Saturday, February 28, 2009

Views on Old Age May Become Reality Later

"If people hold more negative views of aging, they may be less likely to walk the extra block or engage in healthy behaviors as they get older," explained study author Becca Levy, an associate professor of epidemiology and psychology at Yale School of Public Health.

The findings don't confirm that negative assumptions about aging in young people directly cause them to develop cardiovascular problems later. But there's clearly a link, Levy said, and the association held up even when researchers adjusted their statistics to take into account the influence of other factors such as depression.

Levy and colleagues have been studying the stereotypes older people have about aging, trying to gauge how they affect their health. "This is our first study to look at younger adults and the age stereotypes they express, and follow them over time," said Levy.

The researchers looked at an aging study that tracked 386 people aged 18 to 49, beginning in 1968. Only 81 people in the group were women; 305 were men.

The participants took surveys that asked them if they believed various statements about the elderly, such as "old people are helpless."

The researchers then tried to find links between their responses and their likelihood of suffering from a heart attack, heart failure, angina, stroke or "mini-strokes" by 2007.

The findings were published in the March issue of Psychological Science.

After adjusting their figures to account for the influence of other factors, the researchers found that 25 percent of those who believed negative age "stereotypes" had experienced heart problems in the 30 years after answering the initial questions. By comparison, the figure was 13 percent in those who believed positive stereotypes about aging.

Previous research has suggested that people exposed to negative stereotypes have more difficult tolerating stress, Levy said. "I think negative stereotypes have components that are more stress-inducing."

It's also possible that genetics play a role, said S. Jay Olshansky, a professor at the School of Public Health at the University of Illinois at Chicago.

"Perhaps younger people with positive views of aging have them, because they are healthier or because they have older relatives who are healthier," Olshansky said. "In either case, the outcome would not be a product of the 'belief,' but rather, the fact that they inherited a genetic potential for a healthier old age that they see and experience in themselves or see in their older relatives."

It's unlikely that simply thinking "happy thoughts" about aging will make people live happily ever after, he said. "Health begets health -- when you see healthy older relatives, you are likely to develop a positive view of aging."

Emotional stress may raise older adults' fall risk

NEW YORK, 28 feb 2009– While physical frailty puts elderly adults at risk of falls and bone fractures, emotional distress can be the immediate trigger of some of those accidents, new research suggests.

In a study of older adults hospitalized for fall-related hip fractures, Swedish researchers found that the patients' odds of suffering a fall were elevated for up to one hour after an emotionally upsetting event.

The risk rose by 12-fold following a bout of anger, and by 20 times after a generally stressful incident. Meanwhile, sadness was linked to a nearly 6-fold increase in the risk of a fall-related fracture, the researchers report in the online journal BMC Geriatrics.

The study cannot reveal why emotional distress might contribute to falls. But one possibility is that it distracts elderly adults' attention away from maintaining their posture and balance, according to Dr. Jette Moller and colleagues at the Karolinska Institute in Stockholm.

Stress might also interfere with older adults' visual focus, another key to maintaining balance and preventing falls.

"We think it is good if elderly adults are aware that emotional stress might interfere with (their) attention while walking, standing or while changing posture," Moller told Reuters Health.

Emotional stress may not be avoidable, she noted, but people can alter their reactions to it. When emotions are running high, older adults might be better off sitting down until the stress has passed, Moller suggested.

That could be especially important for people at high risk of falling due to physical impairments or poor vision, the researcher added.

The study involved 137 patients age 65 and older who were treated for a fall-related hip fracture at one of two hospitals. Nurses interviewed each patient about the injury and the activities they'd been involved in over the two days prior to the accident.

They also asked the patients whether and when they'd had any feelings of anger, sadness, worry, anxiety or stress during that time.

While most patients did not report any emotional stress shortly before their fall, episodes of anger, stress or sadness did appear to precipitate falls in a small number of patients.

This appears to be the first study to find a link between emotional distress and falls, according to Moller's team. More studies, the researchers say, are needed to confirm the findings, and to uncover the reasons for the connection.

SOURCE: BMC Geriatrics, online February 9, 2009.

'Stay Dry' tested to help men with incontinence problems from prostate cancer treatments

CLEVELAND, 28 feb 2009—Following surgery and radiation treatments for prostate cancer, most men suffer some degree of incontinence. For approximately 14 percent of these men, the problem lingers five years later.

Improving the lives of these men is the goal of a new "Stay Dry" intervention being tested by Amy Zhang, assistant professor of nursing at the Frances Payne Bolton School of Nursing at Case Western Reserve University, and colleagues from University Hospitals Case Medical Center, Cleveland Clinic and the Louis Stokes Cleveland Department of Veteran Affairs Medical Center.

Researchers have received a four-year, $2.4 million grant from the National Institutes of Health to determine the effectiveness of teaching pelvic floor muscle exercises combined with biofeedback techniques and subsequent therapy.

The new study will enroll 312 men who have undergone prostate surgery at the three medical centers. Men will be selected at random to be part of one of three groups. The first group will receive exercise instructions with biofeedback and group therapy. The second group will also receive exercise instructions with biofeedback, but will receive six phone sessions instead of group therapy. The third, control group will receive standard care, which includes verbal instructions from their doctors about how to control incontinence .

Men will be assessed over seven months to find the differences between the group that received biofeedback and six group meetings, biofeedback and six phone contacts every other week for three months, and the group that receives usual care.

The study also involves two sub-studies. One research project will examine the overall cost effectiveness of this new intervention technique long term, as compared with standard care. A second project will analyze the physical changes to 51 men with moderate to severe incontinence to determine muscle changes as a result of the interventions.

The consequences of incontinence

Incontinence is suffered by some of the 200,000 men who annually undergo surgery, radiation or a combination of the two after a prostate cancer diagnosis.

Leakage of urine is a common side effect, as the surgical procedure to remove cancerous tumors involves some degree of loss of control of the sphincter muscle, which supports the bladder.

In addition to recovering from surgery and treatment, many men have to deal with the consequences of incontinence, including distress, self-identity issues and increased healthcare costs due to potential loss of work time, nursing care or medical supplies.

Finding an effective intervention is increasingly important, said Zhang. "While most men with prostate cancer are older, sophisticated diagnostic methods are able to find the cancer at a younger age, and the population with prostate cancer is growing," said Zhang.

"Strengthening the pelvic muscles shows promise in benefiting these men," said Zhang.


Research collaborators:

CASE WESTERN RESERVE UNIVERSITY: Shirley Moore, associate dean of research at FPB and director of the Center of Excellence for Self-Management Advancement Through Research and Translation, and Nahida Gordon, professor of medicine and nursing; and formerly from the university, Laura Siminoff, professor and chair of the department of Social and Behavioral Science, Virginia Commonwealth University.

CLEVELAND CLINIC: Eric Klein, professor of surgery and director of Cleveland Clinic's Section of Urologic Oncology; Alex Fu, assistant professor and health economist at the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University.

VETERAN AFFAIRS MEDICAL CENTER: Donald Bodner, professor of urology, Dr. Hui Zhu, assistant professor of urology, Gerald Strauss and Kim Schaub, health psychologists.

'Framingham Score' Proposed for Atrial Fibrillation Risk

A patient's 10-year risk for developing atrial fibrillation can be calculated from readily available clinical data, according to a Lancet study.

28 feb 2009--Framingham Study researchers followed a cohort of roughly 4800 middle-aged and older adults, initially without AF, for 10 years. During that period, 10% developed AF. The condition was most strongly associated with age, BMI, systolic pressure, hypertension, PR interval, cardiac murmur, and heart failure. The authors conclude that their score, based on these factors, "is reasonably accurate for stratification of individuals into risk categories."

Commentators call the work a step in the right direction — a step away from the present circumstance in which, rather than attempting prevention, "we have accepted that ... atrial fibrillation is an unavoidable evil and [have become] preoccupied with preventing complications, such as heart failure and stroke."


Lancet article (Free abstract; full text requires subscription)

FDA Calls for Boxed Warning on Gastrointestinal Drug

28 feb 2009--All metoclopramide-containing products must carry a boxed warning on the risk for tardive dyskinesia, the FDA announced on Thursday. (The products' labels currently include a less severe warning on the condition.)

Metoclopramide, used to speed gastric emptying and as an anti-emetic, may put patients at risk when used chronically or in high doses, and treatment beyond 3 months is not recommended. According to the FDA, chronic use "should be avoided in all but rare cases where the benefit is believed to outweigh the risk."

Older individuals, especially women, appear to be at highest risk.

Affected products include metoclopramide oral solution and Reglan sold in tablet, oral disintegrating tablet, and injectable form.


FDA alert (Free)

Friday, February 27, 2009

Drugs for Prostate Cancer Prevention?

27 feb 2009--The American Society of Clinical Oncology and the American Urological Association have concluded that men "may benefit from a discussion" of the benefits and potential risks of using 5-alpha-reductase inhibitors, including finasteride and dutasteride, for preventing prostate cancer, the Journal of Urology reports.

Research suggests that treatment over 7 years reduces the risk for prostate cancer diagnosis by about 25%, relative to placebo.

For men considering use of 5-alpha-reductase inhibitors for chemoprevention, physicians should explain that:

  • the drugs do not eliminate the risk for prostate cancer;
  • the risk for high-grade prostate cancer is uncertain;
  • the drugs' long-term effect on prostate cancer incidence is unknown;
  • patients may experience temporary sexual adverse effects.


Journal of Urology article (Free PDF)

Four Different Diets — Four Similar Results

27 feb 2009--Diets emphasizing foods with varying proportions of fat, protein, or carbohydrate all confer the same degree and duration of weight loss, according to a New England Journal of Medicine study.

Some 800 adults with BMIs between 25 and 40 were randomized to one of four diet groups, with each participant having a caloric deficit of 750 kcal/day relative to baseline. There were diets with high- and low-fat components, high- and average-protein components, and varying degrees of carbohydrate content. (See hyperlinked table below.)

After 2 years, the amount of weight lost was similar among the four groups (most of the loss took place in the first 6 months). Those losing the most weight were those with the best attendance at group meetings.

In Journal Watch General Medicine, Abigail Zuger notes: "Perhaps the average dieter's enthusiasm for counting out 14 walnut halves for a high-fat dinner simply wanes, rendering the nutrient composition of all limited-calorie eating plans pretty much the same."


NEJM article (Free)

NEJM editorial (Free)

Reminders to Patients — but Not Physicians — Increase Colorectal Cancer Screening Rates

27 feb 2009--Mailed reminders to patients that they're overdue for colorectal cancer screening produce "a modest increase" in screening rates, while electronic reminders to their physicians are less successful, reports Archives of Internal Medicine.

Some 22,000 patients overdue for screening and 110 primary care physicians in a group practice were randomized either to receive reminders or not to. Patients' reminders arrived with a fecal occult blood test kit; physicians were reminded electronically during visits with overdue patients.

After 15 months, patients getting reminders showed a modest but significant increase in screening rates over controls (44% vs. 38%); physicians' screening rates showed no difference between groups.

The authors note that nearly half the patients for whom colonoscopy was ordered never had the procedure, thus underscoring "the need for more effective communication with patients." Similarly, about half the physicians considered the electronic reminders "ineffective."


Archives of Internal Medicine article (Free abstract; full text requires subscription)

Alzheimer's Plaques More Complex Than Thought

It was already known that amyloid plaques affect neurons. But the researchers at the MassGeneral Institute for Neurodegenerative Disease in Boston found that amyloid plaques may also increase the activity of astrocytes, nervous system cells that play a supporting role in brain function. This astrocyte hyperactivity isn't confined to regions directly beside the plaques, but extends throughout the brain.

The findings appear in the Feb. 27 issue of Science.

"Our work suggests that amyloid plaques might have a more complex role in altering brain function than we had thought," study author Kishore Kuchibhotla said in a hospital news release. "Plaques develop rapidly and have been shown to cause relatively acute, localized neuro-toxicity. We show that astrocytes could provide a network mechanism that may stretch the impact of plaques to more distant areas of the brain."

Since astrocytes make up about half the volume of the brain, Kuchibhotla and colleagues wanted to determine if astrocyte function may be affected by amyloid plaques. They used imaging techniques that gave them a real-time view of brain cell activity in living mice.

The researchers found that astrocytes flicker on and off at a much higher rate in mice genetically altered to have an abundance of brain plaques than in those without plaques. The plaque-associated astrocyte activity appeared to be synchronized and traveled to distant areas of the brain in a wave-like fashion.

Using another type of imaging technology, the researchers also found that mice with plaques had higher-than-normal resting calcium levels throughout their astrocyte network. Astrocyte activity wasn't reduced when the researchers blocked the activity of neurons. This indicates that the known impact of amyloid plaques on neurons isn't responsible for increased astrocyte activity.

"This is the first clear evidence in a live animal model that amyloid plaques perturb calcium signaling across the astrocyte network via a neuron-independent mechanism," Kuchibhotla said. "It has been suggested that these intercellular calcium waves, which previously had been observed only in response to some sort of external stimulus, indicate the existence of, or response to, a traumatic insult. Our data support this hypothesis, but whether the calcium signals we observed actually protect or harm cells remains to be determined."

"One key question will be how increased astrocyte signaling impacts neuronal function, and another will be whether astrocyte activity limits or intensifies plaque deposition," Kuchibhotla added.

FDA slaps warning on heartburn drug tied to spasms

The Food and Drug Administration said the drug, widely known as Reglan, has been shown to cause spasms and tics when used for long periods of time or at high doses. The problems include uncontrollable movement of the limbs, face and tongue, and are usually irreversible, even after patients stop taking the drug, according to the FDA's warning.

The agency is requiring drugmakers to add a black box warning, the most serious type available, to their products.

Manufacturers also will be required to distribute medication safety guides to patients.

The drug was marketed by Wyeth for a number of years. However, the Madison, N.J.-based company sold the tablet form to Schwarz Pharma in 2001 and the injectable form to Baxter International in 2002. The drug also is marketed by a number of generic companies.

The drug's current labeling already mentions risks of developing the spasms, called dyskinesia, but the agency's action Thursday elevates the warning to the top of the label. Reglan, known generically as metoclopramide, comes in a variety forms, including injections and edible syrups. The drug works by speeding up the muscles used in digestion and relieving painful stomach acid reflux.

More than 2 million U.S. patients use the drugs, according to the FDA.

"The chronic use of metoclopramide therapy should be avoided in all but rare vases where the benefit is believed to outweigh the risk," said Dr. Janet Woodcock, director of FDA's drug center.

Regulators said patients who face the greatest risks include the elderly, especially women, and those who have been taking the drug for more than three months.

The agency based its decision on recently published studies suggesting metoclopramide is the leading cause of pharmaceutical-related movement disorders. One study showed that roughly 20 percent of patients who take the drug longer than three months develop dyskinesia.

Thursday, February 26, 2009

Scientists Spot New Clue to Alzheimer's

They found that cellular proteins called prions activate the process by which amyloid-beta peptides impair brain function in people with the disease.

"It's been a black box. We have known that amyloid beta is bad for the brain, but we have not known exactly how amyloid-beta does bad things to neurons," the study's senior author, Stephen M. Strittmatter, a professor of neurology and director of Cellular Neuroscience, Neurodegeneration and Repair at Yale School of Medicine, explained in a university news release.

The researchers looked at hundreds of thousands of candidates for potential disease-mediating receptors for the specific form of amyloid-beta linked to Alzheimer's and identified cellular prion proteins as the most likely culprit. It appears, they said, that amyloid-beta peptides attach to cellular prion proteins, resulting in damage to brain cells.

"They start the cascade that makes neurons sick," Strittmatter said.

Cellular prion proteins are normally harmless and exist in all cells, but they can change shape and cause disease. And because the proteins are involved in the early stage of disease development, they're a promising target for the development of new Alzheimer's treatments, he said.

The study does not suggest that these proteins convert to an infectious agent in Alzheimer's disease, but the findings do suggest that the role of these normally harmless proteins in common neurodegenerative diseases warrants further study, Strittmatter said.

The study appears in the Feb. 26 issue of the journal Nature.

Women's fertile lifespan linked to Parkinson's risk

"These findings suggest that longer duration of exposure to the body's own (endogenous) hormones may help protect the brain cells that are affected by Parkinson's disease," said the authors of the study.

A woman's fertile lifespan stretches from her first menstruation to menopause. Women with fertile lifespans longer than 39 years had 25 percent lower risk of developing Parkinson's, compared to women with ones 33 years or shorter, said the researchers, who will presented their findings at the annual meeting of the American Academy of Neurology, April 25-May 2 in Seattle, Washington.

They also found that women who had four or more pregnancies were 20 percent more at risk for Parkinson's than those with three or fewer pregnancies.

And women who underwent hysterectomy, or surgical menopause, had almost twice the risk of developing Parkinson's. The risk was double if they had previously taken hormone therapy and stopped than if they had never taken hormone therapy.

Taking hormones did not have any effect on Parkinson's risk for women who had natural menopause, the researchers said.

"This study does not support a role for treatment with hormone therapy in Parkinson's, but there are still many unanswered questions," said study author Rachel Saunders-Pullman, of Albert Einstein College of Medicine in Bronx, New York.

The study, funded in part by the US National Institutes of Health, involved 74,000 women with natural menopause and 7,800 with surgical menopause.

Because Parkinson's disease is more common in men than in women, researchers have long hypothesized about the role of hormones in the disease.

Tests Might Diagnose, Predict Prostate Cancer

Both studies were presented Tuesday at the 2009 Genitourinary Cancers Symposium in Orlando, Fla., sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

"Current methods for diagnosing prostate cancer -- PSA (prostate-specific antigen) and digital rectal exam -- have low specificity," lead researcher Jack Groskopf, a senior research scientist for Gen-Probe Inc., in San Diego, said during a Tuesday teleconference. "As a result, the majority of prostate biopsies are negative, and you could argue that we are doing too many biopsies."

There is a need for a better test and a better way to determine which men need aggressive treatment and which men need only monitoring, Groskopf said.

Toward these ends, Groskopf's team developed a urine test that can identify particular gene fusions associated with prostate cancer. The gene fusions involve the TMPRSS2 gene and the ERG gene. This particular fusion is found in about 50 percent of men with prostate cancer and can be identified in urine, Groskopf said.

"This is an ideal target for a diagnostic test," he said. "Another exciting aspect of the gene fusions is that they potentially provide an explanation for the progression of prostate cancer."

Using their test in 556 men before they underwent a biopsy, the researchers found the exam had a "specificity" for prostate cancer of 84 percent, compared with 27 percent for a PSA reading. The "sensitivity" of the test was 42 percent, but only half of men with the disease have this gene fusion, Groskopf noted.

The urine test also showed that it correlated well with other measures of gauging the aggressiveness of prostate cancer, Groskopf said.

In the second study, Dutch researchers used PSA readings, a family history of prostate cancer, the size of the prostate, and a previous negative biopsy to create a chart to predict the risk of developing prostate cancer.

The researchers tested their formula in 5,176 men who were screened for prostate cancer after four years. "PSA is still the most significant predictor, but there are other factors that also contribute risk," Monique J. Roobol, who's with the Department of Urology at the Erasmus Medical Center in Rotterdam, said during the teleconference.

The overall risk of developing prostate cancer was 5.1 percent, Roobol said. Men whose PSA levels were 1.5 nanograms per milliliter were seven times more likely to develop prostate cancer than men with a lower PSA, she said.

A family history of prostate cancer will increase the risk of the disease, as will having a small prostate, Roobol said. But if you have had a negative prostate biopsy, your risk decreases, she noted.

Men who have higher risk factors may need more frequent screening, Roobol said. "Men below this threshold may need less frequent screening," she added.

Dr. Durado Brooks, director of colon and prostate cancer prevention programs at the American Cancer Society, doesn't think either of these studies will change clinical practice anytime soon.

Discussing the first study, Brooks noted that this gene fusion is only found in half of prostate cancers. "If you don't find it, it doesn't mean prostate cancer isn't there," he said. "From a screening standpoint, this test is not likely to be very helpful at all."

As for the second study, Brooks said he wasn't sure that integrating these risk factors would effect patient treatment. "This is interesting, but I don't see how this is going to alter practice," he said.

A third study presented Tuesday looked at the benefit of using PET scans to diagnose bladder cancer. A research team led by Dr. Andrea B. Apolo, of Memorial Sloan-Kettering Cancer Center in New York City, compared PET scans with CT scans and MRIs to see which imaging technique was better at diagnosing the disease.

PET scans were more sensitive and specific in finding bladder cancer and distinguishing local from metastasized cancer, which is cancer that has spread to other sites in the body. In 68 percent of the cases studied, treatment plans were changed based on the results of the PET scans, the researchers said.

The researchers said these results argue for using PET scans as standard practice in diagnosing bladder cancer.

Just being overweight can shorten lifespan: study

PARIS , 26 feb 2009--– Simply being overweight, but not obese, from an early age boosts the risk of premature death by a third -- as much as smoking up to 10 cigarettes a day, researchers in Sweden reported Wednesday.

People who are clinically obese by the age of 18 more than double that risk, putting themselves in the same danger zone as long-term heavy smokers of normal weight, they found.

And combining the two factors accumulates the risk: an obese heavy smoker, for example, is nearly five times as likely to die prematurely than a non-smoker who is neither too thin nor too fat.

At least a billion people in the world are overweight, and nearly a third of them are obese, according to the World Health Organisation (WHO). Obesity rates have soared over the last three decades, especially among children.

Earlier studies have shown that being excessively fat shortens lifespan and leads to increased rates of chronic disease such as diabetes and arteriosclerosis.

But researchers have disagreed sharply up to now on whether being above ideal weight without crossing the line to obesity takes years off one's life.

Nor have previous studies directly compared the impact on mortality of smoking and excess weight.

The study designed by Martin Neovius of the Karolinska Institute in Stockholm goes a long way to settling the debate, and shows clearly for the first time that being too heavy can be as dangerous as smoking a couple of packs a day.

Neovius and colleagues analysed data for 45,000 men who underwent mandatory military conscription tests in Sweden in 1969 and 1970 at the age of 18.

Data included participants' smoking habits, and their body-mass index (BMI) -- weight in kilogrammes divided by the square of one's height in meters.

A BMI of 25-to-30 indicates being overweight, while above 30 means one is obese. The range of normal weight is 18.5-to-24.9.

The follow up period was, on average, 38 years. During that time, 2,897 subjects died.

The lowest death rate, as expected, was among non-smokers of normal weight. But researchers were surprised to find that being obese carried a greater risk of premature death than being a heavy smoker.

Even more startling, however, were the dangers of being overweight.

"What we show is that for the overweight, there is a significantly increased risk of premature death, similar to smoking one-to-ten cigarettes a day," said Neovius in a phone interview.

Two key studies in the United States -- one at the Center for Disease Control and the famous Nurses' Health Study at Harvard -- had arrived at opposite conclusions on this question.

"Our results confirm the Harvard findings," said Neovius, whose research was published in the British Medical Journal.

The two studies are highly complementary, he added. "We find exactly the same in men and they did in women," erasing any doubts as to possible differences across the sexes.

The Swedish study did find, however, that being severely underweight -- a BMI of under 17 -- carried about the same risk of early death as being overweight or a light smoker.

Policy makers should take note of these results, and increase awareness of the risks related to being too fat, or too thin, Neovius said.

"Anti-smoking campaigns have been very successful. But we don't have any good preventative programmes for overweight and obesity," he said of Sweden, adding that the situation elsewhere is comparable.

More evidence links alcohol, cancer in women

A quarter of the women reported no alcohol use. Nearly all the rest reported fewer than three drinks a day; the average was one drink a day. Researchers compared the lightest drinkers — two or fewer drinks a week — with people who drank more.

Each extra drink per day increased the risk of breast, rectal and liver cancer, University of Oxford researchers reported Tuesday in the Journal of the National Cancer Institute. The type of alcohol — wine, beer or liquor — didn't matter.

That supports earlier research, but the new wrinkle: Alcohol consumption was linked to esophageal and oral cancers only when smokers drank.

Also, moderate drinkers actually had a lower risk of thyroid cancer, non-Hodgkin's lymphoma and renal cell cancer.

For an individual woman, the overall alcohol risk is small. In developed countries, about 118 of every 1,000 women develop any of these cancers, and each extra daily drink added 11 breast cancers and four of the other types to that rate, the study found.

But population-wide, 13 percent of those cancers in Britain may be attributable to alcohol, the researchers concluded.

Moderate alcohol use has long been thought to be heart-healthy, something the new research doesn't address but that prompts repeated debate about safe levels. U.S. health guidelines already recommend that women consume no more than one drink a day; two a day for men, who metabolize alcohol differently.

"You have to balance all those things out," said Dr. Philip J. Brooks, who researches alcohol and cancer at the National Institutes of Health. "This kind of information is important for people to know and to consult with their physician about the various risk factors they have."

Tuesday, February 24, 2009

Patient knowledge of health information influences cancer treatment

24 feb 2009--A new analysis finds that when colorectal cancer patients seek out health information from the internet and news media, they are more likely to be aware of and receive the latest treatments for their disease. Published in the April 1, 2009 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the study indicates that patients can influence their own treatment, in some cases in inappropriate ways.
In their review, authors led by Stacy Gray, M.D. of the Dana-Farber Cancer Institute in Boston note that in the last several decades, patients have become more involved in their health care as patient autonomy has become increasingly important. That change has been accompanied by unprecedented growth in the amount of health information available to patients. Studies show nearly four out of ten of cancer patients seek cancer information on the internet. But the authors say it is unclear how these phenomena influence a cancer patient's treatment.
Dr. Gray and colleagues from the NCI Center of Excellence in Cancer Communication Research at the University of Pennsylvania Annenberg School designed a study to examine the relationship between information-seeking among 633 colorectal cancer patients chosen at random from the Pennsylvania Cancer Registry and the use of novel new agents for the disease. The investigators focused on the use of the targeted therapies bevacizumab (Avastin) and cetuximab (Erbitux) because of these drugs' clinical importance, significant media coverage, and recent approval by the U.S. Food and Drug Administration.
Dr. Gray and her team hypothesized that there would be a relationship between information seeking and awareness of these targeted therapies among colorectal cancer patients. They also hypothesized that patients who seek information may ask their physicians about these targeted therapies and may be more likely to receive them than patients who do not seek information.
The researchers found that high levels of information seeking were strongly associated with both awareness of and receiving treatment using targeted therapies. Patients who sought information about treatments for colorectal cancer were 2.83 times more likely to have heard about targeted therapies and 3.22 times more likely to have received targeted therapies than people who did not seek information. These associations were present for patients with advanced disease where use of targeted therapies is FDA approved as well as for patients with early stages of the disease where their use is not FDA approved.
"These findings emphasize the importance of exploring patient influence on physician prescribing patterns and understanding the impact of information seeking on cancer outcomes," the authors write.
Article: "Colon cancer patient information seeking and the adoption of targeted therapy for on-label and off-label indications." Stacy W. Gray, Katrina Armstrong, Angela DeMichele, J. Sanford Schwartz, and Robert C. Hornik. CANCER; Published Online: February 23, 2009 (DOI: 10.1002/cncr.24186); Print Issue Date: April 1, 2009.
Mechanisms that prevent Alzheimer's Disease: Enzymatic activity plays key role

Journal of Alzheimer's Disease publishes new findings on the protective effects of the enzyme a-secretase

Mainz, Germany,24 feb 2009-- In a project involving the collaboration of several institutes, research scientists of the Johannes Gutenberg University Mainz have succeeded in gaining further insight in the functioning of endogenous mechanisms that protect against the development of Alzheimer's disease. It was found that the activity of the enzyme α-secretase is mainly responsible for the protective effect.
"In the past, we postulated that the enzyme α-secretase was involved in preventing the formation of cerebral plaques characteristic of Alzheimer's disease and also enhanced cerebral functions, such as learning and memory," explained Professor Falk Fahrenholz of the Institute of Biochemistry. His research group has been working in cooperation with the Clinic of Psychiatry and Psychotherapy of the university's Faculty of Medicine and the Central Animal Laboratory Facility (ZVTE) to discover the mechanism for the beneficial effects of α-secretase. The Journal of Alzheimer's Disease (JAD) presents the results of this project in its February 2009 issue.
α-secretase is an endogenous enzyme that is present in the nerve cells of the brain, where it is responsible for the cleavage of an Aβ into Aβ domain. The result is a soluble protein fragment that promotes the growth of nerve cells and thus prevents the development of cerebral deterioration caused by Aβ. However, if the enzyme β-secretase is active, a chain reaction is initiated that subsequently results in the development Aβ initializing the cascade of Alzheimer's disease through formation of Aβ. "You could say that α-secretase is the good enzyme, and β-secretase the bad en-zyme," Fahrenholz commented. "We now want to find out how to activate this 'good' enzyme or increase its concentrations in the brain as a way of combating this disease."
With this in view, the collaborating partners have been investigating whether the positive effects of α-secretase are attributable to its enzymatic activity or whether the protective effect is due to other properties of the enzyme. Enzymes play an important role in the metabolism as they control, regulate and catalyse numerous biochemical processes. "The α-secretase enzyme is a highly complex one, with many other functions. For example, it also relays signals from the intercellular space into cells and interacts with molecules on other cells." Fahrenholz and his colleagues have now established, following investigations in a transgenic mouse model, that it is the enzymatic activity alone that guarantees the protective effects. If this activity is neutralised, the laboratory mice exhibit the symptoms that are characteristic of Alzheimer's disease: impaired learning ability, poor memory capacity and the build-up of Aβ plaques. It is thus possible that the enzymatic activity of α-secretase could represent the starting point for the development of future treatments.
At the same time, the researchers were able to confirm with their experiments that it is not the plaque build-up itself that is responsible for the loss of memory capacity. The cytotoxic substances that accumulate in plaques only destroy neuron synapses when they are still in solution. Prof. Fahrenholz concludes: "It is important to consider other aspects in addition to the plaques themselves, particularly their precursors, which are a real cause of the disease."
Lowering your cholesterol may decrease your risk of cancer

Boston, MA, 24 feb 2009-- — Current research suggests that lowering cholesterol may block the growth of prostate tumors. The related report by Solomon et al, "Ezetimibe Is an Inhibitor of Tumor Angiogenesis," appears in the March 2009 issue of The American Journal of Pathology.
High cholesterol not only leads to atherosclerosis and heart disease, but may also contribute to cancer growth and progression. Prostate cancer is the most common non-skin cancer in the United States, affecting approximately 1 in 6 men. Prostate tumors accumulate high levels of cholesterol, and tumor incidence correlates with eating a high fat/high cholesterol diet "Western" diet. In addition, prostate tumor progression has been linked to serum cholesterol levels.
To examine the role of high cholesterol in prostate cancer, Dr. Keith Solomon and colleagues fed mice a high fat/high cholesterol "Western" diet. They found that high cholesterol levels promoted tumor growth and that Ezetimibe (Zetia™), which blocks the absorption of cholesterol from the intestine, could prevent this increased tumor growth. Ezetimibe also blocked a cholesterol-mediated increase in angiogenesis, the growth of new blood vessels required for tumor progression. These data suggest that reducing cholesterol levels may inhibit prostate cancer growth specifically by inhibiting tumor angiogenesis.
The article from Solomon et al suggests "that cholesterol reduction, which is routinely accomplished pharmacologically in humans, may reduce angiogenesis, ultimately leading to less aggressive tumors." "Lowering cholesterol levels whether through diet, exercise, or the use of safe cholesterol-lowering drugs is known to provide a substantial benefit to patients—in the future it may be possible to add reduced risk of serious prostate cancer to that list of benefits" says Solomon. "We are in the process of working with clinicians to translate these findings into potential human studies. If we can demonstrate the effects noted in our pre-clinical studies in human patients we may be save lives and improve the quality of life," adds Dr. Michael Freeman, senior author of the study.
This work was supported by grants from the National Institutes of Health and the US Army Department of Defense.
Solomon KR, Pelton K, Boucher K, Joo J, Tully C, Zurakowski D, Schaffner CP, Kim J, Freeman MR: Ezetimibe Is an Inhibitor of Tumor Angiogenesis. Am J Pathol 2009 174: 1017-1026
For press copies of the articles, please contact Dr. Angela Colmone at 301-634-7953 or
Calcium tied to lower cancer risk in older people

CHICAGO, 24 feb 2009-- – A study in nearly half a million older men and women bolsters evidence that diets rich in calcium may help protect against some cancers. The benefits were mostly associated with foods high in calcium, rather than calcium tablets.
Previous studies have produced conflicting results. The new research involved food questionnaires from participants and a follow-up check of records for cancer cases during the subsequent seven years. This research method is less rigorous than some previous but smaller studies.
But because of its huge size — 492,810 people and more than 50,000 cancers — the new study presents powerful evidence favoring the idea that calcium may somehow keep cells from becoming cancerous, said University of North Carolina nutrition expert John Anderson, who was not involved in the study.
The study was run jointly by the National Institutes of Health and AARP. The results appear in Monday's Archives of Internal Medicine.
National Cancer Institute researcher Yikyung Park, the study's lead author, called the results strong but said more studies are needed to confirm the findings.
Duke University nutrition researcher Denise Snyder said the results support the idea that food rather than supplements is the best source for nutrients.
Participants were AARP members aged 50 to 71 who began the study in the mid-1990s. A total of 36,965 men and 16,605 women were later diagnosed with cancer. There were more than 10 different kinds of cancer, the most common being prostate, breast, lung and colorectal.
Compared with people who got little calcium, those who consumed the most had the lowest chances of getting colon cancer. Those in that highest category got on average 1,530 milligrams a day among men and 1,881 milligrams daily among women. The recommended amount for older people is 1,200 milligrams, and getting much more than that didn't result in any greater protection. Adults can get that amount from four cups of milk or calcium-fortified orange juice.
Men who got the most calcium from food were about 30 percent less likely to get cancer of the esophagus, about 20 percent less likely to get head and neck cancer and 16 percent less likely to get colon cancer, when compared to men who got low amounts of calcium.
Among women, those who got the most food-based calcium were 28 percent less likely to get colon cancer than low-calcium women.
In men, calcium supplements only seemed to help protect against colon cancer; for women, supplements meant a lower risk for liver cancer, which is rare.
Some previous studies have linked diets high in calcium with prostate cancer but the current study found no such risk.
Adults who ate the most calcium also tended to be healthier overall than the others.
Northwestern University preventive medicine instructor Patricia Sheean called the results impressive. But she noted that all those in the study, AARP members, may have been healthier and wealthier than the general U.S. population so it's not clear if the results would apply to the wider population.
Study: Taking B vitamins can prevent vision loss

CHICAGO, 23 feb 2009-- – Taking B vitamins can prevent a common type of vision loss in older women, according to the first rigorous study of its kind. It's a slight redemption for vitamin supplements, which have suffered recent blows from research finding them powerless at preventing disease.
Age-related macular degeneration is the leading cause of blindness in people 65 and older, with nearly 2 million Americans in the advanced stage of the condition. It causes a layer of the eye to deteriorate, blurring the center of the field of vision and making it difficult to recognize faces, read and drive. There's no cure, but treatment, including laser therapy in some cases, can slow it down.
Preventing it has been more elusive.
"Other than avoiding cigarette smoking, this is the first suggestion from a randomized trial of a possible way to reduce early stage AMD," said William Christen of Harvard-affiliated Brigham and Women's Hospital in Boston, who led the research. He said the findings should apply to men as well.
The women in the study who took a combination of B vitamins — B-6, folic acid and B-12 — reduced their risk of macular degeneration by more than one-third after seven years compared to women taking dummy pills.
The study, involving more than 5,000 women ages 40 and older at risk for cardiovascular disease, appears in Monday's Archives of Internal Medicine.
Allen Taylor, director of the Laboratory for Nutrition and Vision Research at Tufts University in Boston, said the study was strong because patients were assigned at random and followed for a long time. But because the findings were teased out of a larger experiment for heart disease, there wasn't strict categorization of the type and severity of the eye disease, said Taylor, who does similar research but was not involved in the new study.
Among women taking the B vitamins there were 55 cases of AMD. In the placebo group, there were 82 cases. More serious cases, causing significant vision loss, totaled 26 in women taking B vitamins and 44 in those taking dummy pills.
There were too few cases of the most advanced AMD to make claims about vitamins' potential benefits, Christen said.
B vitamins lower homocysteine, a blood substance once thought to raise heart disease risk, but the nutrients weren't helpful for that in the larger study on cardiovascular disease.
The eye's small blood vessels may respond better to B vitamins' effect on homocysteine than the body's large vessels, Christen said.
It's too soon to recommend B vitamins to people who want to prevent age-related vision loss, he said. But people who already have the disease should talk to their doctors about over-the-counter eye-protecting supplements, including vitamins C and E and zinc, which prior studies have shown slow the disease.
Christen and others recommended food sources of B vitamins and folic acid such as meat, poultry, fortified cereals, beans, nuts, leafy vegetables, spinach and peas.
The study was funded by the National Institutes of Health. Vitamins and placebos were provided by chemical maker BASF Corp., which did not participate in the study otherwise. Some of the researchers reported past funding from pharmaceutical and nutritional supplement makers.

Sunday, February 22, 2009

Prostate specific antigen testing may be unnecessary for some older men

22 feb 2009--Certain men age 75 to 80 are unlikely to benefit from routine prostate specific antigen (PSA) testing, according to a Johns Hopkins study published in the April 2009 issue of The Journal of Urology.

The researchers found that men in this age group with PSA levels less than 3 nanograms per milliliter are unlikely to die of or experience aggressive prostate cancer during their remaining life, suggesting that the use of PSA testing in many older men may no longer be needed.

The study, led by researchers from the Johns Hopkins University School of Medicine and the National Institute on Aging's Baltimore Longitudinal Study of Aging (BLSA), reviewed data from 849 men (122 with and 727 without prostate cancer) who were participating in the BLSA and who had undergone regular PSA testing.

Results showed that among men who were over 75 with PSA levels less than 3 nanograms per milliliter, none died of prostate cancer and only one developed high-risk prostate cancer. In contrast, men of all ages with a PSA level of 3 nanograms per milliliter or greater had a continually rising probability of dying from prostate cancer.

If confirmed by future studies, these results may help determine more specific guidelines for when PSA -based screening might be safely discontinued, according to lead investigator Edward Schaeffer, M.D., an assistant professor of urology at Johns Hopkins. While PSA screening remains a useful tool for helping detect early stages of prostate cancer and is credited with decreasing prostate cancer mortality, discontinuing unneeded PSA testing could significantly reduce the costs of screening and also potentially reduce morbidity resulting from additional tests or treatments.

"We need to identify where we should best focus our health care dollars by concentrating on patients who can actually benefit from PSA testing," Schaeffer says. "These findings give a very strong suggestion of when we can start to counsel patients on when to stop testing."


Other Johns Hopkins researchers who participated in this study include H. Ballentine Carter, M.D., Anna Kettermann, M.A., Stacy Loeb, M.D., Luigi Ferrucci, M.D., Ph.D., Patricia Landis, B.S., Bruce J. Trock, Ph.D., and E. Jeffrey Metter, M.D.

Decoding short-term memory with fMRI

Experiments at the University of Oregon bring focus to perceptual and memory storage processing

22 feb 2009--People voluntarily pick what information they store in short-term memory. Now, using functional magnetic resonance imaging (fMRI), researchers can see just what information people are holding in memory based only on patterns of activity in the brain.

Psychologists from the University of Oregon and the University of California, San Diego, reported their findings in the February issue of Psychological Science. By analyzing blood-flow activity, they were able to identify the specific color or orientation of an object that was intentionally stored by the observer.

The experiments, in which subjects viewed a stimulus for one second and held a specific aspect of the object in mind after the stimulus disappeared, were conducted in the UO's Robert and Beverly Lewis Center for Neuroimaging. In 10-second delays after each exposure, researchers recorded brain activity during memory selection and storage processing in the visual cortex, a brain region that they hypothesized would support the maintenance of visual details in short-term memory.

IMAGE: This is University of Oregon psychology professor Edward Awh.

Click here for more information.

"Another interesting thing was that if subjects were remembering orientation, then that pattern of activity during the delay period had no information about color, even though they were staring at a colored-oriented stimulus," said Edward Awh, a UO professor of psychology. "Likewise, if they chose to remember color we were able to decode which color they remembered, but orientation information was completely missing."

Researchers used machine-learning algorithms to examine spatial patterns of activation in the early visual cortex that are associated with remembering different stimuli, said John T. Serences, professor of psychology at UC-San Diego. "This algorithm," he said, "can then be used to predict exactly what someone is remembering based on these activation patterns."

Increases in blood flow, as seen with fMRI, are measured in voxels -- small units displayed in a 3-D grid. Different vectors of the grid, corresponding to neurons, respond as subjects view and store their chosen memories. Based on patterns of activity in an individual's visual cortex, located at the rear of the brain, researchers can pinpoint what is being stored and where, Awh said.

The study is similar to one published this month in Nature and led by Vanderbilt University neuroscientist Frank Tong and colleagues, who were able to predict with 80-percent-plus accuracy which patterns individuals held in memory 11 seconds after seeing a stimulus.

"Their paper makes a very similar point to ours," Awh said, "though they did not vary which 'dimension' of the stimulus people chose to remember, and they did not compare the pattern of activity during sensory processing and during memory. They showed that they could look at brain activity to classify which orientation was being stored in memory."

What Awh and colleagues found was that the sensory area of the brain had a pattern of activity that represented only an individual's intentionally stored aspect of the stimulus. This voluntary control in memory selection, Awh said, falls in line with previous research, including that done by Awh and co-author Edward K. Vogel, also of the UO, that there is limited capacity for what can be stored at one time. People choose what is important and relevant to them, Awh said.

"Basically, our study shows that information about the precise feature a person is remembering is represented in the visual cortex," Serences said, "This is important because it demonstrates that people recruit the same neural machinery during memory as they do when they see a stimulus."

That demonstration, Awh said, supports the sensory recruitment hypothesis, which suggests the same parts of the brain are involved in perception of a stimulus and memory storage.

A fourth co-author with Awh, Serences and Vogel was Edward F. Ester, a UO doctoral student. Serences was with the University of California, Irvine, when the project began. The research was primarily funded by a grant from the National Institutes of Health to Awh, and by support from the UO's Robert and Beverly Lewis Center for Neuroimaging.


About the University of Oregon

The University of Oregon is a world-class teaching and research institution and Oregon's flagship public university. The UO is a member of the Association of American Universities (AAU), an organization made up of the 62 leading public and private research institutions in the United States and Canada. The UO is one of only two AAU members in the Pacific Northwest.

A useful method to diagnose chest pain with foregut symptoms

22 feb 2009--Recent reports have indicated that recurrent chest pain is often a result of esophageal motility disorders or gastroesophageal reflux diseases (GERD), which is known as esophageal chest pain. However, very few studies have been performed about esophageal manometric studies, 24-h intra-esophageal pH monitoring and a Holter electrocardiography for the differential diagnosis of chest pain caused by esophageal dysfunctional and/or myocardial ischemia.

A research team led by Prof. Ru Wen Wang from China addressed this question. Their study will be published on February 14, 2009 in the World Journal of Gastroenterology.

In their study, 61 patients with chest pain and foregut symptoms were included. Thirty-nine patients were diagnosed with non-specific esophageal motility disorders (29 patients with abnormal gastroesophageal reflux and eight patients with myocardial ischemia). Five patients had diffuse spasm of the esophagus plus abnormal gastroesophageal reflux (two patients had concomitant myocardial ischemia), and one patient was diagnosed with nutcracker esophagus.

The study indicated that spasm of the esophageal smooth muscle might cross talk with the heart-coronary smooth muscle, leading to myocardial ischemia. And the combination of esophageal manometric studies, 24-hour intraesophageal pH monitoring and Holter electrocardiography are significant for the differential diagnosis of chest pain, particularly with foregut symptoms. As an added incentive, combined monitoring is very cost-effective to the patients from developing country.


Reference: Deng B, Wang RW, Jiang YG, Tan QY, Liao XL, Zhou JH, Zhao YP, Gong TQ, Ma Z. Diagnosis of chest pain with foregut symptoms in Chinese patients. World J Gastroenterol 2009;15(6): 742-747

Correspondence to: Ru-Wen Wang, MD, Thoracic Surgery Department, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.

Physical activity guidelines are too confusing, say researchers

22 feb 2009--Whether you are defined as leading an active or inactive lifestyle can depend on which country you are in and which guideline your GP picks off the shelf, say researchers at the University of Bath.

Whilst many countries have guidelines recommending the minimum amount of physical activity a person should take to stay healthy, much of this advice is conflicting, making it difficult for healthcare professionals to assess whether a person is getting enough exercise.

Scientists at the School for Health at the University of Bath, working with co-investigator Dr Alan Batterham from the University of Teesside, found that around nine out of every ten men they studied could be categorised as active or sedentary, depending on which guidelines were followed.

Dr Dylan Thompson, senior lecturer at Bath, explained: "Recommended levels of physical activity are supposed to give the public and health providers a guideline of the minimum amount of activity needed for good health, but these messages seem to vary a lot.

"For example, in the UK, the recommendation is that adults should do at least 30 minutes of moderate physical activity per day in periods of 10 minutes or more, five times a week.

"In the US, some guidelines recommend an overall volume of activity, recommending an average of 60 minutes of moderate intensity activity per day, but this includes any activity you might do - even if it lasts less than ten minutes.

"So, if you did a couple of two-hour walks at the weekend, and just a little bit of activity during the week, these US guidelines would define you as sufficiently active but according to the UK guidelines from the Department of Health you would be told that you needed to do more.

"Being physically inactive is a major risk factor for heart disease just like high blood pressure and high cholesterol, so it's really important that healthcare professionals are able to identify which people should be getting more physical activity so they can give them appropriate advice and support.

"If you went to the doctor to get your blood pressure or cholesterol checked, you'd expect to get a consistent result each time – we're saying that assessments of physical activity need to be just as stringent."

The researchers, who published their study in the online open access journal PLoS ONE, hope it will lead to a more consistent approach to gauging physical activity.

Dr Alan Batterham, a researcher in the Health and Social Care Institute at Teesside, remarked: "Deciding on whether people are sufficiently active or not depends on where you set the bar. We found that subtle differences in the definition of the minimum amount of physical activity required for health make a big difference to the proportion of people categorised as active or inactive."

Dr Thompson added: "In the long term, we need better evidence about precisely how much physical activity is needed for health, and we need to offer people consistent advice about their physical activity options.

"At the moment, we seem to have a very prescriptive 'one size fits all' approach but the 'size' varies enormously between guidelines. This confusion and inconsistency may be preventing people from taking the message on board that being active can make a huge difference to your health."

Healthy Behaviors Associated with Halving of Stroke Risk

22 feb 2009--Four behaviors combined — exercise, not smoking, healthy eating, and moderate drinking — are associated with a significant drop in stroke risk among older people, according to a BMJ study.

U.K. researchers ascertained the health behaviors of a cohort of some 20,000 adults aged 40 to 79. The group was then followed for an average of 11 years.

Over that period, those not engaging in any of four specific healthy behaviors had more than twice the risk for stroke as those engaging in all four — exercising regularly (or having a nonsedentary occupation), not smoking, eating five or more portions of fruits and vegetables daily, and drinking moderately. (The risk for stroke increased linearly with increasing numbers of unhealthy behaviors.)

An editorialist comments that modifying lifestyle behaviors "across a population has a greater potential for overall reduction in stroke than modifying more powerful risk factors (such as carotid stenosis and atrial fibrillation) in a smaller number of people."


BMJ article (Free)

BMJ editorial (Subscription required)

Saturday, February 21, 2009

When should prostate-specific antigen testing be stopped?

New York, NY, 21 feb 2009– Although widespread Prostate-Specific-Antigen (PSA) testing has undoubtedly decreased prostate cancer mortality, is there a point of diminishing returns? In a study published in the April 2009 issue of The Journal of Urology, researchers found that in a subgroup of elderly men, among those who were 75 years old or older and had a PSA below 3 ng/ml (nanograms per milliliter), none subsequently died of prostate cancer. The discontinuation of routine PSA screening in these men may not increase the rates of undetected lethal disease, and could avoid potentially unnecessary treatments and reduce diagnostic costs.

Because PSA screening can find cancers that may become life-threatening in 5 to 25 years, there has been increased usage of the test in 40 to 50-year-olds. But the test can also discover cancers that never become life-threatening, perhaps in up to 30% of the cases. Many men who are older than 75 undergo continued PSA screening, potentially leading to unnecessary treatment since death from other causes is more likely than death from prostate cancer.

The study conducted by investigators from the Baltimore Longitudinal Study of Aging (National Institute on Aging, National Institutes of Health) and the Department of Urology at Johns Hopkins School of Medicine involved 849 men (122 with and 727 without prostate cancer) with serial PSA measurements . Researchers found that for men over 75 with PSA <>

Writing in the article, Edward M. Schaeffer states, "The optimal approach to prostate cancer screening remains controversial. To date, there is limited evidence from which to inform the decision on when to discontinue prostate cancer screening. Our findings suggest that men at an age of 75-80 years who have a PSA level below 3ng/ml are unlikely to be diagnosed with a high risk prostate cancer during life. These men may therefore represent an ideal target group for discontinuation of PSA testing, which could dramatically reduce the costs associated with screening and the potential morbidity of additional evaluations and/or treatment in a population unlikely to gain benefit." Dr. Schaeffer emphasized that these findings need to be confirmed in a much larger study, and that men over the age of 75 years should continue to be monitored for development of clinical signs of prostate cancer.


The article is "Prostate Specific Antigen Testing Among the Elderly: When To Stop?" by Edward M. Schaeffer MD, PhD, H. Ballentine Carter MD, Anna Kettermann MA, Stacy Loeb MD, Luigi Ferrucci MD, PhD, Patricia Landis BS, Bruce J. Trock PhD, and E. Jeffrey Metter MD. It appears in The Journal of Urology, Volume 181, Issue 4 (April 2009) published by Elsevier.

Women less likely to receive critical care after a stroke, MSU researchers find

Disparity includes treatment, medication, timeliness of care

EAST LANSING, Mich., 21 feb 2009 — Women are 30 percent less likely than men to receive a critical clot-busting drug than can limit brain damage after a stroke, according to a Michigan State University study.

The study findings were presented Feb. 19 in San Diego at the International Stroke Conference, organized by the American Heart Association and American Stroke Association.

Tissue plasminogen activator, or tPA, first approved as a treatment in the mid-1990s, is a potent blood thinner used to dissolve artery-clogging clots, which cause most strokes. As part of its study, a team of MSU researchers reviewed all stroke studies published between 1995 and March 2008 that presented data on tPA treatment rates. Eighteen studies provided data on more than 2.3 million patients.

Overall, despite some study-to-study variation, women with acute stroke were 30 percent less likely to receive the treatment compared with men, said Archit Bhatt of the Department of Neurology and Opthalmology in MSU's College of Human Medicine.

"More than 60 percent of all stroke deaths are in women, and the functional outcomes and quality of life following stroke are poorer in women than in men," said Bhatt, who presented the study at the San Diego conference. "Clearly, more research is needed to understand the barriers to acute stroke therapy in women so this critical health disparity can be eliminated."

To begin to address the problem, Bhatt encourages the development of a consistent set of operational definitions to determine which patients are eligible for tPA treatment.

Gender differences in stroke care is part of a larger research effort at MSU led by Mathew Reeves, an associate professor in the MSU's Department of Epidemiology who also worked on the tPA study. Reeves and fellow MSU researchers are publishing two additional studies related to gender differences and stroke care, both of which will be published in a special April issue of the journal Stroke published by the American Heart Association:

  • Researchers found women were 14 percent less likely to receive perfect stroke care — referred to as defect-free care — compared to men, said Reeves, lead author on the study. The study compared the use of several evidence-based treatments in more than 380,000 men and women hospitalized with stroke: the timely use of clot-busting drugs, aspirin (both in the hospital and at discharge), blood thinners, cholesterol treatment, smoking cessation and prevention of blood clots in the legs.

    "Although the absolute differences were modest, lower quality of care in women was seen in all measures," Reeves said. "These sex differences in care could not be explained by the obvious gender differences in factors, such as age."

  • MSU researchers using data from a Michigan stroke registry found women who had an acute stroke experienced greater emergency room delays than men, and that the delays were not attributable to obvious gender differences in age or symptom presentation, according to Julia Gargano, a doctoral student in the Department of Epidemiology. Women had 12 percent longer "door-to-doctor" and 16 percent longer "door-to-image" intervals than men.

    "Two critical factors immediately after a stroke are how quickly a patient sees a doctor upon arrival at a hospital and how quickly there is an image taken of the brain," Reeves said. "This study indicates that it takes longer for women to receive both of these care measures."


Both studies can be viewed online at, where the entire April issue of Stroke magazine has been published early as part of Women's Heart Awareness Month during February.

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.

What is the most effective therapy for low-dose aspirin induced peptic ulcer?

21 feb 2009--The incidence of low-dose aspirin-induced peptic ulcer seems to be increasing in Japan in conjunction with the increasing proportion of elderly individuals, in whom metabolic syndrome frequently develops. However, a therapeutic and prevention strategy for such peptic ulcers has not yet been established.

A research team led by Dr. Satoshi Mochida from Japan addressed this question. Their study will be published on February 14, 2009 in the World Journal of Gastroenterology.

In their study, Upper gastrointestinal endoscopy was performed in 68 patients receiving daily low-dose aspirin (81 or 100 mg/day). The endoscopic findings were classified according to the Lanza score, and the scores were compared between groups categorized according to the concomitant use of anti-ulcer drugs and the types of drugs used. In another study, 31 hemorrhagic peptic ulcer patients who had been receiving low-dose aspirin were enrolled. The patients were randomly classified into the proton pump inhibitor (PPI)-treated group and the H2 receptor antagonist (H2RA)-treated group. The administration of low-dose aspirin was continued concomitantly, and endoscopic examinations were performed 8 wk later.

They found that the Lanza scores (mean ± SD) of the gastro-mucosal lesions were 1.0 ± 1.9 and 1.9 ± 2.3 in 8 and 16 patients receiving prevention therapy with a PPI and an H2RA, respectively. Both scores were significantly smaller than the scores in 34 patients who were not receiving prevention therapy (4.7 ± 1.0) and in 10 patients receiving cytoprotective anti-ulcer drugs (4.3 ± 1.6). In the prospective study, 18 and 13 patients received a PPI and an H2RA, respectively. Endoscopic examinations revealed that the tissue in the region of the gastro-mucosal lesions had reverted to normal in all patients in the PPI-treated group and in 12 patients (92%) in the H2RA-treated group; no significant differences were observed between the groups.

Their results indicated that H2RA therapy was effective for both the prevention and treatment of low-dose aspirin induced peptic ulcers, similar to the effects of PPIs, while cytoprotective anti-ulcer drugs were ineffective in preventing peptic ulcers.


Reference: Nakashima S, Ota S, Arai S, Yoshino K, Inao M, Ishikawa K, Nakayama N, Imai Y, Nagoshi S, Mochida S. Usefulness of anti-ulcer drugs for the prevention and treatment of peptic ulcers induced by low doses of aspirin. World J Gastroenterol 2009; 15(6): 727-731

Correspondence to: Satoshi Mochida, MD, PhD, Department of Gastroenterology & Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama 350-0495, Japan.

A revolutionary new model for Alzheimer's disease

Discovery of brain protein provides new therapeutic target

21 feb 2009--A study from the Buck Institute for Age Research offers a revolutionary new model for Alzheimer's disease (AD), a devastating neurodegenerative disorder which afflicts 24 million people worldwide. In an effort to unravel the normal function of a protein implicated in AD, scientists in California and France have discovered a naturally occurring protein that provides a new therapeutic target for the disease. The finding upsets the current theory that AD is a disease of toxicity stemming from damage caused by sticky plaques that collect in the brain – this research points to the condition as a disorder involving an imbalance in signaling between neurons. The study appears online in the Nature publication Cell Death and Differentiation.

One of the mysteries of AD has been the normal function of the amyloid precursor protein (APP) which are concentrated at the points where neurons connect. Even though the sticky amyloid plaques which have been viewed as a hallmark sign of AD result from APP, it seems unlikely that APP exists simply to cause Alzheimer's disease. In their study, scientists from the Buck Institute and the CNRS (Centre Nationale de la Recherche Scientifique) show that APP binds to netrin-1, a protein that helps to guide nerves and their connections in the brain, as well as helping nerve cells to survive. When netrin-1 was given to mice that have a gene for Alzheimer's disease their symptoms were reversed, and the sticky amyloid was reduced. These results suggest that the long-held belief that AD is caused by brain cell damage inflicted by the amyloid plaques may be wrong; instead, it is beginning to appear that the disease stems from an imbalance between the normal making and breaking of connections in the brain, with netrin-1 supporting the connections and the amyloid breaking the connections -- both by binding to APP and activating normal cell programs. Not only did the netrin-1 binding to APP keep the nerve cells alive and connected, but it also shut down the production of the amyloid, all of which makes it an interesting potential therapeutic.

"I think we're going to see an explosion in the next five years involving the dissection of these signaling pathways whose imbalance leads to Alzheimer's disease," said Buck Institute Faculty Member Dale Bredesen, MD, who led the California half of the French-Californian collaborative research. "We now believe that APP is part of a 'plasticity module' that functions in normal memory and forgetting, and that netrin-1 gives us an important starting point to restore the normal balance."

"We believe that Alzheimer's disease is somewhat analogous to cancer, which results from an imbalance between the normal processes that support cell survival and those that cause cell turnover," said Patrick Mehlen, PhD, Director of the Apoptosis, Cancer and Development CNRS Laboratory at the University of Lyon and co-senior author of the study. "Our hope is that this research will lead to therapeutics that will be used to address this imbalance much earlier in the disease process."

Research is underway to develop a drug based on the findings. The Buck Institute and the CNRS in Lyon are partnering with Neurobiological Technologies Inc., (NASDAQ: NTII) to bring the discovery from the laboratory to clinical trials.


Other researchers involved in the study include first author Filipe Calheiros Lourenço, of the University of Lyon, along with co-workers Joanna Fombonne, Véronique Corset and Fabien Llambi; Verónica Galvan of the Buck Institute, and Ulrike Müller of the University of Heidelberg. The work was supported by the Agence Nationale de la Recherche, the CNRS (Centre Nationale de la Recherche Scientifique), the National Institutes of Health, the Joseph Drown Foundation, the John Douglas French Foundation, and the Alzheimer's Association.

About the Buck Institute:

The Buck Institute is the only freestanding institute in the United States that is devoted solely to basic research on aging and age-associated disease. The Institute is an independent nonprofit organization dedicated to extending the healthspan, the healthy years of each individual's life. The National Institute on Aging designated the Buck a "Nathan Shock Center of Excellence in the Biology of Aging," one of just five centers in the country. Buck Institute scientists work in an innovative, interdisciplinary setting to understand the mechanisms of aging and to discover new ways of detecting, preventing and treating conditions such as Alzheimer's and Parkinson's disease, cancer, diabetes and stroke. Collaborative research at the Institute is supported by new developments in genomics, proteomics and bioinformatics technology. For more information:

Global warning: Hotter days, increased hospitalizations for respiratory problems

21 feb 2009--High summer temperatures, pushed higher by global climate change, may bring with them a spike in hospitalizations for respiratory problems, according to an analysis of data from twelve European cities, from Dublin to Valencia. The data comes from the "Assessment and Prevention of Acute Health Effects of Weather Conditions in Europe" (PHEWE), a multi-center, three-year collaboration between epidemiologists, meteorologists and experts in public health collaboration that investigated the short-term effects of weather in Europe.

As climate change has gone from a scientific theory to an accepted and encroaching reality, more extreme weather, including hotter summers, is anticipated around the planet. But the secondary effects of climate change are also coming into sharper focus.

The PHEWE project evaluated the effects of higher temperatures on hospitalizations for a number of different conditions in Europe. They found that for every degree increase over a temperature threshold, there was a four percent average increase in respiratory-related hospitalizations, but not for cardiovascular or neurovascular- related problems.

The results were published in the first issue for March of the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

"The PHEWE project represents the first attempt to evaluate the effect of temperature on several morbidity outcomes using a standardized methodology in a multi-center European study," wrote Paola Michelozzi Ph.D., head of Environmental Epidemiology at the Department Epidemiology of the Local Health Authority, in Rome.

The study tracked hospital admissions in twelve European cities. Each city provided data for a minimum of a three-year period between 1990 and 2001 that included hospital admissions, meteorological and air pollution data. They then computed a "maximum apparent temperature"—Tappmax for each city, using an index that accounted for both air temperature and humidity. At the far ends of the spectrum, the researchers found that Dublin had a Tappmax of 14.7ºC (about 58ºF) whereas Valencia's was 29.5ºC (about 85ºF). In most cities, each degree increase over 90 percent of the Tappmax, respiratory disease-related hospital admissions increased for all ages and especially in the 75+ age group.

Interestingly, while cardiovascular deaths are known to go up with the temperature, there was a slight decrease in hospitalizations. The researchers speculated that the acute onset of cardiovascular events could result in sudden deaths before medical treatment was possible.

"The contrasting pattern between admissions and mortality could also be related to differences in physiopathologic mechanisms," wrote Dr. Michelozzi. "...[C]ardiovascular deaths during hot days tend to occur suddenly in persons whose health is compromised. Respiratory mortality, on the contrary, tends to peak later than cardiovascular mortality, with effects observed up to three weeks after exposure..."

Despite the increase of respiratory-related hospitalizations overall, the observed effect was heterogeneous among cities, indicating the need for further study.

"This is in part due to differences in exposure, the large variability among the cities analyzed, the differences in adaptive capacity and the vulnerability of populations due to their socio-demographic characteristics, as well as differences in the preventive measures in place," said Dr. Michelozzi. "Moreover, across European countries there is wide variation in healthcare and hospital admissions availability. Although all these differences are important, our results document an effect of high temperature on hospital admissions for respiratory causes in several cities, and this is the strength of the study."

"These findings are important for public health because the prevalence of chronic diseases, such as COPD, is expected to increase in developed countries as a result of population aging," wrote Dr. Michelozzi. "Furthermore, under climate change scenarios, the increase in extreme weather events and certain air pollutants, especially ozone, are likely to further aggravate chronic respiratory diseases. Public health interventions should be directed at preventing this additional burden of disease during the summer season. The observed heterogeneity of the health effects indicates a need to tailor programs for individual cities."

Friday, February 20, 2009

Anti-aging pathway enhances cell stress response

People everywhere are feeling the stress of a worldwide recession. Our cells, too, are under continual assault from stress.

20 feb 2009--Hidden from sight, our cells battle challenges such as their environment, bacteria, viruses, too much or too little oxygen, and physiological stressors. Molecular systems protect cells under assault, but those systems can break down, especially with age.

To better understand how cells are protected from stress and damage, a team led by Northwestern University researchers studied the effect of resveratrol, a beneficial chemical found in red wine, on human cells in tissue culture.

The findings may help explain what happens in neurodegenerative diseases, which are age-related, when cell protection fails, proteins misfold, lots of damage accumulates and the system falls apart.

The researchers discovered a new molecular relationship critical to keeping cells healthy across a long span of time: a protein called SIRT1, important for caloric restriction and lifespan and activated by resveratrol, regulates heat shock factor 1 (HSF1), keeping it active. HSF1 in turn senses the presence of damaged proteins in the cell and elevates the expression of molecular chaperones to keep a cell's proteins in a folded, functional state. Regulation of this pathway has a direct beneficial effect to cells, the research shows.

This role of SIRT1 -- a protein already of great interest to pharmaceutical companies -- was not previously known. The results will be published in the Feb. 20 issue of the journal Science.

"When SIRT1 levels are high, you are in a high-protection mode," said Richard I. Morimoto, Bill and Gayle Cook Professor of Biochemistry, Molecular Biology and Cell Biology in Northwestern's Weinberg College of Arts and Sciences. He led the research team.

"Ironically, triggering the stress response and perhaps maintaining the cell in a protective state over a long period of time can keep cells healthy," said Morimoto. "The cell is protected against an accumulation of damage when HSF1 is more active."

SIRT1 levels decrease as humans age, Morimoto explains. Cells can't respond to stress as well. This decrease in SIRT1 may help explain why protein misfolding diseases, such as Alzheimer's, Parkinson's, Huntington's and adult-onset diabetes, are diseases of aging.

"We now have a powerful way to think about addressing neurodegenerative diseases," said Morimoto. "We have identified a pathway that can be manipulated to alter lifespan. Discovering this new basis for therapeutics is very exciting."


In addition to Morimoto, other authors of the Science paper, titled "Stress-Inducible Regulation of Heat Shock Factor 1 by the Deacetylase SIRT1," are Sandy D. Westerheide, from Northwestern; Julius Anckar and Lea Sistonen, from Åbo Akademi University in Turku, Finland; and Stanley M. Stevens Jr., from the University of Florida.