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Something in dark chocolate seems to help protect the heart, and now researchers say they have identified the molecular mechanism by which a compound found in cocoa can guard against the damage of a stroke.

The compound, a flavanol called epicatechin, triggers two built-in protective pathways in the brain, according to a report published online last week in the Journal of Cerebral Blood Flow & Metabolism. The research team was led by Sylvain Dore, an associate professor of anesthesiology and critical care medicine and pharmacology and molecular sciences at John Hopkins University School of Medicine in Baltimore.

Animal studies raise the possibility that epicatechin may someday be used to treat strokes in humans, since its protective effect can be seen more than three hours after a stroke. Existing stroke treatments typically have a shorter window of activity.

While the cardioprotective effect of dark chocolate seen in several human studies appears to open the possibility that eating lots of chocolate is healthy, “I prefer to focus on cocoa,” Dore said. “Cocoa is not like chocolate, which is high in saturated fat and calories. Cocoa can be part of a healthy diet, combined with fruits and vegetables.”

It was a study of the cocoa-drinking Kuna Indians, living on islands off the coast of Panama, that led researchers to study epicatechin. An unusually low incidence of stroke and other cardiovascular disease in that population could not be explained by genetic studies, and eventually was attributed to consumption of a very bitter cocoa drink.

Studies by a number of scientists, including Dr. Norman K. Hollenberg of Harvard Medical School, identified epicatechin as the protective ingredient in dark chocolate and cocoa.

The latest research looked at the mechanism of protection in mice who were induced to have strokes. “We gave different doses of epicatechin in mice 90 minutes before a stroke and found that it reduced infarct [stroke damage] size,” Dore explained. “When we gave epicatechin after a stroke, it had a protective effect up to 3.5 hours later, but not after six hours.”

Detailed studies showed that the flavanol activated two well-known pathways that shield nerve cells in the brain from damage, the Nrf2 and heme oxygenase pathways, Dore said. Epicatechin had no protective effect in mice bred to lack those pathways.

The possibility of using epicatechin to limit human stroke damage is distant, Dore said. “We have to be very careful,” he said. “There are a lot of steps before going to human trials, potential risks and side effects. We need more work and more funding.”

Dore’s long-term plan calls for studies of epicatechin metabolites and derivatives, in cardiac disease as well as stroke. “At this point, we are using only the pure compound,” he said.

Dr. Martin Lajous, a doctoral candidate at the Harvard School of Public Health who took part in one study that showed a reduced incidence of stroke in people who ate dark chocolate regularly, agreed with Dore in saying that eating a lot of chocolate is not a healthy dietary move.

Not all chocolate is created equal, Lajous said. “That’s why we did the study in France, where they eat dark chocolate that is rich in flavanols,” he said. “Chocolate comes with a lot of calories. I would talk about small amounts of dark chocolate rather than chocolate in general.”

And the protective mechanism by which chocolate might prevent stroke isn’t yet clear, Lajous added. The main effect appears to be the lowering of blood pressure, he said. “Flavanols are hypothesized to affect relaxation of smooth vascular muscle, such as the endothelial lining of blood vessels,” Lajous said.

SOURCES: Sylvain Dore, Ph.D., associate professor, anesthesiology, critical care medicine, pharmacology and molecular sciences, Johns Hopkins University School of Medicine, Baltimore; Martin Lajous, M.D., doctoral candidate, Harvard School of Public Health, Boston;

Using magnets to stimulate the brain may ease depression in people who have not found relief from antidepressants, new research has found.

“We have settled a fundamental question about [transcranial magnetic stimulation, or TMS] therapy, which is: ‘Does it work?’” said the study’s lead author, Dr. Mark George, a professor of psychiatry, radiology and neuroscience at the Medical University of South Carolina. “The answer is ‘yes.’”

The researchers administered the magnet therapy to half of a group of 190 adults who had been depressed for at least three months, but not longer than five years, and who had taken medication for depression but were not helped. The others were given a sham treatment — simulated magnet therapy that was mostly indistinguishable from the real thing, the researchers said.

After three weeks, about 14 percent of those receiving magnet therapy were no longer depressed, compared with 5 percent who were getting the fake treatment.

The researchers continued the magnet treatment for three more weeks for those who were still depressed and also offered the real treatment to participants who’d gotten the sham treatment.

After that period, about 30 percent were no longer depressed, the researchers said.

“In a rigorous, industry-free multisite trial with a convincing sham, we found unambiguously that TMS worked better than the sham. It’s watershed,” George stated.

The findings are published in the May issue of Archives of General Psychiatry.

Psychiatrists have been interested in the possibilities of treating depression with magnet therapy for more than a decade, the experts said. Magnets are believed to work by creating electrical currents in the nerve cells in the left prefrontal cortex, a region of the brain involved with regulating mood. The current may jump-start the area, which has been shown to be underactive in people who are depressed, George said.

But testing magnet therapy has been difficult. “Double-blind” studies, in which neither the researchers nor participants know who is getting the real treatment and who is getting the fake, have been difficult to carry out.

The current study overcame that by creating an elaborate sham. During magnet therapy, participants were painlessly zapped by a pulsing electromagnetic coil 3,000 times over 37 minutes. The current created a head-tapping sensation that some people said reminded them of a woodpecker, George said.

The coil, which is aimed at the brain area to be stimulated, creates a magnetic field that passes through the skin and skull, inducing an electrical current in the brain.

Participants receiving the sham treatment felt the same head-tapping, but a metal insert below the magnet blocked the magnetic field from entering the brain while electrodes on the scalp delivered the tapping sensation.

Using electrical current to treat brain disorders has been around in some form since the 1940s and 1950s, said Tony Tang, an adjunct professor in the psychology department at Northwestern University. However, electroconvulsive, or electroshock, therapy can induce seizures, and some studies showed it might cause memory loss and brain damage. Though effective in some people, electric shock was viewed with suspicion by the public, and today is used only as a last resort, Tang said.

Magnet therapy is essentially a much gentler, less invasive form of electric shock therapy, Tang said.

“Transcranial magnet therapy is one of the most exciting new developments in our field,” Tang said. “There are new drugs coming out every year, but they are all fairly similar to each other, and we don’t see much difference in efficacy. With TMS, the mechanism is completely different. It’s a very, very safe and gentle, noninvasive way to do electric shock therapy.”

In 2008, the U.S. Food and Drug Administration approved the marketing of a device used for magnet therapy to treat depression that is considered mildly resistant to treatment, according to background information on the study provided by the U.S. National Institute of Mental Health, which funded the study.

The next step, the researchers said, is to fine-tune the treatment to determine if higher levels of magnetic stimulation or changing the location of the magnetic coil might be even more effective or if magnet therapy might work best in conjunction with medications.

In the study, the only significant side effects were headaches and mild discomfort at the stimulation site. Most participants remained depression-free for several months after treatment stopped, according to the study.

SOURCES: Mark George, M.D., professor, psychiatry, radiology and neuroscience, and director, Brain Stimulation Laboratory, Medical University of South Carolina, Charleston, S.C.; Tony Tang, Ph.D., adjunct professor, department of psychology, Northwestern University, Evanston, Ill.

Adding the antiviral drug telaprevir to a second-round treatment for hepatitis cures about half the people who were not helped in the first round, new research shows.

“This is the first large study in patients who had not responded to standard treatment,” said Dr. John G. McHutchison, associate director of the Duke Clinical Research Institute and lead author of a report in the April 8 issue of the New England Journal of Medicine.

The study is one of the last steps in a series of trials designed to get approval for the use of the drug in clinical practice. Approval of the drug will bring encouragement to people whose hepatitis C infection had not been cured by the existing treatments, McHutchison said.

“There has been no alternative for people who have been treated and have not responded,” he added. “So it holds great promise for them, that potentially something will be available in the future that can cure half of them.”

About 4 million Americans are infected with hepatitis C, a virus that is the leading cause of cirrhosis and liver cancer and the most common reason for liver transplantation. It is usually transmitted by infected blood, most often by using a contaminated needle.

Standard treatment for hepatitis C is a 48-week course of two drugs, peginterferon alpha and ribavirin, which cures about 40 percent to 50 percent of patients but is accompanied by side effects, such as a severe rash, that makes many discontinue the treatment. Previous studies have shown a substantial improvement in cure rates when telaprevir is added to the standard therapy.

Until now, the only recourse for those who were not helped by the first round of treatment was a second round of the same therapy. The newly reported trial, sponsored by Vertex Pharmaceuticals, the maker of telaprevir, included 453 people who had not responded to a first round of treatment. All had the most common, and most difficult to treat, form of the virus, genotype 1.

Just over half, 52 percent, of those who had telaprevir added to the two-drug regimen in the second round were virus-free after six months, compared to 14 percent of those who had a second round of the two-drug treatment.

But the therapy was not problem-free, McHutchison noted. “There were also more side effects, rashes and anemia,” he said. “Also, the rate of discontinuation was higher as well.”

Still, the high cure rate speaks for itself, McHutchison added. Data from the various trials probably will be submitted to the U.S. Food and Drug Administration later this year, he said.

Telaprevir is a protease inhibitor, which works by blocking reproduction of the hepatitis C virus. It is not the only protease inhibitor being tested against hepatitis C, McHutchison said. Another such drug, boceprevir, appears to be running close to telaprevir in the race for regulatory approval. It is being developed by Merck, which acquired it when it bought Schering-Plough.

If and when they are approved, both protease inhibitors probably will be used for first-line treatment of hepatitis C, McHutchison said.

“Having more options for the patient is what it is all about,” he explained.

A number of other protease inhibitors now are in various stages of testing, added Dr. Ira Jacobson, a professor of medicine at Weill Cornell Medical College in New York City and a member of the research team that did the telaprevir study. Jacobson has also been involved in development of boceprevir.

A new era in treatment of hepatitis C will begin when a first protease inhibitor is approved, Jacobson said. “The hope in the medical community is that the regulatory agencies will see fit to approve it for all populations,” he added.

Challenging established medical wisdom about blood pressure and stroke, new British research suggests that extremely variable blood pressure, and not just high blood pressure, can greatly increase a person’s risk of stroke.

“Some people have very stable hypertension, in which case simple hypertension is all that matters, but variability and episodic hypertension is very common and matters much more than mean blood pressure in some patients,” said Dr. Peter Rothwell, a professor of neurology at the University of Oxford and lead author of four papers in the March 13 issues of The Lancet and The Lancet Neurology.

One paper looked at high blood pressure and blood pressure variability in four groups of 2,000 people, each of who had minor strokes called transient ischemic attacks (TIAs), or “mini-strokes.” These are warning signs of stroke risk.

They found that people with the greatest variation in systolic blood pressure (the higher of the 120/80 readings) over seven visits to their doctor were six times more likely to have a major stroke. People with the highest blood pressure readings were 15 times more likely to have a stroke.

“Under-diagnosis and under-treatment of hypertension is a major, seemingly intractable problem in all health-care systems,” Rothwell said. “The new research shows that part of the problem is likely to have been under-recognition of the impact of variability in blood pressure on diagnosis in routine clinical practice in primary care. It shows that doctors have to make diagnoses on the basis of blood pressure measurements that vary substantially from visit to visit.”

The message for doctors is that they have to change the way they view high blood pressure, he said.

“All current clinical guidelines encourage doctors to ignore variability and occasional high readings and to rely exclusively on the average blood pressure from multiple visits or 24-hour monitoring,” Rothwell said. “The new research shows that increased variability in blood pressure, a high maximum blood pressure and episodic hypertension are associated with high risks of stroke and other vascular events, and emphasize that any comfort taken from the fact blood pressure is sometimes normal is false.”

Other papers by Rothwell and his colleagues indicated that doctors should consider blood pressure variability when they choose among the many drugs now prescribed to control high blood pressure. A meta-analysis of 389 controlled trials found that effects on blood pressure variability explained why some classes of blood pressure drugs were more effective than others in preventing stroke. Another paper looked at the greater effectiveness of calcium channel blockers and thiazide diuretics vs. beta blockers in reducing stroke risk.

The result: “Calcium channel blockers and thiazide diuretics reduce [blood pressure] variability and beta blockers increase it,” Rothwell concluded.

He called for development of new drugs that would stabilize and lower blood pressure at the same time. “Drugs that reduced variability without reducing average blood pressure should still prevent stroke and would be likely to be helpful in patients who cannot tolerate reductions in their average blood pressure,” Rothwell theorized.

Variability can easily be measured when people visit their doctors, although “the fact that many people now monitor their blood pressure at home will be helpful in identifying variability,” he said.

“I think these findings are very important and very compelling, and may revolutionize how we treat blood pressure in the future,” said Dr. Philip B. Gorelick, director of the Center for Stroke Research at the University of Illinois, and a leading American expert on blood pressure and stroke. “They provide a very important foundation for change in future treatment.”

Rothwell’s findings already are starting to affect Gorelick’s practice, he said.

“First, we may begin to screen patients with blood pressure measurements for variability to see if we can select for classes of drugs that reduce variability,” Gorelick said. “And we can certainly adopt an at-home program to detect blood pressure variability, although within-visit variability seems to be a more important factor.”

The findings may also affect the choice of the first drugs prescribed for blood pressure control, he said. “We would consider calcium channel blockers and diuretics for initial use,” Gorelick said.

SOURCES: Peter Rothwell, M.D., Ph.D., professor, neurology, University of Oxford, England; Philip B. Gorelick, M.D., professor, neurology, and director, Center for Stroke Research, Chicago; 2010, The Lancet, The Lancet Neurology

Intensive care patients are less likely to die if they’re looked after by a multidisciplinary health care team that includes doctors, nurses, respiratory therapists, clinical pharmacists and others, says a new study.

Researchers analyzed data from more than 107,000 patients admitted to intensive care units at 112 acute care hospitals in the United States between 2004 and 2006. The risk of death was lower among patients in ICUs where a multidisciplinary team conducted daily rounds.

The lowest risk of death was among patients at the 22 (19.6 percent) hospitals that had a trained intensivist physician who consulted on or managed all ICU cases as well as daily rounds conducted by a multidisciplinary care team.

Care by a multidisciplinary team may reduce the risk of death among ICU patients for a number of reasons, said Michelle M. Kim, of the University of Pennsylvania in Philadelphia, and colleagues.

“Multidisciplinary rounds may facilitate implementation of best clinical practices, such as evidence-based treatments for acute lung injury, sepsis and prevention of ICU complications,” they wrote. “Pharmacist participation on rounds is associated with fewer adverse drug events and alone may be associated with lower mortality among ICU patients. Multidisciplinary rounds may also improve communication between health care providers.”

The findings may influence how hospitals look after ICU patients, who are often at high risk of death from conditions such as sepsis and acute lung injury.

“Based on these results and expert opinion voiced in consensus guidelines, it is reasonable for hospitals to implement routine multidisciplinary rounds when staffing capabilities allow,” Kim and colleagues wrote. “Our study shows that hospitals without the ability to implement high-intensity physician staffing can still achieve significant mortality reductions by implementing a multidisciplinary, team-based approach.”

The study appears issue of the journal Archives of Internal Medicine.

SOURCE: JAMA/Archives journals, news release

U.S. researchers have discovered a distinct pattern of brain activity in people with post traumatic stress disorder that may give doctors an objective way to test for it, they said on Wednesday.

Using a brain imaging device called magnetoencephalography, which measures how the brain processes information, a team at the University of Minnesota and the Minneapolis VA Medical Center found differences in brain activity between people with PTSD and healthy people.

Having a test for PTSD could speed treatment and simplify insurance coverage, said Dr. Apostolos Georgopoulos of the University of Minnesota, whose study appears in the Journal of Neural Engineering.

PTSD, an anxiety disorder sometimes caused by wartime trauma, can cause flashbacks, nightmares, anger or edginess.

It currently is considered a “soft disorder,” Georgopoulos said in a telephone interview.

“The thinking is people can suffer from it, but there is no biological marker.”

Georgopoulos and colleagues studied 74 U.S. veterans with PTSD and 250 people with no mental health problems.

They scanned the brains of study participants looking for a signal that might distinguish a PTSD patient from a healthy volunteer.

Georgopoulos said current imaging techniques, including magnetic resonance imaging or MRI and functional MRI, look at brain activity indirectly. To get a direct measure, they used a highly sensitive magnetoencephalography or MEG devices, which measure the magnetic fields produced by electrical activity in the brain.

“What you get out of it is a signal that directly comes from brain activity,” Georgopoulos said.

The scanner has 248 sensors that record the interactions in the brain on a millisecond by millisecond basis, much faster than current methods such as the functional magnetic resonance imaging or fMRI.

These measurements allowed the team to spot biomarkers or signals in the brain scans of those who had PTSD.

When they compared brain scans from PTSD and healthy volunteers, they could accurately pick out the PTSD patients 90 percent of the time.

“What you have in this disorder is a functional disruption of brain activity. This is what we pick up in an extremely highly accurate way,” Georgopoulos said.

The team is now looking to confirm the findings in a study of 500 patients with PTSD and 500 healthy volunteers.

A study last year by the Rand Corp research organization estimates that about 18.5 percent of the U.S. troops sent to Iraq and Afghanistan show signs of either PTSD or depression, conditions linked closely with substance abuse.

(Editing by Cynthia Osterman)

Reuters Health

New research suggests that you should steer clear of using ordinary spoons when taking or giving liquid medicines, because the practice raises the risk of potentially dangerous dosing mistakes.

“Clearly we know that there are a lot of people — despite all the alternatives they are offered — who open the kitchen drawer and grab a spoon to serve up their liquid medicine,” observed study co-author Koert van Ittersum, an assistant professor of marketing in the College of Management at Georgia Institute of Technology in Atlanta.

“But previous work has already shown that the size of your mug or glass influences how much one pours,” he noted. “Just as the size of a plate influences how much one eats. So, here we have found that utensils also have an effect on dosing because our mind plays tricks on us. And so spoon size matters.”

The findings from van Ittersum and his colleague, Brian Wansink of Cornell University, are published as a letter in the Jan. 5 issue of the Annals of Internal Medicine.

The authors point out that the U.S. Food and Drug Administration already cautions against the use of any kitchen utensil for measuring liquid medications.

To gauge the potential for incorrect dosing, the researchers tracked the dosing behaviors of 195 college students who had visited a university health clinic around the time the study was launched.

Each student was first asked to pour out exactly 5 milliliters of a liquid cold medicine, using a normal-sized teaspoon so they could clearly visualize how much that amount would be.

Following that exercise, each participant was randomly asked to attempt two more medicine pours: one into a medium-sized tablespoon and a second into an even larger spoon. Confidence levels were assessed to see how secure the students were in their ability to correctly pour the proper dosage.

Despite the fact that most students had “above average” confidence that they had poured accurate doses while using one or the other tablespoon, the authors found that dosages actually varied depending on the size of the spoon.

When using the medium-sized tablespoon, the students underdosed by more than 8 percent, on average. And when using the larger tablespoon, they overdosed by nearly 12 percent, on average.

The researchers concluded that if even well-educated individuals make mistakes after having essentially been trained to pour correct dosages into a spoon, then anyone — even experienced pourers, such as nurses or caregiving parents — run the risk for making similar dosing errors.

The authors therefore strongly encouraged patients and caregivers alike to stick to more reliable dosing instruments, such as measuring caps or droppers, dosing spoons and/or dosing syringes when administering liquid medicines.

“The bottom line is that there are certain cues in our environment that have a huge impact on our behavior,” explained van Ittersum. “So in this case, you have an idea in your mind of what the right dosage should be, but when given an inappropriately sized spoon, you end up pouring to compensate for the mismatch, and that ends up meaning you are likely to overcompensate or undercompensate, which will mean that you will not end up consuming the proper dosage,” he added.

“Now cough medicine, for example, taken in doses that are too much or too little one time is not going to kill you,” he acknowledged. “But if you’re really sick and you’re doing this over an extended period of time it can really add up, and may have real consequences. Particularly for children.”

So, van Ittersum said, “this is a situation in which sometimes we are our own worst enemy. And so I would say that regardless of the fact that it’s sometimes very tempting to go to the drawer and just simply use a spoon, don’t do it. Use the measuring devices that are specifically designed to help measure accurately.”

Sarah Butler, a registered nurse and diabetes education director for the National Association of School Nurses (NASN), said she “certainly agrees that patients should definitely not be using spoons to measure their medicines.”

Furthermore, NASN President Sandi Delack said in a statement that “since it’s essential that liquid medications are measured accurately to ensure proper dosage, school nurses welcome the use of measuring devices provided by the pharmacy or contained in the medication packaging.”

SOURCES: Koert van Ittersum, assistant professor, marketing, College of Management, Georgia Institute of Technology, Atlanta; Sarah Butler, R.N., diabetes education director, National Association of School Nurses, Silver Spring, Md.; Jan. 5, 2010, Annals of Internal Medicine
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