Antidepressants linked to thicker arteries

Antidepressant use has been linked to thicker arteries, possibly contributing to the risk of heart disease and stroke, in a study of twin veterans. The data is being presented Tuesday, April 5 at the American College of Cardiology meeting in New Orleans.

03 april 2011--Depression can heighten the risk for heart disease, but the effect of antidepressant use revealed by the study is separate and independent from depression itself, says first author Amit Shah, MD, a cardiology fellow at Emory University School of Medicine. The data suggest that antidepressants may combine with depression for a negative effect on blood vessels, he says. Shah is a researcher working with Viola Vaccarino, MD, PhD, chair of the Department of Epidemiology at Emory's Rollins School of Public Health.

The study included 513 middle-aged male twins who both served in the U.S. military during the Vietnam War. Twins are genetically the same but may be different when it comes to other risk factors such as diet, smoking and exercise, so studying them is a good way to distill out the effects of genetics, Shah says.

Researchers measured carotid intima-media thickness – the thickness of the lining of the main arteries in the neck -- by ultrasound. Among the 59 pairs of twins where only one brother took antidepressants, the one taking the drugs tended to have higher carotid intima-media thickness (IMT), even when standard heart disease risk factors were taken into account. The effect was seen both in twins with or without a previous heart attack or stroke. A higher level of depressive symptoms was associated with higher IMT only in those taking antidepressants.

"One of the strongest and best-studied factors that thickens someone's arteries is age, and that happens at around 10 microns per year," Shah says. "In our study, users of antidepressants see an average 40 micron increase in IMT, so their carotid arteries are in effect four years older."

Antidepressants' effects on blood vessels may come from changes in serotonin, a chemical that helps some brain cells communicate but also functions outside the brain, Shah says. The most commonly prescribed antidepressants are selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), which increase the level of serotonin in the brain. Other types of antidepressants also affect serotonin levels, and antidepressants can act on other multi-functional brain chemicals such as norepinephrine.

In the study, researchers saw higher carotid IMT in both participants who used SSRIs (60 percent of those who took antidepressants) and those who used other types of antidepressants.

Most of the serotonin in the body is found outside the brain, especially in the intestines, Shah notes. In addition, serotonin is stored by platelets, the cells that promote blood clotting, and is released when they bind to a clot. However, serotonin's effects on blood vessels are complex and act in multiple ways. It can either constrict or relax blood vessels, depending on whether the vessels are damaged or not.

"I think we have to keep an open mind about the effects of antidepressants on neurochemicals like serotonin in places outside the brain, such as the vasculature. The body often compensates over time for drugs' immediate effects," Shah says. "Antidepressants have a clinical benefit that has been established, so nobody taking these medications should stop based only on these results. This isn't the kind of study where we can know cause and effect, let alone mechanism, and we need to see whether this holds up in other population groups."

Provided by Emory University

Alzheimer's-like brain changes found in cognitively normal elders with amyloid plaques

Researchers using two brain-imaging technologies have found that apparently normal older individuals with brain deposits of amyloid beta – the primary constituent of the plaques found in the brains of Alzheimer's disease patients – also had changes in brain structure similar to those seen in Alzheimer's patients. Results of the study, which has received early online publication in the Annals of Neurology, may help identify individuals who could be candidates for therapies to prevent the development of dementia.

02 april 2011--"Our findings support the theory that Alzheimer's disease begins many years before symptoms appear and that amyloid plaque is an early sign of this process," says Keith Johnson, MD, Massachusetts General Hospital (MGH) Imaging, senior author of the study. "We see that when amyloid deposits are present, even in cognitively normal individuals, the degenerative changes of Alzheimer's are underway. Long-term studies to track these changes and observe how they evolve are ongoing."

Definitive diagnosis of Alzheimer's disease requires finding amyloid plaques and neurofibrillary tangles in the brain at autopsy. In recent years it has been possible to detect amyloid in living brains by PET scanning with an imaging agent known as Pittsburgh Compound B (PiB). Plaques have been observed in the brains of apparently healthy individuals, as well as those with dementia, but whether the presence of plaques indicates the early stages of Alzheimer's disease is not yet known.

High-resolution magnetic resonance imaging studies have identified characteristic changes in brain structure – thinning of key cortical regions and reduced volume of structures such as the hippocampus – in persons with mild cognitive impairment, in individuals known to carry gene mutations that directly cause Alzheimer's disease and in diagnosed Alzheimer's patients. A recent study reported similar brain changes in some cognitively normal elders but did not distinguish those who had amyloid deposits from those who did not.

The current study involved 87 cognitively normal older individuals and 32 patients diagnosed with mild Alzheimer's – matched for age, gender and education – who had enrolled in the long-term Harvard Aging Brain Study. Participants underwent both high-resolution MR imaging of brain structure and PET scanning with PiB to detect amyloid plaques. The results showed that those cognitively normal individuals who had amyloid plaques also had structural changes similar to but less pronounced than the neurodegenerative changes seen in the symptomatic patients. Structural changes were most evident in areas comprising what is called the default network, which is known to be affected early in the course of Alzheimer's disease.

"If amyloidosis – deposits of amyloid plaques – in the brains of clinically normal people is associated with Alzheimer's-like neurodegeneration, then amyloidosis itself may signify 'preclinical' AD," say Johnson, an associate professor of Radiology at Harvard Medical School. "We need to learn more about how long it takes a normal person with amyloid to develop AD, whether there are critical 'second hit' factors that convert amyloidosis to Alzheimer's disease, and if there are measures that can halt the process of neurodegeneration."

Provided by Massachusetts General Hospital

Suicide in Musculoskeletal Patients at Older Age

Patients with musculoskeletal diseases use analgesics or nonviolent methods to commit suicide

01 april 2011-- Suicide victims who have back pain or other musculoskeletal diseases (MSD) are older than those without MSD, according to a study published in the April 1 issue of Spine.

Sanna Löfman, M.D., from the University of Oulu in Finland, and colleagues analyzed data from suicides in Oulu during a period of 19 years to compare the characteristics of 133 suicide victims with back pain (including sciatica), 357 with MSD other than back pain, and 1,820 without MSD. Death certificates from official medicolegal investigations were used to extract suicide data.

The researchers found that the age of death of victims with back pain was about 11 years older compared with those without MSD. Nonviolent suicide methods and use of analgesics in poisoning suicides were more common in both genders in the back pain and MSD groups, after adjusting for age. In the back pain and MSD groups, hospital-treated depression or substance-related disorders were more common in men. Women with back pain who committed suicide were more often under the influence of alcohol than any other group.

"Victims with a history of hospital-treated MSD committed suicide at older age. However, the older the person is, the more is the chance that he or she needs to have a treatment for some MSD at some point of life," the authors write.

Abstract
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Genetic alteration may represent early stage of smoking-induced cardiovascular damage

A new study uncovers a previously unrecognized link between tobacco smoking and a gene known to influence the cardiovascular system, possibly identifying an early stage of smoking-associated cardiovascular pathology. The research, published by Cell Press in the April issue of The American Journal of Human Genetics, may serve to guide future research strategies aimed at identifying and counteracting mechanisms of smoking-induced pathology.

01 april 2011--Tobacco smoking is powerfully addictive and damages the pulmonary and cardiovascular systems, leading to malignancy and premature death. "Although the promotion of smoking cessation clearly remains imperative, a better understanding of the pathophysiological processes linking tobacco smoking and its sequelae could yield opportunities to positively influence disease risk in the large population of continuing smokers," explains lead study author Dr. Lutz P. Breitling, from the German Cancer Research Center in Heidelberg, Germany.

One possible mechanism that has the potential for mediating the harmful effects of tobacco smoking is DNA methylation. DNA methylation, the attachment of methyl groups to specific sites within a section of DNA, is recognized as an important mechanism for regulating gene function and may play a significant role in diseases with a complex phenotype. Although previous studies have linked nicotine and smoking with altered methylation of several genes, comparison of methylation status between heavy smokers who do not have cancer and individuals who have never smoked has not been fully examined.

Dr. Breitling and colleagues used a recently developed genetic screening technique to conduct a genome-wide search for differential methylation correlated with tobacco smoking in 177 current, former, and never smokers. The researchers discovered a single section of DNA that exhibited lower methylation in smokers. The site was located within a gene called coagulation factor II receptor-like 3 (F2RL3). F2RL3 has been linked with the process of blood clotting and with other cardiovascular functions. Interestingly, the protein coded by this gene has never been mentioned in the smoking literature.

"Our results show that the gene coding for a potential drug target of cardiovascular importance features altered methylation patterns in smokers," concludes Dr. Breitling. "Intriguing perspectives lie in the possibility that this gene could be causally involved at a very initial stage of smoking-related cardiovascular pathology. A better understanding of its role might open up avenues for preventing the development of associated disease in subjects unable to quit smoking."

Provided by Cell Press

Exercise Plus Dieting Superior in Older Obese Individuals

The combination results in improved physical function compared with either approach alone

31 mar 2011---- Dieting plus exercise may be better than either alone for improvement in physical function in older adults who are obese, according to research published in the March 31 issue of the New England Journal of Medicine. Dennis T. Villareal, M.D., of the Washington University School of Medicine in St. Louis, and colleagues randomly assigned 107 adults aged 65 years or older and obese to a control group, a diet group, an exercise group, or a diet plus exercise group to assess the effects on Physical Performance Test scores, frailty, body composition, bone mineral density, specific physical functions, and quality of life. In the 93 participants who finished the study, scores on the Physical Performance Test increased more in the diet plus exercise group (21 percent) than in the diet, exercise, or control groups (12, 15, and 1 percent, respectively). Body weight decreased by 10 and 9 percent in the diet and diet plus exercise groups, respectively, but not in the exercise or control groups. The diet plus exercise group experienced improvements in strength, balance, and gait. "These findings suggest that a combination of weight loss and exercise provides greater improvement in physical function than either intervention alone," the authors write. Full Text (subscription or payment may be required)

Researchers find many elderly men are undergoing unnecessary PSA screenings

A new study on the use of prostate-specific antigen (PSA)-based prostate cancer screening in the United States found that many elderly men may be undergoing unnecessary prostate cancer screenings. Using data from surveys conducted in 2000 and 2005, researchers report that nearly half of men in their seventies underwent PSA screening in the past year – almost double the screening rate of men in their early fifties, who are more likely to benefit from early prostate cancer diagnosis and treatment. Further, men aged 85 and older were screened just as often as men in their early fifties.

30 mar 2011--Because prostate cancer tends to be slow-growing, data show that many men – particularly those in their seventies and older – will die of other causes before prostate cancer becomes a problem that requires medical attention. The new findings underscore a long-standing concern that overuse of PSA screening and PSA-based treatment decisions may lead to unnecessary treatment of many older men and potential complications such as incontinence, impotence and bowel dysfunction.

"Our findings show a high rate of elderly and sometimes ill men being inappropriately screened for prostate cancer. We're concerned these screenings may prompt cancer treatment among elderly men who ultimately have a very low likelihood of benefitting the patient and paradoxically can cause more harm than good," said senior author Scott Eggener, MD, assistant professor of surgery at the University of Chicago. "We were also surprised to find that nearly three-quarters of men in their fifties were not screened within the past year. These results emphasize the need for greater physician interaction and conversations about the merits and limitations of prostate cancer screening for men of all ages."

While large declines in prostate cancer metastases and death rates in the last 20 years coincide with widespread use of PSA-based screening, questions remain about its use. Data have been unclear about when men should be considered for PSA screening and when screening should stop, and recent studies have provided conflicting evidence on whether routine PSA screening in the general population of men actually reduces the risk of dying from prostate cancer. Based on these concerns, major organizations such as the American Cancer Society now encourage men who expect to live at least 10 years to talk with their doctor about the risks and benefits of screening, starting at age 50 for men with an average risk or at age 45 for men with a higher risk.

In this study, the researchers examined results from health surveys of randomly selected households conducted in 2000 and 2005 as part of the federal government-sponsored National Health Interview Survey. In addition to reviewing survey data, which included information on age, smoking, mass-body index, underlying medical conditions and other factors, the investigators calculated the estimated five-year life expectancy of each man over 40 who had received a PSA test.

They divided survey results of men age 70 and older into five-year age groups (70 to 74, 75 to 79, 80 to 84, and 85 years and older). In all, 2,623 men ages 70 and older were included in the analysis, while nearly 12,000 men between the ages of 40 and 69 served as controls.

The overall PSA screening rate within the past year for men aged 40 and older was 23.7 percent in 2000 and 26.0 percent in 2005. The PSA screening rate was lowest in the 40 to 44 age group (7.5 percent). Researchers found that the PSA screening rate was 24.0 percent in men ages 50 to 54, increasing with age until a peak of 45.5 percent in ages 70 to 74. Screening rates then declined with age, with 24.6 percent of men 85 or older reporting being screened.

Among men who were 70 or older, the investigators did find that PSA screening was more common in men with a greater estimated five-year life expectancy. For example, approximately 47.3 percent of men who were unlikely to die in five years (an estimated chance of 15 percent or less) were screened, 39.2 percent of men with an intermediate chance (16 to 48 percent probability) of dying received screening, and 30.7 percent of those with the highest probability of death (48 percent or greater) in five years were screened.

Eggener offered some possible explanations for the results, noting that screening rates may reflect how frequently men visit primary care physicians. Older men tend to have more health problems that require doctor visits, and this may in turn result in more frequent PSA testing than younger men, who see their doctors less. The authors suggest that physicians should be more selective in recommending PSA testing for older men, particularly those with a limited life expectancy, and consider more routinely screening younger, healthier men who are most likely to benefit from early prostate cancer diagnosis and related treatment. Men are encouraged to talk with their doctor about their individual risk for prostate cancer, and about the risks and benefits of prostate cancer screening.

More information: http://www.cancer. … state+Cancer

Provided by American Society of Clinical Oncology

Almost Two-Thirds of Older Adults Have Hearing Loss

Black race offers significant protection against hearing loss compared to white subjects

29 mar 2011-- Nearly two-thirds of older Americans experience hearing loss, and it is most strongly associated with age, gender, and race, according to a study published online Feb. 27 in The Journals of Gerontology: Series A.

Frank R. Lin, M.D., Ph.D., of the Johns Hopkins School of Medicine in Baltimore, and colleagues investigated the prevalence of hearing loss among 717 adults aged 70 years and older, as well as its associative factors and hearing aid use. They analyzed data from the 2005 to 2006 cycle of the National Health and Nutritional Examination Survey (NHANES). Audiometry results, information on hearing aid use, noise exposure, medical history, and demographics were assessed. Hearing loss was defined as a speech-frequency pure-tone average with 25 dB threshold in the better ear.

The researchers found that the prevalence of hearing loss was 63.1 percent. After adjustment for confounders, the odds of hearing loss were associated with increased age and male gender, whereas black race protected against hearing loss (odds ratio, 0.32). Forty percent of adults with moderate hearing loss used hearing aids; whereas, among those with mild hearing loss, 3.4 percent used hearing aids.

"Hearing loss is prevalent in nearly two-thirds of older adults ≥70 years in the U.S. population. Additional research is needed to determine the epidemiologic and physiologic basis for the protective effect of black race against hearing loss and to determine the role of hearing aids in those with a mild hearing loss," the authors write.

Abstract

Negative attitudes toward fat bodies going global, study finds

Stigma against overweight people is becoming a cultural norm around the world, even in places where larger bodies have traditionally been valued. That's according to a cross-cultural study of attitudes toward obesity to be published in the April issue of Current Anthropology.

29 mar 2011--Researchers from Arizona State University surveyed people in nine diverse locations around the world and found negative attitudes toward fat bodies in every one. The results suggest a rapid "globalization of fat stigma" in which overweight people are increasingly viewed as ugly, undesirable, lazy, or lacking in self control, the researchers say.

In the U.S., slim bodies have been idealized and fat ones stigmatized for several decades. But that has not been true of the rest of the world, says Alexandra Brewis, a biological anthropologist and one of the study's authors.

"Previously, a wide range of ethnographic studies have shown that many human societies preferred larger, plumper bodies," Dr. Brewis said. "Plump bodies represented success, generosity, fertility, wealth, and beauty."

But those fat-positive values are quickly giving way to a more negative Western way of looking at obesity, such as symbolizing personal failing.

The researchers surveyed people in Mexico, Argentina, Paraguay, the U.S., and the U.K. Also included were American Samoa, Puerto Rico, and Tanzania—cultures that have traditionally been thought of as fat-positive. People were asked if they agreed or disagreed with a series of statements about body size. Some statements were fat-negative ("Fat people are lazy"), others were fat-positive ("A big woman is a beautiful woman").

The responses across these diverse cultures were largely congruent with Western attitudes, the researchers found. What's more, the highest fat stigma scores were not in the U.S. or the U.K., "but rather Mexico, Paraguay, and—perhaps most surprisingly—in American Samoa," the researchers write.

The change in attitudes in American Samoa has happened with remarkable speed, says Dr. Brewis. "When I was doing research in the Samoas in the 1990s, we found people starting to take on thinner body ideals, but they didn't yet have discrediting ideas about large bodies," she said. "But that appears to be changing very quickly."

"People from sites that have adopted fat-negative attitudes more recently seem to be more strident," said cultural anthropologist Amber Wutich, another of the study's authors. "The late adopters were more likely to agree with the most judgmental statements like 'fat people are lazy.'"

The study didn't test what is driving this rapid shift in attitude, but the researchers say that "newer forms of educational media, including global public health campaigns" may be playing a role.

Dr. Brewis said the findings reveal another dimension to the global obesity epidemic.

"There are now more overweight than underweight people around the world," she said. "Our results show that this rapid growth in obesity isn't just a concern because it can undermine health. As more people globally gain weight, we also need to be as concerned about the profound emotional suffering that comes with these types of prejudicial ideas about big bodies taking hold."

More information: Alexandra Brewis, Amber Wutich, Ashlan Falletta-Cowden, and Isa Rodriguez-Soto, "Body Norms and Fat Stigma in Global Perspective." Current Anthropology 52:2 (April 2011).

Provided by University of Chicago Press Journals

Walnuts are top nut for heart-healthy antioxidants

A new scientific study positions walnuts in the No. 1 slot among a family of foods that lay claim to being among Mother Nature's most nearly perfect packaged foods: Tree and ground nuts. In a report here today at the 241st National Meeting & Exposition of the American Chemical Society, scientists presented an analysis showing that walnuts have a combination of more healthful antioxidants and higher quality antioxidants than any other nut.

28 mar 2011--"Walnuts rank above peanuts, almonds, pecans, pistachios and other nuts," said Joe Vinson, Ph.D., who did the analysis. "A handful of walnuts contains almost twice as much antioxidants as an equivalent amount of any other commonly consumed nut. But unfortunately, people don't eat a lot of them. This study suggests that consumers should eat more walnuts as part of a healthy diet."

Vinson noted that nuts in general have an unusual combination of nutritional benefits — in addition those antioxidants — wrapped into a convenient and inexpensive package. Nuts, for instance, contain plenty of high-quality protein that can substitute for meat; vitamins and minerals; dietary fiber; and are dairy- and gluten-free. Years of research by scientists around the world link regular consumption of small amounts of nuts or peanut butter with decreased risk of heart disease, certain kinds of cancer, gallstones, Type 2 diabetes, and other health problems.

Despite all the previous research, scientists until now had not compared both the amount and quality of antioxidants found in different nuts, Vinson said. He filled that knowledge gap by analyzing antioxidants in nine different types of nuts: walnuts, almonds, peanuts, pistachios, hazelnuts, Brazil nuts, cashews, macadamias, and pecans. Walnuts had the highest levels of antioxidants.

Vinson also found that the quality, or potency, of antioxidants present in walnuts was highest among the nuts. Antioxidants in walnuts were 2-15 times as potent as vitamin E, renowned for its powerful antioxidant effects that protect the body against damaging natural chemicals involved in causing disease.

"There's another advantage in choosing walnuts as a source of antioxidants," said Vinson, who is with the University of Scranton in Pennsylvania. "The heat from roasting nuts generally reduces the quality of the antioxidants. People usually eat walnuts raw or unroasted, and get the full effectiveness of those antioxidants."

If nuts are so healthful and nutritious, why don't people eat more? Vinson's research shows, for instance, that nuts account for barely 8 percent of the daily antioxidants in the average person's diet. Many people, he said, may not be aware that nuts are such a healthful food. Others may be concerned about gaining weight from a food so high in fat and calories. But he points out that nuts contain healthful polyunsaturated and monosaturated fats rather than artery-clogging saturated fat. As for the calories, eating nuts does not appear to cause weight gain and even makes people feel full and less likely to overeat. In a 2009 U. S. study, nut consumption was associated with a significantly lower risk of weight gain and obesity. Still, consumers should keep the portion size small. Vinson said it takes only about 7 walnuts a day, for instance, to get the potential health benefits uncovered in previous studies.

Provided by American Chemical Society

Even mild stress is linked to long-term disability

Even relatively mild stress can lead to long term disability and an inability to work, reveals a large population based study published online in the Journal of Epidemiology and Community Health.

27 mar 2011--It is well known that mental health problems are associated with long term disability, but the impact of milder forms of psychological stress is likely to have been underestimated, say the authors.

Between 2002 and 2007, the authors tracked the health of more than 17,000 working adults up to the age of 64, who had been randomly selected from the population in the Stockholm area.

All participants completed a validated questionnaire (GHQ-12) at the start of the study to measure their mental health and stress levels, as well as other aspects of health and wellbeing.

During the monitoring period, 649 people started receiving disability benefit - 203 for a mental health problem and the remainder for physical ill health.

Higher levels of stress at the start of the study were associated with a significantly greater likelihood of subsequently being awarded long term disability benefits.

But even those with mild stress were up to 70% more likely to receive disability benefits, after taking account of other factors likely to influence the results, such as lifestyle and alcohol intake.

One in four of these benefits awarded for a physical illness, such as high blood pressure, angina, and stroke, and almost two thirds awarded for a mental illness, were attributable to stress.

The authors say that it is important to consider their findings in the context of modern working life, which places greater demands on employees, and social factors, such as fewer close personal relationships and supportive networks.

These factors lead them to ask: "Are the strains and demands of modern society commonly exceeding human ability?" And they conclude that while mild stress should not be over-medicalised, their findings suggest that it should be taken more seriously than it is.

Provided by British Medical Journal

Researchers uncover novel immune therapy for pancreatic cancer

Researchers at the University of Pennsylvania's Abramson Cancer Center have discovered a novel way of treating pancreatic cancer by activating the immune system to destroy the cancer's scaffolding. The strategy was tested in a small cohort of patients with advanced pancreatic cancer, several of whose tumors shrank substantially. The team believes their findings – and the novel way in which they uncovered them -- could lead to quicker, less expensive cancer drug development.

26 mar 2011--The authors call the results, published in the March 25 issue of Science, a big surprise. "Until this research, we thought the immune system needed to attack the cancer directly in order to be effective," said senior author Robert H. Vonderheide, MD, DPhil, an associate professor of Medicine in the division of Hematology/Oncology and the Abramson Family Cancer Research Institute. "Now we know that isn't necessarily so. Attacking the dense tissues surrounding the cancer is another approach, similar to attacking a brick wall by dissolving the mortar in the wall. Ultimately, the immune system was able to eat away at this tissue surrounding the cancer, and the tumors fell apart as a result of that assault. These results provide fresh insight to build new immune therapies for cancer."

The current study is part of a unique research model designed to move back and forth between the bench and the bedside, with the investigative team consisting of researchers based in both the laboratory and in the clinic. In the clinical trial led at Penn by Peter O'Dwyer, MD, professor of Hematology/Oncology, and Gregory L. Beatty, MD, PhD, instructor of Hematology/Oncology, pancreatic cancer patients received standard gemcitabine chemotherapy with an experimental antibody manufactured by Pfizer Corporation. The antibody binds and stimulates a cell surface receptor called CD40, which is a key regulator of T-cell activation. The team initially hypothesized that the CD40 antibodies would turn on the T cells and allow them to attack the tumor.

The treatment appeared to work, with some patients' tumors shrinking substantially and the vast majority of tumors losing metabolic activity after therapy, although all of the responding patients eventually relapsed. When the researchers looked at post-treatment tumor samples, obtained via biopsy or surgical removal, there were no T cells to be seen. Instead, they saw an abundance of another white blood cell known as macrophages.

To understand what was happening in the tissues of these patients, Vonderheide and Beatty and colleagues turned to a mouse model of pancreatic cancer developed several years ago at Penn. Unlike older mouse models that were simplistic models of human disease, new genetically engineered mice develop spontaneous cancers that are very close reproductions of human tumors. "We can perform preclinical trials in these mice with the same principles we use in our patients," Vonderheide says, noting that the team even used a randomization protocol to assign individual mice to different arms of the study.

When the investigators treated mice that developed pancreatic cancer with gemcitabine in combination with CD40 antibodies, the results looked like those of the human trial. Some mouse tumors shrank and were found to be loaded with macrophages but contained few or no T cells. Closer inspection showed that the macrophages were attacking what is known as the tumor stroma, the supporting tissue around the tumor. Pancreatic tumors secrete chemical signals that draw macrophages to the tumor site, but if left to their own devices, these macrophages would protect the tumor. However, treating the mice (or patients) with CD40 antibodies seemed to flip that system on its head. "It is something of a Trojan horse approach," Vonderheide says. "The tumor is still calling in macrophages, but now we've used the CD40 receptor to re-educate those macrophages to attack – not promote – the tumor."

The researchers believe that the CD40 antibodies also activated T cells in the mice, but the T cells couldn't get into the tumor or its surrounding tissue. "We learned that T cells have a major problem with migration into tumors, and this may be a particular problem for pancreatic cancer," Vonderheide says. "The area surrounding pancreatic cancers is very dense, fibrotic, and hostile. This is one of the main reasons standard therapies for this disease often work so poorly."

The researchers are now working on ways to capitalize on their novel information, testing ways to super-charge the macrophage response and to get the T cells into the tumor microenvironment. Vonderheide thinks his team can speed up clinical research by running pilot trials in the mice to test potential therapeutics. Once they understand responses in the mice, then they can use that information to design better human trials.

"Beyond our specific findings, we think these findings point to a new approach for drug development in cancer -- one where we use state-of-the-art mouse models for preclinical trials to guide which trials we should do next in patients," Vonderheide says. "It should be faster, cheaper and give us a head start in the clinical trials."

Provided by University of Pennsylvania School of Medicine

Subjects at risk of Alzheimer's may now be able to delay the onset of their first symptoms

For elderly subjects at risk of developing Alzheimer's disease, research shows that hope may lie in brain plasticity.

25 mar 2011--The human brain loses 5 to 10% of its weight between the ages of 20 and 90 years old. While some cells are lost, the brain is equipped with two compensatory mechanisms: plasticity and redundancy. Based on the results of her most recent clinical study published today in the online version of Brain: A Journal of Neurology, Dr. Sylvie Belleville, PhD in neuropsychology, the principal author of this study and Director of Research at the Institut universitaire de gériatrie de Montréal (IUGM), which is affiliated with the Université de Montréal, has found that for elderly subjects at risk of developing Alzheimer's disease, hope may lie in brain plasticity.

"Brain plasticity refers to the brain's remarkable ability to change and reorganize itself. It was long thought that brain plasticity declined with age, however, our study demonstrates that this is not the case, even in the early stages of Alzheimer's disease", declares Sylvie Belleville.

These findings open countless new avenues of research including the possibility of improving the plasticity of affected areas of the brain, and slowing the decline in plasticity through pharmacological means or lifestyle changes, thereby allowing subjects with Alzheimer's disease to enjoy several more symptom-free years.

The hypothesis behind this research was that certain cells traditionally involved in other brain processes could, through a simple memory training program, temporarily take over since they themselves are not yet affected. According to Dr. Belleville: "Our research has validated our hypothesis. Not only were we able to use functional imaging to observe this diversification, but we also noted a 33% increase in the number of correct answers given during a post-training memory task by subjects with mild cognitive impairment (MCI) who, incidentally, are ten times more likely to develop Alzheimer's disease".

The training program that was used was designed to help elderly subjects with MCI develop strategies, such as the use of mnemonics, for example, and promote encoding and retrieval, such as word lists, for example, using alternative areas of the brain. "The hypothesis had already been raised, but our team was the first to provide scientific support, using a functional neuroimaging protocol", added Sylvie Belleville.

Researchers worked with thirty elderly subjects: 15 healthy adults and 15 with MCI. Magnetic resonance imaging was used to analyse brain activity in the two groups 6 weeks prior to memory training, one week prior to training and one week after training. Before the memory training, magnetic resonance imaging in both the healthy elderly subjects and those with MCI showed activation in areas of the brain traditionally associated with memory. As expected, decreased activation was observed in subjects with MCI. After training, brain areas in elderly subjects with MCI showed increased activation in areas typically associated with memory, but also in new areas of the brain usually associated with language processing, spatial and object memory and skill learning.

According to Dr. Belleville: "Analysis of brain activity during encoding as measured before and after the training program, indicates that increased post-training activation in the right inferior parietal gyrus is associated with post-intervention improvement. The healthy area of the brain has taken over for the area that is compromised."

Provided by University of Montreal

Time lived with obesity linked with mortalityMonash University researchers have found the number of years individuals live with obesity is directly associated with the risk of mortality.

24 mar 2011--The research shows that the duration of obesity is a strong predictor of mortality, independent of the actual level of Body Mass Index (BMI). As the onset of obesity occurs earlier and the number of years lived with obesity increases, the risk of mortality associated with adult obesity in contemporary populations is expected to increase compared with previous decades.

Using data from the Framingham Heart Study, 5209 participants were followed up for 48 years from 1948. The current study however only included participants who were free from pre-existing diseases of diabetes, cardiovascular diseases and cancer.

The research showed that for those who had a medium number of years lived with obesity (between five years and 14.9 years), the risk of mortality more than doubled than for those who had never been obese. The risk of mortality almost tripled for those with the longest duration of obesity (more than 15 years).

Furthermore, the research showed for every additional two years lived with obesity, the risk of mortality increased by between six and seven per cent.

"Before now, we did not know whether being obese for longer was any worse for you health than simply being obese. However, this research shows for the first time that being obese for longer increases your risk of mortality, no matter how heavy you actually are," Monash University researcher, Dr Anna Peeters said.

"This research provides added support for all the current policy trying to prevent obesity in general. It also indicates that we should try extra hard to prevent obesity at younger ages," said Dr Peeters.

Provided by Monash University

Elderly victims of abuse often use alcohol or drugs, study says

Victims of severe traumatic elder abuse are more likely to be female, suffer from a neurological or mental disorder, and to abuse drugs or alcohol, according to research published in the March issue of the Journal of the American Geriatrics Society.

23 mar 2011--"Past studies have shown that alcohol abuse by the perpetrator plays a substantial role and is strongly associated with physical abuse," says Lee Friedman, assistant professor of environmental and occupational health sciences at the University of Illinois at Chicago and lead author of the study. "Our findings indicate that alcohol abuse among the victims may be an important contributing factor as well."

Twenty-nine percent of abuse victims in the study tested positive for alcohol, compared to 13 percent of controls.

Local researchers examined medical record data at two Chicago-area Level I trauma units from 41 cases of elder abuse and compared them to a random set of other over-60 patients between 1999 and 2006.

The researchers found that elderly victims of physical abuse suffered more severe injuries than their non-abused counterparts. They also suffered disproportionately from pre-existing medical conditions such as heart disease, dementia and Alzheimer's disease, mental illness and alcohol abuse.

All the key measures of injury severity -- length of hospital stay, treatment in an intensive care unit, assisted breathing, injury severity scores, in-hospital case fatality rates -- were higher in the abuse cases, according to the researchers, and are associated with long-term adverse outcomes.

In the study, 20 victims of abuse returned to the environment in which the abuse occurred. In the majority of cases, the perpetrator had been arrested, but 17 percent of the victims expressed a desire to return to the perpetrator and not to press charges.

Eighty-five percent of the perpetrators were family members or intimate partners. In most cases, the abuse was not identified until after the admission process or several days into hospitalization.

The failure of medical staff to properly identify abuse victims and contact adult protective services in the majority of cases shows that clinicians need to better understand elder abuse, Friedman said.

Provided by University of Illinois at Chicago

Study shows polypill to be safe and accepted by physicians and patients in developing countries

For a patient at high risk of cardiovascular disease (CVD), keeping up with what pills to take at different times of the day can be tedious. Window sills lined with prescription bottles – a pill for cholesterol, another for blood pressure, and an aspirin to keep blood thin and flowing – the list can get quite long and, as a result, many people, especially the elderly, often forget doses or take the wrong pill at the wrong time.

22 mar 2011--But what if there was a single pill that had all the benefits of multiple medications in one dose? Would people take it? Would doctors prescribe it? And would it be effective?

A new study done by researchers at Wake Forest Baptist Medical Center provides evidence that, in fact, such a pill may be a viable option for developing countries, where CVD is strongly emerging and the demand for cost-effective, low maintenance treatment is high.

"The idea behind the polypill is that it offers a simpler way to give medications to people so that they will have better adherence to their pills," said Elsayed Z. Soliman, M.D., M.Sc., M.S., director of the Epidemiological Cardiology Research Center (EPICARE) at Wake Forest Baptist and lead author on the study. "It's not always easy for people to consistently take multiple pills, even if they are needed to treat a serious condition, like CVD. This is especially true in developing countries, where cost of CVD medications is another major challenge. This one pill has the potential to improve adherence while being less costly to the population in developing countries."

To adopt the polypill approach in developing countries, a large scale clinical trial is needed, Soliman added. However, before conducting such a trial, research was needed to see if it was even possible to conduct a clinical trial in a developing country.

Going into this study, there were many perceived barriers to doing research in a developing country, Soliman said. Among them, would the country have investigators capable and willing to participate in a study and the necessary follow-up? Would patients sign up to participate? And if the pill was proven to work, would doctors even feel comfortable prescribing it?

So Soliman and colleagues brought the study to Sri Lanka, where they enrolled 216 participants without diagnosed CVD, in the hope of answering some of these questions. Half of the participants received "standard' treatment for CVD risk prevention, and the other half received the polypill. Patients were recruited as planned. Two hundred three patients (94.0%) completed the treatment program and returned for their follow-up visits. No safety concerns were reported.

These findings suggest a high rate of patient acceptability, a finding that is bolstered by the fact that the majority of patients who completed the trial – 90 percent – indicated that they would take the polypill "for life" if proven to be effective in reducing CVD risk. Approximately 86 percent of the physicians surveyed agreed with and supported use of the polypill for primary prevention and 93 percent for secondary prevention of CVD. In terms of reduction in CVD risk, both the polypill and "standard treatment" resulted in marked reductions in systolic blood pressure, total cholesterol and 10-year estimated risk of CVD.

"Our trial has fulfilled its purposes," Soliman said. "We wanted to check the feasibility of doing a large-scale clinical trial with a polypill in a developing country and to examine the acceptability of the polypill by patients and physicians, and we now know that it's feasible and acceptable."

He added that the "standard" treatment in this trial was administered by highly specialized physicians in tertiary-care centers, making it a tough competitor, yet the simple polypill held its own.

Although feasibility has been demonstrated, Soliman explained that there are other important questions about the polypill that still need answers, such as: Which patient population should a polypill target: those who have not yet been diagnosed with CVD (primary prevention) or those who have a CVD diagnosis in their medical history (secondary prevention)? Also, what components should make up the pill and in what doses will they be most effective?

"There are many questions, but a single trial will never answer all of them," Soliman said. "At least now we know that it is possible to begin looking for the answers."

More information: The study was published in Trials.

Provided by Wake Forest University Baptist Medical Center

Gardening linked to increased vegetable consumption in older adults

New research from Texas A&M University and Texas State University found that older adults who participate in gardening may be more likely to eat their veggies. The report, published in HortTechnology, presents the results of an online survey of adults aged 50+ and includes recommendations for promoting gardening "intervention" programs to older adults.

21 mar 2011--According to researchers Aime Sommerfeld, Amy McFarland, Tina Waliczek, and Jayne Zajicek, studies have shown that poor nutrition is one of several factors responsible for mortality and morbidity in the elderly and is comparable to deaths caused from cigarette smoking. "Although older adults tend to report a higher intake of fruit and vegetables than other age groups, over half of the U.S. older population does not meet the recommendation of five daily servings of fruit and vegetables." They added that several previous research studies confirmed that gardening is one way to increase individuals' fruit and vegetable intake.

The objectives of the study were to examine and compare fruit and vegetable consumption of gardeners and nongardeners, and to investigate differences in fruit and vegetable consumption of long-term gardeners compared with newer gardeners. To collect the information, an online survey was posted on a web site for one month; 261 questionnaires were completed by adults aged 50 years and older.

"Our results support previous studies that indicated gardeners were more likely to consume vegetables when compared with nongardeners. Interestingly, these results were not found with regard to fruit consumption", stated Waliczek, corresponding author of the study. The responses also showed that the length of time an individual reported having participated in gardening activities seemed to have no relationship to the number of vegetables and fruits they reportedly consumed. "This suggests that gardening intervention programs late in life would be an effective method of boosting vegetable and fruit consumption in older adults."

The number of hours per week individuals spent gardening did not appear to be a factor in vegetable and fruit consumption; the researchers observed that this indicates that even older adults with limited time or abilities—those who spend less time gardening—may consume greater quantities of vegetables and fruits than their nongardening counterparts.

Finally, the survey results showed that a person's reason for gardening had no relationship with the quantity of vegetables and fruit consumed, implying that programs designed to encourage older adults to participate in gardening need not exclusively promote the health benefits derived from gardening, but may appeal to a range of personal motives.

More information: The complete study and abstract are available on the ASHS HortTechnology electronic journal web site: http://horttech.as … act/20/4/711

Provided by American Society for Horticultural Science

Tai chi beats back depression in the elderly, study shows

The numbers are, well, depressing: More than 2 million people age 65 and older suffer from depression, including 50 percent of those living in nursing homes. The suicide rate among white men over 85 is the highest in the country — six times the national rate.

20 mar 2011--And we're not getting any younger. In the next 35 years, the number of Americans over 65 will double and the number of those over 85 will triple.

So the question becomes, how to help elderly depressed individuals?

Researchers at UCLA turned to a gentle, Westernized version of tai chi chih, a 2,000-year-old Chinese martial art. When they combined a weekly tai chi exercise class with a standard depression treatment for a group of depressed elderly adults, they found greater improvement in the level of depression — along with improved quality of life, better memory and cognition, and more overall energy — than among a different group in which the standard treatment was paired with a weekly health education class.

The results of the study appear in the current online edition of the American Journal of Geriatric Psychiatry.

"This is the first study to demonstrate the benefits of tai chi in the management of late-life depression, and we were encouraged by the results," said first author Dr. Helen Lavretsky, a UCLA professor-in-residence of psychiatry. "We know that nearly two-thirds of elderly patients who seek treatment for their depression fail to achieve relief with a prescribed medication."

In the study, 112 adults age 60 or older with major depression were treated with the drug escitalopram, a standard antidepressant, for approximately four weeks. From among those participants, 73 who showed only partial improvement continued to receive the medication
daily but were also randomly assigned to 10 weeks of either a tai chi class for two hours per week or a health education class for two hours per week.

All the participants were evaluated for their levels of depression, anxiety, resilience, health-related quality of life, cognition and immune system inflammation at the beginning of the study and again four months later.

The level of depression among each participant was assessed using a common diagnostic tool known as the Hamilton Rating Scale for Depression, which involves interviewing the individual. The questions are designed to gauge the severity of depression. A cut-off score of 10/11 is generally regarded as appropriate for the diagnosis of depression.

The researchers found that among the tai chi participants, 94 percent achieved a score of less than 10, with 65 percent achieving remission (a score of 6 or less). By comparison, among participants who received health education, 77 percent achieved scores of 10 or less, with 51 percent achieving remission.

While both groups showed improvement in the severity of depression, said Lavretsky, who directs UCLA's Late-Life Depression, Stress and Wellness Research Program, greater reductions were seen among those taking escitalopram and participating in tai chi, a form of exercise that is gentle enough for the elderly.

"Depression can lead to serious consequences, including greater morbidity, disability, mortality and increased cost of care," Lavretsky said. "This study shows that adding a mind-body exercise like tai chi that is widely available in the community can improve the outcomes of treating depression in older adults, who may also have other, co-existing medical conditions, or cognitive impairment.

"With tai chi," she said, "we may be able to treat these conditions without exposing them to additional medications."

Provided by University of California - Los Angeles

Study: Multi-tasking on the street not a good idea for older people

Older adults may put themselves at risk by talking on cell phones while crossing the street, researchers report in a new study. The researchers found that adults aged 59 to 81 took significantly longer than college students to cross a simulated street while talking on a mobile phone, and their heightened cautiousness in initiating crossing did nothing to improve their safety. Older adults on cell phones also were more likely to fail to cross in the time allotted for the task.

19 mar 2011--The findings, from researchers at the University of Illinois, appear in the journal Psychology and Aging.

In the study, 18 undergraduate students (aged 18 to 26 years) and 18 older adults crossed simulated streets of varying difficulty while either undistracted, listening to music or conversing on a hands-free cell phone. The older adults were significantly impaired on the most challenging street-crossing tasks while also engaged in a second activity, with the most pronounced impairment occurring during cell phone conversations. The younger adults showed no impairment on dual-task performance, the researchers found.

"It should be noted that we have previously found that younger adults show similar performance decrements, but under much more challenging crossing conditions," said lead author Mark Neider, a postdoctoral researcher who conducted the study with Illinois psychology professor and Beckman Institute director Art Kramer<.

"Combined with our previous work, the current findings suggest that while all pedestrians should exercise caution when attempting to cross a street while conversing on a cell phone, older adults should be particularly careful," Neider said.

More information: "Walking and Talking: Dual-Task Effects on Street Crossing Behavior in Older Adults,"


Provided by University of Illinois at Urbana-Champaign

Guided care reduces the use of health services by chronically ill older adults

A new report shows that older people who receive Guided Care, a new form of primary care, use fewer expensive health services compared to older people who receive regular primary care. Research published in the March 2011 edition of Archives of Internal Medicine found that after 20 months of a randomized controlled trial, Guided Care patients experienced, on average, 30 percent fewer home health care episodes, 21 percent fewer hospital readmissions, 16 percent fewer skilled nursing facility days, and 8 percent fewer skilled nursing facility admissions. Only the reduction in home health care episodes was statistically significant.

18 mar 2011--According to the study, Guided Care produced even larger reductions in a subset of patients who received their primary care from one well managed health system. Guided Care patients in Kaiser Permanente of the Mid Atlantic States experienced, on average, 52 percent fewer skilled nursing facility days, 47 percent fewer skilled nursing facility admissions, 49 percent fewer hospital readmissions, and 17 percent fewer emergency department visits; the differences for skilled nursing facility days and admissions were statistically significant.

"These data suggest that Guided Care can reduce avoidable health service use and costs in well managed systems," said lead author Chad Boult, MD, MPH, MBA. "Because they are part of a delivery system in which their health professionals already work as a team, Kaiser Permanente and similarly coordinated systems may be better able to achieve cost savings with a comprehensive, team-based care model such as Guided Care," said Boult. "We would like to further explore which elements of the Kaiser-Permanente culture may have helped Guided Care reduce the use of costly health services."

This multi-site, randomized controlled trial of Guided Care involving 49 physicians, 904 older patients and 319 family members recently concluded in 8 locations in the Baltimore-Washington, D.C. area. The three-year study was funded by a private-public partnership of the John A. Hartford Foundation, the Jacob and Valeria Langeloth Foundation, the Agency for Healthcare Research and Quality, and the National Institute on Aging.

Additional authors of "The Effect of Guided Care Teams of the Use of Health Services: Results from a Cluster-Randomized Controlled Trial" include Lisa Reider, MHS; Bruce Leff, MD; Kevin D. Frick, PhD; Cynthia M. Boyd, MD, MPH; Jennifer Wolff, PhD; Katherine Frey, MPH, RN, MS; Lya Karm, MD; Stephen T. Wegener, PhD; Tracy Mroz, MS, OTR/L; and Daniel O. Scharfstein, ScD.

Previous articles have reported that Guided Care patients and their family caregivers rate the quality of their health care more highly than other patients -- and that Guided Care improves physicians' satisfaction with the chronic care they provide.

Guided Care is a model of proactive, comprehensive health care provided by physician-nurse teams for people with several chronic health conditions. Primary care practices can adopt Guided Care to help become patient-centered medical homes or accountable care organizations. The model is designed to improve quality of care and quality of life, while improving the efficiency of treating the sickest and most complex patients. Guided Care teams consist of a registered nurse, two to five physicians, and the other members of the primary care office staff who work together for the benefit of each patient to:

• Assess the patient and family caregiver at home
  
• Create an evidence-based 'Care Guide' (care plan) and patient-friendly 'Action Plan'
  
• Monitor the patient's conditions monthly
  
• Promote patient self-management
  
• Coordinate the efforts of all the patient's healthcare providers
  
• Smooth the patient's transition between sites of care
  
• Inform and support family caregivers
  
• Facilitate access to community resources

More information: For more information about Guided Care, please visit http://www.GuidedCare.org

Provided by Johns Hopkins University Bloomberg School of Public Health

First successful double-blind trial of gene therapy for advanced Parkinson's disease

A multi-center gene therapy trial for patients with advanced Parkinson’s disease demonstrated reduced symptoms of the progressive movement disorder, according to a new study published in Lancet Neurology.

17 mar 2011--The study was designed to deliver the gene for glumatic acid decarboxylase (GAD) packaged in inert viral vectors into an area of the brain called the subthalamic nucleus. GAD makes an important inhibitory chemical called GABA. The subthalamic nucleus is abnormally activated in Parkinson’s disease and this activity leads to the debilitating movement problems. The idea of the gene therapy is that the billions of AAV-2 GAD viral vectors delivered into the subthalamic nucleus will increase GABA, thereby quieting this brain region.

The lead investigator of the study was Andrew Feigin, MD, associate professor of neurology and molecular medicine at The Feinstein Institute for Medical Research in Manhasset, NY, and the trial was funded by Neurologix, Inc. Early development of the therapy was done Michael Kaplitt, MD, and Matthew During, MD, co-authors of the current study. The study was conducted at seven US medical centers.

A total of 45 patients were enrolled in the study. Roughly half of the patients (23) were randomized into the sham surgery arm of the study, which meant that they had a surgical procedure that did not penetrate the brain, and received infusions of saline under the skin rather than the active GAD-containing viral vectors. A dose-escalation safety study of the gene therapy technique was published in 2007 and paved the way to this expanded double-blind placebo study to test its effectiveness in reducing motor symptoms.

Everyone in the study had a positron emission tomography (PET) brain scan before the surgery to confirm the diagnosis of Parkinson’s disease. Dr. Feigin and his colleagues found that 11 of 56 patients did not actually have Parkinson’s and they were excluded from the study. Everyone was assessed at one month, three months and six months after the genes were infused. Each patient in the active treatment received about a billion viral vectors. It is not clear how long the genes will pump out GAD to make GABA.

The scientists only included patients who got bilateral infusions delivered to the correct area of the brain, the subthalamic nucleus. There were also a few cases where the pumps delivering the treatment (the real and the placebo) malfunctioned during surgery and those cases were taken out of the analysis as well. The final analysis included 16 patients who received active (AAV2-GAD) treatment and 21 who received the sham surgery.

The main outcome measure was a change on a rating scale that assesses motor symptoms. The treated group showed a 23 percent improvement on the United Parkinson’s Disease Rating Scale, compared to a 12 percent improvement in those who received sham surgery. Normally over a six-month period patient scores remain stable or worsen. The 12 percent improvement among the sham treated group suggests a placebo response.

“This is a completely novel treatment for advanced Parkinson’s disease,” said Dr. Feigin. “The treatment was remarkably well tolerated, with mostly only mild adverse events in the AAV2-GAD treated group that were felt to be unrelated to the treatment, and completely resolved,” said Dr. Feigin. He added that other secondary clinical assessments also provided evidence for improvements from the gene therapy.

Provided by North Shore-Long Island Jewish (LIJ) Health System