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These deletions are rare, each found in less than 1 percent of schizophrenia patients. But each one boosts the risk of disease by as much as 15-fold, by one estimate.

Scientists said studying such abnormalities may help them find new medications by shedding light on what causes the disease. And if enough rare aberrations can be found eventually, they may be combined into a test to help in diagnosis, said Kari Stefansson, chief executive officer of deCode Genetics of Reykjavik, Iceland, and an author of one of the studies.

Schizophrenia is currently diagnosed by its symptoms.

The human DNA can be thought of as a very long string of letters - about 3 billion of them - that sometimes form words (genes). Each newly identified deletion removes a section of about half a million to 2 million letters.

In the past, scientists have found specific genes and deletions linked to schizophrenia risk. But the new work is notable because two large studies independently identified the same two DNA deletions, and those aberrations have such a big impact on disease risk. Stefansson's paper also reports evidence for a third deletion.

While the DNA deletions are linked to only a tiny fraction of schizophrenia cases, it's not unusual that a very rare cause of a disease provides insights that apply more generally, said Dr. Pamela Sklar of Massachusetts General Hospital, an author of the other paper. She said such knowledge can lead to treatments for many people.

Both papers were published online Wednesday by the journal Nature. Experts not connected with the work praised the results.

"This is tremendous" for basic research into the disease, said Dr. Linda Brzustowicz of Rutgers University. But since the deletions found so far are related to such a small fraction of schizophrenia cases, she said it's too early for companies to offer to test people for them.

Stefansson's paper, which included authors from more than a dozen centers in the United States, Europe and China, reported findings from DNA tests in about 4,700 people with schizophrenia and more than 40,000 healthy people. Sklar's paper, which included scientists from 11 institutes in the United States, Europe and Australia, tested about 3,400 people with schizophrenia and 3,200 others.

Both papers found that while the deletions were rare in schizophrenia patients, they were even rarer in people without the disease. Scientists say the disease results from a combination of genetic predisposition and environmental influences.

The two deletions found by both research groups boost schizophrenia risk 12-fold and 15-fold, Stefansson's group calculated. A third deletion his group found appears to raise risk about threefold.

Sklar said she was "absolutely delighted" that the papers found the two deletions independently, using different methods.

Anne Pulver, a schizophrenia genetics expert at Johns Hopkins University, said the papers represent a welcome shift in focus for finding genetic variants that affect risk of schizophrenia.

Traditionally, that search has centered on relatively common variants, each with little effect on an individual's risk. The new approach seeks rare variants that play a larger role. The new approach should help identify subgroups of patients with different genetic causes for their disease, she said. Eventually that could lead to treatments that are tailored to the differing biological causes, with improved outcomes, she said.

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On the Net:

Nature: http://www.nature.com/nature

Information on schizophrenia: http://www.nimh.nih.gov/health/topics/schizophrenia

© 2008 The Associated Press.

Dr. David Acheson, the Food and Drug Administration's food safety chief, called the finding a key breakthrough in the case, as did another health official.

"We have a smoking gun, it appears," said Dr. Lonnie King, who directs the center for foodborne illnesses at the Centers for Disease Control and Prevention.

Acheson said the farm is in Nuevo Leon, Mexico. Previously, the FDA had traced a contaminated jalapeno pepper to a farm in the Mexican state of Tamaulipas. Both farms shipped through a packing facility in Nuevo Leon, raising the possibility that contamination could have occurred there.

The FDA advised consumers to avoid raw serrano peppers from Mexico, in addition to raw jalapeno peppers from Mexico, and any foods that contain them.

In a statement Wednesday, Mexico's Agriculture Department said it "rejects" the FDA's conclusion that the source of the salmonella outbreak had been located in the Mexican farm's irrigation water.

"The farm unit in question ended its harvest more than a month ago, so the sample they say they have lacks scientific validity" because the sample "was taken recently from a tank holding rain water that was not used in production," the statement said.

"The government reiterates its call for the FDA to use information responsibly and, above all, to base it on scientific evidence," the statement concluded.

Acheson and other officials were grilled at a congressional hearing about why the investigation originally focused on tomatoes. Industry representatives complained that they have lost more than $300 million and had to dump tons of perfectly good tomatoes they could not sell because of government warnings. The probe was slowed even more because FDA investigators were unfamiliar with the workings of the tomato industry and were reluctant to share information, they said.

"For weeks and weeks, investigators were on the trail of the wrong product," Thomas Stenzel, president of the United Fresh Produce Assn., told the House Agriculture Committee.

But federal officials insisted that tomatoes still cannot be ruled out and that it is quite possible the outbreak was caused by several different kinds of contaminated produce.

"I don't think we can say that (tomatoes) were needlessly dumped," Acheson told reporters after the hearing. "The early part of the investigation clearly implicated tomatoes."

The outbreak has sickened more than 1,300 people since April.

Tomatoes had been the prime suspect in the nationwide outbreak for weeks. But last week, the FDA said only jalapeno peppers grown in Mexico were currently implicated in the nationwide salmonella outbreak. The FDA said then it had found the same strain of salmonella responsible for the outbreak on a single Mexican-grown jalapeno in a south Texas produce warehouse. The agency explained that any contaminated tomatoes would be out of the food supply chain by now.

For now, the focus of the investigation is on the two farms in Mexico, which Acheson said are quite far from each other.

The Tamaulipas farm also grew tomatoes and peppers, said Acheson. But the tainted pepper traced to that farm was found at a warehouse facility in McAllen, Texas, raising the possibility it could have been contaminated along the way. Acheson said samples have been taken from the Tamaulipas farm, and lab results are pending.

The Nuevo Leon farm did not grow tomatoes.

Lawmakers are considering a range of reforms to prevent future outbreaks and speed their investigation. These include improving communication between investigators and the industry, imposing standards for good agricultural practices and improving traceability.

"You could describe our current food safety system as 'outbreak roulette,'" said Rep. Dennis Cardoza, D-Calif., chairman of the subcommittee holding the hearing. "One spin of the outbreak wheel, and your industry may be bankrupt, your loved ones sickened."

© 2008 The Associated Press.

Anemia is a frequent side effect of cancer treatment, and can leave already frail patients in an even more debilitated condition. The drugs at issue, Aranesp and Procrit, are commonly used to treat such patients and are made by California-based Amgen. But recent studies have indicated that the treatments could worsen some cancers, and might even shorten patients' lives.

Dr. Richard Pazdur, head of the FDA's oncology section, said Wednesday's directive was the first time the agency has invoked new powers Congress granted it last year to order drug makers to make changes in their prescribing literature, also known as the drug label. Previously, such changes had to be negotiated.

The FDA ordered two specific changes:

The agency said the drugs should not be used with patients who are expected to be cured of cancer. Amgen had pressed for language that would have allowed the medications to be used for some patients who are expected to be cured, but who are not able to receive transfusions of red blood cells.

The second change said patients should not be treated with the drugs unless their hemoglobin levels drop below 10 grams per deciliter of blood. The company had asserted the drugs should also be an option for treating some patients with a slightly higher hemoglobin level.

The FDA's action brings the agency into line with a new Medicare policy that restricts payment for the drugs.

Amgen said in a statement the changes ordered by the FDA were "consistent" with the company's expectations.

© 2008 The Associated Press.

The study is the largest of its kind, and provides the most detailed information to date on types of birth defects that befall the infants of diabetic mothers, including heart defects, missing kidneys and spine deformities.

The study lists nearly 40 types of birth defects found to be significantly more common in the infants of diabetic mothers than in those who weren't diabetic or who were diagnosed with diabetes after they became pregnant.

The study's list of diabetes-associated birth defects is surprising - it's much longer than was previously understood, said Janis Biermann, senior vice president for education and health promotion at the March of Dimes.

"It adds more information about the specific types of birth defects associated with pregestational diabetes and gestational diabetes," said Biermann, who was not involved in the research.

Researchers from the Centers for Disease Control and Prevention led the study, which is being published in the American Journal of Obstetrics and Gynecology. CDC officials released the study Wednesday.

Birth defects affect one in 33 babies born in the United States, and cause about one in five infant deaths. The cause of most birth defects isn't known but some risk factors include obesity, alcohol, smoking and infections.

Doctors have known for decades about the threat diabetes poses to pregnancies. Past research has focused on dangers to the infant by the extra amounts of glucose - sugar - circulating in the womb of a diabetic mother. Studies with rats and mice clearly show excess sugar harms fetal tissue development, said Dr. E. Albert Reece, a study co-author, who directs birth defects research at the University of Maryland School of Medicine.

The new study draws from the birth records between 1997 and 2003 at hospitals in 10 states - Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas and Utah.

The study focused on the 13,000 births involving a major birth defect, and compared them to nearly 5,000 randomly selected healthy births from the same locations.

Mothers were asked if they had been diagnosed with diabetes before or during their pregnancy. The researchers said those who were diagnosed while pregnant either had a temporary, pregnancy-induced condition called gestational diabetes or had diabetes that had gone undiagnosed until they were pregnant.

The study found that there was no diabetes involved in 93 percent of the birth defects.

About 2 percent of the children with single birth defects were born to mothers who had diabetes before they became pregnant. About 5 percent of the infants with multiple defects were born to mothers with that condition. In healthy births, the percentage of mothers who were diabetic before pregnancy was much lower.

The study also showed a wide range of birth defects that included malformation of the heart, spine, limbs and gastrointestinal tract.

"Diabetes is not discriminating" in which birth defects it's linked to, said Dr. Adolfo Correa, a CDC epidemiologist who was the study's lead author.

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On the Net:

CDC: http://www.cdc.gov/ncbddd/bd/facts.htm

© 2008 The Associated Press.

The new policy from the American Academy of Pediatrics renews a debate over the safety of the powerful stimulants. More than half of the 4 million U.S. children diagnosed with attention-deficit disorders are being treated with stimulant drugs.

As Seattle heart specialist Peter Hesslein put it, the dispute among influential doctors "is more than a tempest in a teapot."

ADHD drugs like Ritalin, Adderall and Concerta can help children focus more, behave less impulsively and perform better in school. But they also can increase blood pressure and heart rate and carry warnings about risks for sudden deaths in patients with heart problems.

The pediatricians' group says advice earlier this year from the American Heart Association recommending EKGs was overzealous because these rare deaths are more common in the general population than among children on stimulants.

According to the academy, sudden heart-related deaths occur in about four out of 2.5 million U.S. children on stimulants each year, versus between 8 and 62 such deaths yearly among all U.S. children.

The heart doctors' advice subjects healthy children to unnecessary and costly heart work-ups, and it could limit access to effective ADHD treatments, which "could have serious implications," according to the pediatricians' policy.

The academy says children starting stimulants should get a careful physical exam and be checked for family history of heart problems including sudden death, but that routine EKGs aren't needed in most cases.

When the heart association's policy was announced in April, its advice was widely construed as a mandate.

"We immediately in the cardiology world started getting all these phone calls from people saying, 'I've got to have this test, my kid's got to have this medicine,'" said Dr. Mary Mehta, a heart specialist in Pensacola, Fla.

Because of the confusion and criticism, the heart association clarified its stance in May, issuing a little-publicized statement that said physicians should use their own judgment about the screening and that ADHD treatment should not be withheld if an EKG isn't done.

The pediatricians' academy joined in that statement, but decided that a more forceful stance against routine EKGs made more sense. With little fanfare, their new policy was posted online later that month; it's now being published in the August edition of the academy's medical journal, Pediatrics.

"We really were hearing from our members and parents that things were not at all clear," said policy co-author Dr. James Perrin, a Massachusetts General Hospital pediatrician.

He said the academy's policy makes clear that there's no scientific evidence to support "this fairly dramatic practice change."

The heart association's initial statement noted that evidence presented to the Food and Drug Administration showed that between 1998 and 2003, 19 sudden deaths occurred in children taking ADHD medicine. It also noted that from 1,000 to 7,000 U.S. children and teens die of sudden cardiac death each year, often from conditions that EKGs can detect.

Dr. Tim Gardner, the heart association's president, said his group's stance is based partly on the fact that children with heart abnormalities have a higher incidence of ADHD. He downplayed his group's differences with the pediatrics academy, saying both groups emphasize the importance of careful medical evaluations for children starting ADHD drugs.

Cleveland Clinic heart specialist Dr. Steven Nissen, a drug safety watchdog, said the academy appears to be dismissing concerns that stimulants are used excessively in children with insufficient evidence about long-term risks.

He said the group's pro-drug stance is troubling, coming only a few weeks after it advocated cholesterol drug treatment for children as young as 8 years old.

Hesslein, a heart specialist at Seattle's Swedish Medical Center, said EKGs are inexpensive - less than $100 per test - and easy to do, but that false-positive results are common, often leading to more expensive testing to rule out problems.

Still, Hesslein said other countries have had success with mass EKG screening in certain groups of children, including Italy, where he said sudden heart death rates in young athletes have decreased.

For that reason, he said he thinks routine EKGs for all children "would be worthwhile."

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On the Net:

American Academy of Pediatrics: http://www.aap.org

American Heart Association: http://www.heart.org

© 2008 The Associated Press.

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