitation of ankle sprains, for example. This is a very reliable effect, and the current study demonstrates that persons with Parkinson disease benefit from an external attentional focus as well," Wulf explained.

"Findings from this study not only have the potential to enhance the rehabilitation strategies of physical therapists working with patients with Parkinson disease, but may ultimately give patients with postural instability more control over their lives through the use of strategies that help them manage their own balance safely and effectively," said Rebecca Lewthwaite, PhD, of Rancho Los Amigos National Rehabilitation Center, a co-author on the study.

Routine Tests Can Induce Stress Cardiomyopathy

Reversible cardiac dysfunction can occur when using catecholamines and beta-receptor agonists

28 mar 2009- Routine procedures and tests using catecholamines and beta-receptor agonists can precipitate stress cardiomyopathy, according to study findings released online March 25 in advance of publication in the April 14 issue of the Journal of the American College of Cardiology.

Jacob Abraham, M.D., of Johns Hopkins University School of Medicine in Baltimore, and colleagues report on nine cases of stress cardiomyopathy, of which six occurred immediately after intravenous administration of epinephrine, while three cases occurred after administration of dobutamine. Seven of the patients were women and the mean age of the patients was 44 years.

Within 24 hours of administration of the drug, all nine patients developed corrected QT interval prolongation, and the investigators observed apical, mid-ventricular and basal left ventricular ballooning. Within a median seven days of follow-up, all the patients recovered left ventricular systolic function, the researchers note.

"The precise mechanism of catecholamine-mediated myocardial stunning in stress cardiomyopathy remains unknown. Ischemia due to epicardial spasm seems unlikely and would not readily explain the various ballooning patterns seen with this syndrome," the authors write. "This observational series provides compelling evidence that exaggerated sympathetic stimulation is sufficient to precipitate the syndrome of stress cardiomyopathy in susceptible individuals. Although many questions regarding stress cardiomyopathy remain unanswered, this report offers unique insight into the pathogenesis of this increasingly recognized clinical syndrome."

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Carotenoid supplements tied to lung cancer risk

NEW YORK , 27 mar 2009 – Based on the findings from a new study, it appears that people who take higher than recommended doses of carotenoid supplements hoping to keep from getting sick, may actually be doing themselves harm. The long-term use of beta-carotene, retinol, and lutein supplements at doses higher than in multivitamins, increases lung cancer risk, especially in smokers and former smokers, according to investigators from the Vitamins and Lifestyle (VITAL) study.

High-dose beta-carotene supplements increase the lung cancer rates in high-risk individuals, even though carotenoids from dietary sources tend to lower risk, Dr. Jessie A. Satia and co-researchers note in the American Journal of Epidemiology. "Whether effects are similar in the general population is unclear."

Satia's team analyzed data from 77,126 subjects ages 50 to 76 who filled out questionnaires in 2000-2002 regarding supplement use over the previous decade. The group was predominantly white and generally healthy, the authors note, and while there were few who never smoked among the lung cancer cases, there were fewer current smokers in the overall group than in the general population.

By linking the data to the national cancer registry, Satia, at the University of North Carolina at Chapel Hill, and her colleagues identified 521 cases of lung cancer. They then estimated the risk associated with the individual supplements after considering the possible effects of age, gender and smoking history.

Each supplement raised the risk of non-small-cell lung cancer, the most common type of lung cancer, with retinol and lutein also having a modest association with lung cancer overall.

When beta-carotene was used for at least 4 years, the overall risk of lung cancer was not significantly increased, but the risk of small-cell lung cancer rose by more than 3-fold.

For retinol, the overall risk of lung cancer increased by more that 50 percent and for non-small-cell lung cancer, it increased by 80 percent.

For lutein, the overall risk increased by 2-fold, while the corresponding risk for non-small-cell lung cancer increased by 2.5-fold.

The researchers speculate that "these nutrients from supplements may be more bioavailable than those from dietary sources" and large amounts of these supplements might interfere with the absorption, transport and or metabolism of micronutrients or other carotenoids that may be protective against lung cancer.

"Too high a dose of an antioxidant vitamin may interfere with generation of reactive oxygen species needed for beneficial processes, such as normal immune response and apoptosis," Satia's team adds.

Whatever the reason, they conclude that the "long-term use of individual beta-carotene, retinol, and lutein supplements should not be recommended for lung cancer prevention, particularly among smokers."

SOURCE: American Journal of Epidemiology, April 1, 2009.

Combating weight gain caused by antipsychotic treatments

Philadelphia, PA, 27 mar 2009– Antipsychotic drugs, such as olanzapine (Zyprexa), risperidone (Risperdal) and quetiapine (Seroquel), are commonly used to treat psychotic disorders like schizophrenia, but also bipolar disorder and even behavioral problems related to dementia. Unfortunately, the weight gain commonly experienced with antipsychotic treatment is an important side effect for many patients, and causes many patients to discontinue their use leading to even further problems. Biological Psychiatry, in its April 1st issue, is now publishing a new study that has evaluated an add-on treatment to potentially reduce treatment-associated weight gain.

In a randomized, double-blind, placebo-controlled trial, Dr. James Roerig and colleagues evaluated the effect of modafinil on olanzapine-associated weight gain in normal volunteer subjects. Modafinil is a drug currently used to increase wakefulness in individuals with sleep disorders, such as narcolepsy. All of the subjects received olanzapine, and half also received modafinil treatment while the other half instead received placebo. After three weeks, although the body mass index was increased in both groups, those receiving olanzapine/placebo showed significantly greater weight increase than those receiving olanzapine/modafinil.

Dr. Roerig notes that now that this short-term study in healthy individuals has shown promise, modafinil can now be evaluated as a "viable candidate for a larger, more complex clinical trial to determine efficacy in a patient population."

Dr. John Krystal, Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, agrees that further research is warranted. "Psychiatrists are now working more closely with patients to manage the side effects of antipsychotic treatment. The finding that modafinil reduces weight gain may encourage more research to see whether there are other benefits associated with modafinil prescription with regards to symptoms or cognitive impairments associated with schizophrenia."

Burden of Alzheimer's Disease Triples Health Costs

Millions of elderly people with dementia add to burden on Medicare and Medicaid

27 mar 2009-- People aged 65 and older with Alzheimer's disease and other forms of dementia make Medicare and Medicaid claims that are three times higher than those of their counterparts without the condition, according to a report, 2009 Alzheimer's Disease Facts and Figures, released March 24 by the Alzheimer's Association.

According to 2004 data, the high usage of health care and long-term care services by Alzheimer's disease and dementia patients resulted in average per-person Medicare, Medicaid and other payments of $33,007 a year versus $10,603 for those with no dementia or Alzheimer's disease.

There are 5.3 million people in the United States with Alzheimer's disease, and they also often have comorbid conditions such as diabetes or coronary heart disease, the report states. The costs of these diseases are inflated by the medical management challenges posed by Alzheimer's disease.

"With the country facing unprecedented economic challenges and a rapidly aging baby boomer population, now is the time to address the burgeoning Alzheimer crisis," Harry Johns, chief executive officer of the Alzheimer's Association, said in a release. "A strategy to immediately confront Alzheimer's has the potential to save millions of lives and billions of dollars by reducing the burden on Medicare and Medicaid."

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High Meat Consumption Linked to Higher Death Risk

Red and processed meat associated with more deaths from cancer and higher heart disease risk

27 mar 2009-- People who consume large amounts of red and processed meats have a higher risk of death, particularly from cancer and cardiovascular disease, according to a study in the March 23 issue of the Archives of Internal Medicine.

Rashmi Sinha, Ph.D., and colleagues from the National Institutes of Health in Rockville, Md., prospectively studied the association between death and intake of red, white and processed meat through a 124-item food frequency questionnaire given at baseline to 322,263 men and 223,390 women.

During 10 years of follow-up, 47,976 men and 23,276 women died. The researchers found that men and women who consumed large amounts of red and processed meats had a higher risk of overall mortality (hazard ratio approximately 1.3 and 1.2 for highest quintile versus lowest quintile). High consumption of red and processed meats was associated with a higher risk of cancer-specific mortality (hazard ratio approximately 1.2 and 1.1, respectively) and a higher risk of cardiovascular disease for red (hazard ratio 1.27-1.50) and processed meats (hazard ratio 1.09-1.38). White meat was not associated with an increase in mortality, the authors note.

Practitioners "have the role of advising their clients to consume small to moderate amounts of red meat and processed meats as a way to reduce the risk of a large number of chronic diseases," Barry M. Popkin, Ph.D., from the University of North Carolina in Chapel Hill, writes in an accompanying editorial.

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Age, Diabetes May Affect Coronary Disease Treatments

Mortality among diabetics and older patients is lower with coronary artery bypass graft than with percutaneous coronary intervention

27 mar 2009-- In most patients with multivessel coronary disease who are suitable for either coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), long-term mortality is similar for either treatment. In diabetics and older patients, however, CABG may be associated with a significant survival advantage, according to an article published online March 20 in The Lancet.

Mark A. Hlatky, M.D., of the Stanford University School of Medicine in Stanford, Calif., and colleagues conducted a meta-analysis of 10 randomized trials involving 7,812 patients. PCI was performed with balloon angioplasty in six trials and with bare-metal stents in four trials.

After a median follow-up of 5.9 years, the researchers found that mortality was not significantly different in the CABG and PCI groups (15 percent versus 16 percent). But they found that CABG was associated with significantly lower mortality among diabetics (hazard ratio, 0.70) and in patients aged 55 to 64, and 65 and older (hazard ratios, 0.90 and 0.82, respectively).

"Our finding that patient age modifies the relative effectiveness of CABG and PCI on survival has not previously been reported by individual randomized trials," the authors write. "The interaction of age with assigned treatment might be mediated by the more favorable clinical characteristics in younger patients; however, we found that the effect persisted after multivariable adjustment for such characteristics."

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Americans Fear Chronic Disease Above All Else

Despite worries, they do little to change habits that put them at risk

26 mar 2009-- Although Americans fear chronic disease above debt, divorce or unemployment, their lifestyle choices put them at risk for diseases such as diabetes, according to a report released March 24 by the American Diabetes Association.

The ADA conducted a survey of 2,516 U.S. adults, of whom 52 percent rated chronic illness as the worst thing that could happen to them, versus 19 percent who cited heavy debt, 13 percent who cited divorce or living alone and 11 percent who cited losing their job. Despite their concerns about chronic illness, half of the respondents had not discussed common chronic illnesses with their doctor, the researchers found.

Although 83 percent correctly identified overweight and obesity as a diabetes risk factor, over half also mistakenly cited excessive consumption of sugar as a risk factor, the report states. Moreover, about one-fourth did not consider smoking a risky behavior, and between 30 percent and 40 percent did not view maintaining an unhealthy weight or a poor diet as risky, the report reveals.

"We know Americans view activities like bungee jumping as especially risky and so they avoid them," Richard M. Bergenstal, M.D., president-elect, medicine and science at the American Diabetes Association, said in a statement. "However, these same people are gambling daily by ignoring risk factors for a life-altering disease like diabetes and doing nothing about it."

A new approach to prostate cancer detection

Sarcosine may distinguish between slow-growing and aggressive prostate cancers

26 mar 2009--On Friday 20 March, US researcher Dr. Chris Beecher from the University of Michigan gave a well attended lecture about sarcosine, an N-methyl derivative of the amino acid glycine, at the 24th Annual EAU Congress in Stockholm, Sweden. Dr Beecher is a colleague of lead author Dr. Arun Sreekumar. The research of Sreekumar, Beecher and their team looked at more than 1,000 small molecules in tissues associated with prostate cancer. These findings suggest that not only is sarcosine a marker of cancer aggressiveness, it also has a role in endowing a cancer with malignant properties.

Sreekumar´s publication in Nature (457, 12 February 2009: 910-914) has attracted a lot of scientific and also popular attention. The EAU Scientific Congress Office inserted a special breaking news session in the congress programme in order to present the most updated scientific information in Stockholm.

Sarcosine may distinguish slow-growing prostate cancers from those likely to spread and become lethal. Conveniently, sarcosine can be identified in urine, a less invasive test than the blood analysis needed for the standard prostate-specific antigen (PSA), a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of healthy men, and is often elevated in the presence of prostate cancer. Quite often men have PSA scores that fall into a grey area. Therefore, invasive biopsy is needed to clarify a diagnosis.

But even when a biopsy reveals cancer, it often remains unclear whether the cancer is aggressive and at risk of spreading, or indolent and likely to stay put. Rather than looking for genes or proteins, Dr. Arun Sreekumar and his team of the University of Michigan measured the levels of chemical by-products of the reaction inside the human cells. These chemicals are called metabolites. They looked into 42 tissue samples, 110 blood samples and the same number of urine samples from patients with advanced prostate cancer, early prostate cancer and men with benign disease. Ten of these chemicals were found at much higher levels in prostate cancer than normal samples. One of these metabolites stood out: sarcosine.

According to Dr. Beecher, the results are promising: "Sarcosine continues to predict the aggressiveness of the tumours". The metabolomic analysis yielded the observation that sarcosine was highly associated with tumour development. The scientific data support a correlation and provide biological insights.

Faster, better diagnosis for patients with heart rhythm disorders

Latest generation of electrophysiology equipment used this week for the first time in North America

TORONTO , 26 mar 2009- Patients with heart rhythm disorders can look forward to better and faster diagnosis and treatment thanks to the latest generation of electrophysiology equipment used this week for the first time in North America at the Peter Munk Cardiac Centre.

"This state-of-the-art equipment allows us to better visualize electrical activity in the heart and localize the source of rhythm disturbance," says Dr. Eugene Downar, cardiologist in the Peter Munk Cardiac Centre. "The improved display helps us diagnose more accurately and treat patients faster."

Atrial fibrillation and flutter – irregular, rapid heartbeats caused by electrical disturbances in the upper chambers of the heart muscle – are the most common arrhythmias in the world and affect about eight per cent of the elderly. The Peter Munk Cardiac Centre specializes in the treatment of patients with various heart rhythm disorders.

John Kelly was debilitated by frequent episodes of "skipping heart beats" for 20 years that left him short of breath and exhausted. These symptoms were not controlled with heart rhythm medications. Mr. Kelly was admitted to hospital earlier this week and is one of the first patients in North America to be treated with this new equipment.

"Climbing stairs was quite difficult and my episodes would last 12-14 hours at a time," reflects Mr. Kelly who is a retired high school teacher. "It was really affecting my quality of life."

The CARTO 3 system, currently under review by Health Canada, is a sophisticated electro-anatomic mapping system that records the heart's electrical activity. Just like geo-positioning systems (GPS) help drivers, this system allows physicians locate where in the heart the abnormality is coming from.

Using a small needle puncture, a few catheters are inserted into the vein of the leg and passed up to the heart. The catheters are like antennas that record electrical waves in the heart which are displayed on a screen and help electrophysiologists localize the source of the abnormal heart rhythm.

"Visualizing the catheters in the heart with CARTO 3 is a tremendous advancement that will be particularly helpful in treating patients with atrial fibrillation, "explains Dr. Vijay Chauhan, Director of Interventional Electrophysiology at the Peter Munk Cardiac Centre. "Once we know where the abnormal rhythm is coming from, we carefully burn the area which can range in size from a few millimeters to a few centimeters."

The Electrophysiology team, led by Drs. Downar and Chauhan, is treating patients with this new technology with special access approval from Health Canada.

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Peter Munk Cardiac Centre

The Peter Munk Cardiac Centre is the premier cardiac centre in Canada. Since it opened in 1997, the Centre has saved and improved the lives of cardiac patients from around the world. Each year, approximately 17,000 patients receive the innovative and compassionate care from the Peter Munk Cardiac Centre multidisciplinary heart team. In addition, the Peter Munk Cardiac Centre trains more cardiologists and cardiovascular surgeons than any hospital in Canada. The Centre is based at Toronto General Hospital – a member of University Health Network, which also includes Toronto Western Hospital and Princess Margaret Hospital. All three are research hospitals affiliated with the University of Toronto.

Older adults concern for personal health linked to walking difficulty

CORVALLIS, Ore., 26 mar 2009 – Older adults who worry about their health engage in less physical activity, and those who participate in less activity are more likely to report having difficulty walking, according to a new study.

The research, featured in the current issue of Research Quarterly for Exercise and Sport, was conducted by lead author Kin-Kit Li of The University of Hong Kong when he was a doctoral student at Oregon State University, and coauthored by Bradley Cardinal and Samuel Vuchinich, faculty members at OSU.

Mobility, which declines with aging, has been identified as one of the key topics in aging research, as walking difficulty reduces quality of life. Most studies have emphasized the behavioral or physiological mechanisms that lead to walking difficulty among older adults. Not until recently have researchers started to look at possible psychological effects.

Health worry has been suggested to have an interesting mix of effects on health behaviors and outcomes. Some studies have suggested health worry may be considered a protective mechanism, which motivates people to engage in health behaviors such as regular physical activity. However, this study showed the opposite relationship. In a representative sample of older adults in the United States, people with a high degree of health worry engaged in less physical activity.

Health worry, physical inactivity, and walking difficulty may actually combine to have a negative effect on each other, the researchers say.

"Our research shows that a key component to avoid walking difficulty in older adults is to resolve health worry issues earlier in life," said Cardinal, a professor in the Department of Nutrition and Exercise Science at OSU.

Health professionals often use warnings of diseases and premature death to promote physical activity. The authors suggest that health-related information should include appropriate self-regulation and coping strategies for health worry. Instead of using health threat as a motivator, evidence-based programs for behavior change should be implemented.

"Using threats and fear-tactics to encourage physical activity in older adults will not work," Cardinal said.

Cardinal's past studies have shown that matching various behavioral change strategies with participants' readiness for change is effective. In addition, implementing screening tools, such as the revised Physical Activity Readiness Questionnaire prior to initiating a physical activity program, should be considered for use more widely among older adults.

These strategies would ease concerns about the associated risks of participating in physical activity, the authors note, and as a result older adults could benefit from increased physical activity participation.

Study: Male circumcision helps prevent 2 STDs

By ALICIA CHANG

LOS ANGELES,26 mar 2009 – Circumcision not only protects against HIV in heterosexual men, but it also helps prevent two other sexually transmitted infections, a large new study found. Circumcised males reduced their risk of infection with HPV, or human papillomavirus, by 35 percent and herpes by 28 percent. However, researchers found circumcision had no effect on the transmission of syphilis.

Landmark studies from three African countries including Uganda previously found circumcision lowered men's chance of catching the AIDS virus by up to 60 percent. The new study stems from the Uganda research and looked at protection against three other STDs. The findings are reported in Thursday's New England Journal of Medicine

"Evidence now strongly suggests that circumcision offers an important prevention opportunity and should be widely available," Drs. Matthew Golden and Judith Wasserheit of the University of Washington wrote in an accompanying editorial.

Worldwide, only about 30 percent of men are circumcised. The figure is higher in the United States, where about 79 percent of men are circumcised, according to surveys by the National Center for Health Statistics.

An international team of researchers who conducted the study said circumcision, the surgical removal of the foreskin from the penis, should be an accepted method to reduce sexually transmitted infections among heterosexuals.

"It must be emphasized that protection was only partial, and it is critical to promote the practice of safe sex," they wrote.

HPV can cause cervical cancer and genital warts. Herpes greatly increases the chances of infection with HIV.

The American Academy of Pediatrics previously said there was not enough evidence to recommend routine circumcision of infants. The doctor's group is reviewing its position based on recent studies. About 2,800 herpes cases in newborns occur in the U.S. every year transmitted from mothers to infants that can lead to disability or death.

The latest research involved 3,393 HIV-negative heterosexual adolescent boys and men from Uganda who were part of the original HIV study. About half were randomly selected to undergo circumcision right away while the rest had the procedure 2 years later. All had physical exams and were offered voluntary HIV counseling and condoms.

After two years, herpes infection was detected in 114 circumcised men compared with 153 uncircumcised men. HPV was detected in 42 circumcised men compared with 80 uncircumcised men. There was no significant difference between the two groups on rate of syphilis infections. The researchers considered condom use, number of sex partners and other factors to calculate the risk reductions.

Why circumcision may reduce the risk of infection is not entirely known. But researchers think cells in the foreskin of the penis may be susceptible to HPV and the herpes virus.

The study was funded by the National Institutes of Health and the Bill and Melissa Gates Foundation. It was conducted by the Rakai Health Sciences Program and Makerere University in Uganda, Johns Hopkins Bloomberg School of Public Health and a division of the National Institutes of Health.

The results were similar to two recent studies from South Africa that found circumcision reduced HPV and herpes by up to a third.

Researchers plan to study whether circumcision reduces the spread of HPV to female sex partners.

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On the Net:

New England Journal: http://www.nejm.org

Loneliness tied to poorer health in old age

By Amy Norton

NEW YORK, 25 mar 2009– Older adults who lack family and friends, or who feel lonely despite having others around them, tend to be in poorer physical and mental health, a new study finds.

Researchers found that among roughly 3,000 U.S. adults ages 57 to 85, those with few social connections were less likely to describe their physical health as good or excellent. Meanwhile, those who felt socially isolated -- even if they had friends, family and social activities -- tended to report poorer physical and mental well-being.

The findings, reported in the Journal of Health and Social Behavior, add to evidence linking social connections to older adults' health.

But they also suggest that older people's actual social support and their perceptions of that support each have independent effects, according to the researchers.

"Most older adults will experience significant changes in their social relationships due to things like retirement and bereavement, for example," said lead researcher Dr. Erin York Cornwell, of Cornell University in Ithaca, New York.

Some people, she told Reuters Health, respond to this by becoming active in social organizations or spending more time with friends and family. Yet some may still end up feeling lonely at the end of the day. On the other hand, some older adults are satisfied with having fewer relationships.

In this study, people's actual social connections were linked to their physical health -- which may be related to practical factors, like having someone to drive you to a doctor's appointment or remind you to take your medicine.

But perceptions of social isolation were related to both physical and mental well-being.

"Given that the perception of one's relationships is also important for health," Cornwell said, "older adults' abilities to cope with changes in relationships are crucial."

"Those who are able to adjust to losses of social relationships will fare better than those who feel lonely or perceive a lack of support," she said.

It will be important, Cornwell noted, to try to find out why some adults are able to deal with relationship losses, while others feel isolated even if they have friends or social activities to fall back on.

Feelings of loneliness and isolation may affect older adults' health in a number of ways, according to Cornwell. They can, for example, create stress, lower self-esteem or contribute to depression, all of which may have physical heath consequences -- either by affecting a person's lifestyle choices or through direct effects on the body, such as dampened immune system functioning.

SOURCE: Journal of Health and Social Behavior, March 2009.

Alarming new data shows TB-HIV co-infection a bigger threat

Disease experts raise alarm amid concerns global health funding will be shortchanged

WASHINGTON, 25 mar 209—The World Health Organization released staggering new data about the threat of tuberculosis and the toll it takes on people with HIV/AIDS today, in recognition of World TB Day.

The TB-HIV co-infection crisis is twice as big as previously thought, the new WHO figures show. In 2007, there were at least 1.37 million cases of HIV-positive TB—or nearly 15 percent of the total incident cases. That's double the previous WHO estimates.

"A global health catastrophe is unfolding," said Gerald Friedland, a professor of Medicine, Epidemiology and Public Health at Yale University School of Medicine and a leading expert on the emerging threat.

In addition, the WHO data shows that drug-resistant TB is on the rise. There were more than 500,000 cases of MDR-TB in 2007, the WHO reported. And by the end of 2008, at least 55 countries and territories had identified at least one case of extensively drug-resistant TB.

In light of the new WHO figures and increasing concern about the threat of drug-resistant TB, leading physicians and scientists are urging the Obama administration to triple the U.S. donation to the Global Fund to Fight AIDS, Tuberculosis and Malaria and to dramatically ramp up the U.S.'s own vastly-underfunded global TB programs.

Right now, nearly 60 countries are seeking new Global Fund grants for anti-TB programs. But the Fund, facing a $5 billion donation shortfall, may not be able to finance any of these desperately needed efforts.

Five world-renown experts on TB and HIV are available to discuss the new WHO data—set to be released on March 24th, World TB Day. They can address the scope of the TB-HIV co-infection crisis and talk about how U.S. policy makers should respond.

Tuberculosis is sometimes a forgotten and neglected disease. But an estimated one-third of the world's population is infected with the bacterium that causes TB, and the disease kills nearly 1.7 million people each year.

Now, virulent new drug-resistant strains of TB are on the rise across the globe. HIV-positive patients are highly vulnerable to TB, because of their weakened immune systems, and tuberculosis is now the No. 1 killer of people with HIV.

These twin epidemics present a stark new global health threat and raise the prospect of a global pandemic of extensively-drug-resistant TB, which is extremely difficult to treat.

The new WHO figures come amid deep concern among global health advocates that the Obama administration will flatline vital HIV/AIDS and TB programs, as the global recession deepens. The president is expected to release his detailed request for global health and other programs in the coming weeks. Advocates are urging full funding for PEPFAR, so the initiative can tackle the growing crisis of HIV-TB co-infection, and a tripling of the U.S. contribution to the Global Fund to Fight AIDS, Tuberculosis and Malaria.

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To arrange an interview with Dr. Friedland or any of the other experts listed below, please contact the Global Center's Senior Communications Officer, Deirdre Shesgreen at 703-740-4954 (office) or 202-330-3890 (cell). Email is dshesgreen@idsociety.org.

Scientists ID New Biomarker for Prostate Cancer

25 mar 2009 -- A newly identified marker for prostate cancer progression may also offer a new target for treatment, University of Michigan researchers say.

Previous research has found that decreased levels of the marker galectin-3 are linked with neoplastic progression in prostate cancer. However, increased levels of galectin-3 are believed to be associated with tumorigenicity in a number of other tumor types.

The University of Michigan team believed this difference was due to the fact that galectin-3 was cleaved during prostate cancer progression. Their study found that cleaved galectin-3 is present in a late-stage prostate cancer and that reducing levels of galectin-3 inhibited development of metastatic prostate cancer.

The findings suggest that cleaved galectin-3 may serve as a diagnostic marker and treatment target for prostate cancer progression.

The study shows "that galectin-3 is cleaved during the progression of prostate cancer and might be associated with metastasis, cell growth and tumorigenicity. Expression of intact versus cleaved galectin-3 thus might be used as a marker for prognosis of prostate cancer and a therapeutic target for the treatment of prostate cancer," wrote study author Avraham Raz and colleagues.

The study appears in the April issue of The American Journal of Pathology.

Cancer cure rates on the rise in Europe: study

LONDON, 25 mar 2009 – More Europeans are beating cancer, perhaps due to more widespread screening and earlier diagnosis, according to a study published on Tuesday.

While there were differences among countries and different groups of patients, new data taken from cancer registries of 23 European nations showed the proportion of people cured of the most common cancers has risen.

"The good news is that for most cancers, survival has increased during the 1980s and 1990s," said Alexander Eggermont, president of the European Cancer Organization, who did not take part in the long-running Eurocare study.

The study compared two periods -- 1988 to 1990 and 1997 to 1999 -- and found that the proportion of men and women cured of lung cancer rose from 6 percent to 8 percent, stomach cancer cures from 15 percent to 18 percent and colorectal cancer cure rates went from 42 percent to 49 percent.

Where people lived played a role in the cancer cure rates, according to the Eurocare study comprising data covering 23 countries and more than 151 million people.

For all cancers combined most men, about 47 percent, were cured in Iceland and most women, 59 percent, were cured in France and Finland. In Poland the fewest men, 21 percent, and women, 38 percent, were cured.

At five percent Denmark, Czech Republic and Poland had the lowest proportion of cured lung cancer patients while France and Spain at more than 10 percent had the highest.

"Without this information, it would be impossible to assess whether improvements in cancer diagnosis, treatment and care are actually having an effect on the outcome for patients," Eggermont said.

The data also highlighted gaps between countries for breast cancer, suggesting that national screening programs adopted in some Western countries are helping fight the disease.

The difference between Poland, the Czech Republic and Slovenia compared to more western European countries was now about 10 percent, the researchers said in the European Journal of Cancer.

"The data also tells us what cancers and which areas of Europe need to be targeted for further research and investment," Eggermont added in a statement.

Hunting tailored care for advanced prostate cancer

By LAURAN NEERGAARD

WASHINGTON, 25 mar 2009 – Prostate cancer has been left behind in the race for personalized medicine but that may be changing: Doctors are starting to attempt gene-guided treatment for men with advanced disease.

It's an approach already offered in treating breast and certain other cancers. The new prostate work is a small initial step at catching up. And it targets the men in most dire need — those whose prostate cancer has spread to the bones or other parts of the body, and hormone treatment to slow its march has quit working.

These are the men who ultimately wind up dying of prostate cancer, some 28,000 a year.

"Prostate cancer has learned some tricks," says Dr. Phillip Febbo of Duke University Medical Center, who is unraveling how to decode those tricks to better direct therapy — by looking directly at the tumor's genetic signature.

The research is very preliminary but if a gene-guided method ultimately works it could ease what the American Cancer Society's Dr. Durado Brooks calls today's "shotgun approach" to advanced prostate cancer. Patients slog their way through a handful of medications in no particular order, changing course only after the cancer quits responding.

"This gives us a more scientifically reasoned, evidence-based approach to treating these men — hopefully. That's the theory," Brooks cautions.

Starting next month, Duke will recruit men for a study that will help determine their treatment.

Tumors carry a pattern of gene and protein activity that signal whether a cancer is more or less aggressive and whether it is susceptible to various treatments. Those signatures already have led to breast cancer tests that predict which tumors are more likely to return, helping patients decide whether to try or skip chemotherapy, for example. Everyone with advanced colon cancer is supposed to get a genetic test before trying one of two leading treatments, to see if their tumor will respond.

Yet even though prostate cancer hits as many men as breast cancer hits women, finding genetic signatures in prostate tumors has been a struggle. Men tend to get prostate biopsies early on, before the cancer has spread. Very few get one after their cancer worsens, when the tumor has evolved, leaving few advanced tumor samples for scientists to examine which genetic activity is most crucial, Febbo explains.

But that's slowly changing, and the result is a race to find genetic signatures that might predict a therapy's usefulness.

First up, the "androgen receptor." It's the male counterpart to the estrogen receptor that determines how strongly estrogen fuels breast cancer growth.

Hormone therapy to block testosterone production is a key prostate cancer treatment. But some cancers keep growing despite low testosterone levels, and researchers in the last few years have found that how tumor cells use their androgen receptor plays a major role. The cancer might make copies of its androgen receptor so a cell now has 10 instead of two, Febbo says, the better to suck in remaining testosterone. Or the receptors may become more sensitive, able to react to the tiniest bit of testosterone instead of usual levels. Prostate tumors sometimes even start making their own testosterone.

Febbo's team genetically profiled more than 100 samples of prostate cancer. A genetic signature separates which men with hormone-resistant advanced cancer still have a very active androgen receptor and which don't — something else, perhaps a gene named Src, is fueling their cancer, he reported this month in the Journal of Clinical Oncology.

Next month, Duke and other hospitals that are part of the Defense Department's Prostate Cancer Consortium will begin recruiting 60 such patients and custom-profile their cancer to decide treatment. Those with highly active androgen receptors will get nilutamide, a receptor blocker. Those whose androgen receptors aren't the problem will receive an experimental treatment, the leukemia drug dasatanib that's known to target prostate-related factors.

Also under way: Testing whether there's a genetic signature that says which men will respond best to a different drug, docetaxel. It's proven to increase survival in hormone-resistant advanced prostate cancer but only in a fraction of patients.

Separately, doctors are closely watching studies of an experimental drug named abiraterone that's supposed to target mutated androgen receptors.

It's way too soon to predict if any of these approaches will pan out. But the genetics rationale appeals to Tim Atkeson, a Denver lawyer whose prostate cancer already had spread to his bones when he was diagnosed at the unusually young age of 49.

Atkeson read up on studies presented at leading cancer meetings and, while systematically working through treatments for the hormone-resistant, he contacted Febbo about volunteering for the gene-guided study. At the very least, he hopes to spur science in case his sons or brothers ever face the same disease.

"I keep my fingers crossed that perhaps I'll be one of the lucky ones," says Atkeson, now 51.

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EDITOR's NOTE — Lauran Neergaard covers health and medical issues for The Associated Press in Washington.