WEDNESDAY, Dec. 12 (HealthDay News)-- Disappointing the hopes of researchers, new trials using a powerful steroid to treat deadly bacterial meningitis have shown little or no benefit from the drugs.

"It was a surprise," said Dr. Matthew Scarborough, a clinical lecturer in infectious diseases at the University of Malawi College of Medicine, and the lead author of one study. "Following publication of a European trial that showed benefits, our results showed none," he said.

The results of the two trials, which were conducted in Vietnam and in the south African nation of Malawi, are published in the Dec. 13 issue of the New England Journal of Medicine.

Despite the results, guidelines for the treatment of bacterial meningitis in the United States will almost certainly continue to recommend use of steroids, in part because of the positive results of the 2003 European trial, Scarborough said.

He noted that there were significant differences between the patients treated in that trial and the 465 participants in the Malawi trial.

"Ninety percent of the patients in Malawi had HIV co-infections," Scarborough said. "They also presented later in the disease. Also there was a high incidence of neurological complications. We don't know which of these factors explains the results."

Meningitis is an infection of the spinal fluid (meninges) that surrounds the spinal cord and brain. The illness can be caused by a virus (typically less severe) or, more rarely, by bacteria. Bacterial meningitis is considered much more dangerous, even lethal.

In the Malawi study, researchers gave participants suspected of having bacterial meningitis either the corticosteroid dexamethasone plus an antibiotic, ceftriaxone, or ceftriaxone alone.

Overall, there was no difference in the incidence of death, disability and severe complications between those who got the steroid and those who did not.

A trial of 435 patients with suspected bacterial meningitis patients treated in Vietnam showed similar results, with similar rates of death and disability at one and six months in groups that got steroids or did not. But a significantly lower rate of death and disability was found in patients where the suspected diagnosis of bacterial meningitis could be confirmed.

The Vietnam trial was led by Dr. Jeremy Farrar of the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam.

The studies suggest that different treatment approaches may be needed in different locales, Scarborough said.

"At the moment, I don't think there is any reason for a change of guidelines in Europe and America," Scarborough said. "In Europe and America, patients will still get steroids as adjuvant therapy. There is no evidence that in Africa or Asia, there is a benefit in children or adults. The guidelines will have to be separated."

"The results of the newly reported studies are not entirely unexpected," said Dr. Dean A. Blumberg, associate professor of pediatric infectious diseases at the University of California, Davis.

"The field has not been entirely clear," Blumberg said. "We have been looking at different patient populations, of different ages, some with a large proportion of HIV-infected individuals. Some have different pathogens."

While the two trials were "exceptionally well done," the relatively small number of participants makes it more difficult to interpret the results, Blumberg said.

"Steroids might be allowing someone to live who might otherwise have died," he said. "I don't think this will affect guidelines here. In less developed areas, it may lead to a change in recommendations there."

More information

There's more on bacterial meningitis at the U.S. National Library of Medicine.

TUESDAY, Dec. 11 (HealthDay News) -- Belief, disbelief and uncertainty activate distinct areas of the brain, says a University of California, Los Angeles study published online in the Annals of Neurology.

The study included 14 adults whose brain activity was monitored using functional magnetci resonance imaging (fMRI) while they evaluated a series of statements as true, false or uncertain. The statements included a broad variety of categories, including mathematics, geography and religion.

Belief was associated with increased activity in the ventromedial prefrontal cortex (VMPFC), a brain area involved in linking factual knowledge with emotion.

"The involvement of the VMPFC in belief processing suggests an anatomical link between the purely cognitive aspects of belief and human emotion and reward," the study authors wrote.

Disbelief triggered increased activity in the anterior insula, a brain region involved in taste, pain and disgust.

"Our results appear to make sense of the emotional tone of disbelief, placing it on a continuum with other modes of stimulus appraisal and rejection," the study authors wrote.

Uncertainty prompted increased activity in the anterior cingulate cortex and decreased activity in the caudate, a region in the basal ganglia, which is involved in motor action. Belief and disbelief both boosted activity in the caudate.

The findings suggest that it may one day be possible to use brain scans to reliably detect belief, disbelief and uncertainty in people.

"This would have obvious implications for the detection of deception, for the control of a placebo effect during the process of drug design, and for the study of any higher cognitive phenomenon in which the differences between belief, disbelief and uncertainty might be a relevant variable," the researchers concluded.

More information

Learn more about the human brain at Harvard University  .

THURSDAY, Oct. 18 (HealthDay News) -- Researchers have identified molecular mechanisms in the brain that may explain why some people are less vulnerable to the stress caused by difficult situations.

While the research was done with mice, the findings could eventually lead to better treatments for chronic stress, depression and the post-traumatic stress disorder suffered by troops in Iraq and other battlefields, said study co-author Dr. Eric Nestler, chairman of psychiatry at the University of Texas Southwestern Medical Center at Dallas.

"One important lesson we have shown even in previous papers is that a series of genetically identical animals respond differently to chronic stress," Nestler said. "Thirty to 40 percent seemed to be resilient and did not develop bad symptoms. The clinical implications are that the ability to identify mechanisms of resistance can help provide new and novel approaches to stress."

The key lies in a pair of molecules used by some brain cells to communicate with one another, said Vaishnav Krishnan, lead author of the report and a student in a University of Texas Southwestern Medical Center program that leads to simultaneous M.D. and Ph.D. degrees.

"Under stress, vulnerable mice increase the frequency of nerve activity using the neurotransmitter dopamine," Krishnan said. "That subsequently causes release of a nerve growth factor called brain-derived neurotrophic factor [BDNF]. Resilient mice overcome these changes by increasing the expression of molecules that prevent the release of dopamine."

A neurotransmitter is a molecule that sends signals from one nerve cell to another.

Mice in the experiments were so inbred that they were genetically identical. Then they were put under stress by being placed in the territory of larger, more aggressive mice. Some of the test mice adjusted well to the stress of the situation, while others avoided contact and showed submissive behavior.

The researchers then made detailed studies of two brain regions -- the ventral tegmental area (VTA) and the nucleus accumbens (NAcc), which are part of the brain's reward area that promotes acts that aid in survival. They found that the excess BNDF production in vulnerable mice occurred in the VTA but not the NAcc region. Chemical signals sent by the protein from the VTA to the NAcc made the mice vulnerable to stress. Experimental compounds that blocked those signals turned vulnerable mice into resistant mice.

The findings, published online Oct. 18 in the journal Cell, raise the possibility of "tools to develop things in the brain that encourage resilience, to help people with stress," Nestler said.

"We have always tried to understand the changes in the brain that lead to such things as the symptoms of post-traumatic stress disorder," Krishnan added. "This study shows we can increase our understanding and development of new therapeutic measures to overcome those changes."

But new therapies might not be easy to develop, Nestler said, since a decrease of dopamine or BDNF activity might be helpful in one part of the brain but harmful in another area.

Dr. Thomas R. Insel, director of the U.S. National Institute of Mental Health, which funded the research, said the findings are "part of a large body of work coming out of Dr. Nestler's laboratory trying to understand what this important neurotrophic molecule, BDNF, does."

"What's exciting here is that it is important for resilience, being able to recover from a traumatic event," Insel added. "One of the great values of this work is to help us understand how mammals, including humans, might be able to recover from the traumas inherent in human existence."

More information

Learn more about the role of stress in sickness and health from the American Institute of Stress  .

THURSDAY, Oct. 18 (HealthDay News) -- Doctors have little quality evidence to rely on when deciding how best to treat post-traumatic stress disorder (PTSD) in returning U.S. veterans, a new government-sponsored review of the data concludes.

The Institute of Medicine study was requested by the U.S. Department of Veterans Affairs, which noted that about 12.6 percent of personnel fighting in Iraq, and 6.2 percent of those returning from Afghanistan, have experienced symptoms of PTSD.

Unfortunately, an overabundance of studies with inadequate or flawed designs make it impossible to say whether drug treatments or most psychotherapies can help fight PTSD, the authors of the report told reporters at a press conference Thursday.

Only exposure therapy -- where the patient is re-exposed to the original stressor in a safe, controlled environment -- shows some solid data bolstering its claim to effectiveness, the researchers said.

As for other therapies, "I think it is important to point out that our assessment of inadequate evidence does not mean that the treatments are ineffective," said Dr. Alfred Berg, chairman of the committee that wrote the report and professor of family medicine at the University of Washington School of Medicine. "In most cases, we just don't know because of the absence of good data," he said.

The report is not meant as a guide for patients and their physicians as they work to fight PTSD, which can involve chronic and frightening nightmares, flashbacks, as well as avoidance behaviors that all diminish quality of life.

Instead, the report is meant to assess the current state of the science when it comes to PTSD research, said Dr. David Matchar, director of the Center for Clinical Health Policy Research at Duke University Medical Center.

"We don't want to see people getting a message that they should avoid seeking care because care doesn't work -- that's not at all the message of this report," said report co-author Matchar, who is also a professor of medicine at Duke. "It would be a mistake to receive this as a guideline -- it is not a guideline."

The Veterans Administration does have PTSD clinical practice guidelines in place, and they were last revised in 2004, Berg said. Any changes in those guidelines would not only affect veterans suffering from the condition, but a much wider population of patients. According to the experts, seven percent of Americans -- about 20 million people -- can expect to experience some form of PTSD during their lifetime.

In their review of the data, the IOM researchers pored through 53 trials investigating the effectiveness of medications against PTSD, including anticonvulsants, selective serotonin reuptake inhibitors (SSRIs) antidepressants (which include drugs such as Celexa, Paxil, Prozac and Zoloft), monoamine oxidase inhibitors, and certain antipsychotics.

They also looked at 37 studies that focused on the use of psychotherapies against PTSD. Those approaches included exposure therapy, cognitive therapy, coping skills training, and hypnosis.

Only studies involving exposure psychotherapy provided enough quality evidence to support the claim that it can ease PTSD, the researchers said.

All of the other pharmaceutical or behavioral treatments failed to reach that threshold, leaving the IOM team uncertain as to whether or not the therapies might be effective.

Much of that uncertainty was due to a preponderance of poorly conducted or incomplete trials, the experts said.

For example, many studies had participant dropout rates between 20 percent and 50 percent, making it nearly impossible for researchers to draw reliable conclusions.

In other cases, investigators weren't "blinded" as to which patients were getting a particular treatment or not, allowing bias to potentially creep into the results.

Furthermore, "the majority of the drug studies have been funded by the pharmaceutical manufacturers, and the majority of the psychotherapy studies have been conducted by the individuals who developed the techniques, or by their close collaborators," Berg noted. To help avoid bias, "We recommend that a broader range of investigators be supported to conduct studies that will replicate and confirm earlier studies," he said.

One expert wasn't surprised by the lack of consistent, quality data on PTSD treatments.

"PTSD does not take the same form in every person, and it doesn't have the same severity in every person," said Dr. Charles Goodstein, a clinical professor of psychiatry at New York University School of Medicine. "So, you're dealing with a very heterogeneous population and, moreover, the treatments for this population probably have to be tailor-made."

That assessment dovetails with the IOM report, which stressed the need for high-quality research on the effectiveness of treatments for particular types of patients. "These subpopulations include people with concurrent disorders such as substance abuse, depression, ethnic minorities and veterans with traumatic brain injuries," Berg said.

Conducting large, rigorous trials will cost money, but it could save the government many more dollars in the end, not to mention easing the burden on patients, Goodstein added.

"Why should people be subjected to forms of treatment that may not work?" he said. "Why should the government be paying money for treatments that don't work? Why should people be suffering with symptoms longer than they have to? These are all important questions, and that's really the bottom line of this report."

More information

Find out more about PTSD at the U.S. Department of Veterans Affairs.