Italian postmenopausal women who have a low calcium intake show a higher risk of developing both osteoporosis and hypertension (a chronic medical condition in which arterial blood pressure is elevated) than those who consume higher levels of calcium according to research presented today at EULAR 2010, the Annual Congress of the European League Against Rheumatism in Rome, Italy.

In this Italian study of 825 postmenopausal women with hypertension, a significantly increased proportion of women (35.4%) who consumed a lower amount of calcium through intake from dairy sources, had a concurrent diagnosis of both hypertension and osteoporosis, compared with women who consumed a higher amount of calcium (19.3% p<0.001).

Further statistical analyses revealed that a lower calcium intake was associated with an increased risk of developing hypertension or osteoporosis over time when compared with controls (Odds Ratio (OR) hypertension: 1.43; 95%CI: 1.12-1.82, osteoporosis: OR 1.46; CI: 1.15-1.85). Women who consumed a lower amount of calcium were shown to be most likely to develop both conditions over time compared with women consuming a higher amount of calcium (OR 1.60; CI: 1.09-2.34).

“Our study confirms that there may be a link between hypertension and low bone mass and that a low calcium intake could be a risk factor for the development of osteoporosis in postmenopausal women” said Professor Maria Manara, Department of Rheumatology, Gaetano Pini Institute, Milan, Italy, and lead author of the study. “Our study has also shown that a low calcium intake from dairy foods may be involved in this association and could be considered a risk factor for the development of hypertension and osteoporosis.”

The 825 subjects involved in the study were recruited from a cohort of 9,898 postmenopausal women referred to the Osteometabolic unit of the Gaetano Pini Institute in Italy, from 2002. Calcium intake from dairy sources was assessed by the number of standard servings of ~300mg calcium consumed by women in a week and subjects were stratified into ‘quartiles'(lower 25%, median 50% and upper 25%). For each case, three controls were selected and matched for age. Women who had been treated with diuretics (drugs known to affect the generation of new bone material) were excluded from the study.

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• European League Against Rheumatism

Studies suggest role for IL-10 in prevention and treatment of potentially devastating neurological disease in newborns

This bacterium, Escherichia coli K1, is the most common cause of meningitis in premature infants and the second most common cause of the disease in newborns. “The ineffectiveness of antibiotics in treating newborns with meningitis and the emergence of antibiotic-resistant strains of bacteria require new strategies,” explains Nemani V. Prasadarao, PhD, associate professor of infectious disease at Childrens Hospital Los Angeles.

Meningitis is the irritation of membranes covering the brain and spinal cord. This irritation can result from viral or bacterial infection. Bacterial meningitis can be very serious, possibly resulting in hearing loss, brain damage, or death, even when treated. Although the mortality rate can be decreased through use of antibiotics significant neurological consequences, like mental retardation, still occur in 30 to 40 percent of survivors.

“A recent surge in antibiotic-resistant strains of E. coli K1 is likely to significantly increase the rates of illness and death,” said Prasadarao. “Also, the diagnosis of meningitis is difficult until the bacteria reach the cerebrospinal fluid. By that time, brain damage has begun. With large numbers of circulating bacteria, treatment with antibiotics can result in biochemical reactions that may cause septic shock and ultimately, organ failure. So identifying alternatives to antibiotic therapy is crucial.”

One of a class of proteins known as cytokines, IL-10 is involved in immune function. “We found that during an episode of bacteremia, when a large number of bacteria are circulating in normally sterile blood, IL-10 acts to clear antibiotic-sensitive as well as antibiotic-resistant E. coli from the circulation of infected mice,” said Rahul Mittal, Ph.D., lead author on the paper and a post-doctoral fellow in Prasadarao’s lab.

They also determined that E. coli infection produced damage to the mouse brain comparable to that seen in humans. Three-dimensional imaging studies of infected animal and human infant brains showed similar gross morphological changes. “When we gave IL-10 to mice 48 hours after infection, those changes to the brain were reversed,” said Mittal.

Tumor necrosis factor (TNF) is a cytokine active in producing inflammation. When the researchers replicated these experiments using antibiotic or anti-TNF, brain damage resulting from E. coli infection was not prevented.

The team also discovered a mechanism of action for IL-10 protection. In culture, using mouse and human white blood cells called neutrophils, they found that exposing these cells to IL-10 produced an increase in the number of a certain type of receptor on the surface of the neutrophils. An increase in the CR 3 receptor led to enhanced killing of bacteria.

Another white blood cell, called a macrophage, works to clear bacteria from the blood by engulfing or “eating” the pathogen. Similar to what was seen in neutrophils, macrophages treated with IL-10 showed an increase in CR 3 receptors that enhanced their ability to destroy invading bacteria.

To confirm that the CR 3 receptor is critical to the protective effect of IL-10 against E. coli, CR 3 expression was suppressed in a group of mice. Before exposing the animals to bacteria, white blood cells were examined and the CR 3 receptor was determined to be absent. These animals were exposed to E. coli and then treated with IL-10. The mice were found subsequently to have bacteria in the CSF and morphological changes indicating brain damage. The protective effect of IL-10 during bacteremia was absent in animals without CR 3 receptors. The researchers further concluded that the crucial increase in CR 3 receptors was a result of IL-10 suppressing an important inflammatory agent, prostaglandin E-2.

“Since diagnosing meningitis is difficult until bacteria reach the central nervous system, finding an agent that can clear the bacteria while also preventing or restoring the damaged brain is very exciting,” said Mittal.

These studies provide a basis for exploring the use of IL-10 in newborns.

Co-authoring the paper published in the Journal of Experimental Medicine (May 24, 2010) are Rahul Mittal and Kerstin Goth, of Childrens Hospital Los Angeles, Ignacio Gonzalez-Gomez, Ashok Panigrahy, and Nemani V. Prasadarao, of Childrens Hospital Los Angeles and the Keck School of Medicine of USC , Los Angeles, and Richard Bonnet, Universite Auvergne, France.

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On the Net:

• Children’s Hospital Los Angeles
• Journal of Experimental Medicine

Researchers conducting a lunch-buffet study involving more than 200 kids between the ages of 8 and 17 found that boys routinely eat more compared to girls of the same age.

The researchers also found that boys in their mid-teens were the most ravenous, downing an average of 2,000 calories during the lunch hour.

Senior researcher Dr. Jack A. Yanovski, of the U.S. National Institute of Child Health and Human Development, says the pattern makes sense, given that boys usually hit their growth spurt in late puberty, putting on height and muscle mass.

Although teenage boys are known for packing away food, there really has not been any real evidence showing this as normal. “There’s a lot of folk wisdom that says boys can eat prodigious amounts, but we haven’t had much data,” Yanovski told Reuters Health.

For the study, Yanovski and his colleagues had 204 boys and girls 8 to 17 years old come to a lunch buffet on two separate days. The first day, researchers told the kids to eat as much as they normally would during lunch. On the second day, they were instructed to eat as much as they wanted.

The researchers found that boys ate more than girls at each stage of puberty. The same was true for prepubescent kids, with boys averaging nearly 1,300 lunchtime calories, compared to 900 among girls.

The biggest increase in appetite for girls came during early- to mid-puberty, between the ages of 10 and 13. Girls consumed an average of 1,300 lunchtime calories, but that figure was only slightly higher among girls in late puberty.

Yanovski said that pattern is in line with girls’ development, as they tend to have their most significant growth spurts in early- to mid-puberty.

Boys, however, tend to develop later; and their calorie needs appear to shoot up drastically in late puberty — between the ages of 14 and 17.

Boys showed little change in calorie intake between pre- and mid-puberty. But those going through late puberty had an intake of as much as 2,000 lunchtime calories. Even for active children, those 2,000 calories would be most of their daily energy needs.

Yanovski said that parents of teenage sons should not worry about a sudden surge in eating by their kids, as long as they are healthy and at normal weight.

However, he added, boys who are overweight should have more limits on how many calories they are taking in. Studies suggest that a majority of overweight children become overweight, or obese, adults.

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On the Net:

• National Institute of Child Health and Human Development
• American Journal of Clinical Nutrition

Scientists have long known that certain types of bacteria boost the immune system. Now, Loyola University Health System researchers have discovered how bacteria perform this essential task.

Senior author Katherine L. Knight, PhD. and colleagues report their discovery in a featured article in the June 15, 2010, issue of the Journal of Immunology, now available online. Knight is professor and chair of the Department of Microbiology and Immunology at Loyola University Chicago Stritch School of Medicine.

The human body is teeming with bacteria. In each person, there are about 10 times as many bacterial cells as human cells. Bacteria live on skin, in the respiratory tract and throughout the digestive tract. The digestive tract alone is home to between 500 and 1,000 bacterial species.

While some bacteria cause infections, most species are harmless or perform beneficial functions, such as aiding digestion. These beneficial bugs are called commensal bacteria. One of the most important functions of commensal bacteria is boosting the immune system. Studies by other researchers have found that mice raised in sterile, germ-free environments have poorly developed immune systems. But until now, scientists have not known the mechanism by which bacteria help the immune system.

Knight’s lab studied the spores from rod-shaped bacteria called Bacillus, found in the digestive tract. (A spore consists of the DNA of a bacterium, encased in a shell. Bacteria form spores during times of stress, and re-emerge when conditions improve.) Researchers found that when they exposed immune system cells called B lymphocytes to bacterial spores, the B cells began dividing and reproducing.

Researchers further found that molecules on the surfaces of the spores bound to molecules on the surfaces of B cells. This binding is what activated the B cells to divide and multiply. B cells are one of the key components of the immune system. They produce antibodies that fight harmful viruses and bacteria.

The findings suggest the possibility that some day, bacterial spores could be used to treat people with weakened or undeveloped immune systems, such as newborns, the elderly and patients undergoing bone marrow transplants. In cancer patients, bacterial spores perhaps could boost the immune system to fight tumors. However, Knight cautioned that it would take years of research and clinical trials to prove whether such treatments were safe and effective.

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On the Net:

• Loyola University Health System
• Journal of Immunology

Consuming more white rice appears to be associated with a higher risk for developing type 2 diabetes, whereas consuming more brown rice may be associated with a lower risk for the disease, according to a report in the June 14 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

“Rice has been a staple food in Asian countries for centuries,” the authors write as background information in the article. “By the 20th century, the advance of grain-processing technology made large-scale production of refined grains possible. Through refining processes, the outer bran and germ portions of intact rice grains (i.e., brown rice) are removed to produce white rice that primarily consists of starchy endosperm.” U.S. rice consumption is lower than that in Asian countries but is increasing rapidly, and more than 70 percent of the rice consumed is white.

Qi Sun, M.D., Sc.D., of Harvard School of Public Health, Boston, and colleagues assessed rice consumption and diabetes risk among 39,765 men and 157,463 women in three large studies: the Health Professionals Follow-Up Study and the Nurses’ Health Study I and II.

After adjusting for age and other lifestyle and dietary risk factors, those who consumed five or more servings of white rice per week had a 17 percent increased risk of diabetes compared with those who consumed less than one serving per month. In contrast, eating two or more servings of brown rice per week was associated with an 11 percent reduced risk of developing type 2 diabetes than eating less than one serving per month.

Based on the results, the researchers estimated that replacing 50 grams (equivalent to one-third of a serving) of white rice per day with the same amount of brown rice would be associated with a 16 percent lower risk of type 2 diabetes. Replacing white rice with whole grains as a group could be associated with a risk reduction as great as 36 percent.

In general, white rice has a higher glycemic index””a measure of how much a food raises blood glucose levels compared with the same amount of glucose or white bread””than brown rice, the authors note. “The high glycemic index of white rice consumption is likely the consequence of disrupting the physical and botanical structure of rice grains during the refining process, in which almost all the bran and some of the germ are removed,” they write. “The other consequence of the refining process includes loss of fiber, vitamins, magnesium and other minerals, lignans, phytoestrogens and phytic acid, many of which may be protective factors for diabetes risk.”

The current Dietary Guidelines for Americans recommend that at least half of carbohydrate intake come from whole grains. “From a public health point of view, replacing refined grains such as white rice by whole grains, including brown rice, should be recommended to facilitate the prevention of type 2 diabetes,” the authors conclude.

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On the Net:

• JAMA and Archives Journals
• Archives of Internal Medicine

By investigating the association between genetic loci related to Alzheimer’s disease and neuroimaging measures related to disease risk, researchers may have uncovered additional evidence that several previously studied genetic variants are associated with the development and progression of Alzheimer’s disease and also may have identified new genetic risk factors for further study, according to a report in the June issue of Archives of Neurology, one of the JAMA/Archives journals.

“The mechanisms underlying Alzheimer’s disease onset and progression remain largely unexplained,” the authors write as background information in the article. Twin studies have suggested that the condition is 60 percent to 80 percent heritable. Until recently, only one genetic variant””known as APOE””was shown to influence Alzheimer’s disease risk and age at onset. However, new findings from genome-wide association studies have identified three additional loci (specific locations of genetic variants on chromosomes) that confer risk of Alzheimer’s disease.

Neuroimaging measures””including the volume of hippocampus, amygdala and other brain structures””also correlate with the risk and progression of Alzheimer’s disease. “The demonstration that recently discovered genetic risk factors for Alzheimer’s disease also influence these neuroimaging traits would provide important confirmation of a role for these genetic variants and suggest mechanisms through which they might be acting,” the authors write.

Alessandro Biffi, M.D., and Christopher D. Anderson, M.D., of Massachusetts General Hospital, Boston, and Broad Institute, Cambridge, Mass., and colleagues studied the associations between genes and neuroimaging results among 168 individuals with probable Alzheimer’s disease, 357 with mild cognitive impairment (a precursor to Alzheimer’s disease) and 215 who were cognitively normal.

The four loci previously associated with Alzheimer’s disease were assessed, along with six neuroimaging traits linked to Alzheimer’s disease. The APOE gene had the strongest association with clinical Alzheimer’s disease, and was associated with all the neuroimaging traits except one. The other candidate genes showed a significant cumulative effect on the neuroimaging measures analyzed.

“Our results indicate that APOE and other previously validated loci for Alzheimer’s disease affect clinical diagnosis of Alzheimer’s disease and neuroimaging measures associated with disease,” the authors write. “These findings suggest that sequence variants that modulate Alzheimer’s disease risk in recent genome-wide association studies may act through their influence on neuroimaging measures.”

In addition, the genetic analysis of neuroimaging traits identified two new target gene locations””BIN1 and CNTN5″”of heightened interest for their relationship with Alzheimer’s disease. “Although our results for these loci can only be considered preliminary, they may help prioritize targets for future genetic studies and genome-wide association studies in Alzheimer’s disease, particularly given their association with neuroimaging correlates of Alzheimer’s disease and disease status,” the authors write. They add that independent evidence for an association between the BIN1 gene location and Alzheimer’s disease emerged in a recent meta-analysis.

(Arch Neurol. 2010;67[6]:677-685. Available pre-embargo to the media at www.jamamedia.org.)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Findings Herald New Era of Genetic Studies

“While we have understood the bases for mendelian, early-onset Alzheimer’s disease for nearly two decades, elucidation of the genetic risks for late-onset disease beyond the apolipoprotein E locus, discovered in 1993, had been painfully slow until last year,” write John Hardy, Ph.D., of University College London Institute of Neurology, and Julie Williams, Ph.D., of the Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff, Wales, in an accompanying editorial.

“With the benefit of hindsight, we now have some indication of why no other risk loci were found during this period; simply, there are no other loci with similar effect sizes to apolipoprotein E to be found. Now, however, with the advent of whole-genome associations, we are beginning to find the weaker risk loci for the disease.”

“These findings, and the genome-wide studies that presaged them, mark a new period of optimism for those of us who study the etiologies of complex diseases of the nervous system,” Drs. Hardy and Williams write. “While the drought of genetic findings in Alzheimer’s disease has lasted a long time, the flood of new findings have been a reward worth waiting for.”

(Arch Neurol. 2010;67[6]:663-664. Available pre-embargo to the media at www.jamamedia.org.)

Editor’s Note: Please see the article for additional information, including author contributions and affiliations, financial disclosures, funding and support, etc.

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On the Net:

• JAMA and Archives Journals
• Archives of Neurology

The Liver Center at Baylor College of Medicine, already renowned for having the highest liver transplant survival rate in Texas among high-volume programs, has something new to celebrate. Dr. John Goss, professor of surgery in the Michael E. DeBakey Department of Surgery at BCM, has performed his 1,000th liver transplant since joining the BCM faculty.

This milestone was reached on June 7 at St. Luke’s Episcopal Hospital.

Goss is director of liver transplant programs at St. Luke’s, Texas Children’s Hospital and the Michael E. DeBakey VA Medical Center. He performed these life-saving operations at these institutions and at The Methodist Hospital over the past 12 years with the support of his team of surgeons, nurses, hepatologists, medical specialists, and support staff.

“Liver transplantation provides the sole chance for survival for children and adults devastated by liver diseases. We are all grateful that the organ families have graciously donated to make this operation possible. The donors and our patients are our heroes,” said Goss, who is also the chief of the division of abdominal transplantation and hepatobiliary surgery at BCM.

The survival rate is more than 95 percent for the BCM liver transplant program. It is the No. 1 program in Texas among programs performing more than 35 transplants yearly.

“The Baylor liver transplant program is an outstanding success,” said Dr. Stephen Spann, senior vice president and dean of clinical affairs at BCM. “Dr. Goss, Dr. Stribling and their team have a commitment to excellence that is evident in their success and the life-saving care they have given to hundreds of patients. Liver transplant patients at Texas Children’s Hospital, the DeBakey VA and St. Luke’s have benefited from the comprehensive team approach that they have championed.”

Goss and Dr. Risë Stribling, associate professor of surgery at BCM and medical director of the St. Luke’s Liver Transplant and VA Medical Center Programs, co-founded the The Liver Center at BCM to provide comprehensive care for all patients with liver diseases.

“Our team of hepatologists, radiologists, oncologists, pathologists and medical consultants collaborate with our surgeons to provide advanced medical and surgical care based on the latest research and technologies,” said Stribling.

Goss and Stribling both credit their UCLA mentor, Dr. Ronald Busuttil, with motivating them to pursue a collaborative approach to improving the care of all patients with liver diseases and the survival of those undergoing liver transplantation.

“I congratulate Drs. Goss and Stribling on this landmark achievement of performing 1,000 liver transplants. One cannot underestimate the skill, dedication and selfless sacrifices that are required to save so many lives. They and their team should feel a great sense of pride on this momentous occasion,” said Dr. Busuttil, professor and executive chairman of the department of surgery at the David Geffen School of Medicine at UCLA in Los Angeles.

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On the Net:

• BCM

Care in first 6 months post stroke soars to more than $2.5 billion annually

Health-care costs for patients in just the first six months after they have a stroke is more than $2.5 billion a year in Canada, according to a study presented today at the Canadian Stroke Congress.

The Canadian Stroke Network’s Burden of Ischemic Stroke (BURST) study found that the direct and indirect health-care costs for new stroke patients tally an average $50,000 in the six-month period following a new stroke. There are about 50,000 new strokes in Canada each year.

Earlier and widely quoted estimates, based on the most recent data from Health Canada’s Economic Burden of Illness (1998), indicated that the total cost of stroke in Canada was $2.4 billion a year for both new stroke patients and long-term survivors. There are 300,000 people living with stroke in Canada.

“Our old estimates of how much stroke costs the economy are way off base,” says Dr. Mike Sharma, who together with Dr. Nicole Mittmann of Sunnybrook Health Sciences Centre, led the BURST study, which is the first prospective national economic analysis on stroke costs.

“The cost of stroke is far more than we expected ““ at least double previous estimates.”

BURST researchers examined the health-care costs of 232 hospitalized stroke patients in 12 sites across Canada at discharge, three months, six months, and one year. The study looked at both disabling and non-disabling stroke.

Hospitalization, medication, physician services, diagnostic imaging, homecare and rehabilitation all contribute to the bill. There are also indirect costs, including disability leave, lost wages, assisted devices, caregivers, and out-of-pocket expenses for families such as personal assistance products or changes to homes to accommodate disabilities.

While costs are much higher than expected, “the idea is to make initial investments in prevention and acute treatment to prevent these costs down the road,” says Dr. Sharma.

For example, health-care costs fall sharply when people get access to the clot-busting drug tPA, which can significantly reduce post-stroke disability, as well as treatment in a specialized stroke unit.

Prevention is the biggest factor in reducing health-care spending overall, Dr. Sharma says. If people maintain a healthy blood pressure, maintain a healthy weight, reduce sodium intake, and exercise, the impact on stroke costs would be dramatic.

While at least 80 per cent of costs during the first six months post-stroke are health-system costs, families take on a greater proportion of stroke-related expenses, including those associated with caregiving, transportation, and lost income, beginning at the seventh month post-stroke and beyond.

Costs rise dramatically as levels of disability increase. People with non-disabling strokes ““ about 25 per cent of patients ““ personally expended about $2,000 in costs during the first six months. The costs for families increased from there to as much as $200,000 for the most severely affected.

“The difference between merely having symptoms to requiring even minimal at-home assistance from others can mean a significant cost difference,” says Dr. Sharma. “The need to have someone drive you around and help with shopping can double personal costs ““ as well as costs incurred by the person helping you.”

Dr. Sharma, who is director of the Ottawa Hospital’s regional stroke program, says that personal costs for stroke survivors continue through their lifetimes. “It’s a burden on individuals, their families, and communities.”

“A stroke doesn’t just affect one person ∴ it has a ripple effect,” says Heart and Stroke Foundation spokesperson Dr. Michael Hill. “It can challenge families, overburden caregivers, and have a tremendous toll on our healthcare system.”

Stroke is the third leading cause of death and a leading cause of disability. The situation may get worse, with aging baby boomers entering their at-risk years.

In 2011 the baby boom generation will enter the period of increasing risk for stroke. “After age 55, the stroke risk doubles every 10 years,” says Dr. Hill. “This will increase the strain on our healthcare services.”

Over the next two decades, the number of Canadians who are age 65 and over will grow from roughly 4.3 million today to 8 million. Their share of the population will rise from about 13 per cent today to more than 20 per cent, says Dr. Hill.

“We have to learn ∴ and learn fast ∴ how to respond to this situation,” says Dr. Antoine Hakim, Canadian Stroke Network spokesperson.

Coordination is key. “Our objective for the study was to identify the cost drivers so decision makers can make informed choices,” Dr. Sharma says.

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On the Net:

• Heart and Stroke Foundation of Canada

Growing body of data suggests Chronix’s serum DNA assays may represent a new approach to diagnostics and prognostics in cancer and other diseases

Chronix Biomedical today reported new data further demonstrating that its serum DNA blood tests have the potential to accurately detect early stage breast cancer and prostate cancer. Chronix’s proprietary technology identifies disease-specific genetic fingerprints based on circulating DNA fragments that are released into the bloodstream by damaged and dying (apoptotic) cells. In this new study of 575 individuals, Chronix’s proprietary assays detected and identified DNA fingerprints in the blood that indicated the presence of prostate cancer and breast cancer with 92% sensitivity and 100% specificity, significantly outperforming the published accuracy data for current diagnostic methods. The new study results were presented in an oral session today at the 2010 ASCO Annual Meeting in Chicago.

Breast cancer expert, Steven Narod, M.D., F.R.C.P.C., noted, “These new data, although early, provide further evidence that Chronix’s proprietary serum DNA assays may represent a new diagnostic and prognostic platform that can identify cancer earlier and more accurately than is currently possible. I am pleased to be working with Chronix to further validate these promising findings.” Dr. Narod is Director of the Familial Breast Cancer Research Unit at Women’s College Research Institute, an affiliate of the University of Toronto.

The tests use proprietary algorithms developed by Chronix researchers to detect, analyze and identify cancer-related fragments of circulating DNA that are released into the bloodstream by apoptotic cells. Chronix researchers consistently find that this apoptotic DNA in the serum is coming from a limited number of regions or “hotspots” on the genome specific to each cancer. According to the data presented today, DNA fragments from any one of the 29 breast cancer “hotspots” and 32 prostate cancer “hotspots” identified by Chronix researchers indicate that cancer is present.

“By focusing on these blood-borne genomic ‘hotspots,’ we can reliably detect the presence of cancer without having to first isolate or analyze the tumor cells,” said Howard Urnovitz, Ph.D., Chief Executive Officer of Chronix and a co-author of the study. “If verified by further studies, our Chronix blood-based assays would make it possible to diagnose cancer at its earliest stages, track progress as patients undergo treatment and possibly even optimize treatment using patients’ disease-specific genomic fingerprints.”

The testing involved 575 individuals: 178 with early stage breast cancer, 197 with invasive prostate cancer and 200 healthy controls. The Chronix assays detected breast cancer with a 92% sensitivity and 100% specificity. Although not directly comparable, for reference it is noteworthy that data from a large study of U.S. mammography screening programs reported an overall sensitivity of just 75%, and specificity of 92.3%, with lower figures for some populations such as younger women. The Chronix assays also detected invasive prostate cancer with a 92% sensitivity and 100% specificity. In contrast, the widely used PSA (prostate specific antigen) test has previously demonstrated 85% sensitivity and a specificity of just 25% to 35%. If the Chronix data are confirmed in larger studies, they have the potential to reduce the current rate of false positive and false negative results that contribute to poorer patient outcomes and higher health care costs.

Previous published studies have demonstrated that the Chronix approach can identify the presence or absence of active disease in multiple sclerosis patients and that it can accurately detect early stage breast cancer with high diagnostic sensitivity and specificity. Commercial applications for veterinary use are already in development in conjunction with the University of Calgary, including tests for the early detection of BSE, or mad cow disease.

Dr. Urnovitz added, “With these encouraging findings, we are launching a ‘For Investigative Use Only’ testing service that for the first time will enable cancer researchers to monitor the status of patients in their clinical trials with a high level of sensitivity and specificity, potentially accelerating clinical trials and increasing their chances for success.”

Patient data collected from this new service for clinical researchers along with additional planned clinical studies are expected to expand the database needed to obtain regulatory approval for the use of Chronix assays in ongoing cancer patient care.

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• BioCom Partners

Adult daughters caring for a parent recovering from stroke are more prone to depression than sons, Marina Bastawrous today told the Canadian Stroke Congress, co-hosted by the Canadian Stroke Network, the Heart and Stroke Foundation, and the Canadian Stroke Consortium.

Caring for a parent who has experienced a stroke results in a dramatic shift from the usual parent-child relationship. “Stroke can be particularly challenging for families,” says Bastawrous, a masters candidate at the University of Toronto. “Taking care of elderly parents can bring out family strengths and family weaknesses.”

The adult child-to-parent bond can result in excellent care when a senior has a stroke. But not always, she says.

The study found that close and secure relationships with parents predicted better mental health and greater satisfaction in adult child caregivers.

“But strained relationships before or following the stroke increases depression in daughters,” she says. “If the relationship between a parent and adult daughter is already strained, a stroke can make things even worse.”

The quality of relationships both before and after the stroke had an equally important influence on wellbeing.

The study found that adult daughters placed greater importance on family relationships than sons and, in turn, were more negatively impacted by poor relationships with their parent.

“When a parent has a stroke, adult children often become their primary caregivers,” says Heart and Stroke Foundation spokesperson Dr. Michael Hill. “It’s important that as part of the recovery process we examine their experiences because they are obviously vital to the ongoing care of the stroke patient.”

Sandwich generation spread too thin

Study co-author Dr. Jill Cameron says adult children providing stroke care for their parents need help and they need it now.

“Adult children are stroke care’s forgotten generation,” she says. “We can’t afford to leave them behind.”

Sixty two percent of stroke caregivers are adult children. Yet stroke care interventions are overwhelmingly designed for spouses.

This imbalance must be addressed, says Dr. Cameron. “We need to make better use of financial resources to enhance the support provided to this growing population of caregivers.”

She notes that adult children caregivers need to balance the challenges of professional life, family life, and the added responsibility of taking on the care of somebody post-stroke. “Caregivers need more support,” she says. “They aren’t trained but their role is essential.”

To remove some of the strain ̢蠫 financial and emotional ̢蠫 innovative thinking is required.

“Our healthcare system is not sustainable in the face of rising costs,” says Dr. Cameron. “We need to plan.”

Here’s what Dr. Cameron envisions as part of this plan:

    * Create work environments that support family members caring for stroke survivors (e.g., caregiving leave).
    * Recognizing that family members perform many caregiving duties after the stroke survivor returns home but receive little if any training; hospitals must train family members for their caregiving role.
    * To ensure post-hospital care plans incorporate the unique circumstances of the family, caregivers should be recognized as members of the care team. “Family caregivers are critical to stroke recovery and typically assume major care roles that are frequently costly to their financial, social, and emotional well-being,” says Dr. Antoine Hakim, spokesperson for the Canadian Stroke Network. “Innovative new ideas to support their balance and quality of life is essential.”

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On the Net:

• Heart and Stroke Foundation of Canada

MD Anderson-led Phase III clinical study determines Sprycel superior to Gleevec as front-line therapy

Dasatanib, a medication currently approved as treatment for drug-resistant chronic myeloid leukemia (CML), provided patients with quicker, better responses as a first therapy than the existing front-line drug, according to researchers at The University of Texas MD Anderson Cancer Center.

The findings were presented at the 46th Annual Meeting of the American Society of Clinical Oncology June 5, and published in the New England Journal of Medicine. Hagop Kantarjian, M.D., professor and chair of MD Anderson’s Department of Leukemia, presented the findings and is the corresponding author on the published study.

Currently, imatinib, or Gleevec ®, is the approved initial therapy for CML, which has increased the five-year survival rate for the disease from 50 percent to 90 percent, said Kantarjian. However, 30-40 percent of imatinib patients do not achieve confirmed cytogenic complete response (CCyR), or the absence of the defective chromosome that causes the disease, within a year. This benchmark is clearly associated with improvements in long-term outcome, said Kantarjian.

“Previous research conducted at MD Anderson found that more patients taking dasatinib were achieving complete responses more quickly than they do on the current standard of care,” said Kantarjian. “In this pivotal Phase III study, we confirmed that dasatinib gets more patients to high-quality remission faster than imatinib, making it a superior front-line therapy. Dasatinib, on average, also has a more favorable side-effect profile.”

For the multinational Phase III study, known as DASSIN (Dasatinib versus Imatinib Study In treatment-naïve CML patients), 519 newly diagnosed CML patients who had received no prior treatment were randomized to receive either dasatinib, also known as Sprycel ®, 100 milligrams once daily (259 patients), or imatinib, 400 milligrams once daily (260 patients). CCyR, confirmed on two assessments, was the study’s primary endpoint. Secondary endpoints included rate of and times to CCyR and major molecular response (MMR), defined as a level of .1 percent or lower of the defective chromosome, as well as safety.

After a minimum follow-up of 12 months, the researchers found that the rates of confirmed CCyR and MMR in those taking dasatinib were 77 percent and 46 percent, respectively, compared to 66 percent and 28 percent, on the imatinib arm.

Therapy failed in nine patients (3.5 percent) in those taking imatinib, compared to five patients (1.9 percent) taking dasatanib. The dasatanib arm reported fewer side effects – nausea, vomiting, muscle inflammation, rash, fluid retention – with most other toxicities being similar in both arms.

“We’ve learned that in cancer therapy, it’s important to use your big guns up front. We know that achieving complete cytogenetic response within a year of starting treatment is associated with more favorable long-term survival; therefore, using this second-generation drug first will likely improve outcomes for patients with chronic myeloid leukemia,” said Kantarjian.

CML is caused by an abnormality known as the Philadelphia chromosome that produces an aberrant protein, Bcr-Abl, which causes the overproduction of one type of white blood cell that drives the disease. Dasatinib, a tyrosine kinase inhibitor, blocks the action of Bcr-Abl; the drug is currently approved by the U.S. Food and Drug Administration for patients who can’t tolerate imatinib or whose CML resists the drug.

The study was supported by Bristol-Myers Squibb, makers of dasatinib. Kantarjian receives research funding from the company.

In addition to Kantarjian, other authors on the ASCO study include: Jorge Cortes, M.D., Department of Leukemia, MD Anderson; Neil Shah, M.D., Ph.D., San Francisco School of Medicine; Andreas Hochhaus, M.D., Universitaetsklinikum Jena; Sandip Shah, M.D., Vedanta Institute of Medical Sciences; Manuel Ayala, M.D., Centro Medico Nacional La Raza; Beatriz Moiraghi, M.D., Hospital General De Agudos J.M. Ramos; Mejia M. Brigid Bradley-Garelik, M.D, Bristol-Myers Squibb; Chao Zhu, Ph.D., Bristol-Myers Squibb, and Michele Baccarani, M.D., University of Bologna.

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On the Net:

• University of Texas M. D. Anderson Cancer Center
• American Society of Clinical Oncology
• New England Journal of Medicine

A new study of spinal fractures and spinal cord injuries associated with mountain biking suggests the sport may be just as risky as diving, football and cheerleading.

“The medical, personal, and societal costs of these injuries are high,” wrote the authors of the study in a report published in the American Journal of Sports Medicine. 

Mountain biking, which involves high speeds and long vertical drops over extreme terrain, is growing in popularity.  But researchers warn the sport invites a risk of serious spinal injuries, with one of every six cases studied resulting in total paralysis.

Such accidents typically affect young, male, recreational riders, they said.

“People need to know that the activities they choose to engage in may carry with them unique and specific risks,” said Dr. Marcel Dvorak of the University of British Columbia in Canada during an interview with Reuters.

“Helmets will not protect you from these injuries, nor will wearing Ninja Turtle-like body armor.”

While prior studies have looked at the range of injuries sustained by mountain bikers, and spinal injuries in general across a broad variety of sports, none had yet examined the specific risks of spinal cord injury among mountain bikers.

Dvorak and his team identified 102 men and 5 women who were treated at British Columbia’s primary spine center between 1995 and 2007 after suffering a mountain biking accident.

On average, the patients were 33 years old, and all but two were recreational riders.

The researchers determined that over the 13-year study period, the annual rate of spinal injury among those that mountain biked was one in 500,000 British Columbia residents.  Furthermore, mountain bikers accounted for 4 percent of all spinal trauma admissions to the center.

Surgery was required for roughly two-thirds of the mountain bikers, but the most serious injuries were the 40 percent involving the spinal cord.  Of those, more than four in ten led to complete paralysis, the researchers found.

“Wrist fractures and facial fractures are common”¦but spine injuries are the most severe with the most profound long-term consequences,” Dvorak said.

The majority of mountain bikers were injured as a result of either being thrust over the handlebars (going “endo”) or falling from significant heights (“hucking”), he said. 

In both cases, the result was often a severe impact to the head that generated trauma down the neck and spine.

“The higher the jump or fall, the higher the risk,” Dvorak said.

In a counterintuitive finding, the researchers discovered no relationship between whether or not a rider wore a helmet and the severity of his or her injuries.

“Helmets are good in preventing head injuries, but they do not in any way protect your neck,” Dvorak explained.

Another unique aspect of mountain biking is its environment, which typically includes remote, mountainous and forested areas.

Some of Dvorak’s patients had fallen while riding solo, or at the back of a group, and were not discovered for an hour or longer after they were injured.    And even then, the remote environments often made it difficult for ambulances and rescue helicopters to reach an injured rider.

Researchers say injury prevention should be the primary goal.  Dvorak advises mountain bikers to be cautious about tricks or jumps, to know their terrain well, to ride in groups and stay together.

The study was published online in the May 20, 2010 American Journal of Sports Medicine.

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On the Net:

• American Journal of Sports Medicine
• University of British Columbia

Lack of quality long-term relationships related to poorer well-being

Moving to a new town or even a new neighborhood is stressful at any age, but a new study shows that frequent relocations in childhood are related to poorer well-being in adulthood, especially among people who are more introverted or neurotic.

The researchers tested the relation between the number of childhood moves and well-being in a sample of 7,108 American adults who were followed for 10 years. The findings are reported in the June issue of the Journal of Personality and Social Psychology, published by the American Psychological Association.

“We know that children who move frequently are more likely to perform poorly in school and have more behavioral problems,” said the study’s lead author, Shigehiro Oishi, PhD, of the University of Virginia. “However, the long-term effects of moving on well-being in adulthood have been overlooked by researchers.”

The study’s participants, who were between the ages of 20 and 75, were contacted as part of a nationally representative random sample survey in 1994 and 1995 and were surveyed again 10 years later. They were asked how many times they had moved as children, as well as about their psychological well-being, personality type and social relationships.

The researchers found that the more times people moved as children, the more likely they were to report lower life satisfaction and psychological well-being at the time they were surveyed, even when controlling for age, gender and education level. The research also showed that those who moved frequently as children had fewer quality social relationships as adults.

The researchers also looked to see if different personality types ““ extraversion, openness to experience, agreeableness, conscientiousness and neuroticism ““ affected frequent movers’ well-being. Among introverts, the more moves participants reported as children, the worse off they were as adults. This was in direct contrast to the findings among extraverts. “Moving a lot makes it difficult for people to maintain long-term close relationships,” said Oishi. “This might not be a serious problem for outgoing people who can make friends quickly and easily. Less outgoing people have a harder time making new friends.”

The findings showed neurotic people who moved frequently reported less life satisfaction and poorer psychological well-being than people who did not move as much and people who were not neurotic. Neuroticism was defined for this study as being moody, nervous and high strung. However, the number and quality of neurotic people’s relationships had no effect on their well-being, no matter how often they had moved as children. In the article, Oishi speculates this may be because neurotic people have more negative reactions to stressful life events in general.

The researchers also looked at mortality rates among the participants and found that people who moved often as children were more likely to die before the second wave of the study. They controlled for age, gender and race. “We can speculate that moving often creates more stress and stress has been shown to have an ill effect on people’s health,” Oishi said. “But we need more research on this link before we can conclude that moving often in childhood can, in fact, be dangerous to your health in the long-term.”

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On the Net:

• American Psychological Association
• Journal of Personality and Social Psychology

Children with autism have a different chemical fingerprint in their urine than non-autistic children, according to new research published tomorrow in the print edition of the Journal of Proteome Research.

The researchers behind the study, from Imperial College London and the University of South Australia, suggest that their findings could ultimately lead to a simple urine test to determine whether or not a young child has autism.

Autism affects an estimated one in every 100 people in the UK. People with autism have a range of different symptoms, but they commonly experience problems with communication and social skills, such as understanding other people’s emotions and making conversation and eye contact.

People with autism are also known to suffer from gastrointestinal disorders and they have a different makeup of bacteria in their guts from non-autistic people.

Today’s research shows that it is possible to distinguish between autistic and non-autistic children by looking at the by-products of gut bacteria and the body’s metabolic processes in the children’s urine. The exact biological significance of gastrointestinal disorders in the development of autism is unknown.

The distinctive urinary metabolic fingerprint for autism identified in today’s study could form the basis of a non-invasive test that might help diagnose autism earlier. This would enable autistic children to receive assistance, such as advanced behavioural therapy, earlier in their development than is currently possible.

At present, children are assessed for autism through a lengthy process involving a range of tests that explore the child’s social interaction, communication and imaginative skills.

Early intervention can greatly improve the progress of children with autism but it is currently difficult to establish a firm diagnosis when children are under 18 months of age, although it is likely that changes may occur much earlier than this.

The researchers suggest that their new understanding of the makeup of bacteria in autistic children’s guts could also help scientists to develop treatments to tackle autistic people’s gastrointestinal problems.

Professor Jeremy Nicholson, the corresponding author of the study, who is the Head of the Department of Surgery and Cancer at Imperial College London, said: “Autism is a condition that affects a person’s social skills, so at first it might seem strange that there’s a relationship between autism and what’s happening in someone’s gut. However, your metabolism and the makeup of your gut bacteria reflect all sorts of things, including your lifestyle and your genes. Autism affects many different parts of a person’s system and our study shows that you can see how it disrupts their system by looking at their metabolism and their gut bacteria.

“We hope our findings might be the first step towards creating a simple urine test to diagnose autism at a really young age, although this is a long way off – such a test could take many years to develop and we’re just beginning to explore the possibilities. We know that giving therapy to children with autism when they are very young can make a huge difference to their progress. A urine test might enable professionals to quickly identify children with autism and help them early on,” he added.

The researchers are now keen to investigate whether metabolic differences in people with autism are related to the causes of the condition or are a consequence of its progression.

The researchers reached their conclusions by using H NMR Spectroscopy to analyse the urine of three groups of children aged between 3 and 9: 39 children who had previously been diagnosed with autism, 28 non-autistic siblings of children with autism, and 34 children who did not have autism who did not have an autistic sibling.

They found that each of the three groups had a distinct chemical fingerprint. Non-autistic children with autistic siblings had a different chemical fingerprint than those without any autistic siblings, and autistic children had a different chemical fingerprint than the other two groups.

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On the Net:

• Imperial College London
• Journal of Proteome Research

U.S. researchers reported on Tuesday that American cigarettes contain more cancer-causing agents than those in Canada, Britain and Australia.

Their study also demonstrated that the amount of these carcinogens in a smoker’s cigarette butts directly correlated with tell-tale compounds in the smoker’s urine.

The study can help researchers try to trace the harmful effects of smoking.

“We know that cigarettes from around the world vary in their ingredients and the way they are produced,” said Dr. Jim Pirkle of the U.S. Centers for Disease Control and Prevention (CDC), who heads a lab using a mass spectrometer to measure levels of chemicals in people’s bodies

“All of these cigarettes contain harmful levels of carcinogens, but these findings show that amounts of tobacco-specific nitrosamines differ from country to country, and U.S. brands are the highest in the study,” Pirkle said in a statement.

CDC’s David Ashley and colleagues did in-depth tests involving 126 smokers in the U.S., Canada, Britain and Australia.

“Seventeen eligible cigarette brands (between 3 and 5 brands from each country) were selected on the basis of national sales and nicotine yield to identify popular brands with a range of ventilation,” the researchers wrote in the June issue of Cancer Epidemiology.

Volunteers had their saliva and urine tested and also turned over their used cigarette butts to the researchers.

These were all tested for nicotine and the chemicals 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK for short) and the breakdown product of NNK in the body, known as NNAL.

These cancer-causing agents are known as tobacco-specifics nitrosamines or TSNAs.

“We have shown a direct association between the 24-hour mouth-level exposure of NNK resulting from cigarette smoking and the concentration of its primary metabolite, NNAL, in the urine of smokers,” the researchers wrote.

“Internal dose concentrations of urinary NNAL are significantly lower in smokers in countries that have lower TSNA levels in cigarettes such as Canada and Australia in contrast to countries that have high levels of these carcinogens in cigarettes, such as the United States.”

The popular U.S. cigarette brands studied contained “American blend” tobacco.  This tobacco is known to have higher TSNA levels than the “bright” tobacco used in the most popular Australian, Canadian, and British brands.

Australian and Canadian smokers got more nicotine than U.S. and British smokers, but not of TSNAs.

The World Health Organization says 5 million people die each due to tobacco-related heart attacks, strokes and cancers.  Another 430,000 adults die annually from second-hand smoke.

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On the Net:

• CDC
• Cancer Epidemiology

Researchers at the Public University of Navarra, the Polytechnic University of Madrid (CBGP), the University of Malaga, the University of Wisconsin and the Valencian Institute of Agricultural Research have managed to sequence the genome of the bacteria responsible for tuberculosis in the olive tree. The study, included in the June issue of Environmental Microbiology, represents the first sequencing of the genome of a pathogenic bacteria undertaken in Spain, being the first genome known worldwide of a pathogenic Pseudomonas in woody plants.

The sequencing of the genome of this pathogen opens the doors to the identification of the genes responsible for the virulence of this bacteria and its survival on the philosphere (leaf surface), thus facilitating the design of specific strategies in the fight against the disease and enabling drawing up programmes for the genetic improvement of olive groves.

Pseudomonas savastanoi is the agent that gives rise to tuberculosis in the olive tree, a disease that causes important losses in the olive crops in Spain. Trees affected present tumours (known as verrucas) that can grow to several centimetres diameter in trunks, branches, stalks and buds. Diseased trees are less robust and have less growth, to the point of being non-productive if the attack is very intense. To date, due to the absence of effective methods of control, preventive strategies have been carried out, reducing populations of bacteria with phytosanitary treatment.

New strategies

Plant diseases produced by pathogenic microorganisms not only reduce production but can also alter the quality of the food and drastically diminish the commercial value of the crops. The new strategies for disease control today involve the analysis of information contained in the genome of pathogenic organisms. Similar to what has happened with the human genome, this technology is generating a great amount of valuable information for the development of innovative technologies, that will enable identifying and controlling the pathogen as well as obtaining new varieties of the host plant that have greater resistance to the disease.

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On the Net:

• Basque Research
• Environmental Microbiology

On average, about five percent of total cancer research funding is spent on investigating metastases (the spread of cancer cells around the body) in Europe, yet metastatic disease is the direct or indirect cause of 90 percent of all cancer deaths, according to an editorial in the European Journal of Cancer (EJC). [1]

The authors of the editorial, which introduces a special EJC issue on metastasis (“Stopping cancer in its tracks: metastasis as a therapeutic target”), highlight this discrepancy in funding and they believe that, although it is difficult to obtain accurate figures, the situation is probably similar in other countries such as the USA and Japan.

It has been known for some time that metastasis is the key problem in cancer and the main reason why people die from the disease. Until recently, the reasons why some people developed metastases and other did not had been unclear, but, as this special issue of the EJC shows, at last there are models and scientific hypotheses that have begun to unravel this process and the EJC reviews the state of the art in this respect. However, research into metastasis has not necessarily attracted the recognition it deserves from funding organisations.

Professor Jonathan Sleeman, one of the two guest editors of the EJC special issue and head of microvascular pathobiology research at the University of Heidelberg (Germany), said: “Metastasis is a process in cancer that is very poorly understood; it kills patients and therefore we believe that it should be funded better. Yet at the European level and, indeed, worldwide, comparatively little emphasis is placed on tackling metastases and in providing appropriate levels of funding for research.”

He continued: “Given the clinical importance of metastasis for cancer patients, the limited treatment options for metastatic disease and the open question of how metastasis works, we need to know how much research funding is being directed at the problem and what proportion of funding for cancer research ends up focused on metastases? I have found it hard to obtain reliable figures, but although there is considerable variation between European countries, I estimate that the average spent on metastasis research is around 5% of total cancer research funding. Given that metastasis is of central importance to the prognosis and outcome of cancer patients, we could argue that in many countries more funding should be directed toward metastasis research.”

Metastasis is the process by which cancer cells split off from the original, primary tumour and travel to other parts of the body via the blood or lymph systems. This leads to the growth of secondary tumours in places such as the bones, brain, lungs and liver, and it is usually these that end up killing the patient.

“Metastatic disease, therefore, represents a major public health problem, affecting cancer patients and their families, as well as health care systems and the broader economy. Despite this, progress in developing treatments for metastatic disease remains slow,” write Prof Sleeman and the second guest editor, Professor Patricia Steeg (chief of the Women’s Cancers Section, Laboratory of Molecular Pharmacology at the National Cancer Institute, Bethesda, USA) in their editorial.

In addition to adequate funding, they call for:

    * effective translational research for metastatic disease, which will take discoveries made in the laboratory quickly into new and better treatments for cancer patients;
    * clinical trials to be designed so that they include information on metastases;
    * clinicians and scientists to work more closely together to design clinical trials that assess the development of new metastases.

“In summary, combating metastasis formation and growth is the key to successfully treating cancer,” they conclude. “Traditional growth control approaches are inadequate and can even be detrimental in the long term: new therapies built upon a solid understanding of the process of metastatic disease are urgently required. In turn, this demands an increased pre-clinical knowledge base that capitalises on major conceptual advances made in recent years, as well as a rational approach to the design of clinical trials with the inclusion of metastasis as an end-point. Together these observations speak for the necessity of increasingly close interactions between basic and clinical scientists, as well as the enhanced levels of research funding required to alleviate this major clinical problem.”

The EJC special issue on metastasis consists of a number of articles looking at the state of current knowledge about the disease and outlining promising areas of research. Prof Steeg said: “We hope that this special issue will highlight the fact that metastasis should be an important consideration during drug development. If more attention was paid to it, we could really improve treatments for cancer patients.”

The special issue will be available on the Elsevier stand at the American Society of Clinical Oncology (ASCO) meeting in Chicago (USA) from June 4-8.

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On the Net:

• ECCO
• European Journal of Cancer

There’s debate about the best treatment approach for patients with certain stages of non-small cell lung cancer (NSCLC), which accounts for about 80 percent of all lung cancers. Patients with early stages of NSCLC are typically treated with surgery, but those with stage IIIA present more of a challenge because they are such a diverse group. However, research from Fox Chase Cancer Center shows that patient’s with stage IIIA NSCLC who receive surgery, lobectomy in particular, have increased overall survival compared to those who received chemoradiation alone”“”“those receiving lobectomy plus chemoradation had survival rates that were higher than previously reported as well.

The research, led by Charu Aggarwal, M.D., M.P.H., Walter Scott, M.D., F.A.C.S., and George Simon, M.D., will be presented at the 46th Annual Meeting of the American Society of Clinical Oncology on Sunday June 6.

Stage IIIA presents challenges because patients classified at that level are such a diverse group. The common denominator is that cancer has spread to lymph nodes on the same side of the chest as the primary tumor, but beyond that, stage IIIA patients may have tumors of any size and may differ in the number and location of affected lymph nodes.

“In the past, patients with advanced stage lung cancer were treated either with surgery alone, chemotherapy alone, or radiation alone,” says Aggarwal. “Scientists and clinicians found that adding radiation to chemotherapy improved survival, so concurrent chemotherapy and radiation together became the standard of care.” Recent large, Phase III clinical trials showed that patients treated with chemoradiation followed by surgery were more likely to be disease-free than counterparts who received chemoradiation without surgery set the stage for Aggarwal’s study.

Looking at data from 249 patients treated at Fox Chase for stage IIIA non-small cell lung cancer from 2000 through 2008, the research team divided patients into three groups based on the treatments they received: chemoradiation only, chemoradiation plus surgical removal of a lung (pneumonectomy), or chemoradiation plus surgical removal of only one lobe of the lung (lobectomy).

Biostatistician Brian Egleston, Ph.D., used a technique called propensity score analysis to balance the three groups in terms of age, gender, smoking status, physical condition, and other variables that could bias the results.

“After we adjusted for all those variables, we saw that patients who received surgery, lobectomy in particular, had increased overall survival compared to those who received chemoradiation alone,” says Aggarwal. “We saw overall survival of 40 percent at five years for chemoradiation plus lobectomy, higher than seen with pneumonectomy.”

Removing the entire lung, a more extensive procedure that poses a greater risk of post-operative complications, offered no additional survival benefit.” This tells us that you don’t have to put the patient through pneumonectomy; you might get superior outcomes with a smaller, safer operation,” says Aggarwal, who received an ASCO Foundation Merit Award for this research.

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On the Net:

• Fox Chase Cancer Center

Fear of the H1N1 virus appears to be the driving factor behind the adoption of preventive behaviors, according to a study published in the June issue of AJIC: American Journal of Infection Control, the official publication of the Association for Professionals in Infection Control and Epidemiology, (APIC). Researchers studying the public response during the recent H1N1 outbreak in Hong Kong concluded that fear about the pandemic prompted residents to frequently wash hands and wear face-masks.

A team led by Joseph T.F. Lau, PhD, a professor at the Chinese University of Hong Kong, investigated the prevalence of self-reported preventive behaviors in response to the influenza A/H1N1 epidemic in Hong Kong, including wearing face-masks regularly in public areas, wearing face-masks after the onset of influenza-like illness (ILI) symptoms, and frequent hand-washing. Previous research shows that both frequent hand-washing and wearing face-masks can control the spread of influenza.

The study’s results showed that 47 percent washed hands more than 10 times per day, 89 percent wore face-masks when having influenza-like illness (ILI) and 21.5 percent wore face-masks regularly in public areas.

The authors note that pandemic outbreaks “have had a sustained impact on personal hygiene and protective behaviors. Our study showed that people with a higher level of mental distress due to A/H1N1 were more likely to adopt some of the three preventive measures.” They go on to say that emerging infectious diseases “provide a window of opportunity for health education to improve personal hygiene.”

According to the authors, these preventive behaviors can play an important role in controlling pandemic influenza, but they cautioned that there is a lack of data on their adoption by the public and see a need for more research.

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On the Net:

• Elsevier Health Sciences
• AJIC

Patterns consolidate features of older theories, may help diagnosis of psychiatric disorders

In a study appearing in the journal PLoS ONE, Massachusetts General Hospital (MGH) scientists describe finding mathematical patterns underlying the way individuals unconsciously distribute their preferences regarding approaching or avoiding objects in their environment. These patterns appear to meet the strict criteria used to determine whether something is a scientific law and, if confirmed in future studies, could potentially be used to guide diagnosis and treatment of psychiatric disorders.

“Law-like processes are important in science for their predictive value, and finding patterns in behavior that meet criteria for lawfulness is extremely rare,” explains Hans Breiter, MD, principal investigator of the MGH Phenotype Genotype Project in Addiction and Mood Disorder (http://pgp.mgh.harvard.edu), who led the study. “The patterns we observed appear to describe the unconscious range of preference an individual has with a specificity suggestive of that of a fingerprint. We look forward to learning what other scientists find about these patterns.” These patterns ““ which the authors group together under the name relative preference theory ““ incorporate features of several older theories of reward and aversion into a single theory.

The PLoS ONE study reports on the outcome of three sets of experiments. In each, healthy participants were presented with a series of images and could vary the amount of time they viewed each image by pressing the keys of a keypad. The first group of participants viewed a series of four human faces ““ average-looking male, average-looking female, attractive male and attractive female. The second group was presented with a series of photographs of images ranging from children, food, sports and musical instruments to war, disaster, and drug paraphernalia. The third group viewed four different images of food ““ two of normal appearing meals, one in which the food was abnormally colored, and one of raw, unprepared food ““ on two different days. For one viewing, participants were hungry, for the other, they had just eaten. Responses were measured by whether participants increased, decreased, or did nothing to change how long they viewed particular images.

All three experiments showed the same patterns in both groups and individuals, patterns that contained a set of features that varied between people. These patterns describe how groups and individuals make tradeoffs between approaching and avoiding items; how value is attributed to objects, which is linked assessments of other objects of the same type; and how individuals set limits to how strongly they will seek or avoid objects.

The authors note that these patterns incorporate aspects of three existing theories in reward/aversion: prospect theory, which includes the fact that people are more strongly motivated to avoid negative outcomes than to attain positive outcomes; the matching law, which describes how the rates of response to multiple stimuli are proportional to the amount of reward attributed to each stimulus; and alliesthesia, which notes that the value placed on something depends on whether it is perceived to be scarce ““ for example, hungry people place greater value on food than do those who have just eaten.

One of the key differences between relative preference theory (RPT) and earlier theories is that RPT evaluates preferences relating to the intrinsic value of items to an individual, rather than relating preferences to values set by external forces ““ such as how the overall economy sets the value of the dollar. The patterns observed in this study are similar at the individual and group levels ““ a relationship known as “scaling.”

“In order for behavioral patterns to be considered law-like, they need to be described mathematically, recur in response to many types of stimuli, remain stable in the face of statistical noise, and potentially show scaling across different levels of measurement,” explains Anne Blood, PhD, deputy principal investigator of the Phenotype Genotype Project, director of the MGH Mood and Motor Control Laboratory, and a co-author of the PLoS ONE report.

“Relative preference theory meets those requirements, but these observations need to be confirmed by other scientists,” she adds. Other work by our team is examining how these RPT patterns are affected by depression and addiction, with the goal of developing RPT as an Internet tool for psychiatric diagnosis.” Earlier studies by the MGH investigators also connected aspects of RPT to reward circuits in the brain, using magnetic resonance imaging, and to measures of genetic variability.

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On the Net:

• Massachusetts General Hospital
• PLoS ONE