Omega-6 PUFAs and risk of cardiovascular disease

AHA stands by advice to include omega-6 PUFAs in heart-healthy diet

31 jan 2009--A new Science Advisory report from the American Heart Association recommends that omega-6 polyunsaturated fatty acids (PUFAs), as found in vegetable oils, nuts and seeds, are beneficial when part of a heart-healthy eating plan. Consumers should aim for at least 5-10% of energy (calories) from omega-6 PUFAs, and will derive most benefit when omega-6 PUFAs replace saturated or trans fats in the diet. Precise recommended daily servings will depend on physical activity level, age and gender, but range between 12 and 22 grams per day.

The AHA report also addresses the recent controversy that omega-6 fatty acids, via linoleic acid, which accounts for 85-90% of dietary omega-6, may actually increase inflammation and thereby increase rather than reduce cardiovascular risk. Any link between omega-6 and inflammation, says the AHA, comes from the fact that arachidonic acid, which can be formed from linoleic acid, is involved in the early stages of inflammation, but anti-inflammatory molecules are also formed; these suppress the production of adhesion molecules, chemokines and interleukins, all of which are key mediators of the atherosclerotic process. Thus, concludes the report, it is incorrect to view the omega-6 fatty acids as pro-inflammatory.

The report also reviewed epidemiological data and found that, in randomised controlled trials, those assigned to the higher omega-6 diets had less heart disease. 
A meta-analysis of several trials indicated that replacing saturated fats with PUFA lowered risk for heart disease events by 24%. Reducing omega-6 intakes, said the report, would be more likely to increase than to decrease the risk of CHD.

Professor Heinz Drexel from the VIVIT Research Institute at Feldkirch, Austria, speaking on behalf of the European Society of Cardiology, adds that the report not only recommends the consumption of at least 5-10% of energy from omega-6 PUFAs but indicates that intakes higher than 10% of energy appear safe and may even be even beneficial. This latter statement, says Professor Drexel, "is somewhat discordant with earlier recommendations made by other authorities".

Commenting on the report, Professor Drexel adds: "This advisory is a resurrection of older recommendations on omega-6 PUFAs, in particular on linoleic acid. It is based on new ecological, case-control, prospective cohort and randomised controlled studies. Concerns raised in the past decade that omega-6 PUFAs may be pro-inflammatory are dispelled with evidence that omega-6 PUFAs have anti-inflammatory properties at the level of vascular endothelial cells. On balance, the advantages outweigh the disadvantages.

"However, the effects of Omega-6 PUFAs appear weak and require long-term interventions. Many studies in the past were not long enough for a nutritional intervention. Moreover, in the intervention studies other nutrients were changed along with the enrichment of omega-6 PUFAs."

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REFERENCES:

1. Harris WS, Mozaffarian D, Rimm E, et al. Omega-6 fatty acids and risk for cardiovascular disease. Circulation 2009; DOI: 10.1161/CIRCULATIONAHA.108.191627.

New pathway is a common thread in age-related neurodegenerative diseases

LA JOLLA, CA, 31 jan 2009—How are neurodegenerative diseases such as Alzheimer's initiated, and why is age the major risk factor? A recent study of a protein called MOCA (Modifier of Cell Adhesion), carried out at the Salk Institute for Biological Studies, provides new clues to the answers of these fundamental questions.

Under normal circumstances, MOCA is a key member of the squadron charged with keeping Alzheimer's disease at bay. A team of researchers led by Salk professor David Schubert, Ph.D., demonstrated what happens when MOCA goes on furlough. In the process Schubert identified a novel pathway with broad implications for both Alzheimer's and other age-related neurodegenerative diseases.

Their findings, reported in the current issue of the Journal of Neuroscience, show how neurodegenerative disease starts, initiating in the nerve ending and inducing gradual changes, like a chain reaction over a long time. The animal model used in the study also will allow scientists to better understand the processes behind the formation of the protein aggregates that are common to most neurodegenerative diseases. In addition, it will provide new opportunities to target the earliest steps for therapy.

MOCA was initially identified as a protein that binds to presenilin, a molecule that when mutated causes familial Alzheimer's disease. MOCA is only found in neurons and regulates the expression of the beta amyloid protein responsible for the Alzheimer's plaques that are the hallmark of the disease. To better understand MOCA's function, Qi Chen, Ph.D., a senior scientist in Schubert's laboratory, created a line of mice genetically engineered to lack the gene for MOCA.

"Because of the initial studies in cultured cells that we had done, we expected these mice to develop plaques," explains Schubert. "What we found was that they develop ataxia—a motor coordination problem—as they age." Chen then studied the pathology of these mice and found that it reflected a common feature of most age-related neurological diseases, not just Alzheimer's.

The main problem turned out to be the degeneration of axons, the long projections that conduct impulses away from neurons. The axonal degeneration was caused by the accumulation of protein aggregates. Although the mice were not born with the problem, they acquired it, along with the ataxia, as they aged, and the ataxia worsened over time.

The aggregates started out small, initially causing few or no symptoms, but as they built up in the axons, they began to destroy the cytoskeleton, the internal framework of the cells, increasingly interfering with the transmission of signals from the nerve cells. Eventually the affected axons died, followed by the death of the nerve cell itself.

"Protein aggregates are common features of most age-related neurological diseases," says Chen, the first author of the study. "So is axon degeneration; we see it in Alzheimer's, ALS, and Huntington's disease. Motor problems such as ataxia may be the most obvious manifestation because the aggregates appear in the long axons of the spinal cord. But the axonal aggregates also appear in the brain and may be the first step in the events that lead to age-associated neurological disease."

After documenting the sequence of physiological and behavioral events that characterize the axon degeneration, Chen then sought to piece together the molecular pathway behind it, starting with MOCA and connecting findings from disparate studies that previously had identified parts of the pathway. He ended up with a single, step-by-step process for axon degeneration that for the first time linked together a number of diseases and conditions, including a form of mental retardation in humans.

"We had known that MOCA affected the cytoskeleton for some time, but no one had put together clear evidence showing how the sequential age-associated changes in the cytoskeleton of the nerve take place. Dr. Chen was able to do this, thereby connecting the disease pathology with the molecular biology," says Schubert. "Now we know that MOCA is essential to the functional integrity of axons and have defined a complete pathway for axon degeneration."

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The study was funded with support from the National Institutes of Health, the Bundy Foundation, the Alzheimer's Association, and the Shirley Foundation for Alzheimer's Research.

Chondroitin slows progression and relieves symptoms of knee osteoarthritis

A new study examined the effect of chondroitins 4 and 6 sulfate on osteoarthritis progression and symptoms

31 jan 2009--Osteoarthritis (OA) causes disability and is a major public health problem. A new study examined the effect of chondroitins 4 and 6 sulfate (CS) on OA progression and symptoms. CS, unlike other chondroitin sulfate products sold as dietary supplements in the U.S., has been approved as a prescription symptomatic slow acting drug for OA in many European countries. The study was published in the February issue of Arthritis & Rheumatism (http://www3.interscience.wiley.com/journal/76509746/home).

Led by Andre Kahan of the University of Paris Descartes in Paris, the randomized, double-blind, placebo-controlled study involved 622 patients with OA from France, Belgium, Switzerland, Austria and the U.S. Patients had knee X-rays at the time of enrollment and at 12, 18 and 24 months. The X-rays were evaluated for joint space loss and patients were also assessed for OA symptoms and pain.

The results showed that "long-term administration of CS over 2 years can prevent joint structure degradation in patients with knee OA," the authors state. Joint space loss was significantly reduced in the CS group, fewer patients had progression of joint space width, and CS reduced pain in those taking it compared to the placebo group. CS was well-tolerated and there were no significant differences in the frequency of adverse events between the two groups.

The study showed that there was faster improvement regarding pain during the first year in the CS group compared to the placebo group. This may be due to the fact that all of the patients had pain symptoms, so the effect of CS was more noticeable early on. Since those who took a placebo also had decreased pain in the first year, it may also be due to the natural course of the disease. The authors note that the study involved CS, which is used as a prescription drug and that the results cannot be generalized to other chondroitin sulfate products or compounds, such as those available in the form of dietary supplements.

The decrease in joint space loss shown in this and another recent study involving 300 patients, suggests better outcomes for OA patients, according to the authors. They conclude: "Further studies with longer followup and different outcome criteria are warranted to assess whether the beneficial structural changes associated with CS demonstrated in our study are predictive of improvement in the long-term clinical progression of OA."

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Article: " Long-Term Effects of Chondroitins 4 and 6 Sulfate on Knee Osteoarthritis," Andre Kahan, Daniel Uebelhart, Florent De Vathaire, Pierre Delmas, Jean-Yves Reginster, Arthritis & Rheumatism, February 2009.

Gene mutations increase risk for aggressive prostate cancer

Genetic testing could shed light on tumor prognosis

31 jan 2009– Men who develop prostate cancer face an increased risk of having an aggressive tumor if they carry a so-called breast cancer gene mutation, scientists from the Albert Einstein College of Medicine of Yeshiva University report in today's issue of Clinical Cancer Research. The findings could help to guide prostate-cancer patients and their physicians in choosing treatment options.

The study, involving 979 men with prostate cancer and 1251 men without the disease, looked at whether participants carried mutations for either of two genes, BRCA1 and BRCA2. Women carrying mutations in either gene face an increased risk of developing breast cancer, ovarian cancer, or both.

All the people enrolled in the Einstein study were of Ashkenazi Jewish descent. The study focused on them because they are five times likelier than people in the general population to carry a mutation of any kind in the BRCA1 or BRCA2 genes. The researchers looked for the presence of three particular mutations–two in BRCA1 and one in BRCA2. Scientists believe that genetic discoveries among the Ashkenazi can benefit society as a whole in terms of preventing and treating major diseases.

Having any of the three mutations did not increase a man's risk of developing prostate cancer, the study found. But for those men who did develop prostate cancer, two of the mutations–BRCA1-185delAG and the mutated BRCA2 gene–increased the risk that tumors would be aggressive or high-grade, as defined by a Gleason score of 7 or above. The Gleason score, based on the microscopic appearance of prostate tissue removed during a biopsy or surgery, assesses the aggressiveness of a prostate tumor on a scale from 2 (least aggressive) to 10 (most aggressive).

Specifically, prostate cancer patients with high-grade, aggressive tumors (Gleason scores of 7 or above) were 3.2 times more likely to carry the BRCA2 gene mutation than were men in the control group. Carriers of the BRCA1-185delAG mutation were also at increased risk of having an aggressive prostate cancer.

Previous investigations into a possible link between prostate-cancer risk and the BRCA1 and BRCA2 genes have yielded conflicting results–perhaps because they involved small numbers of subjects and lacked well-matched control groups. "Our large study shows conclusively that prostate cancer patients with either the BRCA2 gene mutation or the BRCA1-185delAG mutation are more susceptible to aggressive cancers than people without that mutation," says Robert Burk, M.D., professor of pediatrics (genetics) at Einstein and senior author of the study.

Routine genetic testing for BRCA mutations–done by analyzing blood samples or cells swabbed from the inside of one's cheeks–wouldn't be justified for most men, says Dr. Burk: the prevalence of the mutations in the general population is very low; and men with high Gleason scores already know that their prostate cancer is aggressive. But, notes Dr. Burk, "our findings might have practical implications for some men diagnosed with early-stage (low Gleason score) prostate cancers–particularly Ashkenazi Jewish men, who are much more likely to have these mutations."

"One of the biggest problems with early-stage prostate cancer is being able to distinguish between tumors with the potential to become aggressive and those that may persist for many years without enlarging or spreading," notes Dr. Burk. For that reason, he says, Ashkenazi men diagnosed with early-stage prostate cancer might want to consider getting tested for the BRCA2 and BRCA1-185delAG mutations.

Knowing they have the mutation—and that their tumor may become aggressive—may influence treatment options that patients pursue. For example, a prostate cancer patient who has the BRCA2 mutation might vote against 'watchful waiting'—in which the growth of the cancer is monitored and treatment is held in abeyance—and instead opt for surgery or radiation treatments with or without hormone blockade therapy.

For early-stage prostate cancer patients in the general population, knowing they carry the BRCA1 or BRCA2 mutation would also be useful, says Dr. Burk. But these mutations are so rare in the general population—a prevalence of far less than one percent—that testing is unlikely to reveal their presence.

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Other Einstein researchers involved in the study were Dr. Ilir Agalliu and Suzanne Leanza. The authors have no potential conflicts of interest relevant to this article.

Meditation Practice Linked to Less Pain Sensitivity

Experienced Zen meditators needed higher temperature stimulation to feel moderate pain

30 jan 2009 -- Experience in Zen meditation is associated with reduced pain sensitivity, a finding supporting the value of mindfulness-based meditation, according to research published in the January issue of Psychosomatic Medicine.

Joshua A. Grant, and Pierre Rainville, Ph.D., of the Universite de Montreal in Quebec, Canada, analyzed data from 13 experienced Zen meditators and 13 age- and gender-matched controls who were unfamiliar with meditation. All were exposed to a heating device on the calf that provided a series of episodes of non-painful warmth or moderately painful heat. In different experimental conditions, participants were told to focus all attention on the stimulation, observe the sensation in a mindful way, or were given no task.

Meditators needed significantly higher temperatures to produce moderate pain than controls (49.9 Celsius versus 48.2 Celsius), which the authors classified as a large difference. While attending mindfully, meditators had less pain, while control subjects did not, the investigators found. The analgesic effect in meditators was related to their amount of meditation experience, the report indicates.

"Overall, the meditators breathed at a slower rate than control subjects in all conditions and their mean respiratory pattern followed that of their pain ratings. In contrast, respiratory rate did not change noticeably across conditions in the control subjects. Slower breathing rates (typically meditators) were associated with less reactivity and with lower pain sensitivity," the authors write. "These relationships suggested that the meditators were in a more relaxed, non-reactive physiological state throughout the study, which culminated in the mindfulness condition and which influenced the degree to which they experienced pain."

The study was supported by a Mind and Life Institute grant.

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Prolonged Use of Loop Diuretics May Raise Fracture Risk

Medications are normally used by women already at risk for fractures

30 jan 2009-- Postmenopausal women who use loop diuretics are at increased risk of fractures, according to a report published in the Jan. 26 issue of the Archives of Internal Medicine.

Laura D. Carbone, M.D., of the University of Tennessee Health Science Center in Memphis, and colleagues conducted a study using data from the Women's Health Initiative on 133,855 women, of whom 3,411 used loop diuretics and 130,444 did not. They looked at the women's risk of falls and fractures over a mean period of 7.7 years and analyzed data on baseline and three-year bone mineral density for 300 users and 9,124 non-users of loop diuretics.

Women who had ever used loop diuretics were not at significantly increased risk of total, hip and clinical vertebral fractures and falls, the data revealed. However, those who used loop diuretics for more than three years had a 16 percent higher risk of both clinical and total fractures, compared with non-users, the researchers report. There was no association between changes in bone mineral density and use of loop diuretics, the investigators found.

"The relationship of falls to medication use is complex. We hypothesized that loop diuretics might be positively associated with falls because they may cause orthostatic hypotension," the authors write. "Prolonged use of loop diuretics was associated with higher fracture risk in postmenopausal women."

Carbone reported grant support and honorarium from Procter & Gamble and honorariums from Merck, Novartis and Aventis.

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Imaging Detects Cardiac Abnormalities in Endocarditis

Computed tomography effective when compared with echocardiography and surgical specimens

30 jan 2009-- Multislice computed tomography (CT) is effective in detecting valvular abnormalities in patients with suspected infective endocarditis compared with transesophageal echocardiography and surgical specimens, researchers report in the Feb. 3 issue of the Journal of the American College of Cardiology.

Gudrun M. Feuchtner, M.D., from Innsbruck Medical University in Austria, and colleagues compared the value of multislice CT, transesophageal echocardiography and intraoperative findings for the assessment of valvular abnormalities in 37 patients with suspected infective endocarditis.

The researchers found that evident valvular abnormalities were detected by multislice CT with 97 percent sensitivity and 88 percent specificity, with a positive predictive value of 97 percent and a negative predictive value of 88 percent compared with transesophageal echocardiography. Vegetations, abscesses and pseudoaneurysms were detected by CT and transesophageal echocardiography with similar accuracy, the report indicates. Compared with surgical specimens, multislice CT identified 96 percent of patients with valvular vegetations and 100 percent of patients with abscesses or pseudoaneurysms, the authors note.

"Multislice CT shows good results in detecting valvular abnormalities in infective endocarditis and could be applied in pre-operative planning and exclusion of coronary artery disease before surgery," Feuchtner and colleagues conclude.

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BNP Levels Not a Superior Guide for Heart Failure Therapy

Brain natriuretic peptide levels not superior to using symptom management

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30 jan 2009- Using N-terminal brain natriuretic peptide (BNP) levels to guide heart failure therapy does not improve overall clinical outcomes or patient quality of life compared to using symptoms to guide treatment, according to a report published in the Jan. 28 issue of the Journal of the American Medical Association.

Matthias Pfisterer, M.D., of the University Hospital Basel in Switzerland, and colleagues conducted a randomized, controlled multicenter trial to compare 18-month outcomes of the two forms of guided heart failure therapies. A total of 499 patients (60 years or older) with systolic heart failure and an N-terminal BNP level of two times or more the upper limit of normal were randomized to receive treatment to either reduce symptoms or reduce BNP levels.

Both types of interventions resulted in a similar rate of 18-month survival free of all-cause hospitalization (41 percent versus 40 percent for BNP-guided and symptom-guided therapy, respectively), the researchers report. Patient quality of life, which was improved over the 18-month study period, also was similar, the authors note.

"While the BNP level may prove to be a useful tool for guiding therapy, it may be the method of reduction of BNP levels that matters most in improving outcomes for patients with heart failure," the authors of an accompanying editorial write.

The study was partially funded by several pharmaceutical companies.

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Arterial Stiffness Predicts Hypertension Drug Response

Predicts control of systolic blood pressure

30 jan 2009-- Patients with hypertension and high levels of arterial stiffness are less likely to respond to antihypertensive drugs, researchers report in the Feb. 3 issue of the Journal of the American College of Cardiology.

Athanase Protogerou, M.D., from the University of Athens in Greece, and colleagues measured carotid-femoral pulse wave velocity (a measure of arterial stiffness) and blood pressure in 375 patients with hypertension who had been randomly assigned to atenolol or perindopril/indapamide.

After 12 months, the researchers found that patients in the highest tertile of baseline pulse wave velocity had the smallest blood pressure response to treatment and more need for increases in drug dose. Baseline pulse wave velocity was a significant predictor of systolic blood pressure control but not diastolic blood pressure control. The predictive value of pulse wave velocity on systolic blood pressure was independent of age, sex, mean blood pressure and cardiovascular risk factors, the authors report.

"These important findings suggest that aortic stiffness is a strong independent predictor of the likelihood of resistant hypertension and puts the aorta and its age-related degeneration at the center of the pathogenesis of resistant hypertension," Bryan Williams, M.D., from the University of Leicester School of Medicine in the United Kingdom, writes in an accompanying editorial.

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Study: Kidney donors do fine, no long-term issues

By STEPHANIE NANO
NEW YORK, 29 jan 2009 – Donating a kidney doesn't appear to have any long-term health consequences for the donor, a reassuring study shows. Researchers at the University of Minnesota found those who gave up one of their two kidneys lived a normal life span and were as healthy as people in the general population. The donation also didn't raise the risk of having kidney failure later.

Kidney donation has generally been considered safe, although with surgery, there are always risks. The new research of nearly 3,700 donors dating back more than four decades is the largest and longest study to look at long-term outcomes, said the researchers. They reported their findings in Thursday's New England Journal of Medicine.

"It is a confirmation that living donation is a safe thing," said Dr. Matthew Cooper, a transplant surgeon at the University of Maryland, who was not involved in the research.

Kidneys filter waste and excess fluid from the blood. If your kidneys fail, the options are dialysis or a transplant. More than 78,000 people are on the national waiting list to receive a kidney from a deceased donor. The need for kidneys has soared with the rise in diabetes and obesity and the wait can last for years.

Living donation has increased as more people became willing to donate and newer surgery techniques shortened recovery time. In 2007, more than a third of the 16,629 kidneys transplanted in the U.S. came from living donors, according to the United Network for Organ Sharing.

Dr. Hassan Ibrahim, the study's leader, and his colleagues wanted to find out what happened to the 3,698 people who had donated a kidney at the university since 1963. They tried to contact everyone and used government records to find out who had died. A group of 255 donors was randomly selected to have kidney and other tests. Results were compared with health outcomes for the general population.

Overall, 268 of the donors died, which the researchers said was comparable to survival in the general population. Eleven donors developed kidney failure decades later and needed dialysis or a transplant. The researchers said the rate of kidney failure in the donors was lower than that reported in the general population.

Most of the donors tested had good kidney function and reported an excellent quality of life, the study found.

The good outcomes likely reflect the strict criteria used to pick the donors, the researchers said. The donors had to be healthy with no kidney problems, and be free of high blood pressure and diabetes — two main causes of kidney disease.

Ibrahim said he hopes the results will increase donations and encourage transplant centers to continue to carefully select donors and not relax their requirements.

"We think these donors do extremely well because they were screened very well," said Ibrahim.

While there are no regulations for selecting living donors, the transplant network offers guidelines, said Cooper, who heads a UNOS committee on living donors. He said any kidney donor who later needs a transplant is given priority on the waiting list.

"There is a recognition of the sacrifice that these people have made," Cooper said.

Drs. Jane Tan and Glenn Chertow, of Stanford University School of Medicine, who wrote an accompanying editorial in the journal, noted that the study donors were mostly white and were likely younger than donors today. The results may not apply to older, nonwhite donors, they said.

The value of the study is its large size and duration, Tan said.

"We always have to be careful when it comes to potential harm to another individual," she said. "This study is very reassuring."

The University of Minnesota is part of a similar, ongoing study with other transplant centers that will have a larger and more diverse donor group, Ibrahim said.

One of the study donors said she didn't worry about potential problems when she gave a kidney to her oldest brother in 1983.

"I really didn't think too much past that," said Susan Kivi, 52, of Roseville, Minn. "He just deserved another chance to live a normal life."

Her recovery from surgery was a little harder than she expected, said Kivi. But she hasn't had any health problems related to giving up a kidney since then. Her brother died about four years later.

"It was worth it. He got a few good years," she said.

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On the Net:

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

UNOS: http://www.unos.org

Weight loss reduces incontinence for women

Targeted 6-month program diet, exercise and behavior modification cut incontinence by nearly half

BIRMINGHAM, Ala., 29 jan 2009– Starting a weight-loss regimen significantly reduces urinary incontinence for women, according to researchers at the University of Alabama at Birmingham (UAB) and the University of California, San Francisco.

A six-month program of diet, exercise and behavior modification resulted in a loss of 17 pounds and nearly one-half (47 percent) fewer incontinence episodes per week on average, the study authors said.

By contrast, an information-only program on diet and exercise without any direct weight-loss training led to a loss of 3 pounds and 28 percent fewer incontinence episodes per week on average, the researchers said.

The results are published in the New England Journal of Medicine.

"Earlier research has shown that behavioral weight-loss programs have many benefits, including decreasing blood pressure and helping to fight off diabetes. Here we've shown that weight loss has measureable impact on reduced incontinence," said Frank Franklin, M.D., Ph.D., a UAB professor in the School of Public Health and a co-author on the NEJM study.

The NEJM results are from the Program to Reduce Incontinence by Diet and Exercise, or PRIDE study. It included 338 overweight and obese women (BMI 25-30 kg/m²) who experienced up to 10 episodes of incontinence per week.

Those on the diet, exercise and behavior modification program reported feeling significantly more satisfied with the improvements in incontinence compared to the information-only participants, Franklin said.

Urinary incontinence affects more than 13 million women in the United States and has been linked to increased risk of falls and bone fractures.

Considering the PRIDE results and other health benefits, the initiation of weight loss should be added as a first-line treatment in overweight and obese women, said lead study author Leslee Subak, M.D., of the University of California, San Francisco.

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The study was a partnership with UAB, the University of California, San Francisco; Brown University in Providence, Rhode Island and the University of Arkansas for Medical Sciences in Little Rock. Funding is from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the Office of Research on Women's Health (ORWH), both part of the National Institutes of Health.

Proton pump inhibitors increase risk of heart attacks for patients on common cardiac drug

29 jan 2009--Patients taking the common cardiac drug clopidogrel following a heart attack are at a significantly higher risk of a recurrence if they are also taking widely used acid-lowering medications called proton pump inhibitors, a new study published online in CMAJ has found (http://www.cmaj.ca/cgi/rapidpdf/cmaj.082001).

The study, conducted over 6 years in thousands of heart attack patients aged 66 years and older, found a significantly increased risk of readmission for heart attacks if patients were taking one of several proton pump inhibitors, including omeprazole, lansoprazole, or rabeprazole. The investigators found no such association with the proton pump inhibitor pantoprazole or with other acid-lowering medications called H2 receptor antagonists.

Previous research indicates that proton pump inhibitors other than pantoprazole can block the liver's ability to convert clopidogrel to its active form,a critical step required for clopidogrel's anti-platelet effect.

These findings could have significant public health implications. Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs in the world, with more than 12.4 million prescriptions in Canada alone in 2004. Clopidogrel is the second-highest selling drug in the world, with annual sales totalling $7.3 billion.

Recent guidelines from the American Heart Association, the American College of Gastroenterology, and the American College of Cardiology recommend proton pump inhibitor therapy for many patients following a heart attack to prevent bleeding from the stomach, including all patients aged 60 years or older receiving ASA. Because clopidogrel and ASA are often prescribed together following a heart attack, it is probable that millions of patients worldwide will take a proton pump inhibitor with clopidogrel.

"Depending on the exposure to these drugs following a heart attack, we estimate that 5% to 15% of early readmissions for myocardial infarction among patients taking clopidogrel could be the result of this drug interaction," writes Dr. David Juurlink, Head of the Division of Clinical Pharmacology and Toxicology at Sunnybrook Health Sciences Centre and lead author of the study, which was conducted at the Institute for Clinical Evaluative Sciences (ICES). "These findings highlight a widely unappreciated, extremely common and completely avoidable drug interaction in a population of patient at very high risk of reinfarction."

"Our findings suggest that indiscriminate treatment with a proton pump inhibitor could result in thousands of additional cases of recurrent myocardial infarction each year, all of which could be avoided simply by selectively prescribing pantoprazole in patients receiving clopidogrel who require treatment with a proton pump inhibitor," write the authors.

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The article will appear in the March 31, 2009 print version of the journal.

Visit www.cmaj.ca for medical knowledge that matters.

I feel your pain: Neural mechanisms of empathy

29 jan 2009--Is it possible to share a pain that you observe in another but have never actually experienced yourself? A new study uses a sophisticated brain-imaging technique to try and answer this question. The research, published by Cell Press in the January 29th issue of the journal Neuron, provides insight into brain mechanisms involved in empathy.

Brain-imaging studies have shown similar patterns of brain activity when subjects feel their own emotions or observe the same emotions in others. It has been suggested that a person who has never experienced a specific feeling would have a difficult time directly empathizing with a person through a "mirror matching" mechanism that requires previous experience and would instead have to rely on a higher inferential processes called "perspective taking."

"Patients with congenital insensitivity to pain (CIP) offer a unique opportunity to test this model of empathy by exploring how the lack of self-pain representation might influence the perception of others' pain," explains lead author Dr. Nicolas Danziger from the Department of Clinical Neurophysiology and Pain Center at the Pitie-Salpetriere in Paris, France.

Dr. Danziger and colleagues had previously shown that CIP patients underestimated the pain of others when emotional cues were lacking and, in contrast with control subjects, the ability to fully acknowledge others' pain depended on a capacity for empathy. In this study, the researchers used functional magnetic resonance imaging (fMRI) to compare brain activation patterns in CIP patients and controls who were asked to imagine the feelings of a person in a photo that showed body parts in painful situations or facial expressions of pain.

CIP patients showed decreased fMRI activation of visual regions, a result indicative of their reduced emotional arousal to the view of others' pain. On the other hand, in the CIP patients but not the controls, the capacity for empathy strongly predicted activation of key midline brain structures involved in processes linked to inferring the emotional states of others.

These results suggest that in the absence of functional resonance mechanisms shaped by personal pain experiences, CIP patients might rely crucially on their empathetic abilities to imagine the pain of others, with activation of midline brain structures being the neural signature of this cognitive-emotional process.

"Our findings underline the major role of midline structures in emotional perspective taking and in the ability to understand someone else's feelings despite the lack of any previous personal experience of it—an empathetic challenge frequently raised during human social interactions," concludes Dr. Danziger.

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The researcher is Nicolas Danziger, INSERM U713, Paris, France; Isabelle Faillenot, CHU Saint-Etienne, 42100 France; INSERM 342 F-69003 UCB Lyon1 University, Lyon, France; INSERM 342 F42000 and UJM St-Etienne University, St Etienne, France; and Roland Peyron, CHU Saint-Etienne, 42100 France; INSERM 342 F-69003 UCB Lyon1 University, Lyon, France; INSERM 342 F42000 and UJM St-Etienne University, St Etienne, France, CERMEP, Lyon, France.

Is rapid transition through menopause linked to earlier onset of heart disease?

Preliminary study detects a possible connection between shorter menopause and faster progression of atherosclerosis, pointing to the need for more definitive research

LOS ANGELES, 29 jan 2009- An evaluation of 203 women as part of the multifaceted Los Angeles Atherosclerosis Study (LAAS) found that those who transitioned more quickly through menopause were at increased risk for a higher rate of progression of "preclinical atherosclerosis" – narrowing of arteries caused by the thickening of their walls.

Cardiologist C. Noel Bairey Merz, M.D., is principal investigator of the study. She is director of the Women's Heart Center and the Preventive and Rehabilitative Cardiac Center at the Cedars-Sinai Heart Institute. She serves as professor of medicine at Cedars-Sinai and holds the Women's Guild Endowed Chair in Women's Health.

This observational study included 203 women between ages 45 and 60 at the time they entered the study. Fifty-two were premenopausal, 20 were perimenopausal and 131 were postmenopausal. None of the women had been diagnosed with cardiovascular disease. They were evaluated when they entered the study and at two 18-month intervals, providing a snapshot over a three-year period of time.

Evaluations included carotid intimal-media thickness (cIMT) measurements and objective measures of menopausal status based on hormone levels and physiologic changes, not subjective factors, such as hot flashes and estimates of menstrual cycling.

Women who transitioned from being premenopausal to being fully postmenopausal within three years had more buildup of fatty plaque in their carotid arteries, suggesting that women who transition through menopause rapidly are at greater risk of early development of heart disease.

"We know that more fatty plaque accumulation predicts future heart attacks and strokes, but this is our first venture into this particular line of inquiry. This is an observational study, which doesn't provide specific recommendations for patient evaluation and treatment, but it does raise questions," Bairey Merz said.

"The findings suggest that we study this more definitively to possibly determine if women undergoing a more rapid menopause might benefit from early hormone replacement therapy," she said. "In the meantime, physicians could consider using carotid intimal-media thickness measurement or other cardiovascular screenings for women who are rapidly transitioning or who have certain risk factors, such as cigarette smoking or chemotherapy, which are known to accelerate transition through the menopause."

The study should not be used by patients to self-diagnose or presume they may be at higher risk because of symptoms.

"Women will say they're perimenopausal because they're having hot flashes or sleep disturbances or some cycle irregularity, but those are all symptoms. We use a very specific code of definitions to assess hormones and whether or not the ovaries are cycling," Bairey Merz said, adding that all women from the age of 21 should have annual checkups, which include blood pressure, cholesterol, height, weight and other measurements. Those at increased risk for cardiovascular disease may be referred by their physicians for additional screenings.

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Funding for this study was provided by a grant from the National Institutes of Health/National Heart, Lung, and Blood Institute.

Twin study: Diabetes significantly increases risk for Alzheimer's disease and other dementia

Getting diabetes before 65 more than doubles risk for Alzheimer's disease

28 jan 2009--Diabetics have a significantly greater risk of dementia, both Alzheimer's disease — the most common form of dementia — and other dementia, reveals important new data from an ongoing study of twins. The risk of dementia is especially strong if the onset of diabetes occurs in middle age, according to the study.

"Our results . . . highlighted the need to maintain a healthy lifestyle during adulthood in order to reduce the risk of dementia late in life," explained Dr. Margaret Gatz, who directs the Study of Dementia in Swedish Twins.

In a study published in the January 2009 issue of Diabetes, Gatz and researchers from Sweden show that getting diabetes before the age of 65 corresponds to a 125 percent increased risk for Alzheimer's disease. Nearly 21 million people in the United States have diabetes, according to the American Diabetes Association, which publishes the journal.

This risk of Alzheimer's disease or other dementia was significant for mid-life diabetics — as opposed to those who develop diabetes after 65 — even when controlling for family factors. In other studies, genetic factors and childhood poverty have been shown to independently contribute to the risk of both diabetes and dementia.

"Twins provide naturally matched pairs, in which confounding factors such as genetics and childhood environment may be removed when comparisons are made between twins," explained Gatz, professor of psychology, gerontology and preventive medicine at the University of Southern California and foreign adjunct professor of medical epidemiology and biostatistics at the Karolinska Institute in Sweden.

Indeed, the chances of a diabetic developing Alzheimer's disease may be even greater in real life than in the study, the researchers write. They identify several factors that might have led them to underestimate the risk of dementia and Alzheimer's among those who develop diabetes before the age of 65.

Diabetes usually appears at a younger age than dementia does, the researchers note. Diabetes is also associated with a higher mortality rate, which may reduce the size of the sample of older adults. In addition, approximately 30 percent of older adults with diabetes have not been diagnosed.

The results of the study implicate adult choices such as exercise, diet and smoking, as well as glycemic control in patients with diabetes, in affecting risk for Alzheimer's disease and diabetes, according to the researchers.

The sample for the study was 13,693 Swedish twins aged 65 or older in 1998, the year tracking for dementia began. Information about diabetes came from prior surveys of twins and linkage to hospital discharge registry data beginning in the 1960s.

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Weili Xu of the Karolinska Institute was the lead author of the study, which was a part of her dissertation research.

Weili Xu, et al., "Mid- and Late-Life Diabetes in Relation to the Risk of Dementia." Diabetes: January 2009.

The research was supported by grants from the National Institute on Aging, the Alzheimer's Association (U.S.A.), the Swedish Research Council in Medicine, and Swedish Brain Power.

Another Potential Benefit of Cutting Calories: Better Memory

Eating fewer calories may lead to better memory, a new study says.

By PAM BELLUCK

28 jan 2009--The study, published Monday in The Proceedings of the National Academy of Sciences, appears to be the first to link calorie-restricted diets with improved memory in people. Studies with animals have shown memory improvement, but there is debate about the impact of calorie restriction on humans’ cognitive function.

The study was small, involving 50 men and women ages 50 to 72 who ranged from normal weight to overweight.

Members of one group ate food they normally ate but were instructed to cut their calories by 30 percent, primarily by eating smaller portions, said Dr. Agnes Flöel of the University of Münster in Germany, a neurologist and one of the researchers. Members of a second group kept their calories the same but were instructed to increase the unsaturated fat (healthy fat) they ate by 20 percent. A third group made no dietary changes.

Participants were advised by dietitians but monitored their own eating over three months, Dr. Flöel said. Then they took tests involving memorizing words. The calorie-restricted group averaged 20 percent improvement in memory performance. The other groups showed no significant change.

Dr. Flöel said the memory improvement might be linked to a decrease in insulin and inflammation in the calorie-restricted participants, who lost four to seven pounds.

She said lower insulin levels might “increase the sensitivity of receptors” in the brain and improve insulin signaling, allowing memories to be maintained longer. She said inflammation was believed to “promote aggregation of toxic proteins and promote insulin resistance,” so decreased inflammation would help brain function.

Other scientists said the results were intriguing.

“This is the first that I know of in humans that is showing that effect,” said Grant Brinkworth, a research scientist at the Commonwealth Scientific and Industrial Research Organization in Australia. “The fact that they saw these correlations and quite strong correlations between memory and insulin, and also inflammation markers, suggests that there may be some physiological underpinning to the effect.”

Calorie restriction is being studied intently by researchers. Animal studies have shown that eating less leads to less disease and longer life, but human studies have been mixed on that question.

Its effect on cognitive function is unclear. Some studies have associated self-policed dieting with cognitive decline, but some experts say those dieters might have been preoccupied with thoughts of food and weight loss.

Other research, including part of a federally financed study of calorie restriction over two years, called Calerie, found no decline in cognitive performance, but no improvement either.

A principal investigator on the Calerie study, Eric Ravussin, a professor of human physiology at the Pennington Biomedical Research Center in Baton Rouge, La., said Calerie’s results did not undercut the new study. Calerie “didn’t have the same hard testing” on cognitive function, he said, it did not test memory, and “our subjects were much younger,” ages 20 to 50.

Dr. Flöel said researchers were surprised that participants in the unsaturated fat group showed no memory improvement, but that might have occurred because most did not get their unsaturated fats from fish, which is considered beneficial because it is high in omega-3 fatty acids.

She said her team was conducting a larger study in which the unsaturated fat group is eating a lot of omega-3 fats, and was also planning to study calorie cutting and omega-3 in elderly people with mild cognitive impairment, a precursor to dementia.

Omega-6 fatty acids: Make them a part of heart-healthy eating

American Heart Association science advisory

28 jan 2009-- Omega-6 fatty acids found in vegetable oils, nuts and seeds – are a beneficial part of a heart-healthy eating plan, according to a science advisory published in Circulation: Journal of the American Heart Association.

The association recommends that people aim for at least 5 percent to 10 percent of calories from omega-6 fatty acids. Most Americans actually get enough of these oils in the foods they are currently eating, such as nuts, cooking oils and salad dressings, the advisory reports. Recommended daily servings of omega-6 depend on physical activity level, age and gender, but range from 12 to 22 grams per day.

Omega-6, and the similarly-named omega-3 fatty acids (found in fattier fish such as tuna, mackerel and salmon), are called polyunsaturated fatty acids (PUFA), and can have health benefits when consumed in the recommended amounts, especially when used to replace saturated fats or trans fats in the diet. Omega-6 and omega-3 PUFA play a crucial role in heart and brain function and in normal growth and development. PUFA are "essential" fats that your body needs but can't produce, so you must get them from food.

"Of course, as with any news about a single nutrient, it's important to remember to focus on an overall healthy dietary pattern – one nutrient or one type of food isn't a cure-all," said William Harris, Ph.D., lead author of the advisory. "Our goal was simply to let Americans know that foods containing omega-6 fatty acids can be part of a healthy diet, and can even help improve your cardiovascular risk profile."

The American Heart Association's dietary recommendations suggest a broadly defined healthy eating pattern over time – with an emphasis on fruits, vegetables, high-fiber whole grains, lean meat, poultry, and fish twice a week. Diets rich in fruits, vegetables and whole grains have been associated in a large number of studies with reduced cardiovascular risk.

Linoleic acid (LA) is the main omega-6 fatty acid in foods, accounting for 85 percent to 90 percent of the dietary omega-6 PUFA.

There has been some debate within the nutrition community regarding the benefits of omega-6 based on the belief that they may promote inflammation, thus increasing cardiovascular risk. "That idea is based more on assumptions and extrapolations than on hard data," said Harris, a research professor for the Sanford School of Medicine at the University of South Dakota and director of the Metabolism and Nutrition Research Center at Sanford Research/USD

The linking of omega-6 intake to inflammation stems from the fact that arachidonic acid (AA), which can be formed from LA, is involved in the early stages of inflammation. However, the advisory explains that AA and LA also give rise to anti-inflammatory molecules.

For example, in the cells that form the lining of blood vessels, omega-6 PUFA have anti-inflammatory properties, suppressing the production of adhesion molecules, chemokines and interleukins — all of which are key mediators of the atherosclerotic process. "Thus, it is incorrect to view the omega-6 fatty acids as 'pro-inflammatory,'" Harris explained. "Eating less LA will not lower tissue levels of AA (the usual rationale for reducing LA intakes) because the body tightly regulates the synthesis of AA from LA."

The advisory reviewed a meta-analysis of randomized, controlled trials, and more than two dozen observational, cohort, case/control and ecological reports.

Observational studies showed that people who ate the most omega-6 fatty acids usually had the least heart disease. Other studies examined blood levels of omega-6 in heart patients compared with healthy people and found that patients with heart disease had lower levels of omega-6 in their blood.

In controlled trials in which researchers randomly assigned people to consume diets containing high versus low levels of omega-6 and then recorded the number of heart attacks over several years, those assigned to the higher omega-6 diets had less heart disease.

A meta-analysis of several trials indicated that replacing saturated fats with PUFA lowered risk for heart disease events by 24 percent. "When saturated fat in the diet is replaced by omega-6 PUFA, the blood cholesterol levels go down," Harris said. "This may be part of the reason why higher omega-6 diets are heart-healthy."

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Co-authors are: Dariush Mozaffarian, M.D.; Eric Rimm, D.Sc.; Penny Kris-Etherton, Ph.D.; Lawrence Rudel, Ph.D.; Lawrence Appel, M.D.; Marguerite Engler, Ph.D.; Mary Engler, Ph.D.; and Frank Sacks, M.D. Author disclosures are on the manuscript.

Aerobic, resistance best exercises for elderly

CHICAGO, 28 jan 2009 – Older, obese adults who do a combination of aerobic and resistance exercises have less insulin resistance -- a warning sign of type 2 diabetes -- and are better able to do simple tasks, researchers said on Monday.

The findings might be useful to help motivate elderly people, who often fear that exercise is bad for them, another expert said.

A team led by Lance Davidson of Queen's University in Kingston, Ontario, and Columbia University in New York, studied 136 sedentary older adults with abdominal obesity, a build-up of fat around the waist that raises the risk of heart disease and other problems.

They were placed in one of four groups: A group that did resistance exercise three times a week, one that walked on a treadmill three times a week, one that did both types of exercise and one that did neither.

After six months, researchers found older adults who had done combined resistance and aerobic exercise had lower levels of insulin resistance, an age-related condition that often precedes diabetes, stroke and heart disease.

Participants in all of the exercise groups were better able to do simple tasks like standing up from a chair or walking in place, Davidson and colleagues wrote in the Archives of Internal Medicine. But here too, the group that did a combination of exercises fared best.

Dr. William Hall, director of the Center for Healthy Aging at Highland Hospital in Rochester, New York, said bias against older people may be keeping some seniors from exercise.

"You have to show seniors that they will feel better and do better -- that becomes an incredible motivator," he said.

Ovary Removal May Not Be Needed in Endometrial Cancer

By Amanda Gardner
28 jan 2009-- Younger women with early-stage endometrial cancer need not lose their ovaries when undergoing treatment for the cancer, a new study contends.

The largest study to date has found no difference in five-year survival rates among women who kept their ovaries and those who did not. Removal of the ovaries, called an oophorectomy, has long been a standard part of therapy for endometrial cancer.

However, "it appears that this is a safe thing if a woman wants to go ahead and keep her ovaries," said Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge, La.

As always, though, no one decision is right for all women all the time.

"This is a retrospective study, so it's hard to say for sure that we should change practice based on this," said Dr. Jason D. Wright, assistant professor of obstetrics and gynecology at Columbia University College of Physicians & Surgeons in New York City and lead author of the study. "But it's definitely a provocative finding, and it does appear that ovarian preservation is safe."

"This is something that needs to be discussed with young women -- that this is available," he added. "Ideally, this would be tested in a prospective study."

The benefits of preserving the ovaries would be considerable. Young women would be spared the discomfort of hot flashes, vaginal dryness and other symptoms of induced menopause before their time. Also, avoiding the procedure would reduce the risk of cardiac disease and bone loss and would probably result in a longer life span.

The findings were published online Jan. 26 in the Journal of Clinical Oncology.

About 5 percent of endometrial cancer cases occur in women younger than 40. The average age is 60, and removing the ovaries is not really an issue for women after about age 50 because they have already undergone natural menopause, said Dr. Jeffrey Fowler, director of gynecologic oncology at the James Cancer Hospital and Solove Research Institute at Ohio State University in Columbus.

A hysterectomy (surgical removal of the uterus), and often an oophorectomy as well, has been standard with this type of cancer, largely because of concerns that the cancer might also affect the ovaries and that continued production of estrogen could fuel tumor growth.

The study spanned the years 1988 to 2004 and ultimately involved 3,269 women age 45 or younger who had stage I endometrial cancer. All of the women were registered in a national cancer database.

All women had a hysterectomy, and the 12 percent who kept their ovaries tended to be younger, to have been diagnosed later in the span of the study, to have a low tumor grade and to live in the eastern United States.

Removing the ovaries had virtually no effect on five-year survival rates, the study found. Among women who underwent the procedure, 98 percent of those with stage IA cancer, 96 percent who had stage IB disease and 89 percent with stage IC disease lived at least five years, compared with 98, 100 and 86 percent, respectively, of women who did not have their ovaries removed.

But even with oophorectomy dominating treatment for this type of cancer, individualization of treatment has been and should continue to be the standard, Fowler said.

Family history of cancer, stage and grade of the tumor and how aggressive the cancer is should all factor into treatment decisions, he said. So should the person's genetic vulnerability: Women carrying the BRCA cancer gene, for instance, probably have increased survival after undergoing ovary removal, he said.

"We need to individualize and discuss the risks and benefits," Fowler said.

FDA reviews benefits of Plavix in certain patients

By MATTHEW PERRONE
WASHINGTON, 27 jan 2009 – Federal health officials are investigating whether the blood thinner Plavix — the world's second-best-selling drug and used by millions to reduce the risk of heart attack and stroke — may be less effective in some patients.

The Food and Drug Administration said Monday it is reviewing reports that certain heartburn medications can neutralize the benefits of Plavix. The agency said it is also investigating whether patients from certain genetic backgrounds also don't reap the drug's benefits.

In both cases, FDA said patients may have trouble metabolizing Plavix, reducing its ability to prevent deadly blood clots.

Plavix had global sales of $7.3 billion in 2007. The drug is marketed by Bristol-Myers Squibb Co. and Sanofi-Aventis SA and has been prescribed to more than 90 million patients around the world.

In November, researchers found that taking Plavix with popular prescription heartburn drugs like AstraZeneca PLC's Nexium significantly increased patients' chances of being hospitalized for a heart attack, stroke or chest pain. The researchers suggested that the heartburn drugs might interfere with a liver enzyme needed to metabolize Plavix.

However, some heart experts were skeptical of the findings. They noted that patients taking heartburn drugs may already have health problems that skew their risk for heart attack and other problems.

Doctors prescribe so-called proton pump inhibitor drugs to treat heartburn, in which painful stomach acids come back up the esophagus. Because Plavix, known generically as clopidogrel, can upset the stomach, it is often prescribed with the acid-blocking drugs, which include Wyeth's Protonix.

FDA said in a statement it is important to determine how the drugs interact because "decreases in the effectiveness of clopidogrel might be avoided, in part, by using other drugs ... that do not interfere with its metabolism."

FDA said there is no evidence that the "H2 blocker" family of heartburn drugs counteract Plavix. Those drugs include Johnson & Johnson's Pepcid, Boehringer Ingelheim's Zantac and GlaxoSmithKline's Tagamet HB.

Sanofi-Aventis and Bristol-Myers Squibb said they are conducting studies of whether genetic factors or heartburn drugs can interfere with Plavix.

"Individuals do not all respond to the same degree to a specific drug," said Sanofi spokeswoman Elizabeth Baxter. "Many studies are currently ongoing, including studies of clopidogrel, to explore what is responsible for this phenomenon."

The studies will take several months to complete, according to FDA, which said it would issue recommendations after reviewing them.

Until more information is available, the FDA says patients should continue taking Plavix. However, doctors should be cautious when prescribing the heartburn drugs to patients already taking Plavix.

In general, the FDA has begun notifying the public earlier about possible safety issues involving drugs. The policy change came after the agency was criticized for acting too slowly on information about medicines that were later removed from the market due to safety reasons.

Frequent sex and masturbation in 20s and 30s linked to higher prostate cancer risk

But study also shows that risks diminish with age, particularly in a man's 50s

27 jan 2009--Men who are very sexually active in their twenties and thirties are more likely to develop prostate cancer, especially if they masturbate frequently, according to a study of more than 800 men published in the January issue of BJU International.

However the UK research team also found that frequent sexual activity in a man's forties appears to have little effect and even small levels of activity in a man's fifties could offer protection from the disease. Most of the differences were attributed to masturbation rather than sexual intercourse.

The study, led by the University of Nottingham, looked at the sexual practices of more than 431 men who had been diagnosed with prostate cancer before the age of 60, together with 409 controls.

Men who took part in the study were asked about all aspects of their sex life from their twenties onwards, including how old they were when they became sexually active, how often they masturbated and had intercourse, how many sexual partners they had had and whether they had had any sexually transmitted diseases.

"We were keen to look at the links between sexual activity and younger men as a lot of prostate cancer studies focus on older men as the disease is more prevalent in men over 50" says lead author Dr Polyxeni Dimitropoulou, who is now at the University of Cambridge.

"Hormones appear to play a key role in prostate cancer and it is very common to treat men with therapy to reduce the hormones thought to stimulate the cancer cells. A man's sex drive is also regulated by his hormone levels, so this study examined the theory that having a high sex drive affects the risk of prostate cancer."

The study participants, who were recruited by their family doctors, were asked to fill in a questionnaire about their sexual habits in each decade of their life since their twenties.

All the men with prostate cancer had been diagnosed in their fifties. Most of the men who took part in the study (97%) were white and the majority were currently married (84%) or widowed, separated or divorced (12%).

A number of interesting points came out of the study:

• 59% of the men in both groups said that they had engaged in sexual activity (intercourse or masturbation) 12 times a month or more in their twenties. This fell steadily as they got older, to 48% in their thirties, 28% in their forties and 13% in their fifties.
• 39% of the cancer group had had six female partners or more, compared with 31% of the control group.
• Men with prostate cancer were more likely to have had a sexually transmitted disease than those without prostate cancer.
• More men with prostate cancer fell into the highest frequency groups in each decade when it came to sexual activity (intercourse and masturbation) than men in the control group. 40% of men in the cancer group fell into the highest frequency category in their twenties (20 or more times a month) compared to 32% in the control group. Similar patterns were observed in the men's thirties and forties. By the fifties it had evened out, with 31% in each group falling into the most frequent category (ten or more times a month).
• Men with prostate cancer were also more likely to masturbate frequently than men in the control group, with the greatest difference in the twenties (34% versus 24%) and thirties (41% versus 31%). The differences were less pronounced in their forties (34% versus 28%) and by the fifties the cancer group was slightly lower (25% versus 26%).

"What makes our study stand out from previous research is that we focused on a younger age group than normal and included both intercourse and masturbation at various stages in the participants' lives" says Dr Dimitropoulou.

"Overall we found a significant association between prostate cancer and sexual activity in a man's twenties and between masturbation and prostate cancer in the twenties and thirties. However there was no significant association between sexual activity and prostate cancer in a man's forties.

"A possible explanation for the protective effect that men in their fifties appear to receive from overall sexual activity, and particularly masturbation, is that the release of accumulated toxins during sexual activity reduces the risk of developing cancer in the prostate area. This theory has, however, not been firmly established and further research is necessary."

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Notes to editors

Sexual activity and prostate cancer risk in men diagnosed at a younger age. Dimitropoulou et al. BJU International. 103, pp 178-185. (January 2009).

Patients starting Parkinson's drug rasagiline earlier do better

Long-term study suggests drug may slow progression of movement disorder

Tampa, FL ,27 jan 2009– There is hope that the drug rasagiline can do what no other medication for Parkinson's disease now does -- slow the progression of a devastating degenerative brain disease that eventually robs people of their ability to move and function.

Now a new study looking at the long-term effects of rasagiline (Azilect) on newly diagnosed patients indicates that people who began the drug earlier continued to do better than those for whom treatment was delayed six months. The study "Long-term Outcome of Early Versus Delayed Rasagiline Treatment in Early Parkinson's Disease" was recently published in the early online version of the journal Movement Disorders.

"Patients who received rasagiline right from the beginning rather than after a six-month delay experienced less progression of the clinical signs and symptoms of Parkinson's disease that interfere with activities of daily living such as eating, walking and dressing," said the study's lead author Robert A. Hauser, MD, director of the University of South Florida Parkinson's Disease and Movement Disorders Center. "This is potentially consistent with a slowing of underlying disease progression, although other possible mechanisms also need to be considered."

The study, sponsored by Teva Pharmaceutical Industries Ltd. (Israel), Teva Neuroscience, Inc. (USA) and H. Lundbeck A/S (Denmark), was a long-term open label extension of the multisite trial "TVP-1012 (rasagiline) in Early Monotherapy for Parkinson's Disease Outpatients" study, known as TEMPO. In TEMPO, more than 400 untreated patients with early Parkinson's disease were randomly assigned to rasagiline for a year (1 mg daily or 2 mg daily) or to placebo for six months followed by rasagiline for six months (2 mg daily). At the end of a year, patients receiving rasagiline from the start fared better as measured by the Unified Parkinson's Disease Rating Scale. They experienced less worsening of motor symptoms, such as rigidity and tremor, and had fewer problems with activities of daily living than patients who began rasagiline six months later.

The open-label extension study followed more than 300 patients from the TEMPO study for up to 6.5 years. In this extension study, all patients continued on rasagiline (1 mg. daily) and could take other Parkinson's disease medications as needed. The researchers found those who started rasagiline right from the beginning of the TEMPO study continued to fare better than patients in the delayed-start group. Over the course of the entire study, the early-start group had 16 percent less progression of the signs and symptoms of Parkinson's disease, and this greater clinical benefit was observed even as patients received conventional Parkinson's disease medications in addition to rasagiline. Rasagiline appeared to be well tolerated in this long-term study.

If the clinical outcomes from the TEMPO and extension study hold up under further scrutiny, it may indicate that early initiation of rasagiline confers a protective effect against disease progression, Dr. Hauser said. "If this is the case, it reinforces the importance of individuals being diagnosed and treated as soon as possible."

The study authors point out that early initiation of any drug to relieve symptoms of Parkinson's disease may lead to a better clinical outcome compared to delayed administration -- something that will be elucidated as more delayed-start studies are performed with other Parkinson's medications.

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USF Health is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida's colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $360 million in research grants and contracts last year, USF is one of the nation's top 63 public research universities and one of 39 community-engaged, four-year public universities designated by the Carnegie Foundation for the Advancement of Teaching. For more information, visit www.health.usf.edu

Common medication associated with cognitive decline in elderly

Study suggests use of certain medications in elderly populations may be associated with cognitive decline

New Haven, Conn., 27 jan 2009- A study published in Journal of the American Geriatrics Society suggested that the use of certain medications in elderly populations may be associated with cognitive decline. The study examined the effects of exposure to anticholinergic medications, a type of drug used to treat a variety of disorders that include respiratory and gastrointestinal problems, on over 500 relatively healthy men aged 65 years or older with high blood pressure.

Older people often take several drugs to treat multiple health conditions. As some of these drugs also have properties that affect neurotransmitters in the brain that are important to overall brain function, the researchers examined the total effects of all medications taken by the patients, both prescription and over-the-counter, that were believed to affect the function of a particular neurotransmitter, acetylcholine.

The findings show that chronic use of medications with anticholinergic properties may have detrimental effects on memory and the ability to perform daily living tasks, such as shopping and managing finances. Participants showed deficits in both memory and daily function when they took these medications over the course of a year. The degree of memory difficulty and impairment in daily living tasks also increased proportionally to the total amount of drug exposure, based on a rating scale the authors developed to assess anticholinergicity of the drugs.

According to study co-author Dr. Ling Han of the Yale University Department of Internal Medicine, elderly patients may be more vulnerable to these types of medications due to neurological and pharmacokinetical changes related to aging..

"This study extends our previous findings on acute cognitive impairment following recent anticholinergic exposure in older medical inpatients," says Han. "Prescribing for older adults who take multiple prescription and over-the-counter medications requires careful attention to minimize the risk of potential harms of the drugs while maximizing their health benefits."

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This study is published in Journal of the American Geriatrics Society. Media wishing to receive a PDF of this article may contact medicalnews@bos.blackwellpublishing.net

Ling Han, M.D., Ph.D., MSc, is a senior epidemiologist and biostatistician at the Program on Aging, Internal Medicine, at Yale University and can be reached for questions at ling.han@yale.edu.

Sleep disordered breathing and obesity: independent effects, causes

Sleep Apnea Linked to Insulin Resistance, Independent of Obesity

27 jan 2009--In a study that addressed the issue of insulin sensitivity with respect to sleep disordered breathing (SDB), Naresh Punjabi, M.D., Ph.D. sought to examine the relationship between SDB and insulin resistance using the best tools at his disposal to do so.

The results definitively link SDB to pre-diabetic changes in insulin production and glucose metabolism. It was published in the first issue for February of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

"In the past researchers have used body mass index, or BMI, as a proxy measure for body fat, but we know this to be a variable and crude tool to assess the true percentage of body fat," said Dr. Punjabi. "In addition, previous studies have used surrogate measurements to assess the body's response to insulin without investigating the interaction that occurs between reduced insulin sensitivity and increased insulin production in the body."

To address the shortcomings of previous studies, Dr. Punjabi and colleagues used two tools in their investigation into the link between SDB and insulin resistance: dual-energy x-ray absorptiometry (DEXA), a highly precise technique for assessing body fat, and frequently sampled intravenous glucose tolerance test (FSIVGTT), which provides a detailed picture of the subject's insulin sensitivity over time, rather than a simple snapshot at a specific moment.

They recruited 118 subjects, 39 who had no SDB, and 79 who were newly diagnosed with SDB but who had not been treated. Each subject underwent a sleep study to assess their level of SDB, and then underwent a FSIVGGT to determine their glucose metabolism and insulin sensitivity/production the following day.

"Our major finding was that, as we suspected, SDB was strongly associated with a decrease in the three major metabolic pathways that the body uses to metabolize glucose— insulin sensitivity, glucose effectiveness, and pancreatic cell function— independent of adiposity," said Dr. Punjabi. "What our research tells us is that SDB is characterized by multiple physiological deficits that increase the predisposition for type 2 diabetes mellitus."

Sleep Apnea linked to the Progression of Liver Disease

In another study published in the same issue of the Journal, other researchers from Johns Hopkins Bayview Medical Center Bariatric Surgery Clinic found that the chronic intermittent hypoxia that often characterizes OSA, a common form of SDB, is also independently linked to the progression of liver disease.

In this study, researchers recruited 90 severely obese patients presenting for bariatric surgery at without known diagnoses of obstructive sleep apnea. Each patient underwent a sleep study and blood tests for markers of liver function, insulin resistance, and systemic inflammation. And, because standard practice for patients undergoing bariatric surgery is to biopsy the liver, the researchers were able to analyze liver tissue for signs of disease and link it to the severity and type of sleep disordered breathing they observed during the sleep study.

The results validated the link between OSA and insulin resistance, and further linked it to the level of hypoxemia experienced during the night versus simply the number of apneic events. Strikingly, of the patients whose liver tissue was analyzed, those who were observed to have severe nocturnal hypoxemia also exhibited "ballooning" of their hepatocytes and a pericellular fibrosis of the liver, indicating liver injury.

"We demonstrated that the severity of nocturnal oxyhemoglobin desaturation predicted the severity of insulin resistance and might be implicated in the development of liver disease. In contrast, severe obesity was associated with high levels of serum c-reactive protein (CRP), indicating systemic inflammation," said lead researcher, Vsevolod Y. Polotsky, M.D., Ph.D., of Johns Hopkins' Asthma and Allergy Center. "Interestingly, there was no relationship between the severity of nocturnal hypoxemia and serum CRP. This suggests that that obesity and OSA have distinct metabolic, inflammatory and hepatic profiles, which act in different detrimental ways on the liver."

"We hypothesize that severe obesity per se acts as a 'first hit' in the progression of liver disease, inducing hepatic steatosis, whereas the presence of the chronic intermittent hypoxemia that often characterizes OSA acts as a 'second hit'. The hypoxic stress of OSA may induce oxidative stress in the livers of patients with severe obesity, leading to further inflammation."

The clinical implications of the findings are clear: obesity and obstructive sleep apnea exert separate and perhaps additive negative effects on insulin resistance and the liver, and each disorder must be treated concomitantly in order to address the secondary complications.

"Our data suggest that patients with OSA and severe nocturnal hypoxemia should be screened for liver disease and, conversely, patients with liver disease should be screened for OSA," said Dr. Polotsky.

"We have developed a mouse model of intermittent hypoxia and have demonstrated that a combination of a high-fat diet and intermittent hypoxia leads to liver disease in those mice. We plan on continuing to use the model in future research. We plan to examine whether treatment of OSA with continuous positive airway pressure can improve or reverse liver disease."

Severity of OSA Linked to Sedentary Lifestyle

Not only is OSA linked to insulin resistance and liver disease independent of obesity, but at least one risk factor is also common to obesity and OSA: prolonged daytime sitting or standing. Even when the sedentary lifestyle does not lead to obesity, it may still lead to OSA and its concomitant health risks, according to another research article in the first issue for February of the American Journal of Respiratory and Critical Care Medicine.

"Overnight fluid displacement from legs, related to prolonged sitting, may play a previously unrecognized role in the pathogenesis of OSA," wrote principle investigator, T. Douglass Bradley, M.D., professor of medicine and director of the Centre for Sleep Medicine and Circadian Biology at the University of Toronto,

The research also found that the volume of fluid shift was directly linked to the hours in a day that the subject reported sitting or standing and was independent of the excess weight that often accompanies sedentary lifestyles.

"In more recent years, the introduction of modern technologies into the workplace has greatly reduced the need for physical activity and increased the number of jobs requiring prolonged sitting, during which absence of the contraction of calf muscles leads to dependent fluid accumulation in the legs that is proportional to the time spent in that position," explained Dr. Bradley. "When assuming the recumbent position at bedtime, the fluid retained in the legs during the day in redistributed to the upper body. It is therefore plausible that some of the displaced fluid might reach the neck and predispose to upper airway constriction."

To determine whether that, in fact, was the case, the researchers recruited 23 nonobese subjects who were being evaluated for suspected OSA and performed standard sleep studies that assessed each subject for sleep stages and number of arousals, as well as oxygen saturation of the blood. The circumferences of their calves and necks were also measured at bedtime and upon awakening, before they got up.

Indeed, they found that the only significant correlate factor with respect to severity of OSA was the overnight change of fluid volume in the leg, which explained 67% of the variance in OSA severity. The change in fluid in the leg was, in turn, directly related to the amount of time the subject reported sitting each day.

"An important implication of our observations is that sedentary living may predispose to OSA not only by promoting obesity, but also by causing dependent fluid accumulation in the legs, which can shift rostrally to the neck overnight," said Dr. Bradley.

This finding may also help explain why 40 percent of patients with OSA are not obese, and why a reduction in OSA has been described when subjects begin exercise programs, even in the absence of weight loss.