Slower brain maturity seen in ADHD kids
Tue, 13 Nov 2007 02:21:41 GMTBy RANDOLPH E. SCHMID, AP Science Writer
WASHINGTON - Crucial parts of brains of children with attention deficit disorder develop more slowly than other youngsters' brains, a phenomenon that earlier brain-imaging research missed, a new study says.
Developing more slowly in ADHD youngsters — the lag can be as much as three years — are brain regions that suppress inappropriate actions and thoughts, focus attention, remember things from moment to moment, work for reward and control movement. That was the finding of researchers, led by Dr. Philip Shaw of the National Institute of Mental Health, who reported the most detailed study yet on this problem in Monday's online edition of Proceedings of the National Academy of Sciences.
"Finding a normal pattern of cortex maturation, albeit delayed, in children with ADHD should be reassuring to families and could help to explain why many youth eventually seem to grow out of the disorder," Shaw said in a statement.
But not all children do outgrow the disorder, and co-author Dr. Judith Rapoport, also of the NIMH Child Psychiatry Branch, said the researchers are working to determine the differences between those that have a good outcome and those who do not.
Between 3 percent and 5 percent of school-age children are thought to have attention deficit hyperactivity disorder.
Dr. Louis J. Kraus, chief of child psychiatry at Rush University Medical Center in Chicago, said "what is really important about this study is it shows us there is clearly something biologically driven for children with ADHD."
Kraus, who was not part of the research team, said that with this finding no one can argue that children are making it up. "We don't know what the meaning is yet, whether it would change any type of treatment, but it is showing that there is something biologically different."
It is important that parents don't immediately jump out and want to get some type of MRI of their child's brain, or functional study to support a diagnosis," Kraus added in a telephone interview.
Shaw agreed: "Brain imaging is still not ready for use as a diagnostic tool in ADHD. Although the delay in cortex development was marked, it could only be detected when a very large number of children with the disorder were included. It is not yet possible to detect such delay from the brain scans of just one individual. The diagnosis of ADHD remains clinical, based on taking a history from the child, the family and teachers."
The research team used scans to measure the cortex thickness at 40,000 points in the brains of 223 children with ADHD and 223 others who were developing in a typical way. The scans were repeated two, three or four times at three-year intervals.
In both groups the sensory processing and motor control areas at the back and top of the brain peaked in thickness earlier in childhood, while the frontal cortex areas responsible for higher-order executive control functions peaked later, during the teen years, they said.
Delayed in the ADHD children was development of the higher-order functions and areas which coordinate those with the motor areas.
The only part of the brain that matured faster in the ADHD children was the motor cortex, a finding that the researchers said might account for the restlessness and fidgety symptoms common among those with the disorder.
Earlier brain imaging studies had not detected the developmental lag, the researchers said, because they focused on the size of the relatively large lobes of the brain.
The sharp differences were discovered only after a new image analysis technique allowed the researchers to pinpoint the thickening and thinning of thousands of cortex sites in hundreds of children and teens, with and without the disorder.
"If you're just looking at the lobes, you have only four measures instead of 40,000," explained Shaw. "You don't pick up the focal, regional changes where this delay is most marked."
Slowest to mature in ADHD children were parts of the front and side of the brain that integrate information from the sensory areas with the higher-order functions. One area lagged five years in those with the disorder.
Also participating in the study were researchers at the Montreal Neurological Institute, McGill University, Canada. The research was funded by the Intramural Research Program at NIH.
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On the Net:
PNAS: http://www.pnas.org
Study assays marrow transplant troubles
Tue, 13 Nov 2007 00:36:20 GMTBy LAURAN NEERGAARD, AP Medical Writer
WASHINGTON - Bone marrow transplants are one of cancer care's striking successes, but they have a dark side: The transplanted cells can turn on patients, attacking their skin and organs.
The potentially deadly side effect with the unwieldy name of graft-versus-host disease, or GVHD, strikes several thousand each year. The last decade has brought little progress in battling it.
Last month brought another blow, as the Food and Drug Administration rejected the new drug closest to market.
But that drug, called orBec, isn't dead; its manufacturer is pledging additional research to satisfy FDA's concerns. And it joins a list of other promising experiments into ways to ease the misery — from novel stem-cell infusions to drugs that block immune cells-run-amok.
The burst of research comes none too soon, as a long-lasting form of GVHD is on the rise.
"I love my doctors, but they throw up their hands. They don't know what to do," laments Stephen Dugan, 54, of Radnor, Pa., who longs for an alternative to the problematic steroid that is today's treatment mainstay.
His transplant four years ago saved Dugan from cancer. But two months later he barely survived a harsh bout of GVHD; now he battles a less severe but chronic form of the disease.
When someone receives a transplanted organ, the big fear is that their own immune system will attack the new "foreign" tissue. GVHD is the opposite problem. It occurs when patients receive donated bone marrow or the stem cells that produce it, pieces of someone else's immune system. Sometimes the donor's T cells, whose job is to hunt foreign invaders, become super-aggressive and attack the recipient's body.
It happens in at least half of the more than 6,000 Americans who receive allogeneic — or donated — marrow or stem-cell transplants every year. Many times, GVHD is mild or moderate, causing skin rashes or blistering, vomiting, liver or lung damage. But one of every five cases is life-threatening. A particularly dangerous form ravages the stomach and intestines, causing unremitting vomiting and diarrhea.
The only treatment: Super-high doses of the steroid prednisone for weeks, to suppress out-of-control immune cells and the inflammation they cause. But the treatment's side effects are severe, even deadly: Patients fall prey to infections; it debilitates bone and muscle until some become bedridden; and it can cause violent mood swings. Plus, about half of seriously ill patients fail to improve, prompting doctors to frantically add other steroids.
"They're our best friends but our greatest enemies," is how Dr. Steven Pavletic of the National Institutes of Health describes prednisone and its cousins.
Now in advanced testing are treatments that aim to calm GVHD without that body-wide steroid toxicity:
_OrBec is a milder kind of steroid, a pill version of the beclomethasone that asthma patients have long inhaled. Dr. George McDonald of Seattle's Fred Hutchinson Cancer Research Center reformulated the drug to coat the gastrointestinal tract, not roam the body.
Adding orBec to standard prednisone seemed to improve survival, a year after gut GVHD first struck, by 45 percent. But because of a statistical issue with the research, the FDA told Dor BioPharma to show more evidence that orBec works. The company pledged to do so, and already has a different Phase III trial under way — to see if giving orBec with the transplant can prevent gut GVHD in the first place.
_The experimental drug Prochymal aims to soothe the source of GVHD's inflammation without suppressing immunity. It's made of a different kind of stem cell, mesenchymal cells. Your own mesenchymal cells are damaged during a bone marrow transplant. But when donated ones are infused into patients' bodies, they steer to wherever GVHD is attacking. There, overly aggressive T cells spur high levels of chemicals called cytokines that in turn inflame tissue.
The mesenchymal cells "change the chemical environment and basically put the brakes on" that damaging process, explains Dr. Hans Klingemann, bone marrow transplant chief at Tufts New England Medical Center. He is the independent safety monitor for Osiris Therapeutics' studies of the drug.
In a small study, adding Prochymal to steroid treatment doubled the chances of a complete recovery. Now a large Phase III trial is beginning to try to prove that effect.
_Johns Hopkins University researchers are studying if two doses of an old cancer drug, cyclophosphamide, at the time of transplant could prevent GVHD anywhere in the body. It's a drug thought to block the function of only bad-acting immune cells, while allowing the rest of the immune system to build back up after the transplant. Of roughly 100 patients tested so far, 65 percent have needed no further anti-GVHD protection, says Dr. Leo Luznik of Hopkins Kimmel Cancer Center. Larger studies at other hospitals are about to begin.
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EDITOR'S NOTE — Lauran Neergaard covers health and medical issues for The Associated Press in Washington.
Senators to study light cigarettes
Mon, 12 Nov 2007 23:33:42 GMTBy KEVIN FREKING, Associated Press Writer
WASHINGTON - The nation's largest tobacco company knew as early as the 1970s that smokers of light cigarettes took larger puffs that delivered greater amounts of tar, according to a newly released memo.
The 1975 Philip Morris USA correspondence was released by the Senate Commerce Committee in advance of a hearing Tuesday examining the rating system that allows tobacco companies to market cigarettes as regular, light or ultra-light.
The current rating system gives smokers a false sense that cigarettes with less tar and nicotine are healthier, according to a memorandum produced by Democratic congressional staffers.
The Federal Trade Commission allows companies to make statements about tar and nicotine levels as long as they're based on a standardized system. That system uses a machine that smokes every cigarette the same way.
People, however, don't smoke the same way. Some breathe in more deeply. Others hold their fingers over the cigarette's vent holes, which increases smoke intake. Research has shown that smokers of "light" cigarettes take longer, deeper puffs and smoke more cigarettes a day to compensate for the lower level of nicotine.
"In a lot of ways switching to light cigarettes can be more deadly," said Sen. Frank Lautenberg, D-N.J.
Lautenberg, a member of the committee, sponsored legislation last year that would prohibit manufacturers from using descriptions such as "light" or "low tar" on a package label or in advertising. He hopes the hearing could generate more support for banning such labels.
Among the documents to be reviewed is the one from Philip Morris, which said the larger puffs taken by smokers of light cigarettes "increased the delivery of the cigarette's particulate matter," which consists mostly of tar.
Philip Morris, part of Altria Group Inc., acknowledges on its Web site that smokers should not assume that light or ultra light cigarettes are safer than full-flavor brands.
"There is no safe cigarette. 'Medium,' 'mild,' 'light' and 'ultra light' cigarettes are no exception," the company's Web site says.
Despite the warnings, the Campaign for Tobacco-Free Kids says tobacco companies aggressively market light cigarettes to smokers concerned about their health. And smokers of those products feel that their brands offer fewer risks than regular cigarettes.
The National Cancer Institute has for several years called for a change in the way that cigarettes are labeled. In 2001, it said people most concerned about smoking risks are those most likely to use brands labeled as light or ultra light.
"Choosing lower-yield cigarettes is not likely to reduce tar intake and resulting disease risks. Furthermore, marketing and promotion of reduced yield products may delay genuine attempts to quit," the agency said. "There is no evidence that switching to light or ultra-light cigarettes actually assists smokers in quitting."
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On the Net:
Senate Committee on Commerce, Science and Transportation: http://commerce.senate.gov/public/
Hundreds sickened on Hawaiian cruise
Tue, 13 Nov 2007 02:16:28 GMTBy MARK NIESSE, Associated Press Writer
HONOLULU - A highly contagious virus that causes stomach flu sickened about 220 passengers aboard a Norwegian Cruise Lines ship that returned Monday to Honolulu after its weekly seven-day cruise around the islands, officials said.
Lab tests confirmed a norovirus — which causes nausea, vomiting and diarrhea — aboard the Pride of Hawaii, said Janice Okubo, spokeswoman for the Hawaii Department of Health.
"It's one of the common viruses we've been seeing on cruise lines," Okubo said. "Most of the time, people recover."
The Norwalk-like virus infected about 9 percent of the ship's 2,500 passengers, and no one was hospitalized, the cruise line said. Virus symptoms typically last a day.
Passengers who felt sick, as well as their cabinmates, were asked to remain in their rooms for 24 hours. Norwegian said it was giving those passengers a $200 on-ship credit.
Surfaces in the ship were cleaned to eliminate lingering viruses, it said.
The U.S. Food and Drug Administration is investigating, Okubo said.
Norwegian describes Pride of Hawaii as the largest and most expensive U.S.-flagged cruise ship ever built. It began service last year.
Norwegian was acquired in February 2000 by Star Cruises PLC of Malaysia, according to the cruise line's Web site.
Condom use reduces risk of bacterial vaginosis
Mon, 12 Nov 2007 19:59:29 GMTNEW YORK - For women who have a high risk of contracting a sexually transmitted disease, their risk of developing bacterial vaginosis and the associated changes in vaginal microflora is reduced if they use condoms during every sexual encounter, according to a report in the journal Epidemiology.
Bacterial vaginosis is caused by an imbalance of the bacteria normally found in a woman's vagina, referred to as vaginal microflora, which is upset by an overgrowth of bacteria not usually present. It is the most common vaginal infection in women of child-bearing age. Symptoms include discharge, odor, pain, itching and burning.
Although any woman can get bacterial vaginosis, some activities or behaviors can upset the normal balance of bacteria in the vagina and put women at increased risk. These include having a new sex partner or multiple sex partners and using an intrauterine device for contraception.
It remains unclear how effective condoms are at reducing bacterial sexually transmitted infections, explain Dr. Roberta B. Ness and colleagues from the University of Pittsburgh, Pennsylvania. They therefore investigated condom use, bacterial vaginosis and the growth of vaginal microorganisms associated with bacterial vaginosis in 871 women at high risk for sexually transmitted diseases.
Overall, women who consistently used condoms (10/10 sex acts) had a 45-percent decreased risk of bacterial vaginosis compared with women who did not use condoms, the authors report.
For women at an intermediate stage of bacterial imbalance, consistent condom use had even more protective effects (63 percent risk reduction),&; the researchers found.
The study findings &;lend some support to the theory that bacterial vaginosis is sexually transmitted, and provides a further rationale for recommending that women use condoms to reduce the risk of bacterial vaginosis,&; the investigators conclude.
SOURCE: Epidemiology, November 2007.
Brain development found to be slower in children with ADHD
Mon, 12 Nov 2007 22:00:54 GMTBy Julie Steenhuysen
CHICAGO - Children and teenagers with attention deficit hyperactivity disorder have developmental delays of up to three years in some regions of the brain, U.S. researchers said on Monday.
&;The sequence in which different parts of the brain matured in the kids with ADHD was exactly the same as in healthy kids. It's just that everything was delayed by a couple of years,&; said Dr. Philip Shaw National Institutes of Health's National Institute of Mental Health.
Shaw said the delays are most pronounced in regions of the brain that are important for controlling thought, attention and planning.
ADHD is a condition suffered by about 2 million U.S. children that often becomes apparent in preschool and early school years. Children with ADHD have a tougher time controlling their behavior and paying attention.
Shaw said the study helps settle the question of whether the brain develops differently in children with ADHD or is just delayed. &;This is very much in favor of a delay,&; said Shaw, whose study appears in the Proceedings of the National Academy of Science.
The finding was based on imaging studies involving 223 children and teens with ADHD and 223 without the disorder.
Researchers used magnetic resonance imaging, or MRI, scans to look at the brain structure at various ages, measuring the thickness of the developing cortex, a key area for attention and impulse control.
While prior imaging studies have mostly relied on measuring the four lobes of the brain, Shaw and colleagues used a new technique that enabled them to measure the thickness of brain tissue in 40,000 different sites in the cortex.
They focused on the age at which cortex thickening peaks during childhood, then starts to thin after puberty as unused neural connections are pruned.
They found that in children with ADHD, the cortex reached peak thickness at an average age of 10.5, compared with age 7.5 in normal children.
&;The delay was carried forward into adolescence,&; Shaw said in a telephone interview.
He said the study was not able to answer the question of why some kids grow out of ADHD, nor does it address any questions about the benefits of treating children.
&;What I wouldn't take away from this study is: 'Just sit and wait three years and your kid will be OK,&;' Shaw said.
&;We know ADHD is a real problem for children and their families and the schools, and it does need treatment,&; he said.
Treatment often includes drugs like Ritalin, or methylphenidate, a stimulant intended to lower impulsiveness and hyperactivity and boost attention. It also may include behavioral strategies to help children and their families manage the disorder.
A study published in September found that fewer than half of U.S. children who meet diagnostic criteria for ADHD receive treatment.
(Reporting by Julie Steenhuysen, editing by Will Dunham and Stuart Grudgings)
