High calcium level in arteries may signal serious heart attack risk

OAK BROOK, Ill., 30 july 2009-– Researchers may be able to predict future severe cardiac events in patients with known, stable coronary artery disease (CAD) using coronary calcium scoring, according to a study published in the online edition of Radiology.

"The amount of calcium in the coronary vessels, as measured by CT, is of high predictive value for subsequent serious or fatal heart attack in these patients, independent of the patient's age, sex and other coronary risk factors," said the study's lead author, Marcus Hacker, M.D., resident physician in the Department of Nuclear Medicine, leader of the research unit for nuclear cardiology and assistant medical director at Ludwig Maximilians University in Munich, Germany.

CAD is the most common type of heart disease. According to the National Heart, Lung and Blood Institute, it is the leading cause of death in the U.S. for both men and women, killing more than 500,000 Americans each year.

CAD is a condition in which plaque, consisting of cholesterol, calcium, fat and other substances, builds up inside the arteries that supply blood to the heart. When plaque builds up in the coronary arteries, blood flow to the heart is reduced and may lead to arrhythmia, heart attack or heart failure.

Single photon emission computed tomography (SPECT) myocardial perfusion imaging is a nuclear medicine diagnostic procedure that provides excellent three-dimensional images of the coronary arteries to assist in the diagnosis and treatment of CAD.

Currently, calcium scoring—measuring the amount of calcium in the arteries—is used as a screening exam and in cases of suspected CAD, but not in cases of known CAD.

Dr. Hacker and colleagues set out to determine if calcium scoring would lend additional prognostic value to SPECT findings in patients with known, stable CAD.

For the study, 260 patients with CAD underwent coronary artery calcium scoring in addition to SPECT myocardial perfusion imaging. Over a median period of 5.4 years, the patients were followed up for severe cardiac events, meaning cardiac death or nonfatal heart attacks. Twenty-three of the 260 patients had a fatal or severe heart attack, and 40 additional patients underwent bypass surgery.

The results showed that patents with an initial calcium score greater than 400 were at significantly increased risk for severe cardiac events.

"We found that coronary calcium seems to play an important role in predicting subsequent heart attack or sudden cardiac death, and adds prognostic value to SPECT findings," said co-author Christopher Uebleis, M.D., member of the research unit for nuclear cardiology at Ludwig Maximilians University.

Dr. Hacker pointed out that combining calcium scoring and SPECT can help to identify patients with known CAD who are at highest risk for serious or fatal heart attacks.

"In these patients, intensified medical therapy, shorter follow-up intervals and, if necessary, bypass procedures may be required to prevent future severe cardiac events."

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"Stable Coronary Artery Disease: Prognostic Value of Myocardial Perfusion SPECT in Relation to Coronary Calcium Scoring —Long Term Follow-up." Collaborating with Drs. Hacker and Uebleis were Alexander Becker, M.D., Ines Griesshammer, Paul Cumming, Ph.D., Christoph Becker, M.D., Michael Schmidt, M.D. and Peter Bartenstein, M.D.

Organic food is no healthier, study finds

LONDON, 30 july 2009-- Organic food has no nutritional or health benefits over ordinary food, according to a major study published Wednesday.

Researchers from the London School of Hygiene & Tropical Medicine said consumers were paying higher prices for organic food because of its perceived health benefits, creating a global organic market worth an estimated $48 billion in 2007.

A systematic review of 162 scientific papers published in the scientific literature over the last 50 years, however, found there was no significant difference.

"A small number of differences in nutrient content were found to exist between organically and conventionally produced foodstuffs, but these are unlikely to be of any public health relevance," said Alan Dangour, one of the report's authors.

"Our review indicates that there is currently no evidence to support the selection of organically over conventionally produced foods on the basis of nutritional superiority."

The results of research, which was commissioned by the British government's Food Standards Agency, were published in the American Journal of Clinical Nutrition.

Sales of organic food have fallen in some markets, including Britain, as recession has led consumers to cut back on purchases.

The Soil Association said in April that growth in sales of organic products in Britain slowed to just 1.7 percent in 2008, well below the average annual growth rate of 26 percent over the last decade, following a plunge in demand at the end of the year.

Physical Activity Intensity Linked to Cancer Mortality Risk

In men, moderate-intensity activity more beneficial than low-intensity for preventing death

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30 july 2009-- Leisure-time physical activity at a moderately intense level or greater appears to offer more benefit in preventing cancer-related death in men than low-intensity physical activity, according to research published online July 28 in the British Journal of Sports Medicine.

Jari A. Laukkanen, M.D., of the University of Kuopio in Finland, and colleagues analyzed data from 2,560 middle-aged men who were free from a history of cancer at baseline. Participants self-reported their leisure-time physical activity over 12 months, and were followed for an average of 16.7 years.

The researchers found that an increase of 1.2 metabolic equivalents of oxygen consumption in mean intensity of leisure-time physical activity was associated with a decrease in cancer mortality (relative risk, 0.85), after adjustment for age, smoking, alcohol consumption, and other factors. The relationship mainly involved gastrointestinal and lung cancers. The authors further note that the intensity of physical activity was related to cancer deaths only in men exercising an average of more than 30 minutes daily.

"In conclusion, this prospective study indicates that the mean intensity of leisure-time physical activity is inversely and independently associated with the risk of premature death from cancer, mainly due to lung and gastrointestinal cancers in men. The intensity of leisure-time physical activity should be at least moderate so that beneficial effect of physical activity for reducing overall cancer mortality can be achieved," Laukkanen and colleagues write.

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Save Swine Flu Drugs for Younger Patients, Study Urges

29 july 2009-- Antiviral drug treatment of swine flu may be wasted on the elderly and should be reserved for young people, suggest researchers who created a model of the effect of antiviral treatment on the spread of the H1N1 virus.

If the current swine flu pandemic behaves like the 1918 flu, antiviral drugs would not significantly reduce death rates among people older than 65 and, in fact, might cause the H1N1 virus to develop increased drug resistance, according to Stefano Merler, of the Bruno Kessler Foundation in Italy, and his colleagues.

Their report appears online in BMC Infectious Diseases.

"Although it is too early to confidently predict some important features of the ongoing influenza pandemic, the use of antivirals is confirmed to be the most effective single intervention, in the absence of vaccines," Merler said in a news release from the journal's publisher. "It requires, however, a very large stockpile of antiviral drugs. Our work demonstrates that, even in countries where the antiviral stockpile is not sufficient to treat 25 percent of the population, the minimum level suggested by [the World Health Organization], it is possible to reduce morbidity and excess mortality by prioritizing the use of antivirals by age."

"Although a policy of age-specific prioritization of antiviral use will be controversial ethically, it may be the most efficient use of stockpiled therapies," he said. "This is of particular importance for countries where the amount of drug stockpiled is well below the WHO's suggested level."

The researchers concluded that developing early estimates of the impact of the swine flu pandemic and of age-specific death rates could prove important in optimizing the use of antiviral drugs during the pandemic.

More information

The U.S. Centers for Disease Control and Prevention has more about swine flu.

Men Who Have Prostate Cancer Surgery Do Well

29 july 2009-- A major study has good news for men who have prostate cancer surgery but leaves unanswered the complicated question of whether a man should have that operation, another treatment or just watchful waiting.

The study of almost 13,000 American men who had a radical prostatectomy -- surgical removal of a cancerous prostate gland -- between 1987 and 2005 found that only 12 percent of them died of the cancer, according to the report in the July 27 issue of the Journal of Clinical Oncology.

"Patients with what we thought of as high-risk prostate cancer had a much lower risk of dying of their cancers than we ever thought," said Dr. Peter T. Scardino, chairman of the department of surgery at Memorial Sloan-Kettering Cancer Center, and a member of the research team. "Patients with more favorable prostate cancers did remarkably well, so well that you have to begin to question whether they should have been treated."

The choice of surgery, radiation therapy or watchful waiting must be made each year for more than 190,000 American men, most middle-aged or older, who are diagnosed with prostate cancer. Most choose some kind of treatment, said Dr. Andrew Stephenson, head of urological oncology at the Cleveland Clinic's Glickman Urological and Kidney Institute, and another member of the research team. From 40 percent to 50 percent choose surgery, about 10 percent choose watchful waiting, and the rest choose some form of radiation therapy, Stephenson said.

For men who have surgery, the new research has produced a tool that can allow them to predict their chance of survival for at least 15 years, Scardino said. Survival is measured by essentially three elements: the clinical stage of the cancer when it is detected, determined in great part by how large it is; the Gleason score, a measure of how much of its normal structure the prostate gland has lost; and blood levels of prostate-specific antigen, a protein produced by the gland.

The study found that the score had an accuracy of 82 percent in predicting 15-year survival, Scardino said. "If you could predict what would happen in the stock market in the next 15 years with 82 percent accuracy, you would be a genius," he said.

Overall, there was a greater chance that a man in the study would die of a cause other than prostate cancer. The rate of death from other causes was 38 percent, compared to 12 percent attributed to prostate cancer.

The new predictive method will be made public soon, after medical review, so that physicians and men can learn about their anticipated survival after surgery, Scardino said.

"Any person can look at it and put in the numbers," he said.

The new predictive tool is an improvement over the existing method, which relies essentially on readings of prostate-specific antigen levels, Stephenson said.

But no such predictive method exists for newly diagnosed men who must chose between treatment and watchful waiting, and so the study presents a predicament for those men and their physicians, he said.

"It questions the lethality of prostate cancer," Stephenson said. "Perhaps a similarly low risk might have been seen if the men did not have prostatectomy. We can't say whether a cancer poses enough of a threat to the patient so that therapy is needed."

Prostate cancer surgery is not free of problems, Stephenson said. Its major side effects are incontinence and loss of sexual function.

Many prostate cancers grow slowly -- so slowly that an old medical byword is that "more men die with their prostate cancer than of it." No existing method can single out the cancers that will be fatal if left untreated.

"We really need better tools for really identifying prostate cancers that pose a threat to longevity," Stephenson said. "Many have been proposed. All are being investigated, and hopefully in the future we will have better tools that accurately predict the risk of dying from prostate cancer."

Until those tools are available, the question is often "a balance between quantity and quality of life," he added. "That is a very complicated decision that must take many factors into consideration."

More information

Basic facts about prostate cancer are provided by the U.S. National Cancer Institute.

Obesity costs US health system $147 billion: study

CHICAGO, 29 july 2009-– Obesity-related diseases account for nearly 10 percent of all medical spending in the United States or an estimated $147 billion a year, U.S. researchers said Monday.

They said obese people spend 40 percent more -- or $1,429 more per year -- in healthcare costs than people of normal weight.

"It is critical that we take effective steps to contain and reduce the enormous burden of obesity on our nation," Dr. Thomas Frieden, director of the U.S. Centers for Disease Control and Prevention, told a news conference at a CDC obesity meeting where the study was presented.

"Reversing obesity is not going to be done successfully with individual effort," Frieden said. "It will be done successfully as a society."

The CDC outlined 24 new recommendations on how communities can combat obesity in their neighborhoods and schools by encouraging healthier eating and more exercise.

Democratic Senator Tom Harkin, a member of the Senate Health, Education, Labor and Pensions committee and chairman of the Senate Committee on Agriculture, Nutrition and Foresty, said the report underscores why prevention and wellness efforts must be part of any plan to reform the U.S. health system.

"Report after report shows that if we fail to take meaningful steps now on prevention of chronic disease like obesity, healthcare costs will continue to spiral out of control," Harkin said in a statement.

26 PERCENT OBESITY RATE IN U.S.

More than 26 percent of Americans are obese, which means they have a body mass index of 30 or higher. BMI is equal to weight in kilograms divided by height in meters squared. A person 5 feet 5 inches tall becomes obese at 180 pounds (82 kg).

For the study, Eric Finkelstein of the non-profit RTI International and researchers at the CDC and the Agency for Healthcare Research and Quality analyzed medical cost data from 1998 and 2006.

They found U.S. obesity rates rose 37 percent between 1998 and 2006, driving an 89 percent increase in spending on treatments for obesity-related diseases such as diabetes, heart disease and arthritis.

Obesity now accounts for 9.1 percent of all medical spending in the United States, up from 6.5 percent in 1998.

"What we found was the total cost of obesity increased from $74 billion to maybe as high as $147 billion today, so roughly double over that time period," said Finkelstein, whose study also was published in the journal Health Affairs.

An obese Medicare beneficiary spends $600 more a year on drug costs than a Medicare patient of healthy weight.

The CDC's new obesity prevention strategies aim to address issues such as a lack of access to healthy food in poor neighborhoods and sedentary lifestyles that contribute to America's obesity epidemic.

Frieden said soda and sugar-sweetened beverages "play a particular role in the obesity epidemic," noting that Americans consume an extra 150 calories more per day in sugar-sweetened beverages than two to three decades ago.

He said adding a tax to soft drinks might curb consumption but that was not a position held by the Obama administration.

Low blood count ups death risk in elderly people

NEW YORK, 28 july 2009-- New research indicates that low red blood cell blood counts, regardless of other diseases that might be present, is a risk factor for death in very elderly individuals. In the study, anemia was associated with a twofold increased risk of death during follow-up.

Prior reports have linked low red blood cell counts, also known as anemia, with death, but it was unclear if this was simply due to the chronic diseases that often accompany anemia or the anemia itself, Wendy P. J. den Elzen and colleagues, from Leiden University Medical Center, the Netherlands, note in the Canadian Medical Association Journal.

Red blood cells carry oxygen around the bloodstream, from the lungs to the body's tissues.

The researchers analyzed data from 562 subjects who were at least 85 years of age. Just more than a quarter of subjects had anemia at baseline, and another quarter developed it during the five years of follow-up.

Anemia was linked to an increased risk of death during follow-up, and was also associated with increased difficulties with activities of daily living.

In an accompanying editorial, Dr. A. Mark Clarfield, from McGill University, Montreal, and Ora Paltiel, from Hadassah-Hebrew University, Jerusalem, comment that further research is needed to determine if anemia actually causes increased mortality and to determine if treating anemia in very elderly people improves survival and functional outcomes.

SOURCE: Canadian Medical Association Journal, July 27th online issue, 2009.

All-in-1 nanoparticle: A Swiss Army knife for nanomedicine

28 july 2009--Nanoparticles are being developed to perform a wide range of medical uses – imaging tumors, carrying drugs, delivering pulses of heat. Rather than settling for just one of these, researchers at the University of Washington have combined two nanoparticles in one tiny package.

The result is the first structure that creates a multipurpose nanotechnology tool for medical imaging and therapy. The structure is described in a paper published online this week in the journal Nature Nanotechnology.

"This is the first time that a semiconductor and metal nanoparticles have been combined in a way that preserves the function of each individual component," said lead author Xiaohu Gao, a UW assistant professor of bioengineering.

The current focus is on medical applications, but the researchers said multifunctional nanoparticles could also be used in energy research, for example in solar cells.

Quantum dots are fluorescent balls of semiconductor material just a few nanometers across, a small fraction of the wavelength of visible light (a nanometer is 1-millionth of a centimeter). At this tiny scale, quantum dots' unique optical properties cause them to emit light of different colors depending on their size. The dots are being developed for medical imaging, solar cells and light-emitting diodes.

Glowing gold nanoparticles have been used since ancient times in stained glass; more recently they are being developed for delivering drugs, for treating arthritis and for a type of medical imaging that uses infrared light. Gold also reradiates infrared heat and so could be used in medical therapies to cook nearby cells.

But combine a quantum dot and a gold nanoparticle, and the effects disappear. The electrical fields of the particles interfere with one another and so neither behaves as it would on its own. The two have been successfully combined on a surface, but never in a single particle.

The paper describes a manufacturing technique that uses proteins to surround a quantum dot core with a thin gold shell held at 3 nanometers distance, so the two components' optical and electrical fields do not interfere with one another. The quantum dot likely would be used for fluorescent imaging. The gold sphere could be used for scattering-based imaging, which works better than fluorescence in some situations, as well as for delivering heat therapy.

The manufacturing technique developed by Gao and co-author Yongdong Jin, a UW postdoctoral researcher, is general and could apply to other nanoparticle combinations, they said.

"We picked a tough case," Gao said. "It is widely known that gold or any other metal will quench quantum dot fluorescence, eliminating the quantum dot's purpose."

Gao and Jin avoided this problem by building a thin gold sphere that surrounds but never touches the quantum dot. They carefully controlled the separation between the gold shell and the nanoparticle core by using chains of polymer, polyethylene glycol. The distance between the quantum dot core and charged gold ion is determined by the length of the polymer chain and can be increased with nanometer precision by adding links to the chain. On the outside layer they added short amino acids called polyhistidines, which bind to charged gold atoms.

Gao compares the completed structure to a golden egg, where the quantum dot is the yolk, the gold is the shell, and polymers fill up the space of the egg white.

Using ions allowed the researchers to build a 2- to 3-nanometer gold shell that's thin enough to allow about half of the quantum dot's fluorescence to pass through.

"All the traditional techniques use premade gold nanoparticles instead of gold ions," Gao said. "Gold nanoparticles are 3 to 5 nanometers in diameter, and with factoring in roughness the thinnest coating you can build is 5-6 nanometers. Gold ions are much, much smaller."

The total diameter of the combined particle is roughly 15-20 nanometers, small enough to be able to slip into a cell.

Incorporating gold provides a well-established binding site to attach biological molecules that target particular cells, such as tumor cells. Gold could also potentially amplify the quantum dot's fluorescence by five to 10 times, as it has in other cases.

The gold sphere offers one further benefit. Gold is biocompatible, is medically approved and does not biodegrade. A gold shell could thus provide a durable non-toxic container for nanoparticles being used in the body, Gao said.

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The research was supported by the National Institutes of Health, the National Science Foundation, the Seattle Foundation and the UW's Department of Bioengineering.

Most older long-term cancer survivors have poor health habits

28 july 2009--A new study finds that most older long-term cancer survivors who are interested in diet and exercise actually have poor health habits. The study also reveals that those survivors who do exercise and watch their diet have improved physical health and quality of life. Published in the September 1, 2009 issue of Cancer, a peer-reviewed journal of the American Cancer Society, the research indicates that greater efforts are needed to encourage elderly cancer survivors to live healthier lives.

More than half of the estimated 11 million cancer survivors in the United States are aged 65 years or older. There are relatively few studies looking at older cancer survivors' health behaviors, but evidence suggests that many older long-term cancer survivors have suboptimal health habits.

Catherine Mosher, Ph.D., of the Memorial Sloan-Kettering Cancer Center in New York City and colleagues reviewed data from a total of 753 older (aged 65 years or over), long-term (five or more years post-diagnosis) breast, prostate, and colorectal cancer survivors to estimate the prevalence of poor health habits in this population. Participants were recruited through the North Carolina Central Cancer Registry, the Duke Cancer Registry, and self-referral. The study included telephone interviews to determine individuals' eligibility for a diet and exercise intervention trial. Interviews assessed exercise, diet, weight, and quality of life, including physical functioning and mental health.

The researchers found that older cancer survivors, all of whom were interested in a diet and exercise intervention study, generally had poor health habits. For example, they reported an average of only 10 minutes of moderate-to-vigorous exercise per week. This is far short of the national recommendation of more than 150 minutes of exercise per week. Also, only 7 percent met healthful eating recommendations set by national guidelines. Despite their suboptimal health behaviors, cancer survivors reported a level of mental and physical quality of life that actually exceeded levels typically found among older individuals. This may be explained in part by the study's design: investigators excluded survivors with significant health problems and functional limitations.

The study also found that interviewees who exercised more and had better dietary habits experienced better vitality and physical functioning. On the other hand, individuals who were obese had worse physical quality of life.

"Our findings point to the potential negative impact of obesity and the positive effect of regular exercise and a healthy diet on physical quality of life outcomes among older, long-term cancer survivors," said Dr. Mosher. "Only randomized clinical trials, however, can reveal whether lifestyle modification improves older, long-term cancer survivors' physical outcomes," she added.

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Article: "Associations between lifestyle factors and quality of life among older, long-term breast, prostate, and colorectal cancer survivors." Catherine E. Mosher, Richard Sloane, Miriam C. Morey, Denise Clutter Snyder, Harvey J. Cohen, Paige E. Miller, and Wendy Demark-Wahnefried. Cancer; Published Online: July 27, 2009 (DOI: 10.1002/cncr.24436); Print Issue Date: September 1, 2009.

Allergy drugs may fight diabetes, obesity

HONG KONG, 27 july 2009-- Over-the-counter allergy and asthma drugs helped obese, diabetic mice lose weight and control their blood sugar, researchers reported on Monday.

Three other studies strongly linked obesity and type-2 diabetes to a dysfunctional immune system, and researchers said these findings could lead to better drugs or perhaps even vaccines to treat the effects of both conditions.

Rates of obesity and type 2 diabetes are surging around the world as people eat more and exercise less. The four studies published in the journal Nature Medicine help explain how obesity might cause diabetes and how the two together can cause organ damage, heart disease and death.

Guo-Ping Shi at Brigham and Women's Hospital and Harvard Medical School in the United States and colleagues found that mast cells -- the immune cells that get out of control in allergy and asthma -- were abundant in fat tissues of obese and diabetic people and mice.

They created obese and diabetic mice by overfeeding them. Then they gave some of the mice two antihistamines, one called ketotifen fumarate, sold by Novartis AG under the brand name Zaditor and generically available cromolyn.

Both help stabilize mast cells in people with allergy or asthma, Shi said in a statement.

Mice fed a healthy diet improved moderately, while those given either cromolyn or Zaditor showed dramatic improvements. But mice given the drug and switched to a healthy diet showed nearly 100 percent recovery in all areas.

"The best thing about these drugs is that we know it's safe for people," Shi said. "The remaining question now is: Will this also work for people?"

Shi will test both in monkeys.

IMMUNE RESPONSE

Type 1 diabetes is an autoimmune disease -- one in which the immune system mistakenly attacks healthy tissue. The studies in Nature Medicine suggest that type 2 diabetes and obesity also involve the immune system.

Satoshi Nishimura of the University of Tokyo and colleagues found a surge in immune cells or lymphocytes called CD8 T-cells in obese mice fed a high-fat diet.

Mice engineered to be deficient in CD8 T-cells had markedly less inflammation, even when fed a high-fat diet.

"So if we can find the molecule that triggers (the production of) CD8 T-cells, we can block or inhibit it (the molecule) using drugs," Nishimura said in a telephone interview.

Harvard pathology professor Diane Mathis and colleagues found T-cells were abundant in the abdominal fat tissue of normal-weight humans and mice, but absent in obese and diabetic humans and mice.

Obese mice and people had another class of immune cells called macrophages in their fat while normal weight people and animals did not have them.

This could cause the body to stop using insulin correctly -- a hallmark of type 2 diabetes, said Harvard's Steven Shoelson, who worked on the study.

"It's possible that the inflammation caused by macrophages results in insulin resistance," Shoelson said. T-cells may help control this, he said.

Michael Dosch of the Hospital for Sick Children in Toronto, Canada, and colleagues made similar findings. It may be possible to vaccinate people against type 2 diabetes, they suggested.

Using Ultrasound To Detect Early Signs Of Osteoarthritis

Researchers at The University of Nottingham are hoping to find out if inflammation of the knee could be an early sign of osteoarthritis - a condition which leads to pain, stiffness, swelling and disability.

27 july 2009--Up to six million people in the UK suffer from osteoarthritis in the knee. Now 200 patients, over the age of 55, from GP practices across Nottingham are to take part in a study led by research physiotherapist Michelle Hall in the School of Nursing, Midwifery and Physiotherapy.

Mrs Hall, who is a lecturer in the Division of Physiotherapy Education, said: "It has been shown that people who have inflammation may develop more severe and progressive osteoarthritis and experience greater pain and disability. The ability to detect the presence of inflammation using Ultrasound could therefore be important in terms of prognosis and selection of certain treatments."

With a three-year training fellowship from the Arthritis Research Campaign of £192,000 Mrs Hall will use new ultrasound techniques to identify if this common condition, in people over 55, can be linked to osteoarthritis.

At the moment osteoarthritis can only be identified by x-ray, which is limited to revealing changes to bones and degeneration of cartilage. It does not show up any changes or inflammation to the surrounding soft tissue or joint lining. This inflammation may also contribute to pain and stiffness and could, in fact, be a precursor to osteoarthritis.

Osteoarthritis is known as a "wear and tear" condition in which cartilage wears away, leaving bones rubbing together. Recently scientists have shown that inflammation in the joint lining may also play a role in its development.

The team from The University of Nottingham's physiotherapy education and academic rheumatology departments aim to find out if people with knee pain and/or knee osteoarthritis also have inflammation in their knees.

Patients will attend the Clinical Sciences Building at the University for the ultrasound scans which will repeated three months later or if participants report a change in their knee pain, to chart the progress of the inflammation to see whether this correlates with x-ray changes or with increases in pain. A control group of healthy volunteers will also undergo ultrasound on their knees as a comparison group.

Source:
Michelle Hall
University of Nottingham

Unhooking the Obesity-Diabetes Connection

27 july 2009-- Scientists may be closer to solving a medical mystery with huge implications for personal and public health: Why obese people are prone to developing type 2 diabetes.

A series of studies appearing online July 26 in Nature Medicine suggest that inflammation within the fat tissues of heavy individuals could trigger the blood sugar disease.

What's more, each of the four completely independent studies, from two continents and three countries, showed that interfering with these immune-cell processes actually reversed diabetes in mice.

The long-term implications of the findings are enticing: perhaps one day a cure for type 2 diabetes, a condition that now plagues more than 23 million people in the United States alone.

"This group of papers suggests that cellular immunity may regulate inflammation in fat," said Dr. Vivian Fonseca, professor of medicine at Texas A&M Health Science Center College of Medicine and director of the Diabetes Institute at Scott & White. "The authors do suggest that if you change the inflammatory response by changing the way the body cells respond to a trigger for inflammation, you might be able to get at the real heart of diabetes and that suggests you could cure it."

But Fonseca warned, all these studies were conducted in mice and have yet to be proven in humans

In type 2 diabetes, the body often becomes resistant to insulin and doesn't use it effectively. In the last decade or so, researchers have presented evidence that suppressing inflammation in animals could improve insulin resistance and other processes involved with diabetes. Inflammation is now widely believed to be involved in many metabolic diseases afflicting obese individuals. Inflammation in fat tissue, in particular, seems to be a culprit, by changing fat tissue function, thereby contributing to insulin resistance.

But the exact mechanisms of the phenomenon have been unclear.

Three papers, one from Japan, one from Canada and one from the United States, showed that immune system cells known as T cells were deficient in obese mice, pushing the immune system to somehow initiate insulin resistance.

Restoring T cells to more normal levels actually reversed weight gain and improved insulin resistance, even when the mice continued on a high-fat diet.

The fourth study looked at another class of immune cells called mast cells, which are more commonly linked to allergies.

An over-abundance of mast cells contributed to obesity and diabetes in mice, but when mast cells were removed from the system the problem was corrected, explained study senior author Guo-Ping Shi, a biochemist with Brigham and Women's Hospital in Boston.

"We gave mice a high-fat diet for three months and they developed obesity and diabetes," he said. But mice that had been stripped of mast cells did not. "These mice are protected from the disease if they are without these cells," Shi said.

Shi's team also gave wild-type ("normal") mice allergy medicines, which work to "stabilize" mast cells. This also led to improvements in the mice.

"We can use the drugs to manipulate cell activity or prevent disease in this case," Shi said.

Shi said he has signed a contract with a local company to develop a version of the drugs to combat diabetes in humans.

More information

There's more on type 2 diabetes at the American Diabetes Association.

Swine flu vaccine being tested

Clinical trials of newly developed vaccines for swine flu have begun in the USA and Australia. These human studies will gather data on the safety and effectiveness of the vaccine.

26 july 2009--The National Institute of Allergy and Infectious Diseases (NIAID), which is part of the National Institutes of Health in the USA, announced yesterday that a network of medical research institutions is about to begin a series of clinical trials to gather safety and efficacy data about some of the new influenza vaccines.

• At the same time, two vaccine manufacturers in Australia (CSL and Vaxine) have also begun testing their vaccine in healthy adult volunteers.
• The clinical trials will provide important early safety and efficacy data about the vaccines. In particular, the researchers will be monitoring adverse effects and immunogenicity (how well the vaccine provokes an immune response). They will also be assessing the dose required to be effective and whether the vaccine can be given alongside seasonal influenza vaccination.
• The American trials will be in healthy adult volunteers and in elderly volunteers who are also receiving the seasonal vaccine. If early results are positive, further studies may begin in healthy adolescents and children.
• The trials may take some months to complete, and the vaccination programmes are likely to begin before the full results are available. However, there should be sufficient results by September or October to spot real safety concerns and to allow governments to begin planning for the use and distribution of the new vaccines. Safety will continue to be monitored through surveillance when vaccination programmes are introduced nationally.

What are the WHO’s current recommendations for vaccines?

At a special meeting of the Strategic Advisory Group of Experts (SAGE) on July 07 2009, the WHO considered the potential options for vaccine use. They came up with some recommendations that were endorsed by the WHO Director-General, including:

• Healthcare workers should be immunised first.
• For other groups it is suggested that countries should decide their own vaccination policies and priority orders depending on country-specific conditions, possibly commencing with pregnant women and anyone aged over six months with one of several chronic medical conditions, followed by healthy young adults between 15 and 49 years of age, healthy children, healthy adults aged 50 to 64 years and healthy adults aged 65 years and above.
• Post-marketing surveillance of the vaccine is very important, particularly in certain population groups. This is because some new technologies are involved in the production of these vaccines and these have not yet been fully tested in certain groups. It is also important that results of this surveillance are shared widely in the international community so that countries can make any necessary adjustments to their vaccination policies.
• The production of particular types of vaccine formulations was also promoted, including live attenuated viruses and those that have oil-in-water adjuvants, which would help to protect against drifted strains of the virus (slightly mutated versions of the virus).

How are vaccines made?

To make a vaccine, a large amount of the virus or bacteria is needed. In the case of swine flu, the US Centers for Disease Control and Prevention (CDC) began isolating and preparing strains of the swine flu virus as soon as the first human case became known. These strains were sent to its counterparts in other countries including the National Institute for Biological Standards and Control (NIBSC) in the UK. These organisations prepare the virus strains to be used in making the vaccine.

Viruses can be grown in hens’ eggs, but often the infectious influenza virus strains do not grow well in eggs. To get around this, the infectious virus is injected into the eggs with another influenza virus that thrives in eggs. The two viruses swap pieces of their genetic material and produce hybrids, some of which both grow well in hens’ eggs and also have the elements of the disease-causing virus needed for a vaccine. These hybrids are isolated and the best candidate for making a vaccine is selected. This chosen hybrid strain is then grown and distributed to vaccine manufacturers.

The vaccine manufacturers use dead or weakened virus to create the vaccine. Other constituents can also be added to the vaccine, such as a suspending fluid to carry the virus into the body, preservatives and stabilisers that allow the vaccine to be stored safely, and chemicals to help the vaccine to promote an immune response.

When will a vaccine be available?

Vaccine development usually takes about six months and it began in April 2009. The WHO suggests that the first doses of influenza A H1N1 vaccine are expected as early as September 2009. The UK government says that the first batches of vaccine are expected to arrive in the autumn, and 30m double doses (enough for half the population) are expected to be available by the end of the year. The government has ordered enough vaccine for the whole population, and when it becomes available will focus on those at the greatest risk first.

Who will be a priority for vaccination?

The administration of the vaccines will need to be prioritised. The decision on prioritisation of the population will be taken on the basis of which groups are being most affected by the virus, when the vaccine arrives and how best to protect the NHS from being over-stretched.

How effective and safe will the vaccine be?

Vaccination is very effective in preventing and reducing the impact of serious illness. Although vaccines are not 100% effective and can become less effective if the virus mutates, they still offer some protection. Current flu vaccines last for about a year and give about 70-80% protection against infection with strains of influenza virus that are very similar to those used to make the vaccine. It is too early to predict how the swine flu virus might mutate. The WHO is closely monitoring it for changes, and this will help countries to make a quick response if the virus undergoes important changes.

The human trials that are currently underway will provide some evidence of the short-term safety and effectiveness of the vaccines. In particular, the researchers will be monitoring side effects and also how effectively the vaccine prompts a response from the immune system (its immunogenicity). The vaccines will be approved for use by national authorities. In this country the Medicines and Healthcare products Regulatory Agency (MHRA) is responsible for monitoring the safety of flu medicines and vaccines. Safety monitoring will be ongoing once the vaccine programme is introduced.

Links to the headlines

NIH news: NIAID Set to Launch Clinical Trials to Test 2009 H1N1 Influenza Vaccine Candidates

CIDRAP: H1N1, seasonal flu vaccines to be tested together

Further reading

National Institute for Biological Standards and Control website

NHS Immunisation website

NHS Immunisation Influenza factsheet 2008

WHO Influenza A(H1N1 ) vaccine webpage

WHO: Pandemic (H1N1) 2009 briefing note 2: WHO recommendations on pandemic (H1N1) 2009 vaccines

US Centers for Disease Control (CDC) Pandemic Flu webpage

US CDC Pandemic Flu vaccine question webpage

Long-life milk?

26 july 2009--”A pint of milk a day cuts chances of heart disease and stroke by up to a fifth,” The Daily Telegraph has said. The nation’s favourite dairy drink is also said to cut risk of developing diabetes and colon cancer. The findings may challenge the view held by some that too much dairy is bad for you.

These findings come from a systematic review that has combined the results of several observational studies, which found that consuming higher amounts of milk or dairy products is associated with reduced risk of heart disease, stroke and diabetes.

However, there are some limitations of the study that have to be considered when drawing conclusions from these results, in particular that the studies reviewed used variable methods for assessing milk consumption and it is possible participants misreported the milk they drank. Several other factors not measured in this study could be playing a role in disease risk, such as other dietary patterns, physical activity and lifestyle habits. Furthermore, variable and inconclusive results were also obtained for fat content of milk, meaning the study could not compare whole milk with low-fat milk.

Where did the story come from?

Peter Elwood and colleagues of Cardiff University, the University of Reading and the University of Bristol carried out this research. No sources of funding were reported. The study was published in the peer-reviewed Journal of the American College of Nutrition.

What kind of scientific study was this?

This is a systematic review and meta-analysis in which the researchers used cohort and case-control studies to investigate whether milk and dairy consumption affected the outcomes of vascular disease and diabetes.

The authors searched the Medline medical database for relevant studies using the phrases milk, milk protein, dairy, dairy calcium, heart disease, coronary artery disease, myocardial infarction, ischaemic heart disease, stroke, diabetes or metabolic syndrome.

The authors included studies that collected data on milk consumption at the start of the study and then followed people up over a period, examining a range of medical outcomes.

Among the 324 studies identified by the search there were 11 suitable studies on milk products and heart disease, seven on milk and stroke and four on milk and diabetes/metabolic syndrome. The researchers pooled the results of these relevant studies to determine the risk of their respective outcomes in relation to levels of milk consumption.

Within these individual studies there had been attempts to make statistical adjustments to account for the influence of confounders, though the exact methods of adjustment varied between studies. The authors then obtained extra data from studies that gave disease risks in relation to the type of milk consumed, e.g. whole or low-fat.

Finally, the authors summarised conclusions from the recent report by the World Cancer Research Fund and American Institute for Cancer Research, looking at observations between cancer development and milk consumption.

What were the results of the study?

The authors pooled the results of 15 cohort studies examining risk of heart disease and stroke, featuring over 600,000 participants and extensive follow-up times, in the range of 8 to 25 years. They found that the risk of heart disease in subjects with the highest milk or dairy consumption was reduced by 16% compared to those with the lowest consumption (RR 0.84, 95% CI 0.76 to 0.93). When looking solely at the seven studies examining stroke events, the researchers found that stroke risk was reduced by about 21% (RR 0.79, 95% CI 0.75 to 0.82).

The combined results of the four studies examining the development of diabetes depending on milk consumption found that the risk was reduced by 8% among those with the highest milk intake (RR 0.92, 95% CI 0.86 to 0.97).

The studies examined featured adjustments for various confounders including age, sex, BMI, smoking, physical activity, social class, cholesterol and blood pressure.

When the authors looked across all of the studies for any that had given separate results for whole and low-fat milk, risk results were highly variable and were generally not significant.

The researchers also report on other studies carried out that had made similar observations to their own results. Four case-control studies observed that high milk consumption reduced the risk of metabolic syndrome, which is a combination of risk factors occurring together of elevated blood glucose, high cholesterol, being overweight or obese, and high blood pressure (RR 0.74, 95% CI 0.64 to 0.84).

Additionally, four case-control studies asking women who had had a heart attack about their prior consumption of milk, found 17% reduction in risk from drinking the highest quantity of milk (RR 0.83, 95% CI 0.66 to 0.99).

The Report of the World Cancer Research Fund was examined to look at data on the relationships between various cancers and dairy consumption. The report’s results were based on a variety of cohorts and case control studies. Variable associations were found for studies examining prostate, colon and bladder cancer, and no associations were found for other cancers.

What interpretations did the researchers draw from these results?

The authors conclude that the results of their review provide evidence of an overall survival advantage from consuming milk and dairy products, highlighting the high proportion of UK deaths currently attributable to vascular disease, cancer and diabetes.

What does the NHS Knowledge Service make of this study?

This review, which has combined the results of various observational studies, found that consuming higher amounts of milk or dairy products is associated with reduced risk of heart disease, stroke and diabetes.

However, the systematic review pooled the results of studies of varying quality, study length, inclusion criteria, disease outcomes and methods of assessing milk or dairy consumption. These individual studies may have had several biases. There are also other aspects of this study that must be considered when interpreting the results of the study:

• The researchers looked at case-control studies in which a person has already experienced the disease outcome, e.g. heart attack or stroke, and is then asked to recall their past consumption of milk. This may involve recall bias, where a person who has the disease recalls differently compared to those who have not, as a way to try to find a possible explanation.
• Additionally, the review pooled data from cohort studies, which have a design that may be more reliable for assessing causation as the person hasn’t yet developed the disease. However, these individual studies had considerable variability in their methods.
• One important variation was that milk consumption had been variably assessed through food questionnaires or 24-hour food recall, and such estimates are likely to involve some inaccuracy. Also, the studies used variable exposure categories. For example, some studies compared people who drank milk to people who did not. Others looked at number of days of the week milk was drunk on, others at the number of pints or glasses drunk per day or per week. As such, it is very difficult to gain any indication of the optimal quantity of milk to consume. Furthermore, it is unclear whether other dairy sources such as cheese, yoghurt or cream had been assessed.
• There were differences in results between some of the cohort studies. As the authors say when pooling the studies evaluating risk of heart disease they excluded the results of one study, in which reduced risk was observed from consumption of low-fat milk, but increased risk with consumption of whole milk. This finding differed from the other studies pooled.
• The individual studies had attempted to adjust for different confounders but there was inconsistency between studies in the factors that had been considered. Particularly, important lifestyle ones such as other dietary habits or physical activity, smoking or alcohol consumption may be confounding results.
• Randomised controlled trials would be the best way to investigate the health benefits of drinking milk but the researchers think these are unlikely to be practical to perform.
• There were no consistent results associating milk with risk of any type of cancer. Also, variable and inconclusive results were obtained in assessment of whole compared to low-fat milk.
• Conclusions that drinking more milk reduces risk of death are only indirect ones, following on from the fact that heart disease, stroke and diabetes are a significant cause of morbidity and mortality in the UK. The studies in this review have not actually examined death rate, survival or quality of life in those who did or did not develop disease.

Links to the headlines

A pint of milk a day cuts chances of heart disease and stroke. The Daily Telegraph, July 23 2009

Drinking milk cuts ‘risk of dying from heart disease and stroke by one fifth’. Daily Mail, July 23 2009

Links to the science

Elwood PC, Givens DI, Beswick AD et al. The Survival Advantage of Milk and Dairy Consumption: an Overview of Evidence from Cohort Studies of Vascular Diseases, Diabetes and Cancer. JACN, 2008

LIVE DECADES LONGER WITH A PILL?

26 july 2009--“A wonder pill could extend the lifespan of people by up to 23 years,” the Daily Express has reported on its front page. Most other newspapers have also featured stories on an ‘anti-ageing drug’, which contains a chemical made by insects in the soil on Easter Island. They say that it stops cells in mice from ageing by blocking the damaging proteins thought to be responsible for the ageing process.

The lifespan of mice (up to the point where 90% had died) was extended by up to 38% if measured from the time that they were given the drug. The newspapers say this raises the possibility that a similar drug might delay ageing in people by several years. However, it is based on several assumptions, such as equating 10 mouse days to one year of a human life. The research also raises the possibility that the survival rates might vary due to different diets given to mice before they were given the drug.

The drug rapamycin has already been used in humans to prevent rejection after transplants, but the researchers say it is not licensed for healthy people, and may increase risk of infections. The main appeal of this research is the benefit seen in mice that were given the drug later in life. It means that researchers now have a target for the development of new drugs aimed at treating age-related diseases and extending healthy life in humans.

Where did the story come from?

This research was carried out by Dr David E. Harrison from the Jackson Laboratory in Maine, US. Other colleagues from departments and institutes of ageing around the US co-authored the paper, which was supported by grants from the National Institutes of Ageing and the Department of Veterans Affairs in the US. The study was published in Nature, the peer-reviewed scientific journal.

What kind of scientific study was this?

This animal study testing how the drug rapamycin might affect lifespan in specially bred mice.

Rapamycin, which was discovered in the 1970s in the hunt for new antibiotics, is a drug that inhibits the ‘TOR signalling pathway’. The TOR signalling pathway has been studied in yeasts and invertebrates, and it controls cell growth by activating and inhibiting important cell processes. In the laboratory, parts of this pathway have been inhibited by several things, such as low nutrient levels, caffeine and rapamycin. New TOR inhibitor drugs might potentially have roles in several areas of disease, particularly in the fight against cancer.

Rapamycin is currently used to suppress immune systems of patients who have had transplant operations, to prevent their bodies rejecting organs. It is also used in heart operations, and is being tested for its anti-cancer properties. It is not licensed for use in healthy people.

The research was conducted at three test sites in the US: The Jackson Laboratory, the University of Michigan and the University of Texas Health Science Center. All the mice were supplied by the Jackson Laboratory, and had been bred to be genetically unique despite the fact that they were all siblings. The researchers say that a 600-day-old mouse is roughly equivalent to a 60-year-old human. The initial research, which began in 2005, looked at 1,960 mice.

The researchers weaned the mice on a standard, specially formulated diet (mouse chow) until they were 600 days old, and then added rapamycin to the feed of the “rapamycin-fed group”. The remainder, “the control group”, continued to be fed on their normal diet. Rapamycin was prepared in capsule form so that it could pass through to the intestine undigested.

After the mice had been divided into the two groups at 600 days, they were followed until they died naturally or were judged to be too sick and “euthanised”. The researchers measured the average (median) survival and the number alive up to the last tenth of expected lifespan for a mouse. This was calculated by recording the day on which 90% of the mice had died. This is a measure of the mouse maximum survival, but not the actual length of time that all the mice lived.

What were the results of the study?

The researchers say that rapamycin extended the median and maximal lifespans of both male and female mice when fed the drug from 600 days of age. Combining results from the three test sites showed that rapamycin led to an increased survival time of 14% for females and 9% for males when measured from the start of the study to the point where 90% of the mice had died. The control female mice lived 1,094 days, which increased to 1,245 days in the treated females. The respective lifespan for males was 1,078 days, which increased to 1,179 days with treatment.

Patterns of disease did not differ between control mice and normal mice.

What interpretations did the researchers draw from these results?

The researchers say that “these are the first results to demonstrate a role for the mTOR signalling in the regulation of mammalian lifespan” and the “pharmacological extension of lifespan in both genders”.

They suggest that their findings have implications for the further development of interventions which target the mTOR pathway for the treatment and prevention of age-related diseases. They also suggest that rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or through a combination of the two.

What does the NHS Knowledge Service make of this study?

This study has several interesting features and will provide an added impetus to research in this area. However, there are important points to consider when interpreting this study.

Across the groups mice actually had about the same lifespan, about 1,250 days, and the survival improvements reported are due to the measures used in this study, and the fact that fewer mice in the treated group died in the first 90% of their lifespan, and instead died in the last 10%. This difference is apparent from an examination of the survival curves reported in the study. Survival curves simply report the proportion of mice surviving at all time points throughout the study.

Looking at these curves, it is apparent that in two of the laboratories the survival curves begin to separate before the 600-day point. This suggests that there was a difference in the number of mice surviving in the control and treated groups, even before they were given the active drug.

This is a puzzling finding, which indicates that a factor other than the drug had affected their rates of survival. The researchers say that this difference was partly due to the control mice in the two labs receiving a different formula of mouse feed.

On this basis, the researchers say they cannot rule out the possibility that improved survival among these two groups of males might reflect differences in nutritional or health status between control and rapamycin groups before 600 days, rather than solely the effects of rapamycin.

Finally, it should be noted that this was an experiment in mice, therefore the benefit of longer lifespan found in this study may not translate directly into humans. On this basis, rapamycin should not yet be considered to ‘extend life by 20 years’. A further consideration of potentially extending lifespans must also be the quality of life experienced during any extra years gained.

Links to the headlines

Tests raise life extension hopes. BBC News, July 09 2009

Secret to a longer life lies on Easter Island. The Independent, July 9 2009

Easter Island drug 'adds decade to life'. The Sun, July 9 2009

Rapamycin extends life in mice, raising hopes of life-prolonging drug for humans. The Times, July 9 2009

New pill can add 20 years to life. Daily Express, July 9 2009

Scientists discover Easter Island 'fountain of youth' drug that can extend life by ten years. Daily Mail, July 9 2009

Dirty secret to staying young. Daily Star, July 9 2009

Links to the science

Harrison DE, Strong R, Sharp ZD, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature [advance online publication] 8 July 2009

Further reading

Webster AC, Lee VWS, Chapman JR, Craig JC. Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients.

Celiac disease may strike elderly, too

NEW YORK, 25 july2009- Celiac disease doesn't only affect the young, new research from Finland confirms, but can strike a person for the first time in later life.

In people with celiac disease, eating gluten-a protein found in many types of grain-causes the immune system to launch an attack on the small intestine. This can eventually damage the organ and lead to poor absorption of nutrients, especially fat. But people with celiac disease who cut gluten out of their diet can avoid symptoms and complications.

It's now possible to use blood tests to determine whether or not a person has celiac disease, which affects over 1% of Western populations, Dr. Anitta Vilppula of Päijät-Häme Central Hospital in Lahti and her colleagues note. In the United States, celiac disease is four times more common now than it was in the 1950s. (See Reuters Health eLine report, July 10, 2009.)

While people may think of the condition as a problem for children and young adults, they add, Vilppula and her team recently identified cases of celiac disease in elderly people. In some individuals, the condition had not been detected.

In the current study, the researchers investigated whether some older people had actually developed celiac disease later in their lives, or the disease had simply gone undetected. They looked at 2,815 people over 55 who had undergone blood tests for celiac disease in 2002, 2,216 of whom were screened again in 2005. The researchers also did biopsies of patients' small intestines to confirm the blood test findings.

In 2002, 2.13% of the study participants had biopsy-confirmed celiac disease, while 2.34% did in 2005. There were five new cases among people whose blood tests had initially been negative for the disease, and only two of these individuals had symptoms. That led the researchers to conclude that the elderly could develop the disease late in life.

Past research has shown that undetected celiac disease can lead to significant health problems in older people, the researchers note; in one study including 35 people 60 and older, 15 had been seeing their doctor for 28 years, on average, with symptoms without being diagnosed.

Doctors should be aware of the possibility that their older patients may have or develop celiac disease, Vilppula and colleagues say, and they should use blood tests to confirm the diagnosis-even though a negative test doesn't mean a person won't develop the condition later on.

SOURCE: BMC Gastroenterology, online June 29, 2009.

Lung volume reduction surgery shown to prolong and improve life for some emphysema patients

25 july 2009--Lung volume reduction surgery (LVRS) can have a significantly beneficial effect in patients with severe emphysema, according to the first ever study to randomize emphysema patients to receive either LVRS or non-surgical medical care.

"We found lung reduction surgery is good treatment alternative for selected emphysema patients since it not only improves survival but also meaningfully improves quality of life for a period of at least five years after the operation," said lead author of the study, Roberto Benzo, M.D., MSc. of the Mayo Clinic. "Patients who underwent LVRS, with the exception of those who had non-upper-lobe-predominant emphysema, had both a survival and quality of life benefit when compared to similar patients undergoing medical treatment only."

The results of the National Emphysema Treatment Trial (NETT) study were reported in the August 1 issue of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

The NETT group recruited 1,218 patients with severe emphysema and randomized them to either undergo LVRS or non-surgical medical treatment, which generally consisted of customized use of medication, oxygen support, smoking cessation and pulmonary rehabilitation. LVRS consists of removing a portion of emphysematous lung tissue in the patient. While removing lung tissue in patients whose breathing is compromised may seem counterintuitive, severe emphysema causes "air trapping", where the patient can inhale, but is unable to force the air back out of the lung. This is one of the main causes of shortness of breath in patients with emphysema.

"By removing the section of lung that is primarily affected with severe emphysema, we can decrease air trapping and consequently the shortness of breath, which can thereby improve the patient's perceived quality of life," explained Dr. Benzo.

A total of 608 patients underwent LVRS and 610 received standard medical care. The patients were followed for five years or until they died. All endpoints except death were measured at six-month intervals. The primary outcome was a composite endpoint consisting of death or an "unquestionable and meaningful deterioration" in quality of life, defined as an 8-point or greater drop on the Saint George's Respiratory Questionnaire, a widely used standardized measure of quality of life in patients with respiratory disease.

In the total sample, the average time until a "composite event"—either death or a serious decline in quality of life— was one year for medically treated patients and two years for patients who had undergone LVRS. Patients whose emphysema was predominantly found in the upper lobes of their lungs—about 65 percent of emphysema patients— also showed quality of life and survival benefits greater than survival benefits alone, suggesting that they lived longer and better.

However, LVRS has a small but inherent danger of perioperative mortality.

"LVRS has risks that patients need to understand and acknowledge," said Dr. Benzo. "In NETT, close to five percent of the patients undergoing lung reduction died in the post-operative period. However, once the post operative period is over, the quality of life benefit comes right away."

"NETT was landmark study: randomization was necessary at that point as we did not know the true benefits of the surgery," said Dr. Benzo. "We now know the individuals that benefit from it. Randomization would be unethical now in the group of individuals that we now know get benefit. This study shed light on the palliative (overall well-being) benefits of the surgery, which many patients consider as important as the survival benefit

Macular Degeneration: The 'See Food' Diet

25 july 2009--Current research suggests that a diet high in omega-3 fatty acids may help prevent one of the leading causes of legal blindness among the elderly. The related report by Tuo et al, "A high omega-3 fatty acid diet reduces retinal lesions in a murine model of macular degeneration," appears in the August 2009 issue of the American Journal of Pathology.

Age-related macular degeneration (AMD), loss of vision in the center of the visual field (macula) due to retinal damage, is one of the leading causes of legal blindness among the elderly. Approximately 10% of people from 66 to 74 years of age will develop some level of macular degeneration, making it difficult for them to read or even recognize faces.

A diet high in omega-3 fatty acids has been found to protect against a variety of diseases including atherosclerosis and Alzheimer's disease. Retrospective studies have suggested that diets high in fish oil or omega-3 fatty acids may also contribute to protection against AMD. A group led by Dr. Chi-Chao Chan at the National Eye Institute in Bethesda, MD examined the direct effect of omega-3 fatty acids on a mouse model of AMD. A diet with high levels of omega-3 fatty acids resulted in slower lesion progression, with improvement in some lesions. These mice had lower levels of inflammatory molecules and higher levels of anti-inflammatory molecules, which may explain this protective effect.

Tuo et al suggest that "a diet enriched in EPA and DHA can ameliorate the progression of retinal lesions in their mouse model of AMD" and that "the results in these mice are in line with the epidemiological studies of AMD risk reduction by long chain n-3 fatty acids." The results "further provide the scientific basis for the application of omega-3 fatty acids and their biologically active derivatives in the prevention and treatment of AMD." In future studies, Dr. Chan and colleagues plan to use this murine model "to evaluate [other] therapies that might delay the development of AMD." Their ongoing projects include the "testing of systematic delivered pharmacochaperones and antioxidative molecules, as well as intraocularly delivered gene therapies."

This work was supported by grants from The Intramural Research Program of the National Eye Institute, the National Institutes of Health, and the American Health Assistance Foundation.

Tuo J, Ross RJ, Herzlich AA, Shen D, Ding X, Zhou M, Coon SL, Hussein N, Salem Jr N, Chan C-C: A high omega-3 fatty acid diet reduces retinal lesions in a murine model of macular degeneration. Am J Pathol 2009 175: 799-807

Source:
Angela Colmone
American Journal of Pathology

Some blood pressure drugs may help protect against dementia, study shows

WINSTON-SALEM, N.C., 24 july 2009-– A particular class of medication used to treat high blood pressure could protect older adults against memory decline and other impairments in cognitive function, according to a newly published study from Wake Forest University School of Medicine.

Research suggests that some of the drugs classified as angiotensin-converting enzyme (ACE) inhibitors, specifically those types of ACE inhibitors that affect the brain by crossing the blood-brain barrier, may reduce inflammation that could contribute to the development of Alzheimer's disease, a major cause of dementia.

The study appears in the current issue of Archives of Internal Medicine.

"High blood pressure is an important risk factor for Alzheimer's disease and vascular dementia," said Kaycee Sink, M.D., M.A.S., lead author of the study, geriatrician and an assistant professor of internal medicine – gerontology. "Our study found that all blood pressure medications may not be equal when it comes to reducing the risk of dementia in patients with hypertension."

Dementia is the broad term used to describe conditions in the brain that cause loss of brain function. There are several different causes of dementia, but Alzheimer's disease and strokes are two of the most common. People with dementia begin to lose their memory and may not be able to think well enough to do normal activities, such as getting dressed or eating, may lose their ability to solve problems or control their emotions, may experience personality changes and/or may become agitated or see things that are not there.

While memory loss is the hallmark of dementia, it does not, by itself, mean an individual has dementia. People with dementia have serious problems with two or more brain functions, such as memory and problem solving.

Someone is diagnosed with dementia every 70 seconds. It is estimated that the number of people in the United States living with dementia will increase to about 13 million by the year 2050. Therefore, delaying the onset of dementia, even by one year, would have a substantial impact on public health.

Hypertension, or high blood pressure, is a major contributor to the development of all types of dementia. Many of the estimated one in three U.S. adults who have hypertension are treated with ACE inhibitors, a class of drugs that help lower blood pressure by causing the blood vessels to relax and widen.

Some ACE inhibitors are known as "centrally-acting" because they can cross the blood-brain barrier, a specialized system of tiny blood vessels that protects the brain from harmful substances in the blood stream. Centrally-acting ACE inhibitors include captropril (Capoten®), fosinopril (Monopril®), lisinopril (Prinivil® or Zestri®), perindopril (Aceon®), ramipril (Altace®) and trandolapril (Mavik®).

For the study, researchers analyzed data from the Cardiovascular Health Study, a long-term study of cardiovascular risk factors that involved 5,888 people over 65 years old from Forsyth County, N.C.; Sacramento County, Calif.; Pittsburgh, Pa.; and Washington County, Md.

The investigators specifically looked at 1,074 study participants who were free of dementia when they entered the study and who were being treated for hypertension. They evaluated whether exposure to ACE inhibitors in general – and to the centrally-active versus non-centrally active drugs – was related to dementia development and cognitive decline.

Compared to other classes of anti-hypertensive drugs, researchers found no association between exposure to ACE inhibitors as a class and the risk of dementia. There was a significant cognitive benefit, however, seen in those individuals treated with the centrally-active ACE inhibitors specifically.

The study found an association between taking centrally-active ACE inhibitors and lower rates of mental decline as measured by the Modified Mini-Mental State Exam, a test that evaluates memory, language, abstract reasoning and other cognitive functions. The research showed that participants who were exposed to ACE inhibitors that cross the blood-brain barrier saw an average 65 percent less cognitive decline per year of exposure compared to participants taking other blood pressure medications.

Researchers also found that non-centrally active ACE inhibitors were associated with an increased risk of dementia and the people taking them were more likely to develop difficulty performing daily activities. Specifically, participants who, for three years, took ACE inhibitors that do not cross the blood-brain barrier were at a 73 percent greater risk of developing dementia than were the individuals taking other anti-hypertensive drugs.

"ACE inhibitors have been shown to be beneficial to the heart and kidneys, and this study gives evidence that they may also be beneficial to the brain—at least the ones that are able to get into the brain," Sink said. "We already know it is important to treat high blood pressure and keep it under good control. But our study finds that some blood pressure medications, such as the ACE inhibitors that cross the blood brain barrier, may offer benefits to the brain that others do not. If a patient has an indication for an ACE inhibitor, it makes sense to choose one that crosses the blood brain barrier. This is quite different from the typical recommendations for physicians to avoid medications in older adults that get into the brain."

###

The research was supported by the National Heart, Lung and Blood Institute, the Wake Forest University Pepper Older Adults Independence Center, the Kulynych Center for Research in Cognition at Wake Forest University, the Hartford Geriatrics Health Outcomes Research Scholars Program, the National Institute of Neurological Disorders and Stroke, and the National Institute on Aging.

Treatment Can Reduce Bone Turnover in Prostate Cancer

Study finds that denosumab reduces bone turnover better than bisphosphonates

24 july 2009-- Treatment of bone metastases in prostate cancer patients with denosumab, which blocks bone resorption, reduces bone turnover compared with bisphosphonates, according to a study in the August issue of the Journal of Urology.

As part of a Phase II trial, Karim Fizazi, M.D., from the Institut Gustave Roussy in Villejuif, France, and colleagues randomly assigned 50 patients with prostate cancer and bone metastases, despite the use of intravenous bisphosphonates, to continue receiving intravenous bisphosphonates every four weeks or to receive 180 mg subcutaneous denosumab (an antibody to block bone resorption) every four weeks or 180 mg every 12 weeks.

The researchers found that, at week 13, more denosumab-treated patients had urine N-telopeptide (a marker of bone turnover) less than 50 nM bone collagen equivalents per mM creatinine compared with bisphosphonate-treated patients (69 versus 19 percent), which continued at week 25 (69 versus 31 percent). Grade 4, asymptomatic, reversible hypophosphatemia was observed in one denosumab-treated patient.

"In patients with prostate cancer related bone metastases and increased urine N-telopeptide despite intravenous bisphosphonate treatment, denosumab normalized urine N-telopeptide levels more frequently than ongoing intravenous bisphosphonates," Fizazi and colleagues conclude.

The study was supported by Amgen Inc.; several authors reported financial or other relationships with pharmaceutical companies.

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Antihypertensive Drugs Associated With Cataracts

Study finds users of beta blockers more likely to require cataract surgery

24 july 2009-- Patients treated with beta blockers for hypertension are more likely than their counterparts not using the drugs to develop cataracts and require cataract surgery, according to a study published online July 23 in the British Journal of Ophthalmology.

Gowri L. Kanthan, of the University of Sydney in Australia, and colleagues conducted a study of 3,654 people aged 49 years and above who were examined at baseline, of whom 2,454 were examined again after five years, 10 years, or both. The subjects' eyes were examined and they provided information on medication use.

There was a borderline association between the use of oral or topical beta blockers and nuclear cataracts, and both types of drugs were a significant predictor of incident cataract surgery, the investigators found. The association persisted after adjusting for confounding factors such as age, gender, blood pressure and intraocular pressure. The authors further note that cataract incidence and surgery were not predicted by any other antihypertensive medication except angiotensin-converting enzyme inhibitors, which were associated with incident cataract surgery.

"Given the limitations and the possibility of various biases in our study, these findings should be interpreted with caution," the authors write. "Nevertheless, the biological plausibility for an association between beta-blocker use and cataract, and the internal consistency of this finding for use of both oral and topical beta blockers, warrants further study."

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