Medicine Card The Discovery Of Power Through The Ways Of Animal

WASHINGTON (AP) -- The AIDS virus has hideouts deep in the immune system that today's drugs can't reach. Now scientists finally have discovered how HIV builds one of those fortresses - and they're exploring whether a drug already used to fight a parasite in developing countries just might hold a key to break in.

Researchers have long struggled unsuccessfully to attack what they call reservoirs of dormant HIV, and the new work is in very early stages.

But University of Rochester scientists say it may be fairly straightforward to attack one of these reservoirs, blood cells called macrophages that HIV hijacks and turns into viral hideaways.

The new discovery shows the exact steps that HIV takes to do that - and found that some existing drugs, including a long-used treatment for leishmaniasis called miltefosine, can block the main step and thus cause these cells to self-destruct.

"It's a very smart virus," said lead researcher Dr. Baek Kim. "They have to have a very good fence to protect their house for a long time. ... Get rid of the fence, and now their house is gone."

Today's drugs have turned HIV from a quick death sentence into, for many, a chronic infection. Yet those drugs don't eliminate HIV because they can't reach the two known pools of cells where the virus can lie dormant, ever ready to resurface.

So-called memory T cells form one such pool. As the name implies, these are the cells that ensure if you get, say, measles as a child, you're forever immune. They live for years, even decades, making them a logical HIV hideout, and one that scientists have repeatedly sought to dismantle to no avail.

Macrophages, another type of immune cell, form the second pool. They roam the body looking for invaders like bacteria to gobble up. If they get harmed, such as becoming infected by a virus, they're supposed to commit suicide. But HIV instead keeps them alive long past their normal lifespan.

"Up to now, nobody has really thought about how to eliminate the macrophage reservoir," said Dr. Kuan-Teh Jeang, an HIV specialist at the National Institutes of Health. "The imagination now has turned toward, 'How do we eliminate reservoirs?' ... The best way to address our problem is to simply kill those cells."

The Rochester team found that HIV produces a protein that turns on a particular cell-survival pathway. After a multistep process, it ultimately activates an enzyme called Akt that in turn prevents cell suicide, the researchers reported Thursday online in the journal Retrovirology.

That was good news, Kim said, because the Akt pathway is a culprit in certain cancers - meaning oncologists have been trying to target it for some time. So Kim put human HIV-infected macrophages in lab dishes and started adding drugs known to block the Akt pathway, to see if any killed the cells.

He had luck: Miltefosine and a cousin named perifosine both rapidly killed the macrophages, thus depriving HIV of this hideout.

Perifosine is currently being studied as a possible cancer drug. But miltefosine is known to be safe through its use in leishmaniasis patients. So Kim's goal is to rapidly study the already available miltefosine in animals, to see if it truly targets infected macrophages well enough to then test in HIV patients.

"The evidence they show is in fact pretty good," said NIH's Jeang, who says the next step should be a test of miltefosine in monkeys infected with SIV, the monkey version of the AIDS virus.

© 2008 The Associated Press.

NEW YORK (AP) -- Doctors can cut the risk of cerebral palsy in half for very premature babies by giving their mothers magnesium sulfate just before they give birth, new research shows.

The mineral compound, also known as Epsom salts, is already used to treat preganancy-related high blood pressure and to stop early labor. Doctors should consider giving it to women about to deliver an extremely preterm infant, said one of the researchers, Dr. John Thorp of the University of North Carolina.

"It's cheap. It's readily available. It doesn't harm anybody. I think it will be widely adopted," said Thorp.

The research was led by Dr. Dwight Rouse at the University of Alabama at Birmingham and was presented Thursday at a meeting of the Society for Maternal-Fetal Medicine in Dallas.

Cerebral palsy is a serious complication of premature birth. It's caused by damage to the part of the brain that controls movement and results in poor muscle control and coordination.

Thorp said it isn't clear how magnesium sulfate works, but it is thought to open up blood vessels in the newborn's brain.

In the government-funded study, researchers gave an infusion of magnesium sulfate to women about to give birth to a premature baby to see if it would reduce the risk of cerebral palsy. Enrolled in the study were 2,241 women who were 24 to 31 weeks pregnant. Infants born before 37 weeks are considered premature.

Most of the women were in early labor because their water broke. They were given either the compound or a fake solution. The infants were examined for signs of cerebral palsy at birth and over the next two years.

Of the babies who survived, moderate or severe cerebral palsy occurred in about 2 percent of those in the treatment group compared to about 4 percent of those whose mothers didn't get the compound.

The number of infants who died was about the same in both groups.

"Cerebral palsy is not a terribly common outcome in preterm infants but when it does happen, it's devastating," said Dr. Judy Aschner, chief of neonatology at Vanderbilt Children's Hospital, who was not involved in the study.

She said doctors will want to see the details on side effects when the study is published before making any changes in the care of mothers in preterm labor. Magnesium sulfate acts like a sedative and can make moms and infants groggy and sleepy, she said.

"This is a really important study and potentially one that could change general practice," Aschner said.

In another study presented at the conference, researchers found that women who take folic acid for at least a year before they become pregnant may reduce their chances of early premature birth by 50 to 70 percent. Taking folic acid is already recommended for women of childbearing age to prevent birth defects to the brain and spinal cord, such as spina bifada.

"Here we have an added reason to motivate women to take it and to take it early in their lives," said Dr. Alan Fleischman, medical director of the March of Dimes. The group was giving the research an award at the Dallas meeting.

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On the Net:

March of Dimes: http://www.marchofdimes.com

© 2008 The Associated Press.

NEW YORK (AP) -- For rabid fans of the New York Giants and New England Patriots, this Sunday's Super Bowl won't be just a game. It may be a health hazard. Heart attacks and other cardiac emergencies doubled in Munich, Germany, when that nation's soccer team played in World Cup matches, a new study reports.

While history suggests European soccer fans can get a bit more worked up than the average American football fan, doctors think there are some valid warnings to be shared.

"I know a little bit about the Super Bowl," study author Dr. Gerhard Steinbeck of Ludwig Maximilians University in Munich said in a telephone interview. "It's reasonable to think that something quite similar might happen."

He and his colleagues present their results in Thursday's New England Journal of Medicine. They blamed emotional stress for the heart problems, but they note that lack of sleep, overeating, wolfing down junk food, boozing and smoking might have played a role too.

Previous studies suggest that events like earthquakes and war can boost the risk of heart problems. Findings for soccer have been inconsistent.

The new work "confirms something people have been highly skeptical about ... that soccer (would) produce that kind of emotional investment that might trigger a heart attack," said psychologist Douglas Carroll of the University of Birmingham in England.

"People who are not interested in sport find it very difficult to comprehend this," said Carroll, who in 2002 reported a link between World Cup soccer and heart attacks in England.

The new paper included heart attacks, cardiac arrests, episodes of irregular heartbeat and activations of automatic implanted defibrillators. The researchers noted the number of cases reported in the greater Munich area during World Cup competition in Germany in the summer of 2006. They compared that to the totals for similar periods in 2003 and 2005, and for several weeks before and after the tournament.

In all, the study included 4,279 patients. Analysis showed that on the seven days when the German team played, the overall number of cardiac emergencies was more than double the norm. For men, it tripled.

The effect was strongest in people with known heart disease. So on Super Bowl Sunday, such people and others with known risks for heart disease - like high blood pressure or diabetes - should take extra care of themselves, said Dr. Lori Mosca, director of preventive cardiology at New York-Presbyterian Hospital.

She said that means:

- Take medications as prescribed.

- Avoid tobacco smoke and fatty meals.

- Get plenty of sleep the night before.

- Don't over-exert yourself physically.

- If you drink alcohol, limit yourself to one drink for a woman and two for a man.

- Try "not to get too angry with the refs."

People with known heart conditions should also keep their nitroglycerin and aspirin handy, she said.

And if heart symptoms appear, she said, call emergency services right away. "Don't just chew that aspirin and think it'll go away."

In fact, research by Dr. David Jerrard, an associate professor of emergency medicine at the University of Maryland, indicates that some men do put off seeking emergency treatment if they're watching a game.

On a typical Super Bowl Sunday, "the number of patients waiting to be seen dries up dramatically," Jerrard said. But delaying that visit to stick with a sportscast is a bad idea, especially for people with a history of heart trouble, he says.

"Much of the chest pain or upper abdominal pain that people might be experiencing is mostly likely related to the food they're eating, the alcohol they're ingesting," he said. "But of course, you never know."

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On the Net:

New England Journal of Medicine: http://www.nejm.org

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

© 2008 The Associated Press.

WASHINGTON (AP) -- Thousands of Iraq war veterans who could have suffered traumatic brain injury may be getting unnecessary or inadequate health care because Veterans Affairs officials have yet to determine whether their initial screening tests are reliable, investigators say.

A draft report by the Government Accountability Office, obtained this week by The Associated Press, highlights the Bush administration's continuing difficulties in treating traumatic brain injury, a leading problem among soldiers struck by roadside bombs in the Iraq war. It also comes as a provocative military study this week found that symptoms of memory loss and irritability that have been tied to brain injury might be more accurately attributed to post-traumatic stress and depression.

The GAO review of nine VA medical centers found that months after former VA Secretary Jim Nicholson in April promoted new screenings for brain injury and pledged personal responsibility in seeing them through, the department was still struggling to determine how to best gauge the clinical accuracy of its screenings.

In the report, the VA also acknowledged problems with follow-up appointments after veterans initially tested positive under the VA's screening tool. One medical center reported 27 cases in which their doctors failed to notify patients for additional evaluation because of glitches in the computerized program.

The department has since put in place safeguards to help track whether such patients are given follow-up appointments, but it was not immediately clear how many other veterans who might have needed care were missed at dozens of other VA centers around the country, the report said.

Two VA medical centers also acknowledged they did not follow department protocol for up to three months after procedures were established when they failed to use a symptom checklist. The centers said they either did not know the checklist existed or did not have adequate staffing to follow protocol.

"Until VA evaluates the TBI screening tool's validity and reliability, VA providers will continue to use the screening tool without knowing how effective the tool is in identifying which veterans are and are not at risk for having mild TBI," GAO investigators wrote.

Such false results, the investigators said, could result not only in injured veterans failing to receive proper care, but also in VA medical centers facing growing, unmanageable workloads due to high numbers of veterans being unnecessarily referred for follow-up and treatment.

Responding, VA spokeswoman Alison Aikele said that because research is still being formulated on traumatic brain injury, the VA decided to move forward last April with the best screening tool it knew of at the time. In the coming months, Aikele said, the VA planned to contract with outside researchers to test the validity of its screening, but she could not provide a specific date.

A group representing disabled veterans expressed frustration with the continuing problems.

"The Department of Defense and the Department of Veterans Affairs are nowhere near where they need to be in screening, evaluating and treating vets from Iraq and Afghanistan with mild or moderate traumatic brain injury," said Dave Autry, spokesman for Disabled American Veterans.

In recent weeks, President Bush has released at the request of Congress $3.7 billion in emergency money for additional case workers and services for injured veterans. A defense bill recently signed by Bush also provides money for research, screening and care for those who might have PTSD or traumatic brain injury, which in its mild form is known as a concussion.

As many as 20 percent of U.S. combat troops who fought in Iraq or Afghanistan are believed to leave with signs of possible brain injury, and as of last August, VA officials said about 61,000 Iraq war veterans who sought VA care had been screened. A study being published in Thursday's New England Journal of Medicine found that brain injury may be less to blame for soldiers' symptoms than doctors once thought.

Other GAO findings:

-Inconsistent follow-up. Iraq war veterans face greater burdens in keeping appointments because they tend to be younger than other VA patients, with daytime work, school or child-care commitments. Some Iraq veterans also said they were under the impression that VA facilities catered to an elderly population and did not want to treat younger patients.

-Poor rural access. Two medical centers reported no-show rates of 50 percent or greater for Iraq war veterans with possible brain injury, in part because they lived in small towns or farms and would have to drive 100 miles or so to reach a VA facility.

Last April, a presidential task force chaired by Nicholson announced the new VA screenings and other measures in the wake of disclosures of poor outpatient treatment at the Pentagon-run Walter Reed Army Medical Center.

Nicholson later submitted his resignation in July, and former Army surgeon general James Peake became the new VA secretary last month. Peake has said he wants to improve collaboration between the Pentagon and VA, which hold joint responsibility in treating veterans.

The nine VA medical facilities reviewed by GAO are in Decatur, Ga.; Augusta, Ga.; Baltimore; Dublin, Ga.; Richmond, Va.; Washington, D.C.; Hines, Ill.; Iron Mountain, Mich.; and Tomah, Wis. They were chosen based on high usage by Iraq war veterans as well as geographical representation.

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On the Net:

Government Accountability Office: http://www.gao.gov/

Department of Veterans Affairs: http://www.va.gov/

© 2008 The Associated Press.

LONDON (AP) -- A small number of flu viruses resistant to Tamiflu, a top antiviral drug, have been detected in Europe, health authorities said this week.

Data from more than a dozen European countries show that Tamiflu doesn't work in about 13 percent of H1N1 viruses, the main flu strain causing illness this year. Normally, resistance levels are well below 1 percent.

"It's an unexpected finding and a signal worth watching," said Fred Hayden, a flu expert at the World Health Organization. The resistant strains most likely emerged elsewhere, but were first identified in Europe.

The strain is resistant because of a single mutation. It doesn't cause more serious disease than regular strains, and can be treated with other antivirals. But experts are worried that if the resistance becomes widespread, Tamiflu, one of the best tools for fighting flu, might become useless.

"If I had only a single drug to choose for influenza, oseltamivir (Tamiflu) is the one I would go for," said Dr. Angus Nicoll, influenza coordinator for the European Centre for Disease Prevention and Control. Tamiflu, made by Roche Holding AG, has been stockpiled by WHO and by countries around the world for possible use in a flu pandemic.

But the resistant H1N1 strains do not mean that H5N1, the bird flu many experts fear could spark a flu pandemic, will develop similar resistance.

"The chance of this happening in an H5N1 virus is not zero, but probably very rare," said Dr. Joseph Bresee, chief of epidemiology and prevention at the United States' Centers for Disease Control and Prevention. At least two Tamiflu-resistant H5N1 strains have been found in Asia in the last few years.

Experts said that relying exclusively on Tamiflu is unwise. "This is a very good reminder that we don't know what the next pandemic strain will be sensitive to," Nicoll said. "Perhaps we should have more mixed antiviral stockpiles."

At the moment, health authorities are scrambling to find out how prevalent the resistant strain is worldwide. The highest levels have been found in Norway, where nearly 70 percent of tested strains have been resistant.

Resistance varies across Europe, with Italy reporting no resistant strains, and Britain, France and Denmark all reporting low but significant percentages.

In the United States, nearly 3 percent of tested flu samples have been resistant. "We don't know right now if this is a trend on the upswing or just a small blip," Bresee said.

Laboratories worldwide are also sequencing the mutated virus to try to determine where it came from and how it developed. Usually, resistant strains arise in people who have been treated with the drug. But that's not the case here.

In Norway, none of the viruses were from people who had been treated with Tamiflu. And in Japan, where Tamiflu use is the highest in the world, no resistant viruses have been reported this year. Investigations are ongoing in other countries.

Until now, experts had also believed that if viruses developed resistance, they would be less transmissible. "That assumption appears to have been incorrect," Hayden said.

As the flu season has only just started in Europe and North America, experts will be anxiously monitoring any further spread of the resistant H1N1 strains.

None of the other circulating human flu strains have so far been found to be resistant. Public health agencies say their recommendations on Tamiflu use remain unchanged.

It's still too early to know for sure what this means," Nicoll said. "But watch this space."

© 2008 The Associated Press.