Personal Health


Friday, July 16, 2010


Computers Help Beat Hospital Infections


HealthDay News

Friday, July 16, 2010

FRIDAY, July 16 (HealthDay News) -- A new survey suggests that U.S. acute care hospitals can best minimize the risks for the spread of dangerous in-hospital infections if they harness automated computer technologies to quickly identify, track and respond to infections as they occur.

The survey of California acute care hospitals found that only one-third of them use automated computer systems that streamline the tracking of in-hospital infections by quickly identifying clusters of infections.

Those that do, however, were found to be more likely to have infection-combating strategies that public health officials have identified as the most effective means to reduce and prevent the spread of serious infections such as MRSA, ventilator-associated pneumonia and those associated with surgical procedures.

The finding stems from a phone survey of "quality directors" at more than 240 general acute care hospitals in California, representing more than 80 percent of all hospitals in the state.

Poll results -- collected between 2008 and 2009 -- were to be presented this week at the Association for Professionals in Infection Control and Epidemiology (APIC) meeting in New Orleans.

"Our findings suggest that hospitals that use automated surveillance technology are able to put more (healthcare-associated infection) elimination strategies into place that will ultimately reduce the risk of infection," study lead author Helen Halpin, a professor of health policy at the University of California, Berkeley, said in an APIC news release.

"Manual identification of infections is costly, time-consuming and diverts staff time from prevention activities," she added. "The advantages of automated surveillance are enormous in an era where the Centers for Medicare and Medicaid Services and many private insurers will no longer pay for the additional costs attributable to certain (healthcare-associated infections), and many states report infection rates publicly."

The authors stress that this does not mean that those hospitals with computer tracking systems experience fewer such infections, but rather that they are more likely to have established a "best practices" response to infection outbreaks than those facilities which rely on more low-tech manual tracking methods.

In its release, APIC cited World Health Organization estimates that every day, up to 1.4 million patients worldwide contract an infection in a healthcare setting. In the United States, hospital-associated infections cause 99,000 deaths and $30 to $40 billion in excess healthcare costs annually.

More information

For more on healthcare-associated infections visit the U.S. Centers for Disease Control and Prevention .

"Gluten-free" foods may be contaminated: study


By Genevra Pittman

Reuters Health

Friday, July 16, 2010

NEW YORK (Reuters Health) – People with celiac disease and others who avoid gluten should beware that foods that are supposed to be naturally gluten-free are often contaminated, warns a new study.

Gluten is a kind of protein found in wheat, barley, and rye. In people with celiac disease - a condition that affects up to about 1 percent of the U.S. population - gluten triggers an immune reaction that causes damage to the small intestine and keeps the body from absorbing nutrients.

Grains such as oats, millet, and rice don't have this protein. But in a new survey of grains, seeds, and flours that should be gluten-free, researchers found that some of these products had picked up traces of gluten - probably from being grown or processed near grains that do naturally contain gluten.

"There was some general assumption (among people with celiac disease) that those naturally gluten-free grains and flours weren't contaminated," Tricia Thompson, a nutrition consultant on celiac disease and the lead author on the study, told Reuters Health.

Thompson and her colleagues analyzed 22 naturally gluten-free grains, seeds, and flours off supermarket shelves, only looking at products that weren't specifically advertised as being gluten-free. They tested the amount of gluten in those products against a proposed Food and Drug Administration limit for any product labeled gluten-free, 20 parts contaminant per million parts product.

Seven of the 22 products wouldn't pass the FDA's gluten-free test - and one product, a type of soy flour, had a gluten content of almost 3,000 parts per million, the authors found. Other products from the sample that weren't truly gluten-free included millet flour and grain, buckwheat flour, and sorghum flour.

The study was too small to give consumers a good idea of how common it is for these products to be contaminated or what products should make people with celiac disease especially wary, Thompson said.

But "it is a red flag," Cynthia Kupper, the executive director of the Gluten Intolerance Group of North America, who was not involved with the research, told Reuters Health.

Even companies that do explicitly label their products as gluten-free, she said, might not always test products they assume won't contain any gluten. The study "is a wake-up call to the food industry," said Kupper. Companies "need to make sure (their products) are truly gluten-free."

Without an FDA regulation in place, there is still no hard-and-fast government definition of what gluten-free means, Thompson said.

That makes it harder to keep companies that might skimp on their testing accountable.

"It's hoped but certainly not assumed that manufacturers who are putting the (gluten-free) label on their single-ingredient grains and flours are testing their ingredients," Thompson said. "Do all manufacturers test? Probably not."

Under the proposed gluten-free labeling rule, the FDA could conduct inspections of manufacturers that claim their products are gluten-free and analyze those products.

Thompson and Kupper agreed that more research needs to be done to find out the scope of the contamination problem. In the meantime, Thompson said, people with celiac disease are probably better off purchasing grains, seeds, and flours with the gluten-free label. The products can't be guaranteed to be completely free of gluten, but it is more likely that they will have been tested, she said.


Journal of the American Dietetic Association, June 2010.

Knee Replacements Can Fail for Various Reasons, Expert Says


HealthDay News

Friday, July 16, 2010

FRIDAY, July 16 (HealthDay News) -- Knee implants perform well for at least 15 to 20 years in more than 95 percent of patients but can fail for five main reasons, a U.S. expert reports.

"A failed knee implant is usually caused by wear and tear with subsequent loosening of the implant. Other causes are infection, instability, fracture, or stiffness," Dr. Amar Ranawat, a hip and knee specialist at the Hospital for Special Surgery in New York City, said in a hospital news release.

Ranawat explained these problems in more detail in the news release:

  • When joint surfaces rub against each other, the friction wears away the surface of the implant, which can result in bone loss and loosening of the implant.
  • Infection may occur if bacteria latches onto the surfaces of metal and plastic implants.
  • For those who experience fractures around the implant, knee stability can be disrupted and revision surgery may be needed.
  • If the knee feels unstable (like it's buckling), it could be because the soft tissue that supports the knee is weak, or it could be because the implant was improperly placed.
  • When the knee joint feels stiff and the patient experiences a loss of their range of motion, the result is often pain and poor knee function.

Common signs of a failed knee implant include pain, instability, swelling and stiffness, Ranawat noted. And patients with a failed implant may require revision total knee replacement, which usually takes longer than the original knee replacement.

More than 80 percent of patients who undergo revision knee surgery have good to excellent results, but "up to 20 percent of patients may still experience pain following surgery for months or even years," Ranawat said.

More information

The American Academy of Orthopaedic Surgeons has more about knee implants.

New Discovery Brings Hope to Treatment of Incurable Blood Cancer



Friday, July 16, 2010


ScienceDaily (July 16, 2010) — Multiple myeloma is one of the most common blood cancers, and at present considered to be incurable. In a new study from Uppsala University, researchers now present a conceptually new model for the development and progression of multiple myeloma. The study was done in collaboration with Vrije Universitet Brussels and is published in the July edition of the online journal PLoS ONE.


Using large cohorts of myeloma patients the researchers have identified a profile of genes that are silenced by epigenetic mechanisms in the malignant plasma cell.


"This silencing may lead to the uncontrolled growth of the malignant cells," says Helena Jernberg Wiklund, professor at the Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University and one of the investigators in the study.


The silenced gene profile was compared and contrasted to normal plasma cells, which are highly specialised and for which growth and lifetime is tightly controlled.


The silenced genes have a common denominator in being targets and controlled by the Polycomb repressor complex (PcG). This complex has previously been implicated in self-renewal and division of normal embryonic stem cells. In the study the researchers found that inhibitors of PcG also could decrease the growth of tumour cells in an animal model of myeloma.


"A new strategy for treating multiple myeloma could be to develop drugs that are targeted to the PcG complex, leading to reactivation of the silenced gene profile," says Helena Jernberg Wiklund.

Journal Reference:

Antonia Kalushkova., Marten Fryknas, Miguel Lemaire2 Charlotte Fristedt, Prasoon Agarwal1, Maria Eriksson, Sarah Deleu, Peter Atadja, Anders Osterborg, Kenneth Nilsson, Karin Vanderkerken, Fredrik Oberg, Helena Jernberg-Wiklund (2010). Polycomb Target Genes Are Silenced in Multiple Myeloma. PLoS ONE, 5(7): e11483 DOI: 10.1371/journal.pone.0011483

Health Tip: What May Cause an Aneurysm


HealthDay News

Friday, July 16, 2010

(HealthDay News) -- Aneurysm is the medical term for a bulging area of an artery that's stretched out like a balloon. It occurs when the artery wall becomes weak or damaged.

The U.S. National Heart, Lung, and Blood Institute lists these possible causes of an aneurysm:

  • Being older.
  • Having plaque buildup inside an artery (atherosclerosis).
  • Having high blood pressure.
  • Being a smoker.
  • Having an infection or illness that leads to inflammation of the blood vessels.
  • Having a family history of aneurysm.
  • Having a genetic condition that weakens blood vessels.
  • Sustaining an injury or trauma, such as being in a car accident.


Thursday, July 15, 2010


U.S. groups target 20 possible causes of cancer


By Maggie Fox,

Health and Science Editor


Thursday, July 15, 2010

WASHINGTON (Reuters) – The American Cancer Society and three federal agencies named 19 chemicals and shift work on Thursday as potential causes of cancer that deserve more investigation.

The group published a report with the backing of international experts who said the 20 potential causes they identified had fairly good evidence that they may be a danger and deserved more follow-up.

Most are familiar names, such as chloroform, formaldehyde and polychlorinated biphenyls or PCBs, but the list includes indium phosphide, a relatively new compound used in making flat-screen televisions.

All have been classified as possible carcinogens by the International Agency for Research on Cancer or IARC, the United Nations cancer agency.

"These particular ones were picked for two reasons. One is there is more of a hint in most cases that they might be involved with cancer," Elizabeth Ward of the American Cancer Society, who helped lead the work, said in a telephone interview.

But at the same time, she said, the studies that could make a definitive link are missing.

The second reason is that some of the potential agents or causes are very common. "We are focusing on things like formaldehyde, where there really has been widespread exposure in many industries," Ward said.

"Or in some cases the exposure is not widespread but is something that is increasing and there is insufficient data."

The National Institute for Occupational Safety and Health or NIOSH, National Institute of Environmental Health Sciences and the National Cancer Institute also helped sponsor the report, which names the following agents:

·         Lead and lead compounds

·         Indium phosphide

·         Cobalt with tungsten carbide

·         Titanium dioxide

·         Welding fumes

·         Refractory ceramic fibers

·         Diesel exhaust

·         Carbon black

·         Styrene-7,8-oxide and styrene

·         Propylene oxide

·         Formaldehyde

·         Acetaldehyde

·         Dichloromethane, methylene chloride (DCM)

·         Trichloroethylene (TCE)

·         Tetrachloroethylene (perc, tetra, PCE)

·         Chloroform

·         Polychlorinated biphenyls (PCBs)

·         Di(2-ethylhexyl) phthalate (DEHP)

·         Atrazine

·         Shift work

The study is published in the journal Environmental Health Perspectives and at

Ward said indium caught the group's attention because it is becoming increasingly common. Used to make microelectronics, animal data suggested it might cause lung damage and genetic changes when breathed in, she said.

"It is a particularly important component of the flat displays of TVs that have been so popular," she said. Workers in assembly plants and those recycling discarded televisions might be most at risk, she said.

"Some of this kind of work done is in developing countries," she noted. "They are broken apart and valuable components extracted. It is an example of a newly emerging hazard."

Cancer is the No. 2 killer of Americans and people in most industrialized countries, after heart disease.

In May the President's Cancer Panel said Americans are being "bombarded" with cancer-causing chemicals and radiation but many experts said it overplayed some causes for which there is very little evidence of a cancer-causing effect, such as cell phones.

(Editing by Julie Steenhuysen and Eric Walsh)

Stroke Risk May Rise First Hour After Drinking


By Steven Reinberg
HealthDay Reporter
HealthDay News

Thursday, July 15, 2010

THURSDAY, July 15 (HealthDay News) -- For an hour after drinking even a small amount of alcohol, the risk of stroke increases, a small, preliminary study suggests.

But even though your risk may rise over that short time, the researchers noted that moderate drinking over the long-term might actually reduce your risk of heart attack and stroke.

"The risk of ischemic stroke may be transiently elevated in the two hours after drinking as little as one serving of beer, wine, or liquor," said lead researcher Elizabeth Mostofsky, a member of the Cardiovascular Epidemiology Research Unit at Beth Israel Deaconess Medical Center in Boston.

However, conclusive evidence about the association between alcohol consumption and the acute risk of stroke would require a long-term clinical trial, she added.

"Nonetheless, these results suggest that there is an acute elevated risk of ischemic stroke that may be offset by the potential beneficial effects of long-term moderate alcohol consumption," Mostofsky said. But the findings may not apply to patients with severe stroke, she added.

For the study, published in the July 15 online edition of Stroke, Mostofsky's group interviewed 390 patients about three days after their stroke. Patients who could not speak or were too ill were excluded from the study.

In all, 14 patients had been drinking in the hour before their stroke, the researchers found.

"We found that compared with times when alcohol was not consumed, the relative risk of stroke after alcohol consumption was 2.3 times higher in the hour after drinking beer, wine or liquor," Mostofsky said.

"The relative risk was 1.6 in the second hour after drinking. By 24 hours, there was a 30 percent lower risk," she said.

This pattern remained regardless of the type of alcohol consumed or whether the patients had exercised before their stroke. Moreover, when the researchers excluded the one patient who had had more than two drinks, the pattern continued.

This finding may be due to the immediate effects of alcohol, which increases blood pressure and causes blood platelets to become stickier, perhaps increasing the risk of clotting, the authors noted.

But drinking small amounts of alcohol over time appears to have a beneficial effect on blood fats and may make blood vessels more flexible, which might reduce the risk of heart attack and stroke, the researchers said.

Stroke is the third-leading killer and a major cause of long-term major disability in the United States, according to the American Heart Association.

Dr. Larry B. Goldstein, a professor of neurology and director of the Duke Stroke Center at Duke University Medical Center and a spokesman for the American Heart Association/American Stroke Association, said that "current guidelines indicate that for people who drink, men should consume no more than two alcoholic beverages per day and women no more than one, and women should abstain during pregnancy."

Evidence suggests that light to moderate alcohol consumption in this range is associated with a reduction in stroke risk, but heavier drinking is associated with an increase in stroke risk, he said.

"This new research suggests that the risk of stroke may be transiently increased in the first hour after drinking even small amounts of alcohol. But, the numbers of patients were too small to determine whether this risk varied depending on the type of alcohol consumed," Goldstein said.

The findings should not necessarily deter moderate drinking, he added.

"For those who consume alcohol, this transient increase in risk needs to be balanced against the potential long-term reduction in risk with mild-moderate consumption," he said.

More information

For more information on stroke, visit the U.S. National Library of Medicine.

U.S. probing cancer risk of blood pressure drugs


By Lisa Richwine


Thursday, July 15, 2010

WASHINGTON (Reuters) – U.S. health officials are investigating if a class of commonly used blood pressure drugs may increase cancer risk after a recent study raised concern.

An analysis of data from several clinical trials suggested medicines known as angiotensin receptor blockers (ARBs) "may be associated with a small increased risk of cancer," the Food and Drug Administration said in a statement on Thursday.

ARBs include Novartis AG's Diovan, Merck & Co Inc's Cozaar and Avapro from Bristol-Myers Squibb Co and Sanofi-Aventis SA.

The FDA said it had not yet determined if ARBs played any role in the cancer cases. The drugs provide significant benefit in patients with heart failure and high blood pressure, the agency added.

"FDA believes the benefits of ARBs continue to outweigh their potential risks," the agency said.

A study published in June in the Lancet medical journal examined data from more than 1,000 patients in several long-term clinical trials. The rate of new cancer cases was 7.2 percent for patients who took an ARB compared with 6 percent among patients who did not take one of the drugs. There was no difference in the rates of cancer-related deaths.

Most patients in the trials, 86 percent, took German drugmaker Boehringer Ingelheim's medicine, Micardis, which has annual sales of more than $1.5 billion.

The analysis had several limitations "that make it difficult to determine the validity of the findings" without a closer look, the FDA said.

Merck also said the type of analysis used in the study had limitations and the company "fully stands behind the tolerability and efficacy" of Cozaar.

Novartis reviewed four long-term clinical trials of Diovan using similar methods as the study published in the Lancet. Initial results showed no increased risk of new cancers for Diovan, a company spokeswoman said.

Bristol-Myers and Sanofi said "no signal for new cancers has been found" in the companies' ongoing review of health problems reported in patients treated with Avapro.

A Boehringer spokeswoman could not immediately be reached, but the company said in June its own analysis "contradicts the conclusions" of an increased cancer risk.

European regulators also are investigating a possible increased cancer risk with ARBs.

The FDA posted its notice at

(Reporting by Lisa Richwine; editing by Andre Grenon)

New Arsenic Nanoparticle Blocks Aggressive Breast Cancer



Thursday, July 15, 2010


ScienceDaily (July 15, 2010) — You can teach an old drug new chemotherapy tricks. Northwestern University researchers took a drug therapy proven for blood cancers but ineffective against solid tumors, packaged it with nanotechnology and got it to combat an aggressive type of breast cancer prevalent in young women, particularly young African-American women.


That drug is arsenic trioxide, long part of the arsenal of ancient Chinese medicine and recently adopted by Western oncologists for a type of leukemia. The cancer is triple negative breast cancer, which often doesn't respond well to traditional chemotherapy and can't be treated by potentially life-saving targeted therapies. Women with triple negative breast cancer have a high risk of the cancer metastasizing and poor survival rates.

Prior to the new research, arsenic hadn't been effective in solid tumors. After the drug was injected into the bloodstream, it was excreted too rapidly to work. The concentration of arsenic couldn't be increased, because it was then too toxic.


A new arsenic nanoparticle -- designed to slip undetected through the bloodstream until it arrives at the tumor and delivers its poisonous cargo -- solved all that. The nanoparticle, called a nanobin, was injected into mice with triple negative breast tumors. Nanobins loaded with arsenic reduced tumor growth in mice, while the non-encapsulated arsenic had no effect on tumor growth. The arsenic nanobins blocked tumor growth by causing the cancer cells to die by a process known as apoptosis.


The nanobin consists of nanoparticulate arsenic trioxide encapsulated in a tiny fat vessel (a liposome) and coated with a second layer of a cloaking chemical that prolongs the life of the nanobin and prevents scavenger cells from seeing it. The nanobin technology limits the exposure of normal tissue to the toxic drug as it passes through the bloodstream. When the nanobin gets absorbed by the abnormal, leaky blood vessels of the tumor, the nanoparticles of arsenic are released and trapped inside the tumor cells.


"The anti-tumor effects of the arsenic nanobins against clinically aggressive triple negative breast tumors in mice are extremely encouraging," said Vince Cryns, associate professor of medicine and an endocrinologist at Northwestern Medicine and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. "There's an urgent need to develop new therapies for poor prognosis triple negative breast cancer."


Cryns and Tom O'Halloran, director of the Chemistry of Life Processes Institute at Northwestern, are senior authors of a paper on the research, which will be published July 15 in Clinical Cancer Research. Richard Ahn, a student in the medical scientists training program at Northwestern, is lead author.


"Everyone said you can't use arsenic for solid tumors," said O'Halloran, also associate director of basic sciences at the Lurie Cancer Center. "That's because they didn't deliver it the right way. This new technology delivered the drug directly to the tumor, maintained its stability and shielded normal cells from the toxicity. That's huge."


The nanoparticle technology has great potential for other existing cancer drugs that have been shelved because they are too toxic or excreted too rapidly, Cryns noted. "We can potentially make those drugs more effective against solid tumors by increasing their delivery to the tumor and by shielding normal cells from their toxicity," he said. "This nanotechnology platform has the potential to expand our arsenal of chemotherapy drugs to treat cancer."


"Working with both professors O'Halloran and Cryns has enabled us to develop the nanobins and hopefully create a new platform for the effective treatment of triple negative breast cancer," Ahn said. "Having both a basic science mentor and breast cancer mentor is ideal training for me as a future physician-scientist."


Looking ahead, the challenge now is to refine and improve the technology. "How do we make it more toxic to cancer cells and less toxic to healthy cells?" asked Cryns, also the director of SUCCEED, a Northwestern Medicine program to improve the quality of life for breast cancer survivors.


Northwestern scientists are working on decorating the nanobins with antibodies that recognize markers on tumor cells to increase the drug's uptake by the tumor. They also want to put two or more drugs into the same nanobin and deliver them together to the tumor.


"Once you fine-tune this, you could use what would otherwise be a lethal or highly toxic dose of the drug, because a good deal of it will be directly released in the tumor," O'Halloran said.

The research was supported by the National Cancer Institute-funded Northwestern University Center of Cancer Nanotechnology Excellence. Northwestern has one of seven such centers in the United States.

Journal Reference:

R. W. Ahn, F. Chen, H. Chen, S. T. Stern, J. D. Clogston, A. K. Patri, M. R. Raja, E. P. Swindell, V. Parimi, V. L. Cryns, T. V. O'Halloran. A Novel Nanoparticulate Formulation of Arsenic Trioxide with Enhanced Therapeutic Efficacy in a Murine Model of Breast Cancer. Clinical Cancer Research, 2010; DOI: 10.1158/1078-0432.CCR-10-0068

Mediterranean diet may not protect against asthma


By Lynne Peeples

Reuters Health

Thursday, July 15, 2010

NEW YORK (Reuters Health) – Countries on the Mediterranean might enjoy low asthma rates, but their typical diet shouldn't take the credit, suggests a new study.

"At the moment, we cannot give definitive advice about any protective effect of diet on asthma," said study co-author Dr. F.J. Gonzalez Barcala of the Hospital de Pontevedra in Santiago de Compostela, Spain. "But we are sure that more research is needed on the topic."

People have speculated that a diet rich in fish, fruits and vegetables, which is typical of countries surrounding the Mediterranean Sea, could help explain why asthma is so much less common in these places compared to other parts of the world. For example, less than 10 percent of Spanish 13- and 14-year-olds have the chronic lung disease, compared to nearly a quarter of similarly aged British kids.

Mediterranean diets vary, the study authors note, but generally involve more monounsaturated fats than saturated fats, lots of fish, vegetables, fruit, nuts, and grains, and minimal milk and dairy.

Studies have found that people who eat such diets tend to be healthier. But based on earlier conflicting studies and the inherent difficulty of linking diet to health, Gonzalez Barcala and his colleagues had suspicions that the protective effect of asthma wasn't as clear as it seemed.

The team set out to study nearly 15,000 children in their home Mediterranean country. They looked at the diets and asthma rates of Spanish boys and girls aged 6 to 7, and 13 to 14. Each kid was categorized into one of four groups reflecting the extent to which they reported adhering to the Mediterranean diet.

About 40 percent of the younger kids and 20 percent of the older kids had suffered from asthma at some point in their lives. The region studied is known to have particularly high asthma rates relative to the rest of Spain, Gonzalez Barcala noted in an email to Reuters Health.

With the exception of the 6- to 7-year-old girls, no relationships could be found between diet and asthma after accounting for obesity and family lifestyle. And among this group of young girls, greater adherence to the Mediterranean diet actually appeared to increase the risk of asthma.

This unexpected result was likely due to children -- or their parents -- altering their diet because they knew they had asthma, rather than the diet triggering the disease, the researchers report in the journal Pediatric Allergy and Immunology.

Even if diet is truly not a factor, researchers shouldn't stop looking to Mediterranean countries for clues about asthma, noted Dr. Richard Hooper, of the University of London, who has separately studied the link between asthma and diet.

"Asthma is much more common now than it was two generations ago, and that must have something to do with our environment or the way we live our lives," he told Reuters Health by email. "Identifying populations which have somehow avoided the asthma epidemic could help us identify what those factors are, but it's often difficult to tease out the competing explanations."

"For example, your diet may give clues to other lifestyle choices you make," Hooper added. "Across national borders, of course, there may be large cultural differences that go beyond diet."


 Pediatric Allergy and Immunology, online June 14, 2010.

Diabetes Risk: Waist Circumference Gives Better Prediction Than BMI



Thursday, July 15, 2010


ScienceDaily (July 15, 2010) — Waist circumference gives a better prediction of diabetes risk than does BMI. This is the conclusion drawn by Silke Feller and her colleagues from the German Institute for Nutritional Research in Potsdam-Rehbrücke, in the current edition of Deutsches Ärzteblatt International .


Current guidelines recommend that the degree of risk of diabetes from overweight should be based on the determination of the body mass index (BMI). It is only recommended to measure the waist circumference when the BMI is greater than 25 points. Perhaps this strategy should be reconsidered, as the predictive power of waist circumference for diabetes is particularly high for normal and underweight people (BMI <25). Persons with a BMI of less than 25 points, but with a large waist circumference, have just as high a risk of developing diabetes, as pre-obese (25 < BMI < 30) women and men with low waist circumference.


The development of diabetes is particularly influenced by visceral fat tissue, which is metabolically more active than non-visceral fat. Visceral fat can be more accurately assessed from the waist circumference with people of lower weight than with overweight people, as waist circumference in overweight people contains a high proportion of subcutaneous fat.


Journal Reference:

Feller, S; Boeing, H; Pischon, T. Body Mass Index, Waist Circumference, and the Risk of Type 2 Diabetes Mellitus: Implications for Routine Clinical Practice. Dtsch Arztebl Int, 107(26): 470-6

Dramatic rise in painkiller drug abuse: U.S. officials


By Emma Ashburn


Thursday, July 15, 2010

WASHINGTON (Reuters) – U.S. officials reported a 400 percent increase over 10 years in the proportion of Americans treated for prescription painkiller abuse and said on Thursday the problem cut across age groups, geography and income.

The dramatic jump was higher than treatment admission rates for methamphetamine abuse, which doubled, and marijuana, which increased by almost half, according to figures from the Substance Abuse and Mental Health Services Administration.

They said 9.8 percent of hospital admissions for substance abuse in 2008 involved painkillers, up from 2.2 percent in 1998. The percentage of people admitted to treatment for alcohol dropped by 5 percent and for cocaine dropped by 16 percent over the same period.

"The spikes in prescription drug abuse rates captured by this study are dramatic, pervasive, and deeply disturbing," said Gil Kerlikowske, director of the White House Office of National Drug Control Policy.

The admissions for treatment for abuse of prescription drugs such as hydrocodone, oxycodone, and morphine cut across differences in education, employment, race, and geography, according to the analysis.

Admission rates also increased across all age groups, though the largest uptick was among people aged 18 to 24. For this age group, 13.7 percent were admitted because of prescription drug abuse in 2008, compared with 1.5 percent in 1998.

"This really has become a true public health problem," said SAMHSA's Peter Delany, who oversaw production of the report. "Those are our employed people, making big decisions about life -- Am I going to get married? What am I going to do for a living? What's my next job?"

Fifty-six percent of the patients got their drugs for free from a friend or relative, and another 9 percent purchased them from someone they knew.

"Some of the reason is simply the increased availability," said Thomas McLellan, deputy director of the Office of National Drug Control Policy. He said painkiller prescriptions increased between 700 to 1,000 percent over the 10 years.

Abuse of prescription pain medication was the second most common type of illicit drug use in the United States in 2008, according to SAMHSA. More than 6 million Americans admitted to abusing prescription drugs in the month before they were surveyed, behind 15.2 million who said they used marijuana.

"A lot of young people, especially, don't see these as dangerous because they're medications," said Delany. "It's not safer. It's just a different type of drug."

(Editing by Maggie Fox and Stacey Joyce)

Behavior Problems in School Linked to Two Types of Families 



Thursday, July 15, 2010


ScienceDaily (July 15, 2010) — Contrary to Leo Tolstoy's famous observation that "happy families are all alike; every unhappy family is unhappy in its own way," a new psychology study confirms that unhappy families, in fact, are unhappy in two distinct ways. And these dual patterns of unhealthy family relationships lead to a host of specific difficulties for children during their early school years.


"Families can be a support and resource for children as they enter school, or they can be a source of stress, distraction, and maladaptive behavior," says Melissa Sturge-Apple, the lead researcher on the paper and an assistant professor of psychology at the University of Rochester.


"This study shows that cold and controlling family environments are linked to a growing cascade of difficulties for children in their first three years of school, from aggressive and disruptive behavior to depression and alienation," Sturge-Apple explains. "The study also finds that children from families marked by high levels of conflict and intrusive parenting increasingly struggle with anxiety and social withdrawal as they navigate their early school years."


The three-year study, published July 15 in Child Development, examines relationship patterns in 234 families with six-year-old children. The research team identified three distinct family profiles: one happy, termed cohesive, and two unhappy, termed disengaged and enmeshed.


Cohesive families are characterized by harmonious interactions, emotional warmth, and firm but flexible roles for parents and children. "Think the Cosby family," says Sturge-Apple, offering an example from the popular TV series about the affable Huxtable family.


Enmeshed families, by contrast, may be emotionally involved and display modest amounts of warmth, but they struggle with high levels of hostility, destructive meddling, and a limited sense of the family as a team. Sturge-Apple points to the emotionally messy Barone family in the family sitcom Everybody Loves Raymond as a good example of an enmeshed family.


Finally, disengaged families, as the name implies, are marked by cold, controlling, and withdrawn relationships. The seemingly pleasant suburban family in the movie Ordinary People provides a classic illustration of a disengaged family, according to the authors. Reacting to the death of their oldest son, the parents in the film retreat emotionally, creating a barren home environment in which feelings cannot be discussed.


Although the study demonstrates solid evidence of a family-school connection, the authors caution that dysfunctional family relationships are not responsible for all or even most behavior difficulties in school. Other risk factors, such as high-crime neighborhoods, high-poverty schools, troubled peer circles, and genetic traits also influence whether one child develops more problems than another child, explains co-author Patrick Davies, professor of psychology at the University of Rochester.


The new study builds on the long-established family systems theory, which consistently has identified the three types of families using clinical observations. This study, however, is the first to empirically confirm their existence across multiple relationships within the family: in the marriage, in child-parent interactions, and among all three together, says Davies. "We were really able to look at the big picture of the family," he adds, "and what was striking was that these family relationship patterns were not only stable across different relationships but also across time, with very few families switching patterns."


The research found that children from disengaged homes began their education with higher levels of aggressive and disruptive behavior and more difficulty focusing on learning and cooperating with the classroom rules. These destructive behaviors grew worse as the child progressed through school.


By contrast, children from enmeshed home environments entered school with no more disciplinary problems or depression and withdrawal than their peers from cohesive families. But as children from both enmeshed and disengaged homes continued in school they began to suffer higher levels of anxiety and feelings of loneliness and alienation from peers and teachers. The authors conclude that, "children in the early school years may be especially vulnerable to the destructive relationship patterns of enmeshed families."


In the study, families were assessed using parent and teacher reports and through direct observation in the lab. Families came to the lab each year for two visits spaced one week apart. Both parents and the child played Jenga, an interactive game, for 15 minutes, and on alternate weeks each parent interacted alone with the child for five minutes of play and five minutes of clean up. Parents were also asked to discuss two topics picked to elicit disagreement. The sessions were videotaped and evaluated for behavior patterns.


The study examined how the parents related to one another, noting any aggression, withdrawal, or avoidance and observing their ability to work as a team in the presence of the child. The researchers coded the emotional availability of the parent toward the child, whether he or she provided praise and approval or simply ignored the youngster during shared activities. Observers also followed how the child related to his or her mother and father, noting whether attempts made to engage the parents were brief and half-hearted or sustained and enthusiastic.


Funded by the National Institute of Mental Health, the study was co-authored by E. Mark Cummings, professor and Notre Dame Chair in Psychology at the University of Notre Dame.


Farm, food service jobs tied to heart disease risk


Reuters Health

Thursday, July 15, 2010

NEW YORK (Reuters Health) – Americans in certain lines of work, including transportation, food service and farming, may have a relatively high rate of risk factors for heart disease, diabetes and stroke, a new study finds.

At the other end of the spectrum, researchers found, health professionals, scientists and artists are among those with the lowest rates of so-called metabolic syndrome.

Metabolic syndrome refers to a collection of risk factors for diabetes, heart disease and stroke -- including abdominal obesity, high blood pressure, high blood sugar, low levels of "good" HDL cholesterol and high triglycerides (another type of blood fat).

The syndrome is typically diagnosed when a person has three or more of those conditions, and the National Health and Nutrition Examination Survey, a major study, found that it can double the risk of heart attack and stroke.

In the new study, researchers found that among a nationally representative sample of U.S. adults, workers in the farm industry and food service (other than waiters and waitresses) had the highest rates of metabolic syndrome -- at around 30 percent. That compares to an overall U.S. risk of about 22 percent, according to the National Health and Nutrition Examination Survey.

Meanwhile, the risk factors were seen in roughly one-quarter of Americans in the transportation industry (truck drivers and other workers), construction and non-professional health services (excluding people such as doctors and nurses).

At the other end of the heart-risk spectrum were "writers, artists, entertainers and athletes" and the category that included scientists, engineers and architects, where the rates of metabolic syndrome were 8 percent to 9 percent. Doctors, nurses and other health professionals, meanwhile, had a rate of 12 percent.

The findings are published in the journal Diabetes Care.

In most cases, the job-related differences in metabolic syndrome appeared to be explained by differences in other associated factors -- including rates of obesity and smoking, exercise habits and race.

The exception was the transportation industry, where the work itself remained linked to an increased risk of metabolic syndrome even with the other factors taken into account.

The reasons for that finding are not clear, according to the researchers, led by Dr. Evelyn P. Davila of the University of Miami.

But, they note, the finding is in line with past studies that have found relatively higher rates of heart disease and stroke among truck drivers and other transportation workers compared with other lines of work.

It's possible, Davila and her colleagues write, that factors not measured in this study -- such as irregular work schedules and poorer sleep habits, or job stress -- might help explain the link between transportation work and metabolic syndrome.

The findings, according to the researchers, do not prove that any given occupation increases or decreases the risk of metabolic syndrome. They do, however, suggest that people in certain job fields need to be especially aware of ways to control their risk factors for heart disease and diabetes. That includes watching their diets and getting regular exercise, not smoking and, if necessary, taking medication to control their blood pressure and cholesterol.

The researchers say the results also suggest that certain workplaces should be targeted for health-promotion programs that raise awareness of metabolic syndrome and how to help prevent it.


Diabetes Care, online June 28, 2010.

U.S. study may be ideal test for Alzheimer's drugs


By Julie Steenhuysen


Thursday, July 15, 2010

HONOLULU (Reuters) – A study of families who get a rare genetic form of Alzheimer's may offer an ideal way to test drugs at an earlier stage, when they have the best chance of making a difference, researchers said on Thursday.

Progress in developing drugs that arrest the fatal brain disease has been frustratingly slow, in part because the studies largely involve patients whose brains are already wrecked by the disease, they said at the Alzheimer's Association meeting in Honolulu.

An international study known as the Dominantly Inherited Alzheimer Network, or DIAN, is set up to follow families with early onset familial Alzheimer disease, or eFAD, who make up 1 percent to 5 percent of the 26 million cases of Alzheimer's disease globally.

"The only people that we know of that are 100 percent destined to get Alzheimer's disease are these people with these mutations," Dr. Randall Bateman of Washington University in St. Louis and a DIAN investigator, said in an interview at the meeting.

People with the mutation typically develop Alzheimer's disease in their 50s, but symptoms can start as early as in their late 20s. They produce an excess of a protein linked with Alzheimer's known as beta amyloid, which is the main target of most drugs in late-stage testing.

Current Alzheimer's drugs, including Eisai Co and Pfizer Inc's Aricept, or donezepil, and Forest Laboratories' Namenda, or memantine, treat symptoms, but so far nothing has been shown to improve memory and thinking in people with the disease.

Bateman said that may be because they are testing too late in the disease, and he thinks the DIAN study, in which patients are sure to get the disease, may offer a way to test these drugs earlier, before symptoms appear.

"It's nearly impossible to treat someone with a new therapeutic agent that has potential toxicities if you don't know that person is going to get Alzheimer's disease," he said.

The DIAN researchers met this week with drugmakers at the Alzheimer's Association meeting to talk about how to structure clinical trials. So far, 12 major companies are have expressed an interest, Bateman said.

"We're having these discussions with everybody to see what drugs are going to be available, what will the properties be, how they can be implemented," he said.

Next, the companies will submit formal requests to a committee that will pick the best drugs for the study.

"Not all would be ideal. We have to exercise some selection on our end," said Dr. John Morris of Washington University, principal investigator for the DIAN study, which is funded by the National Institute on Aging.

There is no money in the study to pay for drug trials, so companies will have to contribute if they want to participate.

Bateman, who is running the treatment arm of the trial, said he thinks the study will be able to accommodate the most promising drugs already in late or midstage studies in people with the more common, late-onset form of Alzheimer's disease.

Dr. Eric Siemers of Eli Lilly and Co, which has four molecules in clinical development for Alzheimer's disease including two in late-stage clinical trials, said the DIAN study offers a great opportunity to test drugs.

"It's a way to do a proof of concept study. If you have a mutation, you know 100 percent that you will get the disease," said Siemers, who is medical director for Alzheimer's disease at the company.

Researchers say another compound likely to be tested is bapineuzumab, an antibody treatment being developed jointly by Pfizer Inc, Irish drugmaker Elan Corp and Johnson & Johnson.

No drugs have been picked, but it will happen soon. Bateman hopes to get clinical trials started as early as next year.

He likens the drug studies to early testing of popular cholesterol-lowering treatments known as statins, the world's biggest selling drugs, which were first tested in people genetically predisposed to develop high cholesterol.

"I think if (a drug ) is shown to work in this population it will certainly have some impact on Alzheimer's disease," Bateman said.

(Editing by Steve Orlofsky)


Wednesday, July 14, 2010


Early diagnosis can cut Alzheimer's costs: study


By Julie Steenhuysen


Wednesday, July 14, 2010

HONOLULU (Reuters) – Identifying dementia early can cut the cost of care by nearly 30 percent, U.S. researchers said on Wednesday, a finding that may reduce the heavy financial burden of the disease on the health care system.

They said routine screening that identified patients with early signs of dementia helped cut average healthcare costs by nearly $2,000 per patient in the first year, often by eliminating money spent on unnecessary tests and treatments.

"That runs into billions of dollars we could potentially save," Dr. Riley McCarten of the Minneapolis Veterans Medical Center told reporters at the Alzheimer's Association meeting in Honolulu.

On Tuesday experts at the National Institute on Aging and the Alzheimer's Association proposed new guidelines for diagnosing the fatal and incurable brain disease even before patients have symptoms.

The U.S. government, private insurance and individuals spend $172 billion a year to treat people with Alzheimer's disease, a fatal and incurable deterioration of the brain that affects more than 26 million people globally. It is the most common form of dementia.

By 2050, the cost of Alzheimer's care will reach $1.08 trillion a year in the United States, according to the Alzheimer's Association.

McCarten said most people in the United States with dementia are never diagnosed, and they often turn up in the emergency room with an acute problem when what they really have is a fatal brain disease.

"People lurch from one crisis to another," he said. "There is a tremendous amount of healthcare resources dedicated to acutely managing a chronic disease."

Having A Say

McCarten and colleagues at seven Veterans Administration medical centers looked to see how much they could save by routinely screening patients with a two-minute memory test.

More than 8,000 people over age 70 took the test and 26 percent failed. Those who failed were offered a 90-minute work-up to diagnose dementia, and about a third of those who failed the initial screening were tested. Of these, 97 percent had some form of cognitive impairment and 76 percent had dementia.

People who got a diagnosis and their families met with case managers to devise a care plan, and the team tracked their health costs for a year.

After subtracting the cost of the evaluation, patients saved an average of $1,700 annually, McCarten said.

"We found cost savings in the short run -- within one year," he said. McCarten said early diagnosis gives patients the chance to have a say in their own care, and it gives families time to come to grips with the disease.

A separate study by researchers at Johnson & Johnson and Pfizer found that a large portion of the financial burden of caring for Alzheimer's patients falls on families and caregivers.

Their Internet survey of nearly 1,000 families of Alzheimer's patients found they spend an average of $1,000 per month out of pocket to care for a family member in a nursing home, and $375 a month to care for them at home.

The team also found that families spend nearly 70 hours a week caring for an Alzheimer's patient at home, and close to 30 hours a week when their family member is in a nursing home.

(Editing by Maggie Fox and Xavier Briand)

Excess Weight in Older Women Linked to Diminished Memory


By Madonna Behen
HealthDay Reporter

HealthDay News

Wednesday, July 14, 2010

WEDNESDAY, July 14 (HealthDay News) -- Middle-aged women who are overweight may have yet another motivation to take off those excess pounds: The more a postmenopausal woman weighs, the worse her memory, researchers have found.

What's more, the negative impact on memory was more pronounced in "pear-shaped" women who carry excess weight around their hips, and less of a factor in "apple-shaped" women who carry it around their waists, the study authors noted.

In the new study, researchers found that for every one point increase in a woman's body mass index (BMI), her score on a standard memory test -- though still in the normal range -- dropped by one point. BMI is a measurement that takes into account height and weight.

The study, which was based on data from nearly 9,000 women who were enrolled in the Women's Health Initiative, a large government-sponsored study of postmenopausal women, was released online July 14 in advance of publication in the August print issue of the Journal of the American Geriatrics Society.

"This study really underscores the importance of maintaining an ideal body weight," said lead researcher Dr. Diana Kerwin, assistant professor of medicine in the division of geriatrics at Northwestern University's Feinberg School of Medicine in Chicago. "Even if a woman feels that she's generally healthy because her blood pressure and cholesterol levels are good, what these findings suggest is that she also needs to pay attention to her weight, because it's not only good for her heart, it's also good for her brain."

For the study, Kerwin and her colleagues examined data on 8,745 women between the ages of 65 and 79 who had no signs of dementia or other brain abnormalities. In addition to looking at BMI and waist and hip measurements (to determine body fat distribution), they also reviewed the women's scores on a 100-point cognitive functioning test known as the Modified Mini-Mental Status Examination. Roughly 70 percent of the women were overweight or obese.

After controlling for age, level of education and vascular diseases that have been shown to raise the risk of dementia, such as stroke, the researchers found that the association between obesity and poorer memory and brain function persisted. Kerwin, who conducted the study while a geriatrics researcher at the Medical College of Wisconsin, added that although the women's scores were still in the normal range, the added weight clearly had a detrimental effect.

Kerwin said more studies are needed to confirm and explain the apparent disparity between pear- and apple-shaped women. But one possibility is that the type of fat that's deposited on the hips is more likely to release hormones that are detrimental to brain function, she said. A follow-up study now in the planning stages will involve conducting MRIs of women's bodies, "so we can look at how much abdominal fat they have versus hip fat, and see if there's any difference in their brain functioning," Kerwin explained.

This study expands on several others involving body shape, in which obese apple-shaped women -- but not pear-shaped women -- were found to be at higher risk of diabetes, heart disease and dementia.

"What this study is really telling us is that there's something about obesity that puts you at risk for dementia, and it's independent of other factors such as vascular disease," said Dr. Gary Kennedy, director of geriatric psychiatry at Montefiore Medical Center in New York City.

Kennedy added that he hoped the results would coax more older women to exercise regularly in order to maintain a healthy weight. "This is really a call for women to make an effort to get more active, find an exercise partner, and do something every day," he said.

More information

The U.S. National Library of Medicine has more about aging changes in body shape.

Kids with food allergies may be smaller than peers


Reuters Health

Wednesday, July 14, 2010

NEW YORK (Reuters Health) – Young children with food allergies tend to be somewhat smaller than their peers with no such allergies, despite having a similar nutrient intake, a small study suggests.

On average, food-allergic children in the study were still well within the normal ranges of weight and height for their age.

But the findings underscore the importance of making sure kids with food allergies have a well-balanced diet and see the pediatrician for routine growth check-ups, the researchers report in the journal Pediatric Allergy and Immunology.

Research suggests that food allergies are becoming more common among children worldwide. An estimated 4 percent of U.S. children have a food allergy -- most commonly to peanuts, cow's milk and eggs.

Since parents have to be careful about food selection for children with such allergies, there is concern that some kids may not get enough of certain needed nutrients.

For the new study, Dr. Antoine Deschildre and colleagues at Jeanne de Flandre Hospital in Lille, France, assessed 96 children with confirmed food allergies, diagnosed after objective testing. Each was matched with another child the same age and sex but free of food allergies. Children in both groups were 4 years old, on average.

Overall, the researchers found no difference in the average weight and height in the two groups. When they looked at the children's weight-for-age and height-for-age, however, the average figures tended to be lower -- though still normal -- in the food-allergy group.

In addition, nine children with food allergies had a weight-for-age "Z-score" that was more than two standard deviations below the median, or midpoint, for their age and sex -- compared with none of the allergy-free children.

Similarly, seven food-allergic children had a height-for-age score that was two standard deviations below the median, versus two allergy-free children.

Z-scores are a way of gauging a child's weight and height in relation to those of other children of the same age and sex. For a 4-year-old girl, for example, the median Z-score translates to a weight of about 35 pounds; a girl who is two standard deviations below that would weigh about 26 pounds, based on World Health Organization growth charts.

The reasons for the differences are not clear, according to Deschildre's team.

When the researchers had parents complete three-day diet records for their children, they found no significant differences between the two groups as far as calorie, protein and calcium intake. Children with food allergies tended to get more vitamin A and E than their peers.

One possibility, Deschildre's team speculates, is that persistent intestinal inflammation in children with food allergies reduces their nutrient absorption. Whether that is in fact the case is unknown, however.

Parents of most of the children with food allergies -- 88 percent -- had received nutritional counseling from a dietitian, while the rest had gotten advice from their pediatricians, the researchers note.

They say their findings underscore the importance of such counseling, and of regular evaluations of children's growth, to limit any growth disparities in children with food allergies.


Pediatric Allergy and Immunology, online June 14, 2010.

Sniffing insulin may help memory lost to Alzheimer's


By Julie Steenhuysen


Wednesday, July 14, 2010

HONOLULU (Reuters) – Squirting insulin up the noses of patients with early forms of Alzheimer's disease showed signs of improving their memory, U.S. researchers said on Wednesday.

Patients who got the treatment for four months showed improvements in tests of memory recall that lasted for two months.

"We believe our results are very promising and they warrant future trials," said Dr. Suzanne Craft of the VA Puget Sound Health Care System and the University of Washington in Seattle, who presented her findings at a meeting of the Alzheimer's Association in Honolulu.

Alzheimer's disease is a fatal and incurable deterioration of the brain that affects 26 million people globally. It is the most common form of dementia.

Several studies have suggested that people with Alzheimer's have reduced levels of insulin in the brain, even in the earliest stages. Insulin is important for communication between brain cells and is needed for brain function.

Craft's team wanted to see what would happen if they delivered insulin directly to the brain.

They studied 109 non-diabetic patients with Alzheimer's disease or a precursor condition called mild cognitive impairment.

A third of the patients got a placebo and the other two-thirds received different doses of insulin that had been loaded into a nebulizer and squirted up their nose twice daily for four months.

Patients who got the lower dose of insulin showed significant improvements in some tests of memory, but they showed no change in a test of memory and learning or in a test of their ability to do daily activities.

In 15 insulin-treated patients who agreed to a spinal tap, the team found a link between improved memory and improvements in measurements of key proteins linked with Alzheimer's disease.

Craft said the treatment is a long way from being useful to patients, but the findings are strong enough to be studied in a large clinical trial.

Current Alzheimer's drugs only treat symptoms, but so far no drugs have been shown to improve memory in patients with Alzheimer's.

(Editing by Mohammad Zargham)

Antibiotics could help control malaria: study


By Kate Kelland


Wednesday, July 14, 2010

LONDON (Reuters) – People at high risk of malaria may benefit from taking a cocktail of antibiotics as a preventative step, according to the results of a study in mice.

Scientists from Britain, Germany and Kenya said the drugs could prompt healthy people to develop a natural immunity to malaria parasites, providing protection against future malaria infections.

The researchers said that a natural immunization technique like this could only be used in specific settings, where malaria seasons are high risk but relatively short, and where those in danger could be sure to take the protective medicines before being infected.

"The best application for this would be in areas where there is highly seasonal malaria transmission like in the savannah areas of Mali and Burkina Faso, where the malaria transmission only occurs for a short period but is extremely intense," said Steffen Borrmann, from the Kenya Medical Research Institute in Kilifi, who worked on the study.

The antibiotics work by causing a cellular defect in malaria parasites during their journey into the liver of the infected host, the researchers said in a report on their findings published in the Science Translational Medicine journal.

This blocks the malaria parasite's fatal conversion from the liver stage to the disease-causing blood stage. The blocked parasite inside the liver prompts the body to develop a strong protective immunity to malaria, a bit like a traditional vaccination, they said.

"But we are not developing this or proposing this as a vaccine as such," Borrmann said in a telephone interview. "It would be one additional tool in the larger set of weapons against malaria which could be used in certain circumstances."

Malaria kills up to a million people a year, most of them children living in Africa, where a child dies of the disease every 45 seconds, according to the World Health Organization. It is caused by Plasmodium parasites, which are spread by the bites of infected Anopheles mosquitoes.

Mice Protected Against Malaria

Borrmann and his colleagues conducted the study by giving preventative antibiotics to healthy mice and then infecting them with malaria parasites. They found that the mice generated a vaccine-like immunity against re-infection.

The results also showed that even when given low doses of antibiotics, almost all the mice were protected from the fatal brain complications associated with the most dangerous malaria parasite, Plasmodium falciparum.

British drugmaker GlaxoSmithKline is currently carrying out late-stage testing in people of an experimental vaccine against malaria and expects to see results by 2011. The company says that if it proves effective, it will seek regulatory approval for the vaccine, called Mosquirix, by 2012.

Borrmann's team now want to test their findings in clinical trials to see if their approach works in humans.

"If successful, periodic administration of antibiotics in high-risk population groups, such as young children, may prove to be a valuable tool for controlling or eliminating malaria in regions of high transmission," they wrote.

(Editing by Tim Pearce)

Water's Unexpected Role in Blood Pressure Control



Wednesday, July 14, 2010


ScienceDaily (July 14, 2010) — Name a drink that can make you more alert for late-night studying, prevent you from fainting after giving blood, and even promote a teensy bit of weight loss.


Chances are you didn't say water. But that's the right answer.


Researchers at Vanderbilt University Medical Center have shown that ordinary water -- without any additives -- does more than just quench thirst. It has some other unexpected, physiological effects. It increases the activity of the sympathetic -- fight or flight -- nervous system, which raises alertness, blood pressure and energy expenditure.


David Robertson, M.D., and colleagues first observed water's curious ability to increase blood pressure about 10 years ago, in patients who had lost their baroreflexes -- the system that keeps blood pressure within a normal range.


The observation came as a complete surprise, said Robertson, professor of Medicine, Pharmacology and Neurology.


"We had to unlearn the idea that water had no effect on blood pressure, which is what all medical students had been told until the last couple of years."


Although water does not significantly raise blood pressure in healthy young subjects with intact baroreflexes, the investigators found that it does increase sympathetic nervous system activity and constrict blood vessels (which prevents pooling of blood in the extremities).


These findings prompted the American Red Cross to conduct a study of water drinking as a method for reducing fainting responses. The study found that drinking 16 ounces of water before blood donation reduced the fainting response by 20 percent.


"This response to water may turn out to be very important for retaining blood donors," Robertson said. "If you pass out after giving blood, you pretty much never give blood again. If we can reduce fainting by 20 percent, we can reduce the unpleasantness of passing out and really bolster the number of people who can continue to be blood donors."


Julia McHugh, a student in Vanderbilt University School of Medicine's Medical Scientist Training Program, tackled the questions of where water is acting, and how, in a series of studies in mice. The team's latest findings are reported in the June issue of the journal Hypertension.


McHugh and colleagues found that water introduced directly into the stomach or duodenum (the first part of the small intestine) raised blood pressure, which ruled out an oral or esophageal mechanism for the response. They also tested a similar volume of saline (salt-containing solution). This did not raise blood pressure, which suggested that stretch of the tissues was not part of the mechanism and that perhaps water's lack of salt might be important.


The investigators ultimately determined that water dilutes the plasma in the blood vessels leading away from the duodenum and that this short-lived reduction in salt concentration (hypo-osmolality) is responsible for water's blood pressure-raising (pressor) effect. They implicated a protein called Trpv4 in the mechanism: mice lacking the Trpv4 gene did not have a pressor response to water.


While it is clear that water evokes a pressor response, the normal role for this physiological system is not certain.


Because it raises sympathetic nervous system activity -- and consequently energy expenditure -- it does promote weight loss, Robertson said.


"I calculated it might be as much as five pounds a year if you drank three 16 ounce glasses of water a day and nothing else changed. This is not going to be the answer to the weight problem in the United States, but it's interesting that activation of the sympathetic system is enough to do that."


McHugh said she found it fascinating that mice and humans share "such a primitive system, and yet we don't know why it's there or what beneficial effects it might have."


The newly discovered system and its molecular mediators -- such as Trpv4 -- may be targets for blood pressure regulation, particularly in situations of low blood pressure and fainting, the investigators said. The findings also suggest that investigators who use water as a control substance (a "non-drug") in studies may need to take water's pressor effects into account.


Robertson is the Elton Yates Professor of Autonomic Disorders. The National Institutes of Health provided funding for the research.


Tuesday, July 13, 2010


Association Found Between Alzheimer's and Anemia


HealthDay News)

Tuesday, July 13, 2010

TUESDAY, July 13 (HealthDay News) -- Alzheimer's disease may be linked to an increased risk of anemia, new study findings suggest.

Australian researchers analyzed hemoglobin, iron and other blood-based measurements in 211 Alzheimer's patients, 133 people with mild cognitive impairment (MCI) and 768 healthy people. They compared these measurements to tests of participants' short- and long-term memory and cognitive abilities.

Compared to the healthy people, Alzheimer's patients had significantly lower levels of hemoglobin, mean cell hemoglobin concentration, and packed cell volume, the investigators found. The Alzheimer's patients also had a significantly higher erythrocyte sedimentation rate, a possible sign of anemia.

Participants with anemia were 2.56 times more likely to have Alzheimer's disease, while those with Alzheimer's were 2.61 times more likely to be anemic, the researchers noted in a news release from the Alzheimer's Association.

"In our population, we found that people with Alzheimer's disease were more likely to be anemic, and this was not explained by dietary iron deficiency. This suggests that hemoglobin production is deficient in Alzheimer's patients," Noel Faux, of the Mental Health Research Institute in Parkville, Australia, explained in the news release.

"Alzheimer's had not previously been recognized as a risk factor for anemia, which is a common clinical problem for the elderly and can contribute to problems such as heart failure and renal failure. The cause of anemia in Alzheimer's is still uncertain, but we speculate that Alzheimer's is a disease that affects both brain and blood. We are currently investigating this intriguing possibility," Faux added.

The study was slated to be presented Tuesday at the Alzheimer's Association International Conference on Alzheimer's Disease, in Honolulu.

More information

The U.S. National Heart, Lung, and Blood Institute has more about anemia.


High-Risk Prostate Cancer Associated With Significantly Lower Bone Mineral Content Loss



Tuesday, July 13, 2010


ScienceDaily (July 13, 2010) — Men with prostate cancer lose significantly less bone mineral content (BMC) as they age than men who are free of the disease, according to research in the July issue of BJUI. The findings are important because loss of BMC can play a key role in the development of fragile bones, fractures and osteoporosis.


American researchers studied 519 participants who joined the Baltimore Longitudinal Study at an average age of 56 between 1973 and 1984. The maximum follow-up was 35 years and the median was 22 years. Seventy-six men who took part in the study were later diagnosed with prostate cancer, with just under a quarter (24 per cent) falling into the high-risk category.


When they charted the individual BMCs of the study subjects over an extended period, the researchers could clearly see that the decline was much larger in healthy men than in men later diagnosed with prostate cancer, especially those with high-risk prostate cancer. This occurred despite the fact that the initial baseline readings were very similar for all three groups.


The researchers also adjusted the figures to take account of other factors that affect BMC, such as smoking status, body mass index, dietary calcium and vitamin D. However, this did not change the significant differences between the healthy men and those with prostate cancer.


"There are numerous possible mechanisms to explain the relationship between prostate cancer and BMC" says lead author Dr Stacy Loeb, from Johns Hopkins University, Maryland, USA.


"It is well known that prostate cancer frequently metastasizes (spreads) to bone. Although the biology underlying the association between BMC and this form of cancer requires additional research, our findings suggest that common growth factors might be involved in both bone maintenance and the progression of prostate cancer.


"We believe that this may be why the patients with the highest risk prostate cancer also demonstrated the least loss of BMC as they got older, when compared with patients with non high-risk prostate cancer and no prostate cancer."


The baseline demographics between the three groups of men were similar when it came to their body mass index and smoking history.


The authors believe that this is the first study to explore the relationship between longitudinal BMC measurement and the long-term risk of prostate cancer and, more specifically, life-threatening disease. They point out that the study sample was primarily white (96 per cent) and, due to racial differences in bone density, may not be generally applicable to other ethnic groups.


"We would like to see our theories tested further in larger populations of men at risk of developing life-threatening prostate cancer" concludes Dr Loeb. "If we can better understand the link between prostate cancer and bone, it may help us to find ways of preventing the spread of this disease to bone in the future."

Journal Reference:

Stacy Loeb, H. Ballentine Carter, Edward M. Schaeffer, Shari M. Ling, Anna Kettermann, Luigi Ferrucci, E. Jeffrey Metter. Bone mineral content and prostate cancer risk: data from the Baltimore Longitudinal Study of Aging. BJU International, 2010; 106 (1): 28 DOI: 10.1111/j.1464-410X.2009.09109.x

Alzheimer's May Increase Seizure Risk


HealthDay News

Tuesday, July 13, 2010

TUESDAY, July 13 (HealthDay News) -- People with Alzheimer's disease appear to be at increased risk for seizures, researchers have found.

In the study, researchers analyzed data from almost 15,000 Alzheimer's disease patients in the United Kingdom, aged 50 and older, and compared the data with that from an age-matched control group of the same number of people without Alzheimer's disease. The Alzheimer's patients were followed for an average of 2.3 years while those in the control group were followed for an average of 3.4 years.

During the follow-up, the incidence rate of seizures among the Alzheimer's patients was 9.1 per 1,000 people per year, compared with 1.4 for those in the control group. That means the incidence rate of seizures was 6.4 times higher for Alzheimer's patients, the study authors explained in a news release from the Alzheimer's Association.

The researchers also found that the seizure incidence rate was highest among the youngest Alzheimer's patients and decreased with age. In the control group, the incidence rate of seizures increased slightly with age, they noted.

While the increased risk of seizures is cause for concern among all Alzheimer's patients, the substantially increased risk among younger patients means that they and their caregivers need to be especially aware of the problem, the study authors pointed out.

"The connection between Alzheimer's and seizures provides additional avenues for research into the basic biology of both diseases, and possibly interventions and therapies to respond to the overall impact of Alzheimer's disease," study author H. Michael Arrighi, of Janssen Alzheimer Immunotherapy Research & Development in the San Francisco Bay area, stated in the news release.

The study was scheduled to be presented Tuesday at the Alzheimer's Association International Conference on Alzheimer's Disease, in Honolulu.

More information

The U.S. National Institute on Aging has more about Alzheimer's disease.

Depressed Men With ED at Risk for Cardiovascular Problems



Tuesday, July 13, 2010


ScienceDaily (July 13, 2010) — A new study in the Journal of Sexual Medicine found that the presence of depressive symptoms in men with erectile dysfunction constitutes a risk factor for a major cardiovascular event.


Erectile dysfunction and depressive mood are often associated, and both are associated with an increased risk of cardiovascular disease and death. To investigate clinical correlates further, researchers led by Elisa Bandini of the University of Florence studied approximately 2,000 male patients in a clinic for sexual dysfunction using a structured interview while also scoring for depressive symptoms.


Results show that in these subjects with erectile dysfunction, depression increases cardiovascular problems independently from other known risk factors. Furthermore, even the use of antidepressant medications did not alter the relationship between severe depressive symptoms and adverse cardiovascular events.


"Recognizing depressive symptoms in subjects with erectile dysfunction is mandatory not only for improving their sexual life, but also for preventing cardiovascular diseases," Bandini notes.


"What is important about this study is the broader concept of the sexual medicine problem no longer being just about a man's performance in the bedroom, but about his psychological mood and his cardiovascular health," states Irwin Goldstein, Editor-in-Chief of the Journal of Sexual Medicine and director of sexual medicine at Alvarado Hospital in San Diego. "This is a valid reason for a woman to encourage her partner to seek help for his erectile dysfunction."


Longer breastfeeding may raise infants' eczema risk


By Rachael Myers Lowe

Reuters Health

Tuesday, July 13, 2010

NEW YORK (Reuters Health) – Longer breastfeeding may increase, not decrease, the risk of a common itchy skin condition called atopic dermatitis that develops in about 12 percent of babies, a new study from Taiwan suggests.

Atopic dermatitis is a type of eczema, or skin inflammation, that runs in families and usually shows up before a baby's first birthday. Although it can last a lifetime, it often clears up by age 5. Beyond the genetic connection, doctors don't know why some kids develop it and others don't. Researchers from Taiwan wanted to know if breastfeeding and the timing of first solid foods might make a difference.

It is widely believed that prolonged breastfeeding and delaying the introduction of solid foods have benefits with regard to atopic dermatitis, but clearcut scientific evidence that these feeding practices prevent the skin condition is lacking.

To investigate, Chao-Hua Chuang, and colleagues at Chang Jung Christian University and other institutions in Taiwan, looked at information from a large ongoing study of Taiwanese children.

When the children were 6 and 18 months old, their parents provided relevant information about themselves, their babies, and their home environment. The parents answered questions about smoking habits, allergies, and their level of education. They also indicated whether their child was still breastfeeding, if and when solid foods were introduced, and whether their child had been diagnosed by a doctor with atopic dermatitis.

At 18 months, 2,449 of 20,172 children (about 12 percent) had been diagnosed with atopic dermatitis -- a number in line with previous studies.

The researchers excluded a large number of children who were diagnosed before they were 6 months old for fear that their parents might have changed the way their kids were fed after the diagnosis, thus skewing the data. Of the 18,773 children that remained, 1,050 (almost 6 percent) were diagnosed with atopic dermatitis between the ages of 6 and 18 months.

After controlling for possible risk factors for atopic dermatitis -- such as parents' allergies, and pets, mold, and exposure to secondhand smoke in the home -- they found that not only did longer breastfeeding not protect against the skin condition as might have been expected, it appeared to increase the risk that a child would have atopic dermatitis at 18 months.

In the journal Pediatric Allergy and Immunology, the researchers acknowledge that their results fly in the face of some previous studies that have suggested that children who are breastfed are less likely to develop eczema.

Chuang and colleagues point out, however, that most previous studies focused on exclusive breastfeeding, something they could not do because few Taiwanese parents exclusively breastfeed their children without adding other liquids or solids. As a result, they say they "cannot totally dismiss the supposed benefits of exclusive breastfeeding with regard to atopic dermatitis."

In an email to Reuters Health, Chuang emphasized that the evidence from the current study does not warrant a change in breastfeeding practice. "We can not exclude the other potential benefits of breastfeeding," Chuang wrote.

The timing for introducing solid foods was the other focus of the Taiwan study. Delaying solid foods did not appear to affect atopic dermatitis risk one way or the other, prompting the researchers to suggest that current feeding guidelines that recommend delaying solids to reduce allergies "need to be reconsidered."

The latest review (2008) of evidence by the American Academy of Pediatrics concluded that infants at high risk of developing allergic diseases (including dermatitis) might benefit from exclusive breastfeeding for 4 months but for infants in general, "after 4 to 6 months of age, there are insufficient data to support a protective effect of any dietary intervention for the development of atopic disease."


Pediatric Allergy and Immunology, published online June 21, 2010

Problematic Blood Clotting Contributes to Alzheimer’s Disease



Tuesday, July 13, 2010


ScienceDaily (July 13, 2010) — Alzheimer's disease has long been studied primarily as a disease of neurons. But researchers have now shown how the disease may be damaging the brain by choking off blood flow. In experiments published June 10 in Neuron, scientists at Rockefeller University reveal that amyloid-β, which builds up around brain cells in Alzheimer's patients, interacts with a common blood clotting agent to increase clotting in the arteries that feed the brain. Such activity could cut off blood flow to neurons, suffocating them over time. A drug that interferes with that process could reduce the memory loss and dementia that are the most wrenching consequences of the disease, the findings suggest.


"There's at least this one very promising therapeutic angle," says Sidney Strickland, head of the Laboratory of Neurobiology and Genetics at Rockefeller. And what's nice is that a drug that disrupted this particular interaction would not affect clotting elsewhere like regular anticoagulants, because the amyloid-β peptide is primarily found in the brain."


Postdoctoral fellow Marta Cortes-Canteli led the work in Strickland's lab, conducting test tube experiments and experiments in mice genetically engineered with Alzheimer's disease to investigate the interaction of amyloid-β and the blood-clotting agent called fibrinogen. Normally, when the body is injured, fibrinogen forms fibrin clots to stop uncontrolled bleeding. Once the wound is healed, the blood clot is broken down and blood flow returns to normal.


Strickland, Cortes-Canteli and colleagues found that the blood in mice with the extra amyloid-β produced in Alzheimer's disease clotted more quickly and that the clots were more difficult to degrade. They also found that mice with lower levels of fibrinogen had less buildup of amyloid beta in the walls of their blood vessels and performed better on memory tasks.


This led them to propose a new model for the vascular component of the disease, which is increasingly recognized as a key element in its pathology. "The promotion of blood clots and the difficulty of breaking them down would cause a decrease in cerebral blood flow and increase in inflammation that could eventually lead to the neuronal dysfunction in Alzheimer's patients," Cortes-Canteli says. "Of course, Alzheimer's is a multifaceted disease, and a lot of things are going on, but we do think that targeting the association of amyloid-β and fibrinogen could be a very promising treatment."

Journal Reference:

Marta Cortes-Canteli, Justin Paul, Erin H. Norris, Robert Bronstein, Hyung Jin Ahn, Daria Zamolodchikov, Shivaprasad Bhuvanendran, Katherine M. Fenz and Sidney Strickland. Fibrinogen and β-Amyloid Association Alters Thrombosis and Fibrinolysis: A Possible Contributing Factor to Alzheimer's Disease. Neuron, Volume 66, Issue 5, 695-709 (June 10, 2010) DOI: 10.1016/j.neuron.2010.05.014

Danish study: Obese men face higher death risk


The Associated Press

Tuesday, July 13, 2010

STOCKHOLM – A Danish study suggests that men who are obese by age 20 die eight years earlier on average than their non-obese peers, scientists said Tuesday.

The research, presented at the International Congress on Obesity in Stockholm, also indicated that obesity usually develops before the age of 20 and that most people are unlikely to develop obesity later in life.

More than 5,000 military conscripts took part in the study, starting from age 20 through to age 80. Some 2,000 of them were obese when they began the trial.

The research concluded that the risk of premature death in already obese men increased 10 percent for every point surpassing the healthy level of 25 body mass index points. Body mass index is used to determine a person's body fat through a calculation using height and weight.

"At age 70 years, 70 percent of the men in the comparison group and 50 percent of those in the obese group were still alive and we estimated that from middle-age the obese were likely to die eight years earlier than those in the comparison group," said Esther Zimmermann of Copenhagen University Hospital.

Zimmermann, who led the study team at the hospital's Institute of Preventive Medicine, said the research accounted for the influences of smoking, year of birth, and education but not other factors, such as hereditary diseases.

The research did not include women, but confirmed findings made in similar studies.

Last year, an American study published in the medical journal BMJ said obesity could slash women's chances of reaching the age of 80 in good health by nearly 80 percent. The researchers found that for every one-point increase in their body mass index women had a 12 percent lower chance of surviving to age 70 in good health.

A British study published in Lancet in 2009 found that people with a body mass index from 30 to 35 die about three years earlier than normal, while those who were morbidly fat, with an index above 40, die about a decade earlier.

Childhood Cancer Survivors at Risk of Premature Death


By Steven Reinberg
HealthDay Reporter
HealthDay News

Tuesday, July 13, 2010

TUESDAY, July 13 (HealthDay News) -- Childhood cancer casts a long shadow. Those who survive the original cancer are at high risk of dying prematurely decades afterward from new cancers, heart disease and stroke likely caused by the cancer treatment itself, British researchers report.

Although more children are surviving cancer, many have long-term risks of dying prematurely from other diseases. These excess deaths, the researchers say, may be related to late complications of treatment, such as the long-term effects of radiation and chemotherapy.

Equally troubling is that many older survivors are not being monitored for these problems, the researchers added.

Compared to the general population, excess deaths may result from new primary cancers and circulatory disease that surface up to 45 years after a childhood cancer diagnosis, said lead researcher Raoul C. Reulen of the Center for Childhood Cancer Survivor Studies at the University of Birmingham.

Reulen noted that while the risk of death from the effects of new cancers and cancer treatments increases with age, many of the most vulnerable survivors are not monitored for these life-threatening health problems.

"In terms of absolute risk, older survivors are most at risk of dying of a second primary cancer and circulatory disease, yet are less likely to be on active follow-up," he said. "This suggests that survivors should be able to access health care intervention programs even many years" after they pass the mark for five-year survival.

The report is published in the July 14 issue of the Journal of the American Medical Association.

For the study, Reulen's team collected data on 17,981 children who survived cancer. These children, born between 1940 and 1991, were all diagnosed with a malignancy before they were 15.

By the end of 2006, 3,049 of these individuals had died. That was a rate 11 times higher than would be seen in the general population -- something called the general mortality rate. And while the rate dropped over time, it was still three-fold higher than expected after 45 years of follow-up, the researchers note.

While the absolute risk of death from a recurrence of the original cancer dropped over time, the risk of dying from a different cancer, heart disease or stroke increased.

After the 45-year follow-up, the number of deaths among the childhood cancer survivors was 3.6 times higher for a second primary cancer than would be expected in the general population, and 26 percent of all excess deaths were caused by heart disease or stroke, Reulen's team found.

"Beyond 45 years from diagnosis, recurrence accounted for 7 percent of the excess number of deaths observed while second primary cancers and circulatory deaths together accounted for 77 percent," the researchers wrote.

The deaths from heart disease and stroke likely stem from late complications of treatment, the researchers added.

Dr. J. Leonard Lichtenfeld, deputy chief medical officer at the American Cancer Society, said that "long-term problems of childhood cancer survivors give us clues what the impact is of the treatment we offer."

"It is not unexpected that we see an increase in second cancers and increases in heart disease," he added.

However, Lichtenfeld concurs that a key problem is that many of these cancer survivors do not get regular follow-up and screening for cancer and other diseases as they get older.

"The children are well-followed when they are young adults, but as they get older, they tend to do what other people do. They overcome their disease and they are lost to follow-up," he said.

Lichtenfeld also noted that today treatments are less toxic and more targeted than they used to be. So these newer treatments may have fewer long-term adverse consequences.

"The side effect of our success [is] the side effects of the treatment themselves," he said. "Patients and physicians must be vigilant to know what the long-term effects of these treatments may be."

More information

For more information on late effects of childhood cancer, visit the American Cancer Society.

Monday, July 12, 2010


Vitamins D, E Might Help Maintain Brain Health


By Steven Reinberg
HealthDay Reporter
HealthDay News

Monday, July 12, 2010

MONDAY, July 12 (HealthDay News) -- Three new studies suggest that vitamins D and E might help keep our minds sharper, aid in warding off dementia, and even offer some protection against Parkinson's disease, although much more research is needed to confirm the findings.

In one trial, British researchers tied low levels of vitamin D to higher odds of developing dementia, while a Dutch study found that people with diets rich in vitamin E had a lower risk of developing dementia, including Alzheimer's disease.

Finally, a study released by Finnish researchers linked high blood levels of vitamin D to a lower risk of Parkinson's disease.

In the first report, published in the July 12 issue of the Archives of Internal Medicine, a research team led by David J. Llewellyn of the University of Exeter in the United Kingdom found that among 858 older adults, those with low levels of vitamin D were more likely to develop dementia.

In fact, people who had blood levels of vitamin D lower than 25 nanomoles per liter were 60 percent more likely to develop substantial declines overall in thinking, learning and memory over the six years of the study.

In addition, they were 31 percent more likely to have lower scores in the test measuring "executive function" than those with sufficient vitamin D levels, while levels of attention remained unaffected, the researchers found. ("Executive function" is a set of high-level cognitive abilities that help people organize, prioritize, adapt to change and plan for the future.)

"The association remained significant after adjustment for a wide range of potential [factors], and when analyses were restricted to elderly subjects who were non-demented at baseline," Llewellyn's team wrote.

The possible role of vitamin D in preventing other illnesses has been investigated by other researchers, but one expert cautioned that the evidence for taking vitamin D supplements is still unproven.

"There is currently quite a lot of enthusiasm for vitamin D supplementation, of both individuals and populations, in the belief that it will reduce the burden of many diseases," said Dr. Andrew Grey, an associate professor of medicine at the University of Auckland in New Zealand and co-author of an editorial in the July 12 issue of the Archives of Internal Medicine.

"This enthusiasm is predicated upon data from observational studies -- which are subject to confounding, and are hypothesis-generating rather than hypothesis-testing -- rather than randomized controlled trials," Grey said. "Calls for widespread vitamin D supplementation are premature on the basis of current evidence."

In another report involving vitamin D and brain health, researchers led by Paul Knekt and colleagues at the National Institute for Health and Welfare in Helsinki, Finland, found that people with higher serum levels of vitamin D appear to have a lower risk of developing Parkinson's disease.

Their report was published in the July issue of the Archives of Neurology.

For the study, Knekt and his team collected data on almost 3,200 Finnish men and women aged 50 to 79 who did not have Parkinson's disease when the study began.

Over 29 years of follow-up, 50 people developed Parkinson's disease. The researchers calculated that people with the highest levels of vitamin D had a 67 percent lower risk of developing Parkinson's disease compared with those with the lowest levels of vitamin D.

"In conclusion, our results are in line with the hypothesis that low vitamin D status predicts the development of Parkinson's disease," the researchers wrote.

"Because of the small number of cases and the possibility of residual [factors that might influence the results], large cohort studies are needed. In intervention trials focusing on effects of vitamin D supplements, the incidence of Parkinson's disease merits follow up," Knekt and colleagues added.

Dr. Marian Evatt, an assistant professor of neurology at Emory University and author of an accompanying editorial, said that "vitamin D regulates a tremendous number of physiologic processes critical for normal growth, development and survival of human cells, and animal data suggests that this includes development, growth and survival of cells in the nervous system."

However, the animal data also suggests that there may be a range of vitamin D levels that are optimal and if cells are exposed to levels above or below that level, life is not so good, she said.

This study is the first study examining vitamin D levels in a population, then looking at whether there is subsequent associated risk of developing Parkinson's disease, Evatt added.

"Further studies are warranted to see if these findings can be duplicated in other populations," Evatt concluded.

Still another report, published in the July issue of the Archives of Neurology, found that eating foods rich in vitamin E might help stave off dementia and Alzheimer's disease. These foods included margarine, sunflower oil, butter, cooking fat and soybean oil.

For the study, researchers led by Elizabeth E. Devore, from Erasmus Medical Center in Rotterdam, the Netherlands, collected data on the diets of almost 5,400 people 55 years and older who did not have dementia between 1990 and 1993. Over an average of 9.6 years of follow-up, 465 of these individuals developed dementia, and 365 of these were diagnosed with Alzheimer's disease, the researchers reported.

Devore's team found that those who consumed the most vitamin E (one-third of the participants) were 25 percent less likely to develop dementia, compared with the third who consumed the least.

"The brain is a site of high metabolic activity, which makes it vulnerable to oxidative damage, and slow accumulation of such damage over a lifetime may contribute to the development of dementia," Devore and colleagues wrote.

"In particular, when beta-amyloid (a hallmark of pathologic Alzheimer's disease) accumulates in the brain, an inflammatory response is likely evoked that produces nitric oxide radicals and downstream neurodegenerative effects. Vitamin E is a powerful fat-soluble antioxidant that may help to inhibit the pathogenesis of dementia," the authors added.

The researchers concluded that further studies are needed to evaluate the possible benefits of dietary intake of antioxidants.

Dr. Michael Holick, a professor of medicine, physiology and biophysics and director of the General Clinical Research Center at Boston University Medical Center said that "these finding are consistent with what we have been believing for a long time, that the brain has receptors for vitamin D, so to maximize brain function you probably need adequate vitamin D."

Holick also believes that vitamin E is probably important for brain health. "It may be that vitamin E improves the health of the brain cell," he said.

More information

For more information on vitamin D, visit the U.S. National Institutes of Health.

Low vitamin D increases risk of dementia in elderly


By Kate Kelland


Monday, July 12, 2010

LONDON (Reuters) – Older people with low levels of vitamin D appear more likely to have problems with memory, learning and thinking, suggesting low vitamin D could give an early warning for dementia risk, scientists said on Monday.

Researchers from Britain, Italy and the United States studied 850 Italians aged 65 or older and found that those who were severely vitamin D deficient were 60 percent more likely to experience substantial general cognitive decline, and 31 percent more likely to experience problems with mental flexibility.

"This is the first study to identify a clear link between low vitamin D levels and cognitive decline," said David Llewellyn of the Peninsula Medical School at Britain's Exeter University, who led the study.

"We have now been able to demonstrate a connection between having low levels of vitamin D and going on to develop cognitive problems."

Since an estimated that one billion people worldwide have insufficient levels of vitamin D, Llewellyn said the findings were "a cause for real concern."

Giving vitamin D supplements to older people to boost their levels could be "a highly promising therapeutic target for the prevention of dementia," he said, particularly since supplements are cheap, safe and have already been shown to help prevent to reduce the risk of falls and fractures.

Most vitamin D is made by the body as a natural by-product of the skin's exposure to sunlight. It can also be found in a few foods such as oily fish and is vital for health, as it helps cells absorb calcium and is key for bone strength.

Some recent studies have also suggested vitamin D may protect against cancer, artery disease and tuberculosis.

In this study, Llewellyn's team found that older people who were severely deficient in vitamin D -- defined as having blood levels of 25-hydroxyvitamin D of less than 25 nanomoles per liter -- were 60 percent more likely to have substantial cognitive decline over a 6-year period studied.

They were also 31 percent more likely to show decline in a test measuring executive function than those with good vitamin D levels. The findings were published in the Archives of Internal Medicine journal.

Dementia is a brain-wasting condition that affects around 35 million people worldwide.

Its most common form is Alzheimer's disease, in which patients gradually to lose their memory, their ability to navigate and understand the world around them and to look after themselves. Despite decades of research, doctors still have few effective weapons against it.

Llewellyn's team said they thought Vitamin D may help prevent the degeneration of brain tissue by having a role in formation of nervous tissue, maintaining levels of calcium in the body, or clearing of beta-amyloid, the substance that forms the brain plaques that are associated with Alzheimer's disease.

Experts estimated that in the United States and Europe, between 40 percent to 100 percent of older adults are deficient in vitamin D and the problem is aggravated in the elderly as they spend more time indoors and their skin becomes less efficient at producing vitamin D with age.

(Editing by Maria Golovnina)

Honey as an Antibiotic: Scientists Identify a Secret Ingredient in Honey That Kills Bacteria


Monday, July 12, 2010

ScienceDaily (July 12, 2010) — Sweet news for those looking for new antibiotics: A new research published in the July 2010 print edition of the FASEB Journal explains for the first time how honey kills bacteria. Specifically, the research shows that bees make a protein that they add to the honey, called defensin-1, which could one day be used to treat burns and skin infections and to develop new drugs that could combat antibiotic-resistant infections.

"We have completely elucidated the molecular basis of the antibacterial activity of a single medical-grade honey, which contributes to the applicability of honey in medicine," said Sebastian A.J. Zaat, Ph.D., a researcher involved in the work from the Department of Medical Microbiology at the Academic Medical Center in Amsterdam. "Honey or isolated honey-derived components might be of great value for prevention and treatment of infections caused by antibiotic-resistant bacteria."


To make the discovery, Zaat and colleagues investigated the antibacterial activity of medical-grade honey in test tubes against a panel of antibiotic-resistant, disease-causing bacteria. They developed a method to selectively neutralize the known antibacterial factors in honey and determine their individual antibacterial contributions. Ultimately, researchers isolated the defensin-1 protein, which is part of the honey bee immune system and is added by bees to honey. After analysis, the scientists concluded that the vast majority of honey's antibacterial properties come from that protein. This information also sheds light on the inner workings of honey bee immune systems, which may one day help breeders create healthier and heartier honey bees.

"We've known for millennia that honey can be good for what ails us, but we haven't known how it works," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal, "Now that we've extracted a potent antibacterial ingredient from honey, we can make it still more effective and take the sting out of bacterial infections."

Journal Reference:

P. H. S. Kwakman, A. A. te Velde, L. de Boer, D. Speijer, C. M. J. E. Vandenbroucke-Grauls, S. A. J. Zaat. How honey kills bacteria. The FASEB Journal, 2010; DOI: 10.1096/fj.09-150789

Higher vitamin E intake tied to lower dementia risk


Reuters Health

Monday, July 12, 2010

NEW YORK (Reuters Health) – Older adults who get plenty of vitamin E in their diets may have a somewhat lower risk of developing dementia than those who consume less of the nutrient, a study published Monday suggests.

Researchers found that among 5,400 Dutch adults age 55 and older, the one-third who reported the highest vitamin E intake from food were 25 percent less likely to develop dementia, including Alzheimer's disease, over the next decade than the third with the lowest intakes.

The findings, reported in the Archives of Neurology, do not prove that vitamin E itself protects the aging brain. Studies so far have come to conflicting conclusions as to whether vitamin E or other antioxidants may influence older adults' risk of dementia.

However, the new study followed participants for a longer period than most previous studies on antioxidants and dementia. And it supports findings from some previous research that dietary vitamin E, in particular, might be related to a lower risk of dementia.

Researchers have been interested in whether antioxidants like vitamins E and C and beta-carotene might help stave off dementia because, in theory, their actions might interfere with the process of brain-cell degeneration.

Antioxidants neutralize unstable forms of oxygen called reactive oxygen species that can damage cells throughout the body. Reactive oxygen species are produced naturally in the body, as byproducts of metabolism; because the brain is an area of high metabolic activity, it is thought to be particularly vulnerable to accumulating oxidative damage over a lifetime.

However, studies so far have come to mixed conclusions as to whether older adults with a high dietary intake of various antioxidants have a lower risk of dementia. And clinical trials looking at the effects of antioxidant supplements have found no evidence that they cut Alzheimer's risk.

For the new study, researchers led by Dr. Monique Breteler, of Erasmus Medical Center in Rotterdam, used data from 5,395 adults age 55 and older who were dementia-free at the start of the study. At that point, they were interviewed about their usual diet habits, which the researchers used to estimate their intake of vitamins C and E and beta-carotene.

Over the next decade, 465 study participants were diagnosed with dementia, including 365 with Alzheimer's.

Among the one-third of men and women with the highest vitamin E intakes from food, 120 developed dementia. Of the third with the lowest intakes, 164 were diagnosed with dementia.

When Breteler's team considered a number of other factors -- including participants' age, education, weight, and smoking and drinking habits -- high vitamin E intake was linked to a one-quarter reduction in dementia risk.

The one-third of study participants with the highest vitamin E consumption typically got 18.5 milligrams (mg) per day, just over the recommended daily intake of 15 mg.

The researchers acknowledge that they cannot exclude the possibility that factors other than vitamin E explain the connection. Nor is it clear why vitamin E, but not vitamin C or beta-carotene, was linked to a lower dementia risk.

But the finding is in line with a previous study of U.S. adults that found that a higher intake of vitamin E, but not vitamin C or beta-carotene, was related to a lower risk of developing Alzheimer's over two years.

According to Breteler's team, studies should continue to look at the relationship between antioxidant intake and dementia -- including whether antioxidant consumption at different points in life might have different effects on dementia risk.

Food sources of vitamin E include wheat germ, nuts such as almonds and hazelnuts, vegetable oils such as sunflower and safflower oils, and some green vegetables, such as spinach and broccoli.

In the current study, participants' primary vitamin E sources included vegetable oils, margarine and butter.

It is unlikely that people could get too much vitamin E from food. However, high doses of vitamin E from supplements carry a risk of bleeding. Experts advise that adults consume no more than 1,000 mg of vitamin E per day.


 Archives of Neurology, July 2010.

Plasma Protein Appears to Be Associated With Development and Severity of Alzheimer's Disease



Monday, July 12, 2010


ScienceDaily (July 12, 2010) — Higher concentrations of clusterin, a protein in the blood plasma, appears to be associated with the development, severity and progression of Alzheimer's disease, according to a report in the June issue of Archives of General Psychiatry, one of the JAMA/Archives journals.


Individuals with Alzheimer's disease display several findings in their blood and cerebrospinal fluid that may reflect neuropathological changes, according to background information in the article. For instance, in cerebrospinal fluid, individuals with Alzheimer's disease have lower levels of amyloid-beta peptides and higher levels of total and phosphorylated tau concentration, which reflect the formation of hallmark plaques and tangles in the brain. Similarly, numerous articles have suggested that levels of certain metabolites and proteins in the plasma might represent responses to brain changes in Alzheimer's disease, but none have been replicated.


Madhav Thambisetty, M.D., Ph.D., of Institute of Psychiatry, King's College London, and colleagues used a combined proteomic and neuro-imaging approach to identify plasma proteins associated with Alzheimer's disease pathology. Participants in two studies -- some with Alzheimer's disease, some with its precursor mild cognitive impairment and some with no dementia -- underwent standardized clinical assessments and brain imaging scans. Their blood plasma was then assessed for proteins that may be associated with Alzheimer's disease.


Based on findings of two "discovery phase" studies in 95 patients, one protein, clusterin, appeared to be associated with atrophy of the hippocampal region of the brain and with rapid progression of cognitive decline. The researchers then studied clusterin levels in all 689 participants (including 464 with Alzheimer's disease) and found an association between higher plasma levels of the protein and severity of disease, rapid clinical progression and atrophy in the brain area known as the entorhinal cortex, which plays a role in memory. In addition, increased clusterin levels in the plasma were associated with having more amyloid-beta -- which forms the brain plaques associated with Alzheimer's disease -- in the brain's medial temporal lobe.


According to the authors, "previous studies suggest that clusterin belongs to a family of extracellular chaperones," proteins that regulate the formation and removal of amyloid. "Although these findings do not support the clinical utility of plasma clusterin concentration as a stand-alone biomarker for Alzheimer's disease, they reveal a robust peripheral signature of this amyloid chaperone protein that is responsive to key features of disease pathology."


"Our findings clearly implicate clusterin, but there may well be other proteins in plasma related to the disease process, and indeed our previous studies and those of others suggest this is the case," they conclude. "These results may have wider implications for the identification of other amyloid chaperone proteins in plasma, both as putative Alzheimer's disease biomarkers as well as drug targets of disease-modifying treatments."

Journal Reference:

Madhav Thambisetty; Andrew Simmons; Latha Velayudhan; Abdul Hye; James Campbell; Yi Zhang; Lars-Olof Wahlund; Eric Westman; Anna Kinsey; Andreas Guntert; Petroula Proitsi; John Powell; Mirsada Causevic; Richard Killick; Katie Lunnon; Steven Lynham; Martin Broadstock; Fahd Choudhry; David R. Howlett; Robert J. Williams; Sally I. Sharp; Cathy Mitchelmore; Catherine Tunnard; Rufina Leung; Catherine Foy; Darragh O'Brien; Gerome Breen; Simon J. Furney; Malcolm Ward; Iwona Kloszewska; Patrizia Mecocci; Hilkka Soininen; Magda Tsolaki; Bruno Vellas; Angela Hodges; Declan G. M. Murphy; Sue Parkins; Jill C. Richardson; Susan M. Resnick; Luigi Ferrucci; Dean F. Wong; Yun Zhou; Sebastian Muehlboeck; Alan Evans; Paul T. Francis; Christian Spenger; Simon Lovestone. Association of Plasma Clusterin Concentration With Severity, Pathology, and Progression in Alzheimer Disease. Arch Gen Psychiatry, 2010; 67 (7): 739-748 [link]

New guideline says MRI best for diagnosing stroke


Monday, July 12, 2010

WASHINGTON (Reuters) – A kind of scan called an MRI is much better for diagnosing stroke than a CT scan, the American Academy of Neurology said in new guidelines released on Monday.

Magnetic resonance imaging or MRI detected strokes 83 percent of the time, compared to just 26 percent for computed tomography or CT scans, the group advised.

"While CT scans are currently the standard test used to diagnose stroke, the Academy's guideline found that MRI scans are better at detecting ischemic stroke damage compared to CT scans," Dr. Peter Schellinger of the Johannes Wesling Clinical Center in Minden, Germany, who led the team writing the new guidelines, said in a statement.

CT scans are a specialized series of X-rays; MRI uses magnets and radio waves and both use computer programs to arrange the data into an image.

"Specific types of MRI scans can help reveal how severe some types of stroke are. These scans also may help find lesions early," Schellinger said. "This is important because the research suggests finding lesions early may lead to better health outcomes."

Most strokes are ischemic strokes, caused by a blood clot in the brain, and patients do far better when treated within about three hours. Hemorrhagic strokes are caused by bleeding in the brain and require completely different treatment.

Symptoms of a stroke can be subtle and can include sudden numbness or weakness of the face or a limb, sudden confusion, trouble speaking or walking or a sudden headache.

Stroke is the third leading cause of death in the United States, after heart disease and cancer.

The Academy is an international association of more than 22,000 neurologists and neuroscience professionals.

(Editing by Alan Elsner)

Vitamin D Levels Associated With Parkinson's Disease Risk



Monday, July 12, 2010


ScienceDaily (July 12, 2010) — Individuals with higher levels of vitamin D appear to have a reduced risk of developing Parkinson's disease, according to a report in the July issue of Archives of Neurology, one of the JAMA/Archives journals.


Vitamin D is known to play a role in bone health and may also be linked to cancer, heart disease and type 2 diabetes, according to background information in the article. "Recently, chronically inadequate vitamin D intake was proposed to play a significant role in the pathogenesis of Parkinson's disease," the authors write. "According to the suggested biological mechanism, Parkinson's disease may be caused by a continuously inadequate vitamin D status leading to a chronic loss of dopaminergic neurons in the brain."


Paul Knekt, D.P.H., and colleagues at the National Institute for Health and Welfare, Helsinki, Finland, studied 3,173 Finnish men and women age 50 to 79 who did not have Parkinson's disease at the beginning of the study, in 1978 to 1980. Participants completed questionnaires and interviews about socioeconomic and health background, underwent baseline examinations and provided blood samples for vitamin D analysis.


Over a 29-year follow-up, through 2007, 50 of the participants developed Parkinson's disease. After adjusting for potentially related factors, including physical activity and body mass index, individuals in the highest quartile (one-fourth of the study population) of serum vitamin D levels had a 67 percent lower risk of developing Parkinson's disease than those in the lowest quartile of vitamin D levels.


"Despite the overall low vitamin D levels in the study population, a dose-response relationship was found," the authors write. "This study was carried out in Finland, an area with restricted sunlight exposure, and is thus based on a population with a continuously low vitamin D status. Accordingly, the mean [average] serum vitamin D level in the present population was about 50 percent of the suggested optimal level (75 to 80 nanomoles per liter). Our findings are thus consistent with the hypothesis that chronic inadequacy of vitamin D is a risk factor for Parkinson's disease."


The exact mechanisms by which vitamin D levels may affect Parkinson's disease risk are unknown, but the nutrient has been shown to exert a protective effect on the brain through antioxidant activities, regulation of calcium levels, detoxification, modulation of the immune system and enhanced conduction of electricity through neurons, the authors note.


"In intervention trials focusing on effects of vitamin D supplements, the incidence of Parkinson disease merits follow up," they conclude.


Editorial: Findings Add to Research on Neurological Effects of Vitamin D


"The study by Knekt et al in this issue of the Archives is the first longitudinal analysis of vitamin D status as a risk of incident Parkinson's disease and examines a cohort of more than 3,000 participants from the Mini-Finland Health Survey," writes Marian Leslie Evatt, M.D., M.S., of Emory University, Atlanta, in an accompanying editorial.


"A growing body of basic research lends plausibility to a role for adequate vitamin D status protecting against development of Parkinson's disease," Dr. Evatt writes. "Knekt and colleagues' study provides the first promising human data to suggest that inadequate vitamin D status is associated with the risk of developing Parkinson's disease, but further work is needed in both basic and clinical arenas to elucidate the exact role, mechanisms and optimum concentration of vitamin D in Parkinson's disease."


"With the animal data showing a U-shaped curve for neuroprotective effects of vitamin D, it seems prudent to confirm the findings presented in this issue and investigate whether the apparent dose-response relationship observed in the current study maintains its slope, levels off or becomes negative with higher 25-hydroxyvitamin D concentrations. In the interim, data from interventional studies of fractures and falls appear to justify optimizing vitamin D levels to greater than 30 to 40 nanograms per milliliter."

Journal References:

Paul Knekt; Annamari Kilkkinen; Harri Rissanen; Jukka Marniemi; Katri Saaksjarvi; Markku Heliovaara. Serum Vitamin D and the Risk of Parkinson Disease. Arch Neurol, 2010; 67 (7): 808-811 [link]

Marian Leslie Evatt. Beyond Vitamin Status: Is There a Role for Vitamin D in Parkinson Disease? Arch Neurol, 2010; 67 (7): 795-797 [link]

Fewer Excess Pounds May Mean Fewer Hot Flashes

By Ellin Holohan
HealthDay Reporter
HealthDay News

Monday, July 12, 2010

MONDAY, July 12 (HealthDay News) -- Weight loss might help middle-aged women who are overweight or obese reduce bothersome hot flashes accompanying menopause, according to a new study.

"We've known for some time that obesity affects hot flashes, but we didn't know if losing weight would have any effect," said Dr. Alison Huang, the study's author. "Now there is good evidence losing weight can reduce hot flashes."

Study participants were part of an intensive lifestyle-intervention program designed to help them lose between 7 percent and 9 percent of their weight.

Huang, assistant professor of obstetrics and gynecology at the University of California, San Francisco, said the findings could provide women with another reason to take control of their weight. "The message here is that there is something you can do about it (hot flashes)," said Huang.

About one third of women experience hot flashes for five years or more past menopause, "disrupting sleep, interfering with work and leisure activities, and exacerbating anxiety and depression," according to the study.

The women in the study group met with experts in nutrition, exercise and behavior weekly for an hour and were encouraged to exercise at least 200 minutes a week and reduce caloric intake to 1,200-1,500 calories per day. They also got help planning menus and choosing what kinds of foods to eat.

Women in a control group received monthly group education classes for the first four months.

Participants, including those in the control group, were asked to respond to a survey at the beginning of the study and six months later to describe how bothersome hot flashes were for them in the past month on a five-point scale with answers ranging from "not at all" to "extremely."

They were also asked about their daily exercise, caloric intake, and mental and physical functioning using instruments widely accepted in the medical field, said Huang. No correlation was found between any of these and a reduction in hot flashes, but "reduction in weight, body mass index (BMI), and abdominal circumference were each associated with improvements" in reducing hot flashes, according to the study, published in the July 12 issue of Archives of Internal Medicine.

Huang said that caloric intake and exercise were measured by the participants, who were not always accurate, but "weight can be measured by stepping on scale," so weight loss is a "more accurate measure" of what happened.

About 340 study participants, at least 30 years old, were recruited from a larger study of overweight and obese middle-aged women suffering from incontinence. They were not told the study was examining the effect of weight loss on hot flashes.

At the study's start, about half of both the study and control groups reported having hot flashes; about half of these were at least moderately bothered, and 8.4 percent were extremely bothered.

By six months, 49 percent in the study group, compared with 41 percent in the control group, reported improvement by "at least one category of bothersomeness."

That might not seem like a big difference. But Huang added that, "although 41 percent of women in the control group experienced improvement in hot flashes, quite of few of them experienced improvement by only one category of 'bothersomeness' (as opposed to two categories). Also, of those women in the control group who did not experience improvement, relatively more of them experienced actual worsening of hot flashes (as opposed to no change)."

Dr. Elizabeth Poynor, an obstetrician-gynecologist affiliated with Lenox Hill Hospital, said the study findings are "good news."

"I think this study provides a ground work to look at it (hot flashes) in larger, more detailed and comprehensive studies," said Poynor. "It's very promising," she added.

Poynor said the study provides an impetus to women who need to lose weight for other health reasons, such as diabetes or heart disease, because it can reduce problems like sleep disturbance that can lead to problems with concentration and poor functioning in general.

"It can really help to have a very significant altered quality of life," said Poynor, noting that the physiology of hot flashes, "at least in part a vascular event," is poorly understood and needs more study.

"However, this study provides women and their health care professionals who care for them another intervention to help with bothersome hot flashes in women who are overweight."

More information

The U.S. National Women's Health Information Center has more on menopause.

Arsenic Shows Promise as Cancer Treatment, Study Finds


HealthDay News

Monday, July 12, 2010


ScienceDaily (July 12, 2010) — Miss Marple notwithstanding, arsenic might not be many people's favorite chemical. But the notorious poison does have some medical applications. Specifically, a form called arsenic trioxide has been used as a therapy for a particular type of leukemia for more than 10 years. Now researchers at the Stanford University School of Medicine have shown that it may be useful in treating a variety of other cancers.


Combining arsenic with other therapies may give doctors a two-pronged approach to beating back forms of the disease caused by a malfunction in a critical cellular signaling cascade called the Hedgehog pathway. The U.S. Food and Drug Administration has already approved arsenic trioxide for use in humans, which could pave the way for clinical trials of this approach.


"Many pharmaceutical companies are developing anticancer drugs to inhibit the Hedgehog pathway," said Philip Beachy, PhD, professor of developmental biology and the Ernest and Amelia Gallo Professor in the School of Medicine. In addition, Beachy recently identified an antifungal drug commonly used in humans, itraconazole, as a Hedgehog pathway inhibitor. "However, these compounds target a component of the pathway that can be mutated with patients then becoming resistant to the therapy. Arsenic blocks a different step of the cascade."


Beachy is the senior author of the new findings about arsenic, which will be published online in the Proceedings of the National Academy of Sciences July 12. Jynho Kim, DVM, PhD, a postdoctoral scholar in Beachy's lab, is the first author of the study.


The mechanism of action described by the researchers in the current paper differs from what happens during arsenic poisoning, which occurs when higher levels of the compound choke off a cell's energy production system.


Beachy and his colleagues studied the effect of arsenic trioxide in cultured human and mouse cells and in laboratory mice with a brain tumor known as medulloblastoma. (The Hedgehog pathway is known to be overly active in this and other tumors in the skin, brain, blood and muscle.) They found that relatively low levels of the compound, equivalent to those approved for use in treating patients with acute promyelocytic leukemia, block one of the last steps of the Hedgehog pathway; it prevents the expression of a select few of the cell's genes in response to external messages. Because only the tail end of the pathway is affected, a cancer cell has fewer opportunities to mutate and sidestep arsenic's inhibitory effect.


In contrast, another Hedgehog pathway inhibitor called cyclopamine acts near the beginning of the signaling cascade. Cyclopamine, a plant-derived molecule identified as a Hedgehog pathway inhibitor by Beachy in 1998, binds to a protein on the surface of the cell called Smoothened and blocks its ability to transmit the Hedgehog signal to the cell's innards. Drugs mimicking cyclopamine's action are currently being developed for human use. However, the ability of these drugs to disrupt the Hedgehog pathway early on may be lessened by mutations in Smoothened that allow the cascade to get around this initial treatment.


Beachy and Kim became curious as to whether and how arsenic worked to interfere with the signaling cascade as a result of observations that birth defects caused by arsenic exposure resemble the physical effects of having an inactive Hedgehog pathway. They studied human cells in culture and discovered that levels of arsenic trioxide similar to those currently used in patients with acute promyelocytic leukemia inhibit the Hedgehog pathway.


Specifically, the researchers found that arsenic trioxide blocks the ability of a protein called Gli2 to induce gene transcription in the nucleus. It works by stopping Gli2 from moving into the cell's primary cilium, a communication hub, where many of the events of Hedgehog signaling take place. Without Gli2 in the cilium, the Hedgehog message comes to an abrupt, and fruitless, dead end. This occurs even in cells known to be resistant to cyclopamine treatment.


To find out what this might mean for cancer cells, they studied mice with a type of brain tumor known to be dependent on Hedgehog signaling. Treating the mice with arsenic trioxide slowed or stopped tumor growth. They also found that combining arsenic trioxide with cyclopamine was even more effective in blocking the pathway in cultured cells.


"Arsenic might be especially effective for treating some types of cancers in combination with other drugs that act at different levels of the Hedgehog pathway, such as the cyclopamine mimics that pharmaceutical companies are developing, or itraconazole, an approved drug that we have recently shown also acts at the level of Smoothened," said Beachy, who is also a member of the Stanford Cancer Center and the Stanford Institute for Stem Cell Biology and Regenerative Medicine, as well as a Howard Hughes Medical Institute investigator.


In addition to Beachy and Kim, other Stanford researchers involved in the study include postdoctoral scholars John Lee, MD, PhD, and James Kim, MD, PhD. The research was funded by the Stanford Center for Children's Brain Tumors, the Howard Hughes Medical Institute and the National Institutes of Health.

Journal Reference:

Jynho Kim, John J. Lee, James Kim, Dale Gardner, and Philip A. Beachy. Arsenic antagonizes the Hedgehog pathway by preventing ciliary accumulation and reducing stability of the Gli2 transcriptional effector. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.1006822107