Sunday, May 31, 2009

Low vitamin D levels may impair thinking

NEW YORK, 31 may 2009- New research suggests that low vitamin D levels in the body are associated with thinking or "cognitive" impairments in older men, but whether vitamin D supplements can help is not yet known.

In the study, an investigation of European men, subjects with low levels of vitamin D scored worse on a standard test of cognitive ability than did their peers with normal levels, Dr. David M. Lee, from the University of Manchester, UK, and co-researchers found. Although, the authors emphasize, the difference in scores was not that great.

Included in the investigation were 3133 men, 40 to 79 years of age, who were enrolled in the European Male Aging Study (EMAS). The average level of 25-hydroxyvitamin D, an inactive form of vitamin D used to measure levels of the vitamin, was 63 nanomoles per liter. Levels of 90 to 140 nanomoles per liter are typically considered optimal.

The researchers report their findings report in the Journal of Neurology, Neurosurgery, and Psychiatry.

As vitamin D levels fell, so did cognitive performance. Further analysis indicated that this relationship was largely confined to men over age 60 and was strongest with vitamin D levels below 35 nanomoles per liter.

While the magnitude of the association was small, Lee and colleagues note, if a simple measure, such as vitamin D supplementation, could improve cognition, then the findings could have important public health implications.

SOURCE: Journal of Neurology, Neurosurgery, and Psychiatry, May 21, 2009 online issue.

Vitamin D may help prevent knee osteoarthritis

NEW YORK, 31 may 2009- Low levels of vitamin D are associated with the loss of cartilage in the knee joint of older individuals, researchers in Australia report.

"Cartilage loss is the hallmark of osteoarthritis," Dr. Changhai Ding told Reuters Health. By the time patients reach the point of needing knee replacement, 60 percent of cartilage has been lost, he said.

However, "achieving vitamin D sufficiency in osteoarthritis patients could significantly delay total knee replacement," said Ding, at the Menzies Research Institute in Tasmania.

In a study, Ding and colleagues found "osteoarthritis patients with vitamin D sufficiency have approximately 1.5 percent less loss of knee cartilage per year than patients with vitamin D deficiency," said Ding.

The investigators measured levels of vitamin D in blood samples and knee cartilage volume on X-rays from 880 men and women who were 51 to 79 years old. The team then took similar measurements again almost 3 years later among 353 of the study participants, the researchers report in the journal Arthritis & Rheumatism.

Overall, 58 percent of these subjects showed changes in knee cartilage indicating worsening osteoarthritis between the first and second measurements, and half reported knee pain.

Both at the beginning of the study enrollment and at follow up, men and women with vitamin D deficiency had lower knee cartilage volume and were more likely to experience knee pain.

Ding's team concludes that vitamin D plays an important role in cartilage changes, and that vitamin D deficiency may predict knee cartilage loss over time.

The researchers call for further research to see if vitamin D supplementation can delay the progression of knee osteoarthritis and the need for total knee replacement in osteoarthritis patients.

SOURCE: Arthritis & Rheumatism, May 2009

Neighborhood Safety Is Linked to Disability

"Our results suggest that dangerous neighborhoods get from the mind into the body and engender mobility disability through psychosocial or psychological processes," Dr. Cheryl Clark, of Brigham and Women's Hospital in Boston, said in a news release from BioMed Central, which is publishing the study in its journal BMC Public Health.

The study included 1,884 people, age 65 and older, whose perceptions of danger were compared with levels of violent crime reported in their neighborhoods. The two matched up well, the study found, but it was the participants' sense that their neighborhood was unsafe that was most strongly associated with the development of a physical disability.

There may be a number of reasons for this, the researchers suggested. Lower-income seniors in unsafe neighborhoods might have fewer resources to cope with neighborhood stresses, and areas with high crime rates could have difficulty attracting businesses that provide products and services.

"Our findings underscore the importance of neighborhood safety to healthy aging," Clark said. "Specifically intervening to improve perceptions of neighborhood safety at retirement age may be an important step to reduce the risk of mobility disability among elders."

Cancer Survivors Can Still Be Fit, Study Asserts

Researchers from Georgetown University Medical Center in Washington, D.C., reached the conclusion after giving a three-minute step test to 49 diverse women who had recently survived cancer.

"What's really exciting to us was that we found that cardiovascular fitness was not affected by the expected culprits -- cancer treatment, type, duration or time since treatment," researcher Jennifer LeMoine, a fellow with training in exercise physiology at Georgetown University's Lombardi Comprehensive Cancer Center, said in a news release from the university. "That isn't to say there aren't side effects of some treatments that may hinder physical activity, but when it comes to actual cardiovascular fitness as measured in our clinic, many of the standard treatments didn't have a role."

The results of the study were to be presented this week in Seattle at the annual meeting of the American College of Sports Medicine.

A third of the study participants said they lived sedentary lives, and the others described themselves as physically active. About 71 percent of the participants completed the step test, the researchers reported.

"We've modified an in-clinic cardiovascular assessment tool, the three-minute step test, with the goal of finding a test that can easily and quickly be performed in a physician's office," Dr. Priscilla A. Furth, a professor of oncology and medicine at Lombardi, said in the news release. "Having this kind of evaluation tool is critical for physicians, like me, who are interested in prescribing physical activity for this population."

Study: Drug combos may raise breast cancer risk

ORLANDO, Fla., 31 may 2009 – Breast cancer survivors risk having their disease come back if they use certain antidepressants while also taking the cancer prevention drug tamoxifen, worrisome new research shows.

About 500,000 women in the United States take tamoxifen, which cuts in half the chances of a breast cancer recurrence. Many of them also take antidepressants for hot flashes, because hormone pills aren't considered safe after breast cancer.

Doctors have long known that some antidepressants and other medicines can lower the amount of tamoxifen's active form in the bloodstream. But whether this affects cancer risk is unknown.

The new study, reported Saturday at a cancer conference in Florida, is the largest to look at the issue. It found that using these interfering drugs — including Prozac, Paxil or Zoloft — can virtually wipe out the benefit tamoxifen provides.

Many doctors question the magnitude of harm from combining these medicines, and a second, smaller study suggests it may not be very large.

But the bottom line is the same: Not all antidepressants pose this problem, and women should talk to their doctors about which ones are best.

"There are other alternatives we can consider" that are safer, said Dr. Eric Winer, breast cancer chief at the Dana-Farber Cancer Center in Boston.

He had no role in the study, which was done by Medco Health Solutions Inc., a large insurance benefits manager. Researchers used members' medical records to identify 353 women taking tamoxifen plus other drugs that might interfere with it, and 945 women taking tamoxifen alone. Those taking a drug combo did so for about a year on average.

Next, researchers checked to see how many were treated for second cancers in the following two years. Breast cancer recurred in about 7 percent of women on tamoxifen alone, and in 14 percent of women also taking other drugs that could interfere — mainly the antidepressants Paxil and Prozac, and, to a lesser extent, Zoloft.

If women want to take an antidepressant, "you probably want to stay away from those three," said Medco's chief medical officer, Dr. Robert Epstein.

No greater breast cancer risk was seen in women taking the antidepressants Celexa, Lexapro or Luvox with tamoxifen, and there are reasons to think that other antidepressants may be safe as well, Epstein said.

A second study led by Dr. Vincent Dezentje of Leiden University Medical Center in the Netherlands found little risk from combining tamoxifen and popular antidepressants. However, only 150 women in the study took such combos for more than two months, and they were compared to women taking combos for a shorter time — not to women using tamoxifen alone.

The Dutch and Medco studies were presented at a meeting of the American Society of Clinical Oncology.

The federal Food and Drug Administration has been considering a change to tamoxifen's label to warn about the antidepressants drugs and a gene variation some women have that can make tamoxifen less effective. An advisory panel unanimously recommended a change in 2006, but the agency is still considering it.

"This is a very controversial area," said Dr. Claudine Isaacs, a breast specialist at Georgetown University's Lombardi Comprehensive Cancer Center. "Until these data are absolutely clear, I would avoid drugs that impact on tamoxifen metabolism."

Breast cancer is the most common major cancer in American women. More than 182,000 new cases were diagnosed last year, and it caused nearly 41,000 deaths.

Saturday, May 30, 2009

Seniors stay healthier when they live with spouse

NEW YORK , 30 may 2009 - Elderly, community-dwelling men and women appear more likely to obtain preventive health care when they live with their spouse, as opposed to living alone or with an adult child, researchers report in the American Journal of Public Health.

Still, "colorectal cancer screening, routine dental check-up, and influenza vaccination remain well below national targets according to the Centers for Disease Control's Healthy People 2010," report Drs. Denys Lau of Northwestern University in Chicago, Illinois, and James Kirby with the Agency for Health Care Research and Quality in Rockville, Maryland.

Their findings call attention to elders' underuse of preventive health care screenings, the researchers say.

Moreover, Lau told Reuters Health, the findings of this study suggest that "healthcare providers should not assume that elderly patients living with their adult offspring will have adequate family resources to obtain preventive services."

Lau and Kirby assessed medical expenditure information from 2002 to 2005 for 13,038 community-dwelling men and women at least 65 years old.

Most (94 percent) reported needing help with at least one activity of daily living. Seventy-five percent reported having at least one chronic health condition such as angina, asthma, coronary heart disease, diabetes, emphysema, high blood pressure, or had a previous heart attack or stroke.

Overall, 52 percent lived only with their spouse, 38 percent lived alone, 5 percent lived with adult offspring and another 5 percent lived with their spouse and adult offspring.

Those living only with their spouse were more likely than those in other living arrangements to obtain influenza vaccinations, cholesterol screenings, colorectal cancer screenings, routine physical check-ups, and routine dental care. Living arrangements did not alter elders' screenings for high blood pressure, however.

Factoring in the employment and disability status of adult offspring offered no explanation as to why living with adult offspring "had no benefits to elderly persons in terms of accessing timely preventive care," Lau said.

The two researchers call for additional investigations of barriers to the utilization preventive health care by the elderly, and increased education about the benefits of obtaining such care.

SOURCE: American Journal of Public Health, July 2009.

Omega fatty acid balance can alter immunity and gene expression

Appearing in the June 5 issue of JBC

30 may 2009--For the past century, changes in the Western diet have altered the consumption of omega-6 fatty acids (w6, found in meat and vegetable oils) compared with omega-3 fatty acids (w3, found in flax and fish oil). Many studies seem to indicate this shift has brought about an increased risk of inflammation (associated with autoimmunity and allergy), and now using a controlled diet study with human volunteers, researchers may have teased out a biological basis for these reported changes.

Anthropological evidence suggests that human ancestors maintained a 2:1 w6/w3 ratio for much of history, but in Western countries today the ratio has spiked to as high as 10:1. Since these omega fatty acids can be converted into inflammatory molecules, this dietary change is believed to also disrupt the proper balance of pro- and anti- inflammatory agents, resulting in increased systemic inflammation and a higher incidence of problems including asthma, allergies, diabetes, and arthritis.

Floyd Chilton and colleagues wanted to examine whether theses fatty acids might have other effects, and developed a dietary intervention strategy in which 27 healthy humans were fed a controlled diet mimicking the w6/w3 ratios of early humans over 5 weeks. They then looked at the gene levels of immune signals and cytokines (protein immune messengers), that impact autoimmunity and allergy in blood cells and found that many key signaling genes that promote inflammation were markedly reduced compared to a normal diet, including a signaling gene for a protein called PI3K, a critical early step in autoimmune and allergic inflammation responses.

This study demonstrates, for the first time in humans, that large changes in gene expression are likely an important mechanism by which these omega fatty acids exert their potent clinical effects.


From the article: Effect of dietary fatty acids on inflammatory gene expression in healthy humans, by Kelly L. Weaver, Priscilla Ivester, MIchael C. Seeds, L. Douglas Case, Jonathan Arm and Floyd H. Chilton
Article Link:

Policy gurus advocate community-based approaches to senior housing

30 may 2009--The latest installment of Public Policy & Aging Report (PPAR, Vol. 19, No. 1) evaluates current models of creating sustainable lifelong communities for people of all ages. The issue's four articles also explore some of the controversies associated with options presently available.

In the lead article, Jon Pynoos, PhD, and Caroline Cicero, MSW, MPL, track the United States' progress in the development of aging-friendly communities. These include home modification and community-level innovations designed to lessen isolation and increase social interaction.

Stephen Golant, PhD, suggests that aging in place (i.e., using physical and social structures to allow older adults to remain in their homes as long as possible) may be an inappropriate option for many elders due to financial barriers, local policies, and flawed data about its actual appeal. He urges people to recognize when appropriate community alternatives are necessary.

Next, Kathryn Lawler, MPP, and Cathie Berger, LMSW, explore the Atlanta Regional Commission's comprehensive planning and design activities for creating communities that benefit all ages.

Andrew Blechman uses the final article to profile The Villages, an age-restricted community in central Florida. He critiques this upscale option, noting that private ownership impinges on traditional public functions and that troublesome intergenerational and racial issues lurk in the background of such a community.

Additionally, Sarah Frey contributes eight case studies of today's most innovative residential options for seniors.


This issue of PPAR, published by the National Academy on an Aging Society, is titled "Livable and Sustainable Communities" and can be purchased at

The National Academy on an Aging Society is the policy branch of The Gerontological Society of America (GSA), the nation's oldest and largest interdisciplinary organization devoted to research, education, and practice in the field of aging. The principal mission of the Society — and its 5,500+ members — is to advance the study of aging and disseminate information among scientists, decision makers, and the general public. GSA's structure also includes an educational branch, the Association of Gerontology in Higher Education.

Researchers develop light-treatment device to improve sleep quality in the elderly

Troy, N.Y.,30 may 2009 — Sleep disturbances increase as we age. Some studies report more than half of seniors 65 years of age or older suffer from chronic sleep disturbances. Researchers have long believed that the sleep disturbances common among the elderly often result from a disruption of the body's circadian rhythms—biological cycles that repeat approximately every 24 hours.

In recent years, scientists at Rensselaer Polytechnic Institute's Lighting Research Center and elsewhere have demonstrated that blue light is the most effective at stimulating the circadian system when combined with the appropriate light intensity, spatial distribution, timing, and duration. A team at the Lighting Research Center (LRC) has tested a goggle-like device designed to deliver blue light directly to the eyes to improve sleep quality in older adults.

"Light and dark patterns are the major synchronizer of circadian rhythms to the 24-hour solar day," said Mariana Figueiro, Ph.D., Lighting Research Center Light and Health Program director and principal investigator on the project. "Light stimulus travels through the retina, the light-sensitive nerve tissue lining the back wall of the eye, to reach the master clock in the brain. However, a combination of age-related changes in the eye and a more sedentary lifestyle may reduce the amount of light stimulus reaching an older person's retina, therefore reducing the amount of light for the circadian system."

As we age, the lens in the eye thickens and the pupil shrinks, reducing the amount of light passing through to the retina. Making matters worse, in some cases, such as with persons with Alzheimer's disease, the circadian system may require a stronger light stimulus due to deteriorating neural processes in the brain. These physical and neural changes can lead to muted signals to the circadian system. Factor in environmental influences, such as an indoor lifestyle with less access to daylight, and you have a perfect scenario for the development of irregular sleep-activity patterns, according to Figueiro.

The research team explains that a marked increase in daytime lighting levels can counteract the age-dependent losses in retinal light exposure by providing a stronger signal to the circadian system. However, the color and intensity of commercially available lighting systems, like those used in senior residences, assisted-living facilities, and nursing homes, are designed for visual effectiveness and minimal energy use and not necessarily efficacious for generating light to stimulate the older circadian system.

Commercially-available "white" light sources advertised to treat circadian-related sleep disorders are usually very bright light and can cause glare and compromise compliance.

In this project, the light-treatment prototype tested by Figueiro's team was developed by, LLC, based on prior LRC light and health research. The device offers an alternative approach using specially designed goggles that deliver blue light spectrally tuned for optimum circadian response.

"The goal of this phase of the development project was to create a device in a smaller form factor or envelope that allowed for social inclusion and end-user mobility, while still delivering the required dose of light," said Senior Developer Philip H. Bonello, Ph.D.

The device was worn by eleven subjects between the ages of 51 and 80 years of age. Each subject was exposed to two levels of blue light (about 50 lux and 10 lux) from the personal light-treatment device for 90 minutes on two separate nights. Blood and saliva samples were collected at prescribed times to assess levels of nocturnal melatonin, a hormone used as a marker for the circadian clock, with high levels at night when a person is in a dark environment and low levels during the day.

After only one hour of light exposure, the light-induced nocturnal melatonin suppression level was about 35 percent for the low light level and about 60 percent for the high light level. In addition, the higher level of blue light suppressed nocturnal melatonin more quickly, to a greater extent over the course of the 90-minute exposure period, and was maintained after 60 minutes.

Having demonstrated its stimulation effect on the circadian system, the researchers believe the device could be subsequently used to increase sleep consolidation and efficiency in older subjects when worn for a prescribed duration at an appropriate time.

"The study suggests that the light goggles might be a practical, comfortable, and effective way to deliver light treatment to those suffering from circadian sleep disorders. The next steps are to conduct field studies where we will be testing the effectiveness of this personal light-treatment device on those suffering from circadian-related sleep disorders, while also verifying the acceptance of the a device among the test groups," said Figueiro.


Figueiro carried out her research with LRC scientists Andrew Bierman, John Bullough, Ph.D., and Mark Rea, Ph.D. They co-authored a paper detailing the study, "A Personal Light-Treatment Device for Improving Sleep Quality in the Elderly: Dynamics of Nocturnal Melatonin Suppression at Two Exposure Levels," which was recently published in Chronobiology International, Volume 26 Issue 4, 726.

This study was supported by the National Institute on Aging (1R41AG029693) through a Small Business Technology Transfer grant to, LLC, a commercial and residential resource for light bulbs.

UTSA Dean George Perry co-edits textbook chronicling four decades of Alzheimer's research

CDC estimates nearly half of all people 85 and older struggle with Alzheimer's disease

San Antonio, 30 may 2009-- Two of the world's leading Alzheimer's researchers have co-edited a book critically synthesizing the major new developments in the diagnosis and treatment of Alzheimer's disease. Building upon a 2007 Alzheimer's disease conference held in Chile, George Perry, dean of the College of Sciences at The University of Texas at San Antonio (UTSA) and Ricardo B. Maccioni, neurology professor at The University of Chile Medical School have edited "Current Hypotheses and Research Milestones in Alzheimer's Disease," a 254-page text written by academics and medical doctors. The book focuses on the most promising hypotheses that illuminate the path to more effective treatment.

Highlights include:

  • new information about the biology of amyloid-ß, the main component in the amyloid plaques found in the brains of Alzheimer's disease patients, and where the field has concentrated its efforts for nearly 20 years
  • the Tau Hypothesis, which suggests Alzheimer's disease is caused by abnormal chemical changes to tau proteins disrupting the normal cell biology of neurons
  • the Oxidative Stress Hypothesis, which indicates neurons degenerate and die because the brains of patients with Alzheimer's disease have a disrupted oxidative metabolism leading to decreased neuronal energy supply and increased oxidative damage
  • neuroimmunological hypotheses linking Alzheimer's disease to the chronic low level inflammation thought to underlie arthritis, coronary disease and other age-related conditions
  • the development of biomarkers for early diagnosis
  • new horizons for the development of anti-dementia drugs

"Alzheimer's disease is the leading cause of dementia in senior citizens," said Perry, also a professor in UTSA's Department of Biology. "While the scientific community hasn't been able to pinpoint the cause of the disease, researchers around the world are advancing what we know about the disease and how we might be able to treat it in the future."


Perry, ranked one of the top ten Alzheimer's disease researchers in the world in 2009, joined UTSA in 2006 from Case Western Reserve University, where he was a professor of pathology and neurosciences and the chair of Case Western Reserve's Department of Pathology. A prolific researcher, Perry is the second-most published Alzheimer's disease researcher, with 516 publications to his credit. He serves as president of the American Association of Neuropathologists and is on the editorial boards of more than 70 journals including the American Journal of Pathology and the Journal of Biological Chemistry. He also is co-editor-in-chief of the Journal of Alzheimer's Disease, the leading journal for Alzheimer research.

The University of Texas at San Antonio is one of the fastest growing higher education institutions in Texas and the second largest of nine academic universities and six health institutions in the UT System. As a multicultural institution of access and excellence, UTSA aims to be the Next Great Texas University, providing access to educational excellence and preparing citizen leaders for the global environment.

UTSA serves more than 28,400 students in 64 bachelor's, 47 master's and 21 doctoral degree programs in the colleges of Architecture, Business, Education and Human Development, Engineering, Honors, Liberal and Fine Arts, Public Policy, Sciences and Graduate School. Founded in 1969, UTSA is an intellectual and creative resource center and a socioeconomic development catalyst for Texas and beyond.

Friday, May 29, 2009

Middle-aged spread and mortality

29 may 2009--“People who are overweight or obese in middle-age run the risk of being frail in later life,” reported BBC News. It said a study found that men who put on weight in their 40s but lost it when they got older were at the highest risk of death in their 70s. It quoted the study leader as saying, “the unhealthy pattern of weight in their 40s was causing frailty in later life probably due to underlying cardiovascular problems, such as high blood pressure and early stages of diabetes”.

This study had several limitations that restrict its reliability. In particular, it is important to note that it was not necessarily losing the excess weight they carried in their 40s that raised the men’s risk of death. Instead, it may be that these men lost weight because they had undiagnosed health problems, or because of other factors that the study did not investigate. The authors themselves note that “life-long normal body weight is the best option”, and the study’s findings should not be interpreted as encouragement to maintain an unhealthy weight.

Where did the story come from?

The research was carried out by Dr Timo E Strandberg and colleagues from the University of Oulu and other universities and research centres in Finland. The study was funded by Päivikki and Sakari Sohlberg Foundation, the Helsinki University Central Hospital and the Finnish Foundation for Cardiovascular Research. The study was published in the peer-reviewed European Heart Journal.

What kind of scientific study was this?

This study was a new analysis of data collected in a previous cohort study called the Helsinki Businessmen Study. This study involved initially healthy men, mostly business executives, who were born between 1919 and 1934. They started in the study in the 1960s and 70s, and had structured health check-ups as part of the study. The current study aimed to look at how changes in body mass index (BMI) throughout life affected death rates in old age. In particular, they wanted to look at how risk factor for cardiovascular disease (such as obesity) in midlife affected death rates.

In 1974 the 1,815 healthy middle-aged participants (average age 47 years) were examined, had their current height and weight measured, and were asked to recall their weight at age 25. They were also asked to rate how they perceived their health on a five-point scale, ranging from very good to very poor. Men with a history or signs of chronic diseases such as diabetes, high blood pressure or heart problems were not included in the study. Overweight was defined as a BMI (weight in kilogrammes divided by height in metres squared) over 25kg/m2 and normal weight defined as a BMI of 25kg/m2 or less.

In 1985-6, 909 of the men were again assessed, and a measurement taken of their BMI and waist circumference.

In 2000, at an average age of 73 years, all participants that were still alive (1,390 men) were sent questionnaires about their health, present weight, lifestyle (including smoking and alcohol consumption) and demographic factors, and whether they had a history of chronic diseases. This information was used to calculate a standard index that showed how many concurrent medical problems (comorbidities) the men had. Their health was assessed using a standard scale that gave summary scores for overall physical and mental health.

Data on BMI at age 25, and in 1974 and 2000, were available for 1,114 men (61% of original participants, 80% of those surviving to 2000), and these men were included in the analysis. The men were grouped according to their weight pattern from 1974 to 2000: those who had normal weight at both times (345 men), those who were overweight at both times (494 men), those who were of normal weight in 1974 but overweight in 2000 (136 men) and those who were overweight in 1974 but normal weight in 2000 (139 men). At the end of 2006, the researchers used a national population registry database to identify those men that had died and the causes of their deaths. They used statistical methods to look at whether BMI change from 1974 to 2000 was associated with risk of death. These analyses took into account smoking and the men’s perceived health at the start of the study, and self-reported history of disease in 2000.

What were the results of the study?

Of the 1,815 healthy middle-aged men evaluated at the start of the study, about 24% (425 men) had died by 2000. Men who were overweight at the start of the study were more likely to die in this period (about 26%) than those who were of a normal weight (20%).

Among the 1,114 participants with full data from both 1974 and 2000, almost half (44%) were constantly overweight, 31% were constantly of normal weight, 12% became overweight and 12% were overweight in midlife (in 1974) but became a normal weight by their 70s (in 2000). From 2000 to 2006, 188 of these men died (17%). The actual number of men who died in each group was not reported, but deaths were more common in the group of men who had gone from overweight in midlife to normal weight in their 70s than among men in the other groups. Men in the group that lost weight were about twice as likely to die between 2000 and 2006 than men who stayed a normal weight.

The other groups (those that remained overweight and those that became overweight) did not differ significantly from the group that remained a normal weight. These results were largely unchanged by making adjustments for age, smoking, perceived health in 1974 and self-reported diseases in 2000.

What interpretations did the researchers draw from these results?

The researchers conclude that men “who had normal weight in late life, but had been overweight in midlife, had the greatest mortality risk in old age. In contrast, the risk of those men who did not become overweight until after midlife did not differ from that of men with constantly normal weight”. They say that this may “suggest that cardiovascular risk factors may increase risk of frailty” and that their findings “support the implication that some weight gain may be beneficial for those who are not overweight in early adult life”.

However, they say that if deaths before later life are taken into account, men of a normal weight were at a lower risk of death than overweight men, and that “life-long normal body weight is the best option”.

This study has a number of limitations:

  • As with all studies of this type, it is possible that factors other than BMI change (known as confounders) were responsible for the difference seen. Although the authors took some potential confounders into account, these were not assessed in a very thorough way (for example, smoking was assessed only once and amount smoked was not assessed) and this may have reduced the ability of these adjustments to remove their effect. There may also have been other unmeasured and unknown confounders having an effect.
  • It is possible that there were some inaccuracies in weight and health assessment in the study. For example, the men may not have been able to remember accurately their weight at age 25, and, in 2000 when men had to report their own weight, these measurements may not have been accurate. Men also self-reported any diagnosed health problems in 2000, and these reports may not have been accurate.
  • The men were divided into four weight categories based on measurements of their weight on two occasions, 27 years apart. This is a relatively crude measure of weight change over a period this long, and within these categories the men’s weight may have fluctuated in different ways between these two times, which may have influenced the results.
  • This study included only men who were healthy in midlife and who were largely businessmen. The results may not apply to women, men in different socio-economic groups or men who are not healthy in midlife.
  • Regarding their analysis of “frailty” (the analysis that adjusted for self-reported disease in 2000), the authors themselves state that this analysis was “inconclusive and principally aims to be hypothesis-generating for future studies”. Therefore, no firm conclusions can be drawn about the effect of BMI on frailty.
  • In addition, about a quarter of men who were overweight at the start of the study (in 1974) had already died by 2000, and had these been included in the group that were “constantly” overweight between 1974 and 2000, this may have affected the results.
  • The suggestion by the authors that “some weight gain may be beneficial for those who are not overweight in early adult life” is not supported by the results. Those who were of normal weight in midlife and who became overweight in later life did not differ in their risk of death to those who remained a normal weight. This does not indicate that gaining weight is “beneficial”. In addition, death is not the only negative outcome associated with being overweight. Men who became overweight between 1974 and 2000 were more likely to report high blood pressure, diabetes, congestive heart failure and cerebrovascular disease, among other diseases, than men who maintained a constantly normal weight. Again, this does not suggest any “benefit” from gaining weight.

The points outlined above limit the reliability of the findings, which will need to be confirmed in further research. It is important to note that it was not necessarily losing excess weight they had carried in their 40s that put the men at risk of worse outcomes. Instead, it may be that these men lost weight because they had, as yet undiagnosed, health problems. The study’s findings should not be interpreted as encouragement to maintain an unhealthy weight or to gain weight.

Links to the headlines

Middle age spread link to frailty. BBC News, May 26 2009

Links to the science

Strandberg TE, Strandberg AY, Salomaa VV et al. Explaining the obesity paradox: cardiovascular risk, weight change, and mortality during long-term follow-up in men. European Heart Journal 2009; Advance Access published online on May 9

Scientists 'find hair loss gene'

29 may 2009--“A cure for baldness has come a step closer after scientists identified a gene that is connected to hair loss,” The Daily Telegraph has reported. Researchers blocked the activity of the Sox21 gene in mice and unexpectedly found that the mice started losing hair around two weeks after birth and had lost all their hair within a further week. The newspaper reported that this finding “should help scientists develop new treatments as well as help pinpoint early in life which men are likely to lose their hair”.

This study has found that if you remove the Sox21 gene from mice, their hair falls out. This does not necessarily mean that this gene plays a role in human baldness, and further studies are needed to determine whether this is actually the case.

However, this research does further our understanding of the biology of hair development and retention, and in this respect it may eventually play a part in the development of treatments to prevent or reverse hair loss. However, much more research would be needed before a “cure” for baldness becomes a reality.

Where did the story come from?

Dr Makoto Kiso and colleagues from the National Institute of Genetics and other research centres in Japan conducted this study. The research was funded by Solution-Oriented Research for Science and Technology, Japan Science and Technology Agency, and the Ministry of Education, Culture, Sports, Science and Technology, Japan. The study was published in the peer-reviewed scientific journal Proceedings of the National Academies of Science USA (PNAS).

What kind of scientific study was this?

This was an animal study looking at the role of the Sox21 gene in mice.

One method that scientists use to identify the functions of a particular gene is to stop that gene from working in mice and see what effect this has. The Sox21 protein (produced by the Sox21 gene) is capable of binding to DNA and is thought to help control whether the expression of specific genes is switched on or off in the cells.

Previous studies had suggested that the Sox21 gene plays a role in the development of nerve cells. Researchers in this study decided to identify the effects of Sox21 by genetically engineering mice to lack the gene. Once they had generated these mice, the researchers verified that the gene was completely inactive and then looked at the effects this had on their development.

The researchers found that hair development was affected, so they decided to look at normal mouse skin and human scalp tissue to see which cells in the skin and hair follicles the Sox21 gene was normally active in. They also examined samples of skin taken from Sox21-lacking mice and normal mice, looking at them under powerful microscopes (both scanning electron microscopes and transmission electron microscopes) to see whether there were any differences in the structure of their hair follicles. They also compared the activity of a number of genes in skin of both the normal and Sox21-lacking mice, including genes that are important for the development of hair.

What were the results of the study?

The researchers found that mice genetically engineered to lack the Sox21 gene started to lose their fur from 11 days after birth, and by about 20 to 25 days after birth they had lost all of their hair. The mice began to re-grow hair after a few days, but then lost it again. This cycle of hair loss and re-growth continued for at least two years in both male and female mice. These findings relating to hair loss were unexpected, as the Sox21 gene was not previously known to play a role in hair development.

The Sox21 gene was found to be active in normal mouse skin and in human scalp tissue, including in the outer layer of the hair shaft (called the cuticle layer) and also in the cells making new hair shaft cells, including cuticle cells. The researchers also found that mice lacking the Sox21 gene did not show the normal “interlocking” between the inner and outer layers of cuticle that anchors the hair shaft into the hair follicle.

When comparing gene activity between the Sox21-lacking mice and normal mice, the researchers identified five genes that were more active and 114 genes that were less active in the skin of the genetically engineered mice. Many of the genes that were less active in Sox21-lacking mice were those that produced proteins involved with making the “scaffolding” of cells and that allowed cells to stick together. This included a number of keratin proteins produced in cuticle cells and found in the hair.

What interpretations did the researchers draw from these results?

The researchers conclude that the Sox21 gene has an important role in controlling the development of the hair shaft cuticle and that this finding “shed[s] light on the possible causes of human hair disorders”.

What does the NHS Knowledge Service make of this study?

This research has shown that Sox21 is important for normal hair retention in mice and that the gene is also expressed in human hair follicles. However, while removing this gene in mice does cause their hair to fall out, this does not necessarily mean that this gene is a cause of human baldness. Further studies will be required to determine whether or not this is the case.

This study has furthered our understanding of the biology of hair retention, and it is possible that this research may one day lead to development of treatments to prevent or reverse hair loss. However, treatments based on the results of this study remain some way off, and much more research is needed before a “cure” for baldness becomes a reality.

Links to the headlines

Gene linked to hair loss brings cure for baldness nearer. The Daily Telegraph, May 27 2009

Links to the science

Kiso M, Tanaka S, Saba R et al. The disruption of Sox21-mediated hair shaft cuticle differentiation causes cyclic alopecia in mice. PNAS [Published online before print May 26, 2009]

Anemia associated with greater risk of death in heart disease patients

New study has found that anemia in patients with chronic heart failure is associated with a increased risk of death

Wagga Wagga, Australia -29 may 2009– A new study appearing in Congestive Heart Failure has found that the presence of anemia in patients with chronic heart failure is associated with a significantly increased risk of death. The findings also show that anemia is associated with a poorer degree of left ventricular function and a lower left ventricular ejection fraction, an objective measure of cardiac function.

Heart failure is a common and serious chronic illness. A large number of patients with heart failure also have anemia, which is most likely a complication from poor heart function. The aim of this study was to assess the impact of anemia on the clinical outcomes of chronic heart failure (CHF) by a meta-analysis and systemic review of published literature. A total of 97,699 patients with CHF were identified from the published studies. From a collective analysis, researchers found that when anemia occurs, it worsens patient prognosis, making them more likely to be hospitalized or die from heart failure.

"Health professionals may need to improve current practices to better treat anemia in patients with chronic heart failure," says Dr. Lexin Wang, M.D., Ph.D., Head of the Cardiovascular Group at Charles Sturt University and co-author of the study.

Even with contemporary medical treatment, the mortality rate from chronic heart failure is still very high, reaching 40 percent in very sick patients. Given the clear association between anemia and the mortality rate and hospitalization rate, optimal treatment of anemia, on top of other heart-failure-specific therapies, may reduce the rate of mortality and further improve patient's prognosis.

Co-Editor's in Chief, Drs. John Strobeck and Marc Silver are feel that "this publication by Dr. Wang and collaborators give some perspective to nearly a decade of interest on the relationship and role of anemia in patients with chronic heart failure.


This study is published in Congestive Heart Failure. Media wishing to receive a PDF of this article may contact

Daily alcohol intake can lead to bing drink

Study from Universite de Montreal and University of Western Ontario published

Montreal, May 28, 2009 — Sipping wine, beer or spirits three to four times per week increases the risk of binge drinking, particularly among young men, according to a new study published in the journal Addiction. Researchers from the Université de Montréal and the University of Western Ontario analyzed the drinking habits of Canadians and found that frequent alcohol consumption can lead to binge drinking among all gender and all age groups.

The study also found that infrequent drinkers rarely exceed two servings when they do consume alcoholic beverages. "The relationship between drinking frequency and consumption per occasion might be both cultural and biological," says study coauthor Andrée Demers, a Université de Montréal sociology professor and director of the Research Group on the Social Aspects of Health and Prevention. "The Canadian drinking culture has a 'time-out' depiction of drinking. Alcohol is a boundary mark between week and weekend, work and leisure, and therefore between routine and time off."

The investigation established one drink as 5 oz. of wine, 1.5 oz. of liquor, 12 oz. of beer or cooler, 3 oz of port, sherry or vermouth. Regardless of drinking preferences, the study found that many Canadians consume alcoholic beverages on a daily basis to experience its mood-altering affects.

Drinking for a festive feeling

"Regular drinking builds up tolerance, therefore daily drinkers will need more than their usual drink or two to make a difference with everyday life and gain that festive feeling," says lead author Catherine Paradis, a Université de Montréal PhD candidate. "That fosters drinking beyond healthy limits – at least sporadically and perhaps weekly – to five drinks or more per occasion. And five units is above the recommended limits of healthy drinking."

Study data was obtained from the GENACIS Canada project, an international collaboration examining how social and cultural variations can influence the drinking habits of men and women. Close to 11,000 respondents – 5,743 women and 4,723 men – were asked to report on their alcohol consumption within the last 12 months. Participants were asked questions such as:

  • "How often did you usually have any kind of drink containing alcohol?"
  • "How often did you usually have five drinks or more on one occasion?"

According to health-related organizations in Canada and elsewhere, women should never consume more than four drinks per occasion and alcohol is beneficial only when consumed in small quantities. Very little is known concerning the relationship between drinking frequency and risky drinking patterns.

"There is no clear and universal understanding of what is moderate drinking – its meaning varies between cultures and within cultures according to gender, age, socio-economic status and people's self-reported tolerance," says Professor Paradis. "Since regular drinking could increase alcohol abuse, Canadian drinking guidelines should take this aspect of the drinking pattern into account."

About the study:

The study, "The importance of drinking frequency in evaluating individuals' drinking patterns: implications for the development of national drinking guidelines," published in the journal Addiction, was authored by Catherine Paradis, Andrée Demers, Elyse Picard of the Université de Montréal and Kathryn Graham of the University of Western Ontario.


Partners in research: This study was funded by the Canadian Institutes of Health Research.

On the Web:

About the Université de Montréal:
About the Research Group on the Social Aspects of Health and Prevention
About the Université de Montréal's Department of Sociology:
About the University of Western Ontario:

New Roche drug helps shrink breast cancer tumors

The treatment, trastuzumab-DM1, is a combination of Roche's Herceptin and a chemotherapy agent.

About 35 percent of patients 112 in the trial either saw their tumors shrink, or their disease stabilized for at least six months, Roche said.

Thursday, May 28, 2009

Following a healthy lifestyle is on the decline in the US

Researchers urge individuals to adopt healthier lifestyles, particularly in middle age

New York, NY, 28 may 2009– Despite the well-known benefits of having a lifestyle that includes physical activity, eating a diet high in fruits and vegetables, maintaining a healthy weight, moderate alcohol use and not smoking, only a small proportion of adults follow this healthy lifestyle pattern, and in fact, the numbers are declining, according to an article published in the June 2009 issue of The American Journal of Medicine. Lifestyle choices are associated with the risk of cardiovascular disease as well as diabetes.

Investigators from the Department of Family Medicine, Medical University of South Carolina, Charleston compared the results of two large-scale studies of the US population in 1988-1994 and in 2001-2006. In the intervening 18 years, the percentage of adults aged 40-74 years with a body mass index greater than 30 has increased from 28% to 36%; physical activity 12 times a month or more has decreased from 53% to 43%; smoking rates have not changed (26.9% to 26.1%); eating 5 or more fruits and vegetables a day has decreased from 42% to 26%; and moderate alcohol use has increased from 40% to 51%. The number of people adhering to all 5 healthy habits has decreased from 15% to 8%.

The National Health and Nutrition Examination Survey (NHANES) is a national survey of non-institutionalized persons in the US conducted regularly by the National Center for Health Statistics. The researchers used data from a sub sample of the NHANES surveys of 1988-1994 and 2001-2006, adults aged 40-74 years, because this age span is the primary time for initial diagnosis of cardiovascular risk factors and disease. In the NHANES 1988-1994, the number of respondents 40-74 years old was 7340, representing a weighted sample size of 78,794,217. For NHANES 2001-2006, the number of respondents was 7811, for a weighted sample size of 65,476,573.

Since people with diagnosed health conditions such as cardiovascular disease, diabetes, hypertension, or high cholesterol were part of the samples, the researchers sought to determine whether such individuals were adhering to the healthy habits to a greater or lesser degree than people without those conditions, and whether adherence had changed over time. The study also concluded that people with cardiovascular disease, diabetes, high blood pressure or high cholesterol, or risk factors for those conditions, were no more likely to adhere to a healthy lifestyle pattern than people without such risk factors.

Writing in the article, Dana E. King, MD, MS, states, "The potential public health benefits from promoting a healthier lifestyle at all ages, and especially ages 40-74 years, are substantial. Regular physical activity and a prudent diet can reduce the risk of premature death and disability from a variety of conditions including coronary heart disease, and are strongly related to the incidence of obesity. In the US, medical costs due to physical inactivity and its consequences are estimated at $76 billion in 2000 dollars. Research indicates that individuals are capable of adopting healthy habits in middle age, and making an impact on cardiovascular risk."


The article is "Adherence to Healthy Lifestyle Habits in US Adults, 1988-2006" by Dana E. King, MD, MS, Arch G. Mainous III, PhD, Mark Carnemolla, BS, and Charles J. Everett, PhD". It appears in The American Journal of Medicine, Volume 122, Issue 6 (June 2009) published by Elsevier.

Dementia drugs may put some patients at risk, Queen's study shows

More awareness of side effects needed by patients, caregivers and doctors, says geriatrics prof

Kingston, ON, 28 may 2009 – Side effects associated with several commonly-prescribed dementia drugs may be putting elderly Canadians at risk, says Queen's University Geriatrics professor Sudeep Gill.

Cholinesterase inhibitors (Aricept, Exelon and Reminyl) are often prescribed for people with Alzheimer's disease and related dementias because they increase the level of a chemical in the brain that seems to help memory. Although such drugs are known to provoke slower heart rates and fainting episodes, the magnitude of these risks has not been clear until now.

"This is very troubling, because the drugs are marketed as helping to preserve memory and improve function," says Dr. Gill, who is an Ontario Ministry of Health and Long-term Care Career Scientist, working at Providence Care's St. Mary's of the Lake Hospital in Kingston. "But for a subset of people, the effect appears to be the exact opposite."

In a large study using province-wide data, Dr. Gill and his colleagues discovered that people who used cholinesterase inhibitors were hospitalized for fainting almost twice as often as people with dementia who did not receive these drugs. Experiencing a slowed heart-rate was 69 per cent more common amongst cholinesterase inhibitor users. In addition, people taking the dementia drugs had a 49 per cent increased chance of having permanent pacemakers implanted and an 18 per cent increased risk of hip fractures.

Unfortunately, Dr. Gill continues, this class of drugs is one of the few effective dementia treatments available today. Acknowledging that these drugs do have an important role in the management of dementia, he suggests that people who are already at a higher risk (for example, those who have had previous episodes of fainting or slowed heart rate) may want to ask their doctors to reassess the value of taking the drugs.

Slowing of the heart rate from cholinesterase inhibitors, if significant, may cause a person to faint and suffer fall-related injuries such as a broken hip – often debilitating and sometimes fatal for seniors. However, many physicians aren't aware of the connection between these problems and the dementia drugs, Dr. Gill notes.

If the association with dementia drugs is not identified, people who faint may be prescribed a permanent pacemaker: an invasive procedure that can involve serious complications for seniors. Both the injuries incurred from falling and the risks from pacemaker implants are "downstream consequences" of not recognizing this drug-induced phenomenon.

"This study does not suggest that dementia patients shouldn't take these drugs," says Dr. Gill. "What's critical is that patients, caregivers and physicians be aware of the potential side effects, and weigh these risks carefully against the potential for beneficial effects."


The findings are published in the journal, Archives of Internal Medicine. Scientists from the Institute for Clinical Evaluative Sciences, the University of Toronto and Harvard University are also on the research team.

The study uses data housed at the Institute for Clinical Evaluative Sciences (ICES). Ontario's first satellite unit of ICES was established at Queen's in 2007 to provide university researchers with electronic access to Ontario health datasets and population registries by secured and encrypted lines. Areas of focus at Queen's include cancer, pharmacological studies and dementia.

A PDF copy of Dr. Gill's study is available upon request.

U.S. Cancer Death Rates Continue to Fall

The American Cancer Society's Cancer Statistics 2009 report finds an encouraging 19.2 percent drop in cancer death rates among men from 1990 to 2005, as well as an 11.4 percent drop in women's cancer death rates during the same time period.

Overall, cancer death rates fell 2 percent per year from 2001 to 2005 in men and 1.6 percent per year from 2002 to 2005 in women. By comparison, between 1993 and 2001, overall death rates in men declined 1.5 percent per year and, between 1994 and 2002, 0.8 percent in women.

"We continue to see a decrease in death rates from cancer in both men and women and this is mainly because of prevention - mostly a reduction in smoking rates; detection which includes screening for colorectal cancer, for breast cancer and for cervical cancer; and also improved treatment," said report author Ahmedin Jemal, strategic director for cancer surveillance at the American Cancer Society.

"To put this in perspective, the number of lives saved is more than the population of Washington, D.C.," said Dr. Louis M. Weiner, director of the Lombardi Comprehensive Cancer Center at Georgetown University. "In my mind, that's a cause for some celebration. However, there are some sobering trends that we have to be aware of. The death rate for cardiovascular disease has dropped much more dramatically over that period than has the death rate from cancer, indicating the difficulty of developing new strategies to reduce the incidence of cancer and also to treat it more effectively. This is a very complex set of diseases. While we have come a long way, we have a lot further to go."

Hopefully, continued reductions in smoking rates, especially among women, should push cancer rates further down in the future, the researchers noted.

Although some 45 million Americans continue to smoke, for a prevalence rate of about 20 percent, "smoking prevalence is going in the right direction," Jemal said. "We're going to see a reduction in lung cancer death rates, although I don't know when it might be. In particular, we will see a reduction in cancer death rates among women that's going to drive [down] the overall cancer death rate."

Better screening could also further fuel the trend. Only 50 percent of Americans over the age of 50 currently get regular screening for colorectal cancer, he said.

Here is a summary of the report's findings:

  • In 2009, an estimated 1,479,350 new cases of cancer will be diagnosed in the U.S. (766,130 in men and 713,220 in women) and 562,340 people will die of the disease (292,540 men and 269,800 women). This means 1,500 deaths from cancer every day).
  • Between 2001 and 2005, the incidence of cancer in men declined by 1.8 percent per year; from 1998 to 2005 the incidence rate in women dropped 0.6 percent per year. In men, the gains were largely as a result of decreases in the incidence of lung, prostate and colorectal cancer (the three most common cancers). In women, the decline was largely attributable to declines in both breast and colorectal cancer, the two most common tumor types in women.
  • Cancer death rates dropped by 11.4 percent for women between 1991 and 2005, with a 37 percent decline in deaths from breast cancer and a 24 percent decrease in deaths from colorectal cancer.
  • The three leading cancer killers in men are lung, prostate and colorectal cancer. In women, they are lung (accounting for 26 percent of all cancer deaths), breast and colorectal cancer.
  • Men have a 44 percent chance of developing cancer during their lifetime and women a 37 percent chance, although women are more likely to have the disease earlier (before age 60).
  • Lung cancer shows the greatest regional variation in cancer incidence, ranging from a low of 39.6 cases per 100,000 in men and 22.4 per 100,000 in women in Utah to 136.2 in men and 76.2 in women in Kentucky. These statistics correlate directly to smoking rates in the two states, with Utah having the lowest prevalence in adult smoking in the country, and Kentucky the highest.
  • Blacks still assume a disproportionate share of the cancer burden, with black men being 18 percent more likely to develop cancer and 36 percent more likely to die. Black women have a 6 percent lower incidence rate but this is more than made up for with a death rate, which is 17 percent higher than that seen in white women.
  • The five-year survival rate for children with cancer is now 80 percent, up from only 58 percent for those diagnosed in the mid-1970s. But cancer is still the second leading cause of death in youngsters aged 1 to 14 (after accidents), with leukemia being the most common cancer diagnosed.
  • And in a special section, the report finds that cancer survivors are about 14 percent more likely to develop a new cancer than individuals who have never had a cancer diagnosis; almost 900,000 cancer survivors have been diagnosed with more than one cancer. Patients diagnosed with tobacco-related cancers, such as cancers of the oral cavity, lung, esophagus, kidney, and urinary bladder, have the highest risk for a second cancer because smoking is a risk factor for at least 15 types of cancer. Breast cancer survivors comprise almost half of women who develop a second cancer.

Unfortunately, cancer remains the leading killer (surpassing heart disease) for persons under 85, and one-quarter of deaths in the United States still come from cancer, the report stated.

"It's good news that the death rates for the most common cancers are on the decline, but there are still too many Americans dying of cancer every year," said Dr. Alan Astrow, director of medical oncology and hematology at Maimonides Cancer Center in New York City. "It's troubling that African-Americans continue to experience higher rates of mortality from cancer than whites. It's also troubling that Americans with less education have higher death rates. There are continued high rates of deaths from lung cancer. It's hard to feel good about 160,000 Americans dying of lung cancer every year. That's a disturbing statistics which we, as a nation, need to address."

The report appears online and in the July/August print issue of CA: A Cancer Journal for Clinicians.

Plaques, Tangles in Brain Don't Always Lead to Alzheimer's

In fact, the study found that many people over the age of 75 had signs of significant clogging in their brains but still managed to avoid senility.

The findings don't have immediate ramifications for the treatment of Alzheimer's disease, which remains incurable and only somewhat treatable. But in conjunction with other studies, they could redirect ongoing research, said Dr. Gary Kennedy, director of the division of geriatric psychiatry at Montefiore Medical Center in New York City.

"A lot of what is out there that's focusing on reducing the formation of amyloid plaques and tangles may just be off the mark," Kennedy said.

Amyloid plaques are globs of protein that form outside brain cells and stick together. Tangles are bits of protein that develop inside brain cells and create havoc of their own. Both have been linked to Alzheimer's disease.

In the new study, British researchers examined the brains of 456 people who had donated their bodies to science. The subjects were 69 to 103 years old when they died.

The findings appear in the May 28 issue of the New England Journal of Medicine.

The team found a strong link between clogging in the brain and Alzheimer's in 75-year-olds, but the connection lessened by the time people were 95.

In other words, plaques and tangles developed in very old people just as in their younger counterparts, but the very old weren't as likely to develop Alzheimer's.

The picture is not perfectly clear, however. "At all ages, there are some people who don't become demented before they died -- despite having a lot of plaques and tangles," said study co-author Dr. Paul Ince. "We do not know what would have happened if they had survived."

It's possible that Alzheimer's disease shortens life, so people who are susceptible to it simply don't make it into the older age group, reasoned Ince, a professor of neuropathology and head of the Academic Unit of Pathology at Sheffield University Medical School in the U.K.

Also, he added, the study suggests that people who become senile at a very old age may be affected by another factor -- shrinking of the brain.

As for future research, "we need to take account of the ability of some people's brains to withstand Alzheimer's better than others," he said. "If we knew why, it might help us with strategies to delay the onset of dementia."

For now, doctors are very limited in how they can treat Alzheimer's, Kennedy said. Medications can treat symptoms, much as painkillers help some people tolerate arthritis, but they don't cure the disease, he said.

And in many cases, the drugs simply don't work, he said.

FDA group recommends acetaminophen liver warnings

The recommendation covers both prescription doses and over-the-counter medication, of which Johnson & Johnson's Tylenol is the most well-known. Acetaminophen is also widely available as a generic over-the-counter drug.

"There is extensive evidence that hepatotoxicity (liver toxicity) caused by acetaminophen use may result from lack of consumer awareness that acetaminophen can cause severe liver injury," the working group report said.

The outside advisers will meet in June to discuss the report's findings. The recommendations include enhanced public information efforts, stronger labels warning of liver side effects, and dose limitations.

"Consumers may not be aware that acetaminophen is present in many over-the-counter combination products, so they may unknowingly exceed the recommended acetaminophen dose if they take more than one acetaminophen product without knowing that both contain acetaminophen," the report said.

The recommendations also call for limiting the maximum adult daily dose to no more than 3,250 milligrams. The current recommendation stands at 4,000 milligrams per day. Other recommendations include limiting tablet strength for immediate release formulations and limiting options in liquid formulations for children.

Wednesday, May 27, 2009

Is vitamin D deficiency linked to Alzheimer's disease and vascular dementia?

Hypothesis explored in the current issue of the Journal of Alzheimer's Disease

Amsterdam, The Netherlands,27 may 2009 – There are several risk factors for the development of Alzheimer's disease and vascular dementia. Based on an increasing number of studies linking these risk factors with Vitamin D deficiency, an article in the current issue of the Journal of Alzheimer's Disease (May 2009) by William B. Grant, PhD of the Sunlight, Nutrition, and Health Research Center (SUNARC) suggests that further investigation of possible direct or indirect linkages between Vitamin D and these dementias is needed.

Low serum levels of 25-hydroxyvitamin D [25(OH)D] have been associated with increased risk for cardiovascular diseases, diabetes mellitus, depression, dental caries, osteoporosis, and periodontal disease, all of which are either considered risk factors for dementia or have preceded incidence of dementia. In 2008, a number of studies reported that those with higher serum 25(OH)D levels had greatly reduced risk of incidence or death from cardiovascular diseases.

Several studies have correlated tooth loss with development of cognitive impairment and Alzheimer's disease or vascular dementia. There are two primary ways that people lose teeth: dental caries and periodontal disease. Both conditions are linked to low vitamin D levels, with induction of human cathelicidin by 1,25-dihydroxyvitamin D being the mechanism.

There is also laboratory evidence for the role of vitamin D in neuroprotection and reducing inflammation, and ample biological evidence to suggest an important role for vitamin D in brain development and function.

Given these supportive lines of evidence, Dr. Grant suggests that studies of incidence of dementia with respect to prediagnostic serum 25(OH)D or vitamin D supplementation are warranted. In addition, since the elderly are generally vitamin D deficient and since vitamin D has so many health benefits, those over the age of 60 years should consider having their serum 25(OH)D tested, looking for a level of at least 30 ng/mL but preferably over 40 ng/mL, and supplementing with 1000-2000 IU/day of vitamin D3 or increased time in the sun spring, summer, and fall if below those values.

Writing in the article, Dr. Grant states, "There are established criteria for causality in a biological system. The important criteria include strength of association, consistency of findings, determination of the dose-response relation, an understanding of the mechanisms, and experimental verification. To date, the evidence includes observational studies supporting a beneficial role of vitamin D in reducing the risk of diseases linked to dementia such as vascular and metabolic diseases, as well as an understanding of the role of vitamin D in reducing the risk of several mechanisms that lead to dementia."


The article is "Does Vitamin D Reduce the Risk of Dementia?" by William B. Grant, Ph.D. It is published in the Journal of Alzheimer's Disease 17:1 (May 2009).

Carbohydrate restriction may slow prostate tumor growth

DURHAM, N.C., 27 may 2009 -- Restricting carbohydrates, regardless of weight loss, appears to slow the growth of prostate tumors, according to an animal study being published this week by researchers in the Duke Prostate Center.

"Previous work here and elsewhere has shown that a diet light in carbohydrates could slow tumor growth, but the animals in those studies also lost weight, and because we know that weight loss can restrict the amount of energy feeding tumors, we weren't able to tell just how big an impact the pure carbohydrate restriction was having, until now," said Stephen Freedland, M.D., a urologist in the Duke Prostate Center and lead investigator on this study.

The researchers believe that insulin and insulin-like growth factor contribute to the growth and proliferation of prostate cancer, and that a diet devoid of carbohydrates lowers serum insulin levels in the bodies of the mice, thereby slowing tumor growth, Freedland said.

The findings appear in the May 26, 2009 online edition of the journal Cancer Prevention Research. Funding was provided by the United States Department of Veterans Affairs, the Department of Defense Prostate Cancer Research Program; the American Urological Association/ Foundation Astellas Rising Star in Urology Award, and the Robert C. Atkins Foundation.

Animals in the study were fed one of three diets: a very high fat/ no carbohydrate diet; a low-fat/ high carbohydrate diet; and a high fat/ moderate-carbohydrate diet, which is most similar to the "Western" diet most Americans eat, Freedland said. They were then injected with prostate tumors at the same time.

"The mice that were fed a no-carbohydrate diet experienced a 40 to 50 percent prolonged survival over the other mice," Freedland said.

Mice on the no-carbohydrate diet consumed more calories in order to keep body weights consistent with mice on the other study arms.

"We found that carbohydrate restriction without energy restriction – or weight loss – does indeed result in tumor growth delay," he said.

The researchers plan to begin recruiting patients at two sites – Duke and the University of California – Los Angeles – for a clinical trial to determine if restricting carbohydrate intake in patients with prostate cancer can similarly slow tumor growth. The trial should begin within a few weeks.

"It's very exciting – this is a potential new mechanism to fight prostate cancer growth and help patients live longer with their disease," Freedland said.


Other researchers involved in this study include John Mavropoulos, William Buschmeyer, Alok Tewari, Dmitriy Rohkfeld, Phillip Febbo, Gayathri Devi, Eric Westman, Bercedis Peterson and Salvatore Pizzo of Duke; Michael Pollak and Yunhua Zhao of McGill University; Pinchas Cohen and David Hwang of UCLA and Wendy Demark-Wahnefried of the University of Texas – M.D. Anderson Cancer Center.

NEJM study finds drug-eluting stents more effective than bare-metal stents in heart attack patients

Landmark Horizons-AMI study led by NewYork-Presbyterian Hospital and Columbia University Medical Center in collaboration with the Cardiovascular Research Foundation

NEW YORK, 27 may 2009-- NewYork-Presbyterian Hospital and Columbia University Medical Center, together with the Cardiovascular Research Foundation (CRF), announced that its landmark study comparing the safety and efficacy of drug-eluting stents and bare-metal stents was published in the May 7 New England Journal of Medicine. The study, HORIZONS-AMI (Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction), showed that in heart attack patients undergoing angioplasty, the use of paclitaxel-eluting stents reduces rates of target lesion revascularization (TLR) and binary angiographic restenosis when compared to the use of bare-metal stents after one year.

Additionally, the primary safety measure of major adverse cardiovascular events (MACE), including death, reinfarction, stent thrombosis and stroke established the non-inferiority of drug-eluting stents with respect to safety through one year.

The study was led by Dr. Gregg W. Stone, director of cardiovascular research and education in the Center for Interventional Vascular Therapy at NewYork-Presbyterian Hospital/Columbia University Medical Center; and professor of medicine at Columbia University College of Physicians and Surgeons. The research was sponsored and managed by the Cardiovascular Research Foundation with research grant support from Boston Scientific Corporation and The Medicines Company.

In the trial, the use of paclitaxel-eluting stents resulted in a significant reduction of ischemia-driven target-lesion revascularization (TLR) at 12 months (4.5% vs. 7.5%). TLR, which was the primary efficacy endpoint of the trial, refers to the rate at which a particular lesion re-narrows following stent implantation severely enough to require either a repeat angioplasty or bypass surgery operation.

The use of paclitaxel-eluting stents also resulted in a significant reduction in binary restenosis after 13 months, which is the rate at which the artery re-narrows at least 50 percent following implantation of the stent, and was the secondary efficacy endpoint of the trial. The paclitaxel-eluting stent had a rate of 10.0 percent and the bare-metal stent had a rate of 22.9 percent.

"Outcomes from prior registry and randomized trials of drug-eluting stents compared with bare-metal stents in heart attack patients have been conflicting. These results now provide definitive evidence that paclitaxel-eluting stents are superior in efficacy to bare-metal stents and have a comparable safety profile at one year," says Dr. Stone. "The findings from the HORIZONS-AMI trial will have a major impact on how decisions are made regarding drug-eluting and bare-metal stents in the highest-risk patients, those in the early hours of a heart attack. This study removes much of the uncertainty and concern about the efficacy and safety of drug-eluting stents in this clinical setting. Moreover, all of the patients in this trial will be followed long-term to ensure that these favorable results are maintained."

The HORIZONS-AMI trial, a prospective, open-label, multicenter, controlled study, enrolled 3,602 heart attack patients at 123 centers in 11 countries, 3,006 of whom were randomized to paclitaxel-eluting stents versus otherwise identical bare-metal stents.


Co-authors include Drs. Alexandra J. Lansky, George Dangas and Roxana Mehran, Ms. Alison Kellock and Ms. Helen Parise of NewYork-Presbyterian/Columbia; Dr. S. Chiu Wong of NewYork-Presbyterian Hospital/Weill Cornell Medical Center; Dr. Stuart J. Pocock of the London School of Hygiene and Tropical Medicine, London; Dr. Bernard J. Gersh of Mayo Clinic, Rochester, Minn.; Dr. Bernhard Witzenbichler of Charité Campus Benjamin Franklin, Berlin; Dr. Martin Möckel of Charité Campus Virchow-Klinikum, Berlin; Dr. Giulio Guagliumi of Ospedali Riuniti di Bergamo, Bergamo, Italy; Dr. Jan Z. Peruga of Medical University, Lodz, Poland; Dr. Dariusz Dudek of Jagiellonian University, Krakow; Dr. Andrzej Ochala of the Silesian Medical Academy, Katowice, Poland; Dr. Bruce R. Brodie of LeBauer Cardiovascular Research Foundation and Moses Cone Hospital, Greensboro, N.C.

What is the function of lymph nodes?

27 may 2009--If we imagine our immune system to be a police force for our bodies, then previous work has suggested that the Lymph nodes would be the best candidate structures within the body to act as police stations – the regions in which the immune response is organised. However, Prof. Burkhard Becher, University of Zurich, suggests in a new paper – published in this week's issue of PLoS Biology – that lymph nodes are not essential in the mouse in marshalling T-cells (a main immune foot soldier) to respond to a breach of the skin barrier. This result is both surprising in itself, and suggests a novel function for the liver as an alternate site for T-cell activation.

When a child falls off its bike and scratches its skin, the body responds via the immune system. Scavenger cells at the site of the wound pick up antigens –tiny particles derived from invading microorganisms and dirt that the body will recognize as foreign. These antigens are delivered to the nearest lymph node. T and B cells (immune cells) carrying the matching antigen-receptors on their surface will be stimulated by the concentrated antigen now present in these lymph nodes. T cells will then go on and orchestrate the defensive response against the invaders, whereas B cells will transform into antibody-producing cells flooding the body with antibodies which act against the hostile microorganisms.

Mice that lack lymph nodes due to a genetic mutation (alymphoplasia) are severely immuno-compromised and struggle in fighting infections and tumors. New work by Melanie Greter, Janin Hofmann and Burkhard Becher from the Institute of experimental Immunology at the University of Zurich reports that the immunodeficiency associated with alymphoplasia is not due to the lack of lymph nodes, but caused by the genetic lesion on immune cells themselves. The new paper shows that in the mouse T cell function is unperturbed in the absence of lymph nodes, whereas B cell activation and antibody secretion is strongly affected. That T cell responses can be launched outside of lymph nodes is highly surprising, because this means that T cells can encounter antigens elsewhere in order to become activated. By tracing the migration of fluorescent particles from the site of antigen invasion (i.e. the wound) the scientists discovered that the liver could serve as a surrogate structure for T cell activation. During embryonic development, the liver is the first organ to provide us with blood and immune cells. Apparently, at least in the mouse the liver continues to serve as an "immune organ" even during adulthood.

This work suggests an explanation for the curious fact that patients receiving a liver transplant sometimes inherit the donor's allergies and immune repertoire, so in keeping with the idea that donor immune information is being transplanted. It also suggests that the liver as an immune organ is an evolutionary remnant from the time before lymph nodes developed in higher birds and mammals. Cold-blooded vertebrates have functioning T and B cells but no lymph nodes. The main achievement of the development of lymph nodes in mammals is a drastic improvement for the production of better antibodies. T cells on the other hand have not changed their function much during evolution and the work by the Zurich group finally provides solid evidence for the versatility and promiscuity of this cell type.

Medical report: Cancer patient loses fingerprints

The 62-year-old man was taking capecitabine, or Xeloda, to treat head and neck cancer. Upon arriving in the U.S., immigration officials asked him for his fingerprints. But the drug had caused so much redness and peeling to his fingers that the patient, identified only as Mr. S., had none.

Customs officials held Mr. S. for four hours before deciding he was not a security threat, according to the case published Wednesday in a letter to the Annals of Oncology journal.

Capecitabine is a common cancer drug, routinely given to patients with head, neck and kidney cancers as well as lymphomas and leukemias. Doctors said very few patients temporarily lose their fingerprints while on Xeloda, but it does happen.

"Most patients will complain they're having difficulty holding things or sensing things," said Dr. Otis Brawley, chief medical officer of the American Cancer Society, who was not linked to the case. "I've never had a patient running into a problem with police authorities, but this is not an exaggeration. It could actually happen."

After returning home, Mr. S. asked his oncologist, Dr. Eng-Huat Tan at the National Cancer Centre in Singapore, to write a letter certifying he was on capecitabine.

Surprised by Mr. S.'s predicament, Tan recommended in his letter to the journal that patients taking capecitabine carry a similar doctor's note if they are traveling to the United States.

Unlike most other countries, American immigration officials take two fingerprints from foreign visitors.

Tan said up to 40 percent of patients on the drug develop a side effect known as hand-foot syndrome, which causes redness, peeling, numbness and tingling. Of those patients, only a small percentage actually lose their fingerprints.

"Patients probably would not notice anything until they travel to the U.S. and discover to their horror that their fingerprints are gone," Tan said. Mr. S. was Tan's only patient to report such a predicament, but Tan said a handful of other cases were described on cancer blogs.

Once patients stop taking the drug and apply ice to their hands, their fingerprints will return in about a month.

Brawley guessed that U.S. officials became suspicious because criminals sometimes erase their fingerprints with sandpaper or dip them in acid, which would appear very similar to how Mr. S's fingers looked.

But he says there are too many side effects from Xeloda, including a weakened immune system and increased cancer risk, that it would be unlikely anyone would take the drug for less-than-honorable reasons.

"No criminal in his right mind would take this drug to try to get rid of his fingerprints," Tan said.