Agent Orange May Boost Vietnam Vets' Hypertension Risk

(HealthDay News) -- Exposure to the defoliant herbicide Agent Orange during the Vietnam War may be raising blood pressure levels for the aging veterans of that conflict.

That's the biggest change in the latest of a series of reports from the U.S. Institute of Medicine on the long-term health effects of Agent Orange. The report was released Friday.

The IOM's Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides last issued its updated findings in 2005; this report is based on data collected up to 2006. The reports are compiled at the request of the U.S. Department of Veterans Affairs.

"In two new studies, Vietnam veterans with the highest exposure to herbicides exhibited distinct increases in the prevalence of hypertension; the prevalence of heart disease was also increased," the report found, although the IOM committee stopped short of suggesting that wartime exposure to Agent Orange is currently raising veterans' risk of ischemic heart disease.

The group said the latest data on hypertension risk is of a much higher quality than prior research looking at links between Agent Orange and heart disease or heart disease risk factors.

However, the new findings are "consistent" with those gleaned from prior research.

There were other changes to the IOM's latest update of Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam, which is issued every two years (this is the seventh such report).

As new data have emerged, a few important cancer types -- malignancies of the brain, stomach, colon, rectum and pancreas -- were moved from a category labeled "limited or insufficient evidence of no association [with Agent Orange]" to a more neutral category --"inadequate or insufficient evidence to determine association."

The committee was deadlocked and indecisive on whether to move two more tumor types -- breast cancer and melanoma -- as well as ischemic heart disease, from the "inadequate or insufficient evidence to determine association" category up to a category that implies there might be a connection to Agent Orange exposure -- "limited or suggestive evidence of association."

According to the report, "the committee could not reach consensus about the strength of the evidence" on those issues.
Finally, data on an illness linked to multiple myeloma, called amyloidosis, did satisfy the criteria needed to include it in the "limited or suggestive evidence of association" category, associating it for the first time with exposure to the herbicide.

All of these category changes are important, since the VA often consults the committee's reports when making medical or disability coverage decisions for Vietnam veterans. Certain conditions -- sarcomas, non-Hodgkin's lymphomas, chronic lymphocytic leukemia, and Hodgkin's disease -- have been found by the committee to be clearly associated with Agent Orange exposure, for example. The status of other conditions remains more ambiguous.

That ambiguity continues to rile veterans advocates such as Phil Kraft, executive director of the Darien, Conn.-based National Veterans Services Fund. He said that while he "admires the perseverance" of the IOM committee, too many sick Vietnam vets are still fighting for proper care.

"How hard is it to say, 'We're here for you, because you offered your life, and now we're going to help you,' " said Kraft, himself a Vietnam veteran.

He applauded the inclusion of hypertension within the "limited or suggestive evidence" category, but said he wasn't surprised, since, in his opinion, heart disease is rampant among veterans. "I talk to a lot of [veterans'] wives, and they will say, 'Everything was fine until my husband had his heart attack," Kraft said. "And it's not just because we are now all in our 50s and 60s."

Kraft said the evidence-based "bump up" for a number of cancers is also significant, since it may mean better access to medical and disability care for affected veterans. "Anything that is going to add to the list of compensations is a step in the right direction," he said. "I just wish [the committee] would be bolder."

That's because too many veterans are still battling the Veterans Administration for needed coverage, Kraft said. He used the example of a fellow veteran diagnosed with myeloma. The man did end up getting 100 percent disability and care, "but he had to fight for almost three years, while he was sick, because the VA was saying, 'Well, we don't know.' "

With American troops fighting now on a new front, Kraft hopes tomorrow's veterans will be wiser. One big problem for veterans from the Vietnam War is that they have no blood or other samples to demonstrate their baseline level of health before they went off to fight. That means it is often tough to prove that wartime exposures are the cause of an unhealthy change in their genetics or tissue toxicity levels, Kraft said.

"But I know that this time round, soldiers going to Iraq are being told to get a blood sample taken and preserved beforehand," Kraft said. "Guys that are still [in Iraq] are advising the younger guys to do that."

Kraft said it's disheartening that any veteran has to fight another, often lifelong battle to stay healthy and to get the coverage he or she deserves. As for the Institute of Medicine report, Kraft believes its recommendations remain far too cautious.

"I just wish they would loosen up a bit and come down with a recommendation that says, 'Do the right thing for veterans,' " he said. "That's all we have ever wanted."

More information
There's more on Agent Orange at the U.S. Department of Veterans Affairs.

Ovarian Cancer Vaccine Might Extend Survival

(HealthDay News) -- A vaccine to ward off recurrences of ovarian cancer shows promise, both in terms of safety and effectiveness, U.S. researchers report.

The 18 women who received the vaccine went a median of 19 months before their tumor reappeared, the team noted.

"From a clinical standpoint, the assertion that the women had a 19-month progression-free survival is astounding, because these are all recurrent disease patients," said Dr. Robert Morgan Jr., section head of medical gynecologic oncology at City of Hope Cancer Center in Duarte, Calif.

"In general, response rates and progression-free survival you see from someone is usually around six to eight months before the tumors relapse. This is really encouraging," added Morgan, who was not involved in the study.

He did sound one note of caution, however. "Eighteen patients is obviously not going to be enough to draw any firm conclusions," Morgan said. "But I think that this data is certainly data which should be encouraging to continue in larger trials."

Another expert echoed those sentiments.

"This is a very well-done study showing what we all know: that the immune system can play a very important role in our fight against cancers," said Dr. David A. Fishman, director of gynecologic oncology, cancer prevention and early detection at New York University Cancer Institute in New York City. "From a scientific standpoint, it's a very interesting study that shows a lot of promise, but it does not show that we're ready for prime-time yet."

The study, which was led by Dr. Kunle Odunsi of the Roswell Park Cancer Institute, in Buffalo, N.Y., was published Monday in the online edition of the Proceedings of the National Academy of Sciences.

Ovarian cancer is the fifth leading cancer killer of women. Some 20,000 women in the United States are diagnosed with the disease every year, and about 15,000 women will die from it during the same time frame.

As with most cancers, a woman's chances of survival are better if the disease is found early, but ovarian tumors are a "stealth killer," because they are notoriously difficult to detect in their early stages. Only about 20 percent of ovarian cancers are found before the malignancy has spread to other tissues, according to information from the Mayo Clinic.

Although most women with advanced-stage ovarian cancer do respond to chemotherapy, 70 percent still die of the disease within five years of diagnosis.

Researchers are exploring vaccines as one way to extend remission. Vaccines essentially harness the body's own immune system to recognize some component of the cancer, then turn the body's forces against it.

Immune agents called cancer-testis antigens are found in abundance in a variety of cancer types and so are good candidates for vaccination, the researchers explained. An antigen known as NY-ESO-1 has shown particular promise.

"NY-ESO-1 peptide has been recognized and known as a potentially tumor-specific antigen, and that's the one single peptide that they're using for this particular vaccine," Morgan explained.

The Roswell Park team tested the vaccine in 18 women with epithelial ovarian cancer, which originates in the covering of the ovaries. All participants had undergone surgery and had completed chemotherapy. Most of the patients had advanced disease.

The vaccine turned out to be safe and also induced patients' antibody and T-cell responses, both measures of immune responses. The T-cells were able to recognize tumor cells containing NY-ESO-1.

Vaccine-induced immune cells were also found to be present in patients up to a year after immunization.

One woman experienced a complete regression of her disease after 10 vaccinations, although the disease did recur again eight months after the vaccinations were discontinued.

While phase I trials like this one are intended mainly to look at safety issues, they can often yield more information, Morgan said.

"While the classical goal of phase I trials is toxicity evaluation, these kinds of agents are different, because they usually don't have much in the area of toxicity," he explained. "What you're really looking for is a response to the proteins."

"I'm very encouraged," he continued.

Fishman said the findings are promising, but even better vaccine candidates may lie ahead.
NY-ESO-1 "is probably not the best peptide to be used as a vaccine because all vaccines are based on targeting something unique to the disease, and this is not unique to ovarian cancer," Fishman said.

However, the study "does show the promise of immunotherapy," he added, "and as we become more sophisticated, hopefully someday we will be able to have vaccines that will treat or ultimately prevent one from developing cancer. That is the goal -- to vaccinate so you never get the disease."

More information
There's more on ovarian cancer at the U.S. National Cancer Institute.

Low-Carb Diets Combat Metabolic Syndrome

(HealthDay News) -- A low-carbohydrate diet helps people with a condition called metabolic syndrome, a collection of serious risk factors found in some obese individuals.

Now, a new study confirms the diet is effective against the syndrome, and the researchers think they've discovered how it works.

Eating a low-carb diet improves the hormonal signaling involved in obesity and improves the sense of fullness, allowing weight loss, according to study leader Matthew R. Hayes, a postdoctoral fellow at the University of Pennsylvania.

"There is this strong interest in the field in carb-restricted diets in the treatment of obesity," said Hayes, who conducted the research while a doctoral student at Pennsylvania State University. "That [interest] comes from a number of controlled clinical trials that demonstrate overweight or obese people, maintained on low-carb diets, are successful if they adhere to the diet."

"It's definitely a hot debate in the field," Hayes added, whether the diets work. "We wanted to look at not only if it worked but how."

People with metabolic syndrome struggle with excessive abdominal fat; low levels of HDL -- good -- cholesterol; and insulin resistance or glucose intolerance, in which the body doesn't properly use insulin or blood sugar. Metabolic syndrome raises the risk of heart disease, type 2 diabetes and other serious health problems, according to the American Heart Association.

Hayes and his colleagues studied 20 men and women with metabolic syndrome, instructing them to follow a low-carb diet similar to the popular South Beach Diet. For phase one, which lasted two weeks, the study participants were told to get 10 percent of their calories from carbohydrates. For phase 2, which lasted the remaining 10 weeks of the study, they were told to eat up to 27 percent carbs.

"The subjects did lose weight, and they lost total body fat. Their weight was a little over 200 pounds when the study started. By the end of the study, the subjects weighed about 193, 194. They lost close to 10 pounds during the three-month study."

And, Hayes said, "By the end of the study, about 50 percent no longer had metabolic syndrome."

The study participants didn't follow the diets strictly, he found. "Phase one intake was 25 percent [carbohydrates], on average," he said, rather than the 10 percent recommended.

"Phase two carb intake was 35 percent," he said, although 27 percent was recommended. But it was a reduction from the participants' pre-study diet, which included 47 percent of calories from carbohydrates, he said.

To find out why the weight declined, Hayes' team did hormone assays, measuring fasting and post-meal blood levels of hormones associated with appetite and food intake, such as insulin, leptin and cholecystokinin (CCK).

"We found some changes in hormone levels," he said. "We saw a decrease in insulin, a decrease in leptin levels by the end of phase one. It was fast."

"By the end of phase 2, the insulin levels had crept up toward baseline; the leptin levels also rose, but it did not come back to the levels at baseline," Hayes said.

"These alternations in hormone levels acting together help reduce the amount of food consumed," he said. "There's a synergy. Based on the literature already out there, we are speculating that this synergy of hormones may be the mechanism explaining why people are satisfied with less food and [the low-carb diet] results in weight loss."

However, Hayes emphasized that the study, published in the August issue of The Journal of Nutrition, was small and preliminary, and more research is needed.

Connie Diekman, director of university nutrition at Washington University in St. Louis and president of the American Dietetic Association, also urged caution when interpreting the study findings. "The study is small in size, and the population is not extremely diverse," she said, although she thinks the study design was good.

"The study was focused on metabolic syndrome, so the outcomes may not be transferable to people who are overweight but do not have the syndrome, since the cause of the syndrome is still not clear," Diekman said.

More information
To learn more about metabolic syndrome, visit the American Heart Association.

Two-Legged Walking an 'Energy Cheap' Option

(HealthDay News) -- Humans' move to two-footed, upright walking may have evolved because it uses less energy than walking on four legs, new research suggests.

Upright walking, or bipedalism, is a critical difference between humans and apes and is considered a defining characteristic of human ancestors.

Some scientists have speculated that bipedalism evolved in humans because it was a more energy-efficient way of foraging.

"For decades now, researchers have debated the role of energetics and the evolution of bipedalism," David Raichlen, an assistant professor of anthropology at the University of Arizona, said in a prepared statement. "The big problem in the study of bipedalism was that there was little data out there," he said.

In a study published July 16 in the online early edition of the Proceedings of the National Academy of Sciences, Raichlen and colleagues collected data on the energy individual bodies expended when five chimpanzees and four adult humans walked on a treadmill. The chimpanzees had been trained to walk on four legs (quadrupedally) and bipedally.

The humans walking on two legs only used one-quarter of the energy that chimpanzees that "knuckled-walked" on four legs did, the researchers found.

The chimpanzees, on average, used the same amount of energy using two legs as they did when they used four legs. The researchers attributed this to their different gaits and anatomy.

Shorter steps and more active muscle mass was associated with more energy used in walking upright, since the chimpanzee with the longest stride was most efficient walking upright.

"We and many others have found these adaptations [such as slight increases in hindlimb extension or length] in early hominins, which tells us that energetics played a pretty large role in the evolution of bipedalism," said Raichlen.

More information
The Public Broadcasting Service has more about walking upright.

Health Tip: Prevent Poison Ivy Rash

(HealthDay News) -- Poison ivy may be difficult to avoid, but it is possible to prevent the itchy rash even after being exposed to the plant.

If you think you've come in contact with poison ivy, follow these suggestions from the U.S. Food and Drug Administration:
Stay outside until your skin has been properly cleaned.
Cleanse skin with a generous amount of rubbing alcohol.
After the rubbing alcohol, rinse your skin thoroughly with plain water.
Shower, washing the skin thoroughly with soap and water.
Wash clothing with rubbing alcohol and water to remove any residue from the plant.

Inappropriate Prescribing for Older Patients a Growing Problem

(HealthDay News) -- Too many older people are being prescribed too many medicines or the wrong drugs, and more research needs to be done to find out how to fix the problem, say two papers published in this week's issue of The Lancet medical journal.

The complexities of the prescribing process, along with other patient, provider and health system factors, are among the reasons why the use of drugs in elderly patients is often inappropriate, wrote a team led by Dr. Anne Spinewine of the Universite Catholique de Louvain, in Brussels, Belgium.

This inappropriate drug use among older patients includes being prescribed drugs they don't need, being under-prescribed medications they do need or being given inappropriate drugs.
Methods of ensuring appropriate prescribing of drugs to elderly patients include care by a multidisciplinary team of health providers; involvement of pharmacists in patient care; and including patients in the prescribing process, the Belgian authors said.

In a second paper, the team noted that older patients are at high-risk for having drug interactions, but the prevalence of these interactions is not yet well documented.

One European study of 1,601 elderly outpatients in six countries found that 46 percent of them had experienced at least one significant drug interaction, and that 10 percent of these interactions were severe. Another study found that 37 percent of patients were taking drugs without their doctor's knowledge, and six percent were taking drugs not on their doctor's lists.

More information
The U.S. Food and Drug Administration has more about medicines and older adults.

Dementia Gene Mutation Identified

(HealthDay News) -- Researchers have discovered a new gene mutation linked to frontotemporal dementia, a disease that affects language abilities and socially appropriate behavior in the people who have it.

Frontotemporal dementia is the second most common form of dementia after Alzheimer's disease.

After a decade of work on the question, researchers at the Regional Neurogenetic Centre in Lamezia Terme, Italy, and the Centre for Research in Neurodegenerative Diseases at the University of Toronto identified the mutation in a gene named progranulin by studying the genealogy of 15 generations of an extended Italian family. Thirty-six members of the family have had frontotemporal dementia. Researchers conducted DNA tests on 70 family members, including 13 with the disease.

The mutation is in a gene on chromosome 17, which leads to a loss of progranulin, a protein growth factor that helps brain cells survive. The mutation limits production of the protein to half the normal amount, because only one copy of the gene is active. While reduced production of progranulin is related to dementia, an excess has been tied to cancer.

The researchers reported finding the mutation in nine of the family members with the disease and in 10 people who were too young to have the disease. They noted that four people who have the disease did not have the mutation, but were descendants of a line of the family in which three generations had frontotemporal dementia, indicating a second possible genetic link.

They also noted that the age at which people with the mutation began to see symptoms of frontotemporal dementia varied between 35 and 78 years old.

The findings are published in the July 10 issue of Neurology.

More information
To learn about frontotemporal dementia, visit the National Institute of Neurological Disorders and Stroke.

Glucosamine Trials Show Little Benefit Against Arthritis

(HealthDay News) -- Although millions of arthritis sufferers buy glucosamine supplements to ease their joint pain, there's still no convincing proof the product works, according to a major new analysis.

In fact, the results of 15 trials of over-the-counter glucosamine vary so widely that industry bias may be a factor influencing the more positive outcomes, concludes a team writing in the July issue of Arthritis & Rheumatism.

"There's a big difference between trials, much more than you would expect by chance," explained lead investigator Dr. Steven Vlad, a fellow in rheumatology at Boston University Medical Center.

But an editorialist in the journal refutes those claims.

Dr. Jean-Yves Reginster, of the World Health Organization's Collaborating Center for Public Health Aspects of Rheumatic Disease, in Liege, Belgium, counters that industry trials are typically more stringent than independent academic research. He also believes that Vlad's group included trials in their analysis that were very unalike in terms of timeframes and methodology, confusing the results.

So, the years-long scientific debate on glucosamine continues. The popular supplement did take a major hit earlier this year, when a major U.S. study published in the New England Journal of Medicine found glucosamine hydrochloride to be of little help for knee osteoarthritis.

But Vlad also knew that other studies had found a real benefit to regular glucosamine use. Why the differences between trials?

To find out, he and his team combed through the available literature and selected 15 double-blind, placebo-controlled, randomized clinical trials that looked at the use of glucosamine for more than four weeks to help fight hip or knee osteoarthritis pain.

Trials involved either of the two major glucosamine preparations: glucosamine hydrochloride or glucosamine sulfate. Each delivers glucosamine bound to a different chemical salt.

First of all, the team determined one of the preparations to be useless.

"I think we have shown pretty conclusively that glucosamine hydrochloride doesn't work," Vlad said. "The data there is all consistent, it goes together -- there's just no evidence that it works."

But that wasn't the story with the other preparation, glucosamine sulfate.

In that case, results varied widely between the randomized trials. However, that variance went far beyond random chance. In fact, according to Vlad, the spread in results among various trials was four times that which would be normally expected.

No particular feature of the studies' design helped explain this disparity, except for differences among trials in what's known as "allocation concealment" -- the fact that some trials were more lax than others at concealing from the researchers involved which patients would get the drug and which would get a placebo.

One factor did appear to play a role in the variance between the glucosamine sulfate trial results: industry involvement.

"It's really hard to know just how big a factor that is," Vlad said, "whether it's manufacturing the whole effect or just exaggerating an effect that's there." He also stressed that, "If there is a bias from industry, I doubt very much that it is intentional. People want to sell their product, but I think that they rarely go into a study with the intention of twisting the results."

But Reginster, in his editorial, believes Vlad's own analysis is flawed. He agreed with the Boston group that industry involvement can, and often does, influence trial results. But he also notes that many of the industry studies included in the Boston analysis had to pass muster with the European League Against Rheumatism, the expert body which vouched for many of the trials' high quality.

That's important, he said, because -- unlike in the United States -- glucosamine sulfate is approved for sale as a prescription drug by regulatory agencies in Europe. To gain approval, industry-funded trials must conform to regulatory oversight and are often better designed than independent studies, he noted.

But Vlad doesn't buy that argument. "I would agree with [Reginster] that, in general, drug manufacturers do produce better trials," he said. "But I also believe it is too simplistic to say that academic researchers aren't as good at weeding out confounding factors and things that would influence the results. They can produce trials that are every bit as good."

Another expert weighed in on the issue.

"I have worked on both sides [industry and independent]," said Malachy McHugh, director of research at the Nicholas Institute of Sports Medicine and Athletic Trauma, at Lenox Hill Hospital, in New York City. He said one issue at play is the dire lack of quality independent studies.

"In the nutritional supplement area, the bigger problem is that there is a disincentive for companies to have their products tested," he said. "If they can convince people that their product works, why run the risk of proving otherwise? There are also many negative studies that never see the light of day."

Reginster lobbed another major criticism at the Vlad study. In his opinion, the Boston group mixed together trials with widely varying timeframes (four-week studies and three-year trials), glucosamine delivered in both injections and pills, and studies of greatly differing quality. This type of heterogeneity was bound to lead to variety in results, he wrote.

Vlad agreed that his team's analysis did cast a wide net, but he said that's the way meta-analyses are typically performed. "You try and capture all the trials that may be relevant to your question," he said. Select too few trials, he said, and you lose statistical power.
The system is "never going to be perfect," Vlad said.

He stressed that the new analysis does not close the book on glucosamine. And given the supplement's good safety profile, patients who really believe they are reaping a benefit from the glucosamine sulfate should feel free to continue to take it.

Vlad and McHugh remain dubious, however, that the pricey supplement does ease osteoarthritis pain.

"From my perspective," McHugh said, "the New England Journal of Medicine paper provides the most objective take on the efficacy. The bottom line is that there is limited efficacy."

In a related study in the same issue of the journal, U.S. researchers surveyed more than 6,000 people with rheumatoid arthritis and found that most are reluctant to switch to a new medication as long as their condition does not worsen.

The team from the National Data Bank for Rheumatic Diseases in Wichita, Kan., found three-quarters of respondents were happy with their current medications, and almost two-thirds (64 percent) said they wouldn't try a new drug unless their symptoms deteriorated. The findings may explain why many patients hold off trying promising new medications, the researchers said.

More information
There's more on osteoarthritis at the Arthritis Foundation.

Drinking Water Is Key to Kidney Stone Prevention

(HealthDay News) -- Staying hydrated in the summer is important for many reasons, including prevention of kidney stones, says Dr. Gary Faerber, associate professor of urology at the University of Michigan Health System.

A lack of fluid can lead to the development of kidney stones, and typical summer physical activities can shake loose kidney stones and result in painful symptoms.

"One of the best ways to prevent kidney stones is to stay hydrated throughout the entire 24-hour period. I recommend may patients have at least six to eight glasses of water a day, and I ask them to make sure that they spread that throughout the entire day and up until night time. This is important year-round but especially important in the summer months," Faerber said in a prepared statement.

"It is very important for people to be aware of how to prevent kidney stones because many people -- about 13 percent of men and 7 percent of women -- will have kidney stones sometime in their lives," he added.

Faerber offered the following tips on reducing your risk of developing kidney stones:

Drink plenty of water.

Reduce your consumption of soda and iced tea, which contain an acid called oxalate that can increase the risk of certain kinds of kidney stones.

Exercise and lose weight. The large number of sedentary and overweight people in the United States is a major factor in the increasing rate of kidney stones in the country.

Drink lemonade, but not the powdery mix. Real lemonade has been shown to reduce the risk of kidney stones.

Ask your doctor about medications that can help prevent kidney stones.

Ask your doctor if you should continue taking calcium supplements, which may increase the risk of kidney stones.

People with highly acidic urine may have to eat less meat, fish and poultry -- foods that increased the amount of acid in the urine. Discuss this with your doctor.

More information
The American Medical Association has more about kidney stones.